Search PubMed⌕ Search

Biomedical subjects

G Maira

Publications and source records attributed to G Maira.

At least 37 records · Page 2Linked to original sources

In situ detection of telomerase catalytic subunit mRNA in glioblastoma multiforme.

Activation of telomerase may allow unlimited cell proliferation and immortalization. One of the telomerase protein subunits has a reverse transcriptase (hTERT) activity that is essential for telomerase function and regulation. In human gliomas, telomerase is frequently associated with malignant tumor progression. In our study, we investigated the expression of hTERT at the cellular level in 34 primary de novo glioblastoma multiforme (GBM) by in situ hybridization (ISH). The expression of hTERT in tumor tissue was also assessed by RT-PCR. In addition, telomerase activity measured by telomeric repeat amplification protocol (TRAP) and telomere length polymorphism assayed by telomere restriction fragment (TRF) Southern blot were investigated. We found that all GBM, including those with negative TRAP reaction, contained abundant amounts of cytoplasmic hTERT mRNA. Interestingly, the ISH analysis revealed that the hTERT mRNA was homogeneously expressed by the whole tumor cell population in about 60% of the GBM. In the remaining cases, hTERT was absent in subsets of tumor cells. TRF analysis, which shows that both TRAP-positive and TRAP-negative de novo GBM have elongated telomeres, further supports that telomerase activity is present in all de novo GBM. Correlations with tumor size and extent of necrosis suggest that hTERT reactivation is an early event in GBM development and that telomerase activity may be lost in subpopulations of neoplastic cells during tumor progression. Finally, ISH analysis of hTERT mRNA seems to provide a prognostic parameter for primary de novo GBM.

Adult↗

Regression after biopsy of a pilocytic opticochiasmatic astrocytoma in a young adult without neurofibromatosis.

Serial MRI over 60 months demonstrated regression after biopsy of a pilocytic opticochiasmatic astrocytoma in a 20-year-old woman with no signs of neurofibromatosis, together with improvement in vision. The patient did not receive radio- or chemotherapy. Close MRI follow-up of optic gliomas is recommended. Aggressive treatment should be limited to cases with clear clinical and radiological progression.

Adult↗

Craniopharyngiomas of the third ventricle: trans-lamina terminalis approach.

OBJECTIVE: Craniopharyngiomas usually grow on the cisternal surface of the hypothalamic region; these tumors can also grow from the infundibulum or tuber cinereum on the floor of the third ventricle, developing exclusively into the third ventricle. The aim of the present work was to establish the usefulness of the pterional trans-lamina terminalis approach for the removal of these tumors. METHODS: Eight patients who were surgically treated for craniopharyngiomas located exclusively within the third ventricle were considered. The initial symptoms were acute hydrocephalus in two cases, psychological disturbances in two, amenorrhea in two, headaches in one, and hypopituitarism in one. The diagnoses were established, in all cases except one, with magnetic resonance imaging. In all cases, the tumor completely filled the third ventricle. RESULTS: Total removal of the lesion was achieved in seven cases. One patient underwent partial removal. In the immediate postoperative period, no major complications were observed. Five patients required replacement hormonal therapy. All patients returned to a normal life. Many months after surgery, two patients exhibited psychological disturbances and died, the first because of voluntary withdrawal of replacement therapy (12 mo after surgery) and the second because of a severe imbalance in body fluids and electrolytes, with a subsequent hyperosmolar coma (27 mo after surgery). Only one patient who underwent initial total removal experienced a small recurrence of the lesion (30 mo after surgery); after 3 years, the lesion exhibited unchanged size. CONCLUSION: In our experience, the trans-lamina terminalis approach is a valid choice for the removal of purely intraventricular craniopharyngiomas. These tumors can be removed without significant sequelae related to the surgical approach. The proximity to the hypothalamus requires accurate neuroendocrine and electrolyte control in the postoperative period, in some cases even years after surgery.

