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Biomedical subjects

A Kreuter

Publications and source records attributed to A Kreuter.

At least 19 recordsLinked to original sources
PubMed2006

Cytokine mRNA expression in basal cell carcinoma.

There is evidence that cytokines (CKs) play a significant role in the development and/or progression of skin cancer. The aim of the present study was to investigate the mRNA expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8 in biopsy specimens of basal cell carcinoma (BCC), and to compare the results with the mRNA levels of non-lesional skin of BCC patients and healthy subjects. Skin samples were obtained from 22 patients with BCC (lesional, non-lesional) and 25 healthy subjects (controls). Routine histology and real-time RT-PCR was performed. Histological examination revealed 12 nodular BCCs and 10 superficial BCCs. The mRNA levels of CKs observed in healthy controls did not significantly (P > 0.05) differ from non-lesional CK levels of BCCs patients. However, IL-6 and IL-8 levels of lesional skin were significantly (P < 0.05) higher than the CK levels observed in non-lesional skin and controls, respectively. mRNA expression of IL-6 and IL-8 showed a significant positive correlation (r = 0.51; P < 0.05). There was no significant (P > 0.05) difference between lesional mRNA levels of TNF-alpha and those levels observed in non-lesional skin and controls. The mRNA expression of CKs found in nodular and superficial BCCs did not significantly differ (P > 0.05). BCC is associated with a significant increase of IL-6 and IL-8 expression. We have shown for the first time that upregulation of IL-6 mRNA significantly correlates with IL-8 overexpresssion. In accordance with previous studies our data suggest a role for IL-6 and IL-8 in the development and/or progression of BCC, since mRNA expression of both CKs are significantly increased in tumour tissue.

Aged↗
PubMed2006

Pattern of mRNA expression of beta-defensins in basal cell carcinoma.

BACKGROUND: Although the human beta-defensins hBDs today seem to have diverse functional activities in innate antimicrobial immunity, a few reports also indicated an altered expression of these antimicrobial peptides (AMPs) in tissues of cancers such as oral squamous cell carcinoma. The present work was aimed on the study of hBD gene expression in basal cell carcinoma (BCC) which is the most common cancer in humans. METHODS: Twenty-two non-ulcerated BCCs (12 nodular type, 10 superficial type) have been analysed for the presence of hBD (1-3) mRNA by quantitative real-time RT-PCR. As controls, non-lesional skin specimens of BCC patients as well as samples of healthy subjects were assessed by RT-PCR. RESULTS: hBD-1 levels in healthy controls and non-lesional skin of BCC patients were significantly (P < 0.05) higher than the levels observed in tumour tissue. Moreover, BCCs showed significantly (P < 0.05) increased mRNA expression of hBD-2 as compared to controls. There was no significant (P > 0.05) difference between lesional mRNA levels for hBD-3 and those levels observed in controls. The mRNA expression of hBDs (1-3) found in nodular and superficial BCCs did not significantly (P > 0.05) differ. CONCLUSION: The gene expression patterns of hBD-1 and hBD-2 are for the first time shown to be significantly altered in non-ulcerated BCCs as compared to intra-individual and inter-individual controls, respectively. The present findings may indicate that beside the antimicrobial activity of AMPs, hBDs may also play a role in the pathogenesis of BCC. However, functional and immunohistological studies investigating hBDs in patients with BCC are needed to confirm our data.

Adult↗
PubMed2006

Treatment of condylomata acuminata with pegylated interferon alfa-2b in HIV-infected patients.

