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C Botti

Publications and source records attributed to C Botti.

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

Verbal learning strategies in Parkinson's disease.

Word-list learning was studied in patients with Parkinson's disease (PD) and normal control (NC) participants by means of the selective-reminding procedure of H. Buschke and P. A. Fuld (1974) in 3 learning conditions using semantically unrelated items; semantically related items, whose implicit categorical structure had to be spontaneously guessed; and semantically related items, whose explicit categorical structure was known in advance. The PD patients displayed poor learning in all 3 conditions. To identify the functional locus of the PD patients' deficits, the authors performed a stochastic Markov chain analysis, which allowed individual measurements of encoding, retrieval, and category clustering abilities. PD patients were never significantly impaired in encoding word engrams; their impairment was confined to automatic and intentional retrieval and to the ability to benefit from explicit semantic clues.

Aged↗
PubMed2000

Peritonectomy and hyperthermic antiblastic perfusion in the treatment of peritoneal carcinomatosis.

AIMS: Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way. METHODS: Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days. RESULTS: Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months. CONCLUSIONS: After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.

Adult↗
PubMed1999

Host immunosurveillance contributes to the control of erbB-2 overexpression in HLA-A2-breast-cancer patients.

Overexpression of gp185(erbB-2) has been associated with reduced survival in breast-cancer patients. Our earlier results, now confirmed in a larger cohort of patients (798), evidenced that the HLA-A2 allele may participate in the modulation of the erbB-2 tumor phenotype in vivo. In the present study, we evaluated other clinico-biopathologic parameters possibly involved in the host immune response against erbB-2. Localization of the CD3(+) T-cell infiltrate was taken into consideration in 705 primary breast tumors, and expression of HLA-class-I and HLA-A2 antigens was evaluated in a subgroup of 170 frozen primary tumors of HLA-A2-positive patients. The presence or the absence of HLA-class-I and HLA-A2 antigens in primary tumors did not correlate with erbB-2 expression. However, HLA-A2-positive tumors preferentially showed intratumoral lymphocyte localization, whereas the lesions displaying undetectable HLA-class-I expression showed peritumoral CD3(+) T-cell localization. Taking into account erbB-2 immunoreactivity, we found that the relationship between HLA-A2 expression and intratumoral CD3(+) T-lymphocyte localization is significant only in the erbB-2 negative subset, whereas the relationship between lack of HLA-class-I expression and peritumoral CD3(+) T-lymphocyte localization is significant only in the erbB-2-positive subset. These data provide novel in vivo evidence of the possible contribution of the host immune system to control of erbB-2 oncogene overexpression in breast cancer. Int. J. Cancer (Pred. Oncol.) 84:598-603, 1999.

Adult↗
PubMed1999

Immunohistochemical study of fatty acid synthase, Ki67, proliferating cell nuclear antigen, and p53 expression in hyperplastic parathyroids.

Patients with secondary hyperparathyroidism following chronic renal disease frequently develop hyperplastic parathyroids. Hyperplastic parathyroids have an increased number of chief cells, a decreased amount of stromal fat, and a nodular or diffuse histologic pattern. Hyperplastic parathyroids may also express higher proliferative activity compared with controls. We evaluated the morphologic features and immunohistochemical expression of fatty acid synthase (FAS), Ki67, proliferating cell nuclear antigen, and p53 protein in 78 hyperplastic parathyroids from 20 patients with secondary hyperparathyroidism. Twenty normal parathyroids incidentally removed during nonneoplastic thyroid surgery were used as controls. Our results showed that hyperplastic glands overexpress FAS (P =.06). Statistical analysis also revealed a significant association between FAS and p53 protein (P =.006) and between FAS and hyperplastic glands with a predominant nodular pattern (P =.02). Hyperplastic parathyroids from patients with chronic renal failure strongly express FAS. Fatty acid synthase may therefore be a potential biological indicator of highly proliferating parathyroid cells.

Adult↗
PubMed1999

Breast cancer and timing of surgery during menstrual cycle: a 5-year analysis of 248 premenopausal women.

In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease-free and overall survival of 248 premenopausal patients with stage I/II breast cancer who underwent surgery followed by anthracycline-containing adjuvant chemotherapy. With a median follow-up of 5 years, no statistically significant differences were observed in disease-free or overall survival between women operated upon during the follicular (days 0-14) and the luteal (days 15-32) phase of the menstrual cycle. The impact on disease-free and overall survival of lymph-node status, tumor size and hormone receptor expression, but not of the phase of the menstrual cycle at the time of surgery, was confirmed by univariate and multivariate analysis. However, when combined with hormone receptor status, the phase of the menstrual cycle at the time of surgery proved useful to better define the prognosis of primary breast cancer patients, with significantly longer disease-free and overall survival for patients operated upon during the follicular phase and with positive hormone receptors.

