Biomedical subjects

S Philippou

Publications and source records attributed to S Philippou.

At least 19 recordsLinked to original sources

PubMed2003

[Prostate cancer diagnosis using ultrasound elastography. Introduction of a novel technique and first clinical results].

During the last decade screening has improved prostate cancer detection. The main reason for this development is a better understanding of the margins of prostate-specific antigen (PSA) serum levels and the classification of PSA subtypes. In contrast, the introduction of transrectal ultrasound has not led to a measurable change in the prostate cancer detection rate. Our aim was to develop a novel ultrasound system for the acquisition of elastographic images of the prostate and evaluate the system regarding its clinical applicability. We used a technically modified conventional ultrasound system and analyzed the high-frequency ultrasonic data with a computer program. The first patient-based results suggest that elastography allows an accurate measurement of tumor size and localization in contrast to conventional transrectal ultrasound. Elastography visualizes different tissue elasticities to distinguish benign and cancerous tissue. Thus, we were able to even correctly classify prostate cancer lesions which are iso- or hyperechoic in B-mode sonography.

Aged↗

PubMed2003

Ultrasonic tissue characterization for prostate diagnostics: spectral parameters vs. texture parameters.

An ultrasonic multi-feature tissue characterizing system for the detection of prostate cancer is presented. The system is based on the processing of radio frequency (RF) ultrasonic echo data. Data from 100 patients was acquired in a clinical study. Parameters are extracted from the RF echo data and classified using two adaptive network-based fuzzy inference systems (FIS) working in parallel as a nonlinear classifier. Next to spectral parameters, conventional texture parameters are calculated using demodulated and log-compressed echo data. In the first approach, the classifier is trained on both, spectral and texture parameters. In the second approach, the classifier is only trained on texture parameters. Classification results of both approaches are compared and it is demonstrated, that only the use of spectral parameters yields satisfying classification results. Results of a minimum distance classifier (MDC) are presented for comparison with the fuzzy inference system. For the final fuzzy inference systems used in this approach, the area under the ROC curve is between 84% and 86% for the combined approach and between 70% and 74% for the approach based on texture parameters only.

Aged↗

PubMed2002

Health hazards due to the inhalation of amorphous silica.

Occupational exposure to crystalline silica dust is associated with an increased risk for pulmonary diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and lung cancer. This review summarizes the current knowledge about the health effects of amorphous (non-crystalline) forms of silica. The major problem in the assessment of health effects of amorphous silica is its contamination with crystalline silica. This applies particularly to well-documented pneumoconiosis among diatomaceous earth workers. Intentionally manufactured synthetic amorphous silicas are without contamination of crystalline silica. These synthetic forms may be classified as (1) wet process silica, (2) pyrogenic ("thermal" or "fumed") silica, and (3) chemically or physically modified silica. According to the different physicochemical properties, the major classes of synthetic amorphous silica are used in a variety of products, e.g. as fillers in the rubber industry, in tyre compounds, as free-flow and anti-caking agents in powder materials, and as liquid carriers, particularly in the manufacture of animal feed and agrochemicals; other uses are found in toothpaste additives, paints, silicon rubber, insulation material, liquid systems in coatings, adhesives, printing inks, plastisol car undercoats, and cosmetics. Animal inhalation studies with intentionally manufactured synthetic amorphous silica showed at least partially reversible inflammation, granuloma formation and emphysema, but no progressive fibrosis of the lungs. Epidemiological studies do not support the hypothesis that amorphous silicas have any relevant potential to induce fibrosis in workers with high occupational exposure to these substances, although one study disclosed four cases with silicosis among subjects exposed to apparently non-contaminated amorphous silica. Since the data have been limited, a risk of chronic bronchitis, COPD or emphysema cannot be excluded. There is no study that allows the classification of amorphous silica with regard to its carcinogenicity in humans. Further work is necessary in order to define the effects of amorphous silica on morbidity and mortality of workers with exposure to these substances.

Air Pollutants, Occupational↗

PubMed2001

Modulation of angiogenesis and tumorigenicity of human melanocytic cells by vascular endothelial growth factor and basic fibroblast growth factor.

