Adjunctive role of manual lymph drainage in the healing of venous ulcers: A comparative pilot study.

Compression therapy plays a pivotal role in the treatment of venous leg ulcers and clinical observations include lymph stasis as contributing to the maintenance of chronic wounds. This finding raises the question whether further improvement in lymph circulation with manual lymph drainage (MLD) as a part of complex decongestive physiotherapy (CDP) can improve ulcer healing. We examined whether CDP improves healing of venous leg ulcers and compared the efficacy of CDP with that of multilayered compression with short-stretch bandages. Eight patients (mean age: 64.8 years, mean ulcer area: 23.07 cm2, duration of ulcers: 25.37 months) were treated with a 5-day-course of CDP and 9 patients (mean age: 70.77 years, mean ulcer area: 21.47 cm2, duration of ulcers: 15.8 months) were included in a 10-day-course of CDP. Control goup consisted of 9 patients (mean age: 56.33 years, mean ulcer area: 13.87 cm2, duration of ulcers: 6.11 months) receiving multilayered compression. Wound surface measurement was carried out on days 5 and 10 and ulcer area reduction rate was calculated as area (initial)-area (final)/time unit. There was no statistical difference between the 5-daycourse of CDP and compression of the same duration regarding ulcer healing (t=-1.62, df=15, p= 0.125). A 10-day-course of CDP significantly increased ulcer healing compared to compression of the same duration (t=-2.42, df=16, p= 0.039). Our preliminary results suggest that MLD as a part of CDP supports healing of venous leg ulcers.

Decongestion improves cell-mediated immunity in postmastectomy arm lymphoedema: a pilot study.

BACKGROUND: Chronic lymphoedematous limbs have an increased propensity for infections and primary or secondary malignant tumours. It has been attributed to suppressed delayed-type hypersensitivity measured in lymphoedemas related to Stewart-Treves syndrome, Kaposi's sarcoma or breast cancer treatment. Cell-mediated immunity is an effective defence mechanism against bacteria, fungi, viruses and tumour cells. OBJECTIVE: We aimed to examine whether decongestive lymphoedema therapy could improve cell-mediated immunity in breast cancer treatment-related lymphoedema (BCRL). METHODS: Eight women with unilateral BCRL were included in this study. At baseline, tuberculin skin test (TST) was performed on the volar surfaces of the forearms of the affected and non-affected sides using 0.5, 1 and 5 tuberculin units in the form of three consecutive injections with 3-cm spaces in-between, and arm volumes were measured using the Kuhnke's disc model. Decongestive lymphatic therapy was given to swollen arms in 10 consecutive working days. At the end of intensive decongestion, TST on affected side and bilateral volumetry were repeated. RESULTS: Baseline test using undiluted (5 units) and fivefold diluted (1 unit) tuberculin solutions has shown significant differences (P < 0.05) between the mean sizes (11.81 ± 2.32 and 7.75 ± 1.92; 7.12 ± 1.12 and 5.12 ± 0.91 respectively) in favour to healthy arms. Post therapeutically, the mean sizes were significantly increased (P < 0.05) in the dilutions of 1 : 1 and 1 : 5 (7.75 ± 1.92 and 10.56 ± 1.23 mm, 5.12 ± 0.91 and 5.93 ± 1.74 mm respectively). CONCLUSION: Significant increase in TST sizes suggests that decongestive lymphatic therapy is able to partially restore impaired cellular immune function in BCRL.

Intermittent pneumatic compression acts synergistically with manual lymphatic drainage in complex decongestive physiotherapy for breast cancer treatment-related lymphedema.

The application of intermittent pneumatic compression (IPC) as a part of complex decongestive physiotherapy (CDP) remains controversial. The aim of this study was to investigate whether the combination of IPC with manual lymph drainage (MLD) could improve CDP treatment outcomes in women with secondary lymphedema after breast cancer treatment. A randomized study was undertaken with 13 subjects receiving MLD (60 min) and 14 receiving MLD (30 min) plus IPC (30 min) followed by standardized components of CDP including multilayered compression bandaging, physical exercise, and skin care 10 times in a 2-week-period. Efficacy of treatment was evaluated by limb volume reduction and a subjective symptom questionnaire at end of the treatment, and one and two months after beginning treatment. The two groups had similar demographic and clinical characteristics. Mean reductions in limb volumes for each group at the end of therapy, and at one and two months were 7.93% and 3.06%, 9.02% and 2.9%, and 9.62% and 3.6%, respectively (p < 0.05 from baseline for each group and also between groups at each measurement). Although a significant decrease in the subjective symptom survey was found for both groups compared to baseline, no significant difference between the groups was found at any time point. The application of IPC with MLD provides a synergistic enhancement of the effect of CDP in arm volume reduction.

The prevalence of melanocytic naevi among schoolchildren in South Hungary.

