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Biomedical subjects

R Fahlbusch

Publications and source records attributed to R Fahlbusch.

At least 181 records · Page 10Linked to original sources
PubMed1991

Autocrine control of human meningioma proliferation: secretion of platelet-derived growth-factor-like molecules.

We have used cell-culture techniques to investigate growth-factor production by human meningioma cells. Meningioma tissue was dispersed with collagenase and the cells grown to high density in tissue-culture flasks. The cultures were used to generate conditioned medium (MEN-CM), which was used to cultivate IMR32 cells (a human neuroblastoma line) and freshly dispersed primary meningioma cells. MEN-CM profoundly stimulated the in vitro growth of both IMR32 and meningioma cells. In addition, H3-thymidine uptake by cultured meningioma cells was increased in a dose-dependent manner by varying concentrations of MEN-CM. A neutralizing anti-body against platelet-derived growth factor (PDGF) completely abolished the stimulatory effects of MEN-CM, whereas an antibody against TGF-alpha was without effect. The mitogenic activity of MEN-CM, as assayed by promotion of H3-thymidine uptake by cultured meningioma cells, eluted from a Sephadex G-100 column in 3 peaks corresponding to molecular weights of greater than or equal to 150, 56 and 28 kDa. Our results show that proliferation of human meningiomas may be under autocrine control via secretion of PDGF-like molecules.

Cell Division↗
PubMed1991

Long-term follow-up results in hormonally active pituitary adenomas after primary successful transsphenoidal surgery.

The long-term results of transsphenoidal surgery for hormonally active pituitary adenomas were assessed in 3 follow-up studies. Eight out of 50 patients with microprolactinomas developed a persisting postoperative re-increase of prolactin levels during an average follow-up period of 4.1 years. None of the 43 acromegalic patients who had achieved a suppression of growth hormone to below 2 ng/ml during an oral glucose load shortly after surgery relapsed. However, when the remission criterion was only based on basal growth hormone below 5 ng/ml 4 out of 61 patients showed a re-increase of growth hormone levels to persistently elevated values during an average follow-up period of 6.1 years. 14 out of 66 patients followed-up for an average of 8.2 years after successful primary microadenomectomy for Cushing's disease developed recurrent hypercortisolism as documented by an abnormal suppression of cortisol after oral low dose dexamethasone.

Acromegaly↗
PubMed1991

Pontine-mesencephalic cavernomas: indications for surgery and operative results.

Cavernous haemangiomas cavernomas of the brainstem can be diagnosed by MRI and safely removed when elective surgery is performed in the subacute stage after haemorrhage. Recurrent haemorrhage and/or neurological deterioration are indications for surgery. In cases with additional venous malformation the cavernoma should be selectively removed. The experiences with our own series of 18 cases are presented.

Adolescent↗
PubMed1991

Effect of dopamine agonist medication on prolactin producing pituitary adenomas. A morphological study including immunocytochemistry, electron microscopy and in situ hybridization.

Conventional light microscopy, immunocytochemistry, electron microscopy and in situ hybridization were used to evaluate the effect of dopamine agonists (bromocriptine-LAR and bromocriptine) on the morphology of surgically removed prolactin (PRL)-producing pituitary adenomas. Dopamine agonist therapy resulted in decrease of serum PRL, clinical improvement and tumour shrinkage. Using light and electron microscopy cellular atrophy, interstitial and perivascular fibrosis were noted; in several tumours connective tissue accumulation was pronounced. The cellular response was not uniform. In some adenomas populations of large cells and small cells were distinguished. The large cells contained immunoreactive PRL and expressed the PRL gene indicating resistance to dopamine agonists. It appears that these cells retained the potential to secrete PRL and proliferate despite exposure to dopamine agonists. In the small cells, PRL immunoreactivity and PRL gene expression decreased providing evidence that both PRL release and synthesis were blocked. Small cells can persist in tumours after discontinuation of dopamine agonist medication suggesting these small cells are irreversibly suppressed and are not capable of regaining their endocrine function and proliferative capability. The formation of irreversibly suppressed PRL cells may explain why some PRL-producing adenomas do not recur after withdrawal of dopamine agonists.

Adenoma↗
PubMed1991

Delayed hearing loss after surgery for acoustic neurinomas: clinical and electrophysiological observations.

In a series of 26 patients with medium-sized and large acoustic neurinomas and documented hearing before surgery, 7 patients had preservation of hearing initially after the procedure but then developed delayed hearing loss. The most prominent intraoperative electrophysiological finding in these cases was a gradual deterioration of brain stem auditory evoked potentials (BAEP), especially of Wave V. Four additional patients with a similar gradual intraoperative loss of BAEP and severe postoperative hearing deterioration received vasoactive treatment after surgery (low-molecular weight dextran). In all 4 patients, including 1 patient with documented total deafness after surgery, hearing was preserved. Initial preservation of cochlear nerve function after the removal of an acoustic neurinoma does not guarantee postoperative hearing. Intraoperative BAEP help to identify patients at risk for delayed postoperative hearing loss. The pathophysiological mechanism can be attributed to disturbances of the microcirculation in endoneurial vasa nervorum caused by the mechanical manipulation of the cochlear nerve.

