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  • 1995-1999  (277)
  • 1999  (277)
  • Immunohistochemistry  (100)
  • Life and Medical Sciences  (96)
  • Children  (81)
  • Nuclear reactions
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  • 1995-1999  (277)
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Keywords
  • 1
    ISSN: 1432-2307
    Keywords: Key words Tenascin-C ; Laryngeal carcinoma ; Immunohistochemistry ; In situ hybridization ; Cell proliferation ; Cell migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tenascin-C (TN-C) is an extracellular matrix glycoprotein upregulated in various pathological processes. In this study, we investigated its distribution in dysplasia and carcinoma of the human larynx using immunohistochemistry and in situ hybridization (ISH) techniques. In all cancer tissues, TN-C immunostaining was markedly increased in the stroma, especially around the cancer cell nests. In addition, cytoplasmic staining of cancer cells was also observed in 62.5% of the invasive cases, the cells being distributed in the periphery of the nests adjacent to the stroma. TN-C mRNA signals in cancer cells were detected in all six cases examined by ISH. Furthermore, in vitro evaluation of the roles of TN-C demonstrated an increase in the proliferating cell fraction in a dose-dependent manner. In a wound closure assay, the addition of TN-C promoted migration. We conclude that TN-C secreted by cancer cells may be involved in their proliferation and migration in an autocrine fashion.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Key words Breast neoplasms ; Malignant myoepithelioma ; Metastasis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A breast tumor in a 52-year-old female was interpreted as a malignant myoepithelioma based on morphological and immunohistochemical studies. The tumor consisted of elongated cells with clear cytoplasm and lacked glandular components. The tumor cells were stained positively for keratin, S-100 protein, glial fibrillary acidic protein (GFAP) and muscle-specific actin. Distant metastasis in the right jaw developed 8 years after the initial surgery and the metastatic deposit showed a similar morphology and immunoreactivity. Myoepithelial tumors are generally considered as benign or low-grade lesions and distant metastasis has been rarely documented. The present case presents the possibility of delayed occurrence of distant metastasis in myoepithelial tumor of the breast.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 435 (1999), S. 580-589 
    ISSN: 1432-2307
    Keywords: Abstract Adrenal cortex ; Adrenal tumour ; Innervation ; Immunohistochemistry ; Neuronal markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The innervation of the human adrenal gland and of cortical lesions was studied in sections of cortical tissue (n=10), hyperplastic cortical tissue (n=3), and tissue from cortical adenomas (n=5) and carcinomas (n=6). The presence and distribution of nerve structures containing neuronal markers indicating sympathetic and parasympathetic innervation were studied by immunohistochemistry and the co-existence and co-localization patterns of the different markers by immunofluorescence. The cortex and hyperplastic cortical tissue had a moderate to rich supply of nerve structures containing the typical neuronal markers: protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), small vesicle synaptic protein type 2 (SV2), and nerves showing immunoreactivity to the adrenergic marker tyrosine hydroxylase (TH). All these immunoreactive nerves were located predominantly adjacent to blood vessels, but also among parenchymal cells. The cortex showed numerous nerve structures containing the neuropeptide substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal protein (VIP), but few nerves containing these peptides were seen in hyperplastic cortical tissue. Typical markers were occasionally observed in cortical adenomas but were not found in carcinomas, except in a few cases where PGP 9.5 and NSE were present, but only adjacent to necrotic areas. Nerves containing NPY and VIP occurred in varying numbers in both adenomas and carcinomas. NPY- and VIP-immunoreactive nerve structures were seen mostly alongside blood vessels. There were several types of co-existence. For instance, NSE/VIP-, TH/VIP- and TH/NPY-immunoreactive nerve structures were often seen in the same trunk, but were only partly co-localized.
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  • 4
    ISSN: 1432-2307
    Keywords: Key words Hypopharynx carcinoma ; Prognosis ; Proliferation ; Ki-S11 ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  As a potential prognostic factor, the proliferative activity of 131 squamous cell carcinomas (SCC) of the hypopharynx and 47 of their cervical lymph-node metastases was analyzed retrospectively by means of monoclonal antibody Ki-S11 immunostaining, which specifically detects the Ki-67 antigen on paraffin-embedded tissue. Median follow-up time was 37.6 months. Ki-S11 revealed distinctive patterns of proliferating cells related to the degree of differentiation. The proliferation fractions in the primaries and their lymph-node metastases did not differ significantly. Patients with high proliferating hypopharynx carcinomas (〉45% labeled cells) had a significantly lower 5-year-survival rate (16%) than patients with low proliferating tumors, whose 5-year-survival rate was 30% (P=0.01). A statistically significant positive correlation was also observed between proliferative activity and lymph-node status (P=0.012). In conclusion, the proliferative activity as determined by means of Ki-S11 immunostaining is of prognostic value with respect to both survival and metastatic risk in SCC of the hypopharynx.
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  • 5
    ISSN: 1432-2307
    Keywords: Key words Mixed ductal-endocrine carcinoma ; Pancreas ; Gastrinoma ; Immunohistochemistry ; Zollinger-Ellison syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an autopsy case of mixed ductal-endocrine carcinoma of the pancreas presenting as gastrinoma with Zollinger-Ellison syndrome. A 38-year-old Japanese male was found to have Zollinger-Ellison syndrome and pancreatic gastrinoma, and gastrectomy and resection of the pancreatic tumor were performed. However, hypergastrinemia persisted, and the patient died of disseminated carcinomatosis at 62 years of age, 24 years after the onset of Zollinger-Ellison syndrome. At autopsy, the main tumor was present in the residual pancreas, and metastases were noted in many organs. In the pancreas and other organs, ductal and endocrine carcinoma areas were mixed and there was a gradual transition between the two. No acinar differentiation was noted. The ductal elements were positive for mucins and carcinoembryonic antigen but negative for neuroendocrine markers, while endocrine elements were positive for chromogranin A and synaptophysin and to a lesser extent for gastrin, but negative for mucins and carcinoembryonic antigen. The ductal elements comprised about 30% of the tumor cells, and endocrine elements 70%. According to the revised World Health Organization classification, our case was diagnosed as mixed ductal-endocrine carcinoma. Our case is rare because the tumor manifested as gastrinoma with Zollinger-Ellison syndrome and the patient survived for 24 years. To the best of our knowledge, no such case has been reported. Our case suggests that pancreatic endocrine tumors may evolve into mixed ductal-endocrine carcinomas.
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  • 6
    ISSN: 1432-2307
    Keywords: Key words Rhabdomyosarcoma ; Aorta ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We report an intimal sarcoma presenting as an aortic aneurysm. A 68-year-old man suffered from chest pain and speech disturbance. Computed tomography showed a sacciform aneurysm of the aorta, which was resected, revealing a polypoid tumour measuring 1.5×2×2.5 cm projecting into the lumen. This proved to be a poorly differentiated high-grade sarcoma having morphological, immunophenotypic and ultrastructural features consistent with rhabdomyosarcomatous differentiation. Primary sarcomas of the aorta are extremely rare. Many cases have been diagnosed as ”intimal” on the basis of their site of origin, and they are not easy to classify from their histological pattern. Electron microscopy and the use of a more comprehensive panel of immunohistochemical markers should be applied in the histological classification of ”intimal” sarcoma.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 39 (1999), S. 467-471 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Aspiration ; Diagnostik ; Kinder ; Atemwege ; Key words Foreign body ; Aspiration ; Diagnostic imaging ; Children ; Respiratory tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aspiration of foreign bodies is a common cause of respiratory distress in children between the age of 6 months and 3 years. The diagnosis of radiopaque foreign bodies is easy when the whole respiratory tract is depicted. Nonopaque foreign bodies need a more differentiated diagnostic approach. The first step should be plain films in inspiration and expiration. The performance of additional chest radiographs, fluoroscopy and if need be CT or nuclear scans depends on the result of the plain films. The chest radiograph may reveal a variety of findings, the commonest of which is unilateral air trapping. Rarely, atelectasis, recurrent pneumonia at the same localisation and inspiratory obstruction are found. Combinations of the above-mentioned findings are possible. Moreover, the absence of positive radiological findings does not exclude the diagnosis of foreign body aspiration.
    Notes: Zusammenfassung Die Fremdkörperaspiration stellt eine häufige Ursache für Atemnot und respiratorische Insuffizienz bei Säuglingen und Kleinkindern zwischen 6 Monaten und 3 Jahren dar. Röntgendichte Fremdkörper bereiten bei Abbildung des gesamten Respirationstraktes keine diagnostischen Schwierigkeiten. Nicht röntgendichte Fremdkörper erfordern ein differenzierteres Vorgehen, wobei der erste radiologische Schritt in einer konventionellen Thoraxaufnahme in In- und Exspiration bestehen sollte. Zusätzliche Aufnahmen, Durchleuchtungsuntersuchung und gegebenenfalls die Durchführung einer computertomographischen oder szintigraphischen Untersuchung hängen vom Ergebnis der Thoraxaufnahme ab. Häufigstes radiologisches Erscheinungsbild ist die einseitige exspiratorische Ventilstenose mit Überblähung des betroffenen Lungenabschnittes. Seltener finden sich Atelektasen, rezidivierende Pneumonien an identischer Lokalisation und inspiratorische Ventilstenosen. Kombinationsbilder sind möglich, selbst ein unauffälliges Untersuchungsergebnis kann eine Aspiration nicht ausschließen.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Radiologe 39 (1999), S. 472-477 
    ISSN: 1432-2102
    Keywords: Schlüsselwörter Fremdkörper ; Ingestion ; Kinder ; Diagnostik ; Key words Foreign body ; Ingestion ; Children ; Diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Foreign body ingestion is not infrequent in infants and children. The diagnosis of radiopaque foreign body ingestion does not pose a major problem. It is crucial to take an X-ray from the pharynx to the level of the pylorus. If a foreign body that might get stuck at the ileocoecal valve is ingested, it is necessary to perform a radiograph of the whole abdomen. Foreign bodies that do not pass the cardia must be extracted endoscopically. In the case of foreign bodies with a smooth contour that have passed the pylorus, parents are advised to check the child’s stool or collect it and bring it for X-raying. If after a week there is no definite evidence that the foreign body has been excreted a follow-up radiograph is carried out. If the foreign body is still in the stomach or duodenum, endoscopy is necessary. The detection of nonopaque foreign bodies can be facilitated by giving oral contrast medium, making the depiction of the foreign body as a filling defect possible. As a complication, perforation can occur, the diagnosis of which may entail the use of sonography, conventional radiography and, to a lesser extent, CT.
    Notes: Zusammenfassung Fremdkörperingestion ist im späten Säuglings- und frühen Kleinkindalter kein seltenes Ereignis. Die Diagnose röntgendichter Fremdkörper bereitet keine Schwierigkeiten. Hierbei ist jedoch zu beachten, daß die Region vom Pharynx bis zum Pylorus abgebildet sein sollte. Wurden Fremdkörper verschluckt, bei denen die Gefahr der Einklemmung in der Bauhin’schen Klappe besteht, sollte das komplette Abdomen bis zum Anus dargestellt werden. Fremdkörper, welche die Kardia nicht passieren, müssen endoskopisch extrahiert werden. Haben glatt begrenzte Fremdkörper den Pylorus passiert, werden die Eltern aufgefordert, den Stuhl zu untersuchen oder zu sammeln und ihn zur röntgenologischen Untersuchung mitzubringen. Sollte der Fremdkörper innerhalb einer Woche nicht auffindbar sein, wird eine Kontrolluntersuchung durchgeführt. Ist der Fremdkörper dann noch im Magen oder im Duodenum, sollte er ebenfalls extrahiert werden. Der Nachweis nicht röntgendichter Fremdkörper kann mittels Gabe von positivem Kontrastmittel als Aussparungsfigur gelingen. Als Komplikation kann eine Perforation auftreten. Hierbei dienen Sonographie, konventionelles Röntgen und gegebenenfalls CT zur Diagnosefindung.
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  • 9
    ISSN: 1432-2307
    Keywords: Key words Carbohydrates ; N-Sulfation ; O-Sulfation ; Immunohistochemistry ; Rapidly progressive glomerulonephritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Crescentic glomerulonephritis leads to a rapid loss of renal function. Although glomerular crescents are rich in extracellular matrix (ECM), the composition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variability. Recent findings that alterations in HS epitopes are associated with renal pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 724 patients who underwent renal biopsy and found 21 patients with rapidly progressive glomerulonephritis. Immunohistochemistry was performed using monoclonal antibodies (mAbs) against well-defined HS epitopes. One mAb was directed against unsaturated uronic acid residues generated during the selective removal of HS by heparitinase (a), and a further two different mAbs against N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but not to fibrous crescents, the periglomerular areas and noncrescentic intraglomerular areas. We concluded there are regional differences in HS epitope expression, although HS are ubiquitous components of glomerular ECM. N-sulfate-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.
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  • 10
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; Programmed cell death ; Ductular proliferation ; Biliary decompression ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A complex molecular network controls cell homeostasis by inducing apoptosis or proliferation. The balance of Bcl-2 and Bax, members of a protein family, determines whether a cell will become immortal (Bcl-2) or will undergo apoptosis (Bax). To determine the role of Bcl-2 and Bax during proliferation of biliary epithelial cells (BEC) after bile duct ligation (BDL) and their regression after biliary decompression we induced hyperplasia of BEC by BDL in male rats. Regression of hyperplastic BEC by way of apoptosis was induced by biliary decompression through a Roux-en-Y biliodigestive anastomosis. To quantify apoptosis a modified TUNEL assay was used. Expression of Bcl-2 and Bax was visualized by immunohistochemistry and quantified stereologically. BEC increased from 〈1% to 〉20% after BDL; this increase was associated with overexpression of Bcl-2 in up to 30% of hyperplastic BEC. After biliodigestive anastomosis, apoptotic BEC increased from 〈0.1% to a peak of 5.4% after 1 day to reach baseline again 1 week after decompression. This was associated with de novo appearance of Bax. The interaction between Bcl-2 and Bax triggers apoptosis in BEC and acts as a cell rheostat in BEC hyperplasia and its involution after biliary decompression.