Adult↗
PubMed1999

Hyperthermic antiblastic perfusion with alpha tumor necrosis factor and doxorubicin for the treatment of soft tissue limb sarcoma in candidates for amputation: results of a phase I study.

To improve the therapeutic effectiveness of hyperthermic antiblastic perfusion (HAP), the association of recombinant tumor necrosis factor alpha (rTNF alpha), doxorubicin, and true hyperthermia (41 degrees C) was employed for the treatment of soft tissue limb sarcoma. A dose-escalation study according to Fibonacci's modified scheme was conducted, starting with a rTNF alpha dose of 0.5-3.3 mg. The doxorubicin doses (0.7 and 1.4 mg for the upper and lower limbs, respectively) and temperature level (41 degrees C) remained unchanged. Eighteen patients have been treated thus far: 9 males and 9 females of a mean age of 33 years (range: 24-71 years). The tumor was located in the upper limb in one patient and in the lower limbs in seventeen. Only 16 patients were evaluable, as 2 refused further treatment after the perfusion. In terms of local toxicity, a grade I limb reaction was observed in 3 patients, a grade II or III in 10 patients, and a grade IV in 5 patients, showing a strict correlation between the TNF dose and the grade of limb reaction. In fact, a grade III-IV limb reaction was observed in 66.6% of the patients treated with > 1 mg of rTNF alpha. The maximum tolerable dose in association with doxorubicin and true hyperthermia (41 degrees C) was 2.4 mg. Eleven patients showed a good pathological response (> 75%) and five patients showed a partial response (> 25%-< 75%). In no case was stable or progressive disease observed. The postperfusional tumor shrinkage permitted limb-sparing surgery in 75% of the patients, all of whom were candidates for amputation before HAP. No recurrences have been observed thus far. Two patients developed regional disease: one presented with a skip femur metastasis that disappeared after radiotherapy and systemic chemotherapy; the second developed regional node involvement, requiring a radical node dissection. Another patient had pulmonary metastases, 2 months after the HAP, which were resected. At a median follow-up of 12 months, all the patients are living without disease. The results of this phase I study suggest that the association of rTNF alpha, doxorubicin, and true HAP (41 degrees C) by regional perfusion is feasible and safe at a maximum tolerable rTNF alpha dose of 2.4 mg. However, because no correlation was found between the amount of rTNF alpha and the tumor response, 1 mg is recommended as the dose able to provide a high tumor necrosis rate and low local and systemic toxicity. This association appears to play an important role in the neoadjuvant treatment of soft tissue limb sarcoma.

Adult↗
PubMed1999

99Tcm-MIBI scintimammography in 300 consecutive patients: factors that may affect accuracy.

We evaluated the diagnostic yield of 99Tcm-MIBI scintimammography in a relatively large series of consecutive patients referred for breast surgery on the basis of physical examination or mammogram. 99Tcm-MIBI uptake was correlated to tumour size, receptor status, neovascularity, proliferating activity, P-170 glycoprotein expression and the patient's gonadal state. Three hundred consecutive patients referred to our institution, with either a positive mammogram or a palpable mass, were entered into the study. All patients underwent 99Tcm-MIBI scintimammography. Pathological status was obtained after surgery in all patients. Breast cancer was diagnosed in 218 (73%) patients. The MIBI scan was positive in 89% (194/218) cancer patients and in 17% (14/82) of patients with benign masses (false-positives); the scan was negative in 24 (11%) cancer patients (false-negatives). The sensitivity of MIBI scintigraphy was higher for tumours > 1 cm (95 vs 48% in lesions < or = 1 cm) and in pre-menopausal women (95 vs 85%). Conversely, the specificity was better for lesions < 1 cm (100%) and in post-menopausal women (89%). The positive predictive value of MIBI scan was good both in small (< 1 cm) and large tumours (100% and 93%, respectively) and slightly modified by gonadal state (89% and 96% in pre- and post-menopausal state). The negative predictive value was unsatisfactory, especially in small tumours and in older patients. The diagnostic performance increased stratifying data for tumour size, indicating that lesion size is a major determinant in the diagnostic accuracy of MIBI scintimammography. We conclude that 99Tcm-MIBI scintimammography is useful in the diagnostic evaluation of young patients, because it can select patients for further invasive diagnostic procedures. In older patients, a positive 99Tcm-MIBI scan is highly suggestive of malignancy and might be an indication for surgery. In the case of a negative scan, biopsy is advisable given the poor negative predictive value. Small tumour size and a well-differentiated histotype characterize false-negative cases.

Adult↗
PubMed1999

The integrated treatment of peritoneal carcinomatosis. A preliminary experience.

