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Biomedical subjects

G Wozel

Publications and source records attributed to G Wozel.

At least 19 recordsLinked to original sources
PubMed2006

[Pancreatic panniculitis with neuroendocrine pancreatic carcinoma].

Pancreatic panniculitis is a rare complication occurring in 0.3-3% of patients with pancreatic disease. Clinical features include erythematous painful subcutaneous nodules usually on the lower leg and foot. A 72-year-old man was diagnosed in 2002 with a neuroendocrine carcinoma of the head of the pancreas. In 2003 following surgery and radiation therapy, he developed liver metastases and painful nodules on his legs. Lipase was found to be markedly elevated; amylase and alpha1-antitrypsin were in the normal range. Histopathologic examination of a nodule showed subcutaneous fat necrosis with ghost cells surrounded by an acute inflammatory infiltrate. The pathogenesis of pancreatic panniculitis is unclear. The pancreatic enzyme lipase may induce lipolysis and fat necrosis with secondary tissue inflammation.

Aged↗
PubMed2006

[Is the psoriasis plaque test still relevant in the age of biologicals?].

A variety of approaches (in vitro-/ex vivo studies, animal models, human studies and clinical trials) are available to assess compounds with potential antipsoriatic properties. Over the past few years various rodent models that mirror aspects of psoriasis phenotypes and/or pathogenesis have been created (e. g. knockout rodents, xenotransplantation models). Unfortunately these animal models do not reflect the complete pathogenesis of psoriasis. Therefore, screening procedures involving psoriatic lesions in humans are necessary. Even in the era of biologicals, the psoriasis plaque test (PPT) remains an important in vivo tool. In addition to screening potential antipsoriatic substances, the PPT can help answer other questions (frequency of use, dose-response relationship). A prerequisite for correct performance of PPT is knowledge of the toxicological and pharmacological data of the investigational compounds. The PPT is relatively simple, not time-consuming and allows the simultaneous testing of multiple substance. All the results from PPT must be confirmed by controlled clinical trials.

Administration, Topical↗
PubMed2006

A 52-week randomized safety study of a calcipotriol/betamethasone dipropionate two-compound product (Dovobet/Daivobet/Taclonex) in the treatment of psoriasis vulgaris.

BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product Dovobet/Daivobet/Taclonex(LEO Pharma A/S, Ballerup, Denmark) has been shown to be safe and effective in the treatment of psoriasis for up to 8 weeks. As psoriasis is a chronic disease, long-term treatment may be required, so there is a need to investigate the safety of its use over a longer period of time. OBJECTIVES: To investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks in the treatment of patients with psoriasis. METHODS: Patients (n = 634) were randomized double-blind to treatment with: (i) 52 weeks of the two-compound product (two-compound group); (ii) 52 weeks of alternating 4-week periods of the two-compound product and calcipotriol (alternating group); or (iii) 4 weeks of the two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). Treatments in all groups were used once daily when required. RESULTS: Adverse drug reactions (ADRs) occurred in 45 (21.7%) patients in the two-compound group, 63 (29.6%) in the alternating group and 78 (37.9%) in the calcipotriol group. The odds ratio for an ADR in the two-compound group relative to the calcipotriol group was 0.46 (95% confidence interval 0.30-0.70; P < 0.001). ADRs of concern associated with long-term topical corticosteroid use occurred in 10 (4.8%) patients in the two-compound group, six (2.8%) in the alternating group and six (2.9%) in the calcipotriol group; those with the highest incidence were skin atrophy, occurring in four (1.9%), one (0.5%) and two (1.0%) patients, respectively, and folliculitis, in three (1.4%), one (0.5%) and no patients, respectively. CONCLUSIONS: Treatment with the two-compound product for up to 52 weeks appears to be safe and well tolerated whether used on its own or alternating every 4 weeks with calcipotriol treatment.

Adult↗
PubMed2006

Efficacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris.