Human melanoma cells express two prominent angiogenic factors, e.g., vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF/fibroblast growth factor-2). In this study, we report on the relative contribution of these two factors to in vitro and in vivo growth of a tumorigenic melanoma cell line (WM164) and nontumorigenic, immortalized melanocytes (FM516SV). Overexpression of either cytokine significantly boosted tumorigenicity of WM164 cells in immunodeficient SCID mice. Attempting to overexpress bFGF antisense sequences produced no viable clones confirming earlier reports that autocrine bFGF is obligatory to melanoma cell survival and growth. By contrast, down-regulation of endogenous VEGF production did not affect growth of WM164 cells in vitro. In vivo expansion of WM164 cells expressing VEGF antisense was delayed but not abrogated. Forced expression of either bFGF or VEGF in immortalized but nontumorigenic melanocytes did not induce sustained tumor growth in vivo highlighting that neither of the two factors is sufficient for induction of tumorigenicity in this model system. Overexpression of either cytokine in WM164 cells led to the development of atypical large vessels but not to an increase in microvessel density. Taken together our results confirm an essential autocrine role of bFGF in human melanoma and indicate a beneficial but nonessential role of VEGF in the tumorigenic phenotype of human melanoma cells.

Animals↗

PubMed2001

Glutathione transferase activities in renal carcinomas and adjacent normal renal tissues: factors influencing renal carcinogenesis induced by xenobiotics.

In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugation with glutathione. It has mostly been assumed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n = 21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1-chloro-2,4-dinitrobenzene for overall GST activity (except GST theta); 7-chloro-4-nitrobenzo-2-oxa- 1,3-diazole for GST alpha; 1,2-dichloro-4-nitro-benzene for GST mu; ethacrynic acid and 4-vinylpyridine for GST pi; and methyl chloride for GST theta. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling.

Aged↗

PubMed2000

Biomechanical investigations on chondromalacia of the knee after meniscal flap lesion and partial meniscal resection: an experimental model.

Meniscal tears and resections may cause chondral lesions of the knee. To eliminate muscular control during investigation of this problem, we designed a biomechanical setup based on a knee-joint simulator, ensuring physiological, free-motion mobility of the joint. Fresh human knee specimens with intact cartilage were exposed to loads to 2,000 N at a frequency of 0.85 Hz during 48 hours of gait. After a preliminary test series, 18 specimens were divided into three groups: group I was tested with unchanged meniscal status, group II with arthroscopically induced mobile flap tears at the posterior horns of the menisci, and group III after partial resection of the posterior horns. Motion patterns between the groups changed after as little as a few hours due to increased translation in group III. Macroscopic and histological examination and scanning electron microscopy revealed severe chondromalacic changes after meniscal resection. We conclude that meniscal resection-however partial-may have considerable joint-damaging potential if muscle control is lacking whereas mobile flap tears maintain stability. Our findings might explain the differences in clinical reports on cartilage status after partial meniscal resection. This study underlines the importance of muscle training when active stabilisation of the knee is reduced after partial meniscal resection.

Adult↗

PubMed2000

Respiratory syncytial virus-induced chronic bronchiolitis in experimentally infected calves.

Human (RSV) and bovine (BRSV) respiratory syncytial virus cause similar infections of the lower respiratory tract. Therefore, experimentally infected calves are suited to the study of RSV-induced chronic bronchiolitis. Colostrum-fed calves aged 17-24 days were successfully infected with BRSV. BRSV strain 375 was applied as an aerosol on 4 consecutive days. Clinical symptoms were already evident on the 1st day after infection. The calves were necropsied 12 weeks after the first infection. Focal severe chronic bronchiolitis with atelectasis and focal bronchiolitis obliterans were demonstrated. The bronchiolar lumina were filled with secretion. Transmission electron microscopy revealed an alteration of the ciliogenesis and partial loss of cilia. Immunhistochemically virus P protein could still be detected, mainly in the epithelial cells of the inflamed bronchioli.

Animals↗

PubMed2000

[Quantitative vascular analysis in the marginal periodontium using PECAM-1].

BACKGROUND: Systemic sclerosis (SSc) is a generalized disorder of the interstitial tissues and vasculature with distinct abnormalities in three systems, immune and autoimmune, vascular and microvascular, and mesenchymal extracellular matrix (ECM), that lead to exuberant fibrosis. The aim of this study was to compare the number of blood vessel profiles in the marginal gingiva between SSc patients and patients with periodontitis but without SSc by using biopsies. METHODS: Marginal gingiva and gingival papilla were obtained from 13 scleroderma patients and 8 patients with periodontitis after routine tooth extraction and gingival curettage. On the histological sections, immunohistochemical investigations were performed using the avidin-biotin complex method (ABC) and the monoclonal antibody CD 31/Clone JC70A (platelet endothelial cell adhesion molecule-1). Blood vessels were identified by light microscopy (original magnification x400) and counted within 0.3615 mm2. Medians of blood vessel profiles were compared by Mann-Whitney U-test. RESULTS: There is no statistical difference between the median of blood vessel profiles in the marginal gingiva of SSc patients as compared to the median of blood vessel profiles in the marginal gingiva of patients with periodontitis (P = 0.665). We did not discover avascular areas in the subepithelial connective tissue. DISCUSSION: The pathological changes in the microvasculature in the dermis of SSc patients are not transferable to the marginal periodont, as intraindividual histological examinations of dermis and oral mucosa in relation to the degree of the disease are not available yet.

