[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.

[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.

[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.

[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.

[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.

Identification of a novel beta-turn-rich repeat motif in the D hordeins of barley.

The amino acid sequence of the C-terminal part of a barley D hordein seed protein was deduced from the nucleotide sequence of a partial cDNA. It showed high homology with the HMW glutenin subunits of wheat, both proteins consisting predominately of repeated sequences. Whereas the wheat repeats are based on tri-, hexa- and nonapeptides that are rich in glycine, proline and glutamine, the D hordein also contains eleven copies of a novel unrelated motif: Thr-Thr-Val-Ser. The repeated sequences in the wheat glutenin subunits have been demonstrated to form an unusual spiral supersecondary structure based on beta-turns. Conformational analysis of the Thr-Thr-Val-Ser motif by secondary structure prediction and by circular dichroism spectroscopy of an 18 residue synthetic peptide demonstrates that it also forms beta-turns. Thus, D hordein may also have a spiral structure like that of HMW glutenin, despite the presence of a different repeat motif. This conservation of protein conformation in D hordein and the wheat glutenin subunits may indicate a structural role, perhaps in packing of the proteins within the protein bodies of the developing grain.

Crystallization and preliminary crystallographic characterization of aspartic proteinase-A from baker's yeast and its complexes with inhibitors.

The aspartic proteinase from yeast vacuoles, proteinase-A, has been crystallized with and without non-hydrolysable transition-state analogue inhibitors. The native enzyme crystals belong to the space group I2(1)2(1)2(1), with two molecules per asymmetric unit. The inhibitor complex crystals are trigonal with space group P3(2)21 and with one molecule in the asymmetric unit. Preliminary X-ray analysis of both native enzyme and its complexes indicate that the complexes diffract to higher resolution than the native crystals. This is probably due to reduced flexibility in the enzyme-inhibitor complex.

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.

The three-dimensional structure at 2.4 A resolution of glycosylated proteinase A from the lysosome-like vacuole of Saccharomyces cerevisiae.

The crystal structures of glycosylated native proteinase A, an aspartic proteinase found in the vacuole of Saccharomyces cerevisiae, and its complex with a difluorostatone-containing tripeptide have been determined by molecular replacement to 3.5 A and 2.4 A resolutions, respectively. Superposition of the bound and native forms gave an r.m.s. difference of 0.6 A largely reflecting the poor resolution of the native crystal structure. The secondary and tertiary structures are highly similar to those found in porcine pepsin and lysosomal cathepsin D; superposition of the structure of proteinase A bound to the difluorostatone inhibitor on those of pepsin and cathepsin D gave pairwise r.m.s. differences for C(alpha) atoms of 1.36 A and 0.88 A. Most differences occur in loop regions. Comparison of the structure of the proteinase A-difluorostatone complex with that of endothiapepsin bound with the same inhibitor shows that the conformation and hydrogen bond interactions of the inhibitor in the active site are very similar, even though the enzymes have only 27% sequence identity. Electron density for the crystal structure of the proteinase A complex reveals five residues of the oligosaccharide structure attached to Asn67: Man-(1 --> 2)-alpha-Man-(1 --> 3)-beta-Man-(1 --> 4)-beta-GlcNAc-(1 --> 4)-beta-GlcNAc-Asn-67. The first three residues of the oligosaccharide cover the same region of the protein surface as those of the oligosaccharide attached to the equivalent position in cathepsin D. The second carbohydrate attachment site is disordered beyond the first carbohydrate residue in both enzymes.

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.

Unusual differentiation of a combination tumor of the parotid gland. A case report.

A 67-year-old female patient developed a slowly growing swelling in the region of the left mandibular angle. This swelling was tender on pressure. Clinical examinations revealed an immobile, circumscribed, palpable node. Sonography showed an inhomogeneous space-occupying mass with a predominantly poor echo in the cranial and dorsal parts of the parotid gland. Intraoperatively the lesion presented as a smooth-bordered, round, capsulated tumor, which was excised "in toto". The postoperative course was uneventful. Histologic examination revealed a salivary gland tumor consisting of two components. Glandular structures corresponding to a Warthin tumor were seen in the center, whereas differentiation in the periphery of the tumor was that of a sebaceous lymphadenoma. Metaplastic sebaceous glands within salivary glands have been occasionally described, but true sebaceous lymphadenomas of the salivary glands are a rarity. A rare variant of Warthin's tumor is its metaplastic type, in which extensive metaplasia of the squamous epithelium is observed. The morphologic parallels as well as the differences seen in our case are described. We believe that it does not meet the criteria of a metaplastic Warthin tumor and have therefore diagnosed a combination tumor of the parotid gland, which is composed of a Warthin tumor component and a sebaceous lymphadenoma component.

The stair-step flap for nasal alar reconstruction.

The stair-step flap is a simple one-stage replacement of alar tissue with excellent viability, minimal "biscuiting" and notching, and good color and texture match. While not replacing other techniques of alar repair, it appears to be a significant addition to the armamentarium for reconstruction in this area.

Closure of large spina bifida cystica defects with bilateral bipedicled musculocutaneous flaps.

A report of 19 cases of large spina bifida cystica defects closed with bilateral bipedicled latissimus dorsi musculocutaneous flaps is presented. This procedure offers a distinct advantage over other procedures used currently: (1) any large defect in the thoracic, lumbar, and sacral area can be repaired without tension; (2) the flaps have good blood supply; (3) they require no delay, and operative time and blood loss are minimized; and (4) excellent results have been obtained using this safe, predictable technique with a minimum of complications.

Histomorphologic studies of the glottic region to elucidate the pathogenesis and functional significance of fibrinoid vocal cord lesions in infants and young children.

