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Biomedical subjects

Michael Boehm

Publications and source records attributed to Michael Boehm.

11 recordsLinked to original sources
PubMed2007

Evidence for HSP-mediated cytoskeletal stabilization in mesothelial cells during acute experimental peritoneal dialysis.

Low biocompatibility of peritoneal dialysis fluid (PDF) injures mesothelial cells and activates their stress response. In this study, we investigated the role of heat shock proteins (HSP), the main cytoprotective effectors of the stress response, in cytoskeletal stabilization of mesothelial cells in experimental peritoneal dialysis. In cultured human mesothelial cells, cytoskeletal integrity was assessed by detergent extractability of marker proteins following in vitro PDF exposure. Effects of HSP on stabilization of ezrin were evaluated by a conditioning protocol (PDF pretreatment) and repair assay, based on coincubation of cytoskeletal protein fractions with recombinant HSP-72 or HSP-72 antibodies. In the rat model, detachment of mesothelial cells from their peritoneal monolayer during in vivo PDF exposure was assessed with and without overexpression of HSP-72 (by heat conditioning). In vitro, cytoskeletal disruption on sublethal PDF exposure was demonstrated by significantly altered detergent extractability of ezrin and ZO-1. Restoration was associated with significant induction and cytoskeletal redistribution of HSP during recovery. Both the conditioning protocol and in vitro repair assay provided evidence for HSP-72-mediated cytoskeletal stabilization. In the rat model, overexpression of HSP-72 following heat conditioning resulted in significantly reduced detachment of mesothelial cells on in vivo exposure to PDF. Our results establish an essential role of HSP in repair and cytoprotection of cytoskeletal integrity in mesothelial cells following acute in vitro and in vivo exposure to PDF. Repeated exposure to PDF, as is the rule in the clinical setting, may not only cause repeat injury to mesothelial cells but rather represents a kind of inadvertent conditioning treatment.

Actins↗
PubMed2006

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy.

Chronic allograft nephropathy is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to calcineurin inhibitors. In the present study, effects of a conversion protocol were investigated in pediatric chronic allograft nephropathy with declining glomerular filtration rate (GFR), defined by a Schwartz formula clearance below 60 mL/1.73 m(2)/min, steadily increasing serum creatinine and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kg bodyweight (BW), followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. Calcineurin inhibitors were reduced to 50% at the start of sirolimus and discontinued at median 7 days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m(2)/month, p = 0.025). Individual GFR increased in five out of eight patients (p = 0.026), and only one child exhibited unaltered progression of graft failure. In the responders, mean serum creatinine improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, or on time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, and serum lipids increased transiently. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from calcineurin inhibitors to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy-proven chronic allograft nephropathy.

Adolescent↗
PubMed2006

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy.

CAN is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to CNIs. In the present study, effects of a conversion protocol were investigated in pediatric CAN with declining GFR, defined by a Schwartz formula clearance below 60 mL/1.73 m2/min, steadily increasing SCr and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kgBW, followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. CNIs were reduced to 50% at start of sirolimus and discontinued at median seven days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m2/month, p = 0.025). Individual GFR increased in five of eight patients (p = 0.026), only one child exhibited unaltered progression of graft failure. In the responders, mean SCr improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, nor time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, serum lipids transiently increased. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from CNIs to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy proven CAN.

Adolescent↗
PubMed2006

Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries.

