Effect of corticotrophin-releasing hormone administration on growth hormone levels in acromegaly: in vivo and in vitro studies.

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)

Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro.

OBJECTIVE: Somatostatin is a powerful inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogs in humans causes a reduction in size and secretory activity of some endocrine tumors, including somatotropic pituitary adenomas. Less studied are the effects of somatostatin agonists on non-functioning pituitary adenomas (NFPAs). In this study we characterized the effects of somatostatin and its analog lanreotide on the proliferation of NFPAs in vitro and the intracellular mechanisms involved. DESIGN: Twenty-three NFPA post-surgical specimens were analyzed for somatostatin receptor (SSTR) expression and 12 of them were cultured in vitro to study somatostatin's effects on cell proliferation, assessed by means of [(3)H]thymidine uptake, and the intracellular signaling. RESULTS: One or more SSTR subtypes were expressed in 90% of the adenomas tested. Somatostatin and lanreotide treatment inhibited phorbol myristate acetate (PMA)-induced cell proliferation. Vanadate pretreatment reversed somatostatin and lanreotide inhibition of PMA-induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect. In the only adenoma tested, somatostatin directly induced a tyrosine phosphatase activity. Somatostatin and lanreotide caused also a significant inhibition of voltage-sensitive calcium channel activity induced by 40mmol/l K(+) depolarization in microfluorimetric analysis. CONCLUSIONS: These data show that somatostatin and lanreotide inhibit human NFPA cell proliferation in vitro, and suggest that activation of tyrosine phosphatases and inhibition of the activity of voltage-dependent calcium channels may represent intracellular signals mediating this effect.

Osteoplastic opening of the sellar floor in transsphenoidal surgery: technical note.

The authors propose a technique of opening the sellar floor during a transsphenoidal approach by means of two small bone flaps hinged sideward. Both opening and reconstruction of the sellar floor may be improved by this method, which may be used when the floor is paper-like.

Pituitary adenoma and parasellar cysts.

Two cases of pituitary adenoma associated with a parasellar cyst are reported; only one similar case has been described previously. Even though such an association may be coincidental, a pathogenetic relationship between the two lesions in one of our cases may be assumed: shrinkage of the prolactin-secreting pituitary adenoma by means of bromocriptine therapy did, in fact, cause collapse of the cyst. Such an occurrence must not be disregarded in considering the therapeutic approach.

Reconstruction of the pituitary fossa in transsphenoidal surgery: an experience of 140 cases.

Even though the main problems of transsphenoidal surgery are encountered during the intra- and suprasellar portions of the operation, proper reconstruction of the sella turcica plays an important role in the overall results, greatly influencing the final outcome. Improper measures may bring about a complicated postoperative course, whereas a wise and precise method allows one to control any surgical condition, preventing the more dangerous consequences of the transsphenoidal approach (i.e., empty sella, cerebrospinal fluid leakage, hemorrhage, infection, etc.). The authors review the different methods of sellar plugging and, on the basis of their own experience, indicate the most suitable one for each of the more usual situations. A good result is achievable if only natural materials are used and one avoids synthetic prostheses. Extradural packing is the technique of choice whenever a hermetic closure and a particularly effective intrasellar plug are required.

Subarachnoid hemorrhage and "normal pressure hydrocephalus": fatal complication of percutaneous microcompression of the gasserian ganglion. Case report.

A 62-year-old man underwent percutaneous balloon catheter compression of the gasserian ganglion for typical trigeminal neuralgia. After this, a subarachnoid hemorrhage was discovered and normal pressure hydrocephalus developed, which required shunting. Although the neurological function recovered, the patient died 8 months later because of supervening hepatic insufficiency, probably caused by protracted antibiotic therapy. Such a fatal complication, the first one associated with the technique of percutaneous trigeminal compression, was perhaps predisposed by preexistent cerebral atrophy with enlargement of the subarachnoid spaces; the unforeseen piercing of the dilated trigeminal cistern probably permitted the intracranial subarachnoid diffusion of an otherwise trivial hemorrhage. The safety of the procedure may be greatly reduced in such instances.

