Search PubMed⌕ Search

Biomedical subjects

A Azzarelli

Publications and source records attributed to A Azzarelli.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours.

Desmoids are locally aggressive, non-metastasizing soft-tissue tumours, whose aetiology is still unclear. In patients affected with familial adenomatous polyposis (FAP), the incidence of desmoids is much higher than in the general population. The APC gene, which is responsible for FAP, is involved in the development of desmoids associated with this syndrome. In this study 16 sporadic and four FAP-related desmoids were analysed in order to investigate the possible involvement of APC in non-syndromic cases also. The 5' end (exons 1-11) and the coding portion of exon 15 of APC were screened using the in vitro synthesized-protein assay (IVSP). Exons 5, 6, 8-14, and a region of exon 15 spanning codons 1036-1634 were investigated by single-strand conformation polymorphism (SSCP) analysis. APC germline mutations were identified in all FAP patients, but not in sporadic cases. Somatic mutations were found in three FAP-associated desmoids (75%) and two sporadic tumours (12.5%). In one of the latter cases, both alleles were affected. These findings indicate a limited role of the gene in the development of desmoid tumours outside FAP.

Adenomatous Polyposis Coli↗
PubMed1998

Left ventricular size and function in patients with noninsulin-dependent diabetes and postinfarction total or subtotal coronary occlusions.

The aim of this study was to establish the effects of postinfarction total or subtotal coronary occlusion on left ventricular remodeling in patients with noninsulin-dependent diabetes (NIDD) compared with the effects in postinfarct nondiabetic patients. The authors selected 100 patients submitted to coronary angiography between 1 and 5 weeks after acute myocardial infarction (T0: 20.5+/-15.4 days) and classified into three groups: G1: NIDD with coronary occlusion/subocclusion (n=24), G2: controls with coronary occlusion/subocclusion (n=43), G3: controls without coronary occlusion/subocclusion (n=33). At time zero (T0) the following parameters were evaluated: end-systolic and end-diastolic volume indexes (ESVi, EDVi), ejection fraction (EF), echocardiographic wall motion score index (WMI), presence of left ventricular aneurysm, and triple-vessel coronary disease. The frequencies of major cardiovascular events were recorded during follow-up. Significantly greater ESVi and EDVi were noted in G2 compared with G3 (P<0.0001), while no significant differences were observed between NIDD patients and controls. Although left ventricular global and segmental dysfunctions were increased in diabetics, controls with coronary occlusion/subocclusion presented more pronounced EF reduction (P<0.0001 G2 vs G3) and higher elevation in WMI (P<0.005 G2 vs G3). Cardiac events during follow-up were elevated in G1 and G2, particularly as regards the occurrence of congestive heart failure. The authors conclude that NIDD seems to influence in a positive way left ventricular remodeling associated with postinfarct total or subtotal coronary occlusion.

Coronary Angiography↗
PubMed1997

Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms.

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated-dedifferentiated (WD-DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD-DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD-DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD-DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas.

Adolescent↗
PubMed1997

Relevance of cytogenetic and fluorescent in situ hybridization analyses in the clinical assessment of soft tissue sarcoma.

Soft tissue sarcomas are a heterogeneous group of malignant tumors displaying a wide range of clinical presentations, morphological features, and biological behaviors. These characteristics and the recent development of differentiated treatment regimens for the different types of soft tissue sarcomas call for refined histological classification using additional ancillary approaches such as cytogenetic and molecular genetic analyses. We coupled classical cytogenetics and fluorescent in situ hybridization (FISH) on both metaphases and interphase nuclei to show the feasibility of this approach to characterize tumor type-specific chromosome rearrangements in soft tissue sarcomas of different histotype. In 35 cases analyzed, we detected the presence of specific chromosome rearrangements such as t(X;18) in synovial sarcoma (SS), t(12;16) in myxoid liposarcoma (MLS), t(11;22) in peripheral primitive neuroectodermal tumors (pPNET), t(2;13) in alveolar rhabdomyosarcoma (ARMS) and ring chromosomes in dermatofibrosarcoma protuberans (DFSP). In several cases, the presence of these cytogenetic rearrangements was of help for a differential diagnosis. The FISH analysis using painting probes not only confirmed the cytogenetic results but also allowed the identification of tumor-specific chromosome changes in those cases presenting low mitotic index or with poor quality chromosomes. Moreover, in the absence of analysable metaphases, FISH was successfully performed on interphase nuclei. Taken together, these results indicate both the diagnostic and clinical relevance of a molecular cytogenetic analysis in the study of soft tissue sarcomas.

