Biomedical subjects

M Werner

Publications and source records attributed to M Werner.

At least 37 records · Page 2Linked to original sources

PubMed2004

Asthma is associated with single-nucleotide polymorphisms in ADAM33.

BACKGROUND: The ADAM33 gene has recently been associated with asthma and bronchial hyper-reactivity. It codes for a disintegrin and metalloproteinase that triggers intra- and extracellular signalling by protein shedding. OBJECTIVE: We examined whether polymorphisms in ADAM33 are associated with asthma and related traits in two German populations. METHODS: We genotyped 15 intragenic single-nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of allele-specific primer extension products. The transmission disequilibrium test was used for association analysis in the German asthma family study. Additionally, we tested for association of these SNPs in a case-control sample from the European Community Respiratory Health Study using Armitage's trend test. RESULTS: In both studies, we found SNPs that were significantly associated with asthma and related traits. In the family study, significant associations were observed for the SNPs F+1, ST+4 and ST+5 (with the lowest P-value for F+1, P=0.005). Remarkably, this association is seen even in the absence of linkage with two microsatellite markers from a previous genome scan either 3.1 million bases (Mb) up- or 5.6 Mb downstream. In the case-control study, SNP ST+7 (P=0.008) was significantly associated with asthma. Some of these SNPs overlapped with those found to be associated with elevated total IgE levels and bronchial hyper-responsiveness. CONCLUSION: This study replicates the recently published association between asthma and ADAM33 gene variants. However, most of the associated SNPs were at non-identical positions in the German, UK and US samples. As linkage disequilibrium is high among the tested SNPs, and there is no known functional polymorphism, either not-tested variants in ADAM33, unknown regulatory elements or a gene in close proximity is responsible for this association.

ADAM Proteins↗

PubMed2004

The Munich Barrett follow up study: suspicion of Barrett's oesophagus based on either endoscopy or histology only--what is the clinical significance?

BACKGROUND: The incidence of distal oesophageal adenocarcinoma is rising, with chronic reflux and Barrett's oesophagus being considered risk factors. Reliable detection of Barrett's oesophagus during upper endoscopy is therefore mandatory but requires both endoscopy and histology for confirmation. Appropriate management of patients with endoscopic suspicion but negative on histology, or vice versa, or of patients with no endoscopic suspicion but with a biopsy diagnosis of intestinal metaplasia at the gastro-oesophageal junction, has not yet been studied prospectively. PATIENTS AND METHODS: In a prospective multicentre study, 929 patients (51% male, mean age 50 years) referred for upper gastrointestinal endoscopy were included; 59% had reflux symptoms. The endoscopic aspect of the Z line and any suspicion of Barrett's oesophagus were noted, and biopsies were taken in all patients from the Z line (n = 4), gastric cardia (n = 2), and body and antrum (n = 2 each). Biopsies positive for specialised intestinal metaplasia (SIM) were reviewed by a reference pathologist for a final Barrett's oesophagus diagnosis. All patients with endoscopic and/or histological suspicion of Barrett's oesophagus were invited for a follow up endoscopy; the remaining cases (no endoscopic or histological suspicion of Barrett's oesophagus) were followed clinically. RESULTS: Of 235 patients positive for Barrett's oesophagus on endoscopy and/or histology, 63% agreed to undergo repeat endoscopy (mean follow up period 30.5 months). 46% of patients with an endoscopic Barrett's oesophagus diagnosis but no histological confirmation (group A) showed the same distribution, a further 42% did not have Barrett's oesophagus, and 11% had confirmed Barrett's oesophagus on both endoscopy and biopsy on follow up. In the group with a histological Barrett's oesophagus diagnosis but negative on initial endoscopy (group B), follow up showed the same in 26% whereas 46% had no Barrett's oesophagus, and confirmed Barrett's oesophagus (endoscopy plus histology) was diagnosed in 17%. Of the study population, 16 patients had Barrett's oesophagus on initial endoscopy confirmed by histology which remained constant in 70% at follow up (group C). Of the remaining patients without an initial Barrett's oesophagus diagnosis on either endoscopy or histology (group D) and only clinical follow up (mean follow up period 38 months), one confirmed Barrett's oesophagus case was found among 100 patients re-endoscoped outside of the study protocol. However, no single case of dysplasia or cancer of the distal oesophagus was detected in any patient during the study period. CONCLUSIONS: Even in a specialised gastroenterology setting, reproducibility of presumptive endoscopic or histological diagnoses of Barrett's oesophagus at follow up were poor. Only 10-20% of cases with either endoscopic or histological suspicion of Barrett's oesophagus had established Barrett's oesophagus after 2.5 years of follow up. The risk of dysplasia in this population was very low and hence meticulous follow up may not be required.

