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Biomedical subjects

A Alfieri

Publications and source records attributed to A Alfieri.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors.

Atm, the gene mutated in ataxia-telangiectasia (AT) patients, is an essential component of the signal transduction pathway that responds to DNA damage due to ionizing radiation (IR). We attenuated ATM protein expression in human glioblastoma cells by expressing antisense RNA to a functional domain of the atm gene. While ATM expression decreased, constitutive expression of p53 and p21 increased. Irradiated ATM-attenuated cells failed to induce p53, demonstrated radioresistant DNA synthesis, and increased radiosensitivity. Antisense-ATM gene therapy in conjunction with radiation therapy may provide a novel strategy for the treatment of cancer.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2000

Endoscopic endonasal transsphenoidal surgery in recurrent and residual pituitary adenomas: technical note.

Despite a good cure rate after surgery, the recurrence rate in pituitary adenomas is globally high. The decision making in such cases can be problematic for the nature of the lesion, for the anatomic structures involved, for the different pharmacological, surgical, radiotherapeutic and radiosurgical options nowadays available. In the perspective of an improvement and refinement of the surgical procedure an endoscopic endonasal transsphenoidal approach to the pituitary was recently adopted in the Neurosurgical Department of the University of Naples. Its minimal invasiveness and its wider and direct anatomic control of the operative field has allowed a faster, greater and safer potential of tumour excision, with respect of the sphenoid, sellar and parasellar structures. The authors have examined the advantages provided by this technique in 12 patients with recurrent pituitary adenomas and in 2 craniopharyngiomas already treated via a transnasal transsphenoidal approach (TTA), where the anatomy of surgical field had been distorted by the first operation or the radiation therapy. They conclude that the endoscopic transsphenoidal re-operation might be considered the procedure of choice in case of recurrences and its easiness in such conditions could favour its larger use, before other more aggressive therapeutic solutions.

Adenoma↗
PubMed2000

Endoscopic transsphenoidal pituitary surgery: various surgical techniques and recommended steps for procedural transition.

Various techniques in pituitary endoscopy are reviewed in the attempt to assemble the transitional steps necessary to take a neurosurgeon from traditional microscopic transsphenoidal surgery to endoscopic endonasal pituitary surgery. The senior author's (HDJ) experiences of endonasal endoscopy in more than 200 operations as well as the reports in the literature on pituitary endoscopy are reviewed. Two distinct advantages that an endoscope has over an operating microscope are its ability to visualize through a narrow surgical corridor and its ability to provide angled, close-up views. An endoscope can be used to assist the operating microscope (endoscope-assisted microsurgery). Endoscopy can also be used for endonasal retractor placement when microscopic surgery is preferred (endoscopic sphenoidotomy). When endonasal endoscopy is chosen, the surgical approach can be made with a deep-transseptal, a paraseptal, a middle turbinectomy or a middle meatal approach (endonasal transsphenoidal endoscopy). Endonasal endoscopy can be performed via either one or two nostrils. Working-channel endoscopy can be performed for restricted purposes. When a neurosurgeon desires to adopt endoscopy into pituitary surgery, the author recommends endoscope-assisted microsurgery as the first step followed by endoscopic sphenoidotomy as a combined effort between an endoscopic rhinologist and the neurosurgeon as the next step leading finally to endonasal pituitary endoscopy. Various methods of transsphenoidal endoscopy and the authors' recommendations for transitional steps are reported based on the authors' personal experience and literature review.

Acromegaly↗
PubMed2000

Cell lines from the same cervical carcinoma but with different radiosensitivities exhibit different cDNA microarray patterns of gene expression.

