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M Mercuri

Publications and source records attributed to M Mercuri.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging.

BACKGROUND: This study was designed to investigate the effects of lipid-lowering by simvastatin on human atherosclerotic lesions. METHODS AND RESULTS: Eighteen asymptomatic hypercholesterolemic patients with documented aortic and/or carotid atherosclerotic plaques were selected for the study. A total of 35 aortic and 25 carotid artery plaques were detected. Serial black-blood MRI of the aorta and carotid artery of the patients was performed at baseline and 6 and 12 months after lipid-lowering therapy with simvastatin. The effects of the treatment on atherosclerotic lesions were measured as changes in lumen area, vessel wall thickness, and vessel wall area, a surrogate of atherosclerotic burden. Simvastatin induced a significant (P<0.01) reduction in total and LDL cholesterol levels at 6 weeks that was maintained thereafter. At 6 months, no changes in lumen area, vessel wall thickness, or vessel wall area were observed. However, at 12 months, significant reductions in vessel wall thickness and vessel wall area, without changes in lumen area, were observed in both aortic and carotid arteries (P<0.001). CONCLUSIONS: This in vivo human study demonstrates that effective and maintained lipid-lowering therapy by simvastatin is associated with a significant regression of atherosclerotic lesions. Our observation suggests that statins induce vascular remodeling, as manifested by reduced atherosclerotic burden without changes in the lumen.

Aorta↗
PubMed2001

Radiological features of 24 periosteal chondrosarcomas.

OBJECTIVE: To report the imaging findings of 24 periosteal chondrosarcomas diagnosed, staged, treated and followed in a single institution, to analyze and define their pattern, and discuss their practical consequences. DESIGN AND PATIENTS: Plain films, 16 CT examinations and four MRI examinations were reviewed, and compared with the histological evaluation. RESULTS: There were 20 men and four women, aged from 17 to 65 years. Twelve lesions involved the distal femoral metaphyses (8 posteriorly), five the proximal humerus, two the proximal metaphyses of the femur and two of the tibia, two the humeral shafts and one the iliac wing. Size varied from 4 to 11 cm. The cortex was always involved (thick, 15; thin, 13). Typical cartilaginous calcifications and cartilaginous lobules were very frequent. Radial thick periosteal bone formations (n = 6) indicated calcifications between the lobules of cartilage. Medullary involvement was rare (n = 2). All patients are alive and free of disease. CONCLUSIONS: Recognizing periosteal chondrosarcoma is of paramount importance because the prognosis is excellent after adequate local surgery alone. The patterns of other surface tumors of bone are usually different.

Adolescent↗
PubMed2001

Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol.

From January 1993 to March 1995, 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol. 133 patients had localised disease, while 29 had metastases at diagnosis. These last patients were simultaneously operated upon for their primary and metastatic lesions. Chemotherapy consisted preoperatively of two cycles of high dose methotrexate (HDMTX) and one cycle each of cisplatin (CDP)-doxorubicin (ADM), CDP/ifosfamide (IFO) and IFO/ADM. After surgery, patients were treated with the aforementioned drugs used as single agents. The mean follow-up of all patients was 6.5 years (5.5-8 years). Surgery was a limb salvage in 94% of cases, and the 5-year event-free survival (EFS) and overall survival (OS) rates were 56 and 71% for patients with localised disease, and 17 and 24% for patients with metastases at diagnosis. These results did not differ from those achieved in our previous study (IOR/OS-3) in which IFO was used only postoperatively in poor responders.

Adolescent↗
PubMed2001

Metalloproteinase expression and prognosis in soft tissue sarcomas.

BACKGROUND: Degradation of extracellular matrix by tumor-associated proteases can promote cell invasion and metastasis. This study assessed the prognostic role of MMP2, MMP9 metalloproteinases, and of the metalloproteinase inhibitor TIMP2, related to disease-free survival (DFS), in soft tissue sarcoma (STS) patients. MATERIALS AND METHODS: Level and distribution of MMP2, MMP9, and TIMP2 expression were evaluated on 73 biopsies by immunohistochemistry and immunoblotting. Biopsies included 29 liposarcomas, 29 synovial sarcomas, and 15 malignant peripheral nerve sheath tumors (MPNST). Association between DFS and overall survival with different variables was assessed. RESULTS: In terms of DFS, increased MMP2 reactivity and lack of TIMP2 expression were significant for poor prognosis in all samples (P = 0.0005 and P = 0.006 respectively). MMP2 correlated to histologic grade (P = 0.005). Lack of TIMP2 expression was a poor prognostic factor for DFS in synovial sarcoma (P = 0.009), while MMP2 and MMP9 correlated with metastasis (P = 0.008 and P = 0.005, respectively) and grade (P = 0.001 and P = 0.04 respectively) in liposarcoma. CONCLUSIONS: These prognostic markers that influence growth and spread of tumor cells might be useful to define tumor aggressiveness and risk of the metastasic event.