Focal lesions of the vocal cord in form of fibrinoid necrosis and thickening of the basement membrane are morphological findings in infants and young children that receive only scant attention and are also controversially valued. We discuss two causes for the pathogenesis of these findings: (1) recurrent laryngospasms and (2) a laryngeal phonotrauma resulting from frequent spells of shrill, presumably high-frequency crying. The aim of our study therefore was to gain insight into the development and functional significance of these lesions by examining their histological patterns and to draw the pertinent conclusions. In 56 deaths (natural and unnatural causes, fetal life up to 4 years, no pathological or traumatic laryngeal lesions) histological investigations were carried out on putrefaction-free material. For the histomorphological studies, horizontal sections through the region of the vocal cord were obtained and stained according to conventional and immunohistochemical staining methods. In 42 cases the thickness of the basement membrane was determined morphometrically. In 12 of the 56 cases (21%) we observed staged variations of focal lesions, ranging from fibrinoid necrosis to degenerative lesions with pronounced macrophage involvement and deposits of PAS-positive plaques. Measurements at the basement membrane revealed a thickness of 7.9 microm. Separate measurements at the anterior and posterior portions of the vocal fold showed a ratio of 1.7:1. When the cases were subdivided into those with and without fibrinoid necrosis the ratios were 2.5:1 and 1.5:1. This different pattern makes it unlikely that laryngospasm is the sole or essential cause. Pathogenetically more important might be phonatory overstraining due to maximum vibrations in only the anterior portions of the vocal fold, which is not specific for later SIDS victims. This assumption is also supported by the often observed conspicuous phonetic behavior of some later SIDS victims and the absence of these stage-like vocal cord lesions in stillborns and adults. It is presumably an age-specific, temporary finding which is completely reversible.

Histomorphological characteristics of non-metastatic lymph nodes in patients with head and neck cancer according to their site in the neck.

The prognostic relevance of histomorphologically defined reaction patterns of lymph nodes was demonstrated in head and neck cancer. Till today the lymph node site in the neck has not been taken into account. Therefore histomorphologically defined reaction patterns of non-metastatic lymph nodes in the neck were examined according to their site in the neck. A total of 1188 dissected neck lymph nodes of 32 previously untreated patients with carcinoma of the head and neck region were examined histologically by serial sections and classified into 6 different lymph node levels and 6 histomorphological types. The objectivity of the morphological examinations could be evaluated morphometrically by means of an interactive image analysis system (IBAS) and a more precise definition of the lymph node reaction types could be established. The results of the morphological and morphometrical classifications show a statistically highly significant relationship (p < 0.0001) between the reaction types of lymph nodes and their site in the neck. These findings allow a division of the neck in an upper anterior half with immunologically active lymph nodes and a lower caudal-dorsal half, which contains essentially less immunologically active lymph nodes.

Significance of autofluorescence for the optical demarcation of field cancerisation in the upper aerodigestive tract.

BACKGROUND: Second primaries in the upper aerodigestive tract (UADT) are increasingly related to bad prognosis. So early detection of small cancer foci is required to improve the survival rate. Here, autofluorescence (AF) might become useful as in vivo biochemical changes of cancer metabolism can be shown by fluorescence. MATERIAL: For more exact data on AF in cancerous lesions 32 cancer specimens of the UADT and 57 specimens of normal oral mucosa as a control group were examined by using autofluorescent microscopy and spectroscopy, the tissue being activated with light at 365 nm wavelength. Video-controlled in vivo fluorescence examinations in field cancerisation of the UADT were also investigated and compared with pathohistological findings. RESULTS: The intensity of AF of the connective tissue was observed to increase at the tumour border. Contrary to results in the literature, no homogeneous fluorescence gradient could be proved between marginal epithelium and the tumour itself. The brightly shining submucosal elastic fibres allowed fluorescent spectroscopic detection of the tumour margins in vitro in 71%. Even small precancerous lesions were traced in vivo mainly by keratinization when using the autofluorescence diagnostic imaging system. CONCLUSIONS: Our examination proved a multi-factorial genesis of autofluorescence with strong inter-individual variations. Preliminary clinical examination showed that this method can be applied as an additional tool for early detection of cancerous lesions in the UADT.

Leptospira interrogans serovar hardjo associated with bovine abortion in South Africa.

Leptospira interrogans serovar hardjo was isolated from urine from dairy cattle in the Onderstepoort area. This was the first successful isolation of this serovar as sole agent causing an abortion storm in the Republic of South Africa. Abortions occurred as early as at 4 months' gestation.

The impact of quality control materials on the performance of an internal quality control system: 3. Experiences from S-triiodothyronine analysis.

In this subproject a method for S-triiodothyronine was used for evaluation of the specified system of internal quality control. Decisions on acceptance and rejection of series were based on results from a human pool with triiodothyronine concentration at the upper reference limit. In the parallel system specimens from patients and from healthy individuals were used in combination with artificial materials so that changes in accuracy, specificity, and detectability could be disclosed. The results were examined for false rejections and false acceptances. For all the seven rejections in 117 series due to a mean rule of 8 controls with a pfr of 0.01, the parallel system supported the decisions. In eight occasions the series were rejected due to a range rule with a pfr of 0.05; one rejection was confirmed by the parallel system and the remaining seven times out of the 117 series were close to the expected five percent of false rejections. A small systematic change in standardization of about eight percent was too small to be recognized by the quality control system. The specificity was not changed during the investigation period; all of the systematic changes were caused by variations in the standard materials. In conclusion the investigation confirmed the validity of the specified system of internal quality control.

[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.