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  • 11
    ISSN: 1432-2307
    Keywords: Key words Human ; Cytochrome P450 2C ; Cytochrome P450 3A ; Immunohistochemistry ; Neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Organ and cellular distribution and expression constancy of microsomal cytochrome P450 (CYP) 2C and 3A in humans were studied with new polyclonal antibodies to CYP2C (MP-1) and 3A (NF-2) active in formalin-fixed, paraffin-embedded tissues. Antibodies were raised against purified human CYP2C9 and CYP3A4. On western blotting, MP-1 reacted with 2C8, 2C9, 2C18 and 2C19, and NF-2 with 3A4. In both frozen and paraffin sections, hepatocytes showed diffuse immunoreactivity with MP-1 and centrilobular staining with NF-2. Inparaffin sections of 40 kinds of nonneoplastic tissues, epithelium of the small and large intestine, bile duct, nasal mucosa, kidney and adrenal cortex stained positively with both MP-1 and NF-2 antibodies. Epithelium of gastric fundic glands, salivary glands, tracheobronchial glands, Brunner’s glands, the prostate, uterine cervix and nasopharynx showed definite reactivity with MP-1. Epithelium of the gastric mucosa with intestinal metaplasia, duodenum, gallbladder and intercalated ducts of the pancreas and chief cells of the parathyroid and the corpus luteum of the ovary reacted with NF-2. Among the neoplastic tissues, MP-1 reacted with pleomorphic adenoma of the salivary gland and carcinomas of six different organs, and NF-2 with those of 7 different organs. These results indicate that CYP2C and CYP3A are distributed widely and organ specifically, as well as being variably expressed in neoplastic and normal states.
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  • 12
    ISSN: 1432-2307
    Keywords: Key words E-cadherin ; Colorectal cancer ; Immunohistochemistry ; Mutation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.
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  • 13
    ISSN: 1432-2307
    Keywords: Key words Cyclin B1 ; Esophageal squamous cell carcinoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9 % (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P〈0.005) and with venous invasion (P〈0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P〈0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P〈0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC.
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  • 14
    ISSN: 1432-2307
    Keywords: Key words Activin A ; Inhibin A ; Endocrine tumors ; Digestive system ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Activin A and inhibin A, first isolated from the ovary, are dimeric proteins able to modulate pituitary FSH secretion. Inhibin A is a heterodimer composed of one α-subunit and one βA-subunit (α-βA), while activin A is a homodimer of the βA-subunit (βA-βA). Their identification in several tissues has suggested that they have numerous physiological functions, acting as either paracrine or autocrine factors. The aim of this study was to evaluate the expression of activin A and inhibin A in normal endocrine cells and in 70 endocrine tumours from different sites in the gastro-entero-pancreatic system, using specific monoclonal antibodies directed against the α- and βA-subunits of inhibin/activin. Immunoreactivity for the βA-subunit, but not for the α-subunit, was observed in normal G, EC, and GIP cells of the antrum and duodenum, and in pancreatic A cells. βA-subunit expression was observed in G cell and A cell tumours, and in a few insulinomas and ileal EC cell carcinoids. The α-subunit was found in rare cells in 7 of the 70 tumours and was colocalized with the βA-subunit in only 1 tumor. Specific types of endocrine cells from the gut and pancreas appear to produce only activin A, a possible paracrine or autocrine modulator. Activin A is mainly produced by tumours derived from endocrine cells that normally express it.
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  • 15
    ISSN: 1432-2307
    Keywords: Key words Salivary gland ; Pleomorphic adenoma ; Collagen ; Cell culture ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The morphogenesis of salivary gland pleomorphic adenoma was examined in vitro using three-dimensional (3-D) collagen gel culture. Pleomorphic adenoma cells were isolated from three parotid gland tumours and cultured as monolayers, after which they were subcultured in floating-collagen gel sandwiches. Cells cultured in both conditions were immunohistochemically characterized and compared using antibodies against various proteins representative of each histological component of salivary glands. Monolayers had myoepithelial characteristics, being positive for vimentin and α-smooth muscle actin. In collagen gels, however, the cells assembled in epithelial nests, showing an architecture similar to that of pleomorphic adenoma. The nests were composed of duct-lining epithelial cells that were positive for epithelial markers, surrounded by myoepithelial cells. Collagen gel culture induces multi-directional differentiation of adenoma cells, suggesting that pleomorphic adenomas originate from stem or reserve cells.
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  • 16
    ISSN: 1432-2307
    Keywords: Key words Systemic granulomatous arteritis ; Epstein-Barr virus ; Virus-associated haemophagocytic syndrome ; In situ hybridization ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A 61-year-old woman initially presented with symptoms and findings reminiscent of infectious mononucleosis, and her illness then took a rapidly fatal course. Autopsy revealed widespread granulomatous arteritis, with multinucleated giant cells but without eosinophils and fibrinoid necrosis, affecting small arteries and arterioles and infiltration of haemophagocytic histiocytes into many organs. In situ hybridization with Epstein-Barr virus (EBV)-specific oligonucleotide probes showed positive signals in the infiltrating immune cells and epithelial and endothelial cells of the affected organs. EBV-associated haemophagocytic syndrome (EBV-AHS) with systemic granulomatous arteritis was diagnosed. From the immunophenotypes of the infiltrating immune cells, a possible role of CD4+ T-cells in the pathogenesis of this haemophagocytic syndrome and granulomatous vasculitis was suggested.
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  • 17
    ISSN: 1432-2307
    Keywords: Key words Epithelial myoepithelial carcinoma ; Salivary gland tumours ; Immunohistochemistry ; Flow cytometry ; MIB-1 (Ki 67) ; Proliferative markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Three cases of epithelial-myoepithelial carcinoma (EMC) with coexisting areas of high grade carcinoma are reported. In two of the cases there was a previous recurrence, and in all three patients there had been a sudden increase in size before final surgery. The typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of wide spectrum cytokeratins, Cam 5.2 and EMA in the ductal part, and muscle-specific actin, smooth muscle actin, S-100 protein, vimentin and cytokeratins in the myoepithelial component. These areas also had a low mitotic count and low proliferation rate as measured by immunohistochemistry and by flow cytometry. Conversely, areas of high-grade tumour had the features of a large cell carcinoma, with focal mucin secretion in two cases. This high-grade component showed an epithelial immunophenotype in two cases, and was negative for all tested markers in the third one. The mitotic counts and the proliferation rates were much higher in these anaplastic areas. One of the patients died 3 months after treatment; another developed lymph node metastases 1 year later and was alive after 6 years of follow-up. The third patient was alive without evidence of disease 7 months after wide surgical resection of the tumour. The possibility of anaplastic transformation in EMC makes thorough sampling mandatory in this type of neoplasm.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 434 (1999), S. 551-560 
    ISSN: 1432-2307
    Keywords: Key words Systemic amyloidosis ; Brain ; Circumventricular organs ; Choroid plexus ; Immunohistochemistry ; Aβ colocalization.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Amyloid deposits in cerebral vessels are common in β-amyloid diseases (Alzheimer’s disease, congophilic amyloid angiopathy, Down’s syndrome and hereditary cerebral amyloidosis with haemorrhage of the Dutch type). We report of 20 autopsies on patients who had died with systemic amyloidosis of the AA, Aλ and Aκ types: the brains were examined for the occurrence of amyloid. Vascular amyloid was detected in choroid plexus (in 17 of 20 cases), infundibulum (5 of 8), area postrema (6 of 11), pineal body (3 of 7) and subfornical organ (2 of 3), but not in cortical and leptomeningeal vessels. Immunohistochemical classification of the cerebral amyloid and the systemic amyloid syndrome showed identity proving the same origin of both. The distribution is indicative of a haematogenic pattern of amyloid deposition in systemic amyloidosis and is different from that in Alzheimer’s, prion, ATTR and cystatin C diseases. It corresponds to areas of the brain with a ”leaky” blood–brain barrier. Additionally, all the cases with AA amyloidosis exhibited an Aβ coreactivity in choroid plexus vessels. In one exceptional case, Aβ reactivity of AA amyloid also occurred outside of the brain.
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  • 19
    ISSN: 1432-2307
    Keywords: Key words Ductal carcinoma in situ ; Immunohistochemistry ; Myoepithelial cells ; Basal lamina ; Smooth muscle actin ; Calponin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A retrospective study was made of 38 selected brest tumours with a poorly differentiated in situ duct component. These were classified on haematoxylin and eosin (H&E) as ductal carcinoma in situ (DCIS; 10 cases), DCIS with invasion (17 cases) and DCIS with features suggestive of for stromal invasion (11 cases). The last were these lesions composed of neoplastic ducts with irregular outlines and a myoepithelial layer that was not clearly evident or large neoplastic ducts growing close together or surrounded by inflammatory desmoplastic stroma. Cases of DCIS involving areas of sclerosing adenosis were included in this category. Consecutive sections obtained from each case were studied with a panel of antibodies against myoepithelial cells (alpha smooth muscle actin and calponin) and basal lamina (BL) components (laminin and type IV collagen). It was found that in situ lesions showed well-formed basal lamina and/or an evident myoepithelial layer. These features were lacking in the invasive areas. Nine of the 11 cases with suggestive features of stromal invasion were reclassified as invasive duct carcinoma (5 cases)and DCIS (4 cases), according to the absence or presence of a continuous myoepithelial layer and/or basal lamina. In 2 such cases immunohistochemistry yielded equivocal results and the label ”suggestive of invasion” was therefore pertinent. Immunohistochemistry facilitates the diagnosis of breast DCIS; myoepithelial and basal lamina markers are useful in differentiating microinvasive from in situ ductal carcinomas of the breast.
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  • 20
    ISSN: 1432-2307
    Keywords: Key words Autonomic nerve tumour ; Small intestine ; Immunohistochemistry ; Quick-freezing ; Deep-etching
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A case of gastrointestinal autonomic nerve tumour with skeinoid fibres (SFs) of the jejunum in a 79-year-old Japanese man, was examined by the quick-freezing and deep-etching (QF-DE) method. The tumour consisted of spindle cells with immunohistochemical reactions for vimentin, NSE and CD34. Electron microscopically, features of the neural cells of the myenteric plexus were observed. The QF-DE method demonstrated intercellular meshwork structures, consisting of thin filaments (7–15 nm), with granular deposits. Fully developed parts of the deposits formed nodular aggregates composed of irregularly surfaced thick fibrils (30–48 nm) with a tendency to linear arrangement (SFs). We detected many interconnecting thin filaments (ICTFs) between the SFs, which were pre-existing components in the meshwork, avoiding the granular deposits. The focal thickening formed by the connection between SFs and ICTFs revealed a periodicity typical of SFs (33–45 nm). We conclude that SFs are formed by decoration of the granular deposits along pre-existing intercellular meshwork structures.
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  • 21
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    Neuroradiology 41 (1999), S. 512-516 
    ISSN: 1432-1920
    Keywords: Key words Meninges ; Tumours ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours.
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  • 22
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Rhadomyosarkom ; Klassifizierung ; Immunhistochemie ; Genetik ; Prognose ; Key words Rhabdomyosarcoma ; Classification ; Immunohistochemistry ; Genetics ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Rhabdomyosarcoma (RMS) is the most important and a very heterogeneous group of malignant soft tissue tumors of childhood and adolescence.The two major subtypes (embryonal and alveolar) share a common myogenic differentiation, but seem to be histogenetically not related. The so-called ’International Classification of Rhabdomyosarcoma’ includes, besides the two major subtypes, the botryoid and leiomyomatous subtypes of embryonal RMS which are associated with a better prognosis and are treated less aggressively according to current protocols. In addition, the solid variant of alveolar RMS is included in the alveolar group of RMS. The identification of the various subtypes is necessary and important because the treatment with the current protocols is also related to histology. Using conventional stains and immunohistochemistry, these subtypes are distinguishable. Genetic analysis can be helpful in the demonstration of t(2;13) or t(1;13) translocations in alveolar RMS. The identification of alveolar RMS with t(1;13) translocation might become important in the future, because this type of translocation seems to be related to a better prognosis as compared to tumors with a t(2;13) translocation.
    Notes: Zusammenfassung Rhabdomyosarkome stellen eine heterogene Gruppe von ganz verschiedenartigen, histogenetisch wohl nicht zusammengehörenden Tumoren dar. Nach der heute verwendeten „Internationalen Klassifikation” der Rhabdomyosarkome werden neben der Unterteilung in embryonalen und alveoläre Rhabdomyossarkome auch Subtypen des embryonalen RMS identifiziert (botryoider und leiomyomatöser Subtyp), die durch eine günstigere Prognose und durch die Notwendigkeit einer weniger aggressive Therapie gekennzeichnet sind. Durch Einsatz von verschiedenen histologischen und immunhistochemischen Färbungen ist die Identifizierung der verschiedenen Typen der RMS heute möglich und auch zwingend notwendig, da die einzelnen Entitäten nach ganz unterschiedlichen Therapieprotokollen behandelt werden. Der Nachweis typischer molekulargenetischer Veränderungen kann in der Unterscheidung insbesondere von embryonalen und alveolären RMS hilfreich sein. In der Regel ist die Abgrenzung zwischen diesen beiden Entitäten auch an konventionell gefärbten Schnittpräparaten möglich. Die Identifizierung von alveolären RMS mit einer t(1;13)-Translokation könnte in Zukunft eine große Bedeutung haben, da diese genetische Veränderung möglicherweise mit einer günstigeren Prognose assoziert sein könnte als die t(2;13)-Translokation.
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  • 23
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Pleomorphes Adenom ; Äußerer Gehörgang ; Zeruminom ; Differentialdiagnose ; Immunhistochemie ; Key words Pleomorphic adenomas ; Meatus acusticus externus ; Ceruminoma ; Differential diagnosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A tumor was removed from the right external auditory canal of a 69-year old female patient. The histopathological and immunhistochemical evaluation revealed a pleomorphic adenoma (mixed tumor). The differential diagnosis of the tumors derived from the ceruminal glands, their clinical and prognostic implications as well as the histogenesis of pleomorphic adenomas in this localization are discussed.
    Notes: Zusammenfassung Bei einer 69jährigen Patientin wurde aus dem rechtsseitigen äußeren Gehörgang ein Tumorknoten exstirpiert. Die histopathologische und immunhistochemische Untersuchung ergab ein pleomorphes Adenom (Mischtumor). Die Differentialdiagostik der von den Zeruminaldrüsen abgeleiteten Tumoren, deren klinisch-prognostische Konsequenz sowie die Histogenese der pleomorphen Adenome in dieser besonderen Lokalisation werden erörtert.
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  • 24
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    Neuroradiology 41 (1999), S. 929-934 
    ISSN: 1432-1920
    Keywords: Key words Magnetic resonance imaging ; diffusion weighted ; Myelination ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the changes in brain water diffusion in childhood as seen on diffusion-weighted MRI in 30 children from 1 day of life to 17 years to provide a data base and to investigate the correlation of diffusion changes with known patterns of white matter maturation. The apparent diffusion coefficient (ADC) and apparent anisotropy (AA) were calculated in numerous regions of the brain to include major white matter tracts and gray matter. ADC and AA values were directly related to the structural maturity and compactness of the white matter tracts and changed with aging in a way that predated early myelination markers such as signal change on T1- or T2-weighted images. Diffusion of water is sensitive to structural changes in the brain such as white matter maturation and may be useful in investigating white matter disorders.
