[Neurofibroma in Children hand - Case Report and Literature Review]. / Neurofibrome an der kindlichen Hand ­ Fallbericht und Literaturrecherche.

Neurofibromas rarely occur before the age of 7 in children. They are a rarity on the hand, especially if they are accompanied by sensory disturbances and impairment of the gripping function. We report on a 9-year-old girl with symptomatic neurofibroma of the third and fourth ray of the right palm.

[Epithelial neuroendocrine tumors of the upper respiratory tract: New entities, new perspectives]. / Neuroendokrine epitheliale Tumoren des oberen Respirationstrakts : Neue Entitäten, neue Blickwinkel.

Epithelial neuroendocrine tumors of the upper respiratory tract are rare and are classified as typical and atypical carcinoid versus small cell neuroendocrine carcinoma. Furthermore, a giant cell variant of neuroendocrine carcinoma is suggested corresponding to the bronchopulmonary system as well as a recently described subtype of oropharyngeal small cell neuroendocrine carcinoma associated with human papillomavirus. Many arguments relying on clinical as well as on molecular findings indicate that the distinction between carcinoid and poorly differentiated neuroendocrine carcinoma does not only reflect different degrees of differentiation of otherwise related tumors but indicates the existence of substantially different types of neoplasms.

An erosion sensor based on a quartz crystal microbalance for quantitative determination of the cleaning efficiency in an ultrasonic vessel.

The efficiency of ultrasonic cleaning vessels cannot be measured directly in an easy way. In the presented work, a sensor is developed which quantitatively measures the ablation of a test layer. The sensor element is a quartz crystal which is coated with a sacrificial layer. Small changes in mass of this layer can be measured by a frequency shift of the crystal oscillation. For measurements, a 10 MHz AT-cut quartz crystal was used in a cleaning vessel working at 44.9 kHz. To determine the frequency shift by the ablation of the test layer, the quartz crystal was driven by a frequency generator sweeping the frequency in the range of the resonance frequency and a characteristic frequency was determined. The test layer which was applied to the quartz crystal consisted of silica microparticles suspended in varnish. In a preliminary experiment using a commercial cleaner it could be shown that significant changes in resonance frequency by cavitation effect could be detected. The initial frequency shift of the sacrificial layer is reproducible within 10%. The test layer can be adapted to the conditions of the cleaning vessel. By changing the electrical input power of the vessel, a threshold in the cavitation erosion was found.

[A 75-year-old female patient with pleural effusion and gastric metastases of a poorly differentiated carcinoma]. / 75-jährige Patientin mit Pleuraerguss und gastralen Metastasen eines wenig differenzierten Karzinoms.

A 75-year-old woman was found to have left-sided pleural effusion and endoscopy revealed the rare entity of adenoid cystic carcinoma metastases in the gastric mucosa. Approximately 20% of patients with this carcinoma suffer from distant metastases. For the initial staging detection of adenoid cystic carcinoma metastasis with positron emission tomography (PET) or PET computed tomography (CT) is recommended. The recurrent t(6;9)(q22-23;p23-24) translocation that results in a fusion of the two transcription factor genes MYB and NFIB is detectable in half of the cases. As in our case molecular pathology can confirm the correct diagnosis and identification of the localization of the primary tumor.

Small Cell Ovarian Carcinomas - Characterisation of Two Rare Tumor Entities.

Objective: Small cell ovarian carcinomas (SCOC) are differentiated into two types: hypercalcaemic (SCOCHT) and pulmonary (SCOCPT). Unfortunately, little is known about pulmonary-type small cell ovarian carcinoma. Study Design: We carried out a systematic analysis of all available reports in the literature on individual cases of SCOCHT and SCOCPT. Results: We found that patients with SCOCPT were significantly older than those with SCOCHT. Vimentin and chromogranin detection by immunohistochemistry allow good differentiation between the two types. Interestingly, SCOCPT but not SCOCHT was found to be associated with other benign and malignant ovarian tumours in about 44 % of cases. Although the percentage of R0/R1 resections was high (~ 74 %), survival was poor; even in patients with disease limited to the ovaries (stage Ia and Ib) the recurrence rate was 40 %. Chemotherapy with etoposide or anthracyclines could be useful. Conclusion: Taking the limitations of our study such as its retrospective nature into account and based on the results from studies of small cell carcinomas originating from other tumour sites, we conclude that treatment of SCOCPT should be based on the therapies used to treat other small cell carcinomas. Surgery is appropriate, especially in very early stages of disease, but chemotherapy should not be omitted. Newer concepts such as treatment with somatostatin analogues could help to control symptoms and stabilise some slow-growing tumours.

