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Josef Smolle

Publications and source records attributed to Josef Smolle.

At least 19 recordsLinked to original sources
PubMed2006

Efficiency of fleece-bound sealing (TachoSil) of air leaks in lung surgery: a prospective randomised trial.

OBJECTIVE: Persistent air leakage following pulmonary resection is a major limiting factor for discharge from hospital. The aim of this study was to evaluate the sealing capacity of TachoSil for the closure of alveolar air leaks following parenchymal resections and to determine its effect on time to chest drain removal and duration of hospitalisation. METHODS: A total of 173 patients undergoing lobectomy or segmentectomy were enrolled in a single-centre, randomised study to compare the efficacy of TachoSil with standard treatment. Alveolar air leaks were evaluated intraoperatively by submersion of the resection site in saline and were graded according to the Macchiarini scale as 0 (no bubbles), 1 (single bubbles), 2 (stream of bubbles), 3 (coalescent bubbles). Patients with grade 1 or 2 air leaks were randomised to TachoSil or standard treatment. Grade 3 patients received standard treatment until the air leak was downgraded to grade 1 or 2 at which point they were randomised. Patients with grade 0 leakage were excluded. The primary efficacy endpoints of the study were postoperative quantification of air leakage on postoperative days 1 and 2. Other efficacy measurements included mean time to chest drain removal and mean time to hospital discharge. RESULTS: The mean intraoperative post-treatment air leakage was significantly lower in the TachoSil group (153.32ml/min, range: 10-450ml/min) compared with the standard treatment group (251.04ml/min, range: 15-970ml/min; P=0.009). The significant difference in air leakage volume observed intraoperatively post-treatment was maintained postoperatively. TachoSil showed a trend towards reduced incidence of postoperative leakage when measured >48h or >7 days after surgery (30.7% vs 38.96% and 24% vs 32.46%, respectively). The mean times to chest drain removal and to hospital discharge were significantly reduced following the use of TachoSil (5.1 days vs 6.3 days, P=0.022 and 6.2 days vs 7.7 days, P=0.01, respectively). CONCLUSIONS: The use of TachoSil following pulmonary resection resulted in a reduction in air leakage compared with standard techniques. This reduction in air leakage resulted in a significant reduction in both the time to chest drain removal and the period of hospitalisation.

Adult↗
PubMed2006

Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma.

PURPOSE: The recent identification of toll-like receptors (TLRs) and respective ligands allows the evaluation of novel dendritic cell (DC) -activating strategies. Stimulation of TLR9 directly activates human plasmacytoid DCs (PDCs) and indirectly induces potent innate immune responses in preclinical tumor models. We performed an open-label, multicenter, single-arm, phase II pilot trial with a TLR9-stimulating oligodeoxynucleotide in melanoma patients. PATIENTS AND METHODS: Patients with unresectable stage IIIb/c or stage IV melanoma received 6 mg PF-3512676 weekly by subcutaneous injection for 24 weeks or until disease progression to evaluate safety as well as clinical and immunologic activity. Clinical and laboratory safety assessments were performed weekly; blood samples for immunological measurements were taken every 8 weeks. Tumor measurements were performed according to Response Evaluation Criteria in Solid Tumors. RESULTS: Twenty patients received PF-3512676 for a mean of 10.9 weeks with a mean of 10.7 injections. Laboratory and nonlaboratory adverse events were limited, transient, and did not result in any withdrawals. Two patients experienced a confirmed partial response; one response is ongoing for 140+ weeks. Three patients experienced stable disease. Immunologic measurements revealed induction of an activated phenotype of PDC, elevation of serum levels of 2',5'-oligoadenylate, a surrogate marker of type I interferon production, and significant stimulation of natural killer cell cytotoxicity (the latter was associated with clinical benefit). CONCLUSION: These results indicate that TLR9-targeted therapy can stimulate innate immune responses in cancer patients, identify biomarkers that may be associated with TLR9-induced tumor regression, and encourage the design of follow-up studies to evaluate the ability of this therapeutic approach to target human cancer.