BACKGROUND: The calcipotriol/betamethasone dipropionate two-compound product is safe and effective in the short-term treatment of psoriasis. OBJECTIVE: The primary objective was to investigate the safety of two treatment regimens involving use of the two-compound product over 52 weeks. The efficacy results are presented here. METHODS: Six hundred and thirty-four patients were randomised double-blind to treatment (once daily, when required) with either: 52 weeks of two-compound product (two-compound group), 52 weeks of alternating 4-week periods of two-compound product and calcipotriol (alternating group), or 4 weeks of two-compound product followed by 48 weeks of calcipotriol (calcipotriol group). RESULTS: There was a trend towards a difference between treatments from the overall treatment effect for the percentage of satisfactory responses for each patient during the study (p = 0.071). This appeared to be due to the comparison of the two-compound and calcipotriol groups (p = 0.025). CONCLUSION: There was a trend towards the efficacy of the two-compound product used for up to 52 weeks being better than that of 4 weeks of the two-compound product followed by 48 weeks of calcipotriol.

Anti-Inflammatory Agents↗
PubMed2005

[Alefacept. Successful long-term therapy of a severe psoriasis].

Alefacept, a recombinant protein produced by fusion of human LFA(3 )and IgG(1), was the first biologic specially designed and approved for the treatment of psoriasis. Results of clinical trials reveal both an efficacy comparable to established systemic therapies and a high drug safety. A 62-year old male patient with psoriasis and incomplete response to several standard therapies was treated with alefacept (baseline PASI 23.1). After three courses of 15 mg alefacept i.m. weekly for 12 weeks, each followed by a 12 week post-dosing observation period, the PASI regressed to 2.0. Adverse drug reactions were not observed.

Alefacept↗
PubMed2005

[Etanercept. An effective TNF alpha-antagonist in the treatment of psoriatic arthritis and chronic plaque psoriasis].

Etanercept, an inhibitor of TNF alpha, has been found effective in the treatment of psoriatic arthritis and psoriasis vulgaris. Etanercept is a fusion protein made up of domains of the soluble, fully human p75-TNF alpha receptor and the F(c) portion of human IgG(1). The drug is a protein which must be administered subcutaneously. Several controlled studies have highlighted its efficacy for both skin symptoms and joint involvement. The usual dose is 25 mg s.c. twice weekly. Higher dosages of 50 mg twice weekly may be used in severe cases. Before starting the therapy with etanercept, infections including tuberculosis have to be excluded. Methotrexate and other pharmacological immunosuppressive agents can be combined with etanercept, as can all standard topical agents. Etanercept in off-label use has been found to also be useful in several other inflammatory dermatologic conditions. If patients are carefully monitored, etanercept is generally well-tolerated and has a good safety profile. The development of novel biologic agents such as etanercept is one of the most important therapeutic innovations of recent years.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Leflunomide as a novel treatment option in severe atopic dermatitis.

BACKGROUND: Based on the increasing knowledge of T-cell-mediated pathogenesis in atopic dermatitis (AD), systemic immunosuppressive drugs are increasingly applied. The chronic, relapsing course of severe AD necessitates a drug, both efficacious and safe in long-term application. Leflunomide is a pyrimidine de novo synthesis-inhibiting immunosuppressant exhibiting an extremely long in vivo half life of its active metabolite. OBJECTIVES: To evaluate the efficacy of leflunomide in long-term treatment of AD. METHODS: As a proof of principle, we treated two patients with severe AD, recalcitrant to different systemic treatment modalities, for 20 months with leflunomide (loading dose 100 mg daily during 3 days; maintenance dose 20 mg daily). At regular visits physical examination, eczema area and severity index (EASI), visual analogue scale (VAS) for itching, and laboratory findings were assessed with according adjustment of the leflunomide dose. RESULTS: At the initiation of leflunomide therapy, both patients presented with almost erythrodermic AD (patient 1, EASI 40.0, VAS 10; patient 2, EASI 43.0, VAS 8). Partial remission was observed within 4 and 7 weeks, respectively, and maintained over 20 months (patient 1, median EASI 4.2, median VAS 2; patient 2, median EASI 8.4, median VAS 2) except for one episode of exacerbation in each case. In one patient, remission was stable even after cessation of drug dosing. Severe adverse events were not observed. CONCLUSIONS: Leflunomide was efficient in the long-term treatment of recalcitrant AD. Controlled studies will be necessary to evaluate the subset of severe AD patients benefiting most from this drug.

