Search PubMed⌕ Search

Biomedical subjects

R Hein

Publications and source records attributed to R Hein.

At least 19 recordsLinked to original sources
PubMed2006

Photodynamic therapy induces less pain in patients treated with methyl aminolevulinate compared to aminolevulinic acid.

Photodynamic therapy (PDT) with topical application of either aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is increasingly used for the treatment of actinic keratoses (AKs). Although PDT is a well-tolerated treatment, pain is the most severe side effect. Sixty-nine patients (mean age 69 years, 61 male, 8 female) suffering from multiple AKs on the scalp (field cancerization) were included in the study. PDT treatment was performed, using red light (Waldmann PDT 1200) with a light dose of 100 J/cm2 delivered at a dose rate of 160 mW/cm2. Either ALA or MAL were used as photosensitizer. Patients were asked to rate their pain on a scale from 0 to 10 (0 = no pain, 10 = unbearable pain). Upon reaching a score of 10 treatment was discontinued. Comparison of ALA and MAL in patients with AK revealed that MAL induced less pain than ALA. While 14% of the patients treated with MAL discontinued treatment before reaching the required light dose of 100 J/cm2, the number of patients treated with ALA who discontinued treatment reached 54%. PDT using MAL appears to be a better tolerated treatment for multiple AKs on the scalp compared to ALA-PDT. Differences in selectivity for tumor cells and transport of ALA in peripheral neurons may play a role.

Aged↗
PubMed2005

"Melanoma inhibitory activity" (MIA): a promising serological tumour marker in metastatic uveal melanoma.

PURPOSE: To assess the role of "melanoma inhibitory activity" (MIA) as a potential serum marker for screening and detection of metastatic uveal melanoma. DESIGN: Prospective, clinical study. MATERIAL AND METHODS: Serum samples of 305 patients with uveal melanoma were collected. Serum samples were analysed by a one-step enzyme-linked immunosorbent assay (ELISA) to quantify the MIA serum levels. All patients underwent a standardized echography of the globe to evaluate maximum tumour height and were checked for systemic metastasis of the tumour by liver enzyme tests and ultrasonography of the liver. RESULTS: Twenty patients (6.6%) had proven metastatic disease; eight of them developed it during follow-up. The mean serum concentration of MIA in the 285 patients without metastasis was 6.72 ng/ml, whereas the mean serum concentration of MIA in the 20 patients with metastasis was 13.03 ng/ml (P<0.001). The eight patients who developed metastatic disease during follow-up showed an MIA of 5.92 ng/ml before detection of metastasis and 12.21 ng/ml afterwards (P<0.001). MIA serum levels did neither correlate with the tumour height or to whether local therapy had been applied. CONCLUSION: The elevation of MIA serum levels in patients with metastatic disease from melanoma supports its promising role as a serum marker for monitoring patients with uveal melanoma.

Adult↗
PubMed2005

A secreted form of P-cadherin is expressed in malignant melanoma.

Cadherins are Ca-dependent homophilic cell-cell adhesion molecules which are responsible for correct location of cells and tissue integrity. They are critical for development and maintenance of epithelial architecture. Aberrantly expressed cadherins are known to be involved in malignant transformation of different types of tissues. In this study, we show the expression of a short truncated 50 kDa form of the N-terminal part of P-cadherin in seven melanoma cell lines compared to melanocytes and keratinocytes. In vitro protein analysis on cell culture supernatant as well as immunohistochemistry of primary and metastatic melanoma tissue revealed the expression of this short form of P-cadherin. Furthermore, analysis showed that this short 50 kDa form of P-cadherin is secreted by melanoma cells in contrast to the membrane bound form in melanocytes. Analysis on mRNA level detected only exon 1 to 10 of P-cadherin resulting in the 50 kDa form missing the transmembrane and cytoplasmatic region. Genomic sequence analysis did not show any mutations in melanoma cells neither in the exons nor in the exon-intron boundaries. Furthermore, there was no loss of exons 11-16 on the genomic level. Functionally, the secreted form of P-cadherin could play a role as regulator of the homophilic interaction between P-cadherin molecules by antagonizing their biological role acting as a dominant negative form to interrupt cell-cell attachment.

Alternative Splicing↗
PubMed2005

Successful UVA1 phototherapy in a patient with scleredema adultorum.

Scleredema adultorum is a rare connective tissue disorder of unknown cause. Both bath-PUVA and cream-PUVA therapy were reported to be effective. We describe a patient with scleredema adultorum who showed a striking clinical improvement with a medium-dose UVA1 phototherapy (single dose, 50 J/cm(2); 35 treatments).

Humans↗
PubMed2004

Elevated MIA levels in the serum of pregnant women and of children.