PURPOSE: To compare the inhibition of neointimal proliferation by using non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. MATERIALS AND METHODS: Experiments were conducted with permission of the animal protection committee of the local government. Paclitaxel was either dissolved in a nonionic contrast medium or coated on balloons. Stents were crimped on the coated balloons. Effectiveness was tested in 22 pigs. Two coronary stents were placed in each pig, and slight overstretch was applied. The animals were treated as follows: group A (control group), uncoated balloons, bare stents, and "plain" contrast medium; group B, same treatment as group A, but with paclitaxel in the contrast medium; group C, paclitaxel-coated balloons, with premounted bare stents and plain contrast medium; and group D, sirolimus-eluting stents, noncoated balloons, and plain contrast medium. Stenosis was assessed 4 weeks later at angiography and histomorphometry. For exploratory purposes, continuous variables of quantitative coronary angiography and histomorphometry were compared by using analysis of variance. RESULTS: Results at follow-up angiography indicated a mean of 1.00 mm +/- 0.18 (standard deviation) lumen diameter loss in the control group and 0.14 mm +/- 0.18 loss in the group treated with the paclitaxel-coated balloon (group C; P < .001). Findings at histomorphometry confirmed the effectiveness of drug delivery, with the most impressive inhibition of neointimal proliferation from coated balloons-the neointimal area was 2.4 mm2 +/- 0.3 (P < .01 vs all other groups), compared with 5.2 mm2 +/- 0.3 in group A (control group), 4.3 mm2 +/- 0.3 in group B, and 3.8 mm2 +/- 0.3 in group D. CONCLUSION: In spite of the short intima contact time, paclitaxel coated on the balloon inhibits neointimal formation in the porcine model of coronary stent placement.

Analysis of Variance↗
PubMed2005

Risk factors for peritonitis in pediatric peritoneal dialysis: a single-center study.

Recent US registry data and a European multicenter study described increased risk of peritonitis in young children on peritoneal dialysis (PD). No underlying age-specific risk factors could be defined in these reports. Therefore, we analyzed risk factors for peritonitis in children treated by PD as primary renal replacement therapy at the Kinderdialyse, Vienna, and particularly searched for age-specific aspects. Thirty children (15 boys, mean age 4.6 years) received PD [21 automated peritoneal dialysis (APD), nine continuous ambulatory peritoneal dialysis (CAPD)] for 13 months (3-49 months). During the total observation period of 395 dialysis months, 27 peritonitis episodes were diagnosed (1:14.6 months or 0.82/patient per year). Of our population, 43% remained peritonitis free; seven patients suffered from more than one peritonitis episode. Ten potential risk factors [age, gender, PD modality, duration of PD, exit-site status, urine volume, residual glomerular filtration rate (GFR), Kt/V, normalized protein catabolic rate (nPCR), albumin] and four indices of peritonitis outcome (peritonitis incidence, peritonitis burden, risk of suffering more than one episode of peritonitis and chance of staying free from peritonitis) were analyzed. Our study identified six risk factors in univariate analysis, namely age, APD treatment, exit-site infections, low urinary volume, low residual GFR and low nPCR, which were significantly correlated with two or more of the outcome indices. Multivariate analysis identified exit-site infection and residual urine volume as strong independent predictors. In summary, our study identified several age-dependent and age-independent risk factors for peritonitis in pediatric PD. These data demonstrate that the risk for peritonitis in small children is not pre-determined but might be open to therapeutic interventions, such as optimizing exit-site care, dialysis prescription and nutrition management.

Aging↗
PubMed2005

Detection of herpes simplex virus, cytomegalovirus and Epstein-Barr virus DNA in atherosclerotic plaques and in unaffected bypass grafts.

BACKGROUND: Herpes virus infections are suspected to be involved in the pathogenesis of atherosclerosis. OBJECTIVE AND METHOD: Viral DNA of herpes simplex virus (HSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) was analyzed by real-time PCR on 48 biopsies from atherosclerotic plaques extracted by end-arterectomy (46 coronary arteries, 2 carotid arteries), and in tissue from non-atherosclerosis vessels from the same patient as controls (23 internal mammary arteries, 43 saphenous veins). RESULTS: HSV-1 DNA was detected significantly more frequently in plaques (35%) than in control veins (9%, P = 0.006). However, the frequency of HSV-1 DNA detection in the internal mammary artery grafts was as high as in plaques (22%, P = 0.28). CMV and EBV DNA were exclusively found in plaques but not in controls, with 10% for CMV (P = 0.06 versus veins, P = 0.17 versus graft arteries) and 2% for EBV (P = 1.0), respectively. HSV-2 was neither detected in plaques nor in controls. Herpes viral DNA was significantly associated only with arterial hypertension but not with other classical risk factors (P = 0.02), in accordance with the hypothesis that herpes viral infection may alter the vessel wall. CONCLUSION: We conclude that herpes viral infections may have a role in atherosclerosis and that the presence of herpes viral DNA in the grafts used for bypass surgery might constitute a potential risk for atherosclerosis or restenosis.