Adolescent↗

Conus medullaris hematomyelia associated with an intradural-extramedullary cavernous angioma.

A unique case of a 50-year-old woman with a conus medullaris hematomyelia associated with a low thoracic intradural-extramedullary cavernous angioma localized 2 cm above is reported. The patient had a 2-month history of progressive paraparesis, hypoesthesia of legs, and bowel and bladder disturbances. The symptoms worsened acutely during the last days before admission. A thoraco-lumbar MRI showed a space-occupying lesion at T10-T11 (vertebral interspace associated with a hematomyelia localized about 2 cm below. A T10-L1 laminectomy was performed and complete removal of both lesions was obtained with microsurgical technique. A non-traumatic hematomyelia should always prompt the suspicion of a spinal AVM or, more rarely, of a cavernous angioma. The possible anatomical and clinical correlations of this unusual association are discussed.

Dura Mater↗

Molecular and neurochemical evaluation of the effects of etizolam on GABAA receptors under normal and stress conditions.

The thienobenzodiazepine derivative etizolam (CAS 40054-69-1, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo-(3,4-c)thienol(1 ,4) diazepine) is a potent anxiolytic with a pharmacological profile similar to that of classical benzodiazepines. In order to rationalize the therapeutic use of etizolam, its pharmacodynamics properties on GABAA receptors were investigated by a comparative study with other ligands on human recombinant GABAA as well as rat brain native receptors. Etizolam inhibited in a concentration-dependent manner [3H]flunitrazepam (CAS 1622-62-4) binding to rat cortical membranes, with an affinity of 4.5 nmol/l greater than that of alprazolam (CAS 28981-97-7) (7.9 nmol/l). Ethizolam enhanced GABA-induced Cl- currents in oocytes expressing human cloned GABAA receptors. With alpha 1 beta 2 gamma 2S subunit combination, etizolam produced a 73% increase in GABA-induced currents with an EC50 of 92 nmol/l. At the same receptor type, alprazolam showed a higher degree of potentiation and potency (98%, EC50 56 nmol/l). At alpha 2 beta 2 gamma 2S or alpha 3 beta 2 gamma 2S subunit constructs, the effects of etizolam were similar to those of alprazolam. Flumazenil (CAS 78755-81-4) completely blocked both etizolam and alprazolam effects on GABA-induced currents. Etizolam, administered i.p., was uneffective in changing ex vivo t-[35S]butylbicyclophosphorothionate ([35S]-TBPS) binding to rat cerebral cortex, whereas alprazolam and abecarnil (CAS 111841-85-1) significantly reduced this parameter. However, etizolam similarly to abecarnil and alprazolam, antagonized isoniazid-induced increase (61%) in [35S]-TBPS binding to rat cortical membranes. Further, etizolam inhibited in a dose-dependent manner basal acetylcholine release from both hippocampus and prefrontal cortex, and reversed foot-shock-induced increase of basal acetylcholine release to a control level. Altogether, these results suggest that etizolam may have a reduced intrinsic activity, at least at specific subpopulations of GABAA receptors. This property, together with the pharmacokinetic indication of a short-acting drug, may characterize etizolam as a ligand endowed with less side-effects typical of full agonits such as diazepam (CAS 439-14-5) and alprazolam. Finally, given its marked efficacy under conditions of GABAergic deficit, etizolam may represent a possible drug of choice with reduced liability to produce tolerance and dependence after long-term treatment of anxiety and stress syndromes.

Acetylcholine↗

Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody.

