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Biomedical subjects

M Giovanelli

Publications and source records attributed to M Giovanelli.

At least 55 records · Page 3Linked to original sources

Nerve growth factor and bromocriptine: a sequential therapy for human bromocriptine-resistant prolactinomas.

Nerve growth factor (NGF) administration to athymic mice with transplanted human bromocriptine-resistant prolactinoma, results in the expression of dopamine D-2 receptors in the tumour and restores sensitivity to subsequent treatment with bromocriptine, which then produces normalisation of plasma prolactin and tumour regression. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.

Animals↗

Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin.

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.

Astrocytoma↗

Sellar and parasellar extra-axial cavernous hemangiomas.

Cavernous hemangiomas can grow extra-axially within dural sinuses, particularly the cavernous sinus and present like tumours. Five cases of cavernous hemangiomas arising within or from the wall of the cavernous sinus are reported. Three of them had an "endophytic" growth within the cavernous sinus with a lateral extension into the middle cranial fossa, a medial extension into the sella and an anterior extension into the superior orbital fissure. Two cases presented with an "exophytic" extension from the sinus wall at the point of entry of the third and fourth cranial nerves respectively. These patterns of growths are best appreciated by MRI. Keeping in mind that these lesions are contained within a pseudocapsule will help in planing surgical strategy. Characteristic MRI findings of cavernous hemangiomas in this location include hypo-intensity on T 1-weighted images, marked hyperintensity on T2-weighted images and Gadolinium enhancement.

Adult↗

Acute effects of a single administration of dexamethasone on basal and growth hormone-releasing hormone stimulated GH secretion in acromegaly.

UNLABELLED: A single administration of dexamethasone causes both an early stimulatory and a late inhibitory effect on GH secretion in normal subjects. OBJECTIVE: We investigated the effects of a single administration of dexamethasone on basal and GH-releasing hormone-stimulated GH secretion in eight patients with active acromegaly. DESIGN: On three different days the patients received 4 mg i.v. dexamethasone, 1 microgram/kg body weight GH-releasing hormone 1-29, or matched placebos in different order. PATIENTS: Eight subjects with active acromegaly, five of whom had not been treated previously, while the other three had received octreotide therapy which was stopped at least 7 days before testing. MEASUREMENTS: Serum GH levels were measured in duplicate by a commercially available RIA kit. RESULTS: Dexamethasone administration caused a significant decline of mean +/- SE GH levels from 51.8 +/- 13.8 to 30.0 +/- 9.2 mU/I at 180 minutes, that was not influenced by placebo administration at 180 minutes. On the contrary, when GH-releasing hormone substituted placebo administration, GH levels increased from 34.0 +/- 9.8 mU/I at 180 minutes to 56.0 +/- 15.6 mU/I at 195 minutes. The GH increase was higher when GH-releasing hormone was given without dexamethasone pretreatment (from 52.4 +/- 13.0 mU/I at 180 minutes to 86.4 +/- 25.4 mU/I at 195 minutes). Analysis of the GH area under the curve confirmed the significant inhibition of GH secretion after dexamethasone administration and the significant reduction of the GH response to GH-releasing hormone in the study with dexamethasone pretreatment. CONCLUSIONS: At variance with data in normal subjects, acute i.v. administration of dexamethasone inhibits basal GH secretion and partially suppresses the GH response to GH-releasing hormone in acromegaly. Both alterations in the regulatory mechanism of adenomatous cells and perturbations of hypothalamic regulatory influences, induced by the state of chronic GH hypersecretion, are likely explanations of the different response to dexamethasone.

Acromegaly↗

Nerve growth factor suppresses the transforming phenotype of human prolactinomas.

The most effective therapy of human prolactinomas is represented by dopamine D-2 receptor agonists; there is, however, a population of nonresponder patients who require surgical intervention. In the present study, we report that prolactinomas totally resistant to pharmacological therapy have a high potential of both growing in soft agar and forming tumors in nude mice and lack D-2 receptors for dopamine. These tumors express the receptors for nerve growth factor (NGF) and are sensitive to its differentiating activity. After exposure to NGF for 4 days, prolactinoma cells decreased their proliferation rate, lost their capability to form colonies in soft agar, lost their tumorigenic activity in nude mice, and reexpressed the lactotroph-specific D-2 receptor protein inhibiting prolactin release. These effects were permanent after NGF withdrawal and were reproducible in vivo in nude mice transplanted with the tumors. NGF in fact remarkably and lastingly depressed tumor growth and induced expression of D-2 receptors when injected intravenously once a day for 5 days into prolactinoma-bearing nude mice. These data suggest that NGF may induce a long-lasting switch of gene expression in human prolactinomas, modifying their transforming phenotype and reverting them to more differentiated, less malignant, dopamine-sensitive lactotroph-like cells. The possibility thus arises that short-term treatment with NGF may restore the refractory patients to conventional pharmacological therapy with D-2 agonists.

Animals↗

Solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa: a case report and review of the literature.