Adult↗
PubMed1991

Recurrence following transsphenoidal surgery for acromegaly.

The long-term results of transsphenoidal adenomectomy and the incidence of possible recurrences were studied in 61 patients who had normal basal serum growth hormone (GH) levels 1 week after surgery. The patients were followed up for an average of 6.0 years (range: 1.5-14.0 years) by repeated measurements of GH, oral glucose tolerance testing (OGTT) and at the last follow-up visit also by assaying somatomedin C levels. In 4 of the patients, the basal GH levels had increased to values above 5 ng/ml. In 43 patients, a normal suppression of GH during an oral glucose load was observed shortly after surgery. In only 2 of these cases did a transiently inadequate suppression develop during the follow-up period, although clinical acromegaly did not recur and the somatomedin C levels remained normal. It is concluded that recurrence of active acromegaly is unlikely to occur in patients who achieve a normal glucose-induced suppression of GH levels shortly after adenomectomy. As such, an OGTT provides better prognostic information than basal human GH level measurements and may give a clearer and earlier indication of surgical success.

Acromegaly↗
PubMed1991

[Surgical significance of cavernous hemangioma of the brain stem].

Cavernous hemangiomas are identified as source of brainstem hemorrhage in increasing numbers by magnetic resonance imaging. The optimal treatment of this rare vascular malformation, indication for surgery and time of intervention is still under discussion as the experience so far is mainly based on case reports. We have investigated a series of 20 patients with cavernous hemangiomas of the brainstem between 1986 and 1990, 10 of them underwent surgical removal of the lesion. Based on these experiences we conclude: Surgical removal of cavernous hemangiomas should be attempted in patients with recurrent hemorrhage, persistent or progressive neurological deficit. In cases with additional venous malformation the cavenoma should be selectively removed. Surgery should be radical, as residual cavernoma can cause recurrent bleedings. Surgery should be performed during the subacute stage. Late surgery increases the risk for additional neurological deficit. Neurophysiologic monitoring can be helpful to minimize surgical risk.

Adolescent↗
PubMed1991

Pituitary microcirculation: physiological aspects and clinical implications. A laser-Doppler flow study during transsphenoidal adenomectomy.

The anterior and posterior pituitary lobes (AL and PL, respectively) are assumed to differ in the type of vascular supply and structure of their microvascular networks. Animal experiments have shown that the pituitary microvascular flow differs between the two lobes, being extremely high in the PL and low in the AL. For technical reasons, it has hitherto not been possible to study pituitary microflow in humans. Laser-Doppler flowmetry (LDF) is now a well-established method for real-time monitoring of microcirculation, applicable also in humans. In a prospective clinical study, the microflow in the AL and PL was measured during transsphenoidal microsurgery in 52 patients with adenomas of different size, growth characteristics, and endocrinological activity. The mean microflow in the PL (177.7 +/- 12.6 [flux]) was found to be about six times higher than that in the AL (27.4 +/- 2.7 [flux]). No difference in the laser-Doppler fractional volume of the lobes could be detected (0.73 +/- 0.06 [] vs. 0.77 +/- 0.07 [], where [] designates the ratio of the alternating current output to the direct current output signals). Microflow within the pituitary lobes was influenced neither by the histological type nor the size of the adenoma. Additionally, LDF signal-averaging triggered by the electrocardiogram allowed detection of different characteristic pulsatile microvascular flow patterns in the AL and PL. Our findings provide strong physiological support for the idea that the angioarchitecture of the pituitary lobes differs. With this method, the AL and PL can be identified objectively during surgery. LDF might provide useful information concerning intraoperative surgical approach.

Adenoma↗
PubMed1990

Intraocular pressure in patients with Cushing's disease.

Externally applied corticosteroids increase the intraocular pressure in one-third of the general population. We evaluated the intraocular pressure in 62 patients with endogenously elevated serum cortisol levels due to hypothalamic pituitary-dependent Cushing's disease. All patients underwent transphenoidal microsurgical sella exploration within 4 years after the onset of subjective symptoms. The intraocular pressure (preoperative mean, 14.9 +/- 3.5 mm Hg) exceeded 21 mm Hg in four eyes before surgery and in one eye after surgery (postoperative mean, 14.3 +/- 2.8 mm Hg). In patients attaining postoperative remission and whose pressure readings were taken at least 3 months after surgery, the postoperative intraocular pressure was significantly (P = 0.04) lower than that measured preoperatively (14.2 +/- 2.7 vs 13.0 +/- 2.0 mm Hg). Biomorphometry of the optic disc topography and the retinal nerve-fiber layer in 19 patients revealed no glaucomatous changes. In contrast to topically applied corticosteroids, endogenously elevated serum cortisol levels in patients with hypothalamic pituitary-dependent Cushing's disease increased intraocular pressure only slightly, with no great risk of glaucomatous optic nerve damage.

