Biomedical subjects

M Buchfelder

Publications and source records attributed to M Buchfelder.

At least 55 records · Page 3Linked to original sources

PubMed2001

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone-secreting and non-functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans.

The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.

Adenoma↗

PubMed2001

Elevated inferior petrosal sinus levels of PTHrP in a patient with Cushing's disease.

PTHrP has been found in various tissues, including prolactinomas and growth hormone producing adenomas. The function and clinical importance of PTHrP are poorly understood. We report the case of a 25-year-old female patient with hirsutism. Autonomous ACTH-dependent hypercortisolism was documented by endocrine testing. Magnetic resonance imaging (MRI) revealed a 3-mm intrasellar hypointense lesion in the left side of the pituitary gland. The inferior petrosal sinus sampling disclosed a gradient of ACTH left central/peripheral of 30.5 and right central/peripheral of 2.0 and suggested the diagnosis of a left-sided pituitary ACTH secreting microadenoma. Interestingly, we found elevated PTHrP levels in the left inferior petrosal sinus with a gradient of 4.7 compared to peripheral venous blood and of 3.6 compared to the right sinus. Our results fit very well to the concept of a para-/autocrine secretion of PTHrP which has been proposed recently and suggest a role in the regulation of cell growth of pituitary adenomas.

Adenoma↗

PubMed2001

Magnetic resonance spectroscopy and histopathological findings in temporal lobe epilepsy.

PURPOSE: In some patients with temporal lobe epilepsy, histopathological evaluation of resected brain tissue after surgical treatment may reveal several features indicative of discrete cortical malformations. We sought to determine whether these histopathological features were accompanied by hippocampal changes detectable preoperatively by proton magnetic resonance (MR) spectroscopy and to evaluate their relationship with postoperative outcome. METHODS: In 25 consecutive temporal lobe epilepsy patients who were scheduled for surgical treatment, MR spectroscopy was performed, and resected brain tissue was analyzed histopathologically for the presence of discrete cortical malformations (e.g., microdysgenesis). Outcome was assessed in all patients with an average postoperative period of 26 months. RESULTS: In 13 patients, we found subtle, histopathologically detectable signs of cortical malformation: 6 of them with concomitant hippocampal sclerosis (dual pathology) and 7 without. The latter subgroup had a worse surgical outcome and showed enhanced bilateral and/or contralateral pathological changes in the hippocampal formation when investigated by MR spectroscopy. CONCLUSIONS: These data suggest that by showing contralaterally or bilaterally abnormal spectra, MR spectroscopy might be able to indicate pathological changes in subtle developmental disorders that are possibly more widespread over the brain. This observation may improve noninvasive diagnosis in presurgical evaluation and the neurobiological understanding of cortical malformations in pharmacoresistant temporal lobe epilepsy.

Adult↗

PubMed2001

Intraoperative magnetic resonance imaging combined with neuronavigation: a new concept.

OBJECTIVE: Intraoperative image data may be used not only to evaluate the extent of a tumor resection but also to update neuronavigation, compensating for brain shift. To date, however, intraoperative magnetic resonance imaging (MRI) can be combined only with navigation microscopes that are separated from the magnetic field, thus requiring time-consuming intraoperative patient transport. To help solve this problem, we investigated whether a new navigation microscope can be used within the fringe field of the MRI scanner. METHODS: The navigation microscope was placed at the 5-G line of a 0.2 MRI device. Patients were positioned lying down directly on the table of the scanner, with their heads placed approximately 1.5 m from the center of the magnet, fixed in an MRI-compatible ceramic head holder. Standard operating instruments were used. For intraoperative imaging, we slid the table into the center of the magnet in less than 30 seconds. RESULTS: By use of this setup, we operated on 22 patients. In all patients, anatomic neuronavigation could be used in combination with intraoperative MRI. In addition, in 12 patients, functional data from magnetoencephalographic or functional MRI studies were integrated, resulting in functional neuronavigation. We did not encounter adverse effects of the low magnetic field during navigation. Moreover, intraoperative imaging was not disturbed by the navigation microscope and vice versa. CONCLUSION: Functional neuronavigation and intraoperative MRI can be used essentially simultaneously without the need for lengthy intraoperative patient transport. The combination of intraoperative imaging with functional neuronavigation offers the opportunity for more radical resections and fewer complications.