A rare case of solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa is reported. A 50-year-old woman with a history of diplopia and a mass in the sphenoid sinus and the sellar region, documented by computed tomography, was referred to our department with a presumed diagnosis of nonfunctioning pituitary adenoma. The clinical and biochemical characteristics were unrevealing, but magnetic resonance imaging examination demonstrated the extrapituitary origin of the lesion. The patient was operated on by the transsphenoidal approach, and the lesion was histologically diagnosed as a plasmacytoma. Review of the literature disclosed 11 previously described cases of myelomatous disease presenting clinically as a pituitary adenoma. Our case demonstrates that magnetic resonance imaging investigation may help in distinguishing the extrapituitary origin of a mass involving the pituitary fossa.

Adenoma↗

Monitoring of brain function by means of evoked potentials in cerebral aneurysm surgery.

Deliberate arterial hypotension is currently used to operate upon cerebral aneurysms. However, it is not ascertained whether this practice is really safe for all patients, especially those presenting with preoperative vasospasm. 50 patients, requiring surgical treatment for cerebral aneurysm, have been submitted, during surgery, to the recording of Somatosensory Evoked Potentials (SEPs) on median nerve stimulation. This technique allows the functional evaluation of neural pathways mediating the somatosensory stimuli and of primary somatosensory cortex; it is known that a decrease of cerebral perfusion may affect the SEP waveforms in terms of reduced subcortical conduction velocity (i.e., increased central conduction time, CCT) and of reduced cortical response amplitude. These changes may be apparent before a permanent neurological damage is produced. Preoperative SEP recording demonstrated a prolonged CCT, possibly related to vasospasm, in 9 patients, a normal clinical evaluation notwithstanding (grade I and II). During intraoperative deliberate hypotension, a SEP change has always been produced. No postoperative damage has been observed, however, as long as the CCT did not exceed 9 msec for 10 minutes (maximum normal CCT value is 6.7 msec) and as the cortical response had been visible throughout the whole surgical procedure. The critical value of CCT has been reached at a mean arterial pressure (MAP) lower than 60 Torr in patients with a normal preoperative SEP recording; at the opposite, in patients presenting with a prolonged preoperative CCT, the value of 9 msec was arrived at with a MAP value that is generally accepted as safe for all patients (75 Torr).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Pituitary function before and after transsphenoidal adenomectomy in patients with Cushing's disease.

Over the past 4 years 11 patients with Cushing's disease have been operated on by a transsphenoidal microsurgical technique. All patients had small intrahypophyseal adenomas found at operation. Eight of the 11 patients had a remission of the disease on the basis of clinical evaluation and hormonal studies. The endocrinological results revealed a transient state of hypocorticism in all successfully treated patients. Within 6-8 months after operation recovery of hypothalamic-pituitary-adrenal function and other tropin function took place. These findings, together with the absence of recurrence up to now, further confirm the efficacy of transsphenoidal surgery in the management of patients with Cushing's disease.

Adolescent↗

Traumatic brain lacerations in children: surgical results and follow-up.

75 children ranging in age from 3 months to 14 years, operated on for post-traumatic cerebral lacerations, within an 18-year period, have been analyzed. These represent 2.1% of 3,460 children sustaining head injury and hospitalized during this same period. Total mortality was 16%. The cases were divided into 2 groups: (A) cerebral lacerations underlying a depressed fracture (coup lesion) -- 68 cases. In 42 cases the lacerations were focal without edema and/or intracerebral hematoma. 1 child died and 41 survived. In 26 cases the laceration was diffuse and accompanied by cerebral edema and/or intracerebral hematoma. 6 children died and 20 survived. (B) Brain lacerations following a contrecoup lesion -- 7 cases, 5 of these children died and 2 survived. The follow-up of the surviving patients in the above two groups has been discussed.

Adolescent↗

Long-term results in 62 cases of post-traumatic complete apallic syndrome.

After the transition state of decerebrate coma, at least four different kinds of the so-called apallic status can be identified: 1. Complete apallic syndrome: coma vigil, alertness without any awareness, mass movements only, impairment of sleep rhythm, absence of any emotional responses, postural abnormalities, some primitive motor responses, tetraplegia, and alteration of muscle tone. 2. Incomplete apallic syndrome: some of the features of the complete apallic syndrome are lacking, and the patient shows emotional reactions with appropriate grimacing and some appropriate motor responses. 3. False apallic syndrome: most signs of complete apallic syndrome are present, but the patient is in touch with the environment. This condition is somewhat similar to the so-called locked-in syndrome. 4. Functional apallic syndrome: full clinical picture of the complete apallic syndrome but full recovery within a few days. Long-term results in 62 patients, aged between 4 and 62, affected by a post-traumatic complete apallic syndrome are reported. Thirty two patients were operated upon and 30 were not operated upon. Out of these cases, 38 died after weeks or months; 3 patients entered a chronic apallic status; 2 patients are improving; 10 recovered with severe neurological or psychic sequels or both; 4 recovered with minimal sequels, and 5 without sequels; no patients in these two last groups were aged more than 20.

Adolescent↗

Skull changes and intellectual status in hydrocephalic children following CSF shunting.

A total of 76 shunt-treated hydrocephalic children were examined at least once between two and 12-years after surgery to determine what skull changes had occurred and to assess the children's intellectual status. The high incidence of skull changes in shunt-treated, non-tumoral, hydrocephalic children was confirmed. A strict relationship existed between skull changes and low intracranial pressure. The results indicate that impairment of mental development parallels the degree of skull changes, suggesting a close relationship between impaired mental development and cerebrospinal fluid hypotension.

Cerebrospinal Fluid Shunts↗