Adolescent↗

PubMed2003

Identification of occult tumor cells in node negative lymph nodes of colorectal cancer patients by cytokeratin 20 gene and protein expression.

BACKGROUND AND AIMS: Evaluation of cytokeratin 20 (CK20) specific quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) and immunohistochemistry (IHC) for detection of occult tumor cells in lymph nodes of 72 patients with colorectal carcinoma (UICC stage I and II). METHODS: Serial sections of formalin-fixed, paraffin-embedded lymph nodes (mean 14.3/case) were used for microdissection, RNA isolation and QRT-PCR and for CK20 IHC using routine protocols. Results of QRT-PCR and IHC were compared and correlated to the CK20 expression pattern of the primary tumors and clinical follow-up. RESULTS: IHC revealed CK20-positive tumor cells in lymph nodes of 14.5% (10/69) and 0% (0/3) cases with a CK20-positive and CK20-negative primary tumor, respectively. CK20 mRNA was detected in the lymph nodes of 36.8% (7/19) cases by QRT-PCR with all 7 cases also expressing CK20 mRNA in the primary tumor. CK20 mRNA (QRT-PCR) and protein (IHC) detection in serial sections did not agree in 25% (5/20) of cases. A trend was seen towards a worse disease course for patients with CK20-positive lymph nodes by IHC (incidence of recurrent disease) and QRT-PCR (disease-free survival, incidence of recurrent disease). CONCLUSION: CK20-specific IHC and QRT-PCR are supportive tools to conventional histology for detection of occult tumor cells in archival tissues, with the restriction that a laborious QRT-PCR procedure is necessary to achieve appropriate specificity. A prognostic value of CK20 IHC or QRT-PCR for stratification of UICC stage I and II patients into those likely to develop recurrent disease was not evident.

Biomarkers, Tumor↗

PubMed2003

[Pathomorphology of parosteal osteosarcoma. Experience with 125 cases in the Hamburg Register of Bone Tumors].

Parosteal osteosarcoma is a rare low-grade bone tumor. It occurs between the 2nd and 8th decade of life. In our own series of 125 parosteal osteosarcomas, most patients were aged between 30 and 40. The most frequent location was the distal dorsal femur. Until clearly proven otherwise, a bone-forming tumor in this location has to be regarded as a parosteal osteosarcoma. Of all parosteal osteosarcomas 77% are located in the lower extremity, with a female sex predominance in this location (62%); 18% are located in the upper extremity; 15% of all parosteal osteosarcomas are located in the humerus. Just 6% of all parosteal osteosarcomas are observed in the skull, the spine, and the pelvis. The tumor is characterized by hyalinized fibrous stroma with a low cell content without substantial nucleus polymorphism and variably dense bony trabeculae. The diagnosis can be difficult due to highly differentiated areas with fat tissue within the marrow and very uniformly bony structure. The operation material has to be analyzed very carefully, because the extent of dedifferentiated areas and most probably also the extent of invasion of the medullary cavity determine the prognosis and occurrence of recurrencies. The tumor is most commonly misinterpreted as osteochondroma or heterotopic ossification. Paying attention to all radiologic and histologic criteria,osteoblastic eccentrically located high-grade osteosarcomas can be clearly distinguished from parosteal osteosarcoma. An intramedullary located low-grade osteosarcoma,which is differentiated like a parosteal osteosarcoma,is histologically indistinguishable from the parosteal variant. This variant requires the synthesis of all available data to find the correct diagnosis. The parosteal osteosarcoma shows like no other tumor the necessity of close cooperation of all involved disciplines for diagnosis and therapy.