Ewing's sarcoma arising primarily in the spinal epidural space: fifth case report.

Ewing's sarcoma is found exceptionally as a primary epidural tumor of the spine. Four cases have been described in the literature. We describe the fifth case: a 10-year-old boy who underwent operation followed by radiotherapy and chemotherapy. For 1 year he then had a complete remission with no local recurrence and his neurological condition was satisfactory, although metastases developed later. Comparison with the cases described previously shows all five to possess interesting features in common.

Forced subarachnoid air in transsphenoidal excision of pituitary tumors (pumping technique)

Inversion and prolapse into the sella of the superior capsule and the diaphragma sellae is the only condition that warrants, at least macroscopically, radical removal of tumors with suprasellar extension operated on via the transsphenoidal route. If this does not occur spontaneously, air can be introduced into the subarachnoid space through a lumbar spinal catheter to produce forced dissection of the suprasellar cisterns and collapse of the tumor capsule ("pumping technique"). This method permits complete removal of the neoplastic tissue. In a series of 124 transsphenoidal operations for tumors with suprasellar extension, spontaneous descent of the capsule occurred in only 26 cases. Forced dissection using air distension of the cisterns was carried out in 88 cases, with complete success in 56 cases, partial success in 20, and no effect in 12. There were no complications or unwanted side effects in any patient.

Luigi Rolando and his pioneering efforts to relate structure to function in the nervous system.

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."

Spinal metastases with neurological manifestations. Review of 600 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.

Nitric oxide biphasically modulates GH secretion in cultured cells of GH-secreting human pituitary adenomas.

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.

Usefulness of immunoscintigraphy in the follow-up of surgically treated gastrointestinal carcinomas using 111In-labelled anti-CEA monoclonal antibodies.

Twenty-five patients treated surgically for gastrointestinal carcinomas (16 rectum-sigmoid colon, 6 colon, 3 stomach) were investigated by immunoscintigraphy (IS) using 111In-labelled anti-CEA antibody (mouse monoclonal F023C5) F(ab')2 fragments in order to visualize questionable abdominopelvic recurrences (excluding the liver). Fifteen (60%) patients showed a rise in serum CEA levels above 5 ng/ml. Planar scans and emission computed tomographic (ECT) imaging were carried out without reference to the results of computed tomographic (CT) scans and gastrointestinal endoscopic examinations done 1-2 weeks before IS. Final diagnoses were based on biopsies and autopsies (13 cases) or on follow-up findings over at least 2 years (12 cases). Sixteen patients had a final diagnosis of recurrent malignant disease in the extrahepatic abdomen or pelvis. Of these, six were correctly diagnosed by both IS and conventional diagnostic procedures, six by IS only and two by conventional methods only. Two tumour recurrences remained undetected by both diagnostic approaches. However, five tumour recurrences were detected by IS more than 4 months earlier than by any other diagnostic procedures performed during clinical follow-up. Of the nine disease-free patients (disregarding the liver) three were correctly identified by both IS and the other diagnostic methods, four by IS only and two by conventional diagnostic procedures only. Overall sensitivity (75%) and specificity (89%) of 111In-IS were higher than figures obtained using CT scanning and endoscopy (50% and 78% respectively). True positive IS was observed in 6/15 (40%) CEA seropositive patients and in 6/10 (60%) CEA seronegative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of carotid-cavernous fistula by trans-venous anterior (trans-orbital) approach. Case report and review of previous report.

A case is reported of successful occlusion of a dural carotid-cavernous fistula (type D) by means of a transvenous anterior approach. Through the left angular vein, the distal superior ophthalmic vein (SOV) and the cavernous sinus were cannulated and three Gianturco coils were delivered close to the fistulous communications. Obliteration of the carotid-cavernous communication was achieved sparing the internal carotid artery and its branches. The major advantage of entering the sinus from the venous route is to preclude any damage to the artery, distal migration of the detachable balloon or of thrombi, intracavernous pseudoaneurysm formation. The trans-orbital approach may be considered chiefly when the openings are in the antero inferior compartment and the SOV is enlarged. Its applications, quite sporadic until now, probably will become more popular, mainly in treating D type fistulas, thanks to the good results achieved and to its safety.

