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Biomedical subjects

R Fahlbusch

Publications and source records attributed to R Fahlbusch.

At least 163 records · Page 9Linked to original sources

Pulsatile administration of gonadotrophin releasing hormone as a diagnostic tool to distinguish hypothalamic from pituitary hypogonadism following neurosurgery.

Nine patients suffering from severe amenorrhoea following neurosurgical or radiotherapy for pituitary tumour or craniopharyngeoma were treated with pulsatile gonadotrophin releasing hormone (GnRH) administration. Seven patients did exhibit ovulatory cycles when GnRH was administered i.v. at a dose of 20 micrograms/pulse, but not at lower doses or when GnRH was administered s.c. Pulsatile GnRH administration may be used to assess the functional integrity of pituitary gonadotrophs and to distinguish pituitary from hypothalamic site of lesion resulting in hypogonadotrophic hypogonadism. It may also be used successfully for treatment of infertility in such patients.

Adolescent↗

Does an analysis of the pulsatile secretion pattern of adrenocorticotropin and cortisol predict the result of transsphenoidal surgery in Cushing's disease?

The endocrinological, surgical, and histological findings of patients with ACTH-dependent Cushing's disease were correlated with the pulsatile secretion pattern of ACTH and cortisol and the outcome after transsphenoidal pituitary surgery. A total of 28 patients were studied. The preoperative pulsatile secretion of ACTH and cortisol was assessed by sampling blood at 20-min intervals over 24 h. The pulsatile pattern of secretion was analyzed by the Cluster program. In 21 patients, an ACTH-secreting pituitary adenoma was identified and resected. Of these patients, 18 underwent clinical remission, and their cortisol secretion was suppressed to a normal level by low dose dexamethasone. Histological examinations in the patients with persistent disease revealed normal pituitary in 6 cases, nodular hyperplasia in 1, and ACTH-secreting pituitary adenoma in 3 cases. Analysis of the pulsatile pattern of ACTH and cortisol secretion did not reveal significant differences in timing, frequency, and/or amplitude of ACTH and cortisol pulses in normalized patients and those with persistent disease after surgery. It is concluded that analysis of the secretory pattern is not a suitable method for predicting the outcome of transsphenoidal surgery in patients with ACTH-dependent Cushing's disease.

Adenoma↗

Immunohistochemical expression of protein kinase C type III in human pituitary adenomas.

Immunohistochemical expression of the three major isozymes of protein kinase C--Types I, II, and III--was studied in 32 cases of human pituitary adenomas, and the results were compared in detail with their clinical data. Immunoreactivity for the Type I and Type II isozymes was negative in tumor cells of all pituitary adenomas. Moderate to strong cytoplasmic immunoreactivity for the Type III isozyme was constantly seen in acromegaly, Cushing's disease, and nonfunctioning adenomas, which indicated overexpression of the isozyme, since only slight cytoplasmic immunoreactivity was observed in the normal human anterior pituitary cells. Among 13 prolactinomas, 5 cases showed positive immunoreactivity for Type III in all tumor cells, whereas 8 cases showed negative immunoreactivity for the isozyme in all or more than 85% of tumor cells. The sizes of the tumors in this protein kinase C Type III negative group of prolactinomas tended to be smaller than those of the Type III positive prolactinomas. Also, the negative immunoreactivity for Type III was predominantly observed in those cases where prolactinomas were relatively well controlled by continuous oral dosage of dopamine agonists before operation. These results suggest that protein kinase C Type III is closely involved in human pituitary adenomas. The exceptional negativity for the isozyme in prolactinomas may be relevant to the suppression of tumor growth by dopamine agonists.

Acromegaly↗

Cerebral hemodynamics in subarachnoid hemorrhage evaluated by transcranial Doppler sonography. Part 1. Reliability of flow velocities in clinical management.