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  • 25
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    International journal of colorectal disease 14 (1999), S. 212-218 
    ISSN: 1432-1262
    Keywords: Key words Cyclo-oxygenase ; Colon carcinogenesis ; Crohn’s disease ; Familiar adenomatous polyposis coli ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Deregulation of cyclo-oxygenase isozyme expression has been shown to be a consistent feature of inflammatory bowel diseases and colorectal cancer in humans. This study investigated the cellular localization of aberrant cyclo-oxygenase expression in normal and diseased colon. Biopsies of seven normal colonic tissues, eight tissue samples from patients suffering from Crohn’s disease, five polyps from patients with familiar adenomatous polyposis coli, and ten sporadic adenocarcinomas were analyzed using isozyme-selective immunoprecipitation, western blotting, and immunohistochemistry. Cyclo-oxygenase-1 expression was demonstrated in normal human colon, Crohn’s disease, and colorectal tumors. In normal colon and also in adenomatous polyps, cyclo-oxygenase-1 specific immunosignals were localized to epithelial cells of the upper part of the crypts and endocrine cells of the lower part. In Crohn’s disease cyclo-oxygenase-1 expression was restricted to cells of the inflammatory infiltrate. While barely detectable in normal colon, cyclo-oxygenase-2 protein was strongly increased in epithelial cells located in the uppermost part of the crypts, in surface epithelial cells, and in mononuclear cells of the lamina propria of Crohn’s disease. The constitutive overexpression of cyclo-oxygenase-2 protein observed in the majority of the adenomatous polyps and all adenocarcinomas was attributed to both epithelial and interstitial cells in that the latter predominated in adenomas, and epithelial cells were the prevailing cyclo-oxygenase-2 expressing cell type in adenocarcinomas. In conclusion, both autocrine and paracrine effects of aberrant cyclo-oxygenase-2 expression may contribute to the development of Crohn’s disease and colonic tumor development.
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  • 26
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    International journal of colorectal disease 14 (1999), S. 272-276 
    ISSN: 1432-1262
    Keywords: Key words  Colorectal cancer ; Angiogenesis ; Vessel density ; Prognosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a ×200 field in the area of the most dense neovascularization. Vascular density was found to be 75±27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (〉75) than in those of less vessel density (〈75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.
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  • 27
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    Der Nervenarzt 70 (1999), S. 1-10 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Tic-Störung ; Zwangsstörung ; Kinder ; Jugendliche ; Neurobiologie ; Psycho- pharmakologie ; Verhaltenstherapie ; Key words Tic-disorder ; Obsessive-compulsive disorder ; Children ; Adolescents ; Neurobiology ; Psychopharmacology ; Behavior therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamo-cortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administerd to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.
    Notes: Zusammenfassung Motorische/vokale Tics und zwanghafte Verhaltensweisen kommen bei Kindern und Jugendlichen häufig gemeinsam vor; dabei kann ein Symptomkontinuum von solitär auftretenden Tics über ein Mischbild von Tics und Ritualen/zwanghaften Gedanken und/oder Handlungen bis hin zu eindeutigen Zwangsphänomenen beschrieben werden. Neurobiologisch können diesem Symptomkontinuum unterschiedlich ausgebreitete Dysfunktionen entsprechender kortiko-striato-pallido-thalamo-kortikaler Regulationssysteme zugrunde liegen. Therapeutisch lassen sich bei beiden Verhaltensauffälligkeiten mittels verhaltenstherapeutischer Techniken Steuerungs- und Kontrollmöglichkeiten zur Gegenregulation der Auffälligkeiten verbessern sowie durch Einsatz von Psychopharmaka Dysbalancen von Neurotransmittersystemen ausgleichen. Bei einem Mischbild von Tics und Zwängen sind therapeutische Interventionen für beide Zielbereiche erforderlich. Nur so können umfassende Verbesserungen erreicht und günstige Entwicklungsbedingungen für die betroffenen Kinder und Jugendlichen eröffnet werden.
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  • 28
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    HNO 47 (1999), S. 535-540 
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörschäden ; Knalltrauma ; Kinder ; Tinnitus ; Erweiterte Hochtonaudiometrie ; Key words Hearing loss ; Acoustic trauma ; Children ; Tinnitus ; High-frequency audiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The study presents an analysis of 20 cases of acute acoustic trauma caused by toy pistols. The problem generally involves boys within the age range from 6 to 11 years. Half of the incidents involved attacks with toy pistols used as weapons. Auditory damage appeared in two types, each of which had a notch in the audiogram at the frequency range between 10 and 14 kHz. In children, a shot close to one ear can damage both ears. Great differences in the severity of tinnitus were apparent. The most severe cases of tinnitus were observed in the children with no or minor premanent auditory damage. Children experiencing long periods of uninterrupted tinnitus suffer significantly. This is not only detrimental to family-life but also to the performance of the children at school. The total expenses of treatment for these 20 cases were estimated to be approximately 80,000 DM (40.000 Euro).
    Notes: Zusammenfassung Im Rahmen einer Studie wurden 20 Fälle von Knalltraumata durch Kinderpistolen erfaßt und ausgewertet. Die Problematik betrifft fast nur männliche Personen und schwerpunktmäßig den Altersbereich von 6–11 Jahren. Die Hälfte der Vorfälle waren Angriffe, bei denen die Kinderpistole als Waffe eingesetzt wurde, 2 Typen von Hörschäden sind festzustellen, die jedoch beide durch eine Senke im Bereich von 10–14 kHz charakterisiert sind. Bei Kindern kann der Schuß in eines der Ohren auch das andere Ohr schädigen. Sehr große Unterschiede bestehen im Auftreten von Tinnitus. Die Fälle mit starkem Tinnitus haben keine oder nur geringe bleibende Hörschäden. Die von Knalltraumata betroffenen Kinder leiden oft sehr stark unter langanhaltendem Tinnitus. Dabei wird nicht nur das Leben der Familien beeinträchtigt, sondern auch die schulischen Leistungen der Kinder leiden teilweise sehr stark darunter. Für die Therapie dieser 20 Fälle entstanden Gesamtkosten von ca. 80.000,- DM
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  • 29
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    Monatsschrift Kinderheilkunde 147 (1999), S. 328-332 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Asthma bronchiale ; Schulkinder ; Türkische Kinder ; Key words Asthma ; Children ; Turkish children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: In Germany 4.2% (in Munich 8.6%) of all children under 15 years of age are of Turkish origin, representing the largest ethnic minority in this age group. However, very little is known about the prevalence, severity and management of asthma and other atopic diseases in Turkish children living in Germany. Methods: In a cross-sectional survery the prevalence, severity and treatment of asthma and other atopic diseases was assessed in 7,445 schoolchildren aged 9 to 11 years, living in Munich, southern Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin-prick tests and cold-air hyperventilation challenge. Results: Of those returning the questionnaires (n = 6490/87%), 5,030 (77.5%) were of German and 451 (7%) of Turkish origin. Turkish children showed a significantly lower prevalence of asthma (5.3% versus 9.4%, P 〈 0.05) than their German peers. Furthermore, Turkish children with asthma were less frequently free of symptoms (10.5% versus 34.6%, P 〈 0.05), reported more severe symptoms (41.2% versus 10.9%, P 〈 0.05) and more hospital admissions (55.6% versus 21.6%, P 〈 0.05) due to asthma than German children. Conclusions: The results of this study indicate that despite the lower prevalence of asthma and allergy in the Turkish population living in Germany, asthma is a major health problem for Turkish children. Furthermore, these findings suggest inadequate management of asthma in Turkish children.
    Notes: Zusammenfassung Fragestellung: Türkische Kinder stellen in der Bundesrepublik Deutschland mit 4,2% und in München mit 8,6% den größten Anteil nicht-deutscher Kinder in der Altersgruppe bis 15 Jahren. Wenig ist jedoch bisher über Häufigkeit, Symptome und Behandlung von Asthma bronchiale und anderer atopischer Erkrankungen der türkischen Minderheit in Deutschland bekannt. Methodik: In einer Querschnittstudie wurde bei 7445 Schulkindern im Alter von 9 bis 11 Jahren im Großraum München die Häufigkeit, der Schweregrad und die Behandlung des Asthma bronchiale und anderer atopischer Erkrankungen untersucht. Fragebögen wurden von den Eltern ausgefüllt, Lungenfunktionsuntersuchungen und Hautpricktests wurden bei den Kindern durchgeführt. Ergebnisse: Von denen, die die zugeschickten Fragebögen ausfüllten (n = 6490/87%), waren 5030 (77,5%) deutscher und 451 (7%) türkischer Nationalität. Die türkischen Kinder zeigten eine niedrigere Prävalenz von Asthma bronchiale (5,3% versus 9,4%, p 〈 0,05) und Neurodermitis (1,6% versus 12,9%, p 〈 0,001) im Vergleich zu den deutschen Kindern. Signifikante Unterschiede bestanden zwischen türkischen und deutschen Kindern in Art der Symptome und der Krankheitswahrnehmung. Türkische Kinder mit Asthma bronchiale waren seltener beschwerdefrei (10,5% versus 34,6%, p 〈 0,05) berichteten von schwereren Symptomen (41,2% versus 10,9%, p 〈 0,05) und von einer größeren Anzahl von Krankenhausaufenthalten (55,6% versus 21,6%, p 〈 0,05) aufgrund von Asthma bronchiale. Schlußfolgerung: Die Ergebnisse der Studie legen den Schluß nahe, daß Asthma bronchiale trotz der niedrigeren Prävalenz in der türkischen Bevölkerungsgruppe ein erhebliches Gesundheitsproblem bei türkischen Schulkindern darstellt. Die höhere Anzahl von Fehltagen in der Schule und die deutlich höhere Anzahl von Klinikaufenthalten aufgrund von Asthma bronchiale sprechen für eine mangelhafte präventive Behandlung dieser Erkrankung bei türkischen Kindern.
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  • 30
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    Monatsschrift Kinderheilkunde 147 (1999), S. 351-355 
    ISSN: 1433-0474
    Keywords: Schlüsselwörter Latexallergie ; Neuogene Blasenentleerungsstörung ; Kinder ; Key words Latex allergy ; Neurogenic bladder dysfunction ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Objectives: The risk to suffer from natural latex allergy is increased in children with congenital neurogenic bladder dysfunction. We, therefore, evaluated whether or not a serologic screening for detection of sensitization to latex is reasonable in these children. Patients and Methods: 40 children aged from 6 months to 17 years were examined by specific questionnaire-based patient histories, and by determination of total serum immunoglobuline E (total IgE) and natural latex-specific serum immunoglobulin E (latex-IgE) by solid-phase immunoassays. Results: 5 children had a history of allergic reaction to rubber containing materials. In 10 children, latex-IgE was elevated 〉 0.35 kU/l, 6 out of these 10 children without a history of allergic reactions to rubber containing materials. There was a positive correlation of elevated latex-IgE values and the number of former surgical procedures (p 〈 0.006), while no correlation was found between elevated latex-IgE values and clean intermittent catheterization (p = 0.408). Conclusion: Compared to questionnaire-based patient histories, serologic screening examination including determination of latex-IgE values may better identify children at risk to suffer from sensitization to natural latex.
    Notes: Zusammenfassung Fragestellung: Naturlatexallergien kommen bei Kindern mit angeborener neurogener Blasenentleerungsstörung gehäuft vor. Es wurde deshalb untersucht, ob bei dieser Patientengruppe ein serologisches Screening zur Erfassung einer Sensibilisierung gegenüber Naturlatex sinnvoll ist. Patienten und Methode: Untersucht wurden 40 Kinder im Alter von 6 Monaten bis 17 Jahren. Die Untersuchung umfaßte eine gezielte Anamneseerhebung durch Fragebogen sowie die Bestimmung des Gesamtimmunglobulin E (Gesamt-IgE) und des naturlatexspezifischen Immunglobulin E (Latex-IgE) im Serum durch Festphasenimmunoassays. Ergebnisse: 5 Kinder hatten anamnestisch Zeichen einer allergischen Reaktion nach Gummikontakt. 10 Kinder wiesen im Serum erhöhte Werte des Latex-IgE auf, wobei 6 dieser Kinder bisher noch keine Zeichen einer Latexallergie hatten. Pathologische Werte für das Latex-IgE korrelierten statistisch signifikant mit der Anzahl operativer Eingriffe (p 〈 0,0006), nicht aber mit einem durchgeführten sauber intermittierenden Einmalkatheterismus (p = 0,408). Schlußfolgerung: Im Vergleich zur alleinigen fragebogengestützen Anamneseerhebung können durch ein serologisches Screening mit Bestimmung des Latex-IgE mehr Kinder entdeckt werden, die durch eine Sensibilisierung gegenüber Naturlatex gefährdet sind.
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  • 31
    ISSN: 1432-0533
    Keywords: Key words Polyglucosan body ; Periodic ; acid-Schiff-positive granules ; Mouse brain ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Periodic acid-Schiff-positive granules (PGs) appear in the mouse brains in relation to advancing age. The exact location and pathophysiological significance of PGs, however, are not fully understood. The incidence, staining properties, and topographical distributions of PGs in the brains of 17 AKR mice ranging in age from 7 to 18 months were examined histochemically and immunohistochemically using antibody KM279 raised against a polyglucosan. In addition, to define the precise site of PG formation, we investigated the brains of 4 AKR mice of 24 months of age using conventional and immunoelectron microscopy. PGs were seen in all mice examined and the levels were increased with age. The PGs were located predominantly in the hippocampus and, to a lesser extent, in the cerebellum and olfactory bulb. Immunohistochemically, PGs in the hippocampus and cerebellum were labeled uniformly with KM279. On immunoelectron microscopy with this monoclonal antibody, the fibrillar or membranous structures corresponding to PGs seen using light microscopy were labeled specifically with gold particles. With conventional electron microscopy, fibrillar or membranous structures were seen along with synaptic vesicles and dense-core granules. Moreover, around the cells containing PGs, a few synaptic junctions with neighboring cells were observed, indicating that the cells contributing to formation of PGs were neuronal cells. The positive immunoreactivity of AKR mouse PGs for the antibody KM279 suggests that the PGs and similar structures in other species may share a common antigenicity. Thus, it is assumed that PGs in AKR mice might result from some abnormalities in glucose metabolism.
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  • 32
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    Acta neuropathologica 97 (1999), S. 433-436 
    ISSN: 1432-0533
    Keywords: Key words Congenital nemaline myopathy ; Nebulin ; α-Actinin ; Immunohistochemistry ; Western blot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since the nebulin gene is located in the candidate gene locus of autosomal recessive nemaline myopathy, 2q21.2–q22, we examined five muscle biopsy specimens with monoclonal and polyclonal antibodies against nebulin in combination with the modified Gomori trichrome stain. We were able to demonstrate immunohistochemically that there was no abnormality in nebulin in the muscle fibers both with and without nemaline bodies. Although the molecular weight of nebulin was normal, it was slightly reduced in amount on immunoblotting.
