Search

In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.

Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. They are grouped into four classes based on the position of key cysteine residues: C, CC, CXC, and CX3C. Stromal cell-derived factor 1 (SDF1), the ligand of the CXCR4 receptor, is a CXC chemokine involved in chemotaxis and brain development that also acts as coreceptor for HIV-1 infection. It has been proposed that CXCR4 is overexpressed and required for proliferation in human brain tumor cells. We previously demonstrated that CXCR4 and SDF1 are expressed in culture of cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In this study, we analyzed the expression of CXCR4 and SDF1 in four human brain tumor tissues, showing that CXCR4 is expressed in all tumors analyzed, whereas SDF1 is expressed only in two tumor tissues. We also investigated the possible functions of CXCR4 expressed in rat type I cortical astrocytes, demonstrating that SDF1alpha stimulates the proliferation of these cells in vitro. Moreover, we studied by western blot the intracellular pathway involved in cell proliferation, demonstrating that SDF1alpha induces the ERK1/2 phosphorylation that is reduced by the PD98059 compound, an MEK inhibitor.

Objective and Importance: Several methods have been proposed to achieve transsphenoidal arachnoid mobilization and chiasmapexy in symptomatic empty sella (primary or secondary empty sella syndrome). These procedures are often difficult to perform and have not always had satisfactory long-term outcomes because of the difficulty of achieving adequate and long-lasting sellar filling over time. The volume of fat or muscle packing decreases over time as a result of scar retraction. The same problem may occur with intrasellar balloon placement because of deflation of the balloon., Technique: We propose extradural packing accomplished through a transsphenoidal approach, using a Silastic (Dow Corning, Auburn, MI) coil, fashioned by means of a ventricular catheter arranged as a spiral., Results: This technique was used in four patients with satisfactory and long-lasting clinical results. It presents several advantages over previous methods: it can be tailored to each patient; Silastic is an inert substance, and therefore scarring, with consequent shrinkage, does not occur; and because the coil is very elastic, it presents few risks of inflammatory complications or of excessive compression of sellar, parasellar, and suprasellar structures. Furthermore, this technique does not require a supplementary skin incision to harvest autologous tissues (fat, muscle, or fascia lata). A skilled neurosurgeon can perform the procedure in a few minutes with more ease and less expense than other techniques., Conclusion: The reported technique is a valid alternative to classic transsphenoidal extradural packing.

Objective and Study Design: Leptin is a circulating hormone secreted by adipose tissue and a few other tissues. It has recently been demonstrated that leptin and leptin receptors are expressed in normal and adenomatous pituitary cells. The aim of this study was to investigate the effect of recombinant human leptin on GH release from adenomatous GH-secreting cells in culture. Specimens were obtained from 10 patients with acromegaly who had undergone selective transsphenoidal adenomectomy. Cells (2 x 10(5)/well) preincubated for 24 h with leptin (10(-10)-10(-8) m) or control medium were exposed to GHRH for 2 h. The GH released into the medium was measured before and after GHRH incubation. The expression of leptin receptor isoforms was evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR) in cells obtained from five adenomas., Results: After the first incubation, there was a slight dose-dependent leptin-induced decrease in GH released into the medium. A significant increase in GH release after GHRH was noted from cells previously exposed to leptin in comparison with cells incubated with medium alone. Expression of leptin receptors was found in two out of five GH-secreting adenomas evaluated., Conclusions: Our data confirm that some, but not all, GH-secreting adenomas express leptin receptors. Leptin seems to exert both a slight inhibitory effect on spontaneous GH secretion and a stimulatory effect on GHRH-stimulated GH secretion from GH-secreting adenomatous tissue.