Adolescent↗

PubMed2001

Dopamine D2 receptor gene expression in human adenohypophysial adenomas.

The inhibitory effects of dopamine on adenohypophysial cells are mediated via dopamine subtype 2 receptor (D2R). Dopamine agonists inhibit hormone release and induce tumor shrinkage in most prolactin-secreting adenomas, whereas in other adenoma types such effects are sporadic. We investigated D2R gene expression by in situ hybridization (ISH) and immunocytochemistry in different types of pituitary adenomas. By ISH, a variable D2R signal was detected in 79 of 89 cases: 4 of 6 densely granulated and 8 of 8 sparsely granulated somatotroph, 4 of 4 mammosomatotroph, 7 of 7 mixed somatotroph-lactotroph, 4 of 4 acidophil stem cell, 16 of 16 sparsely granulated lactotroph, 11 of 16 corticotroph (functioning and silent), 3 of 4 silent subtype 3, 5 of 5 thyrotroph, 5 of 6 gonadotroph, 5 of 6 null cell, and 7 of 7 oncocytic adenomas. By immunocytochemistry, D2R protein was localized in cytoplasm and nuclei of 60 of 62 adenomas. In lactotroph adenomas, long-acting bromocriptine (BEC-LAR) induced a major increase in D2R mRNA, which was not accompanied by increased D2R immunoreactivity, suggesting mRNA stabilization. In conclusion, D2R gene is expressed in the majority of pituitary adenomas representing all tumor types. The significance of nuclear localization of D2R protein remains to be clarified.

Adenoma↗

PubMed2001

Intraoperative magnetic resonance imaging during transsphenoidal surgery.

OBJECT: The aim of this study was to evaluate whether intraoperative magnetic resonance (MR) imaging can increase the efficacy of transsphenoidal microsurgery, primarily in non-hormone-secreting intra- and suprasellar pituitary macroadenomas. METHODS: Intraoperative imaging was performed using a 0.2-tesla MR imager, which was located in a specially designed operating room. The patient was placed supine on the sliding table of the MR imager, with the head placed near the 5-gauss line. A standard flexible coil was placed around the patient's forehead. Microsurgery was performed using MR-compatible instruments. Image acquisition was started after the sliding table had been moved into the center of the magnet. Coronal and sagittal T1-weighted images each required over 8 minutes to acquire, and T2-weighted images were obtained optionally. To assess the reliability of intraoperative evaluation of tumor resection, the intraoperative findings were compared with those on conventional postoperative 1.5-tesla MR images, which were obtained 2 to 3 months after surgery. Among 44 patients with large intra- and suprasellar pituitary adenomas that were mainly hormonally inactive, intraoperative MR imaging allowed an ultra-early evaluation of tumor resection in 73% of cases; such an evaluation is normally only possible 2 to 3 months after surgery. A second intraoperative examination of 24 patients for suspected tumor remnants led to additional resection in 15 patients (34%). CONCLUSIONS: Intraoperative MR imaging undoubtedly offers the option of a second look within the same surgical procedure, if incomplete tumor resection is suspected. Thus, the rate of procedures during which complete tumor removal is achieved can be improved. Furthermore, additional treatments for those patients in whom tumor removal was incomplete can be planned at an early stage, namely just after surgery.

Adenoma↗

PubMed2000

A polymorphism in the growth hormone (GH)-releasing hormone (GHRH) receptor gene is associated with elevated response to GHRH by human pituitary somatotrophinomas in vitro.