Recent studies have shown that the protein MIA (melanoma inhibitory activity) is a potent serum marker for malignant melanoma. MIA is expressed in chondrocytes at high levels, and might potentially be elevated during periods of growth in childhood. Therefore, we evaluated MIA serum levels in pregnant women and in growing children. We found that no significant enhancement of MIA serum levels was apparent until 38 weeks of pregnancy. Starting at 38 weeks, a significant increase was noted. The study further revealed that children and teenagers also have increased MIA serum levels. However, from the age of 17 years MIA serum levels are not different from those in healthy adults. In summary, MIA can be used as a serum marker for melanoma in adults starting at the age of 17 years. In pregnant women (> 38th week), children, and teenagers MIA should not be used in serum diagnostics for malignant melanoma until larger studies have been performed to generate cut-off levels for each group.

Adolescent↗
PubMed2003

Laminin, hyaluronan, tenascin-C and type VI collagen levels in sera from patients with malignant melanoma.

In this study, hyaluronan, laminin-1, tenascin-C and type VI collagen were measured in the sera of patients with stage I/II and stage IV melanoma. A significant increase in the serum levels of all four extracellular matrix proteins was found in patients with stage IV melanoma compared to healthy donors. Type VI collagen and hyaluronan serum levels were also significantly increased in stage I/II melanoma. Increased expression of the four matrix proteins was also demonstrated in melanoma cell lines using reverse transcriptase- polmerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). We suggest that tenascin-C, hyaluronan, laminin-1 and type VI collagen are involved in melanoma development and extracellular matrix remodelling during melanoma progression. This finding will be of interest in the development of serum markers for progression of malignant melanoma.

Cell Line↗
PubMed2003

Linear spiradenoma with focal malignant transformation.

Malignant spiradenoma is an exceedingly rare adnexal tumour clinically characterized by rapid enlargement of a pre-existing, long-standing benign spiradenoma. Microscopic examination typically reveals a continuum between benign spiradenoma and areas of malignant transformation. Biological behaviour is unpredictable and it should be regarded as a potentially lethal neoplasm. Treatment recommendations require radical surgical excision. The reported case of a 23-year-old female illustrates the malignant transformation of a 1.5 cm nodule within a large linear spiradenoma almost covering the frontal aspect of the lower leg. In reviewing the literature, malignant transformation seems to occur slightly more often in multiple than in solitary spiradenomas. It is unclear whether excision restricted to the malignant area is an advisable treatment option in comparison to total excision of all spiradenoma nodules. In the presented case, the transformed area was excised. The patient is free of recurrence after 2 years.

Adenoma, Sweat Gland↗
PubMed2003

Histopathological characteristics of small diameter melanocytic naevi.

BACKGROUND/AIMS: The clinical definition of an atypical naevus ("dysplastic naevus" or "naevus with architectural disorder and cytological atypia of melanocytes") stresses size larger than 5 mm in diameter as a major diagnostic criterion. Because malignant melanomas and their precursors may arise in smaller lesions, a histological study of melanocytic lesions smaller than 4 mm in diameter was conducted to evaluate their histological appearance. METHODS: Two hundred and sixty one naevi smaller than 4 mm in diameter were collected and characterised by histological examination into benign naevi without architectural disorder and naevi with architectural disorder and mild, moderate, and severe atypical melanocytes according to criteria used on larger lesions. RESULTS: Small melanocytic naevi covered the same complex histological spectrum from benign naevi to severely atypical naevi when compared with larger lesions. A high proportion of small naevi (72%) exhibited features diagnostic for naevi with architectural disorder and cytological atypia. CONCLUSION: There is a discrepancy between histological and clinically defined atypical naevi. The same generally accepted criteria for the histological diagnosis of atypical naevi should be used for small melanocytic naevi in addition to large ones. Thus, small naevi exhibiting atypical features on histological examination should be categorised as atypical naevi, regardless of their small diameter.

Adolescent↗
PubMed2002

[Keratosis lichenoides chronica. Bath PUVA therapy].

We describe the case of a 51-year-old male patient with characteristic lesions of keratosis lichenoides chronica confined to the back of his hands and feet. The lichenoid papules, linear hyperkeratotic ridges and erythematosquamous plaques appeared first in early childhood and recurred after a short episode of spontaneous remission. They didn't respond to various topical treatment modalities over the years. After a local PUVA therapy all lesions disappeared with no recurrence for over two years now. Our case report indicates a new promising indication for bath-PUVA-therapy.

Balneology↗
PubMed2002

[Scrotal leiomyoma].

Genital leiomyomas of the scrotal skin are extremely rare benign tumors, originating from the tunica dartos of the scrotum. We describe a 55-year-old caucasian male with a 3-year history of a slowly growing asymptomatic scrotal knot which was first clinically regarded as a cyst and finally diagnosed histopathologically as leiomyoma. This typical case demonstrates that leiomyomas should be considered in the differential diagnosis of scrotal tumors.