Biomarkers, Tumor↗
PubMed1996

Variant translocation t(6;10)(p21;q22) in pulmonary chondroid hamartoma.

Banding cytogenetics and fluorescence in situ hybridization analysis of a pulmonary chondroid hamartoma (PHC) showed the presence of a t(6;10)(p21;q22). A cytogenetically identical translocation has previously been found in another case of PHC, suggesting that it could represent a variant form of the standard t(6;14)(p21;q24).

Chromosome Banding↗
PubMed1996

Prior myocardial infarction and prognostic outcome in patients with unstable angina in a postdischarge follow-up.

The authors investigated how a previous myocardial infarction (MI) affects the prognosis of unstable angina pectoris in patients with maintained or slightly reduced left ventricular performance. From January 1991 to August 1993, 131 patients hospitalized with the diagnosis of Braunwald's class II-III unstable angina and ejection fraction > 40% were included. The enrolled patients were divided into two groups: (1) group I: unstable angina with prior MI (n = 70, 49 men, 21 women, aged between fifty-one and eighty years, mean: 65.7 +/- 8.5 years, Braunwald's class III: 71.4%), (2) group II: unstable angina with previous infarction (n = 61, 31 men, 30 women, aged between forty-nine and eighty, mean: 66.3 +/- 7.9 years, Braunwald's class III: 83.6%). The follow-up varied between six and twenty-four months. The frequency of major cardiovascular events (deaths, MI, reinfarction, heart failure, and recurrent unstable angina) and the number of revascularization procedures (percutaneous transluminal coronary angioplasty [PTCA] and coronary artery bypass grafting [CABG]) established during follow-up were evaluated. Hospitalization was 10.1 +/- 2.9 days in group I and 8.6 +/- 2.6 days in group II (P < 0.01). The duration of the follow-up was comparable between the two groups. Based upon predischarge noninvasive evaluation, patients in both groups were selected to undergo coronary and ventricular angiography: 38 of 70 (55.7%) in group I and 39 of 61 (62.3%) in group II; among them, 52.9% in group I and 24.6% in group II (P < 0.05) were submitted to coronary revascularization, while the others received medical treatments: 33 of 70 in group I and 46 of 61 in group II (P < 0.05). In the subset of patients submitted to angiography, the severity of coronary disease did not differ between the groups, and group I showed a statistically lower ejection fraction than group II (P < 0.005). The frequency of major cardiovascular events demonstrated a mortality rate of 2.9% in group I and 1.6% in group II. Acute MI/reinfarction accounted for 2.9% of the cases in group I and 3.3% in group II. Heart failure was present in 2.9% of group I. Recurrence of unstable angina was diagnosed in 11.4% of group I and 6.5% of group II. CABG and PTCA were performed, respectively in 7.1% and 5.7% in group I and in 6.6% and 4.9% in group II. During follow-up 75.7% of patients in group I and 80.3% in group II were asymptomatic. No significant differences in the frequency of cardiovascular events were reported between the two groups. As result of more aggressive therapeutic approaches following the detection of residual ischemia in patients with prior infarction, the authors conclude that the prognosis of unstable angina in the group with previous infarction does not seem to differ from that of unstable angina in the absence of prior necrosis in patients whose left ventricular function is maintained or slightly decreased.