Background: Nitric oxide (NO) biphasically modulates osteoclast function, sperm motility and testosterone production by exerting a positive effect at low concentrations and a negative effect at high concentrations. In this study the effect due to administration of four NO-donors, each releasing an individual amount of NO, was studied on GH secretion from human adenomatous GH-secreting cells., Methods: Sodium nitroprusside (SNP), diethylenetriamine NO adduct (DETA/NO), diethylamine/NO complex sodium salt (DEA/NO), and S-nitroso-N-acetylpenicillamine (SNAP) were administered at a concentration of 10-4 M to cells isolated after transsphenoidal adenomectomy from five acromegalic patients., Results: SNP significantly (p < 0.01) increased GH secretion, while the other NO donors inhibited GH secretion in comparision with the amount of GH spontaneously released by unstimulated cells. Each drug showed an individual degree of inhibitory potency: DEA/NO > DETA/NO > SNAP. Nitrite accumulation in the media was measured as a marker of NO released by each individual drug and was found to be different for each drug (DEA/NO > DETA/NO > SNAP > SNP). A negative correlation (R = -0.93; p < 0.05) was found between nitrite release and GH secretion induced by each drug., Conclusions: These data show that low and quasi-physiological levels of NO, such as those released by SNP, stimulate GH secretion, while high NO levels, such as those released by the other NO-donors, inhibit GH secretion. Thus, NO is shown to be able to modulate GH secretion in a dose-dependent manner in GH adenomatous cells from human pituitary adenomas.

Prevision for the next future in a dramatic advances era we are living now has to be based upon fields consistently correlated to significative and immediately employable developments. Technical improvements in the next future, at the beginning of the third millennium, may schematically identified into two basic domains: the former, concerning surgical techniques; the latter, dealing with endovascular and neuroendoscopic techniques.

Nitric oxide (NO) has recently been shown to modulate pituitary secretion both in vivo and in vitro. The aim of this study was to investigate the effects of this chemical transmitter on spontaneous and growth-hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion in acromegalic patients, as well as from GH-secreting tumors maintained in vitro. The study was carried out in 7 acromegalic patients (46.2 +/- 2 years) and in 5 normal subjects (40.1 +/- 1.5 years). GH and prolactin (PRL) secretion were assayed during the administration of isosorbide dinitrate (ID, 5 mg, orally), an NO donor, GHRH, and ID plus GHRH. During ID, a significant (p < 0.05) increase (37%) over basal GH levels was only observed in acromegalics. There was no change in GH levels in response to GHRH or ID plus GHRH in either group. No significant change in PRL levels was observed in either group during ID, while GHRH, with or without ID, induced a slight increase in PRL levels in acromegalics only. Tumor specimens were obtained by selective transsphenoidal adenomectomy, and the cells were plated and incubated for 1, 2 and 24 h in the presence of sodium nitroprusside, a releaser of NO (SNP, 0.3 or 0.6 mM), of GHRH (10-8 M) or of both. SNP significantly (p < 0.001) increased GH levels in a dose-dependent manner (R = 0.99, p = 0.02), but was unable to modify the GH response to GHRH. In acromegalics, a significant correlation (R = 0.822, p < 0.045) and a correlation near the limit of significance (R = 0.73, NS) were observed respectively between the in vivo GH response to ID and the in vitro response to SNP at 24 h. No significant effect was observed on PRL secretion during SNP incubations, while GHRH produced a significant increase in PRL after 2 and 24 h incubation in acromegalics. These observations indicate that NO plays a stimulatory role in vivo and in vitro on GH secretion in acromegalic patients.

Background: Hemangiomas are benign vascular tumors. Because less than 1% of all hemangiomas are intramuscular, only 8 cases of temporal muscle hemangioma have been described to date. This is a case study of a 13-year-old girl who was referred to our institution because of a soft swelling located in the left temple that has enlarged progressively since birth., Methods: CT scan, angiography and MRI showed a tumor mass lying in the temporal muscle, with homogeneous contrast enhancement. No tumor blush or feeding arteries were detected. At surgical exploration, the tumor appeared to be well demarcated. It was totally excised, sparing the surrounding temporal muscle, which did not present any sign of infiltration. Histopathologic examination showed the lesion to be a cavernous hemangioma., Results: The cosmetic result was excellent, and MRI after 1 month and 2 years showed complete absence of the lesion and no evidence of recurrence., Conclusions: Although this type of tumor may be treated by various methods surgical excision yields the best results in the short and the long term. The surrounding tissue is spared as much as possible when no signs of infiltration are noted at operation, especially when involving small and functionally important muscles, as in our case.