Combining chemotherapy with radiotherapy has improved the cure rate among patients with cancers of the cervix. Although one-half to two-thirds of the patients can be cured by radiation alone, such patients cannot be identified at present and must therefore suffer the burden of chemotherapy. Our long-range goal is to identify those cervical cancers that are radiosensitive and could be cured by radiotherapy alone. The advent of methods that permit the simultaneous analysis of expression patterns of thousands of genes, make it feasible to attempt to identify the molecular events related to radiosensitivity and the associated regulatory pathways. We hypothesize that the sensitivity of tumor cells to ionizing radiation (IR) is determined by the level of expression of specific genes that may be identified with the aid of cDNA microarrays. As the first step in testing this hypothesis, we determined the gene expression differences between two cell lines exhibiting different degrees of radiosensitivity. These were derived from the same tumor prior to treatment from a patient with squamous cell carcinoma of the cervix. The mRNA from these cells was subjected to cDNA analysis on a microarray of 5,776 known genes and ESTs. The expression of 52 genes of the total of 5,776 was elevated (maximum 4.1 fold) in the radioresistant cells as compared to the radiosensitive cells. Ten of the 52 sequences are known genes while 42 are ESTs. Conversely, the expression of 18 genes was elevated in the sensitive cells as compared to the resistant cells. Seven of these 18 are known genes while eleven are ESTs. Among the genes expressed differentially between the resistant and sensitive cells were several known to be associated with response to IR and many more genes and ESTs that had not previously been reported to be related to radiosensitivity. The genes that showed the greatest overexpression in the radioresistant cell line were metal-regulatory transcription factor-1, cytochrome P450 CYP1B1, adenomatosis polyposis coli, translation elongation factor-1, cytochrome-c oxidase, whereas in the sensitive cell line, transcription factor NF-kappa-B, metalloproteinase inhibitor-1 precursor, superoxide dismutase-2, insulin-like growth factor binding protein-3, guanine nucleotide-binding protein and transforming growth factor beta-induced protein were overexpressed.

Cell Survival↗
PubMed1999

Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer.

An ineffective tumor-specific immune response from inadequate/incompetent antigen presentation could contribute to the failure in tumor control and its dissemination. Dendritic cells (DCs) have been shown to present antigen from apoptotic cells. We hypothesized that Flt3-ligand (Flt3L) therapy, which expands DCs in vivo, in combination with local tumor radiotherapy (RT), should improve antigen presentation from dying, irradiated tumor cells. RT + Flt3L reduced pulmonary metastases in a murine model of Lewis lung carcinoma and significantly improved survival in C57Bl/6 mice with established footpad tumors. Mice treated with Flt3L alone showed delayed tumor growth but eventually succumbed to tumor progression. The combination therapy of RT + Flt3L failed to impact survival in immunodeficient athymic mice, implicating the role of T cells in prolonging survival. These results support an attractive strategy of sequential RT and immunotherapy with Flt3L to enhance tumor antigen presentation, which may produce therapeutic responses against disseminated cancer and improvement in survival.

Animals↗
PubMed1999

Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation.

Hepatic tumors often recur in the liver after surgical resection. Postoperative radiotherapy (RT) could improve survival, but curative RT may induce delayed life-threatening radiation-induced liver damage. Because RT inhibits liver regeneration, we hypothesized that unirradiated, transplanted hepatocytes would proliferate preferentially in a partially resected and irradiated liver, providing metabolic support. We subjected F344 rats to hepatic RT and partial hepatectomy with/without a single intrasplenic, syngeneic hepatocyte transplantation. Hepatocyte transplantation ameliorated radiation-induced liver damage and improved survival of rats receiving RT after partial hepatectomy. We further demonstrated that transplanted hepatocytes extensively repopulate and function in a heavily irradiated rat liver.

Animals↗
PubMed1999

Perioperative correlates of malignant ventricular tachyarrhythmias complicating coronary surgery.

