Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study.

AIMS: To compare the efficacy and safety of famciclovir with aciclovir for the treatment of ophthalmic zoster. METHODS: Randomised, double masked, aciclovir controlled, parallel group in 87 centres worldwide including 454 patients with ophthalmic zoster of trigeminal nerve (V(1)) comprised the intent to treat population. Oral famciclovir 500 mg three times daily or oral aciclovir 800 mg five times daily for 7 days. Assessments included day 0 (screening), days 3 and 7 (during treatment), days 10, 14, 21, 28 and monthly thereafter, up to 6 months (follow up). Proportion of patients who experienced ocular manifestations, severe manifestations and non-severe manifestations; loss of visual acuity was the main outcome measure. RESULTS: The percentage of patients who experienced one or more ocular manifestations was similar for famciclovir (142/245, 58.0%) and aciclovir (114/196, 58.2%) recipients, with no significant difference between groups (OR 0.99; 95% CI 0.68, 1.45). The percentage of patients who experienced severe and non-severe manifestations was similar between groups, with no significant difference. The prevalence of individual ocular manifestations was comparable between groups. There was no significant difference between groups for visual acuity loss. CONCLUSION: Famciclovir 500 mg three times daily was well tolerated and demonstrated efficacy similar to aciclovir 800 mg five times daily.

Internet advice in dermatology and allergy: 1 year analysis of telerequests and answers.

The purpose of this study was to analyze the content and objectives of questions asked by internet users who accessed the homepage of the Department of Dermatology and Allergy Biederstein at the Technical University of Munich. Users were offered the opportunity to ask free questions on the Web site. The results of lay and medical individuals seeking advice were collected over a 12 month period and the answers given were reviewed. We received inquiries from 279 laypersons and 31 physicians. The majority of questions (53.8%) asked by non-medical users dealt with dermatology-related problems. Inquiries related to hair (13.3%) and acne or rosacea (11.3%) were most common. 46.2% of e-mail requests were allergy-related. Most of the interest focused on food allergy and adverse food reactions (22.5%) or hay fever and perennial rhinoconjunctivitis (19.4%). Previous consultation of a physician was reported in 40.9%. 13.6% had consulted an allergist or dermatologist. The majority of questions asked by physicians concerned allergy-related topics (64.6%). Most questions were answered by a short letter giving advice and encouraging the non-medical user to visit a dermatologist and/or allergist (72.4%). In 27.6% we felt that the inquiries were answered completely.

[High-mountain climate therapy for skin diseases and allergies-- mode of action, therapeutic results, and immunologic effects]. / Hochgebirgsklimatherapie bei Dermatosen und Allergien--Wirkmechanismen, Ergebnisse und Einflüsse auf immunologische Parameter.

Dermatological-allergologic climatotherapy is interpreted as a therapy within a specific climate with proven therapeutic benefits, immediate and longterm. Intensive classical dermatological in-patient therapy is combined with specific climatic effects. Primarily, the climate of the high mountains (1560 m) and of the North Sea islands is of proven efficacy for dermatoses and allergic diseases such as atopic dermatitis (neurodermatitis), eczema, psoriasis, T-cell lymphoma, bronchial asthma. Specialized therapeutic utilities exist. Directly influencing climatic factors such as insolation, thermic-hygric and aerosol conditions without or with diminished allergic potency and nonspecific stimulating climate factors change immune functions and effect stabilization. The therapeutic immediate and longterm efficacy of the high mountain climate is proven by excellent follow-up results. Its superiority to the dermatological therapy applied at home is evident. Measurement and analysis of climate efficacy has however proven difficult because of its complexity. The findings of several recent clinical and biochemical studies are presented.

The urokinase plasminogen activator system in angiosarcoma, Kaposi's sarcoma, granuloma pyogenicum, and angioma: an immunohistochemical study.