[Significance of frozen section diagnosis for the management of laryngeal tumors]. / Bedeutung der Schnellschnittdiagnostik für das Management laryngealer Tumoren.

The frozen section procedure for immediate intraoperative pathological diagnosis represents a pivotal method in tumor diagnosis. In laryngeal tumors the most frequent indication for the use of this method is the documentation of the residual tumor status, while intraoperative consultation with the purpose of primary tumor diagnosis is less common. The specimen management employed in each case should be chosen depending on the clinical question: while the collection of a maximum amount of tissue is advisable for the determination of the residual tumor status, sparing a portion of the remaining tissue for possible future examinations is advisable in the case of primary tumor diagnosis. Moreover, intraoperative frozen section diagnosis with no immediate consequences should be avoided.

[Dupuytren's disease in children - case report and literature review]. / Morbus Dupuytren im Kindesalter - Fallbericht und Literaturrecherche.

Dupuytren's disease in childhood and adolescence is extremely rare. As in adults most patients are male. We report on a girl at the age of 7 years with a cord in the palm.

[Congenital vascular malformations (Hauert disease)]. / Angiodysplastische Arthropathie ("Hauert disease").

Patients with congenital vascular malformations often suffer from arthralgia, especially of the lower limbs. This orthopaedic disease pattern is defined as destructive, angiodysplatic arthritis or Hauert disease and leads to very early destruction of the joints. By presenting diagnostic and therapeutic algorithms, Hauert disease is emphasized as a possible differential diagnosis in order to minimize the risk of an incorrect diagnosis which might lead to under-, over-, or even incorrect treatment. A minimally invasive transathroscopic therapy in the early stages can lead to significant improvement of symptoms and prevention of progressive joint destruction.

Direct and indirect autofluorescence laryngoscopy in the diagnosis of laryngeal cancer and its precursor lesions.

Autofluorescence endoscopy has proven to facilitate the detection and delineation of precancerous lesions, carcinoma in situ and microinvasive cancer during bronchoscopy. The aim of the present study is to evaluate the diagnostic potential and limitations of this imaging technique applied during direct and indirect laryngoscopy. In a prospective study, 109 patients with suspected precancerous or cancerous lesions were investigated preoperatively by indirect autofluorescence laryngoscopy as well as during microlaryngoscopy. Autofluorescence was induced by filtered blue light (375-440 nm) of a xenon short arc lamp and processed by a CCD camera system (D-light-AF System, Storz, Tuttlingen, Germany). Autofluorescence images were immediately assessed for diagnosis, compared to the direct autofluorescence picture obtained during microlaryngoscopy and compared with pathohistological findings. Comparable to direct autofluorescence images, normal laryngeal mucosa showed a typical green fluorescence signal. Moderate and high epithelial dysplasia, carcinoma in situ, and microinvasive cancer displayed a diminished green fluorescence. False negative results were related to extreme hyperkeratosis. False positive cases showed mild dysplasia with inflammatory reactions or scarring. In 98 cases (90%) we found concordant results. According to our results, the presented technique seems to be a promising diagnostic tool for the early detection of laryngeal cancer and its precursor lesions during direct and indirect laryngoscopy. Scarring, marked hyperkeratosis, and inflammation can limit the predictive value of the method.

[Laryngeal epithelial dysplasia vs. laryngeal intraepithelial neoplasia]. / Laryngeale Epitheldysplasie vs. laryngeale intraepitheliale Neoplasie.

Laryngeal cancer is the most frequent malignancy of the upper respiratory tract. Only the very early treatment of tumors or even of their precursor lesions will be both curative and organ preserving. Microsurgical techniques facilitate early detection and complete removal of limited lesions can be achieved quite frequently, but follow-up data for such lesions are difficult to obtain. The resulting lack of endpoint observations (i.e., malignant transformation, spontaneous involution) hampers the development, testing, and application of grading systems focusing on epithelial alterations, especially changes with only mild nuclear atypia and minimal structural alteration. Such lesions may be entirely benign or may indicate premalignant stages of well-differentiated carcinoma. For diagnosis we recommend a modified Kleinsasser's system to classify premalignant epithelial changes. Only the complete removal of suspicious lesions as far as possible or regular clinical follow-up in cases where complete removal cannot be achieved can prevent the development of advanced stage cancer.

