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Biomedical subjects

E Putz

Publications and source records attributed to E Putz.

6 recordsLinked to original sources

Clinical assessment in ischaemic cardiomyopathy.

Despite the trend of decreasing death rates attributable to ischaemic heart disease and stroke, the prevalence of heart failure and the resultant death rates in the United States have almost tripled between 1974 and 1994 [1]. Coronary artery disease is the commonest cause of heart failure in developed countries, accounting for up to 60% of cases. Advances in medical therapy, particularly the use of angiotensin-converting enzyme inhibitors and beta-blockers, have served to reduce morbidity and mortality in patients with left ventricular (LV) dysfunction due to coronary artery disease [2-5]. However, these improvements have been modest, and despite these therapies, patients with severe ischaemic cardiomyopathy continue to have a high mortality when treated medically. It is increasingly clear that the impaired LV function in these patients is not always an irreversible process. Traditionally, these observations have been made following demonstrable improvements in systolic function after coronary revascularization procedures. Diagnostic testing to evaluate the presence and extent of viable myocardium has therefore become an important component of the clinical assessment of patients with chronic coronary artery disease and LV dysfunction.

Coronary Artery Disease↗

Ultrastructure of the vitreoretinal interface following plasmin assisted vitrectomy.

AIMS: To investigate the ultrastructure of the vitreoretinal interface following plasmin induced posterior vitreous detachment. METHODS: Plasmin (1 or 2 U/0.1 ml) was injected into the vitreous cavity of 24 eyes of freshly slaughtered pigs. The 24 fellow eyes received calcium-free and magnesium-free PBS and served as a control. After incubation at 37 degrees C for 30 and 60 minutes, the globes were placed in fixative and hemisected. Specimens for light, scanning, and transmission electron microscopy were obtained from the posterior pole, the equator, and the vitreous base using a corneal trephine. RESULTS: All plasmin treated eyes showed posterior vitreous detachment. However, the inner limiting membrane (ILM) was covered by remnants of cortical vitreous at the posterior pole and at the equator. There was a direct correlation between the concentration and exposure times of plasmin and the degree of vitreoretinal separation. Eyes exposed to 1 U plasmin for 30 minutes had a dense network of residual collagen fibrils while those exposed to 1 U plasmin for 60 minutes had only sparse collagen fibrils covering the ILM. Eyes treated with 2 U plasmin for 60 minutes had a smooth retinal surface, consistent with a bare ILM. At the vitreous base there was no vitreoretinal separation. In all control eyes the vitreous cortex was completely attached to the retina. There was no evidence of retinal damage in any plasmin treated eye. CONCLUSION: Plasmin induces a cleavage between the vitreous cortex and the ILM without morphological changes to the retina. In contrast with previous reports, plasmin produces a smooth retinal surface and additional surgery is not required in this experimental setting. The degree of vitreoretinal separation depends on the concentration and length of exposure to plasmin.

Animals↗

Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases.

Bone marrow (BM) is a clinically relevant site of micrometastatic disease in patients with solid epithelial tumors. It is, therefore, important to establish suitable models that allow the in-depth characterization of disseminated tumor cells present at low frequencies of 10(-5)-10(-6) nucleated BM cells. The aim of this study was to assess common phenotypic features of nine tumor cell lines established from BM of patients with cancer of the prostate (four cell lines), breast (two cell lines), lung (two cell lines), and colon (one cell line) using immunocytochemistry, flow cytometry, and reverse transcription-PCR. All cell lines stained positive for both cytokeratins, the epithelial intermediate filaments, and the epithelial cell adhesion molecule E-cadherin, and they lacked markers of BM-derived cells. The tumor origin of the cell lines was supported by the expression of the ErbB2 oncogene (seven of nine) and MAGE mRNA (eight of eight). All cell lines coexpressed cytokeratin and vimentin, the mesenchymal intermediate filament, indicating an epithelial-mesenchymal transition of micrometastatic cells. The invasive phenotype of the immortalized cells was also reflected by the consistent expression of several metastasis-associated adhesion molecules, including alpha5 (eight of nine), alpha6 (five of nine), alphaV (nine of nine), beta1 (nine of nine), and beta3 (nine of nine) integrin subunits and the Mr 67,000 laminin receptor (seven of nine). Contrary to our expectations, metastasis-promoting CD44 variant isoforms were only detected on two lines, whereas all cell lines expressed MUC18/melanoma cell adhesion molecule and intercellular adhesion molecule-1, two members of the immunoglobulin superfamily of adhesion molecules that are not frequently found on primary carcinoma cells. The consistent expression of various epithelial and tumor-associated antigens provides evidence that the established cell lines are derived from disseminated cancer cells present in the BM. The invasive phenotype of the immortalized cells was mirrored by their epithelial-mesenchymal transition and the expression of several metastasis-associated molecules, which might be potential candidates for novel therapeutic targets.

Biomarkers, Tumor↗

Clearing of psoriasis by a novel immunosuppressive macrolide.

Accumulating evidence suggests that psoriasis may be a genetically determined immunogenic, inflammatory disorder based on an ongoing autoreactive Th-1 response. Systemic immunosuppressive therapy is highly effective but fraught with longterm side effects. Our research therefore focuses on therapeutic strategies that induce local immunosuppression in the skin by topical, transepidermal delivery of immunosuppressive drugs. SDZ 281-240 is a newly developed macrolide of the ascomycin type. It is immunosuppressive by mechanism of action similar to that of FK506 but has no antiproliferative activity against keratinocytes in vitro. To evaluate whether SDZ 281-240 exhibits antipsoriatic activity when applied topically, we tested 15 patients with severe, recalcitrant psoriasis, using a microplaque assay in randomized, double-blind, placebo-controlled study, comparing the therapeutic efficacy of the macrolide with a potent halogenated corticosteroid and vehicle. All patients showed a significant improvement of psoriatic lesions treated with two concentrations of the macrolide and, as expected, with the corticosteroid but not with placebo. Both concentrations of the macrolide led to clearing of psoriasis after 10 days of treatment and biopsies confirmed a reversal of the histopathological and immunopathological phenotype of psoriasis to that of normal skin. Thus, an immunosuppressive agent that interferes with early T cell activation can be designed to penetrate into psoriatic lesions when applied topically and to be functionally active within the skin to suppress the ongoing psoriatic process.

Administration, Topical↗

[Quality assurance of interstitial irradiation in the breast-conserving therapy of breast cancer].

PURPOSE: The purpose of this communication is to describe the procedure of interstitial implant planning in definitive irradiation of early breast cancer. There are some reports about localization techniques of the boost volume for external irradiation. Less has been reported about the target volume localization of HDR implants of the breast. METHODS: Conservative surgery and following radiation therapy have become a standard treatment in the management of early breast cancer. The use of a boost irradiation in the area of the primary tumour seems to be promising in decreasing local recurrence rates. Most of our patients received a boost dose by interstitial HDR iridium-192 therapy. Therefore we have improved the method of interstitial implantation by CT under general anesthesia. The implant is planned in the simulator room by localizing the radiopaque clips of the tumor bed, the entrance and exit points of the needles are determined by marking the skin. Then the implantation is done in the operating and afterloading room. A device for patient transportation between brachytherapy unit and CT has been constructed. So patients can be shifted under general anesthesia between the different devices without any problems. The implanted needles and the clips are visualized by the means of CT. The target volume can be defined and the source dwell positions determined. CONCLUSION: This method improves the accuracy of target localization. Therefore the treated volume can be adapted and minimized, resulting in less side effects and may contribute to maximize local control.

Brachytherapy↗