Aged↗
PubMed1995

Involvement of chromosomes 17 and 22 in dermatofibrosarcoma protuberans.

Literature on the cytogenetics of dermatofibrosarcoma protuberans (DFSP) is limited; only 10 cases with chromosome aberrations have been reported. They are karyotypically characterized by the presence of supernumerary ring(s), either as the sole cytogenetic abnormality or together with a few additional structural or numerical changes. We report the cytogenetic and fluorescence in situ hybridization (FISH) analysis of three new DFSP, one primary and two recurrent tumors. In two cases we found a supernumerary ring as the sole change, whereas the third had two copies of a marker chromosome and monosomy of chromosome 22. Sequences of chromosomes 17 and 22 were identified by FISH in the supernumerary rings and in the markers. The fluorescence pattern suggested that additional sequences were present in the two rings, but showed that the marker chromosomes were entirely painted by chromosome 17 and 22 probes. The findings indicate that juxtaposition and/or amplification of chromosome 17 and 22 sequences could be crucial in the pathogenesis of DFSP.

Adult↗
PubMed1995

NIDDM as unfavorable factor to the postinfarctual ventricular function in the elderly: echocardiography study.

BACKGROUND: Aging and diabetes mellitus have been recognized as strong predictors of heart failure in patients with acute myocardial infarction. The aim of this study was to assess, by echocardiography, the influence of aging and non-insulin-dependent diabetes mellitus on the changes of left ventricular parietal kinesis in patients with acute myocardial infarction over the 6 months after hospitalization. METHODS: The study population consisted of 82 patients (42 male, 40 female) aged 70 years, consecutively admitted to coronary care unit with acute myocardial infarction from January 1991 to May 1993. They were divided into two groups: group 1 comprised 36 patients with non-insulin-dependent diabetes mellitus, aged 78.8 +/- 6.02 years, 17 men and 19 women; group 2 comprised 46 patients without diabetes aged 78.7 +/- 6.9 years, 25 men and 21 women. Echocardiography was performed at admission to the unit (T0), at discharge (T1), and after 6 months of follow-up (T2). The echocardiographic wall motion score index was calculated by considering the number of akinetic and dyskinetic left ventricular wall segments. Fatal and non-fatal incidents of heart failure were also considered and a multivariate analysis was applied to identify the clinical and instrumental parameters that were independent predictors of wall motion score index changes and heart failure events. RESULTS: At T1 the two groups were comparable in localization of acute myocardial infarction, previous myocardial infarction, creatinine kinase serum peak, ECG score and wall motion score index. A statistically significant reduction in akinesia (P < 0.001) was observed in group 2 at T1 and T2, but was not seen in group 1. At T2 the difference in wall motion score index between the groups became significant (P < 0.05). The occurrence of heart failure was significantly higher in group 1 than in group 2 either during hospitalization (P < 0.03) or during follow-up (P < 0.004). The multivariate analysis identified non-insulin-dependent diabetes mellitus as an independent predictor of lacking recovery in LV kinesis (P < 0.01) and of heart failure development (P < 0.001). CONCLUSION: In elderly patients with non-insulin-dependent diabetes mellitus lack of recovery in wall motion score index after acute myocardial infarction seems to be an important factor, with a higher heart failure prevalence adversely affecting the in-hospital and long-term outcome. Non-insulin-dependent diabetes mellitus appears to be an important factor related to this unfavorable outcome.

Aged↗
PubMed1995

Sudden cardiac death rate in an area characterized by high incidence of coronary artery disease and low hardness of drinking water.