Small nodules of neoplastic cells protruding from the arachnoidal layer surrounding an intracranial meningioma, completely independent from the tumor mass, have been observed in three patients who underwent primary surgery. The high rate of recurrence for meningiomas after a seemingly total excision has been many times reported, and related to histological subtypes, tumor site, and hormonal influence. In the past meningotheliomatous cell aggregates protruding from the inner surface of the dura mater at a distance of 3 cm from the insertion of globoid meningiomas have been described, and the concept of "localized dural multifocality" emphasized. Probably this concept has to be enlarged to consider meningioma as a "neoplastic disease" with different grade of expression. The presence of unidentified macroscopic or microscopic clusters of neoplastic cells, lying around, more or less close to, the line of insertion of lesion, could render any attempt to gain a "radical" excision useless.

The fissure separating the motor from the sensory cortex and the substantia gelatinosa capping the posterior horn of the spinal cord are still known by the name of the Italian anatomist Rolando, Luigi Rolando was born in Turin, Italy, in 1773 and died in 1831. His life was not easy, the first of his problems being the death of his father when Rolando was still very young. Three people were to be influential in his life and career: Father Maffei, his maternal uncle who raised him; Dr. Cigna, the anatomy professor who discovered his talent; and Dr. Anformi, a general practitioner who introduced him to the practice of medicine and to the best circles of the city. Forced to leave Turin by the Napoleonic invasion of the country, Rolando first stopped in Florence, where he learned about anatomical dissection, drawing, and engraving and studied the appearance of nervous tissue under the microscope. Later he went to Sardinia where, although cut off from European cultural circles, he developed his major theories. Rolando pioneered the idea that brain functions could be differentiated and located in specific areas and discovered the fixed pattern of cerebral convolutions, highlighting motor and sensory gyri. He demonstrated the complexity of the central gray matter of the spinal cord, describing the "substantia gelatinosa," and he deduced that nervous structures are connected in a network of nervous fibers linked by electrical impulses. Rolando had to struggle for recognition, however, as the priority of his discoveries was challenged by the almost contemporaneous work of Gall and Spurzheim on cerebral localization and of Flourens on cerebellar function. Nevertheless, his efforts contributed greatly to the clarification of brain function. His observations on nervous anatomy have been especially accurate, as shown by the nomenclature "fissure of Rolando."

Percutaneous retrogasserian glycerol rhizolysis (PRGR) became a diffuse and valuable method for treatment of trigeminal neuralgia, following its introduction by Hakanson in 1981. Its main advantages are: a) mild postoperative facial sensory loss, b) simplification of the technique, c) reduction of costs. Our results in a series of 191 patients treated between September 1983 and September 1990 are reported. The procedure was performed according to Hakanson's method with minor modifications. In 11 cases (5.7%) we failed to pierce the foramen ovale; the procedure was successfully repeated a week or two later. In 17 cases it was impossible to obtain CSF from the needle. Complete relief of pain was achieved in 177 patients (92.7%), in 124 (64.9%) immediately, in 53 (27.8%) within 6 days; the operation was unsuccessful in 14 (7.3%). Postoperative sensory evaluation showed: no sensory loss in 33 cases (17.3%); hypalgesia in 8 (4.2%); mild hypesthesia in 88 cases (46.1%), confined to the affected divisions in 45 (23.6%), exceeding it in 43 (22.5%); moderate hypesthesia in 62 cases (32.4%), restricted to the target divisions in 36 (18.8%), exceeding them in 26 (13.6%). No case of anesthesia occurred. Complications of PRGR were: circum-oral ipsilateral herpetic eruption (herpes simplex type), spontaneously and completely regressing: 63 cases (33%); minor dysesthesia, seldom reported as painful: 33 cases (17.3%); impairment of corneal reflex: 19 cases (9.9%), the first branch being the target of the treatment in 11; regressive masticatory weakness; 11 patients (5.7%); aseptic meningitis, promptly regressed: 2 cases (1.0%). Follow-up ranges from 1 to 7 years (Sept. 1983-Sept. 1990). A recurrence was observed in 44 cases (23%): in 15 patients (7.8%) a partial relapse occurred, well controlled by drug therapy and not requiring further surgical treatment; in 29 cases (15.2%) a new percutaneous procedure was required. The mean time of recurrence was 30.5 months. The recurrence rate in the patients of our series at the end of the follow-up period was 23%. Glycerol produces a weak neurolytic lesion, that generates minor post-operative facial deafferentation; it is the best technique, in our opinion, for treatment of tic douloreux.

