Influence of preoperative bromocriptine therapy on success of surgery for microprolactinoma.
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Biomedical subjects
Publications and source records attributed to M Buchfelder.
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As the research on cellular changes has shed invaluable light on the pathophysiology and biochemistry of brain tumors, clinical and experimental use of molecular imaging methods is expanding and allows quantitative assessment. The term molecular imaging is defined as the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Molecular imaging sets forth to probe the molecular abnormalities that are the basis of disease rather than to visualize the end effects of these molecular alterations and, therefore, provides different additional biochemical or molecular information about primary brain tumors compared to histological methods "classical" neuroradiological diagnostic studies. Common clinical indications for molecular imaging contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as molecular imaging represents a novel technology for visualizing metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. Molecular imaging probes and drugs are being developed to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging helps to close the gap between in vitro and in vivo integrative biology of disease.
AIM: Hormonal deficiencies, visual disturbances, or cerebral symptoms are often the symptoms through which craniopharyngiomas (CP) first become clinically manifest. As these symptoms can exist for a long period of time various specialists are often consulted before the final diagnosis is made. PATIENTS AND METHODS: Between the years 1970 and 1998, 37 children and adolescents with CP were treated in Erlangen. The documents of 35 patients (22 male, 13 female) were evaluated retrospectively. RESULTS: The median age of the children at diagnosis was 9,3 years (1,3 - 15,6 years). The most frequently documented symptoms were: headache 57 % (median duration 7 months; varying from 1 week to 6 years), visual disturbances 45 % (median duration 2 months, range 2 weeks to 10 years), and reduced growth 40 % (median duration 1 year, range 3 months to 5 years). On average the reported symptoms were present for 15 months (median 5 months, time span 1 week to 10 years). CONCLUSION: The clinical symptoms of CP are non-specific and highly varied. Endocrine disturbances are the primary objective finding. Correct interpretation of the symptoms are required for the early diagnosis of CP.
BACKGROUND: Tumours of the central nervous system mostly present with neurological symptoms and signs of intracranial hypertension. Several reports of cerebral tumors in adolescents outline initial symptoms of anorexia and emaciation, leading to the diagnosis of anorexia nervosa. PATIENT: We report on a 15.5-year-old girl with a craniopharyngioma. The girl had a 2 year history of weight loss, dystrophy, no onset of puberty, and a 6 year history of headache. These symptoms had led initially to the clinical diagnoses of migraine and anorexia nervosa, since unenhanced computed tomography of the brain was normal. At presentation, physical examination showed short stature (height SDS - 3.6) and Tanner stage I. Bone age delay was about four years. Laboratory analyses showed hypopituitarism. The diagnosis of craniopharyngioma was made by repeated imaging, depicting an intrasellar and parasellar mass, which was totally removed by neurosurgery. Hormonal substitution with hGH, L-thyroxine, hydrocortisone, and estrogens led to normal physiological development and final height within upper target height. CONCLUSIONS: The reported case illustrates that the diagnosis of craniopharyngioma is often delayed due to unspecific clinical symptoms. Careful evaluation of anthropometrics, ophthalmologic, and endocrine data in patients with suspected eating disorders may give additional clues to the diagnosis of a craniopharyngioma.
Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.
Proopiomelanocortin (POMC) is expressed predominantly in the corticotrophic cells of the pituitary. Regulatory sequences required for the expression of the human (h) POMC gene were investigated using transient expression of hPOMC-CAT fusion genes in pituitary and nonpituitary cells in combination with DNase I footprint and gel retardation assays. Gene transfer experiments revealed that the hPOMC promoter is more efficiently transcribed in AtT-20 pituitary cells than in HeLa cells. Using deletion analysis, negative regulatory elements between nucleotides -676 and -414 and positive regulatory elements between nucleotides -414 and -93 could be identified. When placed in front of the heterologous thymidine kinase (tk) promoter, nucleotides -414/-223 enhance transcription in AtT-20 cells and in primary cultures of human pituitary tumor cells, but not in various nonpituitary cell lines. In contrast, a -112/-93 element enhances transcription of the tk promoter in all cells tested. DNase I footprint analysis revealed five sites protected by nuclear extracts obtained from AtT-20 cells within nucleotides -414 and -83 of the hPOMC promoter region. In contrast, only one of these sites (between nucleotides -115 and -83) was protected by nuclear extracts from HeLa cells. Gel mobility-shift experiments revealed that an oligonucleotide comprising nucleotides -112/-93 binds a novel nuclear protein. This protein may contribute to the non-cell type-specific expression of the hPOMC gene outside the pituitary, whereas at least five transcription factors seem to be required for high basal transcription of the gene in corticotrophic cells.
PURPOSE: In a prospective study, we evaluated the significance of preoperative bilateral chemical shift spectroscopy imaging (CSI) changes for the prognosis of postoperative seizure outcome in the surgical treatment of patients with temporal lobe epilepsy (TLE). METHOD: CSI using multivoxel spectroscopy was performed. Twenty-six consecutive TLE patients scheduled for epilepsy surgery were included. To evaluate the value of the CSI with respect to postoperative seizure outcome, discriminant analysis with ipsilateral and contralateral CSI was performed. RESULTS: The discriminant analysis showed that the contralateral metabolic changes alone are able to predict seizure outcome whereby 92.3% of cases were correctly classified. Upon comparison of the two groups of seizure-free and non-seizure-free patients with respect to contralateral metabolic changes, the difference proved to be highly significant (paired t test: t = -6.3, df = 24, p < 0.001). CONCLUSION: Bilateral metabolic CSI changes have a predictive value for the postoperative outcome in patients with TLE. In patients with severe bilateral metabolic changes, poor seizure outcome is a likely result.
PURPOSE: To document the accuracy of CT and MR of the sella turcica for detecting adrenocorticotropic hormone-secreting adenomas in Cushing disease. METHODS: The radiologic findings of the sella turcica prior to transsphenoidal surgery are reviewed in 141 patients who had biochemical evidence of pituitary-dependent Cushing disease. Axial thin-collimation CT scans with sagittal and coronal reformations before and after contrast enhancement were obtained in 125 patients. Seventy-eight patients had MR examinations with a 1.5-T superconducting magnet. In 11 of the patients gadolinium-enhanced MR scans were also obtained. The preoperative interpretation of the imaging studies was correlated with the surgical findings and patients follow-up. RESULTS: The sella turcica was enlarged in 43 cases (30%). In 125 patients reformatted or direct coronal thin-collimation CT scans were available. Seventy-eight of the patients had MR. In the 12 patients with pituitary macroadenomas, the accuracy of CT (n = 10) and MR (n = 10) in respect to detection of the lesion was 100%. Of the 98 microadenomas assessed by CT, 47 (48%) were directly depicted as distinct hypodense lesions. In only 31 of 73 cases (42%), however, could CT predict the precise anatomic location and extent of the lesions. Only patients in whom the hypercortisolism was corrected by later surgery were considered for the correlation analysis. Of the 52 microadenomas assessed by MR, 28 (53%) were directly depicted as distinct lesions of reduced signal intensity on T1-weighted images, and in only 21 of 41 cases (52%) did MR show good correlation to the surgical findings. Some degree of partially empty sella was found in 22% of the patients. CONCLUSIONS: Although both the sensitivity and the diagnostic accuracy of imaging methods of the sella turcica have been considerably improved in comparison with previous reports, they still provide only a minor contribution to the diagnosis and differential diagnosis of Cushing syndrome.