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Biomedical subjects

I Sulzbacher

Publications and source records attributed to I Sulzbacher.

18 recordsLinked to original sources
PubMed2003

Survivin expression in human osteosarcoma is a marker for survival.

AIMS: Osteosarcoma is the most frequent malignant bone tumor with a peak incidence in the second and third decade of life. Evaluation of prognosis of patients with osteosarcoma is limited to clinical parameters whereas molecular markers of tumor aggression have not yet been identified. Inhibition of apoptotic cell death could play a role in the development or progression of neoplasia. Survivin is a member of the inhibitor of apoptosis (IAP) protein gene family and is expressed both during normal fetal development and in human cancer. METHODS: The localization and distribution of survivin was investigated immunohistochemically in high-grade osteosarcomas by an indirect immunoperoxidase method. RESULTS: Survivin was detected in the cytoplasm in 23/40 and in the nucleus in 20/40 cases of osteosarcoma. Nuclear localization of survivin expression was significantly correlated with a prolonged survival (P=0.0347) but cytoplasmic staining showed no correlation with patient outcome. CONCLUSIONS: The results of this study indicates that the evaluation of survivin expression might be a useful prognostic marker in osteosarcoma. Patients with osteosarcoma exhibiting nuclear survivin expression could potentially benefit from stratification of neoadjuvant chemotherapy.

Adolescent↗
PubMed2002

Pathophysiology and imaging in inflammatory and blastomatous synovial diseases.

Variable pathologies are subsumed under the term "synovial disease", including common pathologies such as rheumatoid arthritis. While formerly radiologists had to rely on conventional radiographs and bone scintigraphy with their inherent problems in visualizing soft tissue, noninvasive imaging of the synovium has recently improved substantially with the technical development of MRI and (Doppler) ultrasound. These imaging modalities allow differentiation of characteristic pathologic features based on a profound knowledge of normal anatomy and pathophysiology.

Arthritis, Infectious↗
PubMed2002

MRI of the cartilage.

With the introduction of fat-suppressed gradient-echo and fast spin-echo (FSE) sequences in clinical routine MR visualization of the hyaline articular cartilage is routinely possible in the larger joints. While 3D gradient-echo with fat suppression allows exact depiction of the thickness and surface of cartilage, FSE outlines the normal and abnormal internal structures of the hyaline cartilage; therefore, both sequences seem to be necessary in a standard MRI protocol for cartilage visualization. In diagnostically ambiguous cases, in which important therapeutic decisions are required, direct MR arthrography is the established imaging standard as an add-on procedure. Despite the social impact and prevalence, until recent years there was a paucity of knowledge about the pathogenesis of cartilage damage. With the introduction of high-resolution MRI with powerful surface coils and fat-suppression techniques, visualization of the articular cartilage is now routinely possible in many joints. After a short summary of the anatomy and physiology of the hyaline cartilage, the different MR imaging methods are discussed and recommended standards are suggested.

Cartilage, Articular↗
PubMed2002

[Coxarthrosis].

Osteoarthritis of the hip joint is a very common disease. There is a minor prevalence of males. By etiology one can distinguish primary (idiopathic) from secondary osteoarthritis. Secondary are due to well-known etiologies as overweight, repetitive traumata, malposture, muscle- and tendon-imbalance etc. Osteoarthritis includes not only cartilage abnormalities, but also such of the subchondral-region, synovialis, synovial fluid and periarticular muscles. The cartilage shows in osteoarthritis typically edema and swelling, defects with tears, fibrillation, and "baldness" and (or) cartilagenous repair-islands and joint space narrowing as well, while subchondrally micro-edema, necrosis, ev. microfractures, "cysts", demineralisation followed by sclerosis, osteophyte-formation and deformity is seen. With conventional radiographs and CT joint space narrowing, subchondral cysts, sclerosis and osteophytes and deformities are well delineated, MRI however allows visualization of subtle bone marrow and cartilage abnormalities. Clinically, the diagnosis of pre-osteoarthritis becomes more and more important. This includes e.g. deformities and malpostures, labrum-pathologies and structural imbalances. There are three prognostic different types of hip-osteoarthritis depending on the migration of the head of the hip joint: the most common are the latero-cranial and the medio-caudal ones, while the central one is found very rarely. Basic imaging method are conventional radiographs, and CT, followed by MRI. The diagnosis of an "activated osteoarthritis" is made by bone-scintigraphy or MRI with i.v. application of contrast-media. The labrum- and cartilage diagnosis should be done with MRI or MR-arthrography. Functional computer-animated analysis will be of great diagnostic value in the near future. MRI indications are differences between clinical results and imaging, missing clinical improvement of an "activated" osteoarthritis under standard therapy, unclear joint-pain and before any arthroscopy.