BACKGROUND: Interferon in a variety of topical, interlesional, and parenteral preparations has been used for condylomata acuminata (CA) in HIV negative patients. - STUDY GOALS: This open trial was initiated to determine the safety and efficacy of a new formulation of interferon, pegylated interferon-alpha2b (PEG-IFN, PegIntron in the treatment of recalcitrant CA in patients with HIV infection. - STUDY DESIGN: 22 HIV-1 infected patients in virologic steady state with clinically demonstrable anogenital CA were enrolled in this study (treatment group, n=12; control group, n=10). Patients in the treatment group received 80 microg PEG-IFN s.c. once a week for 24 weeks. Follow-up period was 6 month. The effects were assessed by a clinical scoring system (complete response; major response; minor response; stable disease; progression of disease). - RESULTS: 2 patients did not finish the study because of side effects. PEG-IFN was well accepted and completed by ten patients. Four patients revealed complete response, four patients had major response and two had minor response after PEG-IFN. In the control group, all patients showed progression of CA during the 24 weeks of this study (p < 0.001). 7/10 patients of the treatment group and 8/10 patients of the control received HAART. - While the differences of CD4 cell counts between treatment group and control group were not significant (increase of the mean CD4 cell count in the treatment group was 31.5 (75.33 without patient 1 with leucopenia under ribavirine), in the control group 69.75 CD4 cells), the HIV RNA decline in the PEG-IFN group was impressive (0.74 log subset10). Biological side effects of PEG-IFN treatment included flu-like symptoms, fatigue, local reaction, leucopenia, and increase of AST. This result makes an educated guess that PEG-IFN enhances the benefit of HAART. - CONCLUSION: PEG-IFN is an effective and safe therapy option in HIV infected individuals with CA with concomitant positive effects on the suppression of HIV-1 replication and CD4 cell count. It might be considered as an alternative in patients that have failed to standard therapies of CA and - at the same time -could improve the benefit of HAART to a great extent. This last hypothesis needs further research.

Adult↗
PubMed2006

[Human papilloma virus-induced disease in HIV-positive patients].

Since the introduction of highly active antiretroviral therapy (HAART), opportunistic infections by bacteria and fungi have been reduced in human immunodeficiency virus (HIV)-positive patients. However, diseases caused by human papilloma virus (HPV) have become more frequent despite HAART. There is an increased incidence of anal and cervical carcinomas, their precancerous lesions such as anal/cervical intraepithelial neoplasia, and condylomas and oral warts. In order to prevent anal carcinomas, HIV-positive patients should receive proctoscopic examinations regularly. The examination should include anoscopy and smears for cytology and HPV polymerase chain reaction.

AIDS-Related Opportunistic Infections↗
PubMed2006

Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma.

BACKGROUND: In previous studies, distinct immunological abnormalities have been reported in localized scleroderma (LS). Several pro-inflammatory cytokines have been demonstrated at increased levels in sera of patients with LS in parallel with disease activity. Human beta-defensins (hBDs) are peptides with antimicrobial activity, but have been also shown to be implicated in tissue injury, scarring and wound healing. hBD expression in LS, a condition resembling pathological scarring due to excessive stimulation of matrix synthesis and fibroblast activation, has so far not been investigated. Ultraviolet (UV) A1 phototherapy, the most recent advance in the treatment of LS, targets T-cell dermal inflammatory infiltrates via induction of various cytokines and soluble factors besides well-known effects on collagen metabolism. OBJECTIVES: We sought to investigate the effects of UVA1 on the expression and modulation of hBDs and several pro-inflammatory cytokines in LS. METHODS: UVA1 phototherapy was performed five times weekly for 8 weeks resulting in a total of 40 treatment sessions (single dose 20 J cm2, cumulative dose 800 J cm2). hBD-1, hBD-2 and hBD-3 mRNA as well as tumour necrosis factor-alpha, transforming growth factor-beta, interleukin (IL) -2, IL-4, IL-6 and IL-8 mRNA expression were determined by quantitative real-time reverse transcription-polymerase chain reaction in lesional and unaffected skin of patients with LS. RESULTS: Skin status markedly improved in all 14 patients, resulting in a significant reduction of the clinical score from baseline to the end of treatment. hBD-1, hBD-2 and hBD-3 mRNA levels were higher in lesional skin compared with unaffected skin and skin from healthy volunteers. Following UVA1 phototherapy, hBD-1 mRNA decreased in lesional, but not in unaffected skin. hBD-3 mRNA levels significantly decreased after UVA1 in lesional skin, whereas an increase of hBD-3 was observed in unaffected skin. IL-6 and IL-8 mRNA levels were significantly elevated in lesional skin and significantly decreased after UVA1 irradiation, whereas mRNA for both cytokines remained unchanged in irradiated unaffected skin. The decrease of hBD-1, hBD-3, IL-6 and IL-8 mRNA paralleled the extent of disease and response to UVA1 phototherapy. CONCLUSIONS: hBDs and IL-6 and IL-8, cytokines with pivotal importance in sclerotic skin diseases, are downregulated by UVA1 in the lesional skin of patients with LS. Their pathogenetic relevance with respect to clinical improvement needs further investigation.