Percutaneous retrogasserian glycerol rhizolysis. Observations and results about 50 cases.

Fifty patients complaining of trigeminal neuralgia have been treated by Percutaneous Retrogasserian Glycerol Rhizotomy (PRGR) from September 1983 to December 1985. In 94% of cases the procedure was successful in relieving pain with minor facial sensory loss, in 29 cases confined to the affected divisions, in 13 cases extending in an adjacent division. A herpes eruption occurred in 39 patients. A partial relapse (not requiring re-operation) verified in 12 patients. Even it firm conclusions cannot be reached as to the efficacy of this therapy, till when longer duration follow-up studies will not available, it seems to offer a manageable and very efficient way of treating trigeminal pain, constituting a valid alternative to other percutaneous techniques of trigeminal rhizolysis.

Solitary osteochondroma of the pedicle of L4 causing root compression. Case report.

Osteochondroma is about 50% of benign bone neoplasms and up to 15% of all primary tumours of the skeleton; metaphysis of long bones are more frequently involved with the spine being interested in 2.5-5% of all cases, usually pertaining to multiple osteochondromatosis, in which many areas of the skeleton are affected. A solitary osteochondroma of the right pedicle of L4 causing sciatalgic pain and difficulty warling and treated by surgery is presented. Only two other cases of solitary osteochondroma involving the lumbar spine have been previously reported.

Central neurocytoma: clinico-pathological study of 5 cases and review of the literature.

Five cases of central neurocytoma, confirmed by immunohistochemical and electron microscopy studies, are reported and 127 cases from the literature are reviewed. Central neurocytomas are more frequent than previously thought, and will be diagnosed with increasing frequency in the future, if intraventricular tumors with histological aspect of oligodendroglioma or ependymoma will be routinely studied by immunohistochemistry and electron microscopy. The occurrence of an intraventricular tumor with a typical MR aspect in a young patient should suggest preoperatively the diagnosis of neurocytoma. The positivity for synaptophysin and neuron specific enolase, the negativity for neurofilament protein and glial fibrillary acid protein, and the finding of elements of neuronal differentiation on electron microscopy, are the main pathological features of these tumors. Complete removal of the tumor mass without radiotherapy is the treatment of choice. The prognosis is usually favorable without recurrence.

'De novo' aneurysm formation: report of two cases.

We report 2 cases of 'de novo' aneurysm formation in a vessel which appeared to be normal at a previous angiography. The first patient developed an anterior communicating artery aneurysm nine years after occlusion of the right internal carotid artery by Gianturco coils for the treatment of a giant intracavernous carotid aneurysm. In the second case a 'de novo' aneurysm of the internal angle A1-A2 segment of the left anterior cerebral artery developed 6 years after successful clipping of another aneurysm of the same location. De novo formation of an aneurysm in a vessel which was found to be normal in a previous angiographic study, may occur as result of hemodynamic changes, such as after internal carotid occlusion or in presence of an arteriovenous malformation or variations of the circle of Willis. However, definite hemodynamic changes may also be absent. We conclude that patients operated on for aneurysm clipping must be periodically explored by magnetic resonance angiography to evaluate the possibility of de novo appearance of another aneurysm.

Percutaneous retrogasserian glycerol rhizolysis for treatment of trigeminal neuralgia. Technique and results in 191 patients.

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.

Paramedian hourglass epidermoid cysts extending in the middle and posterior cranial fossa.

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.

CT in the diagnosis of sellar and parasellar lesions.

The Authors review their recent experience in investigating 185 cases of sellar and parasellar lesions, using as preliminary procedure stratigraphy and CT; further examinations were performed only in cases with unclear diagnosis. Their data confirm the reliability of this non-invasive protocol that allowed the detection of pathological changes in nearly 95% of cases and was able to define with certainty the nature of the lesions in over 72% of cases. However, other investigations were performed in 116 cases (63%): in 57 (31%) for diagnostic purpose, in 59 (32%) as complementary pre-operative studies.