Biomedical subjects

Giulio Maira

Publications and source records attributed to Giulio Maira.

27 records · Page 2Linked to original sources

PubMed2003

Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients.

PURPOSE: To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. METHODS: TMZ pharmacokinetic parameters were characterized in pediatric and adult patients with primary central nervous system tumors treated with doses ranging from 120 to 200 mg/m2 per day, divided into three doses daily for 5 days. Plasma levels were measured over 8 h following oral administration in a fasting state. A total of 40 courses were studied in 22 children (mean age 10 years, range 3-16 years) and in 8 adults (mean age 30 years, range 19-54 years). RESULTS: In all patients, a linear relationship was found between systemic exposure (AUC) and increasing doses of TMZ. Time to peak concentration, elimination half-life, apparent clearance and volume of distribution were not related to TMZ dose. No differences were seen among TMZ C(max), t(1/2), V(d) or CL/F in children compared with adults. Intra- and interpatient variability of systemic exposure were limited in both children and adults. No statistically significant differences were found between the AUCs of children who experienced grade 4 hematologic toxicity and children who did not. CONCLUSIONS: No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.

Administration, Oral↗

PubMed2003

Reinnervation of extraocular muscles by facial-to-oculomotor nerve anastomosis in rats: anatomic nuclear changes.

OBJECTIVE: Oculomotor nerve palsy greatly impairs the patient's daily life. After oculomotor nerve injury, when the central nerve stump is not available, neurotization of the distal nerve stump with a donor nerve may be performed. Here, we present an experimental anatomic study in rats related to the motor nuclear organization after facial-to-oculomotor nerve anastomosis. METHODS: In adult rats, the right oculomotor nerve was transected at the skull base. Then, the ipsilateral facial nerve was exposed at the stylomastoid foramen and connected side-to-end to one extremity of a peroneal nerve autograft. The other extremity of the nerve autograft was connected end-to-end to the distal stump of the transected oculomotor nerve. Twelve weeks later, axonal regeneration in the autograft and brainstem somatotopic representation of the reinnervated extraocular muscles were investigated by use of histological and retrograde axonal tracing techniques. RESULTS: The autograft was reinnervated by a large number of small axons, 1 to 5 microm in diameter. After tracer injection into the superior rectus and medial rectus muscles, retrogradely labeled neurons were seen not only in the ipsilateral facial nucleus (16%) but also in the contralateral nucleus (8%). Labeled neurons were also seen in the ipsilateral abducens (12%), motor trigeminus (7%), trochlear (23%), and contralateral trochlear (34%) nuclei. In normal rats, the extraocular muscles are innervated by unilateral-ipsilateral brainstem motor nuclei, except for the superior rectus and superior oblique muscles, which are innervated by bilateral, primarily contralateral, nuclei. CONCLUSION: The central rearrangement of the extraocular muscle nuclei after facial-to-oculomotor nerve anastomosis represents an original example of plasticity. Functional studies are needed to demonstrate whether this procedure might serve to restore some degree of eye motility.

Anastomosis, Surgical↗

PubMed2003

Chordoma of the skull base: predictors of tumor recurrence.

OBJECT: Chordomas of the skull base are generally regarded as slow-growing tumors; however, approximately 20% of these lesions have been shown to recur as early as 1 year postsurgery. The classic pathological paradigms are poor predictors of outcome, and additional markers are needed to identify patients at risk for early tumor recurrence. In this study the authors describe such a marker. METHODS: In a series of 26 patients with chordomas of the skull base, the authors investigated the relationship between the biological behavior of the tumor, which was determined according to the interval for its recurrence and volume doubling time, and several pathological and molecular features, which included the histological variant, proliferative activity, mutation of p53 protein, expression of human telomerase reverse transcriptase (hTERT) messenger (m)RNA, loss of heterozygosity (LOH), and microsatellite instability. The major finding in this study was that hTERT mRNA expression in chordoma cells identifies those tumors that exhibit unusually fast rates of growth. The expression of hTERT mRNA was frequently associated with mutation of p53 protein, indicating that telomerase dysfunction combines with abnormal p53 function to initiate the unrestrained clonal expansion of the tumor cells. In cases in which the tumor was partially removed, mutation of p53 protein and expression of hTERT mRNA predicted increased doubling time for residual tumor as well as the probability of tumor recurrence. Cell proliferation, as investigated using the Ki-67 method, was significantly related to the tumor doubling time; however, the authors found that the pattern of cell proliferation was not homogeneous throughout the chordoma tissue, and that the proliferative index might change by a factor as high as 8 among different regions of the same tumor. The LOH and microsatellite instability do not seem to affect the prognosis of skull base chordomas. CONCLUSIONS: Reactivation of telomerase in chordomas is a reliable predictor of outcome. The ability to predict the biological behavior of chordomas might have immediate implications in the management of this disease in patients who undergo surgery.