Adult↗
PubMed2006

Changes of antimicrobial peptide mRNA expression in atopic eczema following phototherapy.

BACKGROUND: The epidermal expression of antimicrobial peptides (AMPs) such as human beta-defensin (hBD)-2 and cathelicidin LL-37 is downregulated in atopic eczema (AE) as compared with psoriasis. Hence, AMPs may represent important cofactors in the pathogenesis of AE. OBJECTIVES: In the present pilot study we aimed to investigate whether the cutaneous mRNA expression of AMPs is altered in patients with AE following narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: We studied 12 patients diagnosed with extrinsic AE who underwent a 6-week course of NB-UVB. Skin biopsies were taken from healthy controls (n = 12) and patients with AE at baseline and after the last NB-UVB irradiation. Quantitative real-time reverse transcription-polymerase chain reaction was performed for hBD-1, hBD-2, hBD-3 and LL-37. RESULTS: A significant (P < 0.05) reduction in the clinical score was observed after treatment with NB-UVB. As compared with controls, patients with AE showed a significantly lower hBD-1 mRNA expression and significantly higher hBD-2 levels (P < 0.05). Following NB-UVB treatment of patients with AE we observed a significant increase of hBD-1 expression as well a significant decrease of hBD-2 (P < 0.05). Levels of hBD-3 and LL-37 did not significantly differ between the groups (P > 0.05). CONCLUSIONS: The pattern of mRNA expression of constitutive (hBD-1) as well as inducible (hBD-2) AMPs seems to be altered in AE as compared with healthy controls. The resolution of AE lesions following phototherapy is accompanied by significant changes in mRNA expression of hBDs, indicating that AMPs may play a role in the pathogenesis of AE.

Adult↗
PubMed2006

A randomised controlled trial on photo(chemo)therapy of subacute prurigo.

BACKGROUND: Psoralen ultraviolet A (PUVA) is the standard photo(chemo)therapeutic regimen for patients suffering from subacute prurigo (SP). HYPOTHESIS: Regarding efficacy, bath PUVA is not superior to medium-dose ultraviolet-A1 (MD-UVA1) and narrowband ultraviolet-B (NB-UVB), which may be considered the new photo(chemo)therapeutic options for SP. METHODS: We performed a prospective randomised, controlled, three-arm photo(chemo)therapeutic study. Patients suffering from histopathologically proven SP with a clinical score (PIP score; papules, infiltration and pruritus) of at least 5 points were enrolled into the study. Treatment with bath PUVA was performed 4 times weekly and MD-UVA1 and NB-UVB 5 times weekly. Photo(chemo)therapy was administered over a 4-week period. Outcome measure was the severity of SP investigated by means of the PIP score after 4 weeks of therapy. RESULTS: In total, 33 patients with SP were randomly allocated to photo(chemo)therapy. Bath PUVA (n = 9), MD-UVA1 (n = 11) and NB-UVB (n = 13) resulted in a significant reduction of the baseline PIP score as assessed on the basis of intention-to-treat (ITT) analysis (P = 0.003). However, ITT analysis revealed significantly higher PIP score reduction in patients who were treated with bath PUVA and MD-UVA1 compared with NB-UVB (P < 0.01, 95% CI 1.1-3.63 and P < 0.05, 95% CI 0.42-2.70, respectively). CONCLUSIONS: Photo(chemo)therapy, including bath PUVA, MD-UVA1 and NB-UVB, appears to be an effective and safe treatment option for patients suffering from SP. UVA1 and particularly PUVA seem superior to NB-UVB in the management of SP.

