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Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 55 records · Page 3Linked to original sources
PubMed2003

Charge, orbital and spin ordering phenomena in the mixed valence manganite (NaMn3+(3))(Mn3+(2)Mn4+(2))O12.

Mixed-valence manganites with the ABO3 perovskite structure display a variety of magnetic and structural transitions, dramatic changes of electrical conductivity and magnetoresistance effects. The physical properties vary with the relative concentration of Mn3+ and Mn4+ in the octahedral corner-sharing network, and the proportion of these two cations is usually changed by doping the trivalent large A cation (for example, La3+) with divalent cations. As the dopant and the original cation have, in general, different sizes, and as they are distributed randomly in the structure, such systems are characterized by local distortions that make it difficult to obtain direct information about their crystallographic and physical properties. On the other hand, the double oxides of formula AA'3Mn4O12 contain a perovskite-like network of oxygen octahedra centred on the Mn cations, coupled with an ordered arrangement of the A and A' cations, whose valences control the proportion of Mn3+ and Mn4+ in the structure. The compound investigated in this work, (NaMn3+(3))(Mn3+(2)Mn4+(2))O12, contains an equal number of Mn3+ and Mn4+ in the octahedral sites. We show that the absence of disorder enables the unambiguous determination of symmetry, the direct observation of full, or nearly full, charge ordering of Mn3+ and Mn4+ in distinct crystallographic sites, and a nearly perfect orbital ordering of the Mn3+ octahedra.

Journal Article↗
PubMed2003

Prospective study of high-dose chemotherapy and autologous peripheral stem cell transplantation in adult patients with advanced desmoplastic small round-cell tumour.

A total of 10 desmoplastic small round-cell tumour patients were treated by high-dose chemotherapy with stem cell support. After high-dose chemotherapy, no complete response conversion was obtained and EWS-WT1 fusion transcript detection was positive in the peripheral blood during follow-up in all patients. High-dose chemotherapy did not seem to change the results in desmoplastic small round-cell tumour.

Abdominal Neoplasms↗
PubMed2003

Human pituitary tumours express the bHLH transcription factors NeuroD1 and ASH1.

Among the transcription factors involved in pituitary ontogenesis and physiology, basic helix-loop-helix (bHLH) have been poorly studied. Members of bHLH family include NeuroD1 and ASH1, both involved in neuroendocrine differentiation. We evaluated their mRNA expression patterns, by semi-quantitative RT-PCR analysis (sq-RT-PCR) and/or Northern blot, in a series of 33 pituitary adenomas (PA), anterior pituitaries, and pituitary cell lines. Immunohistochemistry for NeuroD1 was also performed in 25 PA. Low levels of NeuroD1 were observed in normal pituitaries and in the somatomammotroph cell lines GH3/GH4C1, contrasting with high levels in corticotroph AtT20 cells. NeuroD1 mRNA was widely expressed in PA (82%), with measurable levels found especially in those derived from Pit-1 independent lineages, i.e. corticotroph (5/5) and clinically non-secreting (CNS) adenomas (9/11). According to sq-RT-PCR analysis, overexpression of NeuroD1 compared to normal pituitaries was frequent. Variable nuclear NeuroD1 immunopositivity was also present in about 70% of studied cases. ASH1 mRNA was widely detected in normal pituitaries, in all tumour cell lines and in most PA (84%), with measurable levels in corticotroph (5/5) and CNS (9/11) adenomas, and in a significant subset of PA derived from Pit-1 dependent lineages (9/16). We conclude that: a) NeuroD1 is differentially expressed in PA and its possible ontogenetic and/or pathogenetic implications in non-corticotroph PA are discussed; b) ASH1 is a neuroendocrine marker whose expression is largely conserved in normal and neoplastic pituitary cells.

Adult↗
PubMed2003

High rate of remission and low rate of disease recurrence in patients with multiple myeloma allografted with PBSC from their HLA-identical sibling donors.