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  • 33
    ISSN: 1432-0568
    Keywords: Key words Autonomic ; Wholemounts ; Immunohistochemistry ; Myenteric ganglia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nitrergic (NO) neurons play crucial inhibitory roles in the control of gut motility. Variations in the density of these neurons within the gastrointestinal tract (GI) may provide useful functional information, but, most surveys available have employed limited and/or highly localized samples. It remains unclear to what extent (a) NO neurons are concentrated disproportionately in particular GI regions, or (b) variations in NO cell number merely reflect changes in overall myenteric neuron density. This experiment surveyed the distributions of neuronal nitric oxide synthase-positive (NOS+) and other myenteric neurons in the GI tract, using immunohistochemical and Cuprolinic blue counterstaining techniques. Adjustable sampling grids superimposed on wholemounts were used to investigate the topographic patterns in the stomach (90 sampling sites; 45 per side) and proximal duodenum (63 loci). We present four major findings: First, variations were detected in the number of NOS+ neurons in specific regions of the stomach (e.g., corpus〉antrum@forestomach) and along both longitudinal (oral〉anal) and circumferential (mesenteric〉antimesenteric) axes in the duodenum. Second, the variations in NOS+ neuronal counts within each organ covaried with the total number of myenteric neurons at different locations (stomach, r=0.77; duodenum, r=0.59), suggesting that local myenteric plexus density is a factor determining NOS+ cell concentrations. Third, in contrast to such a principle of covariation within each organ, NOS+ neurons constituted a consistently smaller proportion of gastric (20%) than of duodenal (28%) myenteric plexus neurons, suggesting that a second principle controls the characteristic percentages of the myenteric plexus that express NOS in different organs. Fourth, the regional samples were used to extrapolate the overall number of NOS+ and total myenteric cells in the rat stomach (43,000; 217,000) and first 3.5 cm of the small intestine (29,000; 103,000). These results, taken together, also suggest that the surveying protocol used is capable of detecting subtle differences in cellular distributions, thus providing a practical strategy for investigating patterns of chemical phenotypes within the GI tract.
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  • 34
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    Archives of dermatological research 291 (1999), S. 195-200 
    ISSN: 1432-069X
    Keywords: Key words Epidermis ; Immunohistochemistry ; Protease ; Psoriasis ; Stratum corneum chymotryptic ; enzyme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stratum corneum chymotryptic enzyme (SCCE) is a serine protease which may function in the turnover of the stratum corneum by means of degradation of intercellular adhesive structures between corneocytes. It is also potentially an epidermal activating enzyme for cytokines such as interleukin-1β. The aim of this work was to study the expression of SCCE in psoriatic epidermis by means of immunohistochemistry, and to elucidate the nature of the SCCE present in psoriatic scales by means of biochemical analyses. In comparison to normal skin the number of cell layers expressing SCCE in psoriatic lesions was consistently increased. In nonlesional psoriatic skin the pattern of SCCE expression varied. It was similar to the pattern in normal skin in some biopsies, whereas in other biopsies evidence of an increased expression of SCCE was found. By means of zymography and immunoblotting, extracts of psoriatic scales were found to contain active SCCE as well as enzymatically inactive SCCE precursor. Also the effects of inhibitors on the activity towards a chromogenic protease substrate in the extracts after partial purification by gel exclusion chromatography were compatible with the presence of enzymatically active SCCE. We conclude that the expression of SCCE in psoriasis may be upregulated, and that the conversion of inactive SCCE-precursor to active SCCE occurs in the psoriatic lesion. The possible role of SCCE in the pathophysiology of psoriasis remains to be elucidated, but should be considered in future studies.
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    Archives of dermatological research 291 (1999), S. 238-240 
    ISSN: 1432-069X
    Keywords: Key words Cysteine protease ; Bleomycin hydrolase ; Keratinocyte ; Skin cancers ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 36
    ISSN: 1432-069X
    Keywords: Key words Serotonin ; Allergic contact dermatitis ; Immunohistochemistry ; High-performance liquid ; chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients (P 〈 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process.
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  • 37
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    Archives of dermatological research 291 (1999), S. 303-305 
    ISSN: 1432-069X
    Keywords: Key words Langerhans cells ; Sunburn cells ; UV ; erythema ; Apoptosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 38
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; Bunina body ; Guam ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An investigation of Bunina bodies is important when studying the pathoetiology and pathomechanisms involved in amyotrophic lateral sclerosis (ALS). It may serve as a clue essential for the study of the pathogenesis of Guamanian amyotrophic lateral sclerosis (ALS-G), and it may provide a means of answering the question of whether ALS-G is the same disease as classical ALS or a different entity. In ALS-G, however, no precise histochemical, immunohistochemical, or detailed ultrastructural examination has been published to date. To elucidate the pathological differences/similarities of Bunina bodies between classical ALS and ALS-G, we performed histochemical, immunohistochemical, topographic and ultrastructural examinations. Histochemically, hematoxylin and eosin, Masson’s trichrome, methylgreen-pyronin, phosphotungstic acid-hematoxylin, Klüver-Barrera, Bodian and periodic acid-Schiff staining were utilized. Immunohistochemical examination was performed using antibodies for cystatin C, ubiquitin, Tau-2, Cu/Zn superoxide dismutase, phosphorylated neurofilament and glial fibrillary acidic protein. Histochemical findings were consistent with those previously described for classical ALS. The immunohistochemical study showed that in ALS-G Bunina bodies were intensely labeled by an anti-cystatin C antibody. Topographic examination demonstrated that Bunina bodies were distributed in the spinal anterior horns and Clarke’s column in the spinal cord. Ultrastructurally, Bunina bodies were composed of electron-dense amorphous/ granular material accompanied by vesicular structures and neurofilaments. The results of the present study have revealed that the pathological features of Bunina bodies in ALS-G are identical to those seen in classical ALS. These findings strongly suggest that a similar degenerative process occurs in the spinal anterior horn cells in both ALS-G and classical ALS.
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  • 39
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    Acta neuropathologica 98 (1999), S. 197-202 
    ISSN: 1432-0533
    Keywords: Key words Diffuse axonal injury ; Head injury ; β-amyloid precursor protein ; Immunohistochemistry ; Forensic neuropathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Widespread damage to axons in the white matter of the brain is a well-recognised consequence of non-missile head injury. This diffuse axonal injury is characterised by a gradual swelling of the axon associated with an accumulation of cellular organelles and proteins. We have investigated the relationship between the size of the swellings of the damaged axon with survival time in post-mortem brain tissue. Sixty-six cases of head injury with known length of post-traumatic survival were selected for study, and immunohistochemistry for β-amyloid precursor protein (βAPP) was carried out. The minimum diameter of the βAPP-immunolabelled damaged axons was measured in micrometers using the IBAS image analysis system. There was a strong, positive and significant relationship between the mean size of axonal swelling and survival time which plateaued at around 85 h post injury. With longer survival times the situation becomes more complex. βAPP immunolabelling of damaged axons can contribute evidence about trauma and post-injury survival time in the forensic setting but should always be assessed with other evidence.
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  • 40
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    Acta neuropathologica 97 (1999), S. 40-44 
    ISSN: 1432-0533
    Keywords: Key words Pituitary gland ; Immunohistochemistry ; Mitochondria ; Oncocytes ; Oncocytomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunocytochemical examination for mitochondrial protein and cytochrome oxidase was performed to demonstrate oncocytes in normal adenohypophysis obtained from 28 patients of various age. A small number of solitary large epithelial cells showed intense cytoplasmic granular immunoreactivities for mitochondrial protein and cytochrome oxidase. The proportions of the cells positive for the former and the latter ranged from 0% to 5.9% (mean ± SD; 1.5 ± 1.7%) and from 0% to 4.9% (1.4 ± 1.6%), respectively. These cells were either absent or extremely rare in young patients (under 10 years) but tended to increase in number with age (P 〈 0.0001). On the other hand, the mirror section technique showed that most of these cells were negative for adenohypophysial hormones, but a few of them were faintly positive for: α-subunit (8.0%), β-subunits of follicle-stimulating hormone (4.8%), luteinizing hormone (2.5%), thyroid-stimulating hormone (1.0%), and growth hormone (0.5%), and were negative for prolactin and adrenocorticotropic hormone. We considered that these cells represent oncocytes that exist in varying numbers in normal adenohypophysis. It was suggested that oncocytes in normal adenohypophysis share various common features with tumorous oncocytes of pituitary oncocytomas.
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  • 41
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; Advanced glycation endproducts ; Immunohistochemistry ; Superoxide dismutase ; Hyaline inclusions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-1 (SOD1) mutation, we investigated the immunohistochemical localization of N ɛ-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Immunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.
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  • 42
    ISSN: 1432-0533
    Keywords: Key words Serotonin ; Thiamine deficiency ; Immunohistochemistry ; Vulnerability ; Degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined changes in 5-hydroxytriptamine (5-HT, serotonin) neurons in pyrithiamine-induced thiamine deficiency in mice immunohistochemically. Extensive decreases in the densities of 5-HT-immunoreactive fibers were detected in the lateral septal nucleus, the thalamus, the medial mammillary nucleus, the dorsal and the median raphe nuclei, the raphe obscurus nucleus, the tegmental area, the cerebellum and the vestibular nucleus, though only a small decrease was detected in the inferior colliculus. Most remarkably, degenerative winding fibers were detected between the deep mesencephalic nucleus and the ventral tegmental area. Increases in intensity of 5-HT immunoreactivity in the dorsal raphe nucleus and decreases in the number of 5-HT-immunoreactive cell bodies in the dorsal and the median raphe nuclei were detected. These results demonstrated the differential vulnerability of 5-HT neurons in thiamine-deficient mice. This is the first report to demonstrate changes in 5-HT neurons immunohistochemically throughout the brain of pyrithiamine-induced thiamine deficient mouse.
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  • 43
    ISSN: 1432-0533
    Keywords: Key words Cytoskeletal proteins ; Immunohistochemistry ; Myofibrillar myopathy ; Hereditary myopathy ; Holstein-Friesian cattle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the expression, using immunohistochemical and Western blot methods, of some cytoskeletal proteins including desmin, vimentin, actin, α-actinin, and ubiquitin in hereditary myopathy of the diaphragmatic muscles in Holstein-Friesian cattle (the histochemical and electron microscopical aspects have been previously reported). Immunohistochemically, the expression of desmin was observed strongly in the subsarcolemmal regions, but was lacking or faint in the area corresponding to the core-like structures. Vimentin showed almost the same localization as desmin, but no activity could be observed in the core-like structures. In addition, the core-like structures showed strong immunoreactivity for actin and ubiquitin, but no immunoreactivity for α-actinin. F-actin stained with phalloidin-tetramethyl-rhodamine was strongly positive in irregular spots that corresponded to the core-like structures, but was negative for desmin-positive regions. Western blot analysis of the diseased muscles revealed a significant increase in the amount of desmin and vimentin immunoreactivities and similar amounts of actin and α-actinin compared with the control muscles. Two-dimensional electrophoresis revealed no isoforms of desmin, suggesting the absence of abnormal phosphorylated forms of desmin. Since the co-localization of desmin and vimentin and the absence of phosphorylated desmin suggest that the overexpression of desmin may be reflected in the reactive change or regenerating process, the present myopathy should be regarded as an entity separate from desmin-storage myopathy or desmin-related myopathies. We also discuss the possibility that the present myopathy could be considered as myofibrillar myopathy, a recently proposed nosological entity.
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  • 44
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    Acta neuropathologica 97 (1999), S. 215-220 
    ISSN: 1432-0533
    Keywords: Key words Cerebral ischemia ; Inflammation ; Immunohistochemistry ; Nitrotyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inducible or “immunological” isoform of nitric oxide synthase (iNOS) is induced in many cell types by inflammatory stimuli and synthesizes toxic amounts of NO. In rodent models of focal cerebral ischemia, iNOS is expressed in neutrophils invading the injured brain and in local blood vessels. Studies with iNOS inhibitors and iNOS null mice indicate that NO produced by iNOS contributes to ischemic brain injury. In the present study, we sought to determine whether iNOS is also expressed in the human brain after ischemic stroke. Studies were conducted using immunohistochemistry on autopsy brains with neuropathological evidence of acute cerebral infarction. iNOS immunoreactivity was observed in neutrophils infiltrating the ischemic brain and in blood vessels within the ischemic territory. iNOS-positive cells also were immunoreactive for nitrotyrosine, reflecting protein nitration by NO-derived peroxynitrite and nitrites. iNOS or nitrotyrosine immunoreactivity was not detected outside the region of the infarct. These observations provide evidence that iNOS is expressed in the human brain after ischemic infarction and support the hypothesis that iNOS inhibitors may be useful in the treatment of ischemic stroke in humans.
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  • 45
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    Acta neuropathologica 97 (1999), S. 463-468 
    ISSN: 1432-0533
    Keywords: Key words Amyotrophic lateral sclerosis ; β-Amyloid precursor protein ; Immunohistochemistry ; Fast axonal transport ; Anterior horn neuron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the localization and extent of β-amyloid precursor protein (β-APP695) immunoreactivity as a sensitive marker for impairment of fast axonal transport in the spinal cords of 21 patients with amyotrophic lateral sclerosis (ALS), paying special attention to anterior horn neurons. Specimens from 18 patients without neurological disease served as controls. Increased β-APP immunoreactivity was frequently recognized in the anterior horns of the ALS patients with short clinical courses or with mild depletion of anterior horn cells, while no β-APP immunoreactivity was demonstrated in those with severe depletion of anterior horn neurons or with long-standing clinical courses. Increased β-APP immunoreactivity in the anterior horn neurons was mainly confined to the perikarya and no immunoreactivity was recognized in the dendrites or proximal axons directly emanating from the somata, except some spheroids (proximal axonal swellings) which showed increased immunoreactivity of β-APP. Increased β-APP immunoreactivity was spotted or focally aggregated in the perikarya of normal-looking large anterior horn neurons, while it was frequently diffuse in that of degenerative neurons such as central chromatolytic cells and or those with simple atrophy. On the other hand, the controls showed no immunostaining with β-APP in the spinal cord. These findings suggest that increased immunoreactivity of β-APP in neuronal perikarya of the anterior horn cells and in some proximal axonal swellings is an early change of ALS, and may be a response of the increased synthesis of β-APP resulting from neuronal damage, or the impairment of fast axonal transport.
