Biomedical subjects

F Paulsen

Publications and source records attributed to F Paulsen.

At least 19 recordsLinked to original sources

PubMed2003

On biologically conformal boost dose optimization.

A method is described that allows the inclusion of biological imaging data in the optimization of intensity-modulated radiotherapy to produce dose boosts that conform with target subvolumes of potentially reduced radiosensitivity. The biological image (e.g. PET, fMRI, etc) is transformed into a dose efficiency distribution using a piecewise linear calibration function with a prescribed maximum boost factor. Instead of dose alone, the cost function of the optimization algorithm depends on the product of the physical dose times dose efficiency. An example case of a base-of-tongue tumour which was imaged with the hypoxia tracer fluoro-misonidazole is presented, showing the excellent capability of IMRT to produce dose distributions that conform to spatially variable dose prescriptions.

Algorithms↗

PubMed2003

[Multimodal treatment strategy for Langerhans cell histiocytosis at head and neck manifestations].

Langerhans cell histiocytosis (LCH) is a rare disorder with different clinical features. An established standardized treatment does not exist.We present a case report of a patient with localized LCH of the temporal bone and discuss the interdisciplinary treatment strategies. We reviewed the international literature and summarized the current knowledge. Beside a wait and see policy in cases without symptomatic disease, surgery, radiotherapy or chemotherapy, and combinations of these options are used as treatment modalities. While surgery or radiotherapy are preferred in localized (symptomatic) lesions, stage-adapted chemotherapeutic regimens are the treatments of choice in disseminated disease. Treatment selection depends on the individual clinical features.

Adolescent↗

PubMed2002

Expression of pulmonary lactoferrin in sudden-onset and slow-onset asthma with fatal outcome.

The objective of this forensic autopsy study was to determine the immunohistochemical expression pattern of lactoferrin (LF) in pulmonary tissue sections deriving from fatal slow-onset asthma (time interval between onset of asthma attack and death >2.5 h) and fatal sudden-onset asthma (cases in which death occurred within 1 h of the onset of an asphyxic asthma attack) relative to controls (sudden death due to diseases other than respiratory disorders). LF was applied to paraffin sections using a standard peroxidase-labelled streptavidin-biotin technique. LF immunoreactivity was graded semi-quantitatively in relation to different histoanatomic distribution sites of LF on a five category ordinal scale (maximum score of 15). We found a statistically significant difference between an enhanced expression of LF in both asthma groups relative to the controls (P<0.004 and P<0.001, respectively). When comparing both asthma groups, there was a statistically significant difference in LF immunoreactivity between the slow-onset and sudden-onset asthma group (P<0.001). Since LF immunoreactivity was far less intense in the sudden-onset asthma group (mean expression +/-SD: 7.3+/-1.3) than in the slow-onset asthma group (12.5+/-1), and an absent or weak LF expression pattern was observed in the control group (1.4+/-1.3), we assume that our results permit the following cautious estimations: (1) pulmonary LF expression is enhanced in asthma attacks with fatal outcome relative to controls and (2) a different expression pattern of LF can be observed in fatal sudden-onset asthma compared to slow-onset asthma in so far as the pulmonary expression of LF seems to be positively correlated with the preceding period of time between the asphyxic asthma attack and death. Further clinicopathologic studies including in-patient asthma fatalities with a well-known medical history are required to scrutinize if the pulmonary expression of LF is in fact positively associated with the time span of the asthma attack, thus possibly providing further therapeutic opportunities to intervene in severe asphyxic asthma.

Acute Disease↗

PubMed2002

FDG PET for staging of advanced non-small cell lung cancer prior to neoadjuvant radio-chemotherapy.