Adult↗
PubMed2006

Epidermal thickness assessed by optical coherence tomography and routine histology: preliminary results of method comparison.

BACKGROUND: Optical coherence tomography (OCT) is a promising non-invasive imaging technique for studying the epidermis and upper dermis in vivo. As proposed previously by Welzel et al. (J Am Acad Dermatol 1997; 37: 958-963), distance measurements between the entrance peak and the second peak of the A-scan seem to correspond to epidermal thickness (ET). However, there is a lack of systematic studies comparing OCT with histology. METHODS: Sixteen healthy subjects were included in this pilot study. OCT assessments were conducted on the upper back. To determine ET by OCT, the distance between the entrance peak and the second peak of the A-scan was calculated (ET-OCT). After OCT measurement a 4 mm punch biopsy was taken on each subject from the same site previously assessed. The maximum thickness of the epidermis (ET-Histo) was determined microscopically using routine histological slices (formalin-paraffin technique, haematoxylin-eosin staining). Correlation and agreement between the two methods were assessed by means of the Pearson correlation procedure and Bland-Altman plots, respectively. RESULTS: ET-Histo was 79.4 +/- 21.9 microm, including a stratum corneum thickness of 20 +/- 12.1 microm. OCT measurements resulted in an ET of 106 +/- 15.4 microm. No correlation between ET-Histo and ET-OCT was observed (r = 0.29, P = 0.27). There was a considerable lack of agreement between histology and OCT measurements as expressed in a high bias of 26.63 microm [95% confidence interval (CI) 14.49-38.77]. Furthermore, the lower 95% limits of agreement were -18.03 microm (95% CI -37.11 to 1.05) and the upper 95% limits of agreement were 71.28 microm (95% CI 52.2-90.36) indicating that ET-OCT may be 71.28 microm above or 18.03 microm below ET-Histo. CONCLUSIONS: Our preliminary data suggest that the above-described OCT algorithm is probably not a valid measure for the evaluation of ET. The second peak of the A-scan seems not to correspond to the dermo-epidermal junction zone, but rather to fibrous structures in the upper dermis. Nevertheless, further systematic comparison studies between OCT and histology are warranted, using different OCT algorithms for ET determination and cryopreparation, which has a higher reliability than the formalin-paraffin technique.

Adult↗
PubMed2005

Dilated cardiomyopathy in two adult human immunodeficiency positive (HIV+) patients possibly related to highly active antiretroviral therapy (HAART).

Human immunodeficiency virus (HIV) and acute immunodeficiency syndrome are known to be associated with cardiac involvement. In this respect, a relation between HIV and dilated cardiomyopathy has been described. Additionally, highly active antiretroviral therapy (HAART) may independently contribute to cardiac impairment. We here report two cases of severely reduced left ventricular function detected in the context of a recent standardized screening of 132 HIV+ individuals of the German heart failure network. Both patients presented in a poor overall condition and progressive exercise-induced dyspnea accompanied by edema or angina pectoris, respectively. Subsequent examinations revealed left bundle-branch blockade, ventricular arrhythmia, elevated serum BNP-levels as well as pathologic transthoracic echocardiography, left ventricular angiography, electron beam tomography and cardiac magnetic resonance imaging without significant coronary stenoses or immunohistological signs of an ongoing or prior myocarditis. Clinical signs of progressive chronic heart failure developed slowly but constantly following initiation of the HAART regimen. Patients were treated by an implantation of a biventricular implantable cardioverter defibrillator beside conventional conservative standard therapy followed by a significant improvement of clinical symptoms. Antiviral medication could be maintained in both patients. Taking all data into account, the diagnosis of a HAART-associated dilated cardiomyopathy could be assessed. Even though the pathogenesis of secondary heart failure after HAART is still object of investigation a mitochondrial impairment by antiviral drugs is thought to contribute the development of dilated cardiomyopathy. However, due to the coexistence of an eminent HIV infection, a direct effect of the HI virus itself can not be completely excluded.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Expression of beta-defensin 1 and 2 in nasal epithelial cells and alveolar macrophages from HIV-infected patients.