Adult↗
PubMed2006

Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors.

BACKGROUND: Melanoma and nonmelanoma skin cancer are the most frequent malignant tumors by far among whites. Currently, early diagnosis is the most efficient method for preventing a fatal outcome. In vivo confocal laser-scanning microscopy (CLSM) is a recently developed potential diagnostic tool. METHODS: One hundred seventeen melanocytic skin lesions and 45 nonmelanocytic skin lesions (90 benign nevi, 27 malignant melanomas, 15 basal cell carcinomas, and 30 seborrheic keratoses) were sampled consecutively and were examined using proprietary CLSM equipment. Stored images were rated by 4 independent observers. RESULTS: Differentiation between melanoma and all other lesions based solely on CLSM examination was achieved with a positive predictive value of 94.22%. Malignant lesions (melanoma and basal cell carcinoma) as a group were diagnosed with a positive predictive value of 96.34%. Assessment of distinct CLSM features showed a strong interobserver correlation (kappa >0.80 for 11 of 13 criteria). Classification and regression tree analysis yielded a 3-step algorithm based on only 3 criteria, facilitating a correct classification in 96.30% of melanomas, 98.89% of benign nevi, and 100% of basal cell carcinomas and seborrheic keratoses. CONCLUSIONS: In vivo CLSM examination appeared to be a promising method for the noninvasive assessment of melanoma and nonmelanoma skin tumors.

Basal Cell Carcinoma↗
PubMed2006

Dermoscopy patterns of halo nevi.

BACKGROUND: Halo nevi (HN) are benign melanocytic nevi surrounded by a depigmented area (halo). This study aims to evaluate the dermoscopic features of HN and their changes during digital dermoscopic follow-up and to investigate the frequency of the halo phenomenon in a series of melanomas. OBSERVATIONS: In a retrospective study, digital dermoscopic images of HN from patients who attended the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, between October 1, 1997, and March 31, 2004, were reviewed and classified by dermoscopic morphologic criteria. For HN that were followed up with digital dermoscopy, the percentages of changes in the size of the nevus and halo components were calculated. In addition, digital dermoscopic images of histopathologically confirmed melanomas obtained from the same database were reviewed for the presence of an encircling halolike depigmentation. We classified 138 HN in 87 patients (mean age, 22.4 years). The most common dermoscopic structures were the globular and/or homogeneous patterns in more than 80% of HN. Follow-up of 33 HN revealed considerable size reduction of the nevus component, but this was not associated with significant structural changes. Of a total of 475 melanomas, only 2 revealed an encircling halo, but both displayed clear-cut melanoma-specific patterns according to dermoscopy. CONCLUSIONS: Halo nevi exhibit the characteristic dermoscopic features of benign melanocytic nevi, represented by globular and/or homogeneous patterns that are typically observed in children and young adults. Halo nevi reveal considerable changes of area over time during digital dermoscopic follow-up, albeit their structural patterns remain unchanged. For this reason and because melanoma with halolike depigmentation, despite being rare, additionally exhibits melanoma-specific dermoscopic criteria, the role of digital dermoscopic follow-up in the diagnosis of HN is insignificant.

Adolescent↗
PubMed2006

Non-invasive imaging of tissue PO2 in malignant melanoma of the skin.

In various tumor systems, decreased PO2 values have been demonstrated by various methods. This study addresses the question of whether tumor hypoxia can be found in cutaneous melanoma using lifetime imaging of non-invasive sensors showing phosphorescence quenched by oxygen. Twenty-three cases of cutaneous malignant melanoma (average tumor thickness 1.25 mm, range 0.5-8 mm) were examined using the SkinCam lifetime imaging system for the assessment of cutaneous PO2 levels within the tumors and in adjacent clinically normal skin. For comparison, 30 non-melanoma skin tumors were evaluated. In 15 exploitable melanoma cases, the average hypoxic difference of the lesion compared with the surrounding skin was -10 mmHg, typically associated with an inhomogeneous distribution. Only 10% of the non-melanoma lesions showed a similar hypoxia (false positives). The SkinCam equipment uses a non-invasive imaging method and provides further diagnostic hints in the assessment of benign and malignant skin tumors.

Humans↗
PubMed2006

Teledermatopathology: a controlled study about diagnostic validity and technical requirements for digital transmission.

Telepathology is the practice of diagnostic histopathology performed on digital pictures. In this study, we focused on the technical requirements for achievement of a correct diagnosis on digital histopathologic images. A collection of 560 melanocytic lesions was selected from the files of the Department of Dermatology, Medical University of Graz, Austria. From each lesion one histologic slide was completely digitally scanned with a robotic microscope. Digital pictures were reviewed by 4 dermatopathologists using a presentation program, which recorded the number of image calls, applied magnifications, overall time needed, and amount of transmitted bits during the digital sign-out. One month later, the 4 microscopists had to review the corresponding slides and render a direct diagnosis on each case. Telepathologic diagnoses corresponded with the original diagnoses in a range from 90.4% to 96.4% of cases (kappa 0.80 to 0.93; P < 0.001). The median time needed for achievement of a diagnosis was 22 seconds and was significantly higher for melanomas compared with nevi. The median transmission effort for each diagnosis was 510 kilobytes after JPEG compression. Using an ISDN line with a transmission capacity of 64 kilobits/ second, this correlates to a transmission time of about 1 minute. Our results demonstrate that correct reporting on digital histopathologic images is possible with only a little time exposure. For an adequately fast transmission ISDN lines are suffcient after JPEG compression.

Dermatology↗
PubMed2005

GJB2 mutations in keratitis-ichthyosis-deafness syndrome including its fatal form.

Keratitis-ichthyosis-deafness syndrome (KID; MIM 148210) is a rare congenital disorder characterized by vascularizing keratitis, sensorineural hearing loss (HL), and progressive erythrokeratoderma. Clinical variability including a fatal course of KID in the first year of life has been reported. Germline missense mutations in GJB2, encoding connexin-26, were recently found to cause KID in 14 unrelated juvenile and adult patients. We identified a de novo GJB2 mutation G45E in a patient displaying the fatal form of the disease. No mutations were detected in five other connexin and mitochondrial genes. The G45E mutation was not reported previously in Caucasian patients but was the third most common GJB2 mutation (16% of disease alleles) in Japanese patients with autosomal recessive non-syndromic HL. This finding suggests different modes of action of the same GJB2 mutation depending on the genetic background. This hypothesis was further substantiated by our observation of a variable clinical course in unrelated KID patients from Austria harboring the common D50N mutation in GJB2.

Abnormalities, Multiple↗
PubMed2005

Confocal examination of untreated fresh specimens from basal cell carcinoma: implications for microscopically guided surgery.

OBJECTIVE: To evaluate the diagnostic accuracy of confocal examination of basal cell carcinoma (BCC) in microscopy-guided surgery. DESIGN: Four independent observers with no previous experience in confocal laser scanning (CLS) microscopy received standardized instruction about diagnostic CLS microscopic features. Subsequently, 120 confocal images of fresh excisions from BCCs or normal skin were evaluated by each observer, imaged using a commercially available, near-infrared, reflectance CLS microscope. Logistic regression analysis was performed on a combination of all morphologic features using the forward-stepwise (Wald) method. Reliability (interobserver agreement) data were evaluated by kappa statistic. SETTING: Department of Dermatology, Medical University of Graz. PATIENTS: Twenty patients with histologically verified BCC. INTERVENTIONS: Evaluation of fresh BCC excisions by CLS microscopy. MAIN OUTCOME MEASURES: Diagnostic accuracy of the method was evaluated by chi2 test. Diagnostic impact and reliability of each morphologic feature were evaluated by logistic regression analysis and kappa statistic, respectively. RESULTS: Overall, high diagnostic accuracy was achieved by the 4 observers. Logistic regression analysis revealed that mainly tumor cell nuclei and tumor nests should be taken into account for diagnostic decisions, whereas disintegration of tumor cells, peripheral palisading, and retraction of stroma were rarely useful. However, most of the features were highly reliable. CONCLUSIONS: This diagnostic validation study of CLS microscopy in microscopy-guided surgery yielded promising results and opens avenues for further studies. In the future, CLS microscopy may guide microsurgery of any skin cancer.

Basal Cell Carcinoma↗
PubMed2005

The incidence of gastroesophageal reflux after transthoracic esophagocardio-myotomy without fundoplication: a long term follow-up.

OBJECTIVE: Evaluation of the long term results of Heller's myotomy performed over a lateral thoracotomy without additional fundoplication. METHODS: Forty patients (17 males, 23 females; mean age 43.2 years; range: 14-63 years) were operated between 1985 and 2000. Preoperative evaluation included clinical scoring of symptoms, esophagogram, endoscopy, manometry and 24-h ph-metry. At the follow-up investigation, the preoperative evaluation was repeated in all patients, adding a histological workup of the distal esophageal mucosa. The mean duration of follow-up after surgery was 10.3 years, ranging from 3-16 years. RESULTS: The clinical scores improved significantly: Excellent relief from dysphagia was present in 86%, little or no regurgitation was found in 79%, little or no retrosternal spasms were reported by 72% of the patients. Esophagogram showed an overall esophageal dilatation in all patients but no significant obstruction at the esophagogastric junction. Endoscopically, 2.5% had candida-esophagitis, 5% showed signs of a GERD I, 92.5% had a macroscopically insuspect esophageal mucosa. Histologically, 53% showed a mild chronic inflammation. Manometry demonstrated distinct hypomotility of the esophagus in all cases, yet no elevated pressure of the lower sphincter; pH-metry showed moderate reflux in 46%. CONCLUSIONS: Transthoracic cardiomyotomy is a valid method for the treatment of achalasia, but it will not improve the esophageal motility, which slowly deterioriates in these cases. The patient's subjective assessment of the postoperative result was positive in the majority of cases. Although fundoplication was not done in any of these patients, none of them showed signs of clinically relevant reflux.

Adolescent↗
PubMed2005

Diagnostic applicability of in vivo confocal laser scanning microscopy in melanocytic skin tumors.

In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the examination of skin morphology in real time at a resolution equal to that of conventional microscopes. The aim of the study was to test the applicability of CLSM to the diagnostic discrimination of benign nevi and melanoma. five independent observers without previous experience in CLSM received a standardized instruction about diagnostic CLSM features. Subsequently, 117 melanocytic skin tumors (90 benign nevi and 27 melanoma), imaged using a commercially available, near-infrared, reflectance confocal laser scanning microscope, were evaluated by each observer. Overall, sensitivity of 88.15% and specificity of 97.60% was achieved by the five observers. Logistic regression analysis revealed that mainly cytomorphology, architecture and keratinocyte cell borders should be taken into account for diagnostic decisions. Remarkably, using the presence or absence of monomorphic melanocytes as a single diagnostic criterion, the classification results with a sensitivity of 98.15% and a specificity of 98.89% were superior to the intuitive, integrative judgement of the observers. This first sensitivity and specificity study with CLSM has yielded promising results. CLSM provides new and useful information to the clinician diagnosing melanocytic skin tumors.

Cell Shape↗
PubMed2005

Digital image enhancement for in vivo laser scanning microscopy.

BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) is a new method that provides skin images in horizontal plane at a level of resolution that allows to view microanatomic structures. This study examines whether certain digital image-processing steps can increase the visibility of various structures in CLSM. STUDY DESIGN: Fifty images were taken from normal skin of 25 probands, and 39 image enhancement procedures were created. Eight procedures that seemed to provide some quality enhancement were deliberately selected for further evaluation. Subsequently, a collection of random pairs of the original image and an image submitted to any of the eight selected procedures was rated by five independent observers. RESULTS: In three of the eight procedures tested, the modified image was significantly preferred to the original image (chi2-test,: P< or =0.001). In particular, smoothing, shading correction, delineate and grey-level normalization in various combinations were helpful in showing the characteristic honeycomb pattern, pigmented basal cell layer, cell borders and the nuclei more clearly. CONCLUSION: Digital image processing may help to increase visibility of in vivo CLSM images.

Adolescent↗
PubMed2005

[Connexin 26 mutation and keratitis-ichthyosis-deafness (KID) syndrome].

BACKGROUND: Keratitis-ichthyosis-deafness syndrome (KID syndrome) is an extremely rare disorder. Inheritance is autosomal dominant but many cases occur sporadically following a spontaneous mutation. The cause of KID syndrome are missense mutations of the gene GJB2, encoding connexin 26. PATIENTS AND METHODS: We clinically studied two cases of KID syndrome and extracted genomic DNA from peripheral blood. RESULTS: The patients showed different heterozygous mutations of the connexin 26 gene and had quite different clinical courses. CONCLUSIONS: Both patients showed heterozygous mutations of the connexin 26 gene; a different Cx26 dominant mutation can cause a very different clinical course.

Adult↗
PubMed2005

[Computer-based training in dermatooncology--a preliminary report comparing electronic learning programs with face-to-face teaching].

BACKGROUND: Electronic media are increasingly used in medical education. The question arises whether tutorial programs are as effective as innovative face-to-face didactic formats. METHODS: 26 students underwent a special dermatooncology course in an integrated undergraduate medical curriculum. One part of the content was acquired face-to-face with emphasis on team learning and mini-lectures; the other part was presented as web-based electronic computer-based training objects. The performance of the students in a subsequent multiple choice test was evaluated. RESULTS: In total, questions referring to computer-based training contents were answered correctly in 90.4 +/- 12.5 %, which was significantly superior to the questions referring to team learning in the face-to-face teaching format (80.6 +/- 13.1 %; p < 0.001). There was, however, a significant correlation between both results for each individual student (r = 0.52; p < 0.01), but there was no correlation between the results obtained for computer-based training or team learning on the one hand, and the overall performance of the individual student on the other. CONCLUSIONS: Though different contents were concerned, our study provides evidence that computer-based training may be more efficient than face-to-face teaching using team learning to communicate dermatooncology contents in an undergraduate medical curriculum.

Austria↗
PubMed2004

Mofarotene-induced inhibition of melanoma cell motility by increasing vinculin-containing focal contacts.

Tumour cell motility, which is dependent on the organization of the cytoskeleton, is considered to play an important role in the spread of malignant melanoma. Therefore, retinoids, which are modulators of cytoskeletal organization, may affect the motile activity of melanoma cells. In this study, the effects of the arotinoid mofarotene on single cell motility and vinculin organization of the highly metastatic melanoma cell line K-1735-M2 were determined. Melanoma cells were cultivated in a temperature- and CO2-controlled microincubator, which was located on the microscope stage. Cell movements were evaluated quantitatively from time-lapse video recordings using an IBAS image analysis system. Vinculin distribution was evaluated using confocal laser scanning microscopy and a specially developed computerized image analysing program. In addition, melanoma cell invasion was tested on the embryonic chick heart model. Although 10 microM mofarotene did not reduce the translocative movements of melanoma cells, it significantly inhibited stationary motility, including fast plasma membrane movements and changes in shape. Mofarotene also showed a pronounced effect on the organization of vinculin-containing cell-substratum adhesion plaques. In retinoid-treated cells, the numbers of vinculin plaques per cell, and particularly those in the marginal areas of the cells, were significantly increased compared with untreated controls. Furthermore, the compound reduced the invasiveness of melanoma cells in a three-dimensional tissue culture model. In conclusion, our data demonstrate that mofarotene, an already almost forgotten synthetic retinoid, shows interesting effects on melanoma cells, which may be relevant for a slowdown of tumour spread.

Actins↗
PubMed2004

SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases.

Netherton syndrome (NTS) is an autosomal recessive congenital ichthyosis featuring chronic inflammation of the skin, hair anomalies, epidermal hyperplasia with an impaired epidermal barrier function, failure to thrive and atopic manifestations. The disease is caused by mutations in the SPINK5 gene encoding the serine proteinase inhibitor lympho-epithelial Kazal-type inhibitor (LEKTI). Sequence analyses of SPINK5 in seven NTS patients from five different families allowed us to identify two known and three novel mutations all creating premature termination codons. We developed a monoclonal antibody giving a strong signal for LEKTI in the stratum granulosum of normal skin and demonstrated absence of the protein in NTS epidermis. Immunoblot analysis revealed presence of full length LEKTI and of LEKTI cleavage fragments in normal hair roots, whereas in NTS hair roots LEKTI and its cleavage products were completely missing. Transglutaminase1 activity was present throughout almost the entire suprabasal epidermis in NTS, whereas in normal skin it is restricted to the stratum granulosum. In contrast, immunostaining for transglutaminase3 was absent or faint. Moreover, comparable with the altered pattern in psoriatic skin the epidermis in NTS strongly expressed the serine proteinase inhibitor SKALP/elafin and the anti-microbial protein human beta-defensin 2. These studies demonstrate LEKTI deficiency in the epidermis and in hair roots at the protein level and an aberrant expression of other proteins, especially transglutaminase1 and 3, which may account for the impaired epidermal barrier in NTS.

Adult↗
PubMed2004

Sunburn cell formation, dendritic cell migration, and immunomodulatory factor production after solar-simulated irradiation of sunscreen-treated human skin explants in vitro.

Using human skin explants, we investigated the effects of two different sunscreen preparations containing a chemical UVB filter alone [sun protection factor (SPF) 5.2] or UVA+UVB filter [SPF 6.2] on sunburn cell formation, dendritic cell (DC) migration, CD86- and CD1a-positive cell number, and tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1, IL-10, and IL-12 production in the skin after irradiation with different doses of solar-simulated UV radiation. Sunscreen- or placebo-treated skin explants were irradiated with solar-simulated UV radiation at 0.5, 1, and 2 minimal erythematous dose equivalents (MEDE) (as determined in an in vivo human study) multiplied by the SPF of the placebo or sunscreens. After irradiation, skin explants were floated on RMPI medium for 48 h. Cells that had emigrated and the skin explants were histologically analyzed, and the soluble mediators were measured in the supernatants by ELISA. Exposure to UV radiation led to concentration-dependent increases in sunburn cell formation and TNFalpha production but a concentration-dependent decrease in DC migration and CD86- and CD1a-positive cell number in the epidermis. Both chemical sunscreens protected against those alterations. The immunoprotective capacity of the sunscreens correlated with their SPF but was independent of the sunscreens' UVA protection capacity, suggesting that UVA is not a major factor for immunosuppression under the conditions used in the model. UV irradiation did not significantly affect the vitality of emigrated DC; the expression of HLA, CD80, and lag on emigrated cells; the number of CD1a-positive cells in the dermis; or the production of IL-1, IL-10, and IL-12. We conclude that our model may be useful in determining the immunoprotective capacity of sunscreens.

Adult↗
PubMed2004

An automated method for the quantification and fractal analysis of immunostaining.

AIMS: In tissue counter analysis (TCA) digital images of complex histologic sections are dissected into elements of equal size and shape, and digital information comprising grey level, colour and texture features is calculated for each element. In this study we assessed the feasibility of TCA for the quantitative description of amount and also of distribution of immunostained material. METHODS: In a first step, our system was trained for differentiating between background and tissue on the one hand and between immunopositive and so-called other tissue on the other. In a second step, immunostained slides were automatically screened and the procedure was tested for the quantitative description of amount of cytokeratin (CK) and leukocyte common antigen (LCA) immunopositive structures. Additionally, fractal analysis was applied to all cases describing the architectural distribution of immunostained material. RESULTS: The procedure yielded reproducible assessments of the relative amounts of immunopositive tissue components when the number and percentage of CK and LCA stained structures was assessed. Furthermore, a reliable classification of immunopositive patterns was found by means of fractal dimensionality. CONCLUSIONS: Tissue counter analysis combined with classification trees and fractal analysis is a fully automated and reproducible approach for the quantitative description in immunohistology.

Fractals↗