Some low-grade malignant tumors arising in the abdomen, lack of infiltrative attitude and "redistribute" on the peritoneum with no extraregional spreading. In this cases the complete tumor cytoreduction followed by intra- or postoperative regional chemotherapy has curative intent. Peritonectomy is the complete removal of all the parietal peritoneum and the visceral peritoneum involved by disease. After peritonectomy hyperthermic antiblastic perfusion is carried out throughout the abdomino-pelvic cavity for 60 minutes, at a temperature of 41.5 degrees C, with mitomycin C (3.3 mg/m2/Lt of perfusate) and cisplatin (25 mg/m2/Lt) (appendicular or colorectal primary), or cisplatin alone is (ovarian primary). Alternatively the immediate postoperative regional chemotherapy is performed with 5-fluorouracil (13.5 mg/Kg) and Lederfolin (125 mg/m2) (colic or appendicular tumor) or cisplatin (25 ng/m2) (ovarian tumor), each day for 5 days. Twenty patients affected by extensive peritoneal carcinomatosis (12 ovarian, 5 colonic, 1 appendicular, 1 mesothelial and 1 gastric primary) were submitted to peritonectomy with no residual macroscopic disease in all cases except three. Six patients were treated with intraoperative intra-abdominal hyperthermic antiblastic perfusion, while immediate postoperative intra-abdominal chemotherapy was given in 4 patients and systemic chemotherapy in other 5. Hospital mortality was 20%. At a mean follow-up of 11 months 14 patients are alive, 11 without disease and the median overall survival is 10.2 months. The curative potential of the combined therapeutic approach seems high in patients with peritoneal carcinomatosis from ovarian or colorectal primary not responding to systemic chemotherapy. Selection criteria of patients can strictly affect the surgical risk and the treatment has to be reserved for controlled clinical trials.

Abdominal Neoplasms↗
PubMed1999

Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa.

The normal mucosa-adenoma-carcinoma sequence in colon pathology provides an attractive model of tumor progression. The role of tumor suppressor genes, oncogenes, and proliferative markers in tumorogenesis has evolved considerably in the last decade. By immunohistochemistry means, we have studied p53, bcl-2, c-myc, p21-ras, ki67, and fatty acid synthase (a fatty-acid-synthesizing enzyme) in normal, dysplastic, and neoplastic mucosa. The results were correlated with clinicopathological features and overall survival (OS). Formalin-fixed, paraffin-embedded archival material from 100 nonconsecutive adenomas and 100 adenocarcinomas (ADCs), including adjacent-to-tumor nonneoplastic mucosa (ANNM), from patients with a 5-year follow-up period were studied. Negative controls were obtained from colon resections for nonneoplastic disease. Fatty acid synthase was associated with ADC (P = 0.0001). p53 protein was associated with high-grade dysplasia adenoma (AHGD), ADC (P = 0.0001), and pT stage (P = 0.003). bcl-2 was associated with adenomas with low-grade dysplasia (P = 0.009); c-myc was associated with ANNM (P = 0.005) and pT stage (P = 0.006). p21-ras was associated with AHGD (P = 0.0001) and ANNM (P = 0.01). Ki67 was associated with AHGD (P = 0.02) and ADC (P = 0.0001). Univariate analysis on neoplastic tissue revealed histological grade, pT stage, pN stage, p21-ras, and p53 to be significant markers of OS; p21-ras, p53, and c-myc were reliable markers when evaluated on ANNM. Multivariate analysis revealed pT stage, pN stage, and p21-ras to be independent prognosticators of OS on ADC; p21-ras and c-myc staining in the ANNM were correlated with worse survival (OS). We suggest that the evaluation in concert of clinicopathological data and immunohistochemical markers on both normal and abnormal colon tissue provides an attractive model of tumor progression; moreover, it may give important messages about the prediction of survival.

Adenoma↗
PubMed1999

99mTc-MIBI scintimammography using a dedicated nuclear mammograph.

UNLABELLED: This study reports on a prototype single-photon emission mammograph (SPEM) dedicated to 99mTc-hexakis-2-methoxyisobutile isonitrile (MIBI) scintimammography. Main technical features are reported together with physical performance. Preliminary patient data are also reported. METHODS: The SPEM detector head is composed of a CsI(T1) scintillating array coupled to a Hamamatsu R3292 position-sensitive photomultiplier tube with crossed-wire anode. The high-resolution collimator is 35-mm thick with a 1.7-mm hole diameter and a 0.2-mm septal thickness. The electronic acquisition system is composed of five integrated cards with computation based on high-speed programmable microprocessors. The readout electronics include correction maps for on-line energy correction and spatial uniformity. The small size of the detector head allows the use of mechanical breast compression to minimize detection distance and tissue scatter. After physical SPEM performance evaluation in vivo scintimammography was performed in 29 patients and was compared with a state-of-the-art Anger camera. RESULTS: The SPEM showed an intrinsic spatial resolution of 2 mm, an energy resolution of 23% FWHM at 122 keV and spatial uniformities of 18% (integral) and 13.5% (differential). The SPEM imaged one 0.4-cm carcinoma missed by the Anger camera and resolved as separate lumps an irregular focal uptake on the Anger camera image. The remaining cases yielded concordant results. CONCLUSION: The SPEM prototype presented in this study shows adequate physical characteristics for 99mTc-MIBI scintimammography.

