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Biomedical subjects

H Degreef

Publications and source records attributed to H Degreef.

At least 37 records · Page 2Linked to original sources

Reactions to corticosteroids: some new aspects regarding cross-sensitivity.

Patch test results obtained with corticosteroid allergic patients tested with a large corticosteroid series validated the earlier classification of corticosteroid molecules in four groups of cross-reacting molecules: i.e., group A (hydrocortisone type), group B (acetonides), group C (betamethasone type-non esterified) and group D (esters). The latter group can now be subclassified into 2 groups, i.e., group D1 (halogenated and with C16 substitution) and group D2 (the "labile" prodrug esters without the latter characteristics).

Adrenal Cortex Hormones↗

Treatment of acne vulgaris and prevention of acne scarring: canadian consensus guidelines.

Acne affects approximately 95% of the population at some point during their lifetime.1 This common disorder can range from mild to severe forms, cause sometimes extensive scarring, and can last well into the fourth and fifth decades. Effective therapeutic agents are available to both treat acne and prevent ongoing disease. Despite this, dermatologists frequently see patients with significant acne scarring because many patients delay seeking medical attention for acne and many practitioners procrastinate over using effective antiscarring options. In patients who already demonstrate scarring, repeated courses of antibiotics only result in recurring acne and additional scarring. This, in turn, exacerbates the despair and other adverse psychosocial effects of the disease. There are a variety of agents and devices to help acne patients with scarring. However, successful treatment cannot be guaranteed, and in most cases residual scarring will be evident. Thus, the most effective way of managing acne scarring is to prevent its occurrence in the first place. Although we currently have a number of effective antiacne agents to control the disease, such as antibiotics and hormonal agents, isotretinoina is the only agent that has been shown to induce long-term drug-free remission and curative potential.

Acne Vulgaris↗

Randomized double-blind comparison of short-term itraconazole and terbinafine therapy for toenail onychomycosis.

Previous studies evaluating short-term itraconazole and terbinafine therapy for onychomycosis have varied in protocol and size; this double-blind study enabled a large-scale, standardized, direct comparison. Patients with toenail onychomycosis were randomized to itraconazole 200 mg daily (n = 146) or terbinafine 250 mg daily (n = 146) for 12 weeks, with a 36-week follow-up. Mycological cure rates at the follow-up end-point were significantly equivalent (61% with itraconazole vs. 67% with terbinafine). A similar proportion of patients in each group experienced adverse events during treatment (itraconazole, 22%; terbinafine, 23%). More patients receiving terbinafine stopped treatment permanently because of treatment-related adverse events (8% vs. 1%).

Abdominal Pain↗

Cyclosporin in atopic dermatitis: review of the literature and outline of a Belgian consensus.

This paper reflects the consensus reached among Belgian professors of dermatology on the place of cyclosporin (CsA) in the treatment of atopic dermatitis (AD). Existing therapeutic modalities and ways to evaluate efficacy of treatment are reviewed briefly. Based on data from the literature and personal experience, guidelines for the use of CsA in AD are proposed. CsA can be prescribed in recalcitrant cases of AD on a short-term basis, both in adults and children. Long-term treatment, up to 1 year, should be considered only in exceptional cases that cannot be controlled by short-time therapy. Contraindications, drug interactions and necessary controls during treatment are also discussed.

Cyclosporine↗

Panniculitis caused by acinous pancreatic carcinoma.

Subcutaneous fat necrosis is a form of panniculitis associated with pancreatitis or pancreatic carcinoma. The massive release in the bloodstream of lipolytic enzymes such as lipase, amylase and trypsin causes these lesions. As pancreatic disease is often asymptomatic, extensive investigations are mandatory in the presence of panniculitic lesions to search for an underlying disease.

Carcinoma, Acinar Cell↗

The use of itraconazole to treat cutaneous fungal infections in children.

BACKGROUND: Cutaneous mycoses such as tinea capitis, onychomycosis and some cases of tinea corporis/cruris, and tinea pedis/manus require oral antifungal therapy. There is relatively limited data regarding the use of the newer oral antifungal agents, e.g. itraconazole, in the treatment of these mycoses in children. OBJECTIVE: We wished to determine the efficacy and safety of itraconazole continuous therapy in the management of cutaneous fungal infections in children. METHODS: Children with cutaneous mycoses were treated with itraconazole in an open-label manner in 4 studies. For tinea capitis, the treatment regimens using itraconazole continuous therapy were: study 1, 3 mg/kg/day for 4 or 8 weeks; study 2, 5 mg/kg/day for 6 weeks, and study 3, 5 mg/kg/ day for 4 weeks. In a different trial, study 4, itraconazole continuous therapy 5 mg/kg/day was used to treat toenail onychomycosis (duration: 12 weeks), tinea corporis/ cruris (duration: 1 week) and tinea pedis/manus (duration: 2 weeks). RESULTS: The efficacy rates at follow-up 12 weeks from the start of therapy in children with tinea capitis treated using the itraconazole continuous regimen were: clinical cure (CC) and mycological cure (MC) in study 1 (n = 10, Trichophyton violaceum all patients), CC 50%, MC 86%; in study 2 (n = 35, Microsporum canis 22 patients, Trichophyton sp. 12 patients), CC 82.8%, MC 80%, and in study 3 (n = 16, M. canis 11 patients, Trichophyton sp. 5 patients), (CC 66.7%, MC 78.5%. Itraconazole was also effective in the treatment of dermatomycoses in 24 children (study 4). The CC and MC rates at the follow-up 8 weeks from the start of therapy in children with dermatomycoses and 12 months in children treated for onychomycosis were: onychomycosis (n = 1, T. rubrum), CC 100%, MC 100%; tinea corporis (n = 12, M. canis 10 patients), CC 100%, MC 90%; tinea cruris (n = 3, Trichophyton sp. 2 patients), CC 100%, MC 100%; tinea manus (n = 1, T. rubrum), CC 100%, MC 100%, and tinea pedis (n = 7, T. rubrum), CC 100%, MC 100%). Adverse effects consisted of a cutaneous eruption in 1 (1.2%) of the 85 children, with mild, transient, asymptomatic elevation of liver function tests (less than twice the upper limit of normal) in 2 (3.4%) of 58 children in whom monitoring was performed. CONCLUSIONS: Itraconazole is effective and safe in the treatment of tinea capitis and other cutaneous fungal infections in children.

Antifungal Agents↗

Onychomycosis: predisposed populations and some predictors of suboptimal response to oral antifungal agents.

The population groups predisposed to onychomycosis and factors associated with a poor response to antifungal therapy may be subdivided into (a) genetic, (b) environmental, (c) systemic conditions, (d) local nail characteristics, and (e) other miscellaneous items. By paying attention to the scenarios that may lead to a suboptimal response to the therapy and a higher probability of relapse of the onychomycosis, it may be possible to improve the overall cost-effectiveness of treatments for onychomycosis. Besides attempting to achieve a cure when treating onychomycosis it is important to take steps to prevent reinfection with fungal organisms.

Antifungal Agents↗

New Corticosteroids.

Corticosteroids have dominated the class of anti-inflammatory agents for the past 50 years. In the last ten years, seven new corticosteroids have been developed for topical use. Characteristics common to these several chemically different corticosteroids are their class III, or high potency (USP) designation and their improved safety profile. Allergic contact dermatitis is an unexpected adverse effect that is caused by some of them, in particular budesonide and, to a somewhat lesser degree, the labile "prodrug" corticosteroids, such as prednicarbate and prednisone acepontate.

Journal Article↗

Ultraviolet B suppresses vitamin D receptor gene expression in keratinocytes.

Keratinocytes not only produce vitamin D3 in response to ultraviolet B light (UVB) and convert 25-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D) but also possess the vitamin D receptor (VDR) and respond to 1,25(OH)2D. We characterized the regulation of the expression of the VDR gene in primary human keratinocytes following UVB irradiation. We report a marked dose-dependent down-regulation of the VDR mRNA and protein within a few hours after irradiation. This occurs independently of de novo protein synthesis and is not due to a change in the half-life of the VDR mRNA. Interestingly, treatment of the cells with sodium salicylate, caffeic acid phenethyl ester and tosylphenylchloromethylketone inhibited this down-regulation. Our results strongly suggest the existence of a feedback mechanism in that UVB initiates vitamin D synthesis in keratinocytes and at the same time limits VDR abundance. They also provide a rational explanation for the reported lack of any additive effect between 1,25(OH)2D and UVB phototherapy in the treatment of psoriasis.

Caffeic Acids↗

Pharmacological treatment of wounds.

Systemic treatment of patients with wounds can be directed at several physiological aspects of healing during the consecutive phases of tissue repair. Many approaches to pharmacological treatment have been tested in vitro, in animal experiments, or in clinical studies. Investigators and clinicians focus on treating underlying metabolic, infectious, inflammatory, or hemorrheological diseases and their complications. Drug treatment is often adjuvant or complementary to other measures such as compression, surgical intervention, reconstruction, or reopening procedures. This compounding fact can render interpretation of the results more difficult. As systemic treatment is not always without side-effects; local wound management is an option to consider. Topically applied growth factors certainly have the potential to influence the healing process. An indirect way of providing growth factors to wounds and chronic ulcers can be achieved by the application of grafts, cultured keratinocytes, and skin substitutes. Modulation of angiogenesis during wound healing is a recent target for research and treatment. Future reviews probably also will include genetic engineering methods for influencing wound healing.

Anti-Inflammatory Agents↗

Anchorage-dependent expression of the vitamin D receptor in normal human keratinocytes.

Although the nuclear vitamin D receptor (VDR) is involved in the control of keratinocyte proliferation and differentiation by its ligand 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], its role in epidermal physiology remains poorly understood. Because VDR abundance reflects cellular responsiveness to 1,25(OH)2D3, we investigated VDR expression in cultured human keratinocytes and identified cell anchorage and cytoskeletal integrity as essential requirements for the maintenance of VDR levels. Suspension culture rapidly suppressed VDR expression and 1,25(OH)2D3 responsiveness (as estimated by induction of 24-hydroxylase mRNA), due to decreased transcription of the VDR gene. Concomitantly, overt growth arrest with p21WAF1 induction and cyclin D1 and c-myc suppression occurred, together with induction of differentiation markers and retinoid X receptor alpha, the heterodimeric partner for VDR. Reattachment of suspended keratinocytes to fibronectin led to a rapid restoration of VDR expression, which could be blocked by RGD peptides or a blocking anti-beta1 integrin antibody. VDR expression was also reduced by disruption of the actin cytoskeleton with cytochalasin D. Malignant keratinocytes (SCC12B2 and A431), characterized by, anchorage-independent growth, displayed a profound resistance to suspension-induced suppression of VDR, cyclin D1, and c-myc. Taken together, our results associate VDR expression [and 1,25(OH)2D3 responsiveness] with cell adhesion and an organized cytoskeleton, which are also required for cell growth of primary cells.

Actins↗

Hypomelanosis of Ito.

We report two patients with hypomelanosis of Ito, one whose afflictions were limited to the pigmentary skin abnormalities and another with systemic involvement of the neurological and gastrointestinal system. These case reports give support to the importance of establishing hypomelanosis of Ito as occurring with or without systemic involvement.

Adult↗

Early ultraviolet B-induced G1 arrest and suppression of the malignant phenotype by wild-type p53 in human squamous cell carcinoma cells.

Wild-type p53 (wt-p53) negatively controls cell cycle progression after cellular stress mediating either a temporary growth arrest or apoptosis, depending on the cell type and nature of the cellular stress. The aberrant proliferation which is characteristic of tumor cells may be suppressed by exogenous wt-p53 and appears to depend strongly on the level of reexpression. We performed retroviral-mediated gene transfer of wt-p53 into a human squamous cell carcinoma cell line from the head and neck region (A253 cell line) lacking endogenous p53. This allowed us to study the effect of wt-p53 on the malignant phenotype and on the response to the DNA damaging agent ultraviolet B (UVB). Restoration of wt-p53 in malignant keratinocytes suppressed tumorigenicity in nude mice although p53-reconstituted cells eventually formed small tumors with long latency. Cells derived from these tumors showed reduced expression of wt-p53. Exogenous wt-p53 increased baseline mRNA expression of the small proline rich proteins 1 and 2, consistent with a prodifferentiating effect. After exposure to a biological UVB dose, only p53-positive A253 cells underwent an early and transient G1 arrest. Both p53-positive and -negative A253 cells displayed a late G2 delay/arrest. We conclude that reexpression of wt-p53 in squamous cell carcinoma A253 cells decreases their malignant phenotype and reestablishes a G1 checkpoint after UVB.

Animals↗

Suppression of UVB-induced c-fos and c-jun expression in human keratinocytes by N-acetylcysteine.

Irradiation of human keratinocytes with UVB results in the early induction of proto-oncogenes c-fos and c-jun, members of the AP-1 protein family of transcription factors. To explore a possible involvement of oxidant stress in triggering this UVB-induced early gene response, we investigated in human keratinocytes the effect of N-acetylcysteine (NAC), a thiocompound with antioxidant activities, on UVB-induced c-fos, and c-jun expression. Normal human keratinocytes were irradiated with either 16 or 32 mJ cm-2 UVB, which induces a temporary inhibition of DNA synthesis, without compromising cell survival. Preincubation with 1 and 3 mM NAC suppressed c-jun and c-fos induction by UVB in a dose-dependent fashion. These applied concentrations of NAC were not toxic to the keratinocytes, as determined by Trypan Blue exclusion assay and completely suppressed c-jun and c-fos induction by the chemical cadmium chloride (oxidative stress). These results indicate that oxidative stress, at least in part, mediates the transcriptional activation of c-fos and c-jun in human keratinocytes after UVB irradiation.

Acetylcysteine↗

Retinoic acid modulates the anti-proliferative effect of 1,25-dihydroxyvitamin D3 in cultured human epidermal keratinocytes.

Both 1,25-dihydroxyvitamin D3 (VD) and retinoids have potent effects on keratinocyte proliferation. Parallelism in their action as steroid hormones, which involves interaction of their receptors, and in their therapeutic efficacy for hyper-proliferative skin diseases provides a rationale to investigate their combined action on proliferation in pre-confluent human epidermal keratinocyte cultures. As shown by [3H]thymidine incorporation, all-trans retinoic acid (atRA) at subpharmacologic concentrations and 9-cis retinoic acid (9cRA) diminished the anti-proliferative effect of VD. Pre-incubation of the cells with the retinoids clearly enhanced this effect. Cell-cycle analysis revealed G1 arrest upon VD treatment that was attenuated by retinoic acid (RA). Moreover, Northern and Western blot analysis demonstrated that retinoic acid opposed VD-induced accumulation of transforming growth factor-beta1, p21WAF1, and p27KIP1. Finally, retinoic acid reduced VD-elicited hypophosphorylation of the retinoblastoma protein. AtRA at micromolar concentrations conversely potentiated most of the aforementioned VD-dependent actions. In addition, atRA and 9cRA (but not VD) caused a rapid, sustained reduction of RXR alpha protein. VD receptor protein was induced by VD regardless of the presence of RA. In conclusion, RA modulates VD-dependent effects at different levels of keratinocyte proliferation. This could have implications for the use of combinations of both drugs for skin diseases.

Calcitriol↗

Severe erosive stomatitis: association with immunological diseases?

We present 2 cases of severe erosive stomatitis. The first case involves the rare association of an extensive, erosive lichen planus with a Castleman's tumor. The second case involves the association of lichen planus pemphigoides with severe, obstructive lung disease (bronchiolitis obliterans). We believe that in both cases the conjunction of these conditions is not fortuitous but perhaps due to an underlying immune dysfunction. With patients presenting a severe, therapy-resistant, erosive stomatitis, one should be alerted to the possibility of immunological diseases and/or tumors.

Adult↗

Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita.

In this study, we report on a family with X-linked dyskeratosis congenita (DC). Linkage analysis with markers in the factor VIII gene at Xq28 yielded a LOD score of 2 at a recombination of 0. Clinical manifestations of DC, such as skin lesions following the Blaschko lines, were present in two obligate carrier females. Highly skewed X inactivation was observed in white blood cells, cultured skin fibroblasts, and buccal mucosa from female carriers of DC in this family. This suggests a critical role for the DC gene in bone marrow-cell and fibroblast-cell proliferation.

Adult↗