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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 695 (1993), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Notes: The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release exhibited normal firing-dependent properties. By applying various behaviorally arousing stimuli that normally activate the basal forebrain projection systems, we wished to investigate the functional integration of the grafts in the host brain. In the hippocampus, sensory stimulation, immobilization stress and motor activity all resulted in increased release of graft-derived ACh amounting to 25–65% of the normal response. Variations in ACh levels during the day-night cycle was, however, not observed in the grafted rats. In the frontal cortex, immobilization enhanced the graft-derived ACh release (60% of normal response), whereas the response to sensory stimulation did not reach significance. Since the activity of the normal basal forebrain projection systems is under influence of monoaminergic brainstem afferents, we investigated the effects of systemic administration of amphetamine or apomorphine on ACh release in the hippocampus. Both drugs produced increases in graft-derived ACh release although the response was variable and less pronounced than normal. In conclusion, the graft-derived ACh release was affected by behavioral manipulations and catecholaminergic drugs that normally modify cholinergic septo-hippocampal and basalo-cortical activity. This strongly suggests a high degree of functional integration of the graft in the host brain allowing for a regulated release of transmitter that can be adjusted during ongoing behavior.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 733 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 713 (1994), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Deux cas de tumeurs carcinoïdes de l'estomac s'accompagnant d'un syndrome carcinoïde sont rapportés par les auteurs. En raison de l'élévation des taux du 5-HIAA (acide 5 hydroxyindolacétique) le diagnostic de tumeurs carcinoïdes d'origine digestive fut envisagé. L'emploi de la pentagastrine (PG) provoqua un flushing atypique et une broncho-constriction intense plus que probablement provoqués par la libération d'histamine. Une excrétion anormalement élevée du métabolite principal de l'histamine, l'acide acétique téléméthylimidazole (MeImAA) dans l'urine des 2 malades fut mise en évidence. Ils bénéficièrent d'une nette amélioration des symptômes qu'ils présentaient grâce à la prednisolone et au blocage des récépteurs histaminiques. Un des 2 malades accusait une sécrétion excessive de sérotonine (5-HT) et d'histamine; le blocage périphérique des récepteurs 5-HT2 fut de ce fait adjoint au traitement. Ce malade répondit favorablement sur le plan clinique et biochimique à un traitement cystotoxique par la streptozotocine et plus tard par un analogue de la somatostatine. Chez les malades qui sont suspects d'être porteurs d'une tumeur carcinoïde de siège indéterminée l'emploi de la pentagastrine doit être écarté jusqu'à ce que l'excrétion de la MeImAA ait été mise en évidence.
    Abstract: Resumen Se presentan 2 casos de tumores carcinoides gástricos con el síndrome carcinoide del intestino anterior. Los altos niveles urinarios de ácido 5-hidroxiindolacético (5-HIAA) hicieron sospechar la presencia de tumores primarios de origen en el intestino medio. El estímulo con pentagastrina (PG) provocó un “flush” atípico y broncoconstricción severa, muy probablemente causada por liberación de histamina. La excreción excesiva del metabolito principal de la histamina, el ácido tele-metilimidazolacético (MeImAA) fue demostrada en ambos pacientes, y ambos obtuvieron mejoría sintomática con prednisolona y bloqueo de los receptores de histamina. Uno de los pacientes presentó secreción excesiva de serotonina (5-HT) así como de histamina. Por ello se decidió añadir el bloqueo periférico de los receptores 5-HT2 al regimen terapéutico. Este paciente mostró respuesta subjetiva y bioquímica al tratamiento citotóxico con estreptozotocina y ulteriormente respondió bien a un análogo de la somatostatina. Cuando se sospeche de un tumor carcinoide del intestino anterior, o en presencia de pacientes con tumores carcinoides sin ubicación anatómica, la prueba de estímulo con PG no debe ser utilizada hasta cuando se haya determinado la excreción de MeImAA.
    Notes: Abstract Two cases of gastric carcinoid tumors with the foregut carcinoid syndrome are presented. Due to elevated urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), primary tumors of midgut origin were suspected. Provocation with pentagastrin (PG) elicited atypical flushing and severe bronchoconstriction, most probably caused by the release of histamine. Excessive excretion of the main histamine metabolite, tele-methylimidazole acetic acid (MeImAA), in urine of both patients was demonstrated. Both patients had good symptomatic relief with prednisolone and blockade of histamine receptors. One of the patients had excessive secretion of serotonin (5-HT) as well as of histamine. Peripheral blockade of 5-HT2receptors was therefore added to the medical treatment. This patient had a subjective and biochemical response to cytotoxic treatment with streptozotocin and later responded well to a somatostatin analogue. On clinical suspicion of a foregut carcinoid tumor, or in patients with carcinoid tumors without anatomical localization, PG provocation should not be used until the excretion of MeImAA has been determined.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Liver metastases imply a major problem in patients with carcinoid tumors. Patients with localized disease should always undergo resection for cure. Patients with distant metastatic disease can also undergo resection for potential cure or symptom palliation because of the slow growth rate of many carcinoid tumors. In patients with the midgut carcinoid syndrome and bilobar hepatic disease we have performed primary surgery to relieve such symptoms as intestinal obstruction and ischemia, followed by successive embolizations of the hepatic arteries to reduce functional tumor burden in the liver. For optimal palliation, all patients with residual tumor were treated by octreotide. In a consecutive series of 64 patients with the midgut carcinoid syndrome we thus attained a 5-year survival rate of 70%. Fourteen of the patients underwent intentionally curative surgery (e.g., primary surgery followed by liver surgery). Of these patients, none died from their tumor disease during the period of study. The value of adjunctive interferon therapy is currently under evaluation.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28–71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Anaplastic giant cell carcinoma of the thyroid is a rare but highly malignant tumor. At the Karolinska Hospital in Stockholm, surgery, chemotherapy, and radiotherapy have been used separately or in various combinations in 81 patients admitted with this diagnosis during 1971–1997. In this study, we present the various multimodality treatment regimens and their changes over the years and the subsequent differences in survival and local tumor control. Overall, eight patients (10%) survived more than 2 years. All survivors were treated with combinations of chemotherapy, radiotherapy, and surgery. Among the patients who died, local tumor control was achieved by the therapy given in many cases. The results suggest that our current strategy with a combination of preoperative hyperfractionated accelerated radiotherapy, doxorubicin pre- and postoperatively, and debulking surgery whenever possible results in better local tumor control and an increased chance of survival.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-2568
    Keywords: gastric ECLomas ; hypergastrinemia ; histamine ; neoplasia ; gastrin ; Mastomys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Profound and sustained inhibition of gastric acid secretion has been associated with development of carcinoid tumors of the fundic enterochromaffin-like (ECL) cells in rodents. While ECL cell hyperplasia has been recognized in humans, the development of carcinoid tumors is rare and often confined to patients under treatment for gastrinoma related to the multiple endocrine neoplasia type I (MEN1) syndrome. The Mastomys was utilized as a model for the rapid induction of ECLomas by insurmountable acid secretory blockade induced by the pharmacologically irreversible H2-receptor antagonist, loxtidine. Loxtidine-induced ECL cell hyperplasia and neoplasia were compared in the absence of presence of cyproheptadine (0.5 mg/kg), an H1-receptor antagonist. Loxtidine administration resulted in a significant increase in ECL cell hyperplasia and neoplasia as well as an increase in ECL cell number, mucosal thickness, plasma gastrin levels, and stomach weight. Cyproheptadine ameliorated loxtidine-induced ECL cell hyperplasia and neoplasia and significantly decreased loxtidine-stimulated increases in ECL cell number. Nevertheless, cyproheptadine failed to alter the loxtid-ineinduced increase in plasma gastrin, stomach weight or mucosal height. The results indicate that cyproheptadine, an H1-receptor antagonist, inhibits loxtidine-induced ECL cell hyperplasia independent of any effects on serum gastrin.
    Type of Medium: Electronic Resource
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