Adult↗

PubMed2003

Magnetic resonance imaging of intramedullary spinal cord schwannomas. Report of two cases and review of the literature.

Intramedullary spinal cord schwannomas are rare benign tumors for which resection is possible and safe. The purpose of this paper is to present the magnetic resonance (MR) imaging features in two cases of intramedullary spinal cord schwannoma to assist both neurosurgeons and pathologists in preventing misdiagnosis and resultant partial resection. The MR imaging evidence of a small- or medium-sized well-marginated intramedullary spinal cord tumor in a patient in whom no syringomyelia is present but in whom moderate edema with marked Gd enhancement can be seen shouldbe considered in the differential diagnosis of intramedullary spinal cord schwannoma. In cases in which an associated thickened Gd-enhancing spinal nerve root is seen the diagnosis of schwannoma should be assumed.

Female↗

PubMed2002

Anterior pituitary adenomas in patients aged more than 65 years: analysis of growth fraction (using the MIB-1 monoclonal antibody) and of clinical features in comparison to younger patients.

AIMS AND BACKGROUND: The incidence of pituitary adenomas (PA). in patients aged more than 65 years is relatively low. The goal of this study was to evaluate the growth fraction and the clinical features of PA affecting old patients and to compare the results to those of younger subjects. METHODS: We evaluated the Ki-67 LI using the monoclonal antibody MIB-1 in 21 patients of more than 65 years of age affected by PA consecutively operated on and compared the mean LI with that one of 104 patients under 65 operated on in the same period. The clinical behavior of PA was also analyzed in both groups. RESULTS: In older cases PA occurred more frequently with visual disturbances: 17 out of 21 (80.9%) older patients showed pre-operative visual disturbances, versus 43 out of 104 (41.3%) younger patients (P=0.0009). Fifteen out of 21 (71.4%) older patients had a non-functioning PA, versus 38 out of 66 (36.5%) younger patients (P=0.003). In relation to surgically verified infiltration of sellar floor dura and bone, we identified non-invasive (12/21 older cases) and invasive (9 cases) adenomas; the wall of the cavernous sinus was infiltrated in 5 cases. The overall mean Ki-67 LI was 4.06+/-6.73 versus 2.35+/-2.54% of younger patients (P=0.04). CONCLUSIONS: Our data confirm that Ki-67 LI detected by the MIB-1 monoclonal antibody is a useful marker in the determination of the growth fraction of PA. In relation to our preliminary results, PA in the elderly seem to have a higher growth fraction than in younger patients, are more often non-functioning and occur frequently with visual disturbances. In order to confirm our data further larger studies are necessary.

Adenoma↗

PubMed2002

Neurosurgery at the Catholic University in Rome.

Neurosurgery at the Catholic University in Rome was initiated by Gian Franco Rossi in 1969 and has gradually expanded since then. From the beginning, research has been regarded as an essential part of training and daily activities in the university's neurosurgery programs. The professional and research education of all faculty members includes at least 1 year abroad in a reputable neurosurgical center. Subspecialization is encouraged. Today, the faculty is composed of 3 full professors, 4 associate professors, and 16 assistant professors. The university's neurosurgery programs include the Institute of Neurosurgery, the residency program, and the following clinical units: a Division of General Neurosurgery; three subspecialty sections comprising Neurotraumatology, Pediatric Neurosurgery, and Functional and Spine Surgery; a day hospital; and dedicated laboratories. More than 1700 surgical patients are treated annually. Epilepsy, pain management, parkinsonism, spinal cord and vertebral pathologies, clinical and basic neuro-oncology, cerebrospinal fluid and intracranial pressure dynamics, cerebrovascular disease, neurotrauma, developmental malformations, and peripheral and central nervous system neuroregeneration are the main fields of clinical and research activities. The results of the research performed thus far at the Catholic University in Rome have been reported in more than 900 publications, most of which have appeared in prominent journals and books. Members of the faculty are involved in relevant editorial activities and serve as officers of national and international scientific and professional societies. In 1999, Giulio Maira succeeded Dr. Rossi in directing the Institute of Neurosurgery and the Division of General Neurosurgery. In addition to the history of neurosurgery at the Catholic University in Rome, this article describes present challenges and plans for the future in neurosurgery at the university.

Christianity↗

PubMed2002

Surgical treatment of primary supratentorial intracerebral hemorrhage in stuporous and comatose patients.