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  • 46
    ISSN: 1432-0568
    Keywords: Key words Visual system ; Immunohistochemistry ; In situ hybridization ; PNA ; Tenascin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the tree shrew (Tupaia belangeri), the cytoarchitectonic lamination of the lateral geniculate nucleus cannot be detected at birth; it only appears during the early postnatal period. However, a laminated pattern was revealed with rapid Golgi staining and retinal afferents were segregated into the appropriate laminae well before cytoarchitectonic lamination could be seen. Both observations indicate that the extracellular matrix may play a role in the separation of lateral geniculate nucleus cells into laminae. In the present study, the organization of the extracellular matrix was investigated during development using immunohistochemical and in situ hybridization techniques. For immunohistochemistry, peanut agglutinin (PNA) lectin and antibodies against tenascin (TN) were chosen, while for in situ hybridization, mTN riboprobes were used, simultaneously, with antibodies against Vimentin (Vim) and microtubule associated protein (MAP-2). The results showed that the pattern of PNA-binding glycoproteins and that of tenascin were relatively similar, although tenascin appeared later and disappeared earlier. The first interlaminar spaces to be detected were those between layers innervated by opposite eyes. The TN specific mRNA was detected in the lateral geniculate nucleus at P0, but was no longer visible at P7. By comparing TN mRNA and Vim or MAP-2 stainings a correspondence could be observed. The extracellular matrix lamination therefore seems to precede cytoarchitectonic lamination, suggesting that the extracellular matrix may play a role in the development of laminated structures. The TN-producing cells seem to be developing astrocytes and neurons.
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  • 47
    ISSN: 1432-0533
    Keywords: Key words Prostaglandin H2 synthase ; Stroke ; Inflammation ; Immunohistochemistry ; Prostaglandins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2) is up-regulated in the brain of rodents during cerebral ischemia and contributes to ischemic brain injury. This study sought to determine whether COX-2 is also up-regulated in the human brain in the acute stages of cerebral ischemic infarction. Paraffin-embedded sections from patients who died 1–2 days following infarction in the middle cerebral artery territory were processed for COX-2 immunohistochemistry. COX-2 immunoreactivity was observed in infiltrating neutrophils, in vascular cells and in neurons located at the border of the infarct. The data suggest that COX-2 up-regulation is also relevant to cerebral ischemia in humans and raise the possibility that COX-2 reaction products participate in the mechanisms of ischemic injury also in the human brain.
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  • 48
    ISSN: 1432-0533
    Keywords: Key words Xp21 muscular dystrophy carriers ; Muscle biopsy ; Immunohistochemistry ; X chromosome ; inactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report two carriers of Xp21 muscular dystrophy with unusual clinical manifestations and striking variability of dystrophin deficiency within the same muscle biopsy. The first patient was a 60-year-old nun with recent onset of cramps and proximal weakness, mimicking an acquired myopathy. Muscle biopsy disclosed slight alterations in one sample and severe dystrophic changes in another; dystrophin was absent in 7% fibers in the former specimen and in 60% in the second. X inactivation was skewed with 90% cells inactivating the same X chromosome. The second patient was a 17-year-old girl with hyperCKemia, learning disability and a family history of X-linked muscular dystrophy. Muscle biopsy displayed slight fiber size variability and some internal nuclei; dystrophin was absent only in one muscle fiber. A second sample with the same morphological features demonstrated dystrophin deficiency with mosaic distribution. The pattern of X inactivation was normal. These cases emphasize the variability of histopathological changes and dystrophin deficiency in Xp21 muscular dystrophy carriers and the risk of sampling errors in muscle biopsy.
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  • 49
    ISSN: 1432-0533
    Keywords: Key words Glioma ; Cyclooxygenase ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of inflammation. While COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Although COX-1 expression is observed in normal tissue, enhanced COX-2 expression has been attributed a key role in the development of edema, impeding blood flow and immunomodulation observed in pathologically altered tissues. Here, we have analyzed the expression of COX-1 and COX-2 in 50 gliomas and 10 control brains with no neuropathological alterations by immunohistochemistry; 22 glioblastoma multiforme, 9 anaplastic astrocytomas, 5 protoplasmic astrocytomas, 1 gemistocytic astrocytoma and 13 fibrillary astrocytomas were included in the study. Compared with control brains, accumulation of COX-1 was detected in 20–50% of all cells in both low- and high-grade gliomas. Double-labeling experiments revealed COX-1 expression in subsets of macrophages/ microglial cells within the tumor parenchyma and in areas of infiltrative tumor growth. Of the COX-1-positive cells, 90% expressed MHC class II antigens. No COX-1 immunoreactivity was observed in tumor cells. COX-2-positive cells accumulated in tumor cells and in single macrophages/microglial cells in the immediate vicinity of necroses. Further studies are required to determine whether COX-2 is involved in the development of necrosis or, more likely, whether COX-2 is a part of the tumor tissue response to necrosis.
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  • 50
    ISSN: 1432-0533
    Keywords: Key words Calcium-binding protein ; Enkephalin ; Hypoxic encephalopathy ; Immunohistochemistry ; Marbled state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have immunohistochemically analyzed the marbled state in 8 cases of perinatal hypoxic ischemic encephalopathy and 4 cases of infantile hypoxic encephalopathy, using antibodies against calbindin-D28k (CaBD), glial fibrillary acidic protein (GFAP), methionine-enkephalin (MEnk), myelin basic protein (MBP), neurofilament (NF), parvalbumin (PV), substance-P (SuP) and synaptophysin (SP). The marbled state was found in the thalamus in 11 cases, whose age at death was over 10 years. Four cases demonstrated the marbled state in the cerebral cortex, in addition to the striatum and/or the thalamus. The abnormally myelinated fibers in the marbled state were stained with both Klüver-Barrera and Holzer stainings; however, they were partly immunopositive for MBP and completely immunonegative for GFAP, CaBD, MEnk, PV, SuP and SP, although some of the neurons and/or fibers showed immunoreactivities for those calcium-binding proteins and/or neurotransmitters. The axons were visualized in the abnormally myelinated fibers by Bodian staining and/or anti-NF immunostainings in the cerebral cortex and striatum but not in the thalamus. GFAP-positive astrocytes did not show any continuity with the abnormally myelinated fibers. These histological features were seen in the cerebral cortex, striatum and thalamus. Difference of the etiology did not affect the histological features with the exception of anti-PV staining, in which PV-immunopositive neurons were observed only in aged subjects with infantile hypoxic encephalopathy, and seemed to be more severely affected by hypoxic stress during the perinatal period than the early infantile period. These data suggest that the site of lesion or the length of survival period after brain injury might influence the formation of the marbled state rather than the etiology. And the direct relationship between the abnormally myelinated fiber and astrocytic process was not verified.
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  • 51
    ISSN: 1432-0533
    Keywords: Key words Presenilin ; Cerebral infarction ; Astrocytoma ; Glial cells ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Presenilins, some gene mutations of which are associated with familial Alzheimer’s disease (AD), are expressed mainly in neurons in normal brains and brains from patients clinicopathologically diagnosed as AD. They are thought to be related to cell death and survival. We studied the immunolocalization of presenilin to investigate its possible relation to cell death and glial proliferation, using two antibodies against different portions of the presenilin 1 protein, in human brains with cerebral infarction and in astrocytoma, where abundant cell death and glial proliferation are present. Expression of presenilin epitopes was more marked in glial cells than in neurons in and around the ischemic focus, and it was also robust in astrocytoma cells. These findings suggest that presenilins are functioning not only in neurons but also in glial cells in reactive and neoplastic proliferation.
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  • 52
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    Acta neuropathologica 98 (1999), S. 407-413 
    ISSN: 1432-0533
    Keywords: Key words Hemimegalencephaly ; Tuberous sclerosis ; Large neurons ; Balloon cells ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hemimegalencephaly, an uncommon sporadic nonfamilial congenital dysplastic abnormality of the central nervous system, constitutes a pathological spectrum of neuronal migration disorders, but consistently includes abnormal large neurons similar to those in the cortical tubers of tuberous sclerosis. Microscopically, there are also cells with homogeneous and weakly eosinophilic cytoplasm with a single eccentric nucleus, sometimes called balloon cells (likewise prominent in tuberous sclerosis). We looked for immunohistochemical and ultrastructural differences in the large neurons and balloon cells between hemimegalencephaly and tuberous sclerosis. Microtubule-associated protein 1B and 2, phosphorylated and non-phosphorylated neurofilament and synaptophysin identify the large neurons and distinguish them from balloon cells in both entities. Balloon cells in hemimegalencephaly showed no immunoreactivity for TSC2 gene product, tuberin, and vimentin, but similar cells in tuber tissue showed consistent immunoreactivity. Balloon cells in hemimegalencephaly showed no immunoreactivity for glial fibrillary acidic protein, but some cells in tubers showed such immunoreactivity. Ultrastructurally, balloon cells in hemimegalencephaly contained very few lysosomes, microfilaments, and microtubules, but abundant lipofuscin granules. Similar cells in tubers had prominent lysosomes, more microfilaments and microtubules, and very few lipofuscin granules. The resemblance between abnormal cells in hemimegalencephaly and tuberous sclerosis is superficial; their immunohistochemistry and electron microscopic profiles show distinct differences.
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  • 53
    ISSN: 1432-0568
    Keywords: Key words Fish ; Pituitary gland ; Developmental biology ; Cell differentiation ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We previously reported the chronological appearance of adenohypophysial cells in freshwater teleosts using an immunocytochemical technique. The present study investigated the chronological appearance of adenohypophysial cells in the ayu, which is spawned and has its early development in brackish water, and the results were compared with those obtained in freshwater and seawater teleosts, as well as in other vertebrates. In the adult teleostean adenohypophysis, seven or eight types of secretory cells have been distinguished, each of which produce different hormones: prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), gonadotropic hormones (GTH I and GTH II), adrenocorticotropic hormone (ACTH), melanophore stimulating hormone (MSH) and somatolactin (SL). In the pituitary of adult ayu, seven distinct types of glandular cells (PRL, GH, TSH, GTH, ACTH, MSH and SL cells) were identified. Chronologically, a few immunoreactive (ir)-PRL and ir-GH cells appeared in the ventral side of the pituitary one day before hatching. Then, just after hatching, ir-GTH cells were observed in the central to dorsal portion; ir-ACTH cells were found distributed in the anterior portion and some ir-MSH and a few ir-SL cells were seen in the posterior portion of the pituitary. Finally, a small number of ir-TSH cells were identified 50 days after hatching. These results differed from those obtained in other fishes previously reported with regard to the times of appearance of the PRL and GH cells. PRL cells appeared first, followed by GH cells in the freshwater teleosts, PRL and GH cells appeared at the same time in the brackishwater teleosts, while GH cells appeared first and PRL cells appeared last in the seawater teleosts. These results reflect the fact that PRL plays a major role in osmoregulation among freshwater teleosts, as compared with GH, which plays a similar role in seawater teleosts. It seems that both PRL and GH may play important roles in osmoregulation in brackishwater fish.
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  • 54
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    Cancer chemotherapy and pharmacology 44 (1999), S. 203-209 
    ISSN: 1432-0843
    Keywords: Key words Vincristine ; Pharmacokinetics ; Repetitive dosing ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia, non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection. A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total body clearance, apparent volume of distribution at steady state, and area under the concentration–time curve. Intrapatient variability was significantly smaller than interpatient variability for all these parameters except distribution half-life. The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.
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  • 55
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    European spine journal 8 (1999), S. 439-443 
    ISSN: 1432-0932
    Keywords: Key words Low back pain ; Children ; Clinical examination ; Questionnaire ; Prevalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was undertaken to analyse the prevalence of low back pain (LBP) and confounding factors in primary school children in the city of Antwerp. A total of 392 children aged 9 were included in the study. All children completed a validated three-page questionnaire and they all underwent a specific lumbar spine oriented medical examination during their annual routine medical school control. This examination was performed by the city school doctors. The questionnaire was composed of easy “yes/no” questions and visual analogue scales. Statistical analysis was performed using Student’s t-test and chi-squared test at the significance level P 〈 0.05. The prevalence of LBP was high. No gender difference was found. A total of 142 children (36%) reported having suffered at least one episode of LBP in their lives. Of these, 33 (23%) had sought medical help for LBP from a doctor or physiotherapist. Sixty-four percent of children reporting LBP said that at least one of their parents suffered from or complained of LBP. This was significantly higher than for the children who did not report having suffered LBP. The way in which the school satchel was carried (in the hand, on the back) had no bearing on the incidence of LBP. There was significantly more LBP in children who reported playing video games for more than 2 h per day, but this was not so for television watchers. The visual analogue scales concerning general well-being were all very significantly correlated with self-reported LBP, with children who reported LBP being more tired, less happy, and worse sleepers. Of the 19 clinical parameters taken down during the medical examination, only one was significantly more prevalent in the group of children reporting LBP: pain on palpation at the insertion site on the iliac crest of the ilio-lumbar ligament. From this study we can establish that there are few clinical signs that can help to single out school children with LBP.
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  • 56
    ISSN: 1432-069X
    Keywords: Key words Herpes simplex virus ; Cutaneous infection ; Immunohistochemistry ; Polymorphonuclear leukocyte ; Anti-PMN antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We undertook the present study to investigate the role of polymorphonuclear leukocytes (PMN) in defending skin against herpes simplex virus (HSV) infection. For this purpose, we established a mouse model of cutaneous HSV infection. The hind limb footpad skin of 4-week-old ICR mice was abraded linearly once with a feather edge file and infected with various strains of HSV with different virulence. In uninfected control mice, PMN appeared at the abraded skin lesion within 24 h, and were eliminated from the epidermis after 3 days. Mice inducted with a highly virulent strain of HSV demonstrated wide and severe erythematous lesions of the footpad skin and histologically, virus antigen-positive ballooning degenerated keratinocytes were observed. However, in infections with attenuated strains of HSV, the epidermis was regenerated and a viral antigen was discharged within 5 days, together with any infiltrated PMN. Macrophages and NK cells numbered less than PMN. In mice treated with anti-PMN antiserum before HSV infection, PMN infiltration was significantly suppressed 1 day after infection, and these animals developed a severe cutaneous disease even if infected with an attenuated virus. These results indicate the importance of PMN in the control of HSV cutaneous infections, especially in the primary infectious phase.
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  • 57
    ISSN: 1432-1084
    Keywords: Key words: Optic nerves ; Neuritis ; Children ; Central nervous system ; MR imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A 4-year-old boy developed bilateral optic neuritis. Although precise neuro-ophthalmological evaluation was difficult, the diagnosis was made with gadolinium-enhanced MR imaging using fat-suppression technique in the initial stage of the disease. Enhancement and enlargement of the intraorbital and intracanalicular optic nerve were demonstrated bilaterally as well as protrusion of the optic nerve head. The disease responded dramatically to intravenous steroid therapy. The etiologies in children usually differ from those in adolescent and adult patients.