AIMS: To investigate the relation between proliferative activity of anterior pituitary adenomas, quantified by the Ki-67 labelling index, and their invasive behaviour. METHODS: Expression of Ki-67 was evaluated in 103 anterior pituitary adenomas consecutively operated on in a 36 month period and correlated with surgical evidence of invasiveness. RESULTS: Non-invasive (n = 65) and invasive (n = 38) adenomas were identified from surgically verified infiltration of sellar floor dura and bone. The wall of the cavernous sinus was infiltrated in 16 cases. Forty one adenomas were non-functioning and 62 functioning (24 prolactin, 21 growth hormone, 10 ACTH, seven mixed). The overall mean (SD) Ki-67 labelling index was 2.64 (3.69) per cent (median 1.5). The mean index was 3.08 (4.59) per cent in functioning and 1.97 (1.78) per cent in non-functioning tumours; 5.47 (9.52) per cent in ACTH adenomas and 2.33 (2.42) per cent in others (p = 0.01); 3.71 (5.17) per cent in invasive and 2.01 (2.45) per cent in non-invasive adenomas (p = 0.027); and 5.58 (7.24) per cent in cavernous sinus infiltrating v 2.10 (2.39) per cent in cavernous sinus non-infiltrating adenomas (p = 0.0005). To identify a value of labelling index beyond which adenomas should be considered invasive and another beyond which cavernous sinus infiltration should be suspected, normality Q-Q plots were obtained: a threshold labelling index of 3.5% for invasive adenomas and of 5% for cavernous sinus infiltrating adenomas was defined, with statistically significant differences (p = 0.02 and p = 0.004, respectively). CONCLUSIONS: The Ki-67 labelling index can be considered a useful marker in determining the invasive behaviour of anterior pituitary adenomas.

Adenoma↗

Antagonism by abecarnil of enhanced acetylcholine release in the rat brain during anticipation but not consumption of food.

Changes in the extracellular concentration of acetylcholine (ACh) were evaluated in the prefrontal cortex and hippocampus of freely moving rats habituated for 35 days to consume their daily meal during a fixed 2-h period. During the 40 min immediately before presentation, ACh output increased by 49 and 55% in the prefrontal cortex and hippocampus, respectively. ACh release increased further during the first 40 min of consumption phase in the prefrontal cortex (+220%) and hippocampus (175%). Administration of abecarnil (0.1 mg/kg, IP) 40 min before food presentation prevented the increase in ACh output in both brain regions during the anticipatory phase. In contrast, although abecarnil reduced the ACh content achieved during the consummatory phase, it did not prevent the increase in ACh release in the prefrontal cortex or hippocampus induced by food intake. Finally, the binding of [35S]TPBS to cerebral cortex, hippocampus, or septum of rats killed 20 min before food presentation was significantly higher than the values for animals killed 2 h after food presentation. These results suggest that during ingestive behavior ACh release is regulated by at least two independent mechanisms: one, associated with the anticipatory phase, that is sensitive to the activation of GABA(A) receptors. and a second, associated with the consummatory phase, that is insensitive to abecarnil.

Acetylcholine↗

Intraneural capillary hemangioma of the cauda equina.

A case of intraneural capillary hemangioma involving the dorsal root of a spinal nerve of the cauda equina is reported. The patient was a 41-year-old man with a 3-month history of intermittent left lumbosciatalgia. MRI and CT myelography showed a space-occupying mass at the level of the cauda equina. Laminectomy of L5 and complete removal of the lesion were performed without neurological problems. The clinical, diagnostic, and therapeutic aspects of hemangiomas of the cauda equina are analyzed.

Adult↗

Management of complex craniofacial traumas.

We report our experience in the treatment of cranio-facial traumas. The collaboration between neurosurgeons and maxillofacial surgeons is highlighted as well as the importance of the combined approaches, the use of Rigid Internal Fixations and bone grafting techniques in the immediate treatment of complex craniofacial fractures.

Bone Transplantation↗

Cervical spontaneous epidural hematoma as a complication of non-Hodgkin's lymphoma.

Epidural hematoma is a rare cause of spinal cord compression, which usually provokes severe neurological deficits. It is presumed to originate from venous or, more probably, arterial bleeding. Thrombocytopenia and other disorders of coagulation may precipitate the onset of epidural hematoma and facilitate the evolution of the disease. We report the case of a patient suffering from a non-Hodgkin's lymphoma with severe thrombocytopenia during a MACOP-B schedule, who presented with a spontaneous cervical epidural hematoma. We discuss the etiopathological aspects, diagnosis, and treatment of this rare cause of acute cervical spinal cord compression.