Adolescent↗

PubMed2003

[Telecommunication and telepathology in orthopedic oncology. Possibilities in diagnosis and therapy of primary malignant bone tumors].

The rareness of primary malignant bone tumors and the difficulty of differential diagnosis make this field a part of oncology in which the consulting physician must rely on consistent histopathological monitoring of highest quality throughout the diagnostic and therapeutic process. In a pilot project of the Department of Bone Pathology of the University of Hamburg and the Orthopedic Department of the University of Heidelberg, 190 cases of suspected primary bone tumor were the subject of interdisciplinary discussion between July 2001 and March 2003 using a telepathology system established for this purpose. Diligent differential diagnoses were made prior to the biopsy; optimal location and further strategy for the biopsy were discussed and determined according to the guidelines of the international bone tumor centers. This also included the decision if intraoperative pathological examination of frozen sections should be performed. In 51 cases such examinations were performed. Those results immediately influenced the surgical procedure. Telepathology performed as described in this article led to a close interdisciplinary cooperation over a large distance and helped significantly to optimize therapy of patients with malignant bone tumors.

Biopsy↗

PubMed2003

[Pigmented villonodular synovitis of the hip--diagnosis and therapy of an invasive disease].

In the diffuse form of pigmented villonodular synovitis, the transformed synovia invades local bone and cartilage, leading to destruction of the osseous and cartilage tissue. Secondary osteoarthritis and ultimately joint destruction is a result. Malignant development is under discussion. The knee is the most frequently involved joint, followed by involvement of the hip, which is well documented in several studies. This paper introduces a case of pigmented villonodular synovitis involving the hip. Its general diagnostic features and treatment options are introduced and discussed, including the role of reconstructive joint surgery in advanced cases of PVS. The key function of early diagnosis and treatment resulting in joint-salvaging procedures is emphasized.

Adult↗

PubMed2003

Osteotomy with 80-micros CO2 laser pulses--histological results.

Haemostatic and aseptic effects and intricate cut geometry are beneficial aspects of non-contact laser osteotomy. Collateral thermal damage, however, has severely limited the use of conventional lasers. The purpose of this study was to test the side effects on bone after cutting it with short CO2 laser pulses and simultaneous application of a fine air-water spray. The 10.6 microm CO2 laser emitted 80 micros pulses of 46 mJ energy, f=100 Hz, focused to a spot diameter of 130 ìm. Scan rate amounted to 40 mm/s. To approximate live conditions 10 samples of cortical bone and 10 rib segments were prepared immediately after sacrificing of pigs. A reference cut with a bandsaw and three laser cuts with an increasing number of beam passes (4, 16, 64) were performed on each sample. Half of the samples were decalcified in EDTA. The others were embedded in plastic to cut non-decalcified sections. The laser incisions were not accompanied by carbonisation. The incisions with slightly convergent walls were 150 ìm wide. The depths of the cavities increased with the number of the beam passes from approximately 0.5 mm (4 passes) to 3 mm (64 passes). At the border of the incisions two narrow zones of damage were noted: an amorphous intensively stained zone of 1-3 microm width and a wider, also sharply demarcated but faintly stained zone of 7-10 microm. A broader zone of about 50 microm was characterised by empty lacunae and osteocyte damage. These effects were not predictable; intact osteocytes were also observed near to the cut surface. Polarised light microscopy showed no alterations in the inorganic structure of the bone at the cut borders. The histological results indicated only minimal damage to bone ablated at the specified parameters. The described laser procedure might have advantages over mechanical instruments.

Animals↗

PubMed2003

Biopsy surveillance is still necessary in patients with Barrett's oesophagus despite new endoscopic imaging techniques.

