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Biomedical subjects

P Birner

Publications and source records attributed to P Birner.

At least 37 records · Page 2Linked to original sources

Platelet-derived growth factor-alpha receptor expression supports the growth of conventional chondrosarcoma and is associated with adverse outcome.

Bone cells are important targets of platelet-derived growth factors (PDGFs) because they stimulate proliferation of osteoblasts and chondrocytes. In this study we wanted to determine the expression of PDGF-AA and PDGF-alpha receptor in conventional chondrosarcomas and to compare the results with those obtained from benign enchondromas and non-neoplastic cartilage tissue. Sixty-seven chondrosarcomas, 20 enchondromas, and 5 specimens of healthy cartilage as well as 7 specimens of hypertrophic callus cartilage were immunohistochemically analyzed for the expression of PDGF-AA and PDGF-alpha receptor, respectively. Additionally, the proliferation activity was examined with the MIB-1 antibody. Clinical follow-up data were available from 53 patients. A significant overexpression of receptor and factor was found in chondrosarcomas as compared with enchondromas (PDGF-AA p = 0.013, PDGF-alpha receptor p <0.001). MIB-1 values were significantly higher in chondrosarcomas (p <0.001). In healthy joint cartilage no staining was detectable, whereas reactive cartilage of callus formation showed high expression levels. PDGF-alpha receptor expression was significantly higher in grade 3 chondrosarcomas compared with grade 2 (p = 0.022) and grade 1 tumors (p = 0.002). Survival analysis documented a significantly shorter overall survival for patients with high PDGF-alpha receptor expression (p = 0.0172, log-rank test). Because PDGF-alpha receptor expression positively correlates with the aggressiveness of chondrosarcoma, it may be considered as a possible target for novel therapeutic strategies.

Adolescent↗

Fatal late coronary thrombosis after implantation of a radioactive stent: postmortem angiographic and histologic findings--case report.

Postmortem angiography and histologic analysis of a fatal coronary thrombosis 4 months after implantation of a radioactive stent are described. Histologic findings suggested incomplete re-endothelialization in the segment with the stent. Ionizing radiation may delay re-endothelialization after revascularization, thus maintaining the thrombogenicity of the irradiated vessel segment. Thus, prolonged antiplatelet therapy should be considered after intravascular radiation therapy.

Aged↗

DNA repair-redox enzyme apurinic endonuclease in cervical cancer: evaluation of redox control of HIF-1alpha and prognostic significance.

The multifunctional apurinic/apyrimidinic endonuclease (Ape1/ref-1) plays a key role in the human DNA base excision repair pathway. Ape1/ref-1 has also been shown to be involved in the redox control of transactivation activities of hypoxia-inducible factor (HIF)-1alpha. The aim of our study was to investigate the expression of these proteins in early stage invasive cervical cancer. Expression of Ape1/ref-1 and HIF-1alpha was detected immunohistochemically in 88 samples of cervical cancer stage pT1b. The levels of the proteins were compared and the prognostic influence of Ape1/ref-1 expression was investigated. Strong nuclear expression of Ape1/ref-1 was observed in 9 cases (10.2%), moderate in 22 cases (25%), weak in 17 cases (19.3%), and absent in 40 cases (45.5%). Furthermore, no correlation between Ape1/ref-1 and HIF-1alpha expression was observed (p=0.864). We also found no relationship of Ape1/ref-1 expression and survival (p>0.05, log-rank test). From these studies, we have concluded that in cervical cancer there is no correlation between the upstream redox regulatory protein of HIF-1, i.e., Ape1/ref-1, and HIF-1alpha expression. However, these studies do not address any functional relationship between the two proteins.

Carbon-Oxygen Lyases↗

Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer.

Lymphovascular space invasion was shown to play a key role in the progression of cervical cancer. Because of the absence of a specific marker for lymphatic vessels, earlier studies could not reliably distinguish between blood and lymphatic vessel invasion. By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy. Eleven (11.2%) specimens showed invasion of blood vessels, 20 (20.4%) showed invasion of lymphatic vessels, and 15 (15.3%) showed invasion of blood and lymphatic vessels. There was a strong association of lymphatic vessel invasion and lymph node involvement (P < 0.001). In univariate analysis, both blood and lymphatic vessel invasion failed to reach a statistically significant influence on overall survival, but a significant influence on disease-free survival was found (P = 0.0002 and P < 0.0001, respectively). In multivariate analysis of disease-free survival, only blood vessel invasion remained statistically significant (P = 0.0457). Lymphatic vessel invasion reached significance when lymph node status was excluded from the model (P = 0.0025). Both lymphatic vessel and blood vessel invasion occur frequently in early-stage cervical cancer. Determination of the vessel status may be of clinical importance because it signifies the risk of recurrent disease.