Diagnosis, Differential↗
PubMed2002

Chronic urticaria: impact of allergic inflammation.

Urticaria is defined by weals (hives), with or without angioedema, that appear and peak in minutes to hours, usually disappear within 24 h, and are accompanied by pruritus that worsens during the night. Urticaria is caused by cutaneous mast cell degranulation, attributed to immunological, nonimmunological, and idiopathic causes. Chronic idiopathic urticaria (CIU) is the diagnosis when the pathophysiological mechanism of persistent urticaria remains unclear; up to half of patients with CIU have functional autoantibodies directed against the high-affinity receptor for IgE (FcepsilonRI) or against IgE itself, which appear to induce mast cell degranulation. Systemic histamine H1-receptor antagonists, such as desloratadine, are central to the management of CIU. The efficacy and safety of desloratadine, 5 mg once daily, was studied in a double-blind, randomized, placebo-controlled, multicentre trial that included 190 patients, ages 12 and above, with at least a 6-week history of CIU and experiencing a flare of at least moderate severity. Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose, and its superiority was maintained throughout the full 6 weeks of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly improved with desloratadine after the first dose and maintained throughout the study.

Chronic Disease↗
PubMed2002

UV-induced skin changes due to regular use of commercial sunbeds.

BACKGROUND/AIM: Increased pigmentation and thickening of the epidermis are the most important photoprotective skin reactions induced by ultraviolet (UV) radiation. The present study was designed to find out what changes are induced by regular use of commercial sunbeds twice weekly over a period of 6 weeks. METHODS: The parameters analysed were skin pigmentation measured by chromametry, minimal erythema dose (MED) as a parameter of light sensitivity, epidermal thickening as determined by histology, induction of keratinocyte apoptosis as determined by TUNEL staining and antioxidant metabolism as measured by changes of cis- and trans-urocanic acid (UCA) content of the skin. RESULTS: As expected, chromametry confirmed the clinically obvious increased skin pigmentation. However, no increase in MED was observed. In addition, neither epidermal thickening nor sunburn cells were seen. Significant detectable changes in proportion of the UCA isomer content of the UV-exposed skin were seen. The total UCA and cis-UCA content increased significantly between nearly all points of measurement. The amount of trans-UCA first decreased, then increased significantly between the different time points. CONCLUSION: Our data indicate that sunbed-induced tanning is non-protective, which has to be addressed for persons looking for this effect before planning a stay in a sunny climate. However, sunbed-induced tanning may influence immunological reactions.

Adolescent↗
PubMed2001

Role of the ATP synthase alpha-subunit in conferring sensitivity to tentoxin.

Tentoxin, produced by phytopathogenic fungi, selectively affects the function of the ATP synthase enzymes of certain sensitive plant species. Binding of tentoxin to a high affinity (K(i) approximately 10 nM) site on the chloroplast F(1) (CF(1)) strongly inhibits catalytic function, whereas binding to a second, lower affinity site (K(d) > 10 microM) leads to restoration and even stimulation of catalytic activity. Sensitivity to tentoxin has been shown to be due, in part, to the nature of the amino acid residue at position 83 on the catalytic beta subunit of CF(1). An aspartate in this position is required, but is not sufficient, for tentoxin inhibition. By comparison with the solved structure of mitochondrial F(1) [Abrahams, J. P., Leslie, A. G. W., Lutter, R., and Walker, J. E. (1994) Nature 370, 621-628], Asp83 is probably located at an interface between alpha and beta subunits on CF(1) where residues on the alpha subunit could also participate in tentoxin binding. A hybrid core F(1) enzyme assembled with beta and gamma subunits of the tentoxin-sensitive spinach CF(1), and an alpha subunit of the tentoxin-insensitive photosynthetic bacterium Rhodospirillum rubrum F(1) (RrF(1)), was stimulated but not inhibited by tentoxin [Tucker, W. C., Du, Z., Gromet-Elhanan, Z. and Richter, M. L. (2001) Eur. J. Biochem. 268, 2179-2186]. In this study, chimeric alpha subunits were prepared by introducing short segments of the spinach CF(1) alpha subunit from a poorly conserved region which is immediately adjacent to beta-Asp83 in the crystal structure, into equivalent positions in the RrF(1) alpha subunit using oligonucleotide-directed mutagenesis. Hybrid enzymes containing these chimeric alpha subunits had both the high affinity inhibitory tentoxin binding site and the lower affinity stimulatory site. Changing beta-Asp83 to leucine resulted in loss of both inhibition and stimulation by tentoxin in the chimeras. The results indicate that tentoxin inhibition requires additional alpha residues that are not present on the RrF(1) alpha subunit. A structural model of a putative inhibitory tentoxin binding pocket is presented.