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  • 58
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    European journal of pediatrics 158 (1999), S. 12-17 
    ISSN: 1432-1076
    Keywords: Key words Alternative medicine ; Complementary therapies ; Critical care ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interest in alternative medicine (AM) is growing. In the USA and Canada, studies showed that 34% of adults and 11% of children use AM. In a prospective cohort study, we investigated the interest in AM among parents of critically ill children in the paediatric Intensive Care Unit (ICU) of a university hospital. From January 1996 to April 1997, we distributed questionnaires to the parents of critically ill children. These strictly anonymous questionnaires were completed at home and returned by mail. Exclusion criteria were short (〈1 day) or repeated hospitalizations, and insufficient proficiency of the German language. The inclusion criteria were fulfilled by 591 patients; 561 received the questionnaire (95%) and 289 (52%) were returned. Of the respondents, 70% would appreciate AM as a complementary therapy on the ICU, 23% found AM equally or more important than conventional medicine whereas only 7% regarded AM as unimportant. On the ICU, 18% used AM; surprisingly 41% of them did not discuss it with physicians or nurses. An additional 21% would have liked to use AM, but did not do so. Typically, AM-users administered AM also at home to their children and themselves. Their children were however, older. Conclusions A substantial proportion of parents used measures of alternative medicine in the intensive care unit, or would have like to do so. However, few had the confidence to discuss this wish with the medical personal. This suggests that alternative medicine is of great interest, even on an intensive care unit. Nevertheless, discussion about alternative medicine seems to be taboo in doctor-patient relations.
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  • 59
    ISSN: 1432-1076
    Keywords: Key words Gastro-intestinal bleeding ; Children ; Jejunal leiomyoma ; Neurofibromatosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastro-intestinal bleeding is an uncommon presentation in children with neurofibromatosis. Gastro-intestinal involvement caused by jejunal leiomyoma has only been described in adults. To the best of our knowledge, this is the first paediatric case of jejunal leiomyoma associated with neurofibromatosis. We present a 10-year-old girl with a 9-month history of anaemia and low gastro-intestinal bleeding. Abdominal sonography and small bowel series showed a submucosal mass in the proximal jejunum. On surgery, a submucosal tumour was excised and histological examination suggested a diagnosis of “smooth muscle tumour of undetermined malignant potential”. There were no recurrence of symptoms for 4 years after the operation. Conclusion Jejunal leiomyoma should be considered in a child with neurofibromatosis presenting with gastro-intestinal bleeding.
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  • 60
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    European journal of pediatrics 158 (1999), S. S117 
    ISSN: 1432-1076
    Keywords: Key words Stroke ; Coagulation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0–16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0–17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1; combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92–17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6–65.6; P 〈 0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients. Conclusion Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.
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  • 61
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    European journal of pediatrics 158 (1999), S. 519-522 
    ISSN: 1432-1076
    Keywords: Key words Pulmonary function test ; Adjustment ; Children ; Prediction equations ; Population specific
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fitting adequate prediction equations for pulmonary function test (PFT) parameters is crucial in the analysis of lung function tests and their interpretation. Our work aimed at studying the necessity of building population specific prediction equations, rather than using prediction equations built-in in commercial equipment. We used as an example results of studies carried out among Israeli schoolchildren. Second to sixth grade children (7–13 years old), 1064 boys and 1211 girls, were studied in Tel-Aviv. PFT (forced vital capacity, forced expiratory volume in 1st second, peak expiratory flow, forced expiratory flow in 50% volume, forced expiratory flow in 75% volume) performed by these children were adjusted for height, weight and age, for each sex separately, by a multiple regression procedure. Predicted PFT parameters of 300 boys and 301 girls aged 7–13 years, living along the southern shore of Israel, were calculated using the equations built for the same aged Tel-Aviv children as well as the prediction equations built-in in the spirometer used. The ratios between the observed PFT parameters in the southern children and their expected values, using the Israeli population specific equations, were around 1.00. Using the built-in equations resulted in ratios around 0.90. Conclusion The development of population specific prediction equations for PFT parameters is necessary. Such equations should be used both in clinical assessment to minimize misclassification (healthy/sick child) and in epidemiological studies.
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  • 62
    ISSN: 1432-1076
    Keywords: Key words HIV-1 ; T-cells ; CD69 ; Activation ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the use of a whole-blood assay that measures spontaneous and activation-induced CD69 expression on peripheral blood T-cells in vitro for assessment of T-cell function in HIV-1-infected paediatric patients. Heparinized venous blood from 28 HIV-1 positive children and adolescents and 23 healthy controls was incubated for 4 h with or without 5 μg/ml phytohaemagglutinin (PHA). Thereafter, analysis of CD69 expression on CD4+ and CD8+ T-cells was done by flow cytometry; simultaneously we determined CD4+ T-cell counts and plasma HIV-1 viral load. Neither spontaneous nor PHA-induced CD69 expression differed significantly between HIV-1 positive patients and healthy controls. However, T-cells from HIV-1 positive patients with plasma HIV-1 viral load levels above 70 × 103 copies/ml showed a higher spontaneous CD69 expression than T-cells from patients with lower plasma viral load levels in different stages of the disease. Antiretroviral treatment in four patients reduced spontaneous CD69 expression in CD4+ T-cells and PHA-induced CD69 expression in CD4+ and CD8+ T-cells significantly after 8 weeks of therapy. Conclusion Spontaneous and activation-induced expression of the early (activation) antigen CD69 on peripheral blood T-cells does not distinguish HIV-1 positive patients from HIV-1 negative healthy controls and is not correlated with peripheral blood CD4+ T-cell counts. This test may not be a reliable marker for functional T-cell deficiency during early stages of HIV disease. Increased spontaneous as well as PHA-induced CD69 expression on T-cells from HIV-1-infected children and adolescents in vitro may rather reflect HIV-induced pre-activation of T-cells in vivo.
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  • 63
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    European journal of pediatrics 158 (1999), S. 662-667 
    ISSN: 1432-1076
    Keywords: Key words Somatosensory evoked potentials ; Far-field potentials ; Achondroplasia ; Foramen magnum stenosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Children with achondroplasia may have high cervical myelopathy due to stenosis of the cranio-cervical junction resulting in neurological disability and an increased rate of sudden death. To detect myelopathy we recorded somatosensory evoked potentials (SEPs) after median nerve stimulation in 30 patients with achondroplasia aged 13 months to 18 years (mean 6 years). In addition to the conventional technique of recording the cortical N20 and the central conduction time (CCT), we employed a noncephalic reference electrode recording the subcortical waveforms N13b and P13, generated near the cranio-cervical junction. The findings were related to the clinical status and MRI results. Eighteen patients had MRI evidence of spinal cord compression with indentation or narrowing of the upper cervical cord, and 13 showed signs of myelomalacia. Seven patients had neurological abnormalities. The sensitivities of the SEPs were 0.89 for cervical cord compression, 0.92 for myelomalacia and 1.0 for the clinically symptomatic patients. There were no false-positive results. The subcortical SEPs were more sensitive than the conventional recordings. However, the conventional SEPs were highly specific in the most severely affected patients; here the specificity was 1.0 for patients with myelomalacia and 0.96 for symptomatic patients. Postoperative SEPs improved after occipital decompression in two children. Conclusion The analysis of somatosensory evoked potentials, in particular of subcortical tracings, is useful in the detection of early cervical myelopathy in children with achondroplasia. Early neurosurgical decompression may prevent irreversible damage.
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  • 64
    ISSN: 1432-1076
    Keywords: Key words Heparin treatment ; Heparin-induced thrombocytopenia ; HIT antibodies ; Children ; Catheter patency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The immunological form of heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin medication. It is mediated by multimolecular complexes consisting of platelet factor 4 (PF4)-heparin-IgG which bind to platelets via platelet Fcγ receptors. Cross-linking of multiple Fcγ receptors results in platelet activation, platelet aggregation and enhanced thrombin generation with a increasing risk of developing new thrombosis. In children, data on HIT are sparse. This review of the literature reports on 8 children aged 3 months to 15 years and 14 newborns suffering from HIT. Additionally, we report one new case treated with danaparoid sodium. Thrombotic complications were venous (n = 12) and arterial (n = 15). The children received heparin either for a spontaneous thrombotic event, for severe cardiac diseases or to maintain patency of intravascular catheters which are used for nutrition, blood sampling, and for application of medication. After diagnosis of HIT they were further anticoagulated with aspirin, warfarin, danaparoid sodium, lepirudin or low molecular weight heparin. Conclusion Although HIT is less frequently reported in newborns and children, paediatricians should be aware of HIT in childhood as a potential complication of heparin application. The widespread practice of flushing catheters with heparin should also be debated in view of the risk of triggering the primary immune-response of HIT. In 1999, treatment options for further parenteral anticoagulation of HIT patients are danaparoid sodium (a low-molecular weight heparinoid) and lepirudin (a direct thrombin inhibitor).
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  • 65
    ISSN: 1432-1076
    Keywords: Key words Factor V G1691A ; Prothrombin G20210A ; Lipoprotein (a) ; Central venous lines ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single defect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. Conclusion The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.
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  • 66
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    European journal of pediatrics 158 (1999), S. S154 
    ISSN: 1432-1076
    Keywords: Key words Veno-occlusive disease ; Antithrombin ; Children ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hepatic veno-occlusive disease (VOD) is a well-known complication of chemotherapy in Wilms tumor patients, particularly young children. Although this complication resolves uneventfully in most patients, fatal cases have been reported. Severe VOD after transplantation has a high mortality rate ranging from 45% to 98%. New hemostatic therapeutic strategies have significantly improved the prognosis of VOD. Chemotherapy-related VOD in Wilms tumor usually has a good prognosis. We describe two patients with Wilms tumor and one with acute lymphoblastic leukemia, who developed severe veno-occlusive disease of the liver according to the Baltimore criteria while undergoing chemotherapy; the symptoms were hepatomegaly, ascites, hyperbilirubinemia, weight gain and, in one patient, short-term lethargy. Elevated LDH levels of 872 to 12,000 U/l were observed in our patients. All patients had thrombocytopenia between 29,000 and 40,000/μl and decreased antithrombin (AT) and protein C levels; two patients had gastrointestinal bleeding. All patients developed a coagulopathy because of severe hepatic dysfunction. Two patients received low-dose heparin at the onset of VOD. The thrombolytic therapy was rapidly changed to AT supplementation (20–80 IU/kg bw 2× per day) without heparin when thrombocytes were very low or gastrointestinal bleeding occurred. Resolution of VOD was observed in all patients receiving AT alone. The chemotherapy was discontinued in a patient with accidental actinomycin D overdosage in view of the severity of symptoms. The remaining two patients received chemotherapy according to the therapy protocol after restitution. All patients survived without sequelae with a median follow-up of 28 months (range 8–48 months). Conclusion Hepatic veno-occlusive disease is a rare but increasingly recognized complication in pediatric cancer patients receiving conventional chemotherapy. AT supplementation constitutes a good alternative treatment of severe VOD in comparison with other thrombolytic therapies, particularly in patients at high risk of bleeding.
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  • 67
    ISSN: 1432-1076
    Keywords: Key words Antithrombin concentrate ; Children ; Septicaemia ; Acquired antithrombin deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Consumption coagulopathy is a serious problem in childhood. In addition to treatment of the underlying disease, consumption coagulopathy was previously treated with heparin. Nowadays it is treated by substitution of coagulation factors, especially antithrombin (AT) concentrate, alone or in combination with heparin. In this pilot study we administered AT concentrate (dosage 80 U/kgbw/d), without additional heparin treatment, to 29 children beyond infancy with acquired AT deficiency. Antithrombin, platelet count, fibrinogen, PT, and APTT were assayed before and during the course of AT substitution. These coagulation parameters returned to normal 48 hours after normalisation of the plasma AT level. AT levels normalised within 24 h of initial substitution in all children. Lethal outcome due to the underlying disease was observed in only two children. Conclusion Data of this pilot study suggest that, concomitantly with the treatment of the underlying disease, consumption coagulopathy in childhood can be managed successfully with early substitution of AT concentrate.
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  • 68
    ISSN: 1432-1076
    Keywords: Key words Coagulation ; Fibrinolysis ; Head injury ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was designed to evaluate the post-trauma haemostatic changes in 27 children with severe cranio-cerebral trauma defined by a modified Glasgow Coma Score (GCS) 〈10. Blood samples for coagulation studies (fibrinogen, von Willebrand factor (vWf), factor VIII:C, antithrombin, protein C, plasminogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI), D-dimer) were obtained within two hours of admission, 24 h later, and on days 3–5, 7–9, 21 and 35. Data of this study indicate that alterations of coagulation in paediatric patients are similar to those in adults: On hospitalisation, activated haemostasis was found with decreased fibrinogen, antithrombin and protein C along with enhanced t-PA and PAI. Twenty-four hours later, hypercoagulability with significantly increased vWF and fibrinogen started, with a peak level within the second week. Within 24 h of admission, 17 children developed disseminated intravascular coagulation (DIC) with a clear-cut decrease of antithrombin and fibrinogen together with platelet consumption and enhanced D-dimer. The outcome of children with DIC was significantly poorer than in those without DIC. Complete recovery was seen in five patients; sequelae no handicap and moderate disability were each found in six patients. Severe disability was diagnosed in two children, and fulminant DIC with lethal outcome occurred in eight patients. The GCS (P 〈 0.01) and the occurrence of DIC (P 〈 0.005) showed the strongest association with the patients' clinical outcome. Conclusion Our data underline the significance of post-trauma disturbances of the haemostatic system for the clinical course and outcome in children with severe cranio-cerebral injuries.
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  • 69
    ISSN: 1432-1084
    Keywords: Key words: Lung disease ; Pneumoconiosis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. We report two cases of children with malignancies and subpleural nodules found on computed tomography (CT) scan. In both cases the diagnosis was anthracosis. This pathologic condition has never been reported in children. Causes of anthracosis include a smoking environment, living in urban areas and air pollution.
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  • 70
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    Experimental brain research 126 (1999), S. 200-204 
    ISSN: 1432-1106
    Keywords: Key words Motor development ; Anticipatory postural adjustments ; Bimanual coordination ; Children ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anticipatory postural adjustments (APA) are needed to perform a movement without perturbing posture. We investigated the development of APA in 3- to 4-year-old children during a bimanual load-lifting task. The task required maintaining a stable elbow position despite imposed or voluntary unloading of the forearm. Although children can compensate the consequences of unloading by using APA, their performance did not reach an adults’ level. In addition, children showed high intra-individual variability in the voluntary situation, revealed by the coexistence of both adult-like and immature patterns in kinematic and electromyographic data. In conclusion, the present study reports that APA, associated with a bimanual load-lifting task, are still being set up in 3- to 4-year-old-children. The intra-individual variability should decrease with age and be associated with a progressive mastering of the timing parameters characterizing APA.