Aged↗
PubMed2002

The expression of bone morphogenetic proteins in osteosarcoma and its relevance as a prognostic parameter.

AIMS: The expression of bone morphogenetic proteins (BMPs) was analysed in 47 osteosarcomas to determine differences in the expression of BMP subtypes and to correlate expression with response to chemotherapy, in addition to the disease free and overall survival of patients. METHODS: The expression of BMPs was examined immunohistochemically in 47 biopsy specimens of osteosarcoma using commercially available antibodies against different subtypes (BMP-2/4 (A-20), BMP-3 (N-19), BMP-4 (N-19), BMP-5 (N-19), BMP-6 (N-19), BMP-7 (N-19), BMP-8 (N-19)). The avidin-biotin-immunoperoxidase method was used for all antibodies. RESULTS: The expression of BMP subtypes varied considerably: 28 of the 47 tumours expressed BMP-2/4, 24 expressed BMP-3, 41 expressed BMP-5, 31 expressed BMP-6, 43 expressed BMP-7, and 42 expressed BMP-8. High expression of BMP-6 was found in those parts of the osteosarcoma with a chondroid differentiation (p = 0.016, Mann-Whitney test). No correlation was observed between the response to chemotherapy and the expression of BMPs (p > 0.05, Mann-Whitney test). Univariate analysis showed no correlation between overall survival or progression free survival and the expression of BMPs (p > 0.05, log rank test). CONCLUSIONS: BMP-7 and BMP-8 are highly expressed in osteosarcoma. Moreover, high expression of BMP-6 correlates with a chondroid differentiation. In contrast to conclusions derived from previous studies in which small numbers of tumours were investigated, these results indicate that the expression of BMPs does not help to predict the outcome of patients.

Adolescent↗
PubMed2001

[Differential diagnostic problems in assessment of benign bone tumors].

The diagnosis of benign bone tumors can cause many problems and a definitive histological diagnosis is often impossible without the knowledge of clinical datas, age of the patient and anatomical location of the tumor. Therefor cooperation between pathologist, orthopedic surgeon and radiologist is necessary, to reduce the risk of misinterpretation of benign and malignant bone tumors. Benign bone tumors often show a heterogenous histology and overlapping morphology between different entities has to be kept in mind, as well as the sampling error in biopsy- and frozen section material. In most cases the pathologist has to rely on conventional stainings because the immunohistochemistry stainings are often not helpful.

Adolescent↗
PubMed2001

Bilaminar pattern of tibial condyle cartilage layer on the fat-suppressed 3D gradient echo images: artifact or structural and biochemical difference in composition of cartilage?

The purpose of this study was to examine if an unusual bilaminar pattern of lateral tibial condyle cartilage layer on the fat-suppressed three-dimensional (3D) spoiled gradient echo sequence is artifactual or correlates with structural and/or biochemical composition of cartilage. The laminar appearance of the lateral tibial condyle cartilage layer was studied on fat-suppressed 3D spoiled gradient echo MR images of the knee joint in 67 patients (mean age: 28y) performed at 1.0 Tesla. After i.v. administration of gadopentetate dimeglumine, diffusion of the contrast media into cartilage layer was qualitatively analysed over time on inversion recovery spin echo images of knee joints of five asymptomatic volunteers (mean age: 25y). In a patient with osteosarcoma and total knee replacement, MR examination of cartilage layer of lateral tibial plateau was compared with histologic specimens stained with Safranin-O, demonstrating proteoglycan distribution in cartilage. The retrospective analysis of 67 knee joints revealed a bilaminar appearance of lateral tibial condyle cartilage layer in the gradient echo images in the majority of cases (81%) with a statistically significant tendency to a trilaminar pattern in patients older than 20 years. With i.v. contrast administration, the contrast enhancement was only observed in the superficial zone of tibial cartilage layer. Histologic specimens in one patient demonstrated a good correlation between thickness of proteoglycan-free and proteoglycan-rich laminae of lateral tibial condyle on Safranin-O staining with hyperintense and hypointense zones, respectively, on corresponding fat-suppressed 3D spoiled gradient echo images (correlation coefficient of 0.87). Bilaminar pattern of tibial condyle cartilage layer on fat-suppressed 3D spoiled gradient echo images in younger subjects is not an artifact or an intrachondral lesion, but it may represent a regional difference in composition of extracellular cartilage matrix possibly produced by a highly-oriented collagen fiber structure associated with a high concentration of proteoglycans in the middle and deep portion of the cartilage layer.