During recent years, the management of subarachnoid hemorrhage (SAH) has changed, resulting in an increase in early operations and routine administration of nimodipine. Both influenced the indication for transcranial Doppler sonography (TCD). Furthermore, investigations detected discrepancies between Doppler findings and neurological status. In a prospective study, the reliability of TCD was investigated in patients with SAH treated with intravenously administered nimodipine. Patients with large hematomas were excluded. Neurological deficits immediately after surgery or within the first 48 hours were classified as not delayed, and therefore not necessarily due to vasospasm. The most remarkable points of this study are that there is no significant difference between the flow velocities for Hunt and Hess Grades I and II when compared with those for Grade III, and that Grades IV and V seem to be affiliated with the lowest velocities. When the flow velocities of 11 patients who developed delayed ischemic deficits (DIDs) were compared with those of patients with no deficit, no significant difference was seen. A significant increase in velocity in the days before the onset of DID was found only in 3 of 11 cases. Eight patients showed either constant high or constant low velocities or even, in some cases, decreasing time courses. High flow velocities did not necessarily mean impending neurological deficits: 8 of 66 patients tolerated flow velocities over 200 cm/s. Therefore, it no longer seems to be justified to proclaim that TCD is able to predict neurological deficits, although it is doubtless able to detect vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cerebral hemodynamics in subarachnoid hemorrhage evaluated by transcranial Doppler sonography. Part 2. Pulsatility indices: normal reference values and characteristics in subarachnoid hemorrhage.

In previous publications on the diagnostic value of transcranial Doppler sonography (TCD), conflicting results concerning predictive capacities for evaluating vasospasm by measuring flow velocities were reported, and the necessity to examine pulsatility indices (PIs) was stressed. PIs are known to give useful information on cerebral hemodynamics in cases of stenosis of the extracranial internal carotid artery and cerebral arteriovenous malformations. Whether the examination of PIs can give additional information in cases of subarachnoid hemorrhage (SAH) and allow prediction of impending delayed ischemic deficits (DIDs) is still unclear. Normal reference values for the Gosling pulsatility index, the Pourcelot resistance index, and the first Fourier pulsatility index were established in a series of 97 normal subjects. A significant increase in the indices was found as age increased, and there was a strong relation between the indices. There were no statistically significant differences between the right and left sides. An inverse relation was found between the flow velocity and PIs in the middle cerebral artery. In a prospective study of 455 follow-up TCD examinations in 66 SAH patients treated routinely with nimodipine, three different groups were analyzed separately: Group I, patients without DIDs; Group II, patients with DIDs; and Group III, patients with neurological deficits not strictly classifiable as DIDs. The analysis of all three groups together showed a typical time course after the onset of SAH: initially elevated PIs normalized around the tenth day after bleeding. According to Fisher grading, the amount of subarachnoid blood influences the increase in PIs significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical and biochemical characteristics of acromegalic patients harboring gsp-positive and gsp-negative pituitary tumors.

A subgroup of growth hormone (GH)-secreting pituitary tumors carries somatic mutations within the gene coding for the alpha subunit of the stimulatory heterotrimeric guanosine 5'-triphosphate-binding protein, Gs alpha. These so-called gsp mutations result in constitutively activated Gs alpha and the signal transduction cascade downstream of it, with eventual markedly and continuously elevated cyclic adenosine monophosphate levels as a result of constitutive adenylyl cyclase activity. It is this elevation of intracellular cyclic adenosine monophosphate that is thought to be the cause of excessive GH secretion and somatotroph proliferation. We examined the clinical and biochemical characteristics of acromegalics harboring gsp-positive and gsp-negative pituitary tumors. Of 19 tumors studied, 8 (42%) were gsp positive. There was a slight tendency for basal GH levels in serum to be lower and to be further reduced by an oral glucose tolerance test in gsp-positive patients. However, there was no difference between the two groups in terms of clinical features, tumor size, mitotic activity (as assessed by cytosolic deoxyribonucleic acid polymerase and KI-67 staining), and in vitro GH response to GH releasing factor. We conclude that there is, in general, little difference in the clinical and biochemical characteristics between gsp-positive and gsp-negative human pituitary GH-secreting tumors.

Acromegaly↗

Immunological and functional properties of the acetylcholine receptor expressed on the human cell line TE671.

