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Biomedical subjects

W Stolz

Publications and source records attributed to W Stolz.

At least 37 records · Page 2Linked to original sources
PubMed2001

Differences in efficacy between intention-to-treat and per-protocol analyses for patients with psoriasis vulgaris and atopic dermatitis: clinical and pharmacoeconomic implications.

BACKGROUND: Pharmacoeconomic outcome research is based on three criteria: (i) evaluation of objective therapeutic effects; (ii) quality of life; and (iii) treatment costs. Evaluation of therapeutic effect is mainly based on the results of clinical trials using objective clinical measures, e.g: Psoriasis Area and Severity Index (PASI) (score for psoriasis vulgaris) and the Severity Scoring of Atopic Dermatitis (SCORAD) (score for atopic dermatitis). In most studies, only results for a treatment-optimized subpopulation (patients treated according to the protocol) are presented in publications. The relevance of such data for daily routine therapy is doubtful. OBJECTIVES: Our purpose was to investigate the expected loss of effectiveness of switching from a clinical trial to daily routine therapy for the synchronous application of narrow-band ultraviolet (UV) B phototherapy (311 nm) and bathing in 10% Dead Sea salt solution (synchronous balneophototherapy) for patients with psoriasis vulgaris and atopic dermatitis. METHODS: We conducted a multicentre, uncontrolled observational study of outpatients. To achieve data for 'clinical trial' and 'daily routine' situations, two populations were compared: (i) all patients strictly treated according to the protocol (ATP) with no protocol deviations (data published in clinical trials), and (ii) all patients participating in the study who received active treatment at least once, despite treatment irregularities, non-compliance, early withdrawal or other protocol violations [intention-to-treat-population (ITT), model for 'daily routine']. RESULTS: A total of 2526 patients were included in the ITT analysis for psoriasis vulgaris (n = 487 for atopic dermatitis), of which 818 patients could be analysed according to protocol (n = 104 for atopic dermatitis). Striking differences in the therapeutic effect between both groups (ITT and ATP) were found using relative PASI and SCORAD score improvement: 11% (57% 'daily routine' vs. 68% in 'clinical trial') for psoriasis vulgaris and 16% (39% 'daily routine' vs. 55% 'clinical trial') for atopic dermatitis. The main reasons for excluding patients from the 'clinical trial' group were early study withdrawal in 29% (atopic dermatitis, 47%) of patients and fewer treatments per week than planned in the protocol in 24% (atopic dermatitis, 52%). CONCLUSIONS: Our data clearly indicate that for the prediction of the therapeutic effect for daily routine therapy the ITT data appear to be more relevant than the ATP results (i.e. those presented in clinical trials). Although these data are only a first step for evaluating the 'real' therapeutic effect of a treatment modality in daily routine, they seem to support the requirements for ITT analyses in efficacy studies and demonstrate the necessity of ITT data for pharmacoeconomic evaluation.

Adult↗
PubMed2001

Detection of differentially regulated genes in keratinocytes by cDNA array hybridization: Hsp27 and other novel players in response to artificial ultraviolet radiation.

cDNA array technology was used to identify novel genes participating in the ultraviolet response of cultured human keratinocytes. cDNA arrays representing more than 50,000 different cDNA clones were hybridized with complex probes generated by SMART-polymerase chain reaction amplification of 150 ng of total RNA extracted 24 h after ultraviolet irradiation. Fifty-one clones with differential hybridization signals were detected, representing 19 different sequences; 10 known genes (seven ultraviolet induced, three ultraviolet suppressed) and further nine expressed sequence tags of unknown genes. In seven of 10 genes the data from cDNA arrays probed with SMART-cDNA could be confirmed by northern blot analysis. The 27 kDa heat shock protein mRNA was induced. Keratins 6 and 17, markers for the hyperproliferative status of keratinocytes, were among the ultraviolet suppressed genes. The change of expression profile of keratins indicates a differentiation towards a phenotype of keratinocytes present in the suprabasal layers of the epidermis. These mechanisms may contribute to the ultraviolet protective function of the epidermis and to the anti-proliferative action of ultraviolet in the therapy of psoriasis. We also detected an induction of adenylyl cyclase associated protein and the suppression of G(s)alpha (a stimulating subunit of the trimeric membrane bound GTPase).

Blotting, Northern↗
PubMed2001

Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II.