[Phosphoinositide 3-kinase (PI3-K) expression. Tumorigenesis of epithelial carcinoma of the mouth]. / Phosphoinositid-3-Kinase- (PI3-K) Expression. Tumorgenese von Plattenepithelkarzinomen der Mundhöhle.

Phosphoinositide 3-kinase (PI3-K) is a heterodimeric enzyme involved in the regulation of mitogenesis, apoptosis, cell adhesion, and motility. PI3-K was suggested as a protooncogene in human cancer. To determine the expression of PI3-K during cancerogenesis and tumor invasion of HNSCC, we investigated normal and dysplastic epithelium of the oral cavity, squamous cell carcinoma and lymph node metastasis by immunohistochemistry. The strongest immunoreactivity for p85alpha and p110alpha was found in invasive tumors and their metastases. Carcinomas in situ showed a focal positivity. Dysplasias and normal epithelium reacted predominantly negatively. The PI3-K inhibitor LY294002 inhibited proliferation and invasion of the HNSCC cell line CAL-27 and induced apoptosis in vitro. Our data suggest PI3-K as a marker of malignancy and tumor invasion. We suggest including PI3-K in the multistep carcinogenesis model of HNSCC. In addition, PI3-K is a potential target for pharmacological intervention.

Indirect autofluorescence laryngoscopy in the diagnosis of laryngeal cancer and its precursor lesions.

Direct autofluorescence endoscopy of the larynx has proven to facilitate the detection and delineation of precancerous lesions, carcinoma in situ and cancer. The aim of the present study was to evaluate the diagnostic potential and limitations of this imaging technique applied during indirect laryngoscopy. In a prospective study, 116 patients with suspected precancerous or cancerous lesions were investigated preoperatively by indirect autofluorescence laryngoscopy. Autofluorescence was induced by filtered blue light (375-440 nm) of a xenon short-arc lamp and processed by a CCD camera system (D-light-AF System, Storz, Tuttlingen, Germany). Autofluorescence images were immediately assessed for diagnosis, compared to the direct autofluorescence picture obtained during microlaryngoscopy and compared to pathohistological findings. Comparable to direct autofluorescence images, normal laryngeal mucosa showed a typical green fluorescence signal. Moderate and high epithelial dysplasia, carcinoma in situ and cancer displayed a diminished green fluorescence. False negative results were related to extreme hyperkeratosis. False positive cases showed mild dysplasia with inflammatory reactions or scarring. In 103 cases (89%), we found concordant results. According to our results, the presented technique seems to be a promising diagnostic tool for the early detection of laryngeal cancer and its precursor lesions during indirect laryngoscopy. Scarring, marked hyperkeratosis and inflammation can limit the predictive value of the method.

[Numerical modeling of ultrasound thermotherapy]. / Numerische Modellierung der Ultraschall-Thermotherapie.

In ultrasound thermotherapy (USTT) high intensity focused ultrasound (HIFU) is used for noninvasive thermal treatment of human tissue deep inside the body. In this paper a FDTD-model is presented to simulate USTT. It combines nonlinear ultrasound propagation and broadband tissue attenuation together with the bio-heat transfer equation for calculation of temperature distribution in tissue. The temperature dependence of parameters is integrated in the complete model. Simulation results demonstrate the potentialities of this simulation tool to analyze and optimize thermotherapy.

Nuclear texture features for classifying benign vs. dysplastic or malignant squamous epithelium of the larynx.

OBJECTIVE: To search for nuclear features and feature combinations able to assess malignancy and premalignant changes on tissue sections of laryngeal squamous epithelium. STUDY DESIGN: A total of 139 lesions of benign changes (BC) (n = 44), epithelial dysplasias (ED) (n = 50) and invasive laryngeal cancer (LC) (n = 45) were retrieved from archival pathology specimens. The goal of this study was to identify the best features or feature combinations that discriminate BC from LC and also reflect the degree of ED. In order to verify the results on independent data, the groups were split into two separate subgroups, one for training and one for testing. RESULTS: On the test set of slides, the overall correct classification of BC vs. LC cases was 82% using only one feature, fractal2_area. This classification rate could be increased to 91% when a discriminant function based on 10 features was used. However, this gain was not significant. CONCLUSION: Fractal texture features can be used to assess malignancy on tissue sections as an alternative to DNA measurement. In this study feature combinations did not significantly improve classification rates.

X-ray structures of five renin inhibitors bound to saccharopepsin: exploration of active-site specificity.