A previous study has suggested that a G to A base change at position 169 of the GHRH-receptor gene in human somatotrophinomas is a mutation and confers hypersensitivity to GHRH. The alternative base converts codon 57 from GCG to AGC, resulting in replacement of alanine (Ala) with threonine (Thr). In the present study, two of five human GH-secreting somatotrophinomas were found to possess the codon 57 AGC sequence. The GCG allele was also detected, indicating heterozygosity. However, the patients' normal blood-derived DNA also yielded the same sequence pattern, indicating that the Ala --> Thr amino acid change is a normal polymorphism, and not a somatic mutation. Nevertheless, in vitro, the tumors possessing the Ala --> Thr amino acid change responded very strongly to GHRH in terms of cAMP formation, being increased 40- and 200-fold, in comparison to the 2-fold increases by tumors without the alternative GHRH-receptor sequence. Likewise, the in vitro response of GH secretion to GHRH was elevated. One of the two tumors with the alternative Thr residue, and the highest responder to GHRH, possessed a gsp mutation, despite the fact that these defects are thought to reduce responsiveness to GHRH. These results fail to confirm that the GCG --> AGC at codon 57 of the GHRH-receptor gene is a mutation, but do support the concept that the alternative form with Thr confers increased sensitivity to GHRH.

Acromegaly↗

PubMed2000

Intraoperative magnetic resonance imaging in epilepsy surgery.

The aim of this study was to investigate how intraoperative magnetic resonance imaging (MRI) can help in epilepsy surgery to asses immediately whether a resection or disconnection procedure is tailored to the individual needs of a patient, thus ideally meeting the treatment plan and enhancing the efficiency of the procedure. The recently proposed concept of an individually tailored procedure with as limited tissue removal as possible would support a more conservative resection than initially advocated by many centers; such limited removal would preserve as much brain as possible that is not necessarily epileptogenic or involved in propagation of seizures. For intraoperative imaging we used a Magnetom Open 0.2-T scanner located in our "twin-OR" in 61 patients with pharmacoresistant epilepsy. A three-dimensional sequence was used, allowing free slice reformatting. In the nonlesional cases (n = 32) the extent of the tailored temporal resection (n = 28) or callosotomy (n = 4) could be documented exactly. In the 29 lesional cases the complete resection was primarily proved in 23 patients. In three glioma patients a lesion that extended into eloquent areas did not allow for complete removal. A second look (n = 3) could increase the rate of total resection in the lesional cases from 79% to 90%. Intraoperative MRI allowed a reliable evaluation of the extent of resection or disconnection in epilepsy surgery within the operative procedure. It also provided the possibility of a second look in cases of incomplete resection, especially in the lesional cases. Increased knowledge of structure-function relationships as partially defined by intraoperative imaging may reduce the adverse neuropsychological sequelae of epilepsy surgery in the future.

Adult↗

PubMed2000

Supratentorial low-grade glioma: results and prognostic factors following postoperative radiotherapy.

BACKGROUND AND PURPOSE: To assess treatment outcome and prognostic factors following postoperative external radiotherapy in 77 patients with low-grade glioma. PATIENTS AND METHODS: Between 1977 and 1996, 45 patients with astrocytoma, 14 with oligodendroglioma and 18 with mixed glioma received postoperative radiotherapy with a median total dose of 52 Gy (range, 45 to 61 Gy). Sixty-seven patients were treated immediately following surgery, 10 patients with tumor progression. The influence of various factors including histology, gender, age, seizures, duration of symptoms (< or = 6 weeks vs > 6 weeks), CT pattern (enhancement vs no enhancement), type of surgery, total radiotherapy dose and timing of radiotherapy on relapse-free survival and overall survival was investigated. RESULTS: The median overall survival time was 81 months, the 5- and 10-year survival rates were 54% and 31%, respectively. The median time to progression was 56 months, while the 5- and 10-year progression-free survival rates were 45% and 24%. Univariate analyses identified the total radiotherapy dose (p = 0.01), duration of symptoms (p = 0.05), the presence of seizures (p = 0.04), and the CT pattern following intravenous contrast (p = 0.005) as significant prognostic factors for overall survival. Progression-free survival rates were influenced by the total dose (p = 0.04), the duration of symptoms (p = 0.01) and CT pattern (p = 0.006). On multivariate analysis, only the CT pattern (enhancement vs no enhancement) remained as independent prognostic factors for both progression-free survival and overall survival. CONCLUSIONS: A minimum total dose of 52 Gy is recommended for the postoperative radiotherapy in low-grade glioma. Tumors with CT enhancement seem to need further intensification of treatment.