Adolescent↗
PubMed1990

Surgical and electrophysiological observations during clipping of 134 aneurysms with evoked potential monitoring.

Somatosensory evoked potentials (SEPs) were monitored during 113 operations for the clipping of 134 cerebral aneurysms. Changes in peak latency and amplitude of early cortical SEP as well as central conduction time were evaluated. In 58 cases surgical occlusion of arterial vessels or other events occurred, and in 17 of these cases such events were associated with SEP changes or loss. Arterial occlusions resulted from temporary clipping of a feeding blood vessel (22), accidental clipping of a vessel (12), and intentional permanent vessel occlusion (8). A total SEP loss was seen in 2 cases of accidental vessel occlusion and in 6 cases of temporary vessel clipping. Significant SEP changes were found in 6 patients with temporary clipping, and once each with retraction of the cerebellum, retraction of the middle cerebral artery, and after intentional permanent vessel occlusion. Response to these changes included reapplication of aneurysm clips, repositioning of retractors, or removal of temporary clips. Stable SEP signals during 13 cases allowed the surgeon to proceed with the surgical course. Despite the limitations of SEP monitoring in certain anatomical locations, it has been found to be helpful in the operative management of some cases such as multilobed aneurysms of the middle cerebral artery, giant aneurysms, trapping procedures, and procedures requiring temporary vessel occlusion.

Adolescent↗
PubMed1990

Surgical removal of pontomesencephalic cavernous hemangiomas.

Cavernous hemangiomas of the brain stem are usually discovered accidentally during evacuation of a hematoma, and successful surgical treatment of these lesions is seldom achieved. With the increasing use of magnetic resonance imaging, the presence of a cavernous hemangioma can be detected before surgery, allowing an elective surgical approach. We successfully removed pontomesencephalic cavernous hemangiomas from 2 patients and pontomedullary hemangiomas from 2 others. Elective surgery was performed with perioperative bimodal monitoring of somatosensory and auditory evoked potentials. Performing surgery soon after the hemorrhage minimizes the risk of additional postoperative neurological deficit, since surgical excision is facilitated when the hematoma is not completely organized. Pontine hemangiomas are approached via the 4th ventricle. Mesencephalic hemangiomas are removed by a midline supracerebellar approach when they are lateralized by using a subtemporal approach. The lesion can be removed through a small incision in the brain stem at the site of the lesion. The favorable results, which include marked improvement of preoperative neurological deficits and documentation of complete removal of the lesion by magnetic resonance imaging, support a more aggressive approach to the treatment of symptomatic cavernous hemangiomas of the brain stem. Further investigation of the natural history of these lesions is mandatory.

Adolescent↗
PubMed1990

Observations on the pathophysiology of Nelson's syndrome: a report of three cases.

Nelson's syndrome is generally regarded as an unusual sequela of primary bilateral adrenalectomy when performed for Cushing's disease. It is classically defined by cutaneous hyperpigmentation, considerably elevated adrenocorticotropic hormone (ACTH) levels, and an enlarged sella turcica. In this report, we present three cases initially treated by transsphenoidal sellar exploration for Cushing's disease. In two of these cases, remission of hypercortisolism did not occur after the initial pituitary exploration. A microadenomectomy was performed in one case and, in the other, no microadenoma was found. In both, Nelson's syndrome occurred after adrenalectomy. A second transsphenoidal operation and radiotherapy were required to control tumor growth. In another case, transsphenoidal adenomectomy of an ACTH-secreting tumor initially led to a remission of hypercortisolism for 4 years, but recurrent Cushing's disease necessitated adrenalectomy, and again Nelson's syndrome occurred. The documentation of a pre-existing ACTH-secreting basophilic pituitary microadenoma before adrenalectomy, as seen in two of our cases, has not been previously reported, and these observations of "non-classical" courses have major implications for the pathophysiology of Nelson's syndrome.

Adenoma↗
PubMed1990

Growth of cultured human cerebral meningiomas is inhibited by dopaminergic agents. Presence of high affinity dopamine-D1 receptors.