Adult↗

PubMed2000

Mesalazine changes apoptosis and proliferation in normal mucosa of patients with sporadic polyps of the large bowel.

BACKGROUND AND STUDY AIMS: Regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the occurrence of colorectal adenoma and carcinoma, possibly by inducing apoptosis and/or decreasing proliferation in colorectal epithelial cells. Mesalazine is widely used in the treatment of patients with inflammatory bowel disease, and well tolerated. We investigated its effect on apoptosis and proliferation of colorectal mucosa in 21 patients with sporadic polyps of the large bowel. PATIENTS AND METHODS: In total, 17 patients with sporadic colorectal polyps (> or = 5 mm) underwent polypectomy and biopsy of uninvolved mucosa before and after treatment with 1 g/d mesalazine for 1, 3, 7 or 14 days. Four additional patients served as untreated controls. Apoptotic index (AI) was measured by terminal deoxynucleotidyl transferase-mediated d-uridine triphosphate nick-end labeling (TUNEL) assay; proliferation index (PI) was measured by immunohistochemical examination with anti-Ki67 antibody. RESULTS: AI was significantly increased 1 and 3 days after initiation of treatment with mesalazine compared with controls (P= 0.0107 for the 1-day treatment group and P=0.0142 for the 3-day treatment group), and seemed to remain largely unchanged after longer treatment duration. Proliferation appeared to be decreased by mesalazine in all treatment groups, while proliferation in controls did not change (P=0.0107 for the 1-day treatment group and P= 0.0142 for the 3-day treatment group compared with controls. CONCLUSIONS: Mesalazine significantly induces apoptosis and decreases proliferation in colorectal mucosa in patients with sporadic polyps of the large bowel. This may be clinically relevant in that it may lower the rate of polyp recurrence after polypectomy, thereby possibly contributing to the chemoprevention of sporadic colorectal carcinoma.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

[Functional and morphological defects of the mucociliary system in secretory otitis media].

BACKGROUND: One of the main functions of the ciliated cells of the middle ear mucosa is the continuous drainage of fluids from the middle ear cavity to the Eustachian tube. Impaired mucociliary clearance is related to disturbed clearance of middle ear secretions and results in otitis media with effusion. The aim of this study was to evaluate the ciliary beat frequency (CBF) and the ultrastructure of cilia in young patients suffering from otitis media with effusion (OME). METHODS: CBF and ciliary ultrastructure were studied in 36 patients with OME and 10 normal subjects without any history of middle ear effusion. RESULTS: The CBF was significantly decreased in the study group (6.59 Hz, +/- 1.83) compared to the controls (10.68 Hz, +/- 1.87) and the incidence of ultrastructural defects was higher than in controls. The most common defect were compound cilia, random orientation of the ciliary axes, and defects of the central microtubules. Defects of the dynein arms were not observed.

Adult↗

PubMed2000

[Ultrasound elastography of the prostate. A new technique for tumor detection].

AIM: Prostate tumours are often of harder consistency than the surrounding tissue. During digital rectal examination, this fact can be used not only to detect hypertrophy but also localized hardenings. The examination by digital palpation is inaccurate and, even in combination with PSA-value and a transrectal ultrasonic examination, the result is often not reliable. Ultrasound elastography enables us to measure and visualize the elastic properties of a tissue region and is a useful supplement to the examination by digital palpation. Ultrasound elastography is able to measure and visualize the elastic properties of a tissue region, therefore it is a useful supplement to commonly used diagnostic procedures. METHOD: We have developed a new system for elastographic prostate diagnosis which can be used during the transrectal ultrasonic examination. During the examination a sequence of ultrasonic images is acquired while the organ is slightly compressed by the ultrasound probe. Using numerical analysis of image pairs for the acquired sequence we calculate the tissue strain which represents the spatial elasticity distribution of a specific cross-section of the organ. This enables us to distinguish hard areas in the tissue. Image artifacts resulting from lateral motion components, i.e., orthogonal to the direction of the applied force, are compensated for by a special approach. RESULTS: We present results obtained from a typical elastography phantom and also the first in vivo images from patients who were undergoing radical prostatectomy. Our images prove that ultrasound elastography has the potential to detect malignant tissue areas, which are inconspicuous in the B-mode image. Our findings are confirmed by the corresponding histological specimens.