Amino Acid Sequence↗
PubMed2001

Interlaboratory evaluation of a new reverse transcriptase polymerase chain reaction-based enzyme-linked immunosorbent assay for the detection of circulating melanoma cells: a multicenter study of the Dermatologic Cooperative Oncology Group.

PURPOSE: Reverse transcription-polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is the most frequently used laboratory method for the detection of circulating tumor cells in melanoma patients. However, previously published results showed considerable variability in the PCR positivity rates. MATERIALS AND METHODS: We designed a collaborative study to assess the sensitivity, specificity, and clinical relevance of a new standardized RT-PCR-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating melanoma cells. Blood samples of healthy donors mixed with cells of a melanoma cell line were prepared in a blinded fashion, and aliquots were sent to seven participating laboratories experienced in RT-PCR. RESULTS: The results demonstrate a high sensitivity (1 melanoma cell/mL blood) and specificity (no false-negatives and 7.4% [2 of 28] false-positives) of the assay and a satisfactory rate of interlaboratory reproducibility. The analysis of aliquots of blinded samples derived from 60 melanoma patients identified tyrosinase mRNA in 17 of 60 (28.3%): three (20%) of 15 stage I patients, two (13.3%) of 15 stage II patients, five (35.7%) of 14 stage III patients, and seven (43.8%) of 16 stage IV patients. The interlaboratory reproducibility of positive samples, however, was extremely low and indicates the presence of low amounts of target mRNA. CONCLUSION: Reverse transcriptase-PCR ELISA has a high sensitivity and specificity for the detection of tyrosinase mRNA in peripheral blood cells. The low interlaboratory reproducibility for the detection of tumor cells in blood samples of melanoma patients, however, raises the question of relevance of this assay for clinical use.

Adult↗
PubMed2001

Melanoma inhibitory activity (MIA), a serological marker of malignant melanoma.

Melanoma inhibitory activity (MIA) was originally identified as an 11 kDa protein secreted from malignant melanoma cells. We have shown that MIA is strongly expressed in melanoma and melanoma cell lines but not in melanocytes and normal skin. We also observed that MIA mRNA expression correlates with progressive malignancy of melanocytic tumors. Measuring MIA in serum or plasma by a sensitive and quantitative ELISA and investigating the potential of MIA serum levels as a novel marker for malignant melanomas showed that the protein can be used to monitor therapy and follow-up. The present study measured the variations in blood concentrations of MIA in 84 patients with stage II-IV melanoma by ELISA. Patients treated with repeated injections of a polyvalent melanoma vaccine (PMV), interferon-alpha-2b (IFN-alpha 2b) or interleukin-2 (IL-2) were followed during treatment duration. Before treatment, patients treated with PMV or IFN-alpha 2b had comparable low MIA concentrations, whereas most IL-2-treated patients had higher MIA levels. At the end of treatment, MIA concentrations were higher in patients with progressive disease (PD) than in patients with no clinical evidence of melanoma (NPD) for PMV, IFN-alpha 2b or IL-2 therapy (3.7 +/- 0.2 vs 11.5 +/- 5.4 ng/ml, 3.8 +/- 0.2 vs 8.3 +/- 1.7 ng/ml, and 2.3 +/- 0.7 vs 20.2 +/- 7.4 ng/ml, respectively, p < 0.05). In contrast to the stable MIA concentrations measured in NPD patients, significant increase in MIA levels were observed in PD patients over time regardless of treatment. For PMV- and IFN-alpha 2b-treated patients, a rise in MIA levels occurred significantly earlier than clinical diagnosis of melanoma recurrence. In conclusion, our data suggest that quantitation of MIA serum levels may be used for detection of both clinically apparent and non-apparent metastatic melanoma disease and for monitoring therapy.

Animals↗
PubMed2001

[Cylindrospiradenomas in Brooke-Spiegler syndrome].

Brooke-Spiegler syndrome is a rare autosomal-dominant inherited disease, characterized by the development of multiple cylindromas and trichoepitheliomas. We report a case in which tumors were found on the head showing histological features of both cylindromas and spiradenomas. These changes were in continuity within the same lesions. Since cylindromas are thought to be apocrine in nature, whereas spiradenomas are eccrine, a contiguous growth within the same neoplasm indicates a conflict concerning their histogenesis. The available histological, ultrastructural and immunohistochemical studies have not produced any criteria to allow an unequivocal classification, suggesting instead that both tumors arise from similarly differentiated cells, perhaps from pluripotent epithelial cells. In our opinion, it seems impractical to strictly classify cylindromas and spiradenomas into tumors of apocrine or eccrine differentiation. Moreover, at least for those cases of Brooke-Spiegler syndrome, where both tumors are found in immediate vicinity to each other, we propose the term cylindrospiradenoma.

Adenoma↗