From January 1992 to January 1993 the incidence of sudden cardiac death among the population of the Media Valle del Serchio area (Tuscany, Italy), composed of a population of 35,000, was found to be twice that of the European average; 32 cases have been reported over this period in that area (9 per 10,000 in the examined year), with a male/female (M/F) ratio of 2.5:1 (23 M, 9 F). In Italy the mean incidence of sudden death was calculated as 6/10,000 and in Europe 5/10,000. In the examined population hypertension was the coronary risk factor present most frequently (87%). A previous diagnosis of coronary artery disease was documented in 21 cases (66%); 5 of these exhibited previous myocardial infarction and 3 previous myocardial infarction associated with left ventricular heart failure. In 7 subjects no previous cardiovascular disorders were discovered. Prodromal symptoms had been reported in 20 cases (62%), which included chest pain in 8 and dyspnea in 8. In the examined geographic area a high prevalence of coronary artery disease was verified through the records of the Public Health Service, which documents the main causes of mortality in Tuscany, and through the hospitalization data and the services provided for ischemic heart disease at the local coronary care unit compared with the national average. Moreover, research was accomplished on physical and chemical properties of drinking water in the same area, and this revealed a very low total hardness due to the paucity of calcium and magnesium salts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Surgery in soft tissue sarcomas.

The surgical treatment of soft tissue sarcomas improved in the last decade, with better regional control and an increased number of limb sparing operations, but procedures and criteria of indication are not unified. Moreover, a great discrepancy exists in the incidence rate of local recurrence reported in literature, and also major centres denounce a high rate of local failures. The major predictive parameters of adequate regional control are the size and location of primary lesion, the pathological grading, previous treatments and the quality of surgical margins. Results in terms of regional control of 417 cases treated at our institute in the period 1974-1984 are analysed and discussed. Local failure occurred in 113 cases (27% crude, 31% actuarial risk at 5 years) and has been analysed according to factors which had impact on local failures: pathological grading (low grade 24% local recurrence vs. high grade 35% recurrence, P = 0.05), site (extremity and girdle 26% vs. trunk and head and neck 47%, P = 0.001), previous surgical treatment (32% for lesions recurrent at entry vs. 43% for virgin tumours, P = 0.05), quality of margins (adequate surgery 24% vs. marginal surgery 47%, P < 0.001); intralesional operations are excluded from this series. Histopathology is stratified in four categories that can actually influence the treatment schedule: low grade, spindle cell type high grade, small blue cell, miscellaneous sarcomas of different or unclear histogenesis. The size is detailed in different definitions of small or large, in a site-size relationship which may be useful in surgical practice, with no prognostic purposes. Finally, the adequacy of a surgical treatment is evaluated and discussed by the quality of surgical margins, defined according to the concept of compartment. A surgical indication rationale is, therefore, proposed taking into account the above-mentioned parameters and conclusive points of discussion.

Female↗
PubMed1993

[The effect of physical exercise on the response to exertion in the elderly].

BACKGROUND: A decrease in adaptation to exertion has been observed as age progresses. Although this decline may also be affected by factors such as health conditions and age, physical inactivity related to sedentary behaviour plays a dominant role. METHODS: In order to evaluate the influence of physical activity on cardiovascular response to exertion in the elderly, 4 groups of 22 subjects each were submitted to maximal electrocardiographic exercise test on a cycloergometer (multistage program with 30 Watts x 3 min. steps). All subjects were male. The composition of the groups was as follows: 1) veteran long distance runners (mean age: 71 +/- 5.4); 2) sedentary veterans (mean age: 69.8 +/- 3.9); 3) young long distance runners (mean age: 25.4 +/- 4.3); 4) sedentary young adults (mean age: 25.8 +/- 3.9). The endurance athletes, well fitted to competition, had been practicing sport activity for at least 3 years. RESULTS: Heart rate, arterial systolic and diastolic blood pressure were recorded; mean blood pressure and double product were calculated at baseline and at the climax of the stress test; furthermore, total and maximal watts were recorded. For each of the parameters, Student's t test for non-paired observations were used to evaluate statistical differences amongst the four groups. The most interesting result arises in the comparison between veteran long distance runners and sedentary young adults: between the two groups no statistically significant differences in workload, expressed as total watts (1649.55 +/- 296.32 vs 1650.00 +/- 446.32; p = NS) and maximal watts (175.91 +/- 19.19 vs 173.18 +/- 24.38; p = N.S.), were observed. On the contrary, highly significant differences in both total (p < 0.01) and maximal (p < 0.01) watts were noticed by comparing long distance runners and sedentary subjects of the same age. CONCLUSIONS: These data support the hypothesis that the progressive reduction in physical activity, which is usually observed in aging, is the major determinant of exercise deconditioning in the elderly.