In the first part of the present study we compared the antigenicity of affinity-purified acetylcholine receptors from the cell line TE671 and from human skeletal muscle. The reactivities of the two acetylcholine receptor preparations showed a strong correlation (r = 0.96) in a radioimmunoassay using sera from myasthenia gravis patients. In additional functional studies, carbamylcholine stimulated cAMP production in TE671 cells to 130%. This increase was even more pronounced when TE671 cells were grown in the presence of dexamethasone. alpha-Bungarotoxin completely blocked this carbamylcholine-induced cAMP increase. Using the Ca2+ indicator, indo-1, it was shown that intracellular Ca2+ concentrations ([Ca2+]i) were elevated in TE671 cells after stimulation with carbamylcholine. This effect was also completely blocked by alpha-bungarotoxin. To test the functional activity of autoantibodies against the acetylcholine receptor, TE671 cells were preincubated with sera from myasthenia gravis patients. In one third of sera a significant inhibition of the agonist-stimulated [Ca2+]i increase was detected, possibly caused by antibodies directed to functionally important areas of the acetylcholine receptor. There was no correlation between the inhibition rate of [Ca2+]i and anti-acetylcholine receptor antibody titres in these patient sera.

Autoantibodies↗

Inhibitory effect of trapidil on human meningioma cell proliferation via interruption of autocrine growth stimulation.

In a previous study, the authors demonstrated that meningioma cells secrete platelet-derived growth factor (PDGF)-like molecules that stimulate their own growth in an autocrine manner. Based on that finding, a study was undertaken to examine the effect of trapidil, a drug known to have an antagonistic action against PDGF, on cell proliferation of human meningiomas in culture. Trapidil showed a dose-dependent inhibition of meningioma cell proliferation in the absence of any exogenous mitogenic stimulation. The maximum effect was observed at a concentration of 100 micrograms/ml, with the decrease in cell growth ranging from 16% to 54% compared to control samples. Trapidil similarly inhibited the basal deoxyribonucleic acid (DNA) synthesis assessed by [3H]-thymidine incorporation in three of seven meningiomas. While the conditioned medium generated from meningioma cells remarkably stimulated the proliferation of meningioma cells (166% to 277% of control), this effect was strikingly inhibited by the addition of trapidil. Trapidil also inhibited conditioned medium-stimulated DNA synthesis, even when there was no effect on basal DNA synthesis. Furthermore, trapidil significantly inhibited the epidermal growth factor (EGF)-stimulated proliferation of meningioma cells. This inhibitory effect on EGF-stimulated cell proliferation was also observed in nontumorous fibroblasts, demonstrating that trapidil is not an antagonist specific to PDGF. The addition of trapidil (30 micrograms/ml) in combination with bromocriptine (1 microM) showed an additive inhibitory effect on the meningioma cell growth compared to trapidil or bromocriptine alone. The overall results suggest that trapidil exhibits an inhibitory effect on meningioma cell proliferation through blocking the mitogenic stimulation induced by autocrine or exogenous growth factors, and may be considered as a possible new approach to the medical treatment of meningiomas.

Cell Division↗

Intraoperative identification of motor areas of the rhomboid fossa using direct stimulation.

Intraoperative electrical identification of motor areas within the floor of the fourth ventricle was successfully carried out in a series of 10 patients with intrinsic pontine lesions and lesions infiltrating the brain stem. Direct electrical stimulation was used to identify the facial colliculus and the hypoglossal triangle before the brain stem was entered. Multichannel electromyographic recordings documented selective stimulation effects. The surgical approach to the brain stem was varied according to the electrical localization of these structures. During removal of the lesion, functional integrity was monitored by intermittent stimulation. In lesions infiltrating the floor of the fourth ventricle, stimulation facilitated complete removal. Permanent postoperative morbidity of facial or hypoglossal nerve dysfunction was not observed. Mapping of the floor of the fourth ventricle identifies important surface structures and offers a safe corridor through intact nervous structures during surgery of brain-stem lesions. Reliable identification is particularly important in mass lesions with displacement of normal topographical anatomy.

Adult↗

[Intensive therapy of elderly patients in neurosurgery. Specifics of the postoperative phase in advanced age].