BACKGROUND AND AIMS: Endoscopic surveillance including stepwise four quadrant biopsies (4QB) is still regarded as the standard approach in patients with Barrett's oesophagus (BO). Several methods such as dye staining with methylene blue (MB) and tissue autofluorescence (AF) have been advocated to reduce the number of biopsies. We assessed their sensitivity and specificity compared with the standard approach-that is, endoscopy with 4QB-in the surveillance of a mixed BO population. PATIENTS AND METHODS: Thirty five consecutive BO patients (mean age 64.9 years; 30 men, five women) were included in the study. AF endoscopy was followed by high resolution video endoscopy (VE) plus tissue staining with 0.5% MB. Biopsies were taken from any suspicious area found on any of the above tests, in addition to 4QB every 2 cm. The results were classified as either positive or negative for the various tests used. Histopathological results were used as the reference standard. RESULTS: In the 35 study patients, a total of 345 biopsies showed low grade dysplasia (LGD) in 88 biopsies, high grade dysplasia (HGD) in 19 biopsies, and carcinoma in 12 biopsies. The sensitivity and specificity rates for AF and MB for the diagnosis of cancer or dysplasia versus BO mucosa without dysplasia were 21%/91% and 37%/91%, respectively. 4QB revealed five cancer/HGD areas and 76 LGD areas not detected by AF, MB, or VE. The additional yield of MB and AF over VE with 4QB concerned only one HGD area (in the vicinity of a cancer) and seven LGD areas. CONCLUSIONS: Due to their low sensitivity, AF and MB are not suitable techniques for reducing the high numbers of routine biopsies needed for finding additional foci of HGD or cancer. Careful endoscopic observation and stepwise four quadrant biopsy therefore still represent the gold standard for surveillance of Barrett's oesophagus.

Adenocarcinoma↗

PubMed2002

[Histogenesis of giant cell tumors].

The giant cell tumor of bone (GCT) is a local osteolytic tumor with variable degrees of aggressiveness. In rare cases pulmonary metastases can be observed. The lesion most frequently occurs in the epiphysis of long tubular bones of the knee region, predominantly affecting young adults after closure of the growth plate. The characteristic histological appearance of GCT displays a high number of osteoclast-like multinucleated giant cells, which resulted in the classification "osteoclastoma" or "giant cell tumor". Apart from the multinucleated giant cells, there are two mononuclear cell types in the GCT. The first one has a round morphology and resembles a monocyte. The second cell type is the spindle-shaped, fibroblast-like stromal cell. Cell culture experiments with GCT cells revealed the stromal cell to be the proliferating component of the GCT. The other two cell types, the monocyte and the multinucleated giant cell, were lost after a few cell culture passages. Furthermore, latest results from GCT reveal that the stromal cells secrete a variety of cytokines and differentiation factors, including MCP1, ODF and M-CSF. These molecules are monocyte chemoattractants and are essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells. The multinucleated giant cell itself demonstrates properties of a normal osteoclast that is able to resorb bone leading to extended osteolysis. This new model of GCT genesis supports the hypothesis that the stromal cell is the neoplastic component whilst the monocytes and the multinucleated giant cells are just a reactive component of this tumor. Taking this into consideration, the nomenclature of the "giant cell tumor" needs to be reconsidered.

Bone Neoplasms↗

PubMed2002

[Telecommunication and telepathology. New diagnostic routes for orthopaedics and orthopaedic pathology].

In a pilot project of the Department of Bone Pathology of the University of Hamburg and the Orthopaedic Department of the University of Heidelberg, the cases of 121 patients with suspicion of a primary bone tumour have been discussed at weekly interdisciplinary conferences during the period from July 2001 to May 2002., The consequent differential diagnoses were made prior to the biopsy, the optimal location of the biopsy and the further strategy was determined according to the guidelines of the international bone tumour centres. The latter includes the decision if a conventional biopsy or a intraoperative pathology examination on frozen sections should be performed. In 27 cases an intraoperative pathology examination was performed and then assessed in Hamburg. In 24 cases this diagnosis was identical with the final diagnosis. In three cases no definitive diagnosis could be made from the frozen sections. Additionally the pathohistological diagnoses of the cases of the previous week have been discussed in the video-conferences. Through this a unusually close interdisciplinary cooperation over a large distance has evolved, that is highly appreciated especially by the young and less experienced colleagues at the department of bone pathology and the orthopaedic department in Heidelberg. The awareness of the potential and limitations of a medical subject leads to an improved safety in the diagnostic process for bone tumours. The interdisciplinary discussion of all aspects of the diseases may also optimise the therapy of bone tumours.