Adolescent↗
PubMed1993

Preoperative doxorubicin plus ifosfamide in primary soft-tissue sarcomas of the extremities.

A total of 51 patients with large, primary, high-grade soft-tissue sarcomas of the extremities were treated at our institute with two preoperative and three postoperative cycles of doxorubicin plus ifosfamide/mesna. Preoperative doxorubicin was given intra-arterially for lesions of the lower extremities. Of 47 evaluable patients, 22 (47%) showed clinical responses and 21 (45%), pathologic responses. Clinical and pathologic responses, however, were not necessarily coincident in the same patient. Conservative limb-sparing surgery was performed in 41 cases (87%), and in 4 cases amputation was avoided as a result of the local improvement induced by chemotherapy. Local recurrence occurred in 12 cases (25%), 3 of which required further amputation. Although the follow-up period was only 28 months, the 4-year actuarial survival was 91% and the 4-year metastasis-free value was 69%. An evident difference existed between patients who showed a documented clinical response to chemotherapy and those who did not, the 4-year metastasis-free value being 85% and 59% (P = 0.1), respectively. Adjuvant preoperative chemotherapy may allow for limb-salvage surgical procedures in selected cases.

Actuarial Analysis↗
PubMed1993

Perspectives on anthracyclines plus ifosfamide in advanced soft tissue sarcomas.

Doxorubicin and ifosfamide are currently the two main drugs for the treatment of soft tissue sarcomas in adults. Given in combination at full doses, with or without dacarbazine, these agents have induced higher response rates than were obtained with single-agent therapy. Because they involve considerable myelotoxicity, however, full-dose regimens should be reserved for patients with good performance status and without potential septic foci. Obviously, higher response rates do not automatically translate into improved survival. In soft tissue sarcomas, full-dose polychemotherapy will most probably provide a survival benefit only in selected patients in whom surgery can be performed in combination with chemotherapy. Prospective trials in such patients, although difficult to carry out, would be highly desirable. The information they would provide might help the clinician tailor treatment in a more rational way and improve chances of cure or long-term survival in at least some patient subgroups.

Antibiotics, Antineoplastic↗
PubMed1992

Primary childhood osteosarcoma: the role of salvage surgery.

The overall results of salvage surgery for lung metastases were evaluated on 174 consecutive patients with primary osteosarcoma below the age of 20, resected in Milan between 1970 and 1988. Seventy-two children treated in the years 1970-1981 were compared with 102 children treated in the years 1982-1988. In the latter period, adjuvant chemotherapy was replaced by neo-adjuvant programs and salvage surgery was applied systematically to all patients with resectable lung metastases through median sternotomy. During the last period, the overall 5 year survival improved significantly from 35% to 58% (P less than 0.001), while the disease free survival rose from 38% to 45% (median 15 vs. 33 months, P = 0.3). The proportion of patients with completely resected lung metastases rose from 17% (7/42) to 55% (27/49), without operative mortality, and the overall survival from detection of lung metastases (including unresected cases) improved from 0 to 28% at 5 years (P less than 0.001). The survival benefit was observed only in the group of children with resected metastases. These data indicate that systematic bilateral pulmonary resection, combined with neoadjuvant chemotherapy, has contributed to improve the final cure rate of childhood osteosarcoma.

Adolescent↗