Acute Disease↗
PubMed2004

Efficacy of once-daily treatment regimens with calcipotriol/betamethasone dipropionate ointment and calcipotriol ointment in psoriasis vulgaris.

BACKGROUND: A two-compound ointment containing calcipotriol 50 micro g g-1 and betamethasone dipropionate 0.5 mg g-1 has recently been shown to be an effective treatment for psoriasis. OBJECTIVES: This study was designed to investigate efficacy and safety of different treatment regimens with the two-compound product (Daivobet/Dovobet; LEO Pharma, Ballerup, Denmark) and calcipotriol 50 micro g g-1 ointment (Daivonex/Dovonex; LEO Pharma). METHODS: In total, 972 patients with psoriasis vulgaris were randomized to one of three treatment regimens: group 1, the two-compound product once daily for 8 weeks followed by calcipotriol ointment once daily for 4 weeks; group 2, the two-compound product once daily for 4 weeks followed by 8 weeks of treatment with calcipotriol ointment once daily on weekdays and the two-compound product once daily at weekends; and group 3, calcipotriol ointment twice daily for 12 weeks. The efficacy was evaluated by Psoriasis Area and Severity Index (PASI) and investigators' global assessments of disease severity. The primary response criteria were percentage reduction in PASI and proportion of patients with absent/very mild disease according to the investigators' global assessments after 8 weeks of treatment. RESULTS: The mean reduction in PASI from baseline to the end of 8 weeks of treatment was 73.3% for group 1, 68.2% for group 2 and 64.1% for group 3. The proportion of patients with absent/very mild disease at the end of 8 weeks of treatment was 55.3% for group 1, 47.7% for group 2 and 40.7% for group 3. For both primary response criteria, group 1 was statistically superior to group 3 (P < 0.001), whereas group 2 did not differ significantly from group 3. The difference between group 1 and group 2 was statistically significant with regard to PASI but not regarding the proportion of patients with absent/very mild disease. Patients receiving initial therapy with the two-compound product achieved the fastest treatment response, and the maximum treatment effect for these patients was seen after 5 weeks. This effect was maintained with continued treatment with the two-compound product for up to 8 weeks. After 12 weeks of treatment, no significant differences were seen between the three groups with regard to reduction in PASI, whereas the proportion of patients with absent/very mild disease in group 2 was superior to that in group 3. Patients receiving therapy with the two-compound product experienced fewer lesional/perilesional adverse drug reactions than the calcipotriol-treated patients (P < 0.001): 10.9% in group 1, 11.5% in group 2 and 22.3% in group 3. CONCLUSIONS: Two different short-term treatment regimens employing a recently developed two-compound product (calcipotriol/betamethasone dipropionate) provided rapid and marked clinical efficacy and were shown to be safe therapies for psoriasis vulgaris.

Adolescent↗
PubMed2003

[The treatment of atopic dermatitis in adults with topical calcineurin inhibitors].

In about 60% of cases, atopic eczema can persist in adulthood with distinctive clinical features and disease course. The introduction of the topical calcineurin inhibitors pimecrolimus 1% cream and tacrolimus 0.03 and 0.1% ointment clearly improves the long-term management of atopic eczema in adult patients; this has been shown in several large clinical studies and is confirmed by the growing practical experience with these substances. Topical calcineurin inhibitors are, even when applied for weeks and months, safe, well tolerated and efficient; they have a rapid and positive effect on pruritus and the potential--as shown in clinical studies with pimecrolimus 1% cream--to reduce the number of eczema flares, to significantly prolong the time to a first flare and to reduce or even eliminate the need for topical corticosteroids.

Administration, Topical↗
PubMed2003

[Topical treatment of psoriasis: a systematic update].