Adolescent↗
PubMed2001

Predictive factors of disease-free survival for non-metastatic osteosarcoma of the extremity: an analysis of 300 patients treated at the Rizzoli Institute.

BACKGROUND: To identify predictive factors of disease-free survival (DFS) in patients with non-metastatic osteosarcoma of the extremity, treated with primary chemotherapy and delayed surgery. PATIENTS AND METHODS: The relationship between patient-related and treatment-related factors and prognosis was evaluated in 300 patients treated from 1986 to 1992 according to chemotherapy protocols based on high-dose methotrexate, cisplatin and doxorubicin, with the addition of ifosfamide in the post-operative phase. Univariate and multivariate analyses of prognostic factors for disease-free survival were performed. RESULTS: With a median follow-up of 9.2 (4.4-12) years, eight-year DFS was 59% (95% confidence interval (95% CI): 54-64.9). Univariate analyses showed that tumor volume > or = 150 ml (P = 0.002), histologic subtype (P = 0.028), age > 12 years (P = 0.044), high serum lactate dehydrogenase (P = 0.044) and alkaline phosphatase (P = 0.064) levels adversely affected DFS. Gender of patients and site of tumor did not influence DFS. No differences in DFS were found among the three chemotherapy protocols, whereas the use of limb-sparing surgery vs. amputation or rotation plasty (P = 0.006) and a good histologic response to primary chemotherapy (P = 0.014) positively correlated with DFS. After multivariate analyses, tumor volume > or = 150 ml (P = 0.028), age > 12 years (P = 0.051), and histologic subtype (P = 0.052) retained prognostic significance. CONCLUSIONS: In patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy, the disease-free survival is significantly influenced by tumor volume, age, and histologic subtype.

Adolescent↗
PubMed2001

A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.

AIM: Our experience of pre-operative intraarterial (i.a.) vs intravenous (i.v.) infusion of cisplatinum (CDP) in a multiagent neo-adjuvant chemotherapy for osteosarcoma of the extremity is reported. METHODS: Two successive randomized studies were performed. In the first, pre-operatively, CDP i.a. vs CDP i.v. was applied in combination with high-dose methotrexate (HDMTX) and adriamycin (ADM) within a three-drug regimen. In the second, a combination of HDMTX, ADM and IFO, within a four-drug regimen was tested. RESULTS: The rate of responses to chemotherapy (tumour necrosis > or = 90%) was significantly higher (P<0.04) for the 142 patients treated with the four-drug regimen than in the 79 patients treated with a three-drug regimen (76%vs 62%). According to the route of CDP infusion, in the three-drug regimen the rate of responses was significantly higher (P=0.004) in patients treated with i.a. CDP (77%) than in patients treated i.v. (46%); with the four-drug regimen the rate of response was not significantly different in patients treated i.a. (81%) and in patients treated i.v. (71%). No significant differences in the rates of limb salvages, local recurrence and event-free survival (EFS) were seen between the i.a. and the i.v. groups. CONCLUSION: In the treatment of osteosarcoma of the extremity, the i.a. infusion of CDP does not offer any significant advantage when this drug is used within an aggressive, multiagent, pre-operative four-drug regimen.

Adolescent↗
PubMed2001

Relationship between high-density lipoprotein paraoxonase gene M/L55 polymorphism and carotid atherosclerosis differs in smoking and nonsmoking men.