Elasticity↗

PubMed2000

Neoadjuvant, hyperfractionated irradiation induces apoptosis and decreases proliferation in squamous cell cancer of the oral cavity.

Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with a total dose of 20 Gy. Tissue samples for immunohistochemistry were taken at the time of diagnostic biopsy and at surgery after radiotherapy (RX). For detection of proliferating cells, the immunoperoxidase reaction with Ki67 was performed. Apoptotic cells were detected by the TdT-mediated biotin dUTP nick end labeling (TUNEL) method. RX reduced proliferation in 27 patients, only in one case did the proliferation index (PI) increase. Delta PI (PI before RX PI following RX) amounted to 4.11% (SD=3.2%; P<0.0001). The apoptotic index (AI) increased significantly subsequent to neoadjuvant RX. Delta AI (AI after RX--AI before RX) measured 1.82% (SD=0.9; P<0.001). These data indicate that RX of patients suffering from squamous cell carcinoma of the oral cavity with a dosis of 20 Gy induces apoptosis and inhibits proliferation of tumor cells.

Adult↗

PubMed1999

Solid-pseudopapillary tumor of the pancreas--a rare and frequently misdiagnosed neoplasm.

INTRODUCTION: We describe a young woman with an unusual pancreatic tumor. FINDINGS AND DISCUSSION: Intraoperatively, a smoothly demarcated and encapsulated tumor was exposed. It was large (5 cmx4 cm) and of solid consistency, with a small stalk attached to the uncinate process. The tumor was partially surrounded by the pancreatic head. The macroscopic appearance suggested a benign tumor. Frozen sections revealed a benign pancreatic tumor, most likely of endocrine nature. Based on these findings, tumor enucleation was performed. The patient recovered rapidly from the intervention and was discharged from hospital after 2 weeks. One year after surgical treatment, the patient is without recurrence. The final diagnosis of the tumor was a solid pseudo-papillary tumor.

Adult↗

PubMed1999

[Amyloidosis of the tongue as a possible diagnostic manifestation of plasmacytoma].

Plasmocytic non-Hodgkin's lymphoma is the most common tumor of bone and bone marrow, typically diagnosed by symptoms such as monoclonal paraproteinemia, proteinuria, anemia and hypercalcemia. In its progress, deposits of amyloids in almost all organs can be observed. However, plasmacytomas which are diagnosed by macroglossia of primarily unknown etiology are rare. This case report presents a 61-year-old woman who suffered from a persistent swelling of the tongue with painful ulcerations. A biopsy led to the diagnosis of primary systemic amyloidosis of the light-chain type, which subsequently proved to be a plasmacytoma with lambda light-chains stage II after Durie and Salmon. In the course of the disease the patient developed further deposits of amyloids in the whole gastro-enteric system. Macroglossia as a primary manifestation of plasmacytoma is rarely described in medical literature. However, reports on deposits of amyloid in the tongue in advanced stages of disease are well known.

Amyloidosis↗

PubMed1998

Mixed malignant germ cell tumour of the liver.

Germ cell tumours of the liver are rare neoplasms, with fewer than 20 cases reported in the literature following presentation as teratomas, choriocarcinomas or yolk sac tumours. We report a 52-year-old patient who complained of upper abdominal pain and anorexia. Ultrasonography and computed tomography of the abdomen revealed a large hepatic mass. Among the laboratory values we found elevated levels of alpha-fetoprotein and beta-chorionic gonadotropin. Repeated biopsies via CT scan, laparoscopy and laparotomy disclosed a poorly differentiated adenocarcinoma. Subsequently liver function deteriorated and, on the basis of clinical data highly suggestive of a malignant germ cell tumour, a modified chemotherapeutic protocol (PEI) was initiated. The elevated levels of alpha-fetoprotein and beta-chorionic gonadotropin declined rapidly, but the patient died 10 days later of liver dysfunction and bronchopneumonia. Subsequent autopsy confirmed the initial clinical diagnosis of a multilocular extragonadal malignant germ cell tumour of the liver with components of choriocarcinoma and embryonal carcinoma.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed1998

[Problems in diagnosis and therapy of carcinoma in stroma-abundant pleomorphic adenoma of the parotid gland].