A total of 30 multiple myeloma patients (M=23, F=7; age 31-55 years, median 48) were allografted with peripheral blood stem cells (PBSC) from HLA-identical siblings. Time to transplantation was 3-107 months (median 8). Prior chemotherapy lines varied from 1 to 6 (median 1). Four patients were in complete remission (CR), 11 in partial remission (PR), 13 were considered to be nonresponders, and two had progressive disease. Most were conditioned with busulfan-melphalan. PBSC were collected by apheresis after G-CSF or sequential GM-CSF and G-CSF. The patients were grafted with 4.4-24.1 x 10(6)/kg CD34+ (median 7.9) and 0.9-7.9 x 10(8)/kg CD3+ cells (median 2.3). GVHD prophylaxis was methotrexate-cyclosporine. Engraftment was complete and rapid. Grades II-IV acute GVHD (aGVHD) developed in 16 (53%), but was grade III-IV only in five (17%); chronic GVHD (cGVHD) developed in 17 out of the 24 evaluable patients (71%). A total of 18 patients (71%) attained CR after transplantation. TRM was 30% overall, 16% at 100 days. There was only one relapse. Overall survival and event-free survival at 73 months were 60% and 67%, respectively. PCR negativity for IgH-gene rearrangement occurred in all persistently CR patients studied. PBSC allograft can induce long remissions, because of profound suppression of the neoplastic clone that is probably linked to the antitumor effect of cGVHD.

Adult↗
PubMed2003

Detection of minimal residual disease by real-time PCR can be used as a surrogate marker to evaluate the graft-versus-myeloma effect after allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (allo-SCT) is an effective and potentially curative treatment for some cases of multiple myeloma (MM). The curative efficacy of allo-SCT may be largely attributed to its immunological activity, the graft-versus-myeloma (GVM) effect. To evaluate the kinetics of residual myeloma cells, we analyzed the follow-up bone marrow samples of three MM patients by means of a real-time molecular assay. We identified a consistent correlation between onset of graft-versus-host disease and disease response. These data suggest that real-time molecular follow-up can be used to monitor the GVM effect and that it can be employed in the clinical setting to tailor post transplant immunomodulation.

Adult↗
PubMed2003

Metastatic colorectal cancer: integrating irinotecan into combination and sequential chemotherapy.

The chemotherapy of metastatic colorectal cancer (CRC) has undergone a succession of refinements. Through the biochemical modulation of 5-fluorouracil (5-FU) with folinic acid (FA), the use of infusional rather than bolus regimens and the combination of 5-FU/FA with other active agents (notably irinotecan), first-line response rates (RRs) of 40% can be achieved, with patients surviving up to 17 months. Significant benefits on survival are also seen with second-line chemotherapy. The question of how best to sequence combination chemotherapy was addressed in a recent trial in which patients were randomized to receive either an irinotecan-based combination with 5-FU/FA (FOLFIRI) followed by an oxaliplatin-based combination (FOLFOX), or the two regimens in the reverse order. In both arms, RRs were greater than 50% and median survival exceeded 20 months. The primary end point was time to progression after two lines of treatment, and this was not significantly different. However, the sequence FOLFIRI followed by FOLFOX appears preferable because of the better tolerability of FOLFIRI in first-line use. Use of the sequence FOLFIRI/FOLFOX is also supported by the greater chance of a second-line response with FOLFOX. Concern has been expressed about the safety of irinotecan combined with bolus 5-FU/FA. Infusional regimens have a better risk/benefit ratio than bolus regimens. However, the adverse event profile with both approaches is manageable, and irinotecan plus 5-FU/FA can be considered one standard of care in metastatic CRC.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature.

Criteria to define the biochemical remission of acromegaly following surgery have changed over the years, and the current use of stringent criteria needs a critical re-evaluation of the surgical results. On the other hand, few data are currently available concerning the possible impact of pituitary surgery on the quality of life of operated acromegalic patients. In this prospective study, we wished to evaluate the initial outcome and long-term recurrence rate in a large series of acromegalic patients operated on by transsphenoidal surgery (TSS), to carefully analyse predictive factors for surgical outcome and to point out possible additional effects of surgery in these patients. Ninety-two out of 98 operated patients could be considered for follow-up. Biochemical remission was strictly defined as plasma GH levels <1 ng/ml during an oral glucose tolerance test (OGTT) and normalisation of age-related IGF-I levels. Hormonal assessment, including an OGTT, was performed 6 months following surgery and then annually to evaluate pituitary function. Fifty-five per cent of patients achieved a biochemical remission of acromegaly. The remission rate at 6 months was 80% for patients with microadenoma and 50% for macroadenoma. Univariate analysis showed that a large extrasellar extension, preoperative high GH levels and dural invasion were correlated with a poor outcome of surgery while, according to multivariate analysis, only invasion of cavernous sinus and preoperative GH levels > 10 ng/ml were independent negative predictors. Mortality was 0% and the overall complication rate was about 10%. Pituitary function worsened in five patients but improved in 16 out of 30 patients with preoperative pituitary defects. No recurrence was observed during a median follow-up of about 8 years. We conclude that TSS is able to achieve a biochemical remission in more than half of acromegalic patients, and that the current criteria for remission seem to indicate a cure in most cases.