Bone Neoplasms↗

PubMed2002

[Comparative DNA cytometric investigations on aneurysmal bone cysts and giant cell tumors].

Giant cell-rich bone lesions consist of tumor-like lesions and true neoplastic giant cell tumors. In this study it was investigated whether DNA cytometry may contribute to the differential diagnosis between aneurysmal bone cysts and giant cell tumors. Statistically significant differences in the frequency of tetraploid stemlines were detected. Nevertheless, the knowledge of age, localization and radiological signs in addition to morphological findings are essential to distinguish between these lesions.

Adolescent↗

PubMed2002

[Fibrous dysplasia].

The observations in 222 cases of fibrous dysplasia of the Hamburg Bone Tumor Registry will be presented. This benign lesion is based on the appearance of postzygotic point mutations in a gene encoding the Gsa protein. It occurs as a mono- and a polyostotic variant and may affect every bone of the skeleton. Most often affected are the proximal femur, the skull and the ribs. Polyostotic lesions tend to occur on one side of the body. The monostotic form is 7.6 times more frequent, but both variants show no predilection for gender. Most cases are diagnosed during adulthood. On x-rays the lesion has a ground-glass appearance and is located intramedullary with a sharply defined edge. The cortical bone is arroded and the bone is expanded. Histologically typical signs are slender curved fibrous trabeculae with a C and Y shape embedded in a morphologically bland and moderately cellular fibrous stroma. Diagnostically important are collagen fibres emerging perpendicular from the surface of the trabeculae. Cartilage is present in 8% of the cases. Therapeutically, thorough clinical controls are indicated and operative procedures are rarely needed to prevent progressive deformities and fractures. The formerly applied radiotherapy is now obsolete because of the increased occurrence of malignant transformations.

Bone Resorption↗

PubMed2002

[Clinical pathological aspects of Mazabraud's syndrome].

Mazabraud's syndrome is a rare, sporadic disorder characterised by the association of mainly polyostotic fibrous dysplasia and intramuscular myxoma. Fibrous dysplasia is mostly diagnosed at a younger age, while myxomas only occur during adulthood. We report a case of a 42-year-old female with Mazabraud's syndrome where a polyostotic fibrous dysplasia was already diagnosed and at presentation two newly formed intramuscular myxomas were found in the gluteal muscle.

Adult↗

PubMed2002

In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised double-blinded placebo controlled phase I study in healthy individuals.

BACKGROUND: Several studies have been performed in tumour patients to analyse the immunological response to mistletoe extracts. Considering the fact that these extracts are given subcutaneously in most instances, the kind of application resembles a typical immunization schedule. We therefore wanted to see how those extracts act on immunocompetent cells of healthy individuals hoping that this kind of provocation test may give new informations about a more specific application of these extracts in certain diseases. SUBJECTS/METHODS: 47 healthy individuals were exposed for twelve weeks either to Iscador Quercus special (IQ) known to be rich in mistletoe lectin (ML)-1 (n = 16), to Iscador Pini (IP) being poor in ML-1 but enriched in viscotoxins (n = 15), or to placebo (physiological saline) (n = 16) in a randomised, double-blinded placebo-controlled study. Humoral immunoreactivity was analysed by measuring antibodies towards the two compounds ML-1 and viscotoxin VA2 (VA2). Sera were collected in intervals of four weeks up to week 12 and again three months after last exposure. RESULTS: None of the subjects had antibodies to ML-1 or VA2 before exposure. In week 12, anti-ML-1 antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6 of the 15 probands exposed to IP. In contrast, anti-VA2 IgG-antibodies could be detected in all individuals of both groups. The antibodies were preferentially of the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced only in a few probands. Antibodies of the IgE-type occurred only in the IQ-exposed individuals and were directed against ML-1 but not VA2. None of the probands receiving placebo developed antibodies to ML-1 or VA2. Severe side effects were not observed in any of the probands. CONCLUSIONS: These data obtained in healthy individuals clearly indicate that IQ and IP-extracts can induce antigen-specific humoral responses. They may, therefore, provide, a solid basic for the evaluation of the humoral immune response in disease states.