The aim of this study was to evaluate positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) for the staging of non-small cell lung cancer (NSCLC) before combined neoadjuvant, i.e. preoperative, radio-chemotherapy (RCT). From November 1998 until September 2001, 101 patients with NSCLC were investigated prospectively. The inclusion criterion was a histologically proven NSCLC of stage IIIA or B according to conventional staging including biopsy. The results of PET were compared with those obtained by mediastinoscopy, computed tomography (CT), bone scan and abdominal ultrasonography. Validation of discrepant findings was achieved by biopsy or repeated CT. PET proved to be highly accurate for the detection of lymph node metastases (sensitivity 96%, specificity 73%, positive predictive value 88%, negative predictive value 89%, accuracy 88%) as well as distant metastases (in 25/101 patients, all previously unknown). PET findings changed further treatment in 29/101 patients (29%). Twenty-five were excluded from RCT due to the presence of previously unknown distant metastases. One patient was free of metastases and therefore was operated on without pre-treatment. Two patients did not receive any further treatment because a malignant tumour could be excluded after PET. In the final patient PET demonstrated a tumour pattern not typical for NSCLC which could be attributed to a seminoma after repeated biopsy. FDG PET is the most accurate non-invasive diagnostic procedure for the staging of advanced NSCLC. Therefore use of FDG PET is highly recommended in order to select patients for neoadjuvant or other stage-dependent treatment modalities.

Adult↗

PubMed2002

Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma.

The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDu(dd)) was used for the study. For experiments, NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11 x 4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C. Graded top up doses (clamped blood flow: 0-57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits: 17-43) days, fractionated irradiation in 31 (25-35) days and combined Mitomycin C plus fractionated irradiation in 65 (58-73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P<<0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95-1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13-1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model.

Animals↗

PubMed2002

[Mucins in otorhinolaryngology].

BACKGROUND: Mucins are glycoproteins of high-polymer structure. They are an important component of the mucous layer covering the epithelia of the upper aerodigestive tract. Until now there has been little interest with regard to mucins in otorhinolaryngology. METHODS: The present knowledge about mucins of the upper aerodigestive tract is presented. A MEDLINE search was conducted for English- and German-language articles published from 1966 to the present. RESULTS: Thirteen different mucins named MUC 1-13 have been subdivided based on the classification system used by the Human Gene Mapping Committee. Besides mucins, small mucin-associated peptides, called trefoil factor peptides, have attracted much interest. CONCLUSIONS: Classification and attribution of the mucins found in the middle ear, larynx, oropharynx, esophagus, and nasolacrimal ducts has yet to be done. Also, little is known about the distribution of trefoil factor peptides in the upper aerodigestive tract.

Carcinoma, Squamous Cell↗

PubMed2002

[Nasolacrimal ducts and the dry eye].

BACKGROUND: The knowledge regarding the pathogenesis, diagnosis, and treatment of dry eye has made large advances in recent years. However, many questions are still unanswered. Although the nasolacrimal ducts are part of the tear system they have been paid nearly no attention regarding dry eye. METHODS: The present knowledge about the nasolacrimal ducts is presented and discussed in a context with dry eye. A PubMED search was conducted for articles published from 1966 to the present; in addition, review articles as well as book chapters were considered and discussions with investigators in the field were performed. RESULTS: As a draining and secretory system, the nasolacrimal ducts play a role in tear transport and non-specific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a vascular system that surrounds the nasolacrimal sac and nasolacrimal duct. This system is comparable to a cavernous body and it is connected to the blood vessels of the outer eye. Also it is subject to vegetative control. Organized mucosa-associated lymphoid tissue (MALT) is present in the nasolacrimal ducts displaying the cytomorphological and immunophenotypic features of MALT. CONCLUSIONS: The normally constant absorption of tear fluid components into the blood vessels of the surrounding cavernous body that are connected to the blood vessels of the outer eye, could be a feedback signal for tear fluid production, which comes to a halt if these tear components are not absorbed. Thus, dry eye could be initiated. Defective stimulation of tear duct-associated lymphoid tissue (TALT) could result in abnormal immune deviation at the ocular surface leading to an autoimmunological response that causes dry eye pathology.