Acromegaly↗
PubMed2003

Fronto-temporo-orbito-zygomatic approach and variants. Surgical technique and indications.

AIM: In the last decade, development and refìnement of skull base surgery have widened the surgical options available for treatment of mtracramal lesions. Despite the enormous advances made m microsurgical technique, the bony phase is still extremely important for achievmg optimal exposure of vascular and tumoral skull base lesions. The role of anterolateral approaches for such lesions is discussed. METHODS: We collected 87 consecutive patients with 74 neoplasms and 13 vascular lesions involving the floor of the antenor and/or middle cranial fossae, cavernous sinus, orbit, petrous bone, clivus, parasellar region and infratemporal fossa operated throughout 8 and a half years by means of an anterolateral approach and we evaluated the results obtained employing different craniotomies. RESULTS: To simplify the parameters for evaluation of outcome, we considered 2 main aspects: comparison between pre- and postoperative neurological status and the extent of tumour removal on MR imaging. For vascular lesions, we took into consideration the neurological outcome and the successful clipping of the aneurysm or disappearance of the AVM (l case) on postoperative angiography. Satisfactory surgical results were obtained with each type of craniotomy employed (fronto-teniporo-orbito-zygomatic, fronto-temporo-orbital, fronto-temporo-zygomatic, fronto-orbito-zygomatic). CONCLUSION: On the whole, surgical results were satisfactory. By deliberately excluding the microsurgical aspects of the lesions treated, we can observe that the fronto-temporo-orbito-zygomatic approach is principally indicated for lesions requiring a multidirectional approach such as spheno-petro-clival tumours, aneurysms of the basilar tip and intracavemous lesions while the fronto-temporo-orbital approach proved excellent for more medial lesions such as meningiomas of the luberculum sellae and cramopharyngiomas. The fronto-temporo-zygomatic approach is our 1(st) choice for neoplasms involving the Gassenan ganglion and the intratemporal fossa. For lesions of the orbital apex, a fronto-orbito-zygomatic approach can be successfully employed. Introduction of these approaches is relatively recent but promises a further refinement of their indications and surgical technique aimed at mimmismg postoperative morbidity.

Adolescent↗
PubMed2003

A vertebral artery tortuous course below the posterior arch of the atlas (without passing through the transverse foramen). Anatomical report and clinical significance.

A vertebral artery (VA) coursing below the posterior arch of the atlas (C1) without passing through the transverse foramen of C1, combined with a tortuous course within the spinal canal has rarely been reported in the literature. This article describes a case encountered during an anatomical study of the far-lateral approach, and reviews its embryonic development and clinical significance. The suboccipital triangle was filled with numerous venous plexures. After exiting from the transverse foramen of C2, instead of passing upwards through the transverse foramen of C1, the VA turned directly medially towards the spinal canal. At the spinal canal, it first formed an angle downwards, then turned upwards, piercing and entering the lateral part of the dura at C1 level. The diameter of this VA seemed to be within its normal limits. The course of the contralateral (right) VA was normal but with a small caliber and mainly supplied the posterior inferior cerebellar artery (PICA); after PICA, it became much thinner and dysplastic, the basilar artery was mainly supplied by the left VA. The bilateral posterior communicating arteries were large in diameter but there was dysplasia of the P1 segment of the posterior cerebral arteries bilaterally. Marked tortuosity of the bilateral intracavernous internal carotid artery (ICA) was also found. We did not find any osseous abnormality in the occipito-axial region or of C1-C2 joint. An abnormal course of the VA should be kept in mind during exposure of the craniocervical junction, especially in the variety of lateral approaches; due to compression of the nerve roots or the spinal cord, this abnormal course of the VA could give rise to clinical symptoms, which could be resolved by microvascular decompression technique.