Adult↗
PubMed2005

Use of tadalafil in a patient with a secondary Raynaud's phenomenon not responding to sildenafil.

The Raynaud's phenomenon often accompanies systemic rheumatic diseases and is also known as a vascular side effect of chemotherapy. Therapy of the Raynaud's phenomenon with nitrates or calcium-channel-blockers is rarely beneficial. In contrast, the PDE-V-inhibitor sildenafil seems to be effective in these patients. For the first time we report on a patient with Raynaud's phenomenon due to chemotherapy not responding to sildenafil but to the new PDE-V-inhibitor tadalafil in an equivalent dosage. Measurement with a laser Doppler revealed an increased blood flow and a reduction of symptoms. Therefore, therapy of Raynaud's phenomenon with the new PDE-V-inhibitor tadalafil seems to be an effective treatment option in patients not responding to sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2002

Immunophenotype of conjunctival melanomas: comparisons with uveal and cutaneous melanomas.

OBJECTIVE: To characterize the immunophenotypic expression pattern of conjunctival melanomas, with the use of standard melanoma markers as well as microphthalmia transcription factor and p75 neurotrophin receptor. DESIGN: Eleven conjunctival melanomas, including 1 caruncular melanoma, were immunolabeled with a panel of antibodies that included S100, tyrosinase, melan-A, HMB-45 and HMB-50 combination, microphthalmia transcription factor, and p75 neurotrophin receptor. The results were tabulated on the basis of intensity and pervasiveness of labeling and compared with a previous study of uveal melanomas. RESULTS: Immunolabeling with S100 was at significantly higher levels in conjunctival melanomas than in uveal melanomas. Tyrosinase, HMB-45 and HMB-50 combination, melan-A, and microphthalmia transcription factor were expressed at high levels in conjunctival melanomas, whereas p75 neurotrophin receptor was not expressed. CONCLUSIONS: Melanomas of the conjunctiva, including the caruncle, expressed S100, tyrosinase, melan-A, HMB-45 and HMB-50 combination, and microphthalmia transcription factor at high levels, suggesting that these are good markers for this melanoma subtype. Expression of S100 was significantly higher in conjunctival melanomas than in uveal melanomas. The immunophenotypic pattern of conjunctival melanomas is most similar to the epithelioid subtype of cutaneous melanomas.

Biomarkers, Tumor↗
PubMed2002

Immunophenotypic differences between uveal and cutaneous melanomas.

OBJECTIVE: To determine the immunophenotypic differences between uveal and cutaneous melanomas, employing standard melanoma markers as well as p75 neurotrophin receptor (p75NTR) and microphthalmia transcription factor (MITF). DESIGN: Fifteen uveal melanomas (5 spindle, 5 epithelioid, and 5 mixed uveal subtypes) were immunolabeled with a panel of antibodies that included S100, tyrosinase, melan-A, HMB-45 and HMB-50 combination, MITF, and p75NTR. The results were tabulated on the basis of intensity and pervasiveness of the labeling and compared with a prior study on cutaneous spindle and epithelioid melanomas. RESULTS: In contrast to its strong labeling of cutaneous melanomas, S100 immunolabeling of uveal melanomas was weak and variable. p75NTR, known to differentiate spindle from epithelioid melanomas of the skin, did not immunolabel uveal melanomas. HMB-45, HMB-50, tyrosinase, melan-A, and MITF immunolabeled all uveal melanomas strongly, irrespective of the histologic subtype, but not cutaneous melanomas. Microphthalmia transcription factor was especially clear in its labeling of uveal melanomas. CONCLUSIONS: Although cutaneous and uveal melanomas share many molecular markers in common, there are differences between the 2 types of melanoma. First, the level of expression of S100 differs between cutaneous and uveal melanomas. Second, while cutaneous melanomas can be further subdivided into spindle and epithelioid types based on their immunophenotype, the uveal melanomas cannot.

Antigens, Neoplasm↗