INTRODUCTION: Postoperative intensive care of the elderly neurosurgical patient differs considerably from that of the younger patient. INVESTIGATION: Analysis of 106 patients aged between 68 and 92 years. RESULTS: In addition to the cardiopulmonary risk factors, the age-specific changes in the brain have an effect on the spectrum of postoperative complications. Age-related atrophy of the brain and in increase in the fragility of blood vessels due to degenerative processes increase the risk of subdural and intracerebral hemorrhage. The amount of time spent in the intensive care unit as a percentage of overall hospitalization is, at 50%, appreciably greater than that of younger patients. Intensive monitoring, including intracranial pressure and transcranial Doppler ultrasonography are useful for detecting intracranial complications at an early stage. CONCLUSIONS: Despite the appreciably greater duration of postoperative intensive care in the elderly, the overall outcome is comparable with that seen in younger patients in many neurosurgical conditions.

Aged↗

Malignant tumors of the anterior cranial skull base.

Malignant tumors of the anterior cranial skull base are still a challenge for radical surgical treatment. Several different techniques and approaches have been developed over the years and the results, with mortality rates over 50%, are still not encouraging. Here we present our results of an interdisciplinary, one-stage, neurohino transfronto-transbasal surgical approach in twelve patients with such tumors. The long-term survival rate in our patients is now 83% with a mean postoperative follow-up of 19.3 months. Two patients died due to early recurrencies and metastasis after 10 and 13 months after initial treatment and postoperative irradiation. Another five patients with a follow-up of 34.2 months have had tumor recurrencies diagnosed at 19.5 months postoperatively. These patients have survived their recurrent tumor for 14.7 months. Five patients, 41% of the whole group, have been living without evidence of tumor recurrence for between 2 and 35 months.

Adult↗

Transsphenoidal microsurgery for craniopharyngioma.

We report on our series of 32 craniopharyngiomas operated on by the transsphenoidal route since 1983. In 15 of 19 patients (79%) with primary transsphenoidal surgery and in 8 of 13 patients (62%) with a transsphenoidal approach following previous surgical procedures, the craniopharyngioma was totally removed. Primary transsphenoidal surgery is a safe and successful procedure for intrasellar and suprasellar infradiaphragmatic craniopharyngiomas. In secondary surgery and in the presence of tumor calcifications the indication for this approach must be considered more carefully. Postoperative posterior pituitary deficiency is a frequent occurrence. Anterior pituitary function usually remains unchanged after surgery except for normalization of hyperprolactinemia.

Adolescent↗

Acromegaly with 'normal' serum growth hormone levels. Clinical features, diagnosis and results of transsphenoidal microsurgery.

Among 216 consecutive patients with growth hormone secreting pituitary adenomas who underwent primary neurosurgical treatment at the University of Erlangen-Nürnberg, 8 cases of acromegaly with 'normal' basal growth hormone levels (less than or equal to 5 ng/ml) were seen. They all had the typical clinical features of acromegaly, exhibited an abnormal growth hormone secretion following an oral glucose load, and had markedly elevated somatomedin C levels. The GRH- and TRH/GnRH-tests were not found helpful in establishing the diagnosis. Neuroradiology could demonstrate a pituitary adenoma in all of the patients. Following transsphenoidal microsurgical resection of the tumours, growth hormone secretion during oral glucose tolerance testing was normalised in 7 of the 8 patients. Immunohistology and explant culture studies documented growth hormone secreting pituitary adenomas in all cases. The authors conclude that even the finding of repetitive 'normal' (less than or equal to 5 ng/ml) serum GH levels does not exclude active acromegaly and when the clinical diagnosis of acromegaly is suspected, dynamic endocrine testing may reveal abnormal secretion patterns of GH in these cases. Transsphenoidal microsurgical resection of a pituitary adenoma offers a good chance of clinical and endocrinological remission in these cases.

Acromegaly↗

[Orbital, osseous, meningeal and cerebral findings in oculodermal melanocytosis (nevus of Ota). Clinico-histopathologic correlation in 2 patients].