Antineoplastic Combined Chemotherapy Protocols↗

Surgical treatment of clival chordomas: the transsphenoidal approach revisited.

This is a report of 12 cases of clival chordomas that were surgically treated at the Catholic University Medical School, Rome, Italy, over a 7-year period. The study emphasizes the role of the transsphenoidal approach. The study group included seven men and five women whose ages ranged from 26 to 80 years (mean 49.8 years). Diplopia was the most common presenting symptom (eight cases). The tumor involved the upper and middle clivus in five cases, the middle clivus in five, and the lower clivus in two cases. One patient developed spinal metastasis. On histological examination, eight cases proved to be typical chordomas, three cases had a chondroid component, and one case of chordoma had atypical features. Immunohistological staining for vimentin and epithelial membrane antigen was positive in all cases. Follow-up periods ranged from 14 to 86 months (mean 40.2 months). The primary treatment consisted of surgery. Ten patients with chordomas of the upper and middle clivus underwent a total of 13 transsphenoidal procedures. Total tumor removal was achieved in seven cases, subtotal removal in two, and partial removal in one case. In the two cases of lower clival chordomas, total removal was accomplished in one and partial removal in the other. After total removal, no recurrence was noted at 14 to 86 months (mean 37.5 months). In the cases undergoing operation via a transsphenoidal approach, there was zero morbidity and one cerebrospinal fluid fistula that resolved without surgery. The tumor recurred in two patients after subtotal and partial removal, respectively. The authors opted to reoperate in cases of recurrence. Postoperative radiotherapy was administered in only two cases in which further surgery was not indicated because of medical reasons or because such a procedure was contrary to the patient's wishes. When mortality and morbidity rates of this group are compared to those of chordoma patients who were treated with extensive skull-base surgery, the results prompt a reappraisal of the transsphenoidal approach in the treatment of clival chordomas.

Adult↗

Enhancement of acetylcholine release by flumazenil in the hippocampus of rats chronically treated with diazepam but not with imidazenil or abecarnil.

The effects of long-term treatment (three times a day for 3 weeks) with pharmacologically active doses of the novel anxiolytics and anticovulsants abecarnil (0.5 mg/kg, IP) and imidazenil (0.5 mg/kg, IP) on basal hippocampal acetylcholine release in freely moving rats were compared with those of diazepam (3 mg/kg, IP). Challenge doses of diazepam, abecarnil, and imidazenil decreased the extracellular acetyl-choline concentration in the hippocampus by the same extent in animals chronically treated with the respective drug or vehicle. Moreover, the abrupt discontinuation of long-term treatment with diazepam, abecarnil, or imidazenil failed to affect hippocampal acetylcholine release during the first 5 days of withdrawal. In contrast, the acute administration of the benzodiazepine receptor antagonist flumazenil (1 mg/kg, IP) 2 days after diazepam withdrawal elicited a marked increase (65%) in acetylcholine release in the hippocampus. Flumazenil failed to induce the same effect 5 days after diazepam withdrawal or 2 or 5 days after discontinuation of long-term treatment with abecarnil or imidazenil. These results indicate that (i) the inhibitory effects of full (diazepam), partial (imidazenil), and selective (abecarnil) benzodiazepine receptor agonists on acetylcholine output in rat hippocampus are not affected by repeated drug administration; (ii) discontinuation of long-term treatment with each type of agonist does not affect hippocampal cholinergic mechanisms; and (iii) flumazenil increases acetylcholine release only in the hippocampus of rats chronically treated with diazepam. Together, these data further differentiate the pharmacology of benzodiazepine receptor full agonists from that of partial and selective agonists.