Cyclooxygenase-II (Cox-II) overexpression is involved in the progression of various subtypes of cancer. We investigated the significance of Cox-II in the progression of malignant melanomas (MMs). Using immunohistology we determined that Cox-II is not expressed in 70 benign and malignant melanocytic tumours. Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were also analysed as controls: the BCCs were consistently Cox-II negative (n = 11), whereas the SCCs showed moderate to strong Cox-II expression in 53% (n = 17). Reverse transcription-polymerase chain reaction and Western blotting of MM cell lines and MM tissues confirmed the lack of Cox-II expression in MM. However, in vitro the Cox-inhibiting non-steroidal anti-inflammatory drug (NSAID) sulindac sulphide (SIS) was significantly more effective in inducing apoptosis than sulindac sulphone (SOS), a derivative with a negligible effect on Cox (P < 0.01). The SIS doses needed for the induction of apoptosis were not significantly different in MM cell lines versus a Cox-II-positive colon carcinoma cell line (HT29). Furthermore, add-back experiments with high doses of the prostaglandins PGE2 and PGF2beta, major Cox-II products, did not abrogate this effect. We conclude that Cox-II expression is not involved in the progression of MM, and NSAID-induced apoptosis in MM cell lines seems to follow pathways independent of Cox-II. Nevertheless, Cox-II inhibitors are still candidates for therapy, though they act via an unknown mechanism.

Adolescent↗
PubMed2001

Transient and partial effect of high-dose intravenous immunoglobulin in polyarteritis nodosa.

A 57-year-old male patient suffered from polyarteritis nodosa. He presented with articular pain, polyneuropathy, subcutaneous nodules and nodes on the lower legs. After several immunosuppressive agents (methotrexate, mycophenolate mofetil and prednisolone) had proven to be ineffective, 2 g intravenous immunoglobulin (IVIG) per kilogram body weight were administered within 2 days in combination with 10 mg prednisolone per day. Subsequently, 6 cycles of IVIG were applied in increasing intervals from 4 to 6 weeks resulting in a minimum dosage of 0.33 g/kg/week IVIG. The polyarteritis improved within a few days after the first IVIG application. The intensity of polyneuropathy and arthralgia of polyarteritis decreased during the period of IVIG treatment. Finally, a dose reduction of less than 0.25 g/kg/week IVIG resulted in recurring polyarteritis nodosa, which could not be controlled by further administration of IVIG. Therefore, our data indicate that: (1) IVIG is partially effective in cases of polyarteritis nodosa, but the therapeutic effect is only transient; (2) the success of treatment may be correlated with the dose of IVIG per body weight and week; (3) the efficacy/cost ratio of IVIG in polyarteritis nodosa appears to be low.

Dose-Response Relationship, Drug↗
PubMed2000

Bullous pemphigoid of childhood: autoantibodies target the same epitopes within the NC16A domain of BP180 as autoantibodies in bullous pemphigoid of adulthood.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the elderly that rarely occurs in children. Most adult BP serum samples react with epitopes within the NC16A domain of BP180, a glycoprotein of the cutaneous basement membrane zone. OBJECTIVES: To characterize the autoimmune response in childhood BP using recombinant forms of BP180 and to determine the subclass distribution of autoantibodies and their correlation with disease activity. OBSERVATIONS: Serum samples from 2 infants with BP, aged 4 and 5 months, reacted by immunoblot analysis with 4 epitopes clustered within the N-terminal 45 amino acids of the NC16A domain. The same 4 epitopes have previously been shown to be the target in adult BP. Childhood BP antibodies to BP180 NC16A belonged to IgG1, IgG2, IgG3, and IgG4 immunoglobulin subclasses. IgE reactivity was not detected. Serum levels of antibodies targeting BP180 NC16A paralleled disease activity as detected by enzyme-linked immunosorbent assay. CONCLUSIONS: The fine specificity of autoantibodies to BP180 is the same in BP of childhood and adulthood. Childhood BP is a true variant of BP.

Adult↗
PubMed2000

Improvement of early recognition of lentigo maligna using dermatoscopy.