The enzyme paraoxonase (PON) can eliminate lipid peroxides and is believed to protect against low-density lipoprotein oxidation. A common polymorphism in the PON gene (PON1) causes an amino acid substitution of methionine (M) for leucine (L) at position 55 in the protein, which changes the activity of PON and can affect the risk of atherosclerosis. Because smoking is associated with increased lipid peroxidation, we studied the relationship between PON M/L55 polymorphism and the carotid artery intima-media thickness (IMT) in smokers or previous smokers (n = 112) and nonsmokers (n = 87). IMT was measured at 3 standardized segments by B-mode ultrasonography, and the overall mean IMT value of 199 randomly selected men (mean age 54.2 +/- 3.0 years) was calculated. Subjects with IMT > 1.7 mm in at least 1 standard site were considered to have carotid artery atherosclerotic disease (CAAD). For analysis, L55 homozygotes were compared with the M55 allele carriers. Nonsmoking L55 homozygotes had an 8.9% (95% confidence interval [CI], 1.6 to 16.8) higher overall mean IMT than M55 allele carriers. In smokers, however, the M55 allele carriers tended to have higher overall mean IMT values than L55 homozygotes. There was also a statistically significant interaction between M/L55 genotype and smoking status on CAAD (P =.009) by logistic regression analysis. Among nonsmokers, the L55 homozygotes had an odds ratio of 4.22 (95% CI, 1.06 to 16.8) for CAAD compared with nonsmoking M55 allele carriers. Contrary to nonsmokers, the smoking M55 allele carriers had an odds ratio of 2.22 (95% CI, 0.82 to 6.01) for CAAD when the L55/L55 genotype of smokers was a reference group. These data suggest that in nonsmoking men, a PON L55/L55 genotype may represent a genetic risk factor for CAAD. The reverse effect in smokers implies that the ability of PON to protect against CAAD is influenced by cigarette smoking. The efficiency of this inhibition probably depends on the PON M/L55 genotype.

Alleles↗
PubMed2001

Patellar tumors.

Pain in the anterior knee has become synonymous with patella chondromalacia. However, pain also is the first sign of a tumor of the patella. Tumors of the patella are rare, but they often are mistaken for other benign lesions. Benign tumors of the patella are more frequent than malignant tumors (73% versus 27%). The most common benign neoplasms are giant cell tumor and chondroblastoma. Margin of the lesion, cortical involvement, trabecular pattern, and type of the matrix are important features for a radiographic diagnosis. Bone scans, computed tomography scans, and magnetic resonance images are used for staging of the tumor before surgery. Curettage only should be considered for patients with Stage 1 or Stage 2 benign lesions. Patellectomy is indicated for patients with Stage 3 aggressive benign tumors and for patients with Stage IA malignant tumors. A patellectomy with excision of involved soft tissues is used in patients with Stage IB tumors, whereas in patients with Stage IIA tumors, an extensive patellectomy is indicated. In patients with Stage IIB tumors, an extraarticular resection of the knee is preferred when there is a small soft tissue involvement, but amputation is necessary when there is a large soft tissue mass.

Adolescent↗
PubMed2001

Modular prosthetic replacement of the proximal femur after resection of a bone tumour a long-term follow-up.

We describe 25 patients who were treated for a tumour of the proximal femur by resection and replacement with an uncemented, bipolar, modular prosthesis. When followed up after more than ten years four prostheses (16%) had required revision. Two joints showed wear and another necrosis of the acetabulum. One patient with loosening of the stem had been treated by radiotherapy to the femur. Articular cartilage seemed to be a reliable barrier to acetabular wear. Very few signs of the formation of particulate debris were observed. The most obvious feature in the bone-stem relationship was stress shielding, seen as osteoporosis of the proximal part of the femur around the stem in 68%. Functional activity was satisfactory in 68% of the patients. A better system of reattachment of the soft tissues is needed to avoid pain and a persistent limp.

Adolescent↗
PubMed2001

Osteoid osteoma and osteoblastoma of the sacrum.

This retrospective study examined 10 patients with osteoid osteoma and 11 patients with osteoblastoma localized in the sacrococcyx. In the sacrum, the diagnosis was delayed compared to other sites. Curettage through a posterior approach is the treatment of choice. Radiotherapy as well as embolization of feeding arteries may be used for the most aggressive lesions. Prognosis is generally good with a low incidence of local recurrence (<10%).

Adolescent↗
PubMed2001

Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing's sarcoma cells.