Adolescent↗
PubMed2001

Leiomyoma in the space of Retzius: a report of 2 cases.

Leiomyomas most frequently occur in the genitourinary and gastrointestinal system. This report discusses clinical and pathologic findings of 2 leiomyomas in the pubovesical space, a location that has not been described before. Different operative approaches were used for excision. Immunohistochemical examination for the presence of estrogen and progesterone receptors was performed.

Actins↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

[Arthrosis--histology and pathogenetic approaches].

Osteoarthitis is the most common joint disease affecting over 60% of the elderly population. It is characterized by the progressive erosion of articular cartilage leading to incapacity of movement. In the great majority of instances, osteoarthritis appears insidiously, without apparent initiating cause. This primary form is usually oligoarticular involving hip, knee, cervical vertebrae, interphalangeal joints of the fingers or tarsometatarsal joints of the feet. In case of an underlying systemic disease or local injury the cartilage destruction is considered as secondary osteoarthritis. The pathogenesis of primary osteoarthritis suggests an intrinsic disease of cartilage in which biochemical and metabolic alterations result in its breakdown. Within the last decades different models were established which also concentrated on other joint structures such as bone or ligaments. Changes of the subchondral bone were found to precede cartilage damage suggesting a primary alteration of the subchondral region. Other studies concentrated on the metabolic activity of chondrocytes in healthy cartilage of osteoarthritis patients. The precise event that leads to these changes is still not clear. This review concentrates on the histological features in the course of the disease and tries to provide a summary on different pathogenetic concepts.

Aged↗
PubMed2000

Platelet-derived growth factor-AA and -alpha receptor expression suggests an autocrine and/or paracrine loop in osteosarcoma.

Platelet-derived growth factor (PDGF) is a major mitogen and chemotactic factor for mesenchymal cells such as fibroblasts, smooth muscle cells, and osteoblasts. PDGF exists as disulfide-linked homo- or heterodimers composed of two polypeptide chains encoded by distinct genes, designated PDGF-A and PDGF-B. Upon binding to its tyrosine kinase receptor PDGF-alpha, especially PDGF-AA stimulates the proliferation of osteoblastic cells and may exert autocrine and paracrine effects in regulating bone-forming processes. The purpose of this immunohistochemical study was to determine the expression of PDGF-AA and PDGF-alpha receptor in benign and malignant neoplastic bone lesions. Polyclonal antibodies to PDGF-AA and PDGF-alpha receptor were used on paraffin sections of 23 osteosarcomas and 17 osteoblastomas. Immunostaining was assessed quantitatively by evaluating the percentage of reactive tumor cells. In osteosarcomas, the mean expression of PDGF-AA and PDGF-alpha receptor was 33.97% (range, 2 to 80%; SD, 24.26%) and 27.13% (range, 3.2 to 72%; SD, 18.38%), respectively. Osteoblastomas showed significantly lower expression of PDGF-AA than osteosarcomas (mean, 15.71%; range, 5 to 34%; SD, 9.43%; P = .019). Although the mean expression of PDGF-alpha receptor in osteoblastomas was much lower than in osteosarcomas (mean, 17.55%; range, 3.6 to 26.8%; SD, 6.47%), the difference was not significant (P = .122). For osteosarcomas, Spearman correlation coefficient (two-tailed) revealed a significant correlation between the expression of PDGF-AA and PDGF-alpha receptor (r = .688), which was not the case for osteoblastomas (r = .267). These data suggest that in contrast to osteoblastoma, the growth of osteosarcoma may be supported by the coordinate expression of the potent mitogenic growth factor and its receptor that exert their functions by autocrine and paracrine mechanisms.

Autocrine Communication↗
PubMed2000

Periosteal osteoblastoma: a case report and a review of the literature.