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  • 71
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    Experimental brain research 128 (1999), S. 309-314 
    ISSN: 1432-1106
    Keywords: Key words GABA ; Bromodeoxyuridine ; Proliferation ; Immunohistochemistry ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The birthdates of GABAergic amacrine cells in the rat retina were investigated by immunocytochemistry using anti-GABA and anti-bromodeoxyuridine (BrdU) antisera. The ratio of co-localization of GABA to BrdU increased gradually from embryonic-day 13 (E13) and showed a peak value on E18 in the central retina and on E20 in the periphery. After birth, until postnatal-day 3 (P3), a few co-localized cells were observed in the inner nuclear layer (INL). However, in the peripheral retina, co-localized cells were observed in the INL and ganglion cell layer until P5. Our results suggest that the birthdates of GABA-immunoreactive cells vary, depending on cell-type and that there is a temporal lag in the GABA-immunoreactive cell production in the peripheral retina relative to the central retina.
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  • 72
    ISSN: 1432-1106
    Keywords: Key words Lumbar motoneurons ; Immunohistochemistry ; Light microscopy ; GABA and glycine colocalization ; Stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The distribution of γ-aminobutyric acid (GABA) and/or glycine-immunoreactive (IR) terminal-like structures apposed to somatic and dendritic membrane of lumbar α-motoneurons in column 2 was examined in 1- and 3-week-old kittens and in the adult cat. This quantitative study was carried out using a postembedding technique on semithin sections and a stereological method, the disector. Analysis of immunoreactive terminals showed that the percentages of GABA-IR and glycine-IR terminals (these populations include terminals containing both GABA and glycine) apposed to somatic and proximal dendritic compartments of α-motoneurons are almost the same in kittens, while in the adult glycinergic innervation becomes predominant. This change results from: (1) the decrease in numbers of GABA-IR terminals contacting the somatic compartment between 3 weeks and adult stage, while the numbers of glycine-IR terminals show no significant changes after birth and the numbers of terminals containing both neurotransmitters (GABA-IR+glycine-IR) present transient changes and (2) the postnatal increase in the dendritic compartment, in numbers of GABA-IR, glycine-IR and GABA-IR+glycine-IR terminals; the increase being larger for glycine-IR terminals. Furthermore, using a postembedding immunogold technique, observations by electron microscopy showed that GABA-IR P boutons apposed to M boutons can already be identified at 1 week after birth.
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  • 73
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    Experimental brain research 125 (1999), S. 239-247 
    ISSN: 1432-1106
    Keywords: Key words Precision grip ; Motor development ; Motor control ; Children ; Object manipulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent evidence has shown that the anticipatory control of grip and load force is not innate and develops over several years in childhood. The present study examined the development of grasping behavior by quantifying the relationship between grip force and the vertical acceleration of an object. Children and adults were requested to use a precision grip to lift an instrumented object which varied in size and weight. Grip force, grip force rate and the vertical position and acceleration profiles of the test object were measured or calculated. The results demonstrated the presence of distinct developmental milestones in the maturation of precision grip from 2 to 9 years of age. With 2-year-old children, the peak acceleration was negatively correlated (r=–0.51, n=34, P〈0.01) with peak grip force during lifting. By 3 years of age, peak acceleration and peak grip force during lifting became positively correlated (r=0.28, n=104, P〈0.01) and the correlation continued to strengthen up to 9 years of age. Variations in the temporal coupling of both peak grip force and peak acceleration also decreased with maturation. Furthermore, starting at 4-years-old, children clearly controlled the acceleration and deceleration of the object in a symmetrical pattern and used a single burst of grip force rate to grasp the object with some regularity, suggesting that the emergence of an anticipatory control strategy had already begun.
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  • 74
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    European journal of pediatrics 158 (1999), S. 24-28 
    ISSN: 1432-1076
    Keywords: Key words Hashimoto thyroiditis ; Graves disease ; Children ; TSH function-blocking antibody ; Cytotoxic antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT4) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT4 concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated tri-iodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. Conclusion Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study.
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  • 75
    ISSN: 1432-1076
    Keywords: Keywords Liver ; Steatosis ; HIV ; AIDS ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty HIV-infected children were cross-sectionally examined for morphologic hepatic abnormalities, using ultrasonography or histology. Abdominal ultrasonography was performed in 27 children. The liver structure was normal in four patients, one of whom had moderate symptoms of the HIV infection and three of them severe symptoms. Abnormal liver structure, compatible with hepatic steatosis, was found in 23 (85%) patients. Five of them were in an early stage of the HIV infection (category N or A), three patients were ranked in category B and 15 patients in category C. Histological examination of the liver was performed in 11 children and steatosis was documented in ten (91%). In seven (70%) of these ten children steatosis had been suspected by ultrasonography. In conclusion, steatosis is common in HIV-infected children. It is non-specific and has no impact on disease, diagnostic evaluation or management. Conclusion Ultrasonography is a sensitive, accurate, non-invasive screening tool. It is more reliable than liver function tests.
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  • 76
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    Keywords: Key words Respiratory chain ; Mitochondria ; Children ; Infancy ; Liver failure ; AbbreviationsMRCD mitochondrial respiratory chain disease ; OLT orthotopic ; liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or other extra-hepatic symptoms may pre-exist, or appear in the post-transplant follow up. Pre-transplant evaluation should aim to rule out neurological disease, which may be difficult to differentiate from signs accompanying liver insufficiency. Cerebrospinal fluid lactic acid levels, compared to blood lactate, may be suggestive of central nervous system involvement. Of 11 cases with respiratory chain disorders who had liver transplantation in various centres, 4 are alive and well on follow up, and 6 died, three of them having developed neurological disease post orthotopic liver transplantation. All three patients with initial liver and gastro-intestinal disease died early after transplantation, indicating that these may be poor candidates for this procedure. Conclusion Liver transplantation is feasible in hepatic respiratory chain disorders, but extra-hepatic disease should be ruled out before transplantation. Extra-hepatic manifestations may, however, appear and cause patient death despite successful transplantation.
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  • 77
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    European journal of pediatrics 158 (1999), S. S085 
    ISSN: 1432-1076
    Keywords: Key wordsα1-Antitrypsin ; Liver disease ; Liver transplantation ; Children ; AbbreviationsAATα1-antitrypsin deficiency ; OLT orthotopic liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Only a minority of infants born with α1-antitrypsin deficiency will develop serious liver disease during childhood, mostly but not always after neonatal cholestasis. Early prognosis is difficult and all children have to be followed up carefully. The liver disease progresses with varying speed and it lacks specific features. At the time of liver transplantation the young patients have no pulmonary disease induced by the deficiency and in those with renal involvement, the kidney problems can mostly be dealt with by conservative therapy. The peri- and postoperative care of the patients who undergo liver transplantation does not differ from the usual routines.
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  • 78
    ISSN: 1432-1076
    Keywords: Key words Mild head injury ; Fractured bone ; Late sequelae ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two years after an accident resulting in either a mild head injury or a fractured bone, two groups of 22 children each, aged 4–14 years, were examined for the existence of any neurobehavioural symptoms by means of a standardized questionnaire filled out by their caretakers. Selection of the children was based on reports of the Accident and Emergency Department in 1 year. Significantly more symptoms were reported after mild head injury. The main symptoms reported were headache, dizziness, fatigue and memory problems. The total number of symptoms in the children with mild head injury exceeded four times this in the group of children with a fractured bone. Conclusion Even 2 years after a mild head injury there are still residual symptoms in daily life.
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  • 79
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    European journal of pediatrics 158 (1999), S. 298-301 
    ISSN: 1432-1076
    Keywords: Key words Isolated ; Sphenoid ; Sinusitis ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute isolated infectious sphenoiditis is an uncommon, potentially dangerous condition which is often misdiagnosed because of its nonspecific symptoms and paucity of clinical signs. We present eight children with isolated sphenoiditis who were managed in our medical centre during the last 2 years and review the literature. All the patients were adolescents or pre-adolescents and all experienced moderate to severe refractory oppressive headache. Four had a history of sinusitis or allergic rhinitis. None had fever or any other directing clinical sign. Diagnosis was made by cranial computer tomography. All were treated with antibiotics and recovered completely without infectious or neurological complications. Conclusion Acute isolated infectious sphenoiditis should be considered in adolescents and pre-adolescents who present with constant moderate to severe oppressive headache. Awareness of this entity will enable early diagnosis and initiation of antibiotic treatment which is essential to avoid complications and surgical intervention.
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  • 80
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    European journal of pediatrics 158 (1999), S. 362-366 
    ISSN: 1432-1076
    Keywords: Key words Type 1 diabetes ; Children ; Risk factors ; Case control ; Environmental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P 〈 0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). Conclusion In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cow's milk products in early infancy, vaccination and other environmental factors.
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  • 81
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    European journal of pediatrics 158 (1999), S. 550-552 
    ISSN: 1432-1076
    Keywords: Key wordsShigella ; Toxic encephalopathy ; Children ; Brain oedema ; Shiga toxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown. Conclusion Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.
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  • 82
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Kinderdermatologie ; Exanthem ; Kinder ; Key words Pediatric dermatology ; Exanthema ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Unilateral laterothoracic exanthem a (ULE) is a self-limited, probably infectious-allergic skin disease predominately affecting small children. We describe five such cases. The typical unilaterally located or at least unilaterally dominant exanthem usually starts in the axillary region and is characterized by red, partly confluent papules and fine scales. Two of the children presented with atypical manifestations of ULE. Due to its asymptomatic course, therapy is not necessary in the majority of cases.
    Notes: Zusammenfassung 5 Kinder mit der Diagnose eines unilateralen laterothorakalen Exanthems (ULE) werden vorgestellt. Beim ULE handelt es sich um eine selbstlimitierende, vermutlich infektallergische Hauterkrankung, die hauptsächlich im Kleinkindesalter auftritt. Das typischerweise streng einseitig lokalisierte, immer jedoch einseitig dominierende Exanthem geht meist von der Axillarregion aus und zeigt erythematöse, teils konfluierende Papeln. Zwei der fünf Kinder zeigten auch atypische Hautveränderungen eines ULE. Eine Behandlung ist aufgrund seines überwiegend asymptomatischen Verlaufs in der Mehrzahl der Fälle nicht notwendig.
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  • 83
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    Archives of dermatological research 291 (1999), S. 511-516 
    ISSN: 1432-069X
    Keywords: Key words Melanocyte ; Naevus ; Melanoma ; Immunohistochemistry ; Monoclonal antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution of melanocytes in human skin has been observed to vary within and among individuals, yet little is known of the factors that determine the density of these pigment cells. These factors were explored in a molecular epidemiological study conducted among a population-based sample of 97 male subjects aged over 50 years in Queensland, Australia. Information relating to environmental and phenotypic factors was collected through face-to-face interviews and physical examination of all participants. In addition, 2-mm biopsies of representative skin were taken from the dorsum of the hand and another anatomical site. Melanocytes were identified by cytoplasmic staining with the B8G3 (anti-TRP1) monoclonal antibody using standard immunohistochemical techniques. Melanocyte counts were performed blind by two observers. On crude analysis, melanocyte density decreased with advancing age (P = 0.0002), and increased with increasing number of naevi (P = 0.01). Other pigmentary characteristics (such as hair and eye colour and depth of tan) were not associated with epidermal melanocyte density. Melanocyte density varied significantly by anatomical site (P = 0.02), with highest densities observed on the back/shoulders (n = 50, 17.1 ± 8.8 cells/mm, mean ± SD) followed by the upper limbs (n = 11, 12.6 ± 8.8 cells/mm) and lower limbs (n = 14, 14.4 ± 5.9 cells/mm). Lowest melanocyte densities were recorded on the anterior trunk (n = 3, 3.2 ± 2.4 cells/mm). These findings confirm the results of earlier studies in which site-specific differences in melanocyte density have been found. We speculate that the unequal distribution of melanocytes may partially explain the site-specific incidence of melanoma, offering fresh perspectives on the aetiology of this cancer.
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  • 84
    ISSN: 1248-9204
    Keywords: Contralateral hernia ; Children ; Incidence ; Predisposing disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is impossible to determine whether or not a child will develop a contralateral hernia after inguinal hernia repair. There exists no risk score for the occurrence of a contralateral hernia. This well-known fact prompted us to perform the underlying study. In a retrospective trial, we reviewed the files of all children operated on for inguinal hernias in our department from January 1986 until December 1994. During this period, we performed 1721 hernia repairs on 1708 children aged 0–16 years. In 96 (5.6%) of these patients, the indication to operate was a contralateral hernia following previous unilateral repair. Comparison of the ages at the time of primary inguinal repair of those children who developed a contralateral hernia (n=96) and those who did not (n=1612) showed a significantly increased incidence of contralateral hernias if the primary operation was performed before the age of two months (p〈0.0001). Diseases predisposing to hernias were found in 38% of all children (prematurity, dystrophia, ventriculo-peritoneal shunt, ascites, asthma). The authors recommend a contralateral exploration for children under the age of two months if they have any predisposing disease.
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  • 85
    ISSN: 1432-0584
    Keywords: Key words Hypergammaglobulinemia ; Polyclonal ; Acute myeloid leukemia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.
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  • 86
    ISSN: 1432-0584
    Keywords: Key words Thrombopoietin ; Interleukin-11 ; Interleukin-6 ; Thrombocytopenia ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We measured serum levels of thrombopoietin (TPO), interleukin (IL)-11, and IL-6 in 90 different samples from 67 pediatric patients with thrombocytopenia (TP). The cytokine levels were determined by enzyme-linked immunosorbent assays (ELISA), and the biological activity of TPO was measured using a cell line transfected with human c-mpl. In patients with impaired megakaryocytopoiesis, as found in diseases such as aplastic anemia, amegakaryocytic TP, or TP with absent radii, we found TPO levels which were highly elevated compared with normal values (mean=261 AU/ml, n=52, vs. 22 AU/ml in healthy controls). In contrast, patients suffering from idiopathic thrombocytopenic purpura (mean=16 AU/ml, n=31) or platelet function defects (mean=23 AU/ml, n=7) demonstrated normal TPO levels. The biological activity tested in the bioassay correlated well with the ELISA data. However, sera of some patients with amegakaryocytic TP demonstrated a remarkably higher biological activity of TPO than expected from the ELISA data. Within the different groups there was no correlation between platelet counts and TPO levels. Only 27% of all samples had elevated levels of IL-11 (mean=450 pg/ml, n=20). Elevated IL-6 serum levels were detected in only 13% of all samples analyzed (mean=42 pg/ml, n=12). We conclude that megakaryocytopoiesis is regulated mainly by TPO, that it is dependent on the platelet and the megakaryocytic mass, and that IL-11 plays an additional role in supporting the platelet production. IL-6 does not appear to be up-regulated in children with thrombocytopenia.