Innovative treatment modalities are needed for Ewing's sarcoma (ES), a neoplasm with a disappointingly low survival rate despite the use of aggressive multimodal therapeutic approaches. We and others (D. Yee et al., J. Clin. Investig., 86: 1806-1814, 1990; K. Scotlandi et al., Cancer Res., 56: 4570-4574, 1996) have previously shown the existence and the pathogenetic relevance of an autocrine loop, mediated by the insulin-like growth factor-I receptor (IGF-IR), which is crucial for survival and proliferation of ES cells in vitro. Moreover, we reported that the IGF-IR-blocking monoclonal antibody (MAb), alphaIR3, as well as suramin, a drug that can interfere with growth factor by binding to the receptors, inhibited both the tumorigenic and the metastatic ability of ES cells in athymic mice. In this study, we analyzed whether agents that can block the IGF-IR-mediated loop are of value in association with conventional cytotoxic drugs for the design of more effective therapeutic regimens. Both alphaIR3 MAb and suramin treatment significantly increased the antitumor in vitro effects of doxorubicin and vincristine, two drugs with a leader action on ES. These findings were obtained by both simultaneous and sequential treatments. Analysis of the proliferation rate and of apoptosis revealed that alphaIR3 MAb and suramin significantly enhanced the G(1)-phase rate induced by doxorubicin, without substantially affecting doxorubicin-G(2)-M-blockage of cell cycle, and significantly increased the induction of apoptosis, which confirmed that the specific blockage of IGF-IR deprives ES cells of an important tool for the prevention of drug-induced apoptosis. Moreover, combination treatments of doxorubicin plus alphaIR3 MAb significantly increase the doxorubicin-induced impairment of the ability of ES cells to form colonies in soft agar. In conclusion, we showed that, in ES, the blockage of IGF-IR by a neutralizing MAb or by suramin may greatly potentiate the antitumor activity of conventional chemotherapeutic drugs.

Antibodies, Monoclonal↗
PubMed2001

Effects of statins on biomarkers of bone metabolism: a randomised trial.

BACKGROUND AND AIM: Recently, several studies have indicated there may be differences among statins regarding a possible association between therapy and a reduction in risk of fractures. No data from prospective randomised clinical trials designed to assess either biochemical or clinical effects on bone metabolism are yet available. We assayed levels of biochemical markers of bone formation in stored serum samples from a recently completed randomised clinical trial conducted to compare the effects of simvastatin and atorvastatin on the lipid profile of patients with hypercholesterolaemia. METHODS AND RESULTS: This 12-week, randomised, multicenter, open-label study was designed to compare the safety and lipid-lowering efficacy of simvastatin 40 mg or 80 mg with that of atorvastatin 20 mg or 40 mg in 846 hypercholesterolaemic patients. Stored serum samples from this study were analysed to compare the effects of simvastatin and atorvastatin on 2 biomarkers of bone turnover, bone-specific alkaline phosphatase (BSAP), a marker of bone formation, and C-teleopeptide of type 1 collagen (CTx), a marker of bone resorption. Treatment with simvastatin 40 and 80 mg/day, but not atorvastatin 20 and 40 mg/day, led to significant (p < 0.05) reductions in BSAP in both men (4.1-5.4% reduction) and women (4.2-7.4% reduction). In addition, there appeared to be a dose-dependent effect with greater reductions in BSAP seen with the 80 mg dose of simvastatin. Treatment with either 20 mg or 40 mg of atorvastatin had no significant effect on BSAP levels on the groups as a whole or in the gender-specific subgroups. CTx showed a small, but not statistically significant, decrease with simvastatin, again with an apparent dose-related trend. Atorvastatin treatment generally resulted in small, non significant increases in CTx. CONCLUSIONS: The present serum bone biomarker results show that treatment with simvastatin, but not atorvastatin, decreases BSAP and suggest that simvastatin may have a beneficial effect on bone turnover.

Adult↗
PubMed2001

A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial.

OBJECTIVE: At higher doses, simvastatin has been shown to produce significantly greater increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings, a 36-week, randomized, double-blind, dose-titration study was performed in 826 hypercholesterolemic patients to compare the effects of simvastatin and atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety. PRIMARY HYPOTHESIS: Simvastatin, across a range of doses, will be more effective than atorvastatin at raising HDL cholesterol and apo A-I levels. METHODS: A total of 826 hypercholesterolemic patients were enrolled in this double-blind, randomized, parallel, 36-week, dose-escalation study. Patients randomized to simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6 weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6 weeks, and 80 mg/day for the remaining 24 weeks. RESULTS: During the first 12 weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than the comparative doses of atorvastatin, while producing slightly lower reductions in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol and apo A-I differences favoring simvastatin were larger than at the lower doses. In addition, at the maximal dose comparison, the incidence of drug-related clinical adverse experiences was approximately two-fold higher with atorvastatin 80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus 3%, p < 0.001). The incidence of clinically significant alanine aminotransferase elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%). CONCLUSIONS: At the doses compared in this study, simvastatin led to greater increases in HDL cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison, there were fewer drug-related gastrointestinal symptoms and clinically significant aminotransferase elevations with simvastatin.

Adult↗
PubMed2000

Effects of simvastatin (40 and 80 mg/day) in patients with mixed hyperlipidemia.

Mixed hyperlipidemia is characterized by both elevated total cholesterol and triglycerides. It is estