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Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 55 records · Page 3Linked to original sources
PubMed2001

Cyclosporine in severe psoriasis. Results of a meta-analysis in 579 patients.

OBJECTIVE: A meta-analysis of 3 major German studies conducted between 1989 and 1994 with cyclosporine in severe psoriasis was performed to allow an integrated evaluation of the efficacy and tolerability of cyclosporine in this indication. DESIGN AND SETTING: All 3 studies were prospective, randomized, parallel group studies. The studies were conducted in 61 dermatologic centers in Germany. PATIENTS AND INTERVENTIONS: The studies involved 597 patients with severe plaque type psoriasis. Treatment consisted of cyclosporine (at a dosage of 1.25, 2.5 or 5 mg/kg/day), etretinate (at a mean daily dose of 0.53 mg/kg/day) or placebo in a total of 756 treatment cycles with a maximum duration of 12 weeks. MAIN OUTCOME MEASURES: The main outcome measures were the psoriasis area and severity index (PASI) and serum creatinine level. RESULTS: The meta-analysis revealed that cyclosporine given in a dosage of 2.5 and 5 mg/kg/day was significantly superior to etretinate. In addition cyclosporine 1.25 mg/kg/day proved to be significantly more effective than placebo. An increase in serum creatinine level that required intervention occurred in 3.4% of cyclosporine treatment cycles. CONCLUSION: Cyclosporine is highly effective and well tolerated in the short term treatment of severe psoriasis.

Adolescent↗
PubMed2001

Importance of human papillomaviruses for the development of skin cancer.

The frequent detection of HPV DNA in non-melanoma skin cancers was shown in several studies; however, the role of HPV in the development of these cancers remains speculative. We analyzed different skin tumors, normal skin, and hair follicles for HPV DNA using a PCR system designed to detect all HPV types known so far. HPV DNA was found in 93% of common warts, 69% of squamous cell carcinomas (SCC), 52% of basal cell carcinomas (BCC), 41% of actinic keratoses, 31% of extragenital Bowen's disease, 22% of keratoacanthomas, 16% of normal skin tissues and 47% of hair follicles. No individual HPV type predominated in any of the skin tumors. The number of HPV genomes in individual neoplasms (SCC and BCC) seems to be less than I per cancer cell. These results indicate that a direct role of HPV in skin cancerogenesis remains questionable. Possibly, mechanisms different from the activity of HPV oncoproteins in genital cancers are involved in skin neoplastic transformation.

Adolescent↗
PubMed2000

Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic.

The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human beta-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor alpha and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.

Amino Acid Sequence↗
PubMed2000

Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C.

Recent genome scans have established the presence of a major psoriasis-susceptibility locus in the human leukocyte antigen (HLA) complex on chromosome 6p21.3. To narrow the interval for candidate gene testing, we performed a linkage-disequilibrium analysis of 339 families, with the use of 62 physically mapped microsatellite markers spanning the major histocompatibility complex (MHC). As detected by use of the transmission/disequilibrium test (TDT), individual markers yielded significant linkage disequilibrium across most of the MHC. However, the strongest evidence for marker-trait disequilibrium was found in an approximately 300-kb region extending from the MICA gene to the corneodesmosin gene. Maximum-likelihood haplotypes were constructed across the entire MHC in the original sample and across a 1.2-Mb region of the central MHC in an expanded sample containing 139 additional families. Short (two- to five-marker) haplotypes were subjected to the TDT using a "moving-window" strategy that reduced the variability of TDT P values relative to the single-locus results. Furthermore, the expanded sample yielded a sharp peak of evidence for linkage disequilibrium that spanned approximately 170 kb and that was centered 100 kb telomeric to HLA-C. The 1.2-Mb interval was further dissected by means of recombinant ancestral haplotype analysis. This analysis identified risk haplotype 1 (RH1), which is a 60-kb fragment of ancestral haplotype 57.1, on all identifiable HLA risk haplotypes. One of these haplotypes exhibits significant linkage disequilibrium with psoriasis but does not carry Cw6, which is the HLA allele most strongly associated with the disease. These results demonstrate that RH1 is highly likely to carry the disease allele at PSORS1, and they exclude HLA-C and corneodesmosin with a high degree of confidence.

Alleles↗
PubMed2000

Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group.

OBJECTIVE: To investigate the safety and efficacy of using 0.1% tacrolimus ointment for long-term treatment of atopic dermatitis. DESIGN: Open-label, noncomparative study with 6 to 12 months of follow-up. SETTINGS: Outpatient departments in 30 study centers in 11 European countries. PATIENTS: We enrolled 316 patients aged 18 years and older with moderate to severe atopic dermatitis, 200 for 6 months and 116 for 12 months; 77.5% of patients completed the study. INTERVENTION: Twice-daily application of 0.1% tacrolimus ointment on all affected skin. Visits were scheduled on day 1; after 1, 2, and 4 weeks of treatment; and monthly thereafter. MAIN OUTCOME MEASURES: Safety assessments included monitoring of adverse events, clinical laboratory values, and tacrolimus blood concentrations. Efficacy end points included a combined score (modified Eczema Area and Severity Index) and an investigator's global assessment. RESULTS: Local irritation, adverse events such as burning sensation (47% of patients), pruritus (24% of patients), and erythema (12% of patients) were common but tended to occur only when initiating treatment. Laboratory values showed no marked changes over time. Systemic absorption was minimal, with the maximum tacrolimus blood concentration being less than 1 ng/mL in 76% of patients. All efficacy end points showed improvement. The mean (SD) modified Eczema Area and Severity Index score was 23.7 (12.6) at day 1, 13.5 (11.3) at week 1, 6.1 (9.2) at month 6, and 6.1 (8.1) at month 12. Marked or excellent improvement or clearance of disease was reported in 54%, 81%, and 86% of patients at week 1, month 6, and month 12, respectively. CONCLUSION: Up to 1 year of tacrolimus ointment use was safe and effective in patients with atopic dermatitis. Arch Dermatol. 2000;136:999-1006

Administration, Topical↗
PubMed2000

Patients with bullous pemphigoid and linear IgA disease show a dual IgA and IgG autoimmune response to BP180.

Bullous pemphigoid (BP) and linear IgA disease (LAD) are autoimmune subepidermal blistering skin diseases associated with autoantibodies against the transmembrane hemidesmosomal protein BP180/type XVII collagen. It has been demonstrated previously that BP is characterized predominantly by IgG autoantibodies, while autoantibodies in LAD mainly belong to the IgA isotype. The aim of the present study was to investigate the hypothesis that there is a significant overlap in the autoantibody isotype profiles associated with these two diseases. Several new recombinant forms of BP180 were generated in the baculovirus expression system, including the full-length protein. IgG autoantibodies to BP 180 were detectable in 39 of 40 (98%) of BP sera; interestingly, 88% of BP sera also contained IgA anti-BP180 autoantibodies. Similarly, anti-BP180 reactivity in LAD sera (n=22) was also attributed to both an IgA (68%) and an IgG (76%) autoantibody response. IgA and IgG autoantibodies to the intracellular portion of BP180 were found in 14% and 28% of BP sera, respectively, and in 8% of LAD sera (same percentage for both isotypes). Our findings clearly demonstrate that both BP and LAD patients have a dual IgA and IgG autoimmune response to BP180 which is directed not only to the ectodomain, but also to the intracellular portion of this protein.

Adult↗
PubMed2000

[Treatment of scabies with special consideration of the approach in infancy, pregnancy and while nursing].

Infestation of human skin with scabies mites remains an persistent problem in daily dermatological practice. There are several therapeutic regiments against scabies which have been proven effective and without major side effects. Because of known neurotoxicity of lindane as well as intoxication/problems following systemic absorption of benzyl alcohol (the metabolite of benzyl benzoate), these two compounds have to be considered with caution in early childhood scabies as well as during pregnancy and nursing. The pharmacology and spectrum of clinical side effects of the approved anti-scabies preparations (lindane, benzyl benzoate, crotamiton) as well as permethrin (not available in Germany) are reviewed.

Breast Feeding↗
PubMed2000

Detection of human papillomavirus and response to topical 5% imiquimod in a case of stucco keratosis.

Stucco keratosis is a skin disorder with papular warty lesions that usually appear on the lower limbs in elderly people. The aetiology, pathogenesis and treatment is still a matter of debate. We report a 75-year-old non-immunosuppressed man with extensive lesions all over his body, which had not responded to curettage or electrodesiccation. To determine the possible role of human papillomavirus (HPV) in stucco keratosis, we used nested polymerase chain reaction (PCR) to identify HPV DNA in the lesions. To include a broad range of both cutaneous and mucosal HPV types, PCR was performed with two sets of degenerate primers. Using this approach we detected HPV types 9, 16, 23b, DL322 and a variant of HPV type 37 in multiple stucco keratoses. Imiquimod (5% cream), a new compound that modifies the immune response by stimulating production of cytokines, applied overnight, three times a week for 5 weeks, resulted in resolution of all treated lesions.

Aged↗
PubMed2000

[Surgical and adjuvant drug therapy in head and neck cutaneous melanoma].

The rapid incidence rise of cutaneous melanoma resulted in an increasing interest in this particular tumor. During the last years public prevention campaigns enlarged the awareness of melanoma, subsequently as a direct effect the mean tumor thickness of melanoma, the most predictable prognostic factor, decreased. Moreover, the biology of melanoma initiation and metastasis has been studied extensively with special interest in molecular biology. Controlled clinical studies answered several critical questions in respect to the standard care of surgery in melanoma. Yet, the guidelines for the surgical treatment of head and neck melanoma are in accordance to that of other localisations with reduced safety margins around the primary tumor. Elective (prophylactic) lymph node dissection (ELND) of regional lymph nodes is no more considered as a standard tool. Moreover, ELND has been given up by most melanoma centers, since it is known that prospective-randomized trials were not able to demonstrate an increase of overall survival for patients with ELND compared with untreated patients. Instead of this potentially aggressive treatment modality the examination of the first draining regional lymph node, sentinel node biopsy (SNB), has been introduced some years ago. Recently, a large clinical trial demonstrated that the SNB status reflects the most valuable prognostic factor for primary melanoma known so far. First studies in head and neck melanoma figured out that this technique is more complex in this special localisation, but produced comparable results. Systemic adjuvant (prophylactic) therapy of high-risk melanoma should preferentially be applied within controlled clinical trials. Most attractive candidates for an effective treatment are interferons. Several studies ruled out that interferon alpha-treated melanoma patients demonstrate an extended disease-free survival. Adjuvant chemotherapy has not shown a clinically relevant benefit. Thus, patients should preferentially be treated within controlled clinical trials.

Antineoplastic Agents↗
PubMed2000

Frequency and spectrum of HPV types detected in cutaneous squamous-cell carcinomas depend on the HPV detection system: a comparison of four PCR assays.

BACKGROUND: The association of human papillomavirus (HPV) with cutaneous squamous-cell carcinomas (SCCs) has been described recently, but the frequency and spectrum of HPV types identified differed substantially in distinct studies. OBJECTIVE: Comparison of different PCR assays with respect to sensitivity and range of HPV types detected. METHOD: Cutaneous SCC were analyzed for HPV DNA using both consensus PCR assays with degenerate primers and PCR assays with nondegenerate primers derived from HPV types 5 and 8. RESULTS: HPV DNA was found in 50% of SCC specimens using degenerate primers. The rate of HPV-DNA-positive specimens increased to 69% when PCR assays with nondegenerate primers were applied in addition. The spectrum of HPV types detected with each of the PCR assays differed considerably. CONCLUSIONS: The frequency and spectrum of HPV types detected in cutaneous SCC strongly depends on the HPV detection system used and urges the need for standardization of HPV detection and typing in skin lesions in order to characterize HPV types predominating in distinct tumors.

Aged↗