Aged↗
PubMed2002

Discontinuous myelotomy: an alternative to standard myelotomy in the surgical treatment of intramedullary spinal cord tumours.

BACKGROUND: Myelotomy is an essential step for the removal of intramedullary tumours. Often, this manoeuvre requires division of large vessels surfacing the midline, contributing to the development of postoperative sensory deficits. We developed a technique of discontinuous myelotomy to preserve the integrity of these large spinal cord vessels. METHODS: Over a three-year period, we approached 20 intramedullary astrocytomas through a posterior myelotomy consisting of two separate incisions one above and the other below the midline vessel. The tumour was removed using the Cavitron ultrasound aspirator (CUSA), through either incision. Tumour underlying the bridging area between the two incisions was successfully removed through an oblique view. FINDINGS: We retrospectively analysed the clinical outcome in terms of sensory function. Follow-up examinations showed that up to 70% of the patients had their sensory function unchaged. 5 (20%) patients experienced a permanent worsening of their deficits, involving superficial and deep sensation in cases 1 and 4, respectively. Two (10%) patients showed significant improvement. INTERPRETATION: Discontinuous myelotomy is a viable technical option whenever the presence of large vessels on the median raphe would make the standard midline myelotomy unsafe.

Astrocytoma↗
PubMed2002

Atypical tentorial meningioma 30 years after radiotherapy for a pituitary adenoma.

Although the human central nervous system used to be considered relatively resistant to the carcinogenic action of ionizing radiation, several lines of evidence now document a high incidence of secondary tumors in irradiated patients. The numerous reports of radiation-induced cerebral meningiomas generally distinguish those induced by high-dose radiation from those induced by low-dose radiation. We describe the case of patient who underwent subtotal resection of a chromophobe pituitary adenoma at the age of 18 years, who was successively treated by conventional fractionated radiotherapy with gamma rays emitted by a source of 60Co until a total dose of 41 Gy. Over the next 30 years the patient experienced all the known late effects of radiation, including panhypopituitarism, cranial-nerve deficits (II, III and VI), massive radiation necrosis involving the left cerebral hemisphere and causing right hemiparesis and aphasia and, ultimately, an atypical tentorial meningioma with early recurrence after total resection.

Adenoma, Chromophobe↗
PubMed2002

[The hyperplasia-adenoma sequence: a case supporting this hypothesis].

We described the morphological, histochemical and immunohistochemical findings of a polyp detected in the left colon (splenic flexure) in which the diagnosis was atypical hyperplastic polyp. The description is focused on the capability of a hyperplastic polyp to evolve into adenomatous tissue through different modalities.

Adenoma↗
PubMed2002

Reduced intensity conditioning regimen followed by glycosylated G-CSF mobilized PBSCT in patients with solid tumors and malignant lymphomas.

The aim of this pilot study was to exploit the graft-versus-tumor potential of allogeneic transplants while improving safety of the procedure. Twelve patients with advanced hematological malignancies and solid tumors underwent a low intensity conditioning regimen (fludarabine and cyclophosphamide) followed by an allogeneic peripheral blood stem cell transplantation. The median time to achieve an absolute neutrophil count of more than 0.5 x 10(9)/l and an untransfused platelet count of more than 20 x 10(9)/l was 15 and 14 days, respectively. The main extra-hematological toxicities were mucositis and infections. Acute graft-versus-host (GVHD) disease was experienced by 62% of evaluable patients (grade II/B or III/C 80%) responsive to steroids. Extensive chronic GVHD was observed in 62% of patients. Non-relapse transplant-related mortality by day +30 was observed in three patients (25%). Eight out of 12 patients were full donor chimeric by day +100. One patient showed a mixed chimerism at day +37 when he died from progressive disease. One patient was in complete remission (CR) before allogeneic transplantation, and after transplantation four patients achieved CR and four experienced progressive disease. Our study confirms that a low intensity conditioning regimen for allogeneic stem cell transplantation is feasible and effective in heavily pretreated patients.

Adult↗