Saccharopepsin is a vacuolar aspartic proteinase involved in activation of a number of hydrolases. The enzyme has great structural homology to mammalian aspartic proteinases including human renin and we have used it as a model system to study the binding of renin inhibitors by X-ray crystallography. Five medium-to-high resolution structures of saccharopepsin complexed with transition-state analogue renin inhibitors were determined. The structure of a cyclic peptide inhibitor (PD-129,541) complexed with the proteinase was solved to 2.5 A resolution. This inhibitor has low affinity for human renin yet binds very tightly to the yeast proteinase (K(i)=4 nM). The high affinity of this inhibitor can be attributed to its bulky cyclic moiety spanning P(2)-P(3)' and other residues that appear to optimally fit the binding sub-sites of the enzyme. Superposition of the saccharopepsin structure on that of renin showed that a movement of the loop 286-301 relative to renin facilitates tighter binding of this inhibitor to saccharopepsin. Our 2.8 A resolution structure of the complex with CP-108,420 shows that its benzimidazole P(3 )replacement retains one of the standard hydrogen bonds that normally involve the inhibitor's main-chain. This suggests a non-peptide lead in overcoming the problem of susceptible peptide bonds in the design of aspartic proteinase inhibitors. CP-72,647 which possesses a basic histidine residue at P(2), has a high affinity for renin (K(i)=5 nM) but proves to be a poor inhibitor for saccharopepsin (K(i)=3.7 microM). This may stem from the fact that the histidine residue would not bind favourably with the predominantly hydrophobic S(2) sub-site of saccharopepsin.

Purification, co-crystallization and preliminary X--ray analysis of the natural aspartic proteinase inhibitor IA3 complexed with saccharopepsin from Saccharomyces cerevisiae.

The vacuolar aspartic proteinase from baker's yeast, saccharopepsin, has been co-crystallized with its natural inhibitor I(A)3, found in the cytosol. The I(A)3-saccharopepsin complex crystals belong to the space group P6(2)22, with unit-cell parameters a = b = 192.1, c = 59. 80 A and one molecule per asymmetric unit. The initial X-ray analysis of the complex indicates that the crystals diffract to 5.0 A, similar to native saccharopepsin crystals. This is probably a consequence in part of glycosylation of the native saccharopepsin. Full structural analysis of the complex crystal is in progress.

Specific changes of chromatin structure in nuclei of normal epithelium adjacent to laryngeal squamous cell carcinoma. A preliminary study of 82 cases.

The aim of this study was to confirm the existence of specific nuclear texture feature alterations of histologically normal epithelial borders nearby invasive laryngeal cancer (NC). Paraffin sections of NC and of chronic inflammations unrelated to cancer (CI) were analysed for nuclear texture and for integrated optical density (IOD-index) and were compared to normal epithelium of patients without evidence of cancer (NE). Several discriminant functions based on nuclear texture features were trained to separate different subgroups. As the most important result, specific nuclear texture feature shifts were only found in NC with high-density lymphocytic stroma infiltrate (NC+). Classification of nuclei of NE versus NC+ was correct in 70%. The same classifier was correct in only 58% when nuclei of NE were classified versus CI. We also found lower values of IOD-Index within the NC+ group when compared to NE (p < 0.001).

The T-type calcium channel blocker mibefradil reduced interstitial and perivascular fibrosis and improved hemodynamic parameters in myocardial infarction-induced cardiac failure in rats.

Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dt(max)) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dt(max) were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dt(max) were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event.

[Cytokeratin and p53 expression of odontogenic cysts]. / Zytokeratin- und p53-Expression odontogener Zysten.

The histopathologic diagnosis of odontogenic cysts is based mainly on the morphological nature of the epithelial lining of cysts and their origin. We used the international histologic classification set up by the World Health Organisation in 1992. The aim of this study was to investigate the differentiation of various types of cyst using an immunohistochemical technique rather than by conventional morphological assessment. A standard immunocytochemical method (APAAP method), applying anticytokeratin monoclonal antibodies and a p53 antibody, was used for the diagnosis of odontogenic cysts. A total of 57 jaw cysts were diagnosed according to clinical, radiological and pathological criteria as radicular cysts (20), dentigerous cysts (20) and keratocysts (17). The results proved that cyst type can be distinguished by the pattern of staining using the monoclonal antibodies CK7, CK19, CK20 for cytokeratins and the clone DO-7 for the p53 protein. Staining with the monoclonal antibodies CK7 and CK20 did not distinguish type. CK19 was not detected in keratocysts and p53 was only expressed in keratocysts. This may prove to be diagnostically useful for the more precise distinction between different cyst types.