Adult↗

PubMed2000

[Intraoperative magnetic resonance tomography. Experiences with its use in neurosurgery].

Intraoperative magnetic resonance imaging using a 0.2 Tesla, open-configured scanner was applied in a total of 243 patients. The aim of this study was to evaluate the feasibility, clinical application, and indications of this method. No adverse effects of the intraoperative imaging could be observed. The extent of tumor resection could be evaluated in the majority of cases. Resection control in glioma, ventricular tumor, pituitary tumor, and epilepsy surgery were the main indications for the intraoperative application. Especially when combined with functional neuronavigation, intraoperative magnetic resonance imaging allowed more radical resectioning with lower morbidity. Second looks to complete tumor removal during the same surgical procedure were possible to determine tumor remnants. Brain shift, which reduces the accuracy of neuronavigational systems, could be compensated for by intraoperative updates.

Adolescent↗

PubMed2000

Radiation therapy of optico-hypothalamic gliomas (OHG)--radiographic response, vision and late toxicity.

BACKGROUND: Management strategies for optic pathway gliomas include observation, surgery, irradiation, chemotherapy and a combination of these modalities. It has been the policy of our University Hospital to consider radiation as the standard treatment for progressive optic pathway gliomas. This report describes the clinical presentation, treatment patterns and outcome with special emphasis on the long term functional status of patients with optico-hypothalamic gliomas (OHG). PATIENTS AND METHODS: Between 1975 and 1997, 25 patients with OHG were treated by radiation therapy (RT) following surgery or biopsy. All patients received a local RT with a 0.5-1 cm margin around the lesions as depicted on CT or MRI scans. Age adjusted radiation doses ranged from 45 to 60 Gy with a single fraction size of 1.6-2 Gy. Endpoints of the study were: radiographic response, survival, progression-free survival and time to endocrinologic toxicity as well as the visual function during follow-up. The median follow-up time was 9 years (range, 1.5-23 years). RESULTS: A partial response was noted in six (24%) of the patients, 13 (52%) patients had a stable tumour throughout the observation period and six (24%) patients had a tumour progression. Overall survival and progression-free survival rates were 94 and 69% at 10 years, respectively. A significant influence on progression-free survival was noted for age at diagnosis (P=0.04) and total dose (P=0.05). Nine out of 13 (69%) patients aged below 10 years compared with 3/12 (25%) patients aged above 10 years experienced hypothalamic-pituitary deficiency (P=0.008) during follow-up. As for visual acuity, nine patients had an improvement, another 13 patients a stable situation and three patients a measurable deterioration. Visual field deficits improved in three, remained unchanged in 16 patients and worsened in only one patient. CONCLUSION: Postoperative RT with a total dose above 45 Gy should be considered as standard treatment in OHG with documented progression. Close radiographic monitoring and lifelong yearly evaluation for the need of possible hormone replacement are strongly recommended.

Adolescent↗

PubMed2000

Primary spinal germinoma in a patient with concomitant Klinefelter's syndrome.

It is known that patients with Klinefelter's syndrome are inclined to develop concomitant malignant tumours, as well as extragonadal germ cell tumours. The association of a primary spinal germinoma in a patient with Klinefelter's syndrome is reported for the first time, and the coincidence of elevated gonadotropin levels and oncogenesis is discussed.