Classical topical treatment regimens in psoriasis including dithranol and corticosteroids are widely used and have been supplemented in recent years by topical vitamin D preparations, by vitamin D analogues and topical retinoids. The combination of these preparations with each other, with UV light or with systemic drugs often lead to improved effectiveness and tolerability when compared with the respective monotherapy. In private offices, the combination of calcipotriol with various corticosteroids is very commonly prescribed for patients with mild to moderate psoriasis. This combination can be sequentially applied twice daily or--in a newly introduced fixed preparation--once daily. In severe psoriasis requiring systemic treatment a concomitant effective topical treatment regimen can greatly improve the overall longtime management in affected patients.

Administration, Topical↗
PubMed2002

[Leflunomide--a new drug for pharmacological immunomodulation].

The novel immunomodulatory agent leflunomide exhibits a strong anti-inflammatory action. This isoxazole derivative is chemically unrelated to any hitherto applied immunosuppressants. As a prodrug leflunomide is completely converted to its active metabolite A 77 1726 (M1) which blocks the dihydroorotate dehydrogenase, a key enzyme of the pyrimidine de novo synthesis. Drug-related adverse effects are mild, dose-related and reversible, characterising leflunomide as a safe immunosuppressant. While up to now leflunomide has just been approved for therapy of rheumatoid arthritis, its mechanism of action affects multiple inflammatory pathways, thereby suggesting it to be a potent therapeutic agent in autoimmune diseases, graft rejection, and tumour therapy. First dermatological experience has been gained in psoriasis and bullous pemphigoid. The role of leflunomide in the dermatologist's therapeutic armamentarium will evolve during the next years.

Animals↗
PubMed1998

[Langerhans cell histiocytosis in the elderly].

Disseminated Langerhans-cell-histiocytosis (LCH) is most frequent in children at the age of 1-3 years, seldomly seen in adults and extremely rare in the elderly. The clinical course may be acute, subacute or chronic, progressive or stationary. Spontaneous remissions are possible, but rare. In elderly patients often the disease is at first limited to the skin before it becomes systemic. A 73-year-old female patient with chronic stationary disease of 3.5 years duration died 4 weeks after the acute dissemination of her LCH. At the beginning, her skin and liver involvement had responded to chemotherapy with etoposide. Six months later cutaneous relapse occurred with a more disseminated pattern involving the external auditory meatus. Treatment with topical nitrogen mustard followed by thalidomide produced marked improvement. As complications an irritation after topical application of nitrogen mustard and a maculo-papular exanthem after thalidomide were noted. No further visceral involvement was documented for one year. Then the patient developed acute disseminated disease and died within four weeks. As LCH may show a highly unpredictable course with progress and spontaneous remission, the prognosis is difficult. Any therapeutical procedures should be based on the actual state of the disease as determined by careful examination of the organs most commonly involved.

Adult↗
PubMed1997

Dapsone hydroxylamine inhibits the LTB4-induced chemotaxis of polymorphonuclear leukocytes into human skin: results of a pilot study.

OBJECTIVE: Dapsone (4,4'diaminodiphenylsulfone) is effective in treating leprosy, chronic inflammatory conditions and opportunistic infections in HIV patients. By the oral route, the sulfone is metabolized to monoacetyldapsone (MADDS) and dapsone hydroxylamine (DDS-NOH). We have addressed the question as to whether these dapsone metabolites have anti-inflammatory properties of their own in vivo. TREATMENT AND METHODS: After two weeks topical pre-treatment with MADDS (1%), DDS-NOH (1%) and clobetasol proprionate (CP; 0.05%) dissolved in acetone, as a reference, 10 ng leukotriene B4 (LTB4) were applied on the upper arms of eight healthy volunteers. After 24 h, biopsies were taken and the polymorphonuclear leukocytes (PMN) were quantified fluorometrically using elastase as marker enzyme. RESULTS: MADDS did not show any inhibitory activity on trafficking of PMN compared to the corresponding control and nontreated area (untreated: 790 +/- 450 PMN/10 micrograms skin; p > 0.05, acetone: 840 +/- 578 PMN/10 micrograms skin; MADDS: 1099 +/- 556 PMN/10 micrograms skin), whereas DDS-NOH caused a statistically significant inhibition of PMN accumulation as did the reference CP (DDS-NOH: 128 +/- 143 PMN/10 micrograms skin; CP: 86 +/- 131 PMN/10 micrograms skin, p < 0.01). CONCLUSIONS: These results indicate that DDS-NOH has anti-inflammatory potential which might contribute to the effectiveness of dapsone therapy.