Acetylcholine↗

GH response to oral and intravenous glucose load in acromegalic patients.

The lack of inhibition of Growth Hormone (GH) levels after glucose load is considered a marker of inappropriate GH secretion in acromegaly. In order to investigate the physiopathology of this phenomenon, we have studied the GH variations after an oral glucose load (0.75 g/kg BW per os, OGTT) or intravenous glucose bolus (25 g i.v., IVGTT), in a group of 12 acromegalic patients, aged 20 +/- 69 yr (mean 48), 5 males and 7 females, with basal GH levels ranging from 11 to 76.2 ng/ml. The results indicate that only a group of acromegalic patients (group 1) had a partial GH inhibition after OGTT (mean decrease: 56.4 +/- 4.2%), but in no patients GH levels were influenced by intravenous administration of glucose. It is possible that in group 1 patients, the gastroenteric response could partially influence the GH secretion by the pituitary tumor, probably due to an increased peripheral somatostatin release. The dissociation of the GH response to OGTT and IVTT could indicate a supersensitivity to peripheral somatostatin, related to a deficiency in central somatostatinergic tone and therefore represent a more unfavourable prognostic sign.

Acromegaly↗

Surgical treatment of craniopharyngiomas: an evaluation of the transsphenoidal and pterional approaches.

Fifty-seven patients with craniopharyngiomas underwent a total of 64 operations. Their clinical follow-up ranged from 2.5 to 15.5 years, with a mean follow-up of 6.5 years. A transsphenoidal approach was used in 35 patients (61%), whereas 22 (39%) were operated on using a pterional approach (in 16 patients, the tumor was found in the suprasellar cisterns, and in 6, the tumor was found in the third ventricle and was removed passing through the lamina terminalis). Total removal of the tumor was achieved in 43 patients (75%). In six patients (11%), fragments of the capsule remained attached to the hypothalamus (subtotal removal), and, in eight patients (14%), the tumor was partially removed. No recurrence occurred in those patients in whom removal was total. Regrowth was observed in two patients (33%) in whom removal was subtotal and in two (25%) in whom removal was partial. Three of them underwent subsequent operations, and a total removal with good clinical outcome was achieved. All patients except two had good postoperative recovery. Twenty patients (35%) required hormonal replacement therapy. When transsphenoidal surgery was used, a total removal of the tumors was achieved in 23 (66%) of the patients. Good clinical outcome was seen in all 35 patients. Six patients (17%) required hormonal replacement therapy. When the pterional approach was used for tumors in the suprasellar cisterns, we achieved total removal of tumors in 15 patients (94%). Good clinical outcome was seen in 20 patients (91%). Eleven patients (50%) required hormonal replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Reevaluation of the I-dopa test in acromegaly: anatomo-clinical and prognostic correlations].