Adult↗

PubMed2000

Difficult intubation in acromegalic patients: incidence and predictability.

BACKGROUND: Previous studies have suggested that the incidence of difficult intubation in acromegalic patients is higher than in normal patients. However, these studies were retrospective and did not include preoperative assessment of the airways. The aims of this study were to determine the incidence of difficult intubation and to assess the usefulness of preoperative tests in predicting difficult laryngoscopy. METHODS: One hundred twenty-eight consenting acromegalic patients requiring general anesthesia and tracheal intubation were studied. Preoperatively, Mallampati classification, thyromental distance, and head and neck movement were determined in each patient. After induction of anesthesia and muscle paralysis, laryngoscopic grade was assessed during direct laryngoscopy; Cormack and Lehane grade III or IV were classified as difficult. The association of individual airway assessment with laryngeal view was evaluated using the Fisher exact test. Predictors of difficult laryngoscopy were evaluated by calculating their sensitivity and specificity. RESULTS: Laryngoscopy was difficult (grade III) in 33 of 128 patients (26%). Application of external laryngeal pressure improved laryngeal visualization to grade II in 20 of these 33 patients. In the remaining 13 patients (10%), intubation was difficult (more than two attempts, blade change, use of gum-elastic bougie). Mallampati classes 3 and 4 were significantly related to laryngoscopy grade III (Fisher exact test, P = 0.001). CONCLUSIONS: The incidence of difficult laryngoscopy and intubation in acromegalic patients is higher than in normal patients. Preoperative Mallampati scores of 3 and 4 were of value in predicting difficult laryngoscopy. Nevertheless, even this test will miss a significant number of patients with a difficult airway.

Acromegaly↗

PubMed2000

Magnetoencephalography in extratemporal epilepsy.

Epilepsy surgery candidates with extratemporal foci represent a particular diagnostic and therapeutic challenge, because of anatomic and functional features of the pertaining areas. In the last decade, novel developments in the field of electrophysiological techniques have offered new approaches to detailed localization of specific epileptic discharges as well as eloquent regions. Magnetoencephalography, in combination with neuroimaging data and simultaneously recorded EEG, yields promising results to clarify centers of epileptic activity and their relationship to structural abnormalites and functionally significant areas. Examples are given to illustrate the range of applications of this method as a contribution to routine presurgical evaluation.

Adolescent↗

PubMed2000

Expression of members of the interleukin-6 family of cytokines and their receptors in human pituitary and pituitary adenomas.

There is increasing evidence for the role of members of the Interleukin (IL)-6 family in pituitary function, particularly in the regulation of the hypothalamo-pituitary-adrenal axis. However, there is only a limited amount of data available on the expression in human normal and tumorous pituitary tissue. In this study we investigated the expression of members of the IL-6 family of cytokines and their receptors in normal human pituitaries as well as pituitary adenomas using the RT-PCR technique. Eighteen pituitary adenoma biopsies removed in transsphenoidal surgery (six corticotrophic adenomas, four nonfunctioning adenomas, four somatotrophinomas, four prolactinomas) and six normal anterior pituitaries were examined for the expression of IL-6 receptor (-R), leukemia inhibitory factor (LIF), LIF-R, IL-11, IL-11-R, oncostatin M (OSM), OSM-R, ciliary neurotrophic factor (CNTF), CNTF-R and cardiotrophin-1 (CT-1). All pituitaries and pituitary adenomas expressed OSM transcripts, whereas no expression of CT-1 was found. The expression of all other cytokines (LIF, IL-11, CNTF) and receptors (IL-6-R, LIF-R, IL-11-R, OSM-R, CNTF-R) was found in different patterns in the adenoma subtypes and normal pituitaries. However, we did not detect expression of LIF-, IL-11-, IL-6-R and CNTF-R in prolactinomas, of CNTF in normal pituitaries and of OSM-R in ACTH-secreting adenomas. In conclusion, our study provides further evidence for a role of the members of the IL-6 family of cytokines in pituitary function.