Twenty-six consecutive patients with ACTH-dependent Cushing syndrome were subjected to simultaneous, bilateral inferior petrosal sinus sampling for ACTH assay before and after ACTH-releasing hormone (CRH) stimulation. The baseline ACTH inferior petrosal sinus/periphery (IPS/P) ratio was > or = 2 in 12 of 26 patients (46%), whereas the CRH-stimulated IPS/P ratio was > or = 3 in 19 of 26 patients (73%). A pituitary adenoma, ACTH-secreting at immunostaining, was surgically proved in all of the 19 patients who had an ACTH IPS/P ratio > or = 2 basally or > or = 3 after the CRH test but also in three other patients who did not have such ratios. The value of the basal IPS/P ratio and the complete lack of ACTH increase after CRH led to the diagnosis of an ectopic ACTH syndrome in four patients: a bronchial carcinoid was found in three patients, and the site of the tumor was still unknown in the other. In conclusion, the CRH test improved the diagnostic accuracy of inferior petrosal sinus sampling from 61.5% (12 pituitary, 4 ectopic) to 92.0% (19 pituitary, 4 ectopic). Thus it should be performed during the diagnostic process.

The clinical pattern of torticollis and surgical results were evaluated. Head posture and range of motion were measured. The authors use a newly designed device consisting of an orthogonal system to which head position is referred. Preliminary data were obtained on 24 patients with torticollis and 21 healthy control subjects. The examination of posture shows that the head usually twists in opposite directions simultaneously around a vertical and a sagittal axis, and the deflection is greater in one direction. Head position affect body posture, with the trunk often compensating for head deviation. Although there are almost always abnormalities on EMG recordings of neck muscles, these do not indicate the degree and pattern of deformity. Because of the disorder of muscle innervation, head movements are affected, with an asymmetrical decrease in the range of motion in comparison with normals (p < 0.05). Movements are greater toward the direction of postural deviation. Eleven patients were studied before and after undergoing a bilateral C1-C3 rhizotomy and selective section of the XIth rootlets, which carry motor fibers to the sternocleidomastoid muscle. Head posture immediately improved (p < 0.05), with better appearance, despite some residual distortion (less than 10%), and trunk alignment also improved . In contrast to posture, head range of motion was worse than before (p < 0.05). The most improved movement was rotation, followed by flexion/extension. Further improvements were observed at later follow-up. Surprisingly, the range of motion gradually increased, surpassing preoperative limits (p < 0.05). Our study documents the usefulness of surgery in correcting torticollis. Posture is immediately affected; motion increases despite denervation, after an initial decline.

The ability of CRH to cause a paradoxical response of GH in acromegaly is still under debate. In this study, the effect of CRH administration on GH release was evaluated in a large series of patients with active acromegaly, both in vivo, compared to that of TRH and GnRH, and in vitro. The study was organized as follows. In vivo study: 30 acromegalic patients were submitted to TRH, GnRH, and CRH tests on non-consecutive days: blood samples were collected before and 10, 20, 30, 45, 60, 90, and 120 min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300-600 micrograms sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 mumol/l) was tested on pituitary tumor tissue obtained in eight patients during transsphenoidal adenomectomy and immediately placed in sterile Ca2+ and Mg2+ free buffer phosphate. A paradoxical GH response to TRH (evaluated as a GH increase over 50% of basal values) was recorded in 19 patients (63.3%), whereas 7 patients (23.3%) responded to GnRH and 4 others to CRH (13.3%). TRH administration induced a maximal percent GH increase significantly greater than that induced by GnRH and CRH (p < 0.05). Octreotide caused the normalization of GH and insulin-like growth factor-I levels in all the patients, as well as the disappearance of the GH paradoxical response to CRH in 3/4 patients. All four CRH responders and four CRH non-responders, used as controls, were surgically treated and adenomatous tissue was used for the in vitro study.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of a chronic treatment with octreotide were evaluated in 19 patients affected with functionless pituitary adenomas. Octreotide caused a significant decrease of GH and IGF-I levels in all the patients and no significant change in thyroid, adrenal and gonadal function. In contrast, during the therapy, the glucose response to an oral glucose tolerance test considerably increased and was delayed, while the insulin response decreased and was delayed. Serum alpha-subunit (alpha-SU) was above normal in 10 of 16 patients in which this evaluation was performed: octreotide caused a significant decrease (p < 0.01) of alpha-SU levels in 6 of these 10 patients. Octreotide did not induce any significant change in visual fields except in 1 patient, who had a great improvement of visual perimetry and a decrease of alpha-SU levels but unmodified CT scan features. In our series of patients, octreotide was ineffective in reducing tumor mass. The efficacy of octreotide might rely on the presence of somatostatin receptors on adenoma-cell membranes. Therefore patients with functionless adenomas to be treated with octreotide might be identified with pituitary scintiscan using the recently available labeled 111In-octreotide.