The case is reported of a 27-year-old patient who developed multiple recurrences of a carcinoma arising from richly stromal pleomorphic adenoma of the parotid gland over 13 years. Originally the tumor was classified as a benign pleomorphic adenoma because there were no cytological characteristics of malignancy. Later on the diagnosis had to be modified to that of a carcinoma arising from a pleomorphic adenoma because of the infiltrating growth pattern of the tumor. A multicentric local recurrence and metastases on the left side of the neck supported the correct diagnosis. This case demonstrates that, beside the classic cytological criteria of malignancy invasion and penetration of the capsule can be decisive for the diagnosis of malign transformed pleomorphic adenoma. Treatment and prognosis of salivary gland tumors assume a clear determination of their diguity. The unusual course in this case of a pleomorphic adenoma originally diagnosed as benign demonstrates the importance of regular follow-up.

Adenoma, Pleomorphic↗

PubMed1998

Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in patients with non-small-cell lung cancer: correlation with histological expression of ICAM-1 and tumour stage.

The expression of the intercellular adhesion molecule-1 (ICAM-1, CD54) seems to have an influence on the metastatic behaviour of tumour cells via immunological mechanisms. Recently, a soluble form of ICAM-1 was identified in physiological fluids. We analysed the serum levels of sICAM-1 in patients with non-small-cell lung cancer (NSCLC) and healthy individuals using a sandwich ELISA technique. Sera from 51 patients with NSCLC were tested for sICAM-1 (46 male, five female; age 38-81 years, median 64 years), 29 of whom presented with localized and 26 with metastatic disease. The control group consisted of 40 healthy individuals (20 smokers, 20 non-smokers). Immunohistochemical analysis of ICAM-1 in tumour cells was performed in 20 cases. Patients with NSCLC had significantly higher serum levels of sICAM-1 compared with healthy non-smokers (P = 0.00001) and smokers (P= 0.0328). Metastatic disease was associated with higher sICAM-1 than localized tumours (P = 0.0013). Only 11 out of 23 patients with localized NSCLC had sICAM-1 levels >300 ng ml(-1), compared with 25 out of 28 patients with metastatic disease. Histological expression of ICAM-1 was positively correlated with serum slCAM-1 (P = 0.0399). No difference was observed between histological tumour types with regard to sICAM-1 or NSCLC expression of ICAM-1. In sequential analysis (13 patients), rising sICAM-1 levels predicted a short-term fatal outcome (P = 0.0054) but, overall, sICAM-1 levels did not correlate with prognosis. In the control group, smokers showed significantly higher levels than non-smokers (P = 0.0016). In contrast to patients with NSCLC, sICAM-1 in the control group was correlated to the leucocyte count (r = 0.580, P = 0.003). In conclusion, serum levels of sICAM-1 seem to be associated with tumour burden and histological expression of ICAM-1 in patients with NSCLC. However, the (patho-) physiological role of ICAM-1 in NSCLC remains to be determined.

Adult↗

PubMed1998

Proliferative activity, p53 accumulation and neoangiogenesis in pulmonary carcinosarcomas and pulmonary blastomas.

Carcinosarcoma and pulmonary blastomas are rare biphasic tumors. Lung cancer pathogenesis is a multistep process. Proliferative activity, p53 accumulation and angiogenesis are of well-known relevance and ought to be evaluated in the epithelial and mesenchymal components of these tumors. Using antibodies against Ki-67 epitope MIB1 and proliferating cell nuclear antigen (PC 10) in 10 carcinosarcomas, tumors revealed a significantly higher proliferative activity in the epithelial component compared with the mesenchymal component in the MIB1 reaction (p = 0.013). In three pulmonary blastomas of the biphasic subtype, proliferative activity was similar in both parts. In five of 10 carcinosarcomas and in one of three pulmonary blastomas, accumulation of the p53 epitopes Pab 1801 and/or DO-1 was found. At the tumor front, a significantly higher vessel density was found compared with the central parts (p < or = 0.015) using a monoclonal antibody against human endothelium (CD 31). No differences were found between carcinosarcomas and pulmoblastomas. Higher proliferative activity in carcinosarcomas revealed a better prognosis regarding metastasis behavior (p = 0.05) and tumor-associated death in the follow-up (p < or = 0.017). p53 accumulation and microvessel density were of no prognostic value. This is in contrast to results in non-small cell lung cancer, pointing to a different biologic behavior.

Aged↗