A cellular and molecular basis for the selective desmopressin-induced ACTH release in Cushing disease patients: key role of AVPR1b receptor and potential therapeutic implications.

CONTEXT: Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. OBJECTIVE: The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD. DESIGN: A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests was assessed. RESULTS: Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas. CONCLUSIONS: The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

Experience with coflex interspinous implant.

A first generation of Coflex implant for non-rigid stabilization of lumbar spine was presented by Samani (Study of a semi-rigid interspinous U fixation system. Spinal Surgery, Child Orthopaedics: 1707, 2000).We started to treat patients with this Coflex device in 2004 and since then more than 600 patients have been operated in our Neurosurgical Department. We are reporting 156 patients treated between December 2004 and 2006 with complete follow-up. The clinical trials of this and other implants provide evidence that this interspinous non-rigid stabilization is useful against low-back pain due to degenerative instability and without serious complications.

[Solitary fibrous tumors of the meninges: report of three cases and literature review]. / Tumor fibroso solitario meníngeo: descripción de tres casos y revisión de la literatura.

We report 3 patients with fibrous solitary tumor of meningeal location where we described the histological study, as well as evolution after the surgical treatment. The described patients presented ages of 37, 52 and 65 years, after the resection has not appeared an objective sign of recurrence in any case after 4, 6 and 7 years of follow-up respectively. Checking the literature the tumor is indistinguishable clinical and radiolocally of the typical meningioma, doing necessary the use of inmunohistochemistry to do the differential diagnosis, where positiveness for CD34 and the negativeness for EMA define the fibrous solitary tumor. It is about a benign tumor, where total removing is the principal factor in prognosis, nevertheless there are cases of local recurrences and long-distance metastasis. We can find all these characteristics in the showed cases of the present article, having the uncertainty of its local or systemic relapse ability in the future.

[Protective effects of the growth hormone (GH) on the irradiated spinal cord in rats]. / Radioprotección de la médula espinal mediante la hormona de crecimiento (GH). Estudio experimental en ratas.

Radiotherapy or irradiation of SNC AVM's or tumors also presents a high risk for provoking lesions in adjacent surrounding tissue. The objective of our study is to demonstrate radiotherapy induced alterations in a rat spinal cord model and evaluate the protective effect of Growth Hormone (GH) on rats exposed to high radiotherapy doses. The experimental study employed two groups of Wistar rats: Group A (control group):10 rats, which received 30 Gy at the spinal cord . Group B: 10 rats, these animals received 30 Gy and dose of 2mg/kg/day GH. Growth hormone administration was begun three days before radiotherapy and continued until two days after radiotherapy for a total of six days. At 14 days postradiotherapy, all the rats were sacrificed and the spinal cord extracted immediately. Hematoxyline-eosine histologic studies showed that control animals only exposed to radiotherapy had severe alterations with hemorrhage and vacuolisation of the entire irradiated segment while these alterations were much less severe in the GH-treated group. In conclusion, 30 Gy irradiation produced morphological changes including vascular endothelial oedema, necrosis, hemorrhage, and inflammatory exudates. A 2 mg/kg/day dose of GH protected the rat spinal cord against the noxious effects of the radiotherapy, decreasing the clinical, macro and microscopic damage in the treated animals.

[Causes of reoperations in patients with lumbar spinal stenosis treated with instrumentations]. / Causas de reintervención quirúrgica en pacientes con fijación lumbar intervenidospor estenosis de canal.

OBJECTIVE: In present study we analyze the causes leading to reoperation patients treated for lumbar spinal stenosis with laminectomy and lumbar instrumentation. MATERIAL AND METHODS: 74 patients operated between January of 1996 and December of 2000 with a minimum 4 year follow-up were seleted for the study. RESULTS: 16 patients (21.1%) underwent a new surgical intervention. The main cause for reoperation was stenosis of the adjacent level superiorly to the instrumentation (in 50%). Other causes were radicular fibrosis, persistence of stenosis after the surgery, neuropatic pain, failure of the instrumentation system, transpedicular screws misplacement and break of screws. CONCLUSIONS: Complications related with the initial surgical procedure are low, as half of the reoperations were due to stenosis of the segment superior to the fixation.

[Intramedullary spinal cord metastasis as the first manifestation of a renal carcinoma]. / Mestástasis intramedular como primera manifestación de un carcinoma renal

We present the case of a 69 year-old male without known antecedente who presented a clinical loss of distal force in his lower limbs during the last two months. Magnetic resonance imaging (MRI) showed an intramedullary spinal cord mass at the level of the medullaris cone. The patient was operated on; the histological diagnosis was clear cells carcinoma suggestive of metastasis from an unsuspected renal tumor that was later confirmed with an abdominal CT. When the patient's state is good, surgery can correct the neurological deficit produced by an intramedullary spinal cord lesion. The neurological state of our patient improved after the intervention, and 14 months after surgery, he has no neurological deficit in the lower limbs.