Adult↗

Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.

PURPOSE: To investigate the impact of expression of hypoxia-inducible factor (HIF)-1alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors. EXPERIMENTAL DESIGN: Expression of HIF-1alpha protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival. RESULTS: In 68.6% of ovarian cancers and 88% of borderline tumors, expression of HIF-1alpha was observed. There was a significant correlation of HIF-1alpha protein expression and MVD (P < 0.001). HIF-1alpha overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1alpha expression. Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors. CONCLUSIONS: HIF-1alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1alpha protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.

Cell Survival↗

Evaluation of the United States Food and Drug Administration-approved scoring and test system of HER-2 protein expression in breast cancer.

PURPOSE: The purpose of this study was to investigate the prognostic significance of assessment of human epidermal growth factor receptor (HER)-2 oncogene protein overexpression of breast cancer tissue by the United States Food and Drug Administration (FDA)-approved HercepTest and grading system (negative, 0 or 1+; weakly positive, 2+; strongly positive, 3+). Furthermore, results of the HercepTest were correlated with immunohistochemical results obtained using different antibodies and protocols and with HER-2 oncogene gene amplification assessed by fluorescence in situ hybridization (FISH). EXPERIMENTAL DESIGN: HER-2 status in 303 patients with lymph node-positive breast cancer was investigated by using a rabbit polyclonal antibody (DAKO) by conventional immunohistochemistry and by applying the HercepTest. Furthermore, the monoclonal antibody CB-11 was used in conventional immunohistochemistry and with the NexES automatic stainer, which is also under consideration for FDA approval for determination of eligibility for Herceptin therapy. Results were compared with FISH analysis performed in all 2+ and 3+ specimens (103 cases) and 104 HER-2-negative specimens. RESULTS: 3+ positive carcinomas were found in 8.9-15.7% of specimens. FISH revealed that almost exclusively 3+ positive cases were amplified, with the HercepTest and the NexES automatic stainer giving the best results. In univariate analysis, staining with the HercepTest revealed a significantly worse prognosis in 3+ cases. Also, 3+ cases were significantly associated with lower estrogen receptor levels and histological grade III tumors. CONCLUSIONS: This study shows that the results of the FDA-approved HER-2 grading and test system correlated strongly with findings in FISH. Furthermore, HercepTest proved to be of prognostic relevance. Strict adherence to the given protocols is critical.

Adult↗

Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.

Austria↗

Preperitoneal lipoleiomyoma of the abdominal wall in a postmenopausal woman.

OBJECTIVE: Extrauterine leiomyomas are rare events. These tumors may be easily misdiagnosed as ovarian tumors at the clinical investigation. We present the first case of an otherwise healthy postmenopausal woman, hysterectomized 20 years ago, who developed a preperitoneal lipoleimoyoma in the 30-year-old scar of a Pfannenstiel incision. The patient received continuous hormone replacement therapy (HRT) for 5 years with 1.25 mg conjugated estrogen and 5 mg medrogeston per day. METHODS: In sections of the tumor, immunohistochemical reactions with antibodies against actin, desmin, vimentin, estrogen and progesterone receptors and factor VIII related antigen was performed. RESULTS: Histologic findings revealed cellular fascicles of spindle-shaped smooth muscle cells in a whorled arrangement. Mitotic figures were absent. Central degenerative changes and focal edema were observed. Between muscle fascicles, a significant amount of fat cells (20% of tumor volume) was visible. Leiomyocytes showed immunohistochemicaly positive reactions with actin, desmin, vimentin, and steroid hormone receptors. Based on these findings, the tumor was diagnosed as lipoleiomyoma. CONCLUSIONS: Origin of the tumor of smooth muscle cells of vessels located in the abdominal wall and development under influence of oral steroids seems most probable. HRT appears to promote the development of extrauterine leiomyomas in postmenopausal women.