Adult↗
PubMed1998

Neuron-specific enolase evaluation in patients with neuroblastoma.

Neuron-specific enolase (NSE) may be of interest for the prognostic evaluation and follow-up surveillance in patients with neuroblastoma. We evaluated NSE levels in 80 patients with neuroblastoma. The marker correlated with stage (in stage 1 patients, the median NSE level was 9.9 ng/ml, in stage 2, 45.1 ng/ml, in stage 3, 49 ng/ml, in stage 4, 93.9 ng/ml, in stage 4S, 53.4 ng/ml) and with survival. In patients with a favorable or a poor outcome, the difference in basal NSE serum levels was statistically significant (p = 0.0001). Serial measurements revealed that there was a good correlation between NSE levels and disease course. We concluded that NSE is a good marker for neuroblastoma and its quantitative determination in serum is valuable in the management of these patients to confirm the diagnosis, monitor the effect of treatment and detect recurrent disease.

Abdominal Neoplasms↗
PubMed1998

Vasodilator actions of urocortin and related peptides in the human perfused placenta in vitro.

Urocortin, is a recently isolated peptide belonging to the CRH family that binds with high affinity to the CRH2 receptor. Like CRH, urocortin causes hypotension in the rat, but its vasoactive actions have not yet been studied in the human. We have compared the vasoactive properties of urocortin, CRH, and urotensin-1 in the human fetal placental vasculature in vitro. Single placental lobules were bilaterally perfused (maternal and fetal sides, 5 mL/min each; 95% O2-5% CO2; 37 C), and changes in fetal arterial perfusion pressure were recorded. Submaximal vasoconstriction was induced by PGF2alpha (4+/-0.7 micromol/L), which increased perfusion pressure from 19.6+/-1.4 to 100.7+/-3.1 mm Hg (n=38; P < 0.001). Subsequent fetal arterial infusion of urocortin (0.001-1 nmol/L) caused concentration-dependent vasodilatation. Urocortin was equipotent with urotensin-1 and 25 times more potent than CRH in causing vasodilatation. Nevertheless, the maximum vasodilator responses to each of the peptides were similar (P > 0.05). The CRH receptor antagonist, alpha-helical CRH-(9-41) (0.2 nmol/L) significantly attenuated the vasodilatation produced by urocortin, urotensin-1, and CRH (P < 0.05). These results indicate a possible physiological role for urocortin in the modulation of human fetal placental vascular tone by activation of CRH2-like receptors.

Adolescent↗
PubMed1998

[Craniosynostosis: is prenatal diagnosis possible?].

The authors report a case which demonstrates how an interdisciplinary collaboration between the obstetrician and pediatrician may be activated in the event of a suspected fetal malformation, in this case craniosynostosis, although it is important to recognise the diagnostic limitations of ultrasonography regarding this type of pathology.

Adult↗
PubMed1998

[Ethical values in the regulation of the exposure to electromagnetic fields].

The purpose of the present paper is to explore some ethical issues underlying the on-going debate on regulation of human exposure to electromagnetic fields, with special reference to the estimated number of attributable cases. The core issue is how to balance the need for electricity of modern society with the threat to the population's health, given the limited number of affected and the limited resources available. The paper compares a "commensurabilist" and an "incommensurabilist" approach to this problem, and suggests to refer to the metaphor of sacrifice rather to that of trade-off. Both approaches can be found at the core of the epidemiologic profession, they can conflict but also converge; the solution has to be sought case by case, being aware of the moral relevance of this process.

Bioethics↗
PubMed1997

Comparison of three different methods for radiolabelling human activated T lymphocytes.

One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.

Cell Death↗
PubMed1997

Learning and forgetting processes in Parkinson's disease: a model-based approach to disentangling storage, retention and retrieval contributions.

Learning and forgetting a prose passage was studied in 20 patients with Parkinson's disease and in 20 normal control subjects by means of stochastic models, with the aim of identifying the learning and retaining abilities that are affected by Parkinson's disease. Results suggested that Parkinson's disease patients are impaired in developing automatic processing both during learning and retaining, while functions that require active attention are spared. The automatic/intentional dissociation, which is the hallmark of motor disturbance in Parkinson's disease, extends to memory abilities, and, on the grounds of neuroanatomical, neurochemical and neurophysiological correlates, suggests that the memory deficit in Parkinson's disease may be contingent on a dysfunction of the medial prefrontal-cingulate cortex.

Aged↗