UNLABELLED: Background Extracellular matrix proteolysis is one of the most important steps in angiogenesis. The urokinase-type plasminogen activator system (uPAS), consisting of the urokinase plasminogen activator (uPA), the uPA receptor (uPA-R), and their corresponding inhibitors, PAI-1 and PAI-2, is thought to play a role in this process. METHODS: We investigated the expression of the components of uPAS in angiosarcoma (AS, n = 4), Kaposi's sarcoma (KS, n = 31), granuloma pyogenicum (GP, n = 25), angioma (AN, n = 15), and healthy controls (CO, n = 15) with immunohistochemical methods. RESULTS: We found positive immunostaining for uPA-R and uPA in all cases of AS. Only two of four cases were positive for PAI-1, whereas all cases were negative for PAI-2. In KS, we observed positive immunostaining in 16 of 31 (51.6%) cases for uPA-R, in 11 of 31 (35.5%) cases for uPA, in 3 of 31 (9.6%) cases for PAI-1, and in 2 of 31 (6.4%) cases for PAI-2. The GP cases showed the following positive results: 4 of 25 (16%) for uPA-R, 6 of 25 (24%) for uPA, 10 of 25 (40%) for PAI-1, and 11 of 25 (44%) for PAI-2. Four cases (26.6%) of AN were positive for PAI-1 and five cases (25%) for PAI-2. In AN (n = 15), there was staining for neither uPA nor uPA-R. In none of the controls (n = 15) was immunostaining for the components of uPAS found in blood vessels. CONCLUSIONS: uPAS is involved in malignant, benign, and reactive proliferative angiomatous lesions, but is absent in normal blood vessels. The upregulation of uPA and its corresponding receptor, uPA-R, in AS and KS supports the hypothesis of the proliferative nature of these lesions; however, the upregulation of the inhibitors (PAI-1 and PAI-2) in benign and reactive proliferative angiomatous lesions (GP and AN) shows how this process may be limited.

Stromelysin-3 (ST-3): immunohistochemical characterization of the matrix metalloproteinase (MMP)-11 in benign and malignant skin tumours and other skin disorders.

Matrix metalloproteinases (MMP) are involved in remodelling of the extracellular matrix (ECM) proteins suggesting that they play an important role in inflammatory process, in tumour invasion and metastasis. We examined immunohistochemically 330 cases of different skin disorders with the monoclonal antibody against MMP 11, stromelysin-3 (ST-3) protein. We found a positive immunoreactivity in fibroblasts surrounding malignant epithelial tumour cells in 63 of 125 cases (50.4%) of basal cell carcinomas, in four of 25 (16%) squamous cell carcinomas, whereas the tumour cells themselves were negative. Furthermore, the ST-3 protein could be detected in 23 of 40 cases (57.5%) of dermatofibroma, in two of five cases (40%) of atypical fibroxanthoma, in one of eight cases (12.5%) of dermatofibrosarcoma protuberans and, locally, in one of 10 cases (10%) of malignant fibrous histiocytoma. It was not present in the following skin lesions: keratoakanthomas (n = 12), Bowen's disease (n = 10), malignant melanoma (n = 12), melanocytic nevi (n = 28) and Kaposi's sarcomas (n = 25). In eczema (n = 10), psoriasis (n = 10) and virus-induced tissues (i.e. condylomata acuminata, n = 10) we did not observe an expression of ST-3 protein. We conclude first that ST-3 protein is a fibroblastic factor expressed in stromal cells adjacent to carcinoma cells; second, that ST-3 protein seems to be associated with benign fibroblastic tumours; and third, that it does not play a role in eczema, psoriasis or virus-induced skin lesions.

Antihistamines in urticaria.