Sustained ventricular tachyarrhythmias (VT), such as monomorphic or polymorphic ventricular tachycardia, and ventricular fibrillation, represent the most serious arrhythmic events that can complicate the postoperative course of coronary artery bypass grafting (CABG). The perioperative factors potentially associated with post-CABG sustained VT onset have not been thoroughly investigated. As a consequence, the aim of our study was to identify which perioperative variables might predict post-CABG VT occurrence. One hundred and fifty-two consecutive patients who underwent CABG surgery at our Institute were included in the study. Post-CABG VT occurred in 13 out of 152 patients (8.5%, six cases of monomorphic ventricular tachycardia and seven cases of ventricular fibrillation). Univariate analysis revealed that VT patients were significantly younger (54.8 +/- 6.6 vs 60.1 +/- 8.8, P = 0.038), exhibited more severe coronary artery disease (CAD) (no. of diseased vessels, 2.92 +/- 0.3 vs 2.45 +/- 0.7, P = 0.023; and percentage of patients with three-vessel CAD, 91.7 vs 57.3%, P = 0.043), and received a greater number of CABGs than those remaining in sinus rhythm (SR) (percentage of patients receiving three or more CABGs, 76.9 vs 38.8%, P = 0.018) Moreover, VT patients more frequently developed intra- or postoperative myocardial infarction (total CK > 1,000, 76.9 vs 38%, P = 0.016; and MB-CK > normal range, 72.7 vs 30.7%, P = 0.014), electrolyte derangement (84.6 vs 45.6%, P = 0.017), and a severe hemodynamic impairment (need for intra-aortic balloon pump (IABP), 23 vs 2.9%, P = 0.009). On multivariate analysis, total CK > 1,000, postoperative electrolyte imbalance, the need for three or more CABGs, and for IABP all were independent correlates for VT. In conclusion, post-CABG VT seem to be related to the preexistence of a severe underlying coronary artery disease along with perioperative triggering factors, such as acute ischemia, electrolytic disorders, and sudden hemodynamic impairment.

Coronary Artery Bypass↗
PubMed1999

Pituitary macroadenoma and diaphragma sellae meningioma: differential diagnosis on MRI.

Diaphragma sellae meningiomas are unusual tumours often not distinguished from pituitary macroadenomas. Preoperative differentiation is essential, because the trans-sphenoidal approach is used for surgical removal of adenomas, while meningiomas are approached via a craniotomy. We reviewed five patients in whom a diaphragma sellae meningioma was initially diagnosed as a nonsecreting pituitary macroadenoma. MRI criteria for differential diagnosis are discussed. The main findings considered are visibility of the pituitary gland, contrast enhancement, the centre of the lesion and sellar enlargement. These criteria, applied to a blind review, allow correct identification of the tumours.

Adenoma↗
PubMed1999

Perioperative clinical predictors of atrial fibrillation occurrence following coronary artery surgery.

OBJECTIVE: Atrial fibrillation (AF) is the most frequently encountered arrhythmic complication associated with coronary surgery. The aim of this paper was then to identify the clinical predictors of post-CABG AF occurrence. METHODS: 150 consecutive patients were included in this study and divided into two groups according to the absence (SR group, 104 male and 22 female, age 58.4+/-8.8 years) or presence (AF group, 23 male and 1 female, age 65.4+/-6.3 years) of post-CABG AF. Forty-seven perioperative variables were considered. RESULTS: After univariate analysis, advanced age (SR vs. AF: 58.4+/-8.8 vs. 65.4+/-6.3, P < 0.001), an increased BMI (SR vs. AF: 26.1+/-2.7 vs. 27.4+/-2.5, P = 0.026), a prior history of paroxysmal AF (SR vs. AF: 3.2% vs. 16.7%, P = 0.028), left atrial enlargement (SR vs. AF: 21.1% vs. 70.8%, P < 0.001) and a more severe coronary artery disease (CAD) (SR vs. AF: no. of diseased vessels: 2.42+/-0.7 vs. 2.91+/-0.3, P = 0.001; three-vessel CAD (54.1% vs. 91.3%, P = 0.002) were the only factors that statistically differed between the groups. Multivariate logistic regression analysis identified left atrial enlargement (P < 0.0001), a prior history of paroxysmal AF (P = 0.007) and a more severe CAD (P = 0.0047) to be independent correlates for AF. CONCLUSIONS: Post-CABG AF seems to require a well definite anatomical and electrical substrate that is generated by increased left atrial dimensions, a greater extension of coronary lesions and a possible electrical remodeling consequent to prior repetitive episodes of paroxysmal AF.

Age Factors↗
PubMed1999

Endoscopic endonasal transsphenoidal approach: an additional reason in support of surgery in the management of pituitary lesions.