BACKGROUND: Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, is an indispensable step in all primary prevention efforts. OBJECTIVES: This paper aims to assess the prevalence of different pigmented lesions among schoolchildren and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. PATIENTS/METHODS: A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. RESULTS: One to 10 common melanocytic naevi were found in 27% of the participants, and the naevus numbers were in the range of 10-100 in 67%; 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Statistically significant associations were found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, a history of severe painful sunburns and a family history of a large number of melanocytic naevi. CONCLUSION: Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of a large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.

Simultaneous adeno- and squamous cell carcinoma with different phenotypic profiles in a rat model of chronic gastroesophageal reflux.

The aim of our study was to investigate the incidence of duodeno-gastroesophageal reflux-induced malignant transformation in a series of duodeno-esophageal anastomosis operations in rats. This surgical method provides a model for reflux-induced esophageal pathologies, without carcinogen administration. The study design included the follow-up of 31 cases. Thirty weeks of duodeno-gastroesophageal reflux disease significantly increased the risk of the development of Barrett's esophagus, and reflux-induced esophageal adenocarcinoma formation was evident in four animals. In one of these particular cases, a superficial squamous cell cancer was noted in close vicinity to the adenocarcinoma formation. For further analysis, a detailed immunohistochemical staining protocol was used. The immunophenotypes revealed cyclin D1 expression (nuclear positivity in 35% of all the squamous cells), p53 protein accumulation (50% nuclear positivity), with a low expression of cox-2, and negative c-erbB2 staining in the squamous carcinoma cells. The specialized intestinal metaplasia and mucinous adenocarcinoma cells exhibited exclusively diffuse cox-2 positivity (90% of all glandular cells) and weak focal c-erbB2 (5%) staining, without cyclin D1 expression or p53 protein accumulation. Real-time polymerase chain reaction was applied to quantify the abundance of p53, cyclin D1 and cox-2 mRNAs in this biopsy. The most dramatic changes were observed in the level of expression of cyclin D1 (a 9.08-fold expression as compared with the non-treated esophagus samples), while the p53 and cox-2 gene expressions were increased by 1.61 and 2.45-fold, respectively, relative to the non-treated samples. The results afford evidence of the simultaneous activation of more than one possible carcinogenetic pathway in experimental gastroesophageal reflux disease. Synchronous neoplasm formation with different growth pattern characteristics is a rarity in humans, and this phenomenon suggests that the presented model is a suitable means of mimicking the whole spectrum of human gastroesophageal reflux disease pathology.

Treatment of atopic dermatitis with the xenon chloride excimer laser.

BACKGROUND: Narrow-band ultraviolet B phototherapy is an effictive and safe treatment for atopic dermatitis. We have previously found that the 308 nm xenon chloride excimer laser was more effective than the narrow-band ultraviolet B light for the treatment of psoriasis, suggesting that ultraviolet B laser might offer advantages over narrow-band ultraviolet B. OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy of the 308 nm excimer laser in atopic dermatitis. PATIENTS AND METHODS: Fifteen patients with atopic dermatitis (less than 20% body area involvement) were treated with a xenon chloride excimer laser (XTRAC laser, Photomedex Inc.) twice weekly. The severity of the atopic dermatitis was assessed via (i) a clinical score characterizing the intensity of erythema, infiltration, lichenification and excoriation; (ii) the quality of life, determined by means of a questionnaire; and (iii) a visual linear analogue scale, with which the patients scored the severity of their pruritus. RESULTS: After 1 month of laser therapy, the clinical scores were significantly lower than the initial values. Similar decreases were observed for the quality of life and pruritus scores. No serious or unpleasant side-effects were observed. CONCLUSION: These results suggest that the xenon chloride excimer laser is an effective and well-tolerated treatment for localized atopic dermatitis.

Current state and perspectives of dendritic cell vaccination in cancer immunotherapy.

Recent progress in the approach towards immunotherapy of cancer consists in molecular definition of tumor antigens, new tools for phenotypical and functional characterization of tumor-specific effector cells and clinical use of novel adjuvants for optimal stimulation of a cancer-specific immune response such as dendritic cells. In spite of these advances and immunological as well as clinical responses in selected patients, mechanisms involved in dendritic-cell-based cancer immunotherapy are still poorly understood. Therefore, a standardized study design and small pilot trials are needed to explore open scientific questions in future clinical trials. This review focuses on the different parameters of dendritic cell biology relevant to cancer immunotherapy and on innovative approaches to hopefully enhance the efficacy of dendritic cell vaccination.

Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage.

OBJECTIVE AND DESIGN: Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the beta-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model. MATERIALS AND SUBJECTS: Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period. Semiquantitative reverse transcriptase polymerase chain reactions were carried out and the degree of histological damage was evaluated on the 0-16-grade Geisinger scoring scale. RESULTS: Acid exposure was followed by a significant decrease in the level of beta-ATPase expression in the mucosa, and parallel increases in KGF-1 and KGF-R expression. Corresponding changes in the muscle layer were not significant. Bile alone evoked more severe tissue damage, with significantly decreased beta-ATPase levels in both the mucosa and the muscle, whereas the KGF-1 expression did not change significantly. The bile + acid treatment induced an intermediate state, with significant beta-ATPase transcription level decreases in both layers, while the mucosal KGF-1 expression was lower than that following acid treatment alone. CONCLUSIONS: The acid-induced transcriptional level downregulation of mucosal beta-ATPase gene expression in the smooth muscle layer was exacerbated by bile, but the concomitant KGF and KGF-R gene expression changes may indicate the start of a consecutive repair process.