BACKGROUND: The incidence of respiratory infection is high in HIV-infected patients. beta-defensins are anti-microbial peptides derived from epithelia on the mucosal surfaces of the respiratory, gastrointestinal and urinary tract. Nothing is known about the rate of expression of beta-defensin 1 and 2 mRNAs in nasal epithelial cells and alveolar macrophages in HIV-infected patients. METHODS: Semiquantitative rt-PCR measurement of beta-defensins 1 and 2 and beta-actin were carried out on nasal epithelial cells of 109 patients (76 HIV-infected) and alveolar macrophages from 56 patients (18 HIV-infected). RESULTS: The levels of beta-defensin 1 and 2 mRNAs in nasal epithelial cells did not differ significantly between HIV-infected and non-infected patients. In the nasal epithelial cells of HIV-negative patients who suffered from respiratory infections beta-defensin levels were decreased. beta-defensin 1 mRNA expression was significantly reduced in alveolar macrophages from HIV infected patients. beta-defensin 2 mRNA expression in alveolar macrophages was very low. beta-defensins 1 and 2 mRNA expression did not correlate with CD 4 cell numbers in the blood of HIV-infected patients. CONCLUSION: HIV infection and CD 4 cell numbers in the blood do not influence beta-defensin 1 and 2 expressions in nasal epithelial cells. In alveolar macrophages, beta-defensin 1 expression is decreased in HIV-infected patients.

Adult↗
PubMed2005

Fumaric acid esters in necrobiosis lipoidica: results of a prospective noncontrolled study.

BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous skin disease with association to diabetes mellitus. To date, no proven effective therapy for NL has been implemented. The standard treatment is topical application of corticosteroids, but numerous agents have been reported for NL, with varying degrees of success. In recent case reports, fumaric acid esters (FAE) have been reported to be effective in granulomatous skin diseases such as granuloma annulare, cutaneous sarcoidosis and NL. OBJECTIVES: We sought to investigate the efficacy of FAE in a larger number of patients with NL. METHODS: Eighteen patients with histopathologically proven NL were consecutively recruited into a prospective noncontrolled study. Dosage of FAE was given according to the standard therapy regimen for psoriasis. FAE were administered for at least 6 months. The treatment outcome was evaluated by means of clinical and histological scoring and 20-MHz ultrasound assessments. RESULTS: Three patients discontinued therapy with FAE, while the remaining 15 patients finished the study. After a mean +/- SD treatment period of 7.7 +/- 2.9 months, a significant (P < 0.001) decrease in the mean +/- SD clinical score, from 7.4 +/- 1.8 at the beginning to 2.5 +/- 1.3 at the end of therapy, was observed. Significant clinical improvement of NL was accompanied by significant (P = 0.019) increase of dermal density as assessed by means of 20-MHz ultrasound, and significant (P = 0.011) reduction of the histological score. Adverse effects were moderate and consisted mainly of gastrointestinal complaints and flushing. During follow-up of at least 6 months, clinical outcome remained stable in all patients. CONCLUSIONS: The results of this study demonstrate that FAE are beneficial and safe in the treatment of patients with NL.

Adult↗