In 29 consecutive patients with adrenocorticotropin (ACTH)-dependent Cushing's syndrome, we compared the usefulness of multiple baseline ACTH evaluations (10/29), multiple hormone evaluation (29/29) and ACTH-releasing hormone (CRH) stimulation (21/29) during simultaneous and bilateral inferior petrosal sinus sampling. The basal inferior petrosal sinus/periphery ratio for ACTH concentrations was greater than 2 in 18 of the 29 patients and CRH challenge caused the appearance of an inferior petrosal sinus/periphery ratio greater than 3 in 6 other patients. The presence of an ACTH-secreting adenoma was surgically proven in all the 24 patients who had an ACTH inferior petrosal sinus/periphery ratio greater than 2 basally or greater than 3 after the CRH test but also in 1 patient who had an inferior petrosal sinus/periphery ratio lower than 2 basally or 3 after the CRH test. In 4 patients, both the very high peripheral ACTH levels, the inferior petrosal sinus/periphery ratio and the complete lack of ACTH increase after CRH indicated the presence of an ectopic ACTH syndrome: a bronchial carcinoid was found in 2 patients, whereas the site of the tumor is still unknown in the remaining 2. An ACTH intersinus gradient greater than 1.4 was found in 23 patients. Among these 23 patients, the side of the adenoma was correctly predicted in 19 patients and wrongly in 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim of the present study was the evaluation of ACTH and beta-endorphin-like-immunoreactivity (beta-ELI) in the inferior petrosal sinuses (IPS's) and in the peripheral blood of patients with Cushing's disease (Group 1), with GH- or PRL-secreting adenomas or nontumoral hyperprolactinemia (Group 2). These patients had undergone selective and bilateral simultaneous IPS sampling for diagnostic purposes or for neurosurgical indications. In the patients of Group 1, ACTH and beta-ELI levels were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.001). In the patients of Group 2 ACTH and beta-ELI levels were higher in the IPS's than in the peripheral blood (p < 0.001) and, in the 9 patients with GH- or PRL-secreting adenomas, they were higher in the IPS ipsilateral than in the contralateral to the adenoma and in the periphery (p < 0.05). A significant correlation exists between ACTH and beta-ELI in the periphery (p < 0.01; r = 0.72), in the IPS ipsilateral (p < 0.05; r = 0.54) and contralateral (p < 0.01; r = 0.66) to the adenoma in Group 1, but not in Group 2. In conclusion, higher beta-ELI levels were detected in the IPS's than in the peripheral blood not only in patients with Cushing's disease but also in those with other pituitary diseases not involving ACTH secretion. The absence of correlation between ACTH and beta-ELI in patients not bearing Cushing's disease suggests that in these conditions corticotrophs release ACTH and beta-endorphin in an independent manner.

The aim of this retrospective study was to evaluate the existence of a multihormonal gradient between the inferior petrosal sinuses in various pituitary diseases: Cushing's disease (8 cases), acromegaly (4 cases), prolactinomas (7 cases), GH, PRL-secreting adenoma (1 case), functionless adenoma (2 cases), empty sella (3 cases) and in non-tumoral hyperprolactinemia (5 cases). A significant intersinus gradient (more than 1.4:1) was recorded for GH, ACTH and PRL in 16 patients (80%), but in only 9 patients (45%) out of the 20 with hormone-secreting tumors for TSH, FSH and LH. Moreover, of the 10 patients in the remaining groups, only in two cases was a significant intersinus gradient present: one for GH and one for LH. In conclusion, the finding of a multihormonal release in the inferior petrosal sinus ipsilateral to the adenoma is reported, for the first time, in patients with GH- and PRL-secreting adenomas. The possible explanation for such a finding may be either an increased blood flow in this site of sampling or a pituitary multihormone release through a paracrine mechanism primed by the tumoral hypersecreted hormone. In addition, the pulsatile secretory pattern and the short half-life of polypeptide hormones may contribute to better demonstrate this phenomenon in respect to glycoprotein hormones.