BACKGROUND: The clinical differentiation between lentigo senilis/initial seborrheic keratosis and lentigo maligna on the face can be difficult. OBJECTIVE: Our purpose was to determine whether dermatoscopy (eg, skin surface microscopy at 10x magnification) can reliably differentiate between these entities. METHODS: Dermatoscopic slides of 87 consecutive patients presenting 37 malignant and 50 benign pigmented skin lesions on the face were analyzed with the use of 27 dermatoscopic criteria. RESULTS: Univariate analysis selected two criteria specific for lentigo maligna: asymmetric pigmented follicular openings and dark (brown or black) rhomboidal structures. Location-specific importance in relation to facial location was attributed to the color "slate-gray, " especially in combination with structures such as dots, globules, streaks, and homogeneous areas. Multivariate analysis (logistic regression model) revealed the 4 most important features to be asymmetric pigmented follicular openings, dark rhomboidal structures, slate-gray globules, and slate-gray dots with a sensitivity of 89% and a specificity of 96%. CONCLUSION: Three conclusions can be drawn from our study: With a set of 4 dermatoscopic features, early lentigo maligna can be detected with high accuracy; dermatoscopic features on the face differ from criteria used in other locations; and our progression growth model for lentigo maligna delineates the different steps of malignant growth in lentigo maligna.

Analysis of Variance↗
PubMed2000

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris.

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.

Adolescent↗
PubMed2000

Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin.

Diagnosing IgA pemphigus and distinguishing between its 2 subtypes, intraepidermal neutrophilic IgA dermatosis type and subcorneal pustular dermatosis type, is important because treatment of IgA pemphigus has to be different from treatment of other blistering autoimmune dermatoses. We present a patient with subcorneal pustular dermatosis type of IgA pemphigus who rapidly responded to systemic treatment with isotretinoin. Specific diagnosis was established by detecting IgA serum activity to desmocollin 1 by indirect immunofluorescence microscopy on unfixed COS7 cells transfected with desmocollin 1. No IgA or IgG serum reactivity was found to recombinant forms of desmogleins 1 and 3 by an antigen-specific enzyme-linked immunosorbent assay. The disease was not effectively controlled by conventional therapeutic regimens. Systemic treatment with isotretinoin 20 mg daily led to complete clearance of skin lesions within 3 weeks. Assaying IgA serum reactivity to desmocollin 1, desmoglein 1, and desmoglein 3 as a valuable method for establishing the diagnosis and differentiating the 2 subtypes of IgA pemphigus. Isotretinoin was an effective drug in the treatment of subcorneal pustular dermatosis type of IgA pemphigus in this patient.

Aged↗
PubMed2000

Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion.

It is widely assumed that, after ovulation, the human endometrium undergoes specific changes and becomes receptive to the implantation of embryo during the mid-secretory phase. When implantation does not take place, further changes occur which eventually result in the shedding of human endometrium. The present study was carried out to examine whether there are changes in the cytokine gene expression in human endometrium which are correlated with endometrial function in various phases of the menstrual cycle. The RNase protection assay was performed on carefully dated endometria from normal subjects to characterize the expression of cytokines which potentially contribute to endometrial function. These included: tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6, IL-8, leukaemia inhibitory factor (LIF), transforming growth factor beta1 (TGF-beta1), macrophage colony stimulating factor (MCSF or colony stimulating factor-1), and vascular endothelial growth factor (VEGF) mRNAs. A low level of expression of these cytokine mRNAs was found during the proliferative and early secretory phase. Expression of cytokine mRNA increased during the mid-secretory phase and rose to a peak in the late secretory phase. The level of cytokine mRNA expression during gestation was most akin to that observed during the mid-secretory phase. Individuals with habitual abortion presented with an abnormal expression of IL-1beta and IL-6 mRNA in endometrium, during the mid-secretory phase. Taken together, these findings are consistent with a progressive rise in the expression of cytokines in human endometrium during the secretory phase in natural cycles. Furthermore, the findings show that habitual abortion is associated with the abnormal expression of IL-1beta and IL-6 in the mid-secretory phase.

Abortion, Habitual↗
PubMed2000

Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.

We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.

Adolescent↗
PubMed2000

Teledermatology--the requirements of dermatologists in private practice.

Eighty-four dermatologists in private practice in Bavaria were surveyed by postal questionnaire. Of the 45 who responded (a 54% response rate), 96% used a computer in their private practice. Fifty-seven per cent of respondents owned systems with Pentium processors, while 23% were still using 386 or 486 processors. Most of them used the Windows 95, UNIX or Apple operating system. Of the respondents who had a modem, 74% used ISDN. There were few modems connected to the ordinary telephone network. Of all respondents, 56% used email regularly. Several possible teledermatology applications were proposed in the survey (i.e. teleconsultation, on-line/off-line videoconferencing, email attachments). Fifty-six per cent of respondents said that they would perform teleconsultations with dermatology clinics, 40% preferred a teleconsultation via telephone and computer, and 42% sending files via email. The survey demonstrated that a high proportion of dermatologists in private practice would use a teledermatology service.

Adult↗