Abdomen↗

Hybrid capture based human papillomavirus typing in cervical screening compared to cytology and histology.

INTRODUCTION: Cervical cancer is frequently associated with infection from various types of human papillomavirus (HPV) with high a oncogenic potential (high-risk types). Commercial systems for HPV typing are available, but the question as to when HPV typing should be performed has not yet been solved. OBJECTIVES: To assess the value of HPV typing in a clinical setting in a population with opportunistic screening. STUDY DESIGN: Cytology, histology and HPV status of 593 patients from a high-risk collective were evaluated retrospectively. For HPV typing, the hybrid capture (HC) system was used. RESULTS: Infection with high-risk types of HPV was associated with more severe cervical lesions. Women with PAP III or PAP IIID who were infected with high-risk HPV were at increased risk for high-grade cervical lesions (CIN III+) (p = 0.006). Conization influenced HPV status: of 63 patients who were HPV high-risk positive before conization, 4 remained positive afterwards. CONCLUSION: HC appears to be a useful system to triage women with PAP III or IIID and to detect patients with residual HPV infection after conization. However, because of high costs and no significant increase in the sensitivity of cytology, the use of HPV typing in routine cervical screening cannot be recommended in countries with opportunistic annual cytological screening.

Adult↗

Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer.

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a transcriptional factor that regulates genes involved in response to hypoxia and promotes neoangiogenesis, which are considered essential for tumor growth and progression. Using immunohistochemistry, we investigated the influence of HIF-1alpha expression on prognosis in 91 patients with cervical cancer stage pT1b. In univariate and multivariate analysis, patients with strong expression of HIF-1alpha had a significantly shorter overall survival time (P = 0.0307, log-rank test) and disease-free survival time (P < 0.0001, log-rank test) compared with those with moderate to absent HIF-1alpha expression. HIF-1alpha expression is a strong independent prognostic marker in early stage cervical cancer.

Adult↗

Bladder volume determination: portable 3-D versus stationary 2-D ultrasound device.

OBJECTIVE: To investigate how accurately a portable three-dimensional (3-D) scanner and a multipurpose two-dimensional (2-D) real-time scanner determined bladder volumes. STUDY DESIGN: Prospective, controlled clinical trial, single-blind, crossover design. SETTING AND PARTICIPANTS: Twenty-three inpatients with permanent bladder catheters participated voluntarily in this study. METHODS: The bladders of 20 patients were filled through an indwelling catheter with 60, 110, 160, 210, and 260 mL sterile normal saline. Volumes were measured twice with each device. Measurements were compared with the actual bladder volumes. RESULTS: The 2-D device showed better reproducibility, particularly at lower bladder volumes. The 3-D scanner showed a significant difference between the two measurements at 160 mL (p<.05) and had poor reproducibility at 110, 210, and 260 mL. Both devices overestimated actual bladder volume at fillings of <160 mL and underestimated it at fillings of > or =160 mL. The range between the 25th and 75th percentiles was always larger for the 3-D scanner, except for the 210 mL reading. CONCLUSION: Both devices showed sufficient accuracy for clinical practice. Ultrasound measurements of >110 mL should be followed by catheterization to detect potentially harmful bladder volumes.

Cross-Over Studies↗

Psychiatric disorders in patients with blepharospasm - a reactive pattern?

OBJECTIVE: The purpose of this study was to assess the life-time prevalence of all major psychiatric disorders in patients suffering from blepharospasm. METHOD: A total of 31 consecutive patients with blepharospasm attending the Department of Neurology were interviewed at the Department of Psychiatry at the University of Vienna. Patients had been submitted to standard neurological diagnostic procedures, psychiatric diagnoses were made with the help of the SCID, functional impairment was assessed by the General Assessment of Functioning Scale (GAF). RESULTS: A current or life-time psychiatric diagnosis was made for 22 patients (71%). The most frequent disorders were depressive disorders, mainly major depression (five patients, 16.1%), secondary dysthymia (six patients, 19.3%), and recurrent major depression (five patients, 16.1%). A diagnosis of simple phobia was made for seven patients (22.5%), for obsessive-compulsive disorder in three patients (9.6%). The mean GAF score of our sample was 63.1%. CONCLUSION: In contrast to previously published results, we did not find a high rate of a single specific disorder or patterns in our study sample, though by the inclusion of life-time diagnostic criteria, the majority of patients fulfilled criteria for at least one diagnosis. This might indicate the considerable negative impact of blepharospasm on the patients' lives.