This study describes a case of pituitary-dependent Cushing's syndrome where standard biochemical and radiological techniques were discordant in localizing the origin of the autonomous adrenocorticotropic hormone (ACTH) hypersecretion in the pituitary. Hormonal evaluation suggested a pituitary genesis for the disease, but both sellar computed tomography and cranial magnetic resonance (MR) were unable to give clear-cut evidence for a pituitary neoplasm. Simultaneous and bilateral inferior petrosal sinus sampling (SBIPS) correctly identified the left side of the pituitary gland as the source of autonomous ACTH production. One year later, the shaded signs of a pituitary lesion in the left side of the gland were seen with MR imaging, and a 0.5-cm in height adenoma was surgically removed. At the 2-year follow-up the patient's symptoms had completely disappeared, and her menses were restored. In this case, SBIPS correctly diagnosed the presence of an ACTH-secreting pituitary microadenoma one year before shaded signs of the pituitary lesion appeared with MR imaging. This is a clear-cut demonstration of the accuracy of the SBIPS technique in localizing small pituitary lesions.

A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mP ab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP- and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patients surgically treated and in all the 48 mP-bearing patients only treated with BRC; c) in 20 of the 25 patients the treatment with injectable retard BRC caused the normalization of plasma PRL and the shrinkage of the tumor mass in all the patients with MP but one, as revealed by seriate CT scans. In conclusion, the surgical treatment of prolactinomas was ineffective to normalize plasma PRL levels in most patients whereas BRC, in standard or in retard forms, was able to normalize plasma PRL levels, reduce the tumoral mass and preserve the pituitary residual tissue. BRC should be, therefore, used as first choice therapy both for MP and mP.

To examine the reliability of the diagnoses reached on multiple small fragments of cerebral glial tumors obtained via stereotactic biopsy, samples obtained from 100 consecutive glial tumors (during real or simulated biopsy) were studied by cytology and histology. In comparison to the definitive diagnosis made on the whole tumor, a correct positive diagnosis on the biopsy sample was made by histology in 96% of cases and by cytology in 93% of the cases (with 96% correct results when combining both methods). A correct identification of the tumor type and grade was achieved by histology in 82% of cases and by cytology in 80% of the cases (with 85% correct results when combining both methods). The limits of stereotactic biopsy are related to the difficulty of identifying all of the typical tumor features on tiny tissue fragments of a pleomorphic neoplasm, such as a glioma. This study demonstrates that better results may be obtained by using both cytology and histology to study multiple stereotactic biopsy samples from glial tumors.

An experimental trial has been realized in rabbits interposing a polytetra fluoroethylene (PTFE) graft through the left carotid artery. Patency has been compared to one obtained by utilization of vein grafts in identical conditions.

A new experimental trial to investigate the usefulness of early therapeutic measures in case of acute I.V.D. has been performed, on the basis of a previous already reported experience. A combined treatment consisting of hemodilution and revascularization starting 16 hours after the onset of cerebral ischemia was tested. The study was performed in a population of 20 New Zealand male rabbits in which an acute cerebral ischemia was achieved by means of extracranial ligation of both common carotid artery and of one vertebral artery. The animals were divided into two groups. 1st group: no treatment; 2nd group: revascularization + hemodilution. Better results were observed in treated group considering either CBF rates or histological changes.

Patency of vascular microanastomosis was examined in aging (6 months) and hypercholesterolemic rats, reproducing conditions similar to those occurring in human pathology. Results have been compared with those achieved in normocholesterolemic, younger (aging less than 8 weeks) rats.