Innate immune functions of the keratinocytes. A review.

Human keratinocytes are known to kill living microbes. They express different pattern recognition receptors (PRRs) such as the Toll-like receptor 2 (TLR2), TLR4, the CD1d molecule and a keratinocyte mannose-binding receptor (KcMR). In response to challenge with microbes or microbial-derived substances the activation and nuclear translocation of NF-kappaB, the production of nitric oxide (NO) and inflammatory cytokines occur in keratinocytes, in a TLR-dependent manner. Blocking of NF-kappaB activation or NO production inhibit the Candida albicans-killing activity of keratinocytes. This Candida killing activity could be inhibited by blocking of KcMR. Recognition of invading pathogens in the epidermis triggers cytokine production in keratinocytes leading to elimination of pathogens and the activation of the adaptive immune system. These findings stress the importance of the role of keratinocytes in innate immunity.

0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial.

BACKGROUND: Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. OBJECTIVES: This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. PATIENTS AND METHODS: Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. RESULTS: Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes. CONCLUSIONS: 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.

Platelet-activating factor antagonist WEB 2086 inhibits ultraviolet-B radiation-induced dermatitis in the human skin.

It has been suggested that platelet-activating factor (PAF) plays a role in the pathomechanisms of various inflammatory diseases. In an experimental animal model we demonstrated earlier that a selective PAF receptor antagonist gel inhibits ultraviolet-B (UVB) light-induced edema in mouse ears. The goal of our present investigation was to determine whether locally applied WEB 2086, a selective PAF receptor antagonist, alters the dermatitis-causing effect of UVB light on human skin. We induced dermatitis in healthy volunteers by irradiating their skin with UVB light in increasing doses. The irradiated area was treated with WEB 2086 gel (3%) or with a placebo. Erythema was measured spectrophotometrically after 24 and 48 h. After both 24 and 48 h, the WEB 2086 gel significantly inhibited the UVB light-induced erythema at each radiation dose in comparison with the placebo. The PAF antagonist gel therefore proved to be effective against UVB-induced dermatitis. Our results may help to understand the relative importance of mediators in UVB-induced dermatitis and might perhaps pave the way to better therapeutic modalities in this condition.

The role of innate immunity in the pathogenesis of acne.

Acne is a multifactorial disease of the pilosebaceous follicle. The most significant pathogenetic factors of acne are: abnormal ductal keratinization, increased sebum secretion, abnormalities of the microbial flora and inflammation. The pilosebaceous unit is an immunocompetent organ. Keratinocytes and sebocytes may act as immune cells capable of pathogen recognition and abnormal lipid presentation, and they might have an important role in initiating and perpetuating the activation of both innate and adaptive immune responses. The elements of the skin immune system are involved in the development of both noninflammatory and inflammatory acne lesions.

Low-dose dithranol treatment and tape stripping induce tolerance to dithranol in a mouse ear oedema model.

BACKGROUND: It is well known from clinical practice that repeated treatment with dithranol leads to the development of tolerance. OBJECTIVES: To investigate the characteristics and mechanism of such dithranol tolerance. METHODS: The mouse ear was pretreated with a low dose of dithranol or croton oil or, in previously sensitized animals, with dinitrofluorobenzene (DNFB). Twenty-four hours later irritant dermatitis was elicited by painting the mouse ear with a high dose of dithranol, croton oil or DNFB, and the dermatitis was characterized by measurement of ear thickness. RESULTS: Low-dose dithranol significantly suppressed dithranol-induced oedema, whereas it had no effect on croton oil- or DNFB-induced dermatitis, suggesting that dithranol-induced tolerance is specific. Tolerance to dithranol could not be induced by pretreatment of the mouse ear with a low dose of croton oil or DNFB. Mild tape stripping of the mouse ear also inhibited the inflammatory effect of dithranol applied 24 h later. Superoxide dismutase treatment abolished the tolerance-inducing effect of low-dose dithranol or stripping. CONCLUSIONS: These results suggest that superoxide anion radicals are involved not only in the inflammatory effect of dithranol, but also in the induction of tolerance.

Elevated serum caeruloplasmin level in a patient with adult Still's disease.

We report the case of a woman with a characteristic transient skin rash, fever, severe polyarthritis, hepatosplenomegaly, lymphadenopathy and myalgia. The clinical and laboratory data led to a diagnosis of adult-onset Still's disease. The elevated levels of serum ferritin and caeruloplasmin could be important as diagnostic indicators.