The outcome of endoscopic endonasal transsphenoidal surgery in 10 patients with pituitary adenomas was compared with that of traditional transnasal transsphenoidal approach (TTA) in 20 subjects. Among the 10 individuals subjected to "pure endoscopy," 2 had a microadenoma, 1 an intrasellar macroadenoma, 4 had a macroadenoma with suprasellar expansion, 2 had a macroadenoma with supra-parasellar expansion, and 1 a residual tumor; 5 had acromegaly and 5 had a nonfunctioning adenoma (NFA). Among the patients subjected to TTA, 4 had a microadenoma, 2 had an intrasellar macroadenoma, 6 had a macroadenoma with suprasellar expansion, 4 had a macroadenoma with supra-parasellar expansion, and 4 had a residual tumor; 9 patients had acromegaly, 1 hyperprolactinemia, 1 Cushing's disease, and 9 a NFA. At the macroscopic evaluation, tumor removal was total (100%) after endoscopy in 9 patients and after TTA in 14 patients. Six months after surgery, magnetic resonance imaging (MRI) confirmed the total tumor removal in 21 of 23 patients (91.3%). Circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I) significantly decreased 6 months after surgery in all 14 acromegalic patients: normalization of plasma IGF-I levels was obtained in 4 of 5 patients after the endoscopic procedure and in 4 of 9 patients after TTA. Before surgery, pituitary hormone deficiency was present in 14 out of 30 patients: pituitary function improved in 4 patients, remaining unchanged in the other 10 patients. Visual field defects were present before surgery in 4 patients, and improved in all. Early surgical results in the group of 10 patients who underwent endoscopic pituitary tumor removal were at least equivalent to those of standard TTA, with excellent postoperative course. Postsurgical hospital stay was significantly shorter (3.1 +/- 0.4 vs. 6.2 +/- 0.3 days, p < 0.001) after endoscopy as compared to TTA.

Journal Article↗
PubMed1999

Instruments for endoscopic endonasal transsphenoidal surgery.

TECHNIQUE: Endoscopic transsphenoidal surgery. New, developing, minimally invasive technique. Removal of pituitary lesions and tumors of the parasellar region. TECHNICAL DEVELOPMENT: Endoscopic endonasal transsphenoidal surgery. Endonasal, not transnasal, procedure. Great respect of anatomy. Very wide surgical field, without intraoperative use of a nasal speculum, but with less room in which to work (only one nostril) and potential conflict between the surgeon's hands and the endoscope (both when entering the nostril and while working inside). INSTRUMENTATION: New instrument. Secure grip. Barycenter of the instrument is the surgeon's hands. Many different tips with different functions. Elimination of the bayonet-like shape. Handle bent in the horizontal plane to avoid interference with the surgeon's hands and to allow the distal, thin part of the instrument to be used safely and comfortably.

Endoscopes↗
PubMed1999

Propofol in the anaesthetic management of percutaneous rhizolysis for trigeminal neuralgia.

BACKGROUND: To evaluate the efficacy of propofol as the sole anaesthetic agent for the anaesthetic management of the trigeminal rhizolysis. METHODS EXPERIMENTAL DESIGN: retrospective study. SETTING: operating room of the Neurosurgery Department at University. PATIENTS: 200 patients were studied, 115 males and 85 females, with mean age of 62.8 +/- 3.6 years, ASA status I, II or III and with various underlying medical problems. INTERVENTIONS: patients were premedicated with atropine 0.01 mg/kg i.v. 10 min before the induction of anaesthesia. The induction dose of P was titrated to the desired level in according to age and clinical conditions. After induction of anaesthesia the surgeon started the needle placement through the foramen ovale in the trigeminal cistern. MEASUREMENTS: during both procedures the mean dose of P, induction and recovery times, side effects and complications and quality of anaesthesia were assessed. Statistical analysis of the data was carried out using ANOVA for repeated measures and Bonferroni "t"-test and a value of p < 0.05 was considered to be significant. RESULTS: Anaesthesia was successfully induced after a mean dose of 1.9 mg/kg of P during PG and of 2.1 mg/kg during PR. A few side effects and short recovery time were recorded in all cases. P also provided an adequate cardiovascular stability during PG and PR. CONCLUSIONS: In conclusion, P can be considered suitable for this particular neurosurgical procedure requiring short period of anaesthesia and rapid recovery time in order to communicate with the neurosurgeon during the sensory testing.