Adult↗

PubMed2002

Preoperative chemotherapy unmasks underlying Barrett's mucosa in patients with adenocarcinoma of the distal esophagus.

BACKGROUND: Intestinal metaplasia of the distal esophagus frequently cannot be detected in patients with esophageal adenocarcinoma. It has therefore been questioned whether Barrett's esophagus is the primary precursor lesion of such lesions. We hypothesized that the underlying Barrett's mucosa may be masked by tumor overgrowth in the majority of these patients. METHODS: The pretherapeutic endoscopy and biopsy records of 79 patients with locally advanced esophageal adenocarcinoma who had undergone preoperative chemotherapy were reviewed and compared to findings on restaging endoscopy/biopsy and subsequent resection and histopathologic analysis of the resected specimen. RESULTS: Pretherapeutic endoscopy and biopsy showed associated Barrett's esophagus in 59/79 patients, whereas there was no evidence of associated intestinal metaplasia in 20/79 patients on extensive biopsies. Following neoadjuvant chemotherapy, Barrett's mucosa was unmasked and later documented by biopsy or histopathologic assessment of the resected specimen in 18 of the latter 20 patients. This resulted in an overall association of Barrett's mucosa with adenocarcinoma in the distal esophagus of 97.4% CONCLUSION: Underlying Barrett's mucosa is frequently masked by tumor overgrowth in patients with locally advanced adenocarcinoma of the distal esophagus.

Adenocarcinoma↗

PubMed2002

[Low-grade central osteosarcoma . 3 case reports].

Low-grade central osteosarcoma is a well-differentiated subtype of osteosarcoma, which is often confused with benign lesions. Males and females were affected about equally in our study. The tibia and femur were most commonly involved. Three case reports demonstrate the distinct features of the tumor. Excision of the tumor almost invariably led to recurrences. Wide resection was almost never followed by recurrence and seems to be the treatment of choice for this very rare variant of osteosarcoma.

Adolescent↗

PubMed2002

[Molecular pathologic diagnosis in solid tumors. What is clinically relevant?].

There are only a few clinically relevant applications of molecular pathology assays in solid tumors. Among the findings which may influence therapy decisions are the amplification of Her-2/new in breast cancer and specific translocations in sarcomas. Mutation analyses of p53 may be helpful for only a very few cases, e.g. for confirming high grade dysplasia in the upper gastrointestinal tract or for diagnosing malignant soft tissue tumors in isolated cases. Microsatellite analyses are important for HNPCC screening or distinguishing tissue specimens of questionable identity. Other applications of molecular pathology assays such as detection of minimal residual disease or tumor cell dissemination and FISH analysis of urine and effusion specimens, may be increasingly applied in the future.

Biomarkers, Tumor↗

PubMed2002

[Morphological diagnosis of spinal diseases. Current technical possibilities and challenges for the histological preparation of transpedicular biopsies].

The spine is the central component for the mobility of the human body. Both locally limited and diffuse pathologies of the spine are a challenge for the treating physician due to the difficult anatomy. The biopsy of a pathologically altered vertebral body is a fast and reliable basis for further therapy but until now this has not regularly been made use of as a diagnostic standard for spinal diseases, since the tissue gained was often microfractured because of the difficult anatomical position. Our own experience with transpedicular vertebral biopsies of 70 patients with different diseases is reported because of the considerable improvement in the biopsy technique and the methodical possibilities for processing the bony tissue. Methods which have proven particularly valuable are contact radiographs, embedding in plastic, careful decalcifying with EDTA and immunohistological procedures. In this way a definite diagnosis can be made in 97% of the cases. A close cooperation with the clinician carrying out the biopsy and a greater use of methods other than just fast decalcification is recommended.

Biopsy↗