Adult↗
PubMed1995

Determination of epidermal proliferative activity in experimental mouse tail test by AgNOR analysis.

Nucleolar organizer regions are segments of DNA coding ribosomal genes, which can be histologically detected by silver technique as so-called AgNORs. The estimation of AgNOR number and AgNOR size are currently under investigation as markers of cellular proliferation activity. We therefore examined the epidermal AgNOR expression after topical application of different antiproliferative compounds using the mouse tail test. The epidermis of 0.025% fluocinolone acetonide-treated mouse tails had the lowest AgNOR expression. Pretreatment with 0.2% Anthralin, 1% propyl gallate and 2% 3,4-hexaalkylbenzoylacrylic acid, an experimental phospholipase-A2 inhibitor, also revealed significant inhibition effects of epidermal AgNOR expression. Native and petrolatum-treated epidermis as control showed the highest AgNOR expression. The AgNOR results in basal cells proved to be more informative than these in the stratum spinosum, the best parameter was the AgNOR number. The obtained results were closely related to the values of the corresponding studies of PCNA expression. The AgNOR method seems to be useful for estimation of antiproliferative efficiency of pharmacological substances. This technique is simple in handling and can be applied using paraffin-embedded tissue sections.

Animals↗
PubMed1995

Dapsone inhibits the generation of 5-lipoxygenase products in human polymorphonuclear leukocytes.

Dapsone (4,4'-diaminodiphenylsulfone) is effective in treating inflammatory skin diseases. Several lines of evidence suggest that the anti-inflammatory properties of this sulfone are partially due to modulation of functions of polymorphonuclear leukocytes (PMN). The goal of the present investigation is therefore to ascertain possible inhibitory effects of dapsone upon human 5-lipoxygenase (5-LOX) pathway. PMN of healthy donors were pretreated with dapsone in different concentrations (1.6-100 microM) for 5 min following by adding Ca ionophore A 23187 (10 microM) and subsequent incubation for 10 min. Thereupon the eicosanoids were assessed by reversed-phase high-performance liquid chromatography (RP-HPLC). Dapsone exhibited dose-dependent inhibitory activity showing 50% inhibition at 15 microM for leukotriene B4 (LTB4) with 5 x 10(6) PMN. The IC50 (half maximum inhibition concentration) of dapsone for 5-hydroxyeicosatetraenoic acid (5-HETE) and omega-OH-LTB4 amounted to similar values (5-HETE: 9 microM; omega-OH-LTB4: 11 microM). The inhibition of the conversion of arachidonic acid to several eicosanoids mainly suggests an effect on the 5-LOX enzyme. The comparison of inhibition values between intact PMN and a cell-free system (by sonification) indicates an additional effect of dapsone upon enzymes other than 5-LOX. Since the concentrations used are comparable with therapeutic conditions, dapsone may exert part of its anti-inflammatory effect by prevention of the generation of 5-LOX metabolites.

Calcimycin↗
PubMed1995

Anti-inflammatory activity of croconazole, a broad-spectrum antimycotic agent, in the arachidonic acid-induced mouse ear swelling test.

Investigations on croconazole, a novel imidazole compound, suggested antiphlogistic properties in vitro. Hence, its anti-inflammatory capacity was tested in vivo using the arachidonic acid-induced mouse ear swelling test, which is a suitable model for screening inhibitors of the lipoxygenase and/or the cyclooxygenase. Topical application of croconazole (1%/0.01%) to the mouse ear induced a maximal inhibition of edema (inhibition: 39%/33%; p = 0.01) which was as strong as the reference nordihydroguaiaretic acid (inhibition: 38.9%; p = 0.01). These results justify further investigations on croconazole to study potential inhibitory effects on proinflammatory arachidonic acid metabolites.

Animals↗