We have found that microM concentrations of the dopamine agonist bromocriptine significantly decrease the proliferation rate of human meningioma cells in culture (25-56% inhibition). This effect was also seen with direct application of dopamine, as well as the dopamine-D1 agonist (+)-SKF-38393 (both applied in microM concentrations) to meningioma cell cultures. Receptor studies with the dopamine-D1 ligand (125I)SCH-23982 (dopamine-D1 antagonist) indicated that dopamine-D1 binding sites were present in the membranes of meningioma tissue. The mean dissociation constant (Kd) was 325 ( +/- 74.5 SEM) pM and the receptor density (Bmax) was 25.4 ( +/- 1.5 SEM) fmol/mg pellet protein in 5 human meningiomas. The pharmacological specificity was proven by (+)-SKF-38393, ( +/-SKF-83566 or (+)-butaclamol and their inactive isomers (-)-SKF-38393 and (-)-butaclamol in a 1000 fold excess. These results provide evidence that human meningiomas possess high affinity dopamine-D1 receptors and that dopamine agonists have an antiproliferative effect on these tumors in culture. We conclude that the proliferation of cerebral meningiomas may be under dopaminergic control and that dopamine agonists may have a role in the medical treatment of patients with meningiomas.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Hormonal dependency of cerebral meningiomas. Part 1: Female sex steroid receptors and their significance as specific markers for adjuvant medical therapy.

Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas.

Adult↗
PubMed1990

Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas.

Cell culture and biochemical techniques have been employed to examine the effects of steroids, bromocriptine, and epidermal growth factor (EGF) on the growth and proliferative potential of meningiomas. In cell culture, the growth of meningiomas was not altered by progestogens, antiprogestogens, or 17beta-estradiol. The progestogen, norethisterone, had no effect on the uptake by meningiomas cell cultures of 3H-thymidine. Furthermore, cytosolic deoxyribonucleic acid (DNA) polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors. In contrast, the androgen antagonists, cyproterone acetate and 11-alpha-hydroxyprogesterone, and the dopamine agonist, bromocriptine, all inhibited the in vitro growth of meningioma cells. The growth of meningioma cell cultures was stimulated by EGF, and there was a positive correlation between the EGF content and DNA polymerase activity in meningioma cytosols. These results demonstrate that female sex steroids do not influence growth of meningiomas in vitro, whereas antiandrogens and bromocriptine have an antiproliferative effect. Consequently, bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas. In addition, these results suggest that EGF may be involved in the genesis and/or progression of meningiomas.

Bromocriptine↗
PubMed1990

[Glaucoma in central hypothalamic-hypophyseal Cushing syndrome].

One third of a general population reacts to exogenously applied corticosteroids with an increase of intraocular pressure. In this study we investigated the influence of endogeneously elevated serum cortisol levels on the intraocular pressure and the presence of glaucomatous changes in the morphology of the optic disc and retinal nerve fiber layer. 15 patients with hypothalamic-pituitary Cushing's disease due to an ACTH producing adenoma of the pituitary gland and undergoing transphenoidal microsurgical exploration of the sella turcica were ophthalmologically examined pre- and post-operatively. Subjective symptoms had been noticed not earlier than four years before operation. Intraocular pressure was preoperatively and postoperatively within the normal range for all but one patient with readings of 23/23 mm Hg preoperatively. In the subgroup with endocrinological remission the intraocular pressure readings decreased postoperatively. Photography of the retinal nerve fiber layer, morphometry of 15 degree color stereo optic disc diapositives, and perimetry revealed no changes typical for glaucoma. In 4 patients the retinal nerve fiber bundles were remarkably well visible. We conclude that patients suffering from hypothalamic-pituitary Cushing's disease with endogeneously elevated serum cortisol levels and a duration of subjective symptoms of less than 4 years run a lower risk of developing glaucomatous damage than patients with topical administration of corticosteroids.

Adolescent↗
PubMed1989

Neuro-rhinosurgical treatment of aesthesioneuroblastoma.

The results of a combined neuro-rhinosurgical procedure in eight cases of aesthesioneuroblastoma are presented. All patients were suffering from tumours in the advanced stage (stage C according to Kadish). Diagnosis was established by the clinical history, neuro-radiological imaging and by endoscopic endonasal biopsy. Contrary to most reports in the literature the authors performed a one step operative removal of the whole tumour mass by a combined transcranial-transbasal approach alone. A second transfacial operation was unnecessary in all our cases. To the best of our knowledge only Loew (see Jakumeit 1971) already in the 1960ties used a comparable one step transcranial approach for tumour removal. The long-term survival rate in our patients is 50%, a result comparable to reported series in the literature. Mortality is due to early recurrences and metastases within a few months after the initial treatment including post-operative irradiation. Four patients are living without evidence of tumour recurrence 1.5 to 5 years after treatment. The authors surgical technique is presented in detail and compared with the results of other treatment modalities.

Adolescent↗