Primary supratentorial intracerebral hemorrhage can be considered as one of the most devastating forms of cerebrovascular disease. Reduction in intracranial volume buffering capacity and severe intracranial pressure are the most important factors related to a poor prognosis in cases with huge hematoma and altered state of consciousness. The role of surgery in the management of such cases appears still controversial. Nevertheless, it is conceivable that some cases with poor natural outcome might benefit from surgical evacuation. Fifty patients with altered state of consciousness and primary supratentorial intracerebral hemorrhage ranging from 24 to 75 ml were submitted to surgical evacuation of the hematoma. The decision to operate was based on the presence of signs indicating an oncoming severe intracranial hypertension. In 15 patients, in whom a progression in brain swelling was expected to occur after the hematoma evacuation, a decompressive craniectomy, associated with dural enlargement, was performed after the initial surgical procedure. The overall analysis of the clinical results at one year after surgery showed 40% of complete recovery and 38% of improvement. A significant statistical correlation was found between outcome and pre-operative neurological status. The association of decompressive craniectomy and dural enlargement to hematoma evacuation, proved very useful in a group of severely compromised patients. Surgical treatment of patients with primary supratentorial intracerebral hemorrhage and altered state of consciousness can have a positive role, in selected cases, by minimizing the life-threatening progression of intracranial hypertension.

Adolescent↗

PubMed2002

Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor.

OBJECT: After spinal cord transection in adult rats, the axons of the corticospinal tract (CST) degenerate retrogradely and do not regenerate. This phenomenon is thought to be related to either secondary ischemia or deficiency of growth factors. To overcome the deficiency of both blood flow and growth factors, the authors added exogenous vascular endothelial growth factor (VEGF165) to the transected spinal cord either as recombinant protein alone or combined with an adenovirus coding for VEGF165. Because most growth factors are rapidly inactivated in the extracellular environment, the authors used an adenovirus coding for VEGF165 to maintain its activity for several days. METHODS: In adult rats, the dorsal two thirds of the spinal cord were transected at the T-8 level. In experimental rats, either human recombinant VEGF165 or a combination of this factor and a replication-defective adenovirus coding for VEGF165 (Ad.CMV.VEGF165) was applied at the lesion site. Both recombinant VEGF165 alone and combined with Ad.CMV.VEGF165 were mixed with Matrigel, which is a reconstituted membrane basement protein extract. Control rats received Matrigel alone or Matrigel plus an adenoviral vector containing the LACZ gene (Ad.CMV.LACZ). Thirty days after spinal cord injury, the number of newly formed blood vessels was assessed in the injured area. In addition, the sensorimotor cortex was injected with anterogradely transported horseradish peroxidase (HRP) to label the CST axons in the spinal cord and to evaluate the extent of retrograde axonal degeneration and regeneration. Gene transfer was assessed using semiquantitative reverse transcription-polymerase chain reaction analysis, enzyme-linked immunosorbent assay for human VEGF and beta-galactosidase expression in injured rats treated with Matrigel plus Ad.CMV.LACZ, Matrigel plus Ad.CMV.VEGF165, and untreated injured rats. A strong gene transfer in the spinal cord tissue of adenovirus-treated rats was found from Day 3 to Day 10 postinjury, confirming infection. In the injured spinal cord area, a significant increase of blood vessels (300% over control, p < 0.005) occurred both in rats treated with recombinant VEGF165 alone and in those treated with the combination of recombinant VEGF165 and Ad.CMV.VEGF165. Also, in both of these groups of animals the retrograde degeneration of CST axons was significantly reduced compared with rats treated with Matrigel alone or Matrigel plus Ad.CMV.LACZ. Furthermore, in rats treated with recombinant VEGF165 alone or combined with Ad.CMV.VEGF165, a few HRP-labeled CST axons, which were not detectable in control rats, were seen distal to the spinal cord injury, indicating some regeneration across the injured area. CONCLUSIONS: These results indicate that locally applied VEGF exerts angiogenic as well as neurotrophic effects in the injured spinal cord of rats.

Adenoviridae↗

PubMedDate not supplied

Treatment of intracranial aneurysms.

The management of intracranial aneurysms (IAs) remarkably improved due to the development of diagnostic and surgical procedures. Subarachnoid hemorrhage (SAH) from IA rupture constitutes a devastating event, whose prognosis remains unsatisfactory. At present, several researchs are targeted to individuate subjects harboring unruptured IAs and those presenting a higher risk for rupture. Numerous risk factors for the rupture of lAs have been individuated. The prevalence of intracranial saccular aneurysms in the general population is estimated from 0.2% to 6.8%, with an incidence of SAH at 10/100,000/year. The most relevant morbidity and mortality rates after SAH are related to rebleeding and vasospasm. The primary therapeutic target consists in prevention of rebleeding. At present, therapeutic opportunities for intracranial aneurysms are microsurgery and endovascular treatment.

Humans↗