It is known that in acromegalic patients the GH secretion exhibits a pattern of response to various stimuli that differs from that observed in normal subjects. We have evaluated the paradoxical GH response to 1-Dopa in acromegaly, in order to clarify the relationships between this datum and the tumour size, the basal GH secretion, the GH response to TRH and the long-term prognosis. MATERIALS AND METHODS. 34 acromegalic patients, 12 men and 22 women, aged 35-70 yr, participated in this study. They were divided in 4 classes, according to Hardy's classification of pituitary neoplasias: (1) intrasellar microadenomas, < 10 mm (n = 8); (2) intrasellar macroadenomas, > 10 mm (n = 14); 3) adenomas with local expansion (n = 9); (4) adenomas with extrasellar expansion (n = 3). All patients underwent a 1-Dopa-test; 18 of them underwent a TRH-test. Basal postoperative GH and basal pre- and postoperative PRL levels were also determined. RESULTS. The basal preoperative GH values in all patients ranged between 16 and 278 ng/ml. 22 patients showed a paradoxical response to 1-Dopa, 12 were non-responders. The following results were observed in the different classes: [table: see text] Moreover, 10 subjects (56%) were TRH-responders (9 of them were also 1-Dopa-responders, 1 was non-responder) and 8 were TRH non responders (6 were 1-Dopa non-responders, 2 were 1-Dopa responders). Basal postoperative GH values were > 5 in 17 1-Dopa responders and in 9 non responders. Basal preoperative PRL levels were > 25 ng/ml in 7 1-Dopa responders and in 2 non responders. After surgery, basal PRL became normal in 5 responder patients. DISCUSSION. In a previous work we have correlated the paradoxical GH response to TRH with tumour size and GH levels, observing a higher percentage of paradoxical response in patients in class I and II and, postoperatively, lower GH levels in preoperative TRH responders. So, we have underlined the good prognostic feature of a preoperative paradoxical response. In this paper we have evaluated the paradoxical GH response to 1-Dopa in the different Hardy's classes and compared it with the GH levels and the GH response to TRH. The results show that a paradoxical response can be observed more frequently in small (class I) adenomas than in greater size ones, and in presence of lower GH basal levels. Moreover, a concordance between 1-Dopa and TRH tests can be observed. CONCLUSIONS. The results clearly indicate that the responses to dynamic GH tests should be evaluated considering the anatomic characteristics of the neoplasias. It could be suggested that the paradoxical response can be expressed only when hypothalamus-pituitary interactions are intact.

Acromegaly↗

A motion correction algorithm for an image realignment programme useful for sequential radionuclide renography.

The correction of organ movements in sequential radionuclide renography was done using an iterative algorithm that, by means of a set of rectangular regions of interest (ROIs), did not require any anatomical marker or manual elaboration of frames. The realignment programme here proposed is quite independent of the spatial and temporal distribution of activity and analyses the rotational movement in a simplified but reliable way. The position of the object inside a frame is evaluated by choosing the best ROI in a set of ROIs shifted 1 pixel around the central one. Statistical tests have to be ful-filled by the algorithm in order to activate the realignment procedure. Validation of the algorithm was done for different acquisition set-ups and organ movements. Results, summarized in Table 1, show that in about 90% of the simulated experiments the algorithm is able to correct the movements of the object with a maximum error less or equal to 1 pixel limit. The usefulness of the realignment programme was demonstrated with sequential radionuclide renography as a typical clinical application. The algorithm-corrected curves of a 1-year-old patient were completely different from those obtained without a motion correction procedure. The algorithm may be applicable also to other types of scintigraphic examinations, besides functional imaging in which the realignment of frames of the dynamic sequence was an intrinsic demand.

Algorithms↗

[Evaluation of the thyroid function in healthy aged patients residing in 2 geriatric institutions].

Thyroid function assessment in elderly inpatients. It is not well known whether normal ageing might lead to an impairment of thyroid function. We evaluated 297 elderly inmates in two geriatric institutions. After having excluded from the study those who were affected by chronic hepatic or renal disease, were under pharmacologic treatment or had suffered from acute ailments during the previous two months, we assessed thyroid function by determining circulating T4, T3, rT3, FT4, FT3 and TSH in 130 apparently healthy subjects. They could be divided into three groups composed of patients mentally competent, affected by either vascular or senile dementia, or affected by chronic psychosis. Results were also assessed with reference to three different age ranges (65-74, 75-84 and over 85 years). Two patients had subnormal thyroid hormone levels with elevated basal thyrotropin, while other two demonstrated only elevated thyrotropin levels, qualifying respectively for a diagnosis of primary hypothyroidism and subclinical hypothyroidism. In the remaining 126 patients thyroid function was normal, and no differences in thyroid hormone levels could be noticed among the various groups of patients, divided for sex, age range and mental condition. The results of our study confirm the presence of a high percentage of subclinical thyroid dysfunction in old age. They also suggest that in healthy aged subjects thyroid function parameters are not significantly different in reference to sex, age range and mental condition.

Age Factors↗