The present study aimed at evaluating the anterior pituitary hormone levels in the inferior petrosal sinuses and in the peripheral blood of 55 patients affected by various pituitary disorders and undergoing perihypophysial phlebography on neurosurgical indication or for diagnostic purposes. The results indicated that in 6 patients with Cushing's disease and in 4 with hyperprolactinemia the secreting adenoma could be localized by inferior petrosal sinus sampling. Furthermore, the concentrations of all the pituitary hormones were found to be higher in the right and/or in the left inferior petrosal sinus than in peripheral blood, showing a clear gradient between central and peripheral samples. Moreover, the evaluation of hormone central/peripheral concentration ratios revealed noteworthy differences, namely, that central/peripheral concentration ratios of GH, ACTH, and PRL were significantly higher than those of TSH, FSH, and LH (p less than 0.01). On the contrary, no significant differences were found when the concentration ratios of GH, ACTH and PRL or TSH, FSH and LH were compared among themselves. This finding may be attributed to at least two factors: the increased pulsatility and the relatively short biological halftime of polypeptic hormones (GH, ACTH, and PRL) compared with glycoprotein hormones (TSH, FSH, and LH).

The beta-endorphin-like-immunoreactivity (beta-ELI) has been evaluated both in plasma and in cerebrospinal fluid (CSF) in 30 patients during trans-sphenoidal surgery. Blood and liquoral samples were collected in five conditions: (1) "reference", (2) "pain", (3) "analgesia", (4) "end", and (5) "24th hour". A significant rise of both plasma and liquoral beta-ELI levels (p less than 0.00001 and p less than 0.08, respectively) when compared to basal ones occurred following the painful stimulation due to the divarication of the nasal mucosa by speculum. A significant decrease (p less than 0.01) was noticed for plasma concentrations at the third sample followed by a new significant increase at the end of the operation, (p less than 0.05 when compared to the third sample and p less than 0.01 when compared to the reference sample). In CSF, beta-ELI levels decreased at the third sample (p less than 0.01 when compared to the painful levels) and at the end of surgery (p less than 0.01, p less than 0.01 and p less than 0.05 vs first, second and third samples, respectively). Twenty-four hours after surgery either plasma and liquoral beta-ELI levels decreased (p less than 0.05). The modifications of the opiatergic system after acute painful stimuli should be, hence, characterized by an early rise followed by a progressive decrease of beta-ELI concentrations. The increase of plasma beta-ELI levels, at the end of surgery, could be due to pituitary manipulation with massive release in the peripheral blood.

End to side microsurgical anastomoses between vessels of small calibre require interruption of blood flow of about 25-40 min. In terminal vascular beds this time may be incompatible with the cellular survival. The authors refer their experience in rats with a partly original experimental technique requiring less time of clamping the receiving vessel (about 3-4 min), as the main part of the anastomosis is performed between the wall of the donor vessel and the adventitia of the receiving vessel, without interruption of blood flow in this latter. Histological examinations, performed 21 days later, reveal a patency rate of 60%.

Four cases of benign intrasellar cysts are reported. Three of these were treated surgically. Their origin and typical clinical features are discussed, in particular the altered pituitary function and visual disturbances. Computerized tomography has many advantages over traditional neuroradiological tools in reaching a diagnosis. The indication for active treatment and the surgical techniques and the methods used in the prevention of complications are outlined.

The study of pituitary diseases is described, with visualization of the cavernous and intercavernous sinuses accomplished through percutaneous, transfemoral catheterization, using special methods to ensure its reliability. The most characteristic normal and pathological findings are described. The value of this method and the indications for its use in diagnosis are discussed. The possibility of combining morphological investigations with regional functional studies of pituitary hormones by selective blood sampling is suggested. This technical development opens new prospects for the future and further broadens the indications for use of this procedure.

43 consecutive patients with acute inferior myocardial infarction (IMI) were evaluated with 12-lead electrocardiogram plus four additional right precordial lead V3R, V4R, V5R, V6R and equilibrium gated radionuclide angiography (EGRA) to detect ischemic right ventricular involvement. All patients were continuously monitored on the average 6 days; 11 of 43 patients had an episode of second or third degree atrioventricular block. Ischemic right ventricular involvement was diagnosed by electrocardiographic criteria in 60%, and by scintigraphic criteria in 70% of 43 patients with IMI. Utilization of electrocardiogram and EGRA for diagnosis of right ventricular involvement permit us to identify a subgroup of patients with IMI at high risk of developing second or third atrioventricular block (38% with ecg criteria and 33% with radionuclide criteria respectively) as regards those without right ventricular involvement (6% and 8%).