Osteoblastomas located on the surface of cortical bone, so-called periosteal (juxtacortical) osteoblastomas, are extremely rare. A 24-year-old man complained of pain and swelling in the left knee. The clinical and radiological investigation showed a tumor located in the posterior portion of the distal shaft of the femur. The radiological differential diagnosis included parosteal osteosarcoma, periosteal chondroma and periostitis ossificans. A frozen section was obtained and histology revealed an osteoblastoma with large epithelioid-appearing osteoblasts consistent with an aggressive osteoblastoma. An en bloc resection of the tumor was performed and the definitive histology of the whole specimen revealed a typical osteoblastoma. The authors draw attention to the fact that periosteal osteoblastoma is a rare tumor that could be mistaken clinically and histologically for other and more common tumors at this location.

Adult↗
PubMed2000

Subchondral bone and cartilage disease: a rediscovered functional unit.

The role of subchondral bone in the pathogenesis of cartilage damage has likely been underestimated. Subchondral bone is not only an important shock absorber, but it may also be important for cartilage metabolism. Contrary to many drawings and published reports, the subchondral region is highly vascularized and vulnerable. Its terminal vessels have, in part, direct contact with the deepest hyaline cartilage layer. The perfusion of these vessels accounts for more than 50% of the glucose, oxygen, and water requirements of cartilage. Bony structure, local metabolism, hemodynamics, and vascularization of the subchondral region differ within a single joint and from one joint to another. Owing to these differences, repetitive, chronic overloading or perfusion abnormalities may result in no pathological reaction at all in one joint, while in another joint, these same conditions may lead to osteonecrosis, osteochondritis dissecans, or degenerative changes. According to this common etiological root, similar pathological reactions beginning with marrow edema and necrosis and followed by bone and cartilage fractures, joint deformity, and insufficient healing processes are found in osteonecrosis, osteochondritis dissecans, and degenerative disease as well.

Biomechanical Phenomena↗
PubMed1998

[Special diagnostic problems in primary malignant bone tumors].

The diagnosis of primary malignant bone tumors, which only account for 1% of malignancies in humans, represents quite a challenge for the pathologist. Apart from the often overlapping morphology between different entities, heterogeneity within one and the same tumor has to be kept in mind. Furthermore, in most cases the diagnosis must be established based on small biopsy specimens and occasionally even on frozen sections. In this context detailed clinical information including the patient's age and exact localization of the tumor, as depicted by X-ray or MRI, are essential requirements for a correct diagnosis. In addition, multiple biopsies from different tumor sites may be of help. For example, 25% of osteogenic sarcomas (OSA) are chondroplastic. Others may contain areas similar to fibrosarcoma (FSA) or malignant fibrous histiocytoma (MFH). Since 90% of OSA occur in the second decade of life whereas chondrosarcomas, FSA and MFH usually manifest after the age of 40 years, a biopsy solely composed of malignant chondromatous tissue obtained from a tibial lesion of a 10-year-old child should most likely be considered as part of an OSA. In the differential diagnosis of the so-called small, round cell tumors, which include Ewing sarcoma, malignant lymphoma and small-cell OSA, immunohistochemical staining of the paraffin-embedded material and a molecular biological/genetic work-up of frozen material are most helpful. In this paper the histomorphological characteristics and criteria for differential diagnosis of the most common primary malignant bone tumors are discussed.

Bone Neoplasms↗
PubMed1997

Expression of VS38 in osteoblasts and stroma cells of bone tumors.

VS38 is a mouse monoclonal antibody which recognizes an intracytoplasmic antigen of 64 kilodaltons present in normal and neoplastic cells. It was reported to be of potential value in identifying myeloma or plasmacytoma in bone marrow or other tissues. During diagnostic analysis of bone marrow biopsies we noticed a consistent staining of osteoblasts with VS38. This led us to investigate the immunoreactivity in a range of bone lesions. 58 lesions were examined in the current study, including benign and malignant tumors as well as tumor like lesions and processes with reactive bone formation. The Streptavidin-peroxidase complex technique was applied on paraffin embedded sections, with 3-amino-9-ethylcarbazole serving as chromogen. All osteoblasts of reactive origin and part of the osteoblasts of benign neoplasms showed positive immunostaining. The antibody stained stroma cells in 81.25% (13/16) of the cases of benign osteogenic tumors and in 82.35% (14/17) of the osteosarcomas. Additionally, VS38 labelling was observed in bone tumors of fibrohistiogenic origin such as nonossifying fibroma and giant cell tumor, the histogenesis of which is still being debated. On the whole, it can be concluded that antibody VS38 lacks specificity as a plasma cell marker. It shows, however, a striking affinity to osteoblasts and in part also to stroma cells of osteogenic and fibrohistiogenic bone tumors.

Antibodies, Monoclonal↗