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  • 87
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    Italian journal of neurological sciences 20 (1999), S. 303-307 
    ISSN: 1126-5442
    Keywords: Key words Lyme disease ; Chronic neuroborreliosis ; Children ; MRI ; Demyelinating disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lyme disease is a polymorphic and multisystemic disease caused by Borrelia burgdorferi. Neurological manifestations are found in 10%–50% of cases. We present 2 cases followed for 5 and 6 years of chronic relapsing-remitting neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum and cerebrospinal fluid findings. We discuss clinical, neurophysiological, laboratory and instrumental aspects regarding the difficulties of reaching a correct diagnosis. Further studies, especially in the field of immunology, should help identify the mechanisms responsible for the disease becoming chronic. With this knowledge, it may be possible to design immunological therapies for relapses, and to prevent the evolution of the disease.
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  • 88
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    Italian journal of neurological sciences 20 (1999), S. 119-128 
    ISSN: 1126-5442
    Keywords: Key words Learning ; Development ; Memory ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immediate and 15-min delayed recall of semantically related or unrelated word lists was investigated in 144 normally developing children ranging from 5 to 10 years of age. Immediate recall for the related and unrelated lists increased in a parallel fashion as a function of age. The ability to cluster semantically related items during immediate recall also improved with age. However, in no age class recall scores and clustering indexes were significantly associated. Forgetting rate passing from the last immediate to the delayed recall trial increased for the unrelated list but decreased for the related list of words as a function of age. Results of regression analyses revealed that a developmental increase in forgetting on the unrelated list was actually due to the higher number of words recalled in the last immediate trial by older children. As for the related list, instead, the larger reliance on the clustering strategy of recall by older children was responsible for the progressive reduction of forgetting.
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  • 89
    ISSN: 1432-2099
    Keywords: Key words Case-control study ; Children ; CNS tumour ; Environmental exposure ; Indoor radon ; Leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Abstract  A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m–3) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m–3, no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32–5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96–7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature.
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  • 90
    ISSN: 1534-4681
    Keywords: Esophageal cancer ; Treatment ; Prognosis ; Cell cycle ; Immunohistochemistry ; Cyclin-dependent kinases inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: p21Waf1/Cip1 (p21), p27Kip1 (p27), p53, and Rb play critical roles in cell cycle regulation and may influence the clinical behavior of tumors. We examined whether their expression is useful to predict survival of patients with esophageal squamous cell carcinoma (ESC). Methods: Expression of p21, p27, p53, and Rb was studied by the immunohistochemical method in specimens from 62 patients with curatively resected ESC tumors and scored by a computerized image analysis system. Results: The median expression scores of p21, p27, p53, and Rb (14, 12, 27, and 50, respectively) were used as cut-off points to define low and high expression groups for each protein. The 5-year survival rate for the high p21 expression group was 68%; that for the low expression group was 31% (P = .0062). p27, p53, and Rb were not correlated with overall survival. When patients were categorized into four groups based on p21 expression level and lymph node involvement (pN), the survival curves were significantly different (P = .0017). Thus, patients without lymph node involvement but with low p21 expression had survival similar to that of patients with lymph node involvement and high p21 expression. Multivariate analysis showed that age (P = .0102), lymph node involvement (P = .0076), and p21 (P = .0276) were independent prognostic factors. Conclusions: Expression of p21 is an independent prognostic factor in curatively resected ESC. Definition of new subgroups of patients based on p21 expression may help to enhance the stratification of stage.
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  • 91
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    International journal of legal medicine 112 (1999), S. 159-162 
    ISSN: 1437-1596
    Keywords: Key words VCAM-1 ; Selectins ; Wound age ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract To estimate the age of skin wounds, the endothelial adhesion molecule VCAM-1 (CD 106) was detected in paraffin sections after autoclaving and using the ABC technique. The percentage of VCAM-1 positive blood vessels was determined after the blood vessels had been marked with PECAM-1 (CD 31). Low positive staining reactions were observed for VCAM-1 on endothelial cells of uninjured skin in 18% of the samples. In injured skin, 51% of the cases investigated showed a VCAM-1 expression. Strong positive staining reactions were observed 3 h at the earliest and 3.5 days at the latest after the time of injury. The immunohistochemical results for VCAM-1 differed significantly between the injured and uninjured skin (P 〈 0.01). In a few cases VCAM-1 was detected (n = 6) at low intensity in postmortem skin wounds and a moderate to strong expression of VCAM-1 is indicative of the vitality of the wound. The detection of VCAM-1 can be used for estimating the age of wounds in forensic applications if the degree of expression of further adhesion molecules, especially that of selectins, is taken into account.
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  • 92
    ISSN: 1437-1596
    Keywords: Key words Brain injury ; Cortical contusion ; Inflammatory reaction ; Immunohistochemistry ; Wound ; age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively.
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  • 93
    ISSN: 1437-1596
    Keywords: Key words Forensic pathology ; Wound age ; determination ; Immunohistochemistry ; Morphometrical analysis ; Interleukin-1α (IL-1α)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Notes: Abstract An immunohistochemical and morphometrical study on the temporal expression of interleukin-1α (IL-1α) was performed on 40 human skin wounds with different wound ages. Immunohistochemically, polymorphonuclear neutrophils mainly showed positive reactions for IL-1α in wounds aged between 4 h and 1 day, but with increasing wound age, neutrophils were no longer present, and macrophages and fibroblasts were positively stained. Morphometrically, the ratio of the number of IL-1α-positive infiltrating cells to the total number of infiltrating cells was evaluated. A considerable increase in the IL-1α-positive cell ratio was observed in wound specimens aged 4 h to 1 day, and the maximum ratio was 46.5% in a 7 h-old wound. The mean value of the IL-1α-positive ratio in 10 wound specimens with different wound ages between 4 h and 1 day was 32.8 ± 9.7%. In most cases the ratio of IL-1α-positive cells gradually decreased in wounds aged between 1.5 and 21 days to less than 30%, and the mean value was 17.5 ± 7.2% (n = 27). These results suggest that ratios of IL-1α-positive cells considerably exceeding 30%, indicate a postinfliction interval of 1 day or less.
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  • 94
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    Annals of surgical oncology 6 (1999), S. 70-74 
    ISSN: 1534-4681
    Keywords: Angiogenesis ; Melanoma ; Metastasis ; Immunohistochemistry ; Microvessels.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Angiogenesis has been correlated with melanoma progression, but its role in melanoma metastasis is unclear. Methods: To determine whether angiogenesis correlates with the presence of melanoma metastases, we compared the number of microvessels in the primary melanomas of 12 patients presenting with metastases to those of 13 patients without metastases. Patient groups were matched for gender, age, tumor depth, and histological type and anatomical location of the primary melanoma. Microvessels were stained with factor VIII antibody and counted. Results: Microvessel counts were significantly greater for the metastatic than the nonmetastatic melanomas (51.63 ± 14.95 vs. 24.86 ± 8.415; P 〈 .0001). One hundred percent of the metastatic melanomas had a mean microvessel count of ≥ 37, whereas only 8% of the nonmetastatic melanomas had a mean microvessel count of ≥ 37 (sensitivity = 1.00, specificity = .92). Interestingly, patients with lymph node metastases had significantly lower microvessel counts than did patients with distant metastases (42.00 ± .482 vs. 58.50 ± 16.40; P 〈 .05), and significantly higher microvessel counts than did patients without metastases (42.00 ± 3.482 vs. 24.86 ± 8.415; P 〈 .001). Conclusions: An increased number of microvessels in the primary tumors of patients with melanoma correlates with the simultaneous presence of metastases. This suggests that angiogenesis may be important in the process of melanoma metastasis.
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  • 95
    ISSN: 1534-4681
    Keywords: Breast carcinoma ; Sentinel node ; Axillary lymphadenectomy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Sentinel lymphadenectomy is highly accurate for identifying axillary metastasis from a primary breast carcinoma. Nonsentinel axillary lymph nodes (NSNs) are unlikely to contain tumor cells if the axillary sentinel node (SN) is tumor free. We previously showed that the size of the primary tumor and the size of its SN metastasis predict the risk of NSN tumor involvement detected by hematoxylin and eosin staining. This study used immunohistochemical staining (IHC) to determine the likelihood of NSN axillary metastasis in the presence of SN metastasis. Methods: Between 1991 and 1997, axillary lymphadenectomy was performed in 156 women (157 axillary basins) who had primary breast carcinoma with SN metastasis. By hematoxylin and eosin staining, we identified NSN metastasis in 55 axillae (35%). IHC was then used to re-examine all NSNs (1827 lymph nodes) from the remaining 102 axillae. The incidence of IHC-detected NSN involvement was analyzed with respect to clinical and tumor characteristics. Results: By using IHC, we identified NSN metastasis in 15 (14.7%) of the 102 axillae. By multivariate analysis, the size of the SN metastasis (P = .0001) and the size of the primary tumor (P = .038) were the only independent variables predicting NSN metastasis determined by using either hematoxylin and eosin staining or IHC. Only the number of SN metastases (1 vs. 〉1) was a significant (P = .04) predictor of IHC-detected NSN metastasis. Conclusions: Use of IHC increases the likelihood of detection of NSN metastasis, and the risk of IHC-detected metastasis increases with the size of the SN metastasis and the size of the primary tumor. If SN involvement is micrometastatic (≤2 mm) or detected by using IHC, tumor cells are unlikely to be found in other axillary lymph nodes in patients with a small primary tumor. The clinical significance of micrometastatic disease in lymph nodes is controversial, and a prospective randomized study is necessary to resolve this important issue.
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  • 96
    ISSN: 1530-0358
    Keywords: Carcinoembryonic antigen ; Colorectal neoplasms ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Carcinoembryonic antigen is assumed from the results of several experiments to be associated with invasion of colorectal carcinoma by adhesion or contact inhibition. The patterns and the intensity of carcinoembryonic antigen distribution in colorectal carcinoma were assessed to verify whether they were correlated with malignant potential from those biologic characteristics. METHODS: Carcinoembryonic antigen distribution was tested in the archival samples of 149 colorectal carcinomas by immunohistochemistry, using three characterized anti-carcinoembryonic antigen monoclonal antibodies: T84.66, PR1A3, and PR3B10. The distribution patterns in neoplastic tissue were categorized into unstained, apicoluminal, and diffuse-cytoplasmic patterns. Tumor, invasive tumor margin, and tissue surrounding the tumor were examined. RESULTS: Although all three antibodies revealed a positive correlation, T84.66 showed better discrimination than the others. Although none of the negative staining of the tumor or invasive tumor margin showed recurrence, the apicoluminal pattern showed recurrence, and the diffuse pattern showed the most frequent recurrence (P〈0.01). Recurrence was also associated with staining intensity in the apicoluminal pattern in both the tumor and invasive tumor margin (P〈0.05). Infiltrative tumor growth and lymph node metastasis were more frequent in cases of positive staining in tissue surrounding the tumor. Patients with the apicoluminal pattern achieved longer survival than patients with the diffuse-cytoplasmic pattern in the invasive tumor margin (P=0.024) by a multivariate analysis including tumor stage and histologic differentiation. CONCLUSION: The distribution of carcinoembryonic antigen in tumors and surrounding tissue seems to be closely correlated with invasiveness and metastatic behavior in colorectal carcinoma. Carcinoembryonic antigen immune staining can be considered as an efficient tool to determine groups with risk of recurrence.
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  • 97
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Intestinal/diffuse histotype ; P53 ; Immunohistochemistry ; Prognostic factors ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer. Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis. Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P 〈 .05), confirmed by multivariate analysis (P 〈 .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression. Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.
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  • 98
    ISSN: 1437-2320
    Keywords: Key words Von Hippel-Lindau disease (vHL) ; Multiple spinal hemangioblastomas ; vHL protein ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report on a 57-year-old male presenting with radicular pain in the nerve roots of L5 and S1 on the right side and dysuria. Magnetic resonance imaging (MRI) of the lumbar spine showed multiple (up to 20) small, intradural enhancing nodules attached to the cauda equina down to the sacrum, the largest 1 cm in diameter at the level Th12/ L1 compressing the conus. Additionally, small nodules in the cervico-thoracal region adjacent to the cord, but no cerebellar or cerebral abnormalities, were detected in a consecutive MRI of the remaining neuroaxis. The histology of a resected lesion at Th12/L1 revealed hemangioblastoma of the reticular type. Together with a history of left eye enucleation performed 17 years ago for angiomatosis of the retina and the immunohistochemical detection of von Hippel-Lindau (vHL) protein within the removed spinal hemangioblastoma, a diagnosis of vHL disease was established. Family history and screening for visceral manifestations of vHL disease were negative. In contrast to cerebellar or solitary spinal hemangioblastomas, multiple spinal hemangioblastomas without cerebellar involvement in vHL represent unusual manifestations. Unlike the case for solitary lesions in non-syndromic patients, a surgical cure does not seem feasible in this case. The role of treatment modalities is discussed.
    Type of Medium: Electronic Resource
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  • 99
    ISSN: 1435-1544
    Keywords: Key words Implantable cardioverter defibrillator ; Sudden cardiac death ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Implantable cardioverter defibrillators (ICDs) are the treatment of choice in adults with symptomatic ventricular tachycardia or aborted sudden cardiac death. Treatment with implantable defibrillators is also possible in children, although experience in this patient group is scanty. A review of the literature on the subject of defibrillator therapy in combination with epicardial electrodes is provided. Endocardial electrodes, which have now become the gold standard in adult treatment, have only rarely been used in children. However, our own experience shows that endocardial electrodes can be implanted in most children, which generally obviates the need for thoracotomy.
    Type of Medium: Electronic Resource
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  • 100
    ISSN: 1434-5196
    Keywords: Key words Methadone ; Dihydrocodeine ; Substitution ; Poisoning ; Children ; Schlüsselwörter Methadon ; Dihydrocodein ; Substitution ; Intoxikationen ; Kinder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Es wird über 3 überlebte und 4 tödlich verlaufene akzidentelle Intoxikationen, sechs mit Methadon, eine mit Dihydrocodein, berichtet. Die Intoxikationen betrafen nicht die Substituierten selbst, sondern deren Familienangehörige, Bekannte oder Mit-Patienten. In allen Fällen wurden die Substitutionsmittel weitgehend ungesichert und teilweise vermutlich auch unbeschriftet stehengelassen. Den Substituierten selbst war dabei die Gefahr, die von ihrem Substitutionsmittel ausging, offenbar nicht ausreichend bewußt. Diese Fälle zeigen deutlich, daß qualitätssichernde Maßnahmen bei der immer großzügigeren Substitutionspraxis, insbesondere in Hinblick auf „take-home“-Dosen, notwendig sind.
    Notes: Abstract A total of seven cases of accidental ingestion of methadone or dihydrocodeine by four children and three adults are reported of which four were fatal. In each case, someone in the environment was taking methadone or dihydrocodeine as a substitute drug for heroin addiction who obviously did not realize the dangers of methadone for non-addicts. Possible preventive measures are the usage of child-proof containers with adequate labels for take-home medications. Furthermore substituted addicts have to be thoroughly indoctrinated concerning the toxicity and hazards of methadone.
    Type of Medium: Electronic Resource
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