In two patients suffering from congenital oculodermal melanocytosis (nevus of Ota) orbital, osseous, meningeal, and cerebral manifestations are documented. In a 38-year-old European with a nevus of Ota on the right side an ipsilateral orbital tumor was diagnosed and surgically removed. The histological examination revealed a primary spindle shaped malignant melanoma of the orbit. In addition, many benign melanocytes were found in the optic nerve, in the extraocular muscles, in the orbital fat tissue, and in the dura of the sphenoid. In a 17-year-old Ethiopian with a nevus of Ota of the right side an increase in size of the pigmented process was observed during puberty in the orbital fat tissue, in the extraocular muscles, in the optic nerve, in the periorbital bones, in the temporal muscle, and in the cortex of the frontal brain lobe. A deep excision from the lower eye lid revealed a histologically benign oculo-orbito-dermal melanocytosis. An irradiation was performed because of growth again after segmental excision, however without success. In the ipsilateral eye a secondary open-angle glaucoma was diagnosed. In the nevus of Ota an involvement of the orbit and of the meningo-cerebral tissue must be considered.

Adolescent↗

Presence of dopamine D1 receptors and absence of dopamine D2 receptors in human cerebral meningioma tissue.

Preliminary studies have shown that the dopamine D1 receptor is expressed in cerebral meningioma tissue. The current study presents evidence that the iodinated dopamine D1 antagonist [125I]SCH-23982 bound to dopamine binding sites in 33 of the 45 human cerebral meningiomas examined for this. Saturation curves and the linearity of the Scatchard analysis indicate that [125]SCH-23982 binds to a homogeneous population of binding sites. Competition curves reveal the presence of a dopamine D1 receptor by rank order of various dopaminergic and nondopaminergic antagonists ((+)-SCH-23390 greater than (+/-)-SKF-83566 greater than (cis)-flupentixol greater than (+)-butaclamol greater than chlorpromazine greater than 1-sulpiride greater than mianserin greater than (-)-butaclamol). Stereoselectivity was evaluated by (+)- and (-)-butaclamol. The mean (+/- standard deviation) dissociation rate constant was 369 +/- 196 pM with a density of 31.9 +/- 12.5 fmol/mg membrane protein among 33 meningiomas. The dopamine D2 receptor was not present in the 30 meningiomas examined for this. These findings indicate that the dopamine D1 receptor identified is expressed alone and is therefore regulated independent of a D2 receptor in cerebral meningioma tissue. Although the function of the dopamine D1 receptor in cerebral meningiomas has not so far been defined, previous studies have suggested that the D1 receptor might be involved in the control of proliferative growth of meningiomatous tissue.

Adult↗

Postoperative hearing recovery in a case of delayed hearing loss after acoustic neurinoma removal.

Delayed postoperative hearing loss after acoustic neurinoma removal is seldom observed. The presented case illustrates the phenomenon of delayed postoperative hearing loss which was observed 4 days after removal of a large acoustic neurinoma. Intraoperative brainstem auditory evoked potentials (BAEP) revealed a gradual loss of wave V with preservation of wave I. In animal experiments a dissociated loss of BAEP has been associated with impairment of microcirculation due to secondary edema. Vasoactive treatment was initiated and after 11 days a partial hearing recovery could be documented. Transient disturbance in microcirculation of vasa nervorum of the cochlear nerve is assumed to be responsible for postoperative hearing fluctuation.

Audiometry, Pure-Tone↗

Surgical management of acromegaly.

Surgery is generally the primary therapy of choice in acromegaly, and the predominantly used transsphenoidal approach has proved to be efficient and safe. Surgical results are dependent on preoperative tumor size and extension and preoperative growth hormone levels. Invasion appears to be the most important factor in predicting surgical outcome. Growth hormone levels can be normalized in 71% of all cases and in more than 80% of microadenomas. Persistent growth hormone excess may require reoperation, radiotherapy, or medical treatment. With close interdisciplinary cooperation of neurosurgeons, endocrinologists, and radiotherapists, nearly all acromegalic patients can be successfully treated today.

Acromegaly↗