The use of intercavernous sinus phlebography for the diagnosis and neurosurgical treatment of pituitary adenomas has enabled the collection of selective venous samplings of the inferior petrosal sinuses (IPSs), where prolactin (PRL) levels can be measured before the hormone becomes excessively diluted in the systemic circulation. In the present study, plasma PRL levels were studied in the right and/or left IPS and, simultaneously, in the peripheral circulation of: (1) normoprolactinemic patients affected with various pituitary disorders which required phlebographic procedures; (2) hyperprolactinemic patients with negative radiological and computed tomographic (CT) signs of pituitary adenomas and (3) adenomatous hyperprolactinemic patients. In the 17 normoprolactinemic patients, the plasma PRL concentration in the IPSs was significantly higher (3.5 times; p less than 0.01) than in the peripheral circulation. In the 11 hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas, the central gradient for PRL was significantly higher (2.8 times; p less than 0.05) than in the peripheral circulation. No significant difference was detected between PRL concentrations in the left and right IPSs. In the 11 adenomatous hyperprolactinemic patients, there was a significant (p less than 0.01) central gradient for PRL 3.8 times higher than in the peripheral circulation on the ipsilateral side of the tumor. Furthermore, the plasma PRL concentration in the ipsilateral IPS was significantly higher (3.4 times; p less than 0.05) than that in the contralateral sinus. In conclusion, the present study shows that a clear-cut concentration gradient exists between plasma PRL levels in the IPSs and in the peripheral circulation of normoprolactinemic and hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Four cases of large paramedian hourglass epidermoid tumors extending both in the middle and posterior cranial fossa are reported and other 16 cases from the literature are reviewed. The length of the clinical history and the triviality of neurological symptoms in spite of the size of the tumor are emphasized. CT scanning well documents the extension of these epidermoids and usually consents to differentiate them from the arachnoid cysts. The subtemporal transtentorial approach is more advisable, although a two-stage operation by subtemporal and suboccipital route can be necessary in some cases. Nevertheless the difficulties and the risk of the surgical treatment make very hard the complete removal of the tumor in most cases.

The authors have studied 600 cases of spinal metastasis causing a neurological syndrome. The most significant statistical data are reviewed. The cases are examined according to clinical characteristics, type of primary tumor, site of lesion, and survival. Each of these factors influenced the choice and results of treatment. As a general rule, combined treatment (surgery and radiotherapy) was used. Preliminary surgery was performed as an emergency, designed to halt progression of the neurological syndrome and to prevent its more serious manifestations. The technique and usefulness of surgery are discussed for different situations and the short-term results of treatment are related to the various factors involved.

Our statistic consist of 162 cases of metastatic tumors of the brain (M.T.B.), of which 120 verified under surgery or at autopsy, and 42 diagnosed in the pre-operative phase and not undergone surgery. The pseudo-vascular form has been found in 58 cases (36%). If we only consider the supratentorial localizations, this percentage rises to 43,5%. This onset of symptomatology is quite predominant in males (52 cases 42%) compared to females (6 cases: 16%). The MTBs that in our statistics produce a greater frequence of pseudo-vascular forms are the MTBs of melanomas (66%), those of unknown origin (42%) and those of pulmonary origin (35%). These neoplasms are distinctly more frequent in males. On the contrary the mammary metastases responsible for most of the female MTBs originate to a pseudo-vascular form in only 22% of the cases. The etio-pathogenetic mechanism is double; it may be the manifestation either of arterial occlusion by neoplastic cells (embolia neoplastica attiva) or of disruption of the vascular wall and hemorrhage. As far as the diagnosis is concerned this syndrome can be quite easily recognised only when an extraneuraxial tumor is found, especially with a marked neuraxial tropism.

Because of the variability of the structural features of cerebral tumors, the characteristics observed in biopsy samples may not be representative of the whole neoplasm. The reliability of cerebral stereotactic biopsy is therefore greatly debated. In order to test the value of diagnoses based on biopsy samples, the authors compared histological and cytological data obtained from a small fragment of a tumor with the definitive diagnosis obtained from surgical or necropsy specimens. An analysis of 64 cases is reported, where a correct diagnosis from the biopsy sample was achieved in 92.2% of the cases. Neuroglial tumors were more difficult to characterize than other types of intracranial tumors, with an accuracy of 81.5%.