Anesthesia, Intravenous↗
PubMed1999

Endoscopic endonasal transsphenoidal approach to the sellar region: technical evolution of the methodology and refinement of a dedicated instrumentation.

BACKGROUND: Endoscopic treatment of hydrocephalus has in time acquired a primary position in Neurosurgery. Today endoscopy can be employed in the vast majority of neurosurgical procedures in the realization of the so-called endoscope-assisted microneurosurgery. On the basis of the encouraging results obtained by Jho and Carrau, the authors report the pros and cons of the new endoscopic endonasal technique. METHODS: An endoscopic endonasal transsphenoidal approach to the sella was performed in 50 patients: 33 females and 17 males, of age included between 16 and 76 years; 45 were affected by pituitary adenomas (9 micro and 36 macro; 10 were recurrences), 3 by craniopharyngiomas, 2 by clival chordomas. The new instrumentation was realized through straight devices with a handle shifted 10-30 degrees horizontally. The possible danger to the nasal structures is reduced not only by the elimination of the bayonet-like shape but also by hiding the cutting extremity in the handle. RESULTS: The advantages of this technique have been represented by an easier access to the lesion, especially in recurrent tumors, a more complete excision of voluminous neoplasms, a decrease of ENT post-surgical complications and a reduction of hospitalization times and costs. The main limits have been the reduction of field depth and the lack of adequate instrumentation. CONCLUSIONS: In this peculiar surgery the absence of proper instruments has to be overcome because: a) there is less room to work, b) a conflict between the hands of the surgeon and the endoscope may occur, c) the blind introduction of the instruments in the nostril may cause damage to the nasal structures. The secret for the success of the endoscopic endonasal transsphenoidal technique is to create the optimal conditions, in order to avoid improper manoeuvres that may cause potential dangers.

Adenoma↗
PubMed1998

Effect of surgery and radiotherapy on visual and endocrine function in nonfunctioning pituitary adenomas.

The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA) subjected to 1-10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness documented at histology.

Adenoma↗
PubMed1998

Endoscopic endonasal transsphenoidal approach to the sella: towards functional endoscopic pituitary surgery (FEPS).

Standard microscopical transsphenoidal surgery is used world-wide in most sellar lesions, but continuing technological progress leaves room for further possibilities. The authors have employed a slightly modified Jho-Carrau technique for endoscopic endonasal transsphenoidal removal of pituitary lesions. This approach has been successfully used in 15 consecutive patients; the preliminary results are reported. The advantages and the limitations of this technique are discussed and compared to standard transsphenoidal surgery. In consideration of the low invasiveness of this approach and of the improved respect for the inner nose and sinus structures, the authors suggest the new term of Functional Endoscopic Pituitary Surgery (FEPS) to characterize this simple one-nostril endoscopic endonasal procedure.

Adenoma↗
PubMed1998

[Molecular diagnosis in an Argentinian family with multiple endocrine neoplasia type-1 (MEN-1)].

MEN-1 is a hereditary autosomal dominant syndrome characterized by the involvement of parathyroid glands, pancreatic islet cells and anterior pituitary gland. Today molecular genetics permit gene carrier analysis to compare the data obtained with the clinical biochemical tests. The twenty living members of the first, second and third generation of a family with MEN-1 were studied to determine the presence of genetic markers in MEN-1 loci 11q13, by linkage analysis and in affected individuals by biochemical tests and clinical examination. Two very informative polymorphic markers immediately flanking the MEN-1 gene on chromosome 11 band q13 were detected: PYGM and D11S987, haplotypes segregated by two members of the second generation, inherited from their father and two of the third generation: the affected one and one presymptomatic. The third generation had the affected member with renal stones and elevated PTH, PRL and glucagon. The presymptomatic carrier of MEN-1 allele showed elevated PTH. Among the members who inherited the normal allele we found one with elevated gastrin, one with elevated glucagon and one with elevated PTH, all asymptomatic. Of one Argentine family studied, molecular diagnosis allowed us to detect one presymptomatic carrier in the members at risk. As suggested by the available literature, accuracy of molecular diagnosis seems to make it the test of choice to exclude those members at risk for MEN-1 inheriting the normal allele.

Adult↗