Urticaria is one of the most common and, in its chronic course, excruciating dermato-allergic diseases. Apart from the dermatological diagnosis, the identification and evaluation of causal triggering factors is of utmost importance. Here a 'three-step guideline' (according to Ring and Przybilla) has gained acceptance, ranging a general basic examination via an intensive investigation until oral provocation tests for food allergy and oral provocation tests for idiosyncrasy (OPTI) against food additives. Apart from true IgE-mediated allergies, pseudo-allergic reactions against food additives as well as food contents represent a major problem in chronic urticaria. Recently gastric mucosal colonization with Helicobacter pylori as the trigger of chronic urticaria has received attention. New pathophysiological concepts describe autoantibodies that are directed either against IgE or against the high-affinity IgE-receptor on the surface of mast cells and basophil leucocytes. In the intradermal test with autologous serum positive wheal and flare reactions can be observed (Greaves' test). In many patients with chronic urticaria considerable psychosomatic involvement is also observed. Histamine is one of the major mediators of most forms of urticaria although in some cases, especially physical urticaria, other mediators seem to play a role. Therefore antihistamines, and mainly H1 antihistamines, are the mainstay of antiurticaria therapy. Some studies have shown a benefit of combined H1- and H2-antagonist treatment in special forms of urticaria namely urticaria factitia. Similarly pretreatment with combined H1 and H2 antagonists has been proven to reduce effectively the frequency of pseudo-allergic reaction to some histamine-releasing drugs used in radiology or surgery. More than 50 years after the first introduction of an antihistamine into allergy therapy, antihistamines still represent modern and exciting agents contributing to the continuous improvement of antiallergic therapy. Antihistamine therapy can be performed with either the classical or second generation antihistamines. Classical antihistamines are connected with considerable side-effects especially sedation and anticholinergic effects. New non-sedating antihistamines have been developed that do not cross the blood-brain barrier. The efficacy of mizolastine, a new non-sedating H1 antagonist, has been evaluated in several placebo-controlled and comparative clinical trials. Overall, mizolastine 10 mg/day was found to be significantly more effective than placebo and as effective as other second generation antihistamine drugs in the management of patients with chronic urticaria, with a rapid and sustained action.

Economic evaluation of the treatment of chronic wounds: hydroactive wound dressings in combination with enzymatic ointment versus gauze dressings in patients with pressure ulcer and venous leg ulcer in Germany.

OBJECTIVE: The treatment costs for pressure ulcers and venous leg ulcers were estimated based on the hospital administrator's perspective in Germany. DESIGN: A spreadsheet model using input data from various hospitals in Germany was developed. INTERVENTIONS: Five currently used treatment strategies were analysed: gauze, impregnated gauze, calcium alginate and hydroactive wound dressing with enzymatic ointment. PARTICIPANTS: All cases used for and in the analysis were treated in the inpatient setting (4 hospitals and 120 patients were included). MAIN OUTCOME MEASURES AND RESULTS: The outcome distributions were calculated using the Monte Carlo method. For the whole treatment process, the attributable costs for the hospital were calculated for different cases (severity) and all treatment strategies (1997 values). The costs for treatment with gauze were the highest, whereas the costs for treatment with hydroactive wound dressings and enzymatic ointment were the lowest. The relation between personnel and material costs for gauze is approximately 95 to 5% and for hydroactive wound dressings 67 to 33%, respectively. The cost savings per case were between 1196 deutschmark (DM) and DM9826 using hydroactive wound dressings instead of gauze dressings (depending on the severity of the pressure ulcer), and between DM135 and DM677 for venous leg ulcers. The results were robust and did not change in any performed sensitivity analysis (parameter: 'personnel costs per minute', 'time required for changing a wound dressing', 'total number of wound dressing changes'). CONCLUSIONS: Despite the higher material costs of the hydroactive wound dressings in combination with enzymatic wound cleaning compared with other wound dressings, they should be recommended for the treatment of pressure ulcers and venous leg ulcers. This therapy alternative brings about significant reductions in total costs for hospitals because of significant reductions in personnel costs and the duration of treatment.

Expression of cathepsins in dermal fibrous tumors: an immunohistochemical study.