Adenoma↗

PubMed1999

Intrasellar malignant lymphoma developing within pituitary adenoma.

A mixed lymphoblastic T cell lymphoma and gonadotroph cell pituitary adenoma occurred 25 years after first resection of the adenoma. Within 1 year the lymphoma overgrew the adenoma, but was still restricted to the sellar region. Histologically, lymphoma and adenoma components were tightly admixed. Possible pathogenetic pathways for intra-adenomatous lymphoma development include monoclonal expansion of T cell infiltrates, expression of adhesion molecules specific for adenoma endothelium, and production of mitogenic pituitary hormones.

Adenoma↗

PubMed1999

Malignant prolactinoma: case report and review of the literature.

BACKGROUND: Malignant prolactinomas are rare events. To date, only 14 patients with metastases in- or outside the central nervous system have been reported. CASE DESCRIPTION: We present a patient who developed a metastasis to the cauda equina, which is the first case documented with MRI. A giant prolactinoma in this 51-year-old man was partially removed by a transcranial approach. After radiotherapy and treatment with bromocriptine, the patient had a remission for 3 years. Thereafter, a sacral intraspinal tumor was diagnosed. Because of increasing prolactin levels not responding to bromocriptine and a radiologically suspected intrasellar tumor, we operated transsphenoidally first and found only fibrous tissue. We performed a sacral laminectomy and almost totally removed an intradural tumor. Histopathology and immunohistochemistry confirmed the diagnosis of a prolactinoma metastasis. The patient received radiotherapy and bromocriptine and has no evidence of recurrent tumor or metastases after a follow-up of 38 months, thus being the second reported patient with long-term remission of the disease. DISCUSSION: We review the literature on this topic and try to establish common features of the course of this rare malignant disease and the efficacy of therapy in the cases reported hitherto.

Antineoplastic Agents↗

PubMed1999

Clinical correlates in acromegalic patients with pituitary tumors expressing GSP oncogenes.

We herein review published findings on the clinical characteristics of acromegalic patients harboring pituitary somatotrophinomas expressing adenylyl cyclase activating gsp mutations and present an update of our own data on a large series of 176 patients with and without these oncogenes. Gsp oncogenes are the result of point mutations in either codon 201 or 227 of the Gs-alpha subunit of the Gs-protein which controls adenylyl cyclase. They result ultimately in increased intracellular cAMP levels and thus in excessive growth hormone (GH) secretion. Our large series has allowed us to characterise patients with mutations in codon 201 and the far rarer group possessing codon 227 defects. Both groups were compared with patients without gsp oncogenes. In accordance with previous findings, there was no statistically significant difference in age of the patients belonging to each group, the overall average tumor diameter nor in pre-operative serum GH levels, although the latter showed a tendency to be lower in patients with gsp oncogenes. The distribution of different types of response during an oral glucose tolerance test (no change, paradoxical rise or greater than 50% decrease in serum GH levels) did not differ between the 3 groups. However, the incidence of microadenomas was higher in acromegalics expressing gsp oncogenes in patients possessing mutations in codon 227. Additionally, the incidence of invasiveness was much lower (10% v. 33%) in those tumors with mutations in codon 227. Finally, previous in-vitro data indicating that gsp oncogene-expressing tumors may respond more efficiently to the somatostatin analogue, octreotide, have been confirmed by subsequent in-vivo studies showing a better reduction in serum GH levels in patients with gsp oncogenes. These latter findings suggest that presence of gsp oncogenes may be a marker for good reponsiveness to octreotide. Assessment of gsp oncogene status of surgically removed pituitary somatotrophinomas may thus be helpful in designing optimal medical therapies in those acromegalics requiring further post-operative management of the disease.

Acromegaly↗