Aged↗

Molecular mimicry in infectious encephalitis and neuritis: binding of antibodies against infectious agents on Western blots of human nervous tissue.

OBJECTIVES: To study the occurrence of cross-reactivities of antibodies against infectious agents with human nervous tissue. METHODS: Binding of 25 antibodies against 17 neurotropic pathogens comprising Borrelia burgdorferi, Toxoplasma gondii, and various DNA and RNA viruses to Western blots of human cortex and myelin from central and peripheral nervous system was investigated. RESULTS: Fourteen of the 25 antibodies tested showed binding to Western blots of human nervous tissue, suggesting the presence of shared epitopes. Binding of 11 antibodies against 10 pathogens to cortex and/or myelin correlated with the tissue targeted by neuropathological lesions. Three antibodies did not show such correlation; 11 antibodies did not bind at all. CONCLUSIONS: Our results suggest that shared epitopes between infectious agents and human nervous tissues are more common than previously expected. Thus, molecular mimicry should be considered more frequently as a possible pathogenetic mechanism, among others, inducing tissue damage in encephalitis and neuritis caused by various pathogens.

Aged↗

Cardiac autonomic function in patients suffering from primary focal hyperhidrosis.

Cardiac autonomic function in patients (n = 63) with primary focal hyperhidrosis and healthy controls (n = 28) was investigated by short-term frequency domain power spectral analysis of heart rate variability. The power of the very-low-frequency band (0.01-0.05 Hz) was significantly lower in patients with axillary hyperhidrosis than in controls. No differences between groups could be observed at investigation of the low-frequency band (0.05-0.15 Hz), which was a surprising finding because this band represents also sympathetic cardiac innervation. At the high-frequency band (0.15-0.5 Hz), which represents parasympathetic cardiac innervation, an interaction of type and position influencing spectral power was detected. Our highly interesting findings indicate that primary focal hyperhidrosis is based on a much more complex autonomic dysfunction than generalised sympathetic overactivity and seems to involve the parasympathetic nervous system as well.

Adult↗

Alteration of the serotonergic nervous system in fatal familial insomnia.

Fatal familial insomnia (FFI) is a unique hereditary prion disease with characteristic disturbances of sleep. We studied the serotonergic system in 8 FFI-affected subjects by immunohistochemistry for the serotonin-synthesizing enzyme, tryptophan hydroxylase (TH). Quantification of neurons in median raphe nuclei showed no total neuronal loss in FFI but a substantial increase of TH+ neurons (approximately 62%) in FFI subjects compared with controls. Our data indicate an alteration of the serotonergic system that might represent the functional substrate of some typical symptoms of FFI.

Adult↗

[Long-term treatment with botulinum toxin: dosage, treatment schedules and costs].

Local injection of botulinum toxin A (BTX) is considered as the treatment of choice for spasmodic torticollis (ST), blepharospasm (BS) and, with certain limitations, for hemifacial spasm (HFS). Long-term data from 89 patients with ST, 39 patients with BS and 15 patients with HFS were evaluated and subgroups of patients who received at least three (60 ST, 17 BS, 9 HFS), six (35 ST, 10 BS, 8 HFS) and nine (26 ST) re-injections were formed. These groups were investigated in regard of increases in the dosage of BTX and in regard of shorter treatment intervals in cases of repeated treatment. Annual drug costs were calculated from these data. Patients treated at least three times were asked to fill out a questionnaire concerning satisfaction and the quality of life after BTX treatment. Furthermore, the patients' "willingness to pay" for BTX treatment was investigated. Our calculations showed neither a significant increase in the dosage of BTX nor a significant reduction in the length of treatment intervals after 3 or 6 treatment sessions. Annual drug costs for BTX for the treatment of ST were 10,542 ATS, of BS 2847 ATS and of HFS 1029 ATS. 86.1% of patients with ST, 88.9% with BS and 100% with HFS were very satisfied or satisfied with the BTX treatment. In all 3 diagnostic groups, a significant mean improvement of quality of life was measured on a visual analogue scale (p < 0.001). We conclude that the injection of botulinum toxin A is a highly effective and cost effective treatment for ST, BS and HFS, and significantly increases the quality of life of all these patients.

Adult↗