Cathepsins are lysosomal proteases that are distributed in many normal tissues and are primarily responsible for intracellular catabolism and turnover. The increased level of cathepsins in tumors together with their ability to degrade extracellular matrix proteins has led to the hypothesis that they are involved in the process of invasion and metastasis. We studied immunohistochemically the expression of cathepsins B, pro-D and pro-L in 8 cases of dermatofibrosarcoma protuberans (DFS), five cases of atypical fibroxanthoma (AFX) and twenty cases of dermatofibroma (DF). Expression of cathepsins B and pro-D could be detected in 5 of the 8 cases (62.5%) of DFS, whereas cathepsin pro-L was found in 4 (50%) cases. All AFX expressed cathepsin pro-L, whereas cathepsins B and pro-D were observed in 4 out of 5 cases. None of the malignant tumors showed a recurrence or metastasis after a period of four years. We found no expression of cathepsins in DF. In the epidermis and appendages, an expression of cathepsins pro-D, pro-L and B was seen. We conclude that cathepsins may be markers of increased metabolism rather than specific markers of malignancy.

Stromelysin-3: a potent marker for histopathologic differentiation between desmoplastic trichoepithelioma and morphealike basal cell carcinoma.

Histopathological differentiation between desmoplastic trichoepithelioma (DTE) and morphealike basal cell carcinoma (BCC) is a difficult problem because of their similar morphological features. The matrix metalloproteinase stromelysin-3 (ST-3), which is expressed as a specific fibroblastic factor especially surrounding carcinoma cells, was studied in these both conditions of wholly different clinical outcome. Using formalin-fixed paraffin-embedded tissues, we found positive immunoreactivity for ST-3 in fibroblastic cells surrounding morphealike BCC cells in 34 (68%) of 50 cases, whereas the epithelial tumor cells themselves were negative. In none of the 12 cases of DTE did we observe expression of ST-3 in fibroblasts. We conclude that the antibody against ST-3 protein is an immunohistochemical marker to distinguish morphealike BCC from DTE.

Immunohistochemical analysis of procathepsin L and cathepsin B in cutaneous Kaposi's sarcoma.

BACKGROUND: The expression of the proteinases cathepsins L and B are induced in tumors by malignant transformation, growth factors, and tumor promoters suggesting they play an important role in tumor invasion and metastasis. METHODS: By immunohistochemistry, procathepsin L and cathepsin B were studied in patients with Kaposi's sarcoma (KS). Formalin-fixed and paraffin-embedded tissues from 29 cases of KS (AIDS-associated KS, n = 24; non-AIDS-associated KS, n = 5) were immunolabeled with the polyclonal antibody directed against procathepsin L and the antisera directed against cathepsin B. RESULTS: Normal epidermis, eccrine sweat glands, and hair follicle expressed both cathepsins. We also found a positive staining for procathepsin L in normal blood vessels. In both "angiomatous" and "fibroblastic" lesions of KS no expression of these enzymes was observed. CONCLUSIONS: These findings support the hypothesis of a benign autochthonous origin of the lesions, such as a hyperplasia.

Melanoma-associated paraneoplastic retinopathy: case report and review of the literature.

A 51-year-old white male suffering from metastatic malignant melanoma of the skin presented with lymph node metastases and paraneoplastic retinopathy 4 years after resection of the primary tumour. There were no cerebral metastases. Ocular symptoms consisting of night blindness and sensations of 'shimmering lights' persisted after total resection of the inguinal lymph node metastases and administration of dacarbazine and prednisone. Perimetry of both eyes was abnormal with concentric restriction. Electroretinography showed significantly reduced amplitudes in both eyes. Only 11 patients with melanoma-associated retinopathy (MAR) have been described. High titres of autoantibodies against whole retina extract were detected by enzyme-linked immunosorbent assay (ELISA) reactions. Indirect immunohistochemistry showed strong autoantibody activity against retinal bipolar cells.