Autoimmune Diseases↗

PubMed2002

Lectin binding patterns of alveolar epithelium and subepithelial seromucous glands of the bronchi in sepsis and controls--an approach to characterize the non-specific immunological response of the human lung to sepsis.

A delayed or deficient immunological protection as well as an overstimulation of the mucosal immune system may act as possible additional promoters of sepsis-induced lung injury in patients suffering from a severe septic condition. Lectin-binding patterns in pulmonary tissue samples obtained at autopsy from septic patients and control individuals were studied using 11 carbohydrate-specific lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There were no differences in the secretory product of serous parts of bronchial glands detectable in the two study groups, whereas lectin binding patterns of alveolar epithelium and mucous parts of subepithelial seromucous glands were different in sepsis cases when compared to controls. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for Con A, MAA and SNA) in the two study groups, the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) could be detected on alveolar epithelial cells and mucous parts of subepithelial seromucous glands in sepsis cases in contrast to the presence of such binding sites in the control cases. We hypothesize that the finding of an altered secretory product of alveolar epithelial cells and bronchial glands in sepsis may be a result of specific carbohydrate deprivation or consumption, respectively, possibly due to direct bacterial effects or pathogenetic events in response to bacterial toxins during the complex cascade of the host's systemic inflammatory response in sepsis. The altered type of mucus glycoprotein physiologically secreted by alveolar epithelium and mucous parts of subepithelial seromucous glands of the bronchi with subsequent loss of a considerable proportion of protection of the mucosal barrier in sepsis may play an important additional role in the development of sepsis-induced lung injury.

Adult↗

PubMed2002

The arterial supply of the lesser metatarsal heads: a vascular injection study in human cadavers.

The possibility of avascular changes of the metatarsal heads following forefoot surgery has been previously documented. The aim of this study was to investigate the arterial supply of the lesser metatarsal heads with regard to osteotomies of these bones. We used epoxy resin injections and a modified Spalteholz technique in human cadaveric specimens to demonstrate the intraosseous and extraosseous blood supply of the lesser metatarsals. The metatarsal heads had two arterial sources: 1. The dorsal metatarsal arteries, which arose from the dorsalis pedis artery, and 2. The plantar metatarsal arteries, which are branches of the posterior tibial artery. These two vessels typically anastomosed at two sites about the metatarsal heads, forming a vascular ring and provided an extensive extraosseous arterial network around the metatarsal heads. Small arterial branches of this network run distally on the metatarsal cortex to enter the bone of the metatarsal head. The nutrient arteries traversed the cortex of the metaphysis close to the capsular and ligamentous insertions to provide multiple branches for the supply of the subchondral bone. Extensive capsular stripping during metatarsal head osteotomies results in damage to the medial and lateral head vessels.

Aged↗

PubMed2001

[The efferent lacrimal ducts of the human. Morphological and biochemical studies].

PURPOSE: Infections occur frequently in the region of the efferent tear ducts. Exact knowledge of the anatomical structure and of cellular defense mechanisms is necessary to understand the pathological processes. This study analyzed the efferent tear ducts with regard to physiological function and possible defense mechanism against infections. MATERIALS AND METHODS: We used histological, immunohistochemical and electronmicroscopic techniques to investigate the lacrimal systems from 31 body donors aged 54-88 years. RESULTS: The efferent tear ducts are lined by a double-layered epithelium resting on a broad basement membrane. These cells contain many lipid droplets and secretory vacuoles in their apical part. Inside the epithelium cells are arranged partly in cell groups forming mucous glands, which morphologically resemble goblet cells of the tarsus palpebrae. The secretory products of these cells contain various carbohydrates including sialic acid. Lymphocytes and macrophages are found in the submucosa partly penetrating the epithelium. CONCLUSIONS: Lipids and mucins of epithelial and goblet cells form a specialized protective layer on the epithelium of the tear ducts which enables easy drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells the protective layer prevents invasion of pathogenetic agents.

Aged↗

PubMed2001

Comparative evaluation of pulmonary lactoferrin and lysozyme immunoreactivity for the postmortem diagnosis of death due to sepsis.

To determine whether lactoferrin (LF) and lysozyme (LZ) can be used as immunohistochemical postmortem markers of sepsis, pulmonary tissue sections from autopsy cases of sepsis-related fatalities (n = 13) and control cases of non-septic fatalities (n = 14) were evaluated for differences in leucocytic immunoreactivity. LF and LZ were investigated in paraffin sections using the AEC technique. The immunohistochemical expression of both markers was scored, evaluating the quantity of immunopositive cells and the intensity of the intracellular immunoreactivity. There was a statistically significant association between an enhanced expression of LF on pulmonary leucocytes in sepsis-related fatalities in contrast to non-sepsis cases (P < 0.001), whereas no such difference could be observed for LZ immunoreactivity between the two study groups. Pneumonic tissue alterations had no significant influence on LF and LZ immunoreactivity, thus suggesting differences between the degranulation of these non-specific antibacterial agents in local and systemic inflammatory processes. While the variability of LZ immunoreactivity, possibly reflecting a non-specific release from lysosomes according to the length of the postmortem interval, limits its application to the postmortem diagnosis of sepsis, the immunohistochemical detection of an enhanced expression of LF can contribute to the postmortem discrimination between sepsis and non-septic fatalities.

Adolescent↗

PubMed2001

[Meta-analysis of the efficacy of positron emission tomography with F-18-fluorodeoxyglucose in lung tumors. Basis for discussion of the German Consensus Conference on PET in Oncology 2000].

BACKGROUND: : To analyse current literature on FDG-PET for evaluation of lung lesions, N-staging, M-staging, and recurrence of lung cancer for the third German Consensus Conference on PET in oncology. METHODS: Specialists in nuclear medicine, pneumology, radiation oncology, diagnostic radiology, and thoracic surgery reviewed the relevant literature as listed in MEDLINE from 1985 to 1999 for further analysis. Out of the published data cumulative test parameters and summary receiver operating characteristic curves (sROC curves) were computed. RESULTS: Sensitivity, specificity, and accuracy of FDG-PET are 96 %, 80 %, 91 % for evaluating lung lesions (15 studies with at least 35, in total 1144 patients). With corresponding values of 88 %, 92 %, 91 % (20 studies, 1292 patients) for N-staging FDG-PET is superior to CT with 65 %, 76 %, 73 % (19 studies, 1268 patients). With 94 %, 97 %, 96 % (4 studies, 336 patients) M-staging with FDG-PET is very accurate and changed therapeutic management in 18 % of the cases (8 studies, 695 patients), unexpected extrathoracic metastases were found in 12 % (7 studies, 581 patients). FDG-PET is the most accurate non-invasive method to evaluate suspected adrenal metastases (3 studies, 263 patients, sensitivity 96 %, specificity 99 %, accuracy 98 %). Recurrence is detected accurately (4 studies, 224 patients, sensitivity 99 %, specificity 89 %, accuracy 95 %). CONCLUSIONS: Studies with in total more than 1000 patients show the high diagnostic efficacy of FDG-PET and its superiority to conventional imaging in lung cancer. Based on this analysis the third German Consensus Conference on PET in oncology evaluated FDG-PET on lung cancer. 1a-indications are evaluation of lung nodules in patients at risk for complications during surgery, N-staging, M-staging (except brain), and detection of recurrence.

Fluorodeoxyglucose F18↗

PubMed2001

[Mechanical brush-catheter abrasion method for the isolation and culture of human umbilical vein endothelial cells. First in vitro results].

UNLABELLED: Mechanical brush-catheter abrasion method for the isolation and culture of human umbilical vein endothelial cells. First in vitro results. PURPOSE: To determine the value of a nylon brush (Cragg thrombolytic catheter system) with regard to the isolation and culture of viable human vascular umbilical vein endothelial cells (HUVEC). MATERIAL AND METHODS: Fresh human umbilical cords were collected after a maximum of 6 - 8 h post delivery. They were stored in sterile tubes till further preparation. After predilation the umbilical cord veins, a 6 French brush catheter was inserted, expanded, and removed by hand using rotating movements. The nylon brush was shaken out in cell medium containing serum proteins by a connected motor drive. After repeating these procedures, the detached endothelial cells were centrifugated and resuspended. The cell numbers were assessed and cell viability controlled. RESULTS: The endothelial cell (EC) viability depended on the umbilical cord's age and was the highest (29.8 +/- 11.4 %) within 3 h after delivery. The brush abrasion (3.32 x 10(5) +/- 52016 viable EC/10 cm vein segment) enabled us to culture these cells under different cell concentrations. They grew to confluence after 2 - 3 weeks. CONCLUSIONS: The brush-catheter abrasion is an effective method for collecting viable human endothelial cells in vitro.

Catheterization, Peripheral↗

PubMed2001

Expression of natural peptide antibiotics in human articular cartilage and synovial membrane.

In view of frequent present use of invasive procedures on limb joints, it is astonishing that articular joint inflammation is a rare event. We questioned whether antimicrobial peptides play a role in protecting human articular cartilage and synovial membrane against inflammatory agents. Our results implicate defensins in the protection of human articular joints against pathogens.

Anti-Bacterial Agents↗

PubMed2001

Dendritic cells in the mucosa of the human trachea are not regularly found in the first year of life.

BACKGROUND: Dendritic cells (DCs) in the mucosa of the respiratory tract might be involved in the early development of pulmonary allergy or tolerance. To date, little is known about when the first DCs occur in human airways. METHODS: Specimens of the distal trachea from patients who had died from sudden death in the first year of life (n=29) and in older age groups (n=59) as well as from those who had died from respiratory tract infections in the first year of life (n=8) were examined by immunohistochemistry. Transmission electron microscopy was performed in additional samples from two adults. RESULTS: In the sudden death subgroup DCs were absent in 76% of those who died in the first year of life but were present in 53 of the 59 older cases. All infants who had died of respiratory infectious diseases had DCs in the tracheal mucosa. CONCLUSIONS: Mature DCs are not constitutively present in the human tracheobronchial mucosa in the first year of life, but their occurrence seems to be triggered by infectious stimuli. These data support the hypothesis that DCs play a crucial role in immunoregulation in early childhood.

Adolescent↗

PubMed2000

What happens to tears inside the efferent lacrimal passage? An animal experimental study.

BACKGROUND: To determine whether absorption of protein components of the tear fluid occurs in normal efferent tear ducts, an animal experiment was carried out. METHODS: Iodinated albumin was dropped into eyes of female rats. After 10, 20 or 60 min the rats were killed, blood collected and the heads embedded for histological examination. Serum was obtained from the clotted blood and the radioactivity in a protein sediment and the combined supernatants counted. In a second approach, serum was fractionated by molecular mass and radioactivity in the fractions measured. Furthermore, autoradiographs of rat head sections were performed. RESULTS: Uptake of radioactivity into the serum was low, but increased with time. After 60 min maximal incorporation of the applied radioactivity into the blood was 0.13%; most (70-80%) of the incorporated radioactivity was not protein bound. Gel chromatographic separation according to molecular mass yielded fractionated peaks of radioactivity corresponding to albumin with maximal 4.8 Bq/ml serum, iodinated tyrosine (5.5 Bq/ml), and free iodine (237 Bq/ml; each after 60 min). Histologically the rat efferent lacrimal tear ducts showed a multilayered lining epithelium with integrated goblet cells in a characteristic arrangement of several cells. In autoradiographs of rat head sections no transport of radioactivity could be visualized. CONCLUSION: In rats only traces of iodinated albumin are incorporated from the efferent lacrimal tear ducts into the blood. A higher proportion of the radioactivity is taken up as the proteolytic degradation product of bovine serum albumin to free amino acids, and 96% of the radioactivity incorporated was free iodine, probably as a contaminant of the iodinated preparation.

Absorption↗

PubMed2000

Effects of ageing on the insertion zones of the human vocal fold.

The vocal ligaments insert at the anterior and posterior commissures of the larynx. These structures fulfil biomechanical functions, balancing the different elastic moduli of tendon, cartilage or bone and undergo age-related changes that may be responsible for voice changes with increasing age. The aim of this study was to analyse the insertion structures of the vocal ligaments by means of macroscopic, histological, immunohistochemical and electron-microscopic methods and to draw conclusions from age-related structural changes on a functional basis. Investigations were carried out on the larynges of 22 males and 15 females (aged 1-95 y). In adolescence, the insertion zone of the vocal ligament tendon, a dense network of connective tissue rich in sulphated glycosaminoglycans at the thyroid cartilage, is characterised by a layer between tendon and cartilage comparable to fibrocartilage. The insertion zone lacks a perichondrium. Collagen fibrils of the vocal ligament tendon penetrate directly into the thyroid cartilage. In the insertion area, the chondrocytes are surrounded by collagen fibrils, which show positive reactivity to antibodies against type I and type III collagen. Sulphated glycosaminoglycans are integrated between the collagen fibrils. In the area of the posterior glottis, elastic cartilage rests like a cap on the hyaline base of the arytenoid cartilage. There is no distinctive border between the structures. With increasing age, ossification of the laryngeal skeleton occurs, involving hyaline cartilage at the posterior glottis and hyaline and fibrocartilage at the anterior commissure. At the same time, a loss or sulphated glycosaminoglycans is observed inside the vocal ligament tendon. Advanced ossification of the laryngeal skeleton, particularly in the area of the commissures, an increasing loss of glycosaminoglycans in the vocal ligament tendon and changes in the elastic tissue reduce the elastic modulus between tendon, cartilage and bone, thus 'stiffening' the insertion zones, which could be one factor among others favouring voice changes with advancing age.

Aging↗

PubMed2000

Innervation of the cavernous body of the human efferent tear ducts and function in tear outflow mechanism.

The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries comparable to a cavernous body. The present study aimed to demonstrate the ultrastructure of the nervous tissue and the localisation of neuropeptides involved in the innervation of the cavernous body, a topic not previously investigated. Different S-100 protein antisera, neuronal markers (neuron-specific enolase, anti-200 kDa neurofilament), neuropeptides (substance P, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal polypeptide) and the neuronal enzyme tyrosine hydroxylase were used to demonstrate the distribution pattern of the nervous tissue. The ultrastructure of the innervating nerve fibres was also examined by means of standard transmission electron microscopy. The cavernous body contained specialised arteries and veins known as barrier arteries, capacitance veins, and throttle veins. Perivascularly, the tissue was rich in myelinated and unmyelinated nerve fibres in a plexus-like network. Small seromucous glands found in the region of the fundus of the lacrimal sac were contacted by nerve fibres forming a plexus around their alveoli. Many nerve fibres were positive for S-100 protein (S 100), neuron-specific enolase (NSE), anti-200 kDa neurofilament (RT 97), calcitonin gene-related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), and neuropeptide Y (NPY). Vasoactive intestinal polypeptide (VIP) immunoreactivity was only demonstrated adjacent to the seromucous glands. Both the density of nerve fibres as well as the presence of various neuropeptides emphasises the neural control of the cavernous body of the human efferent tear ducts. By means of this innervation, the specialised blood vessels permit regulation of blood flow by opening and closing the lumen of the lacrimal passage as effected by the engorgement and subsidence of the cavernous body, at the same time regulating tear outflow. Related functions such as a role in the occurrence of epiphora related to emotional responses are relevant. Moreover, malfunction in the innervation of the cavernous body may lead to disturbances in the tear outflow cycle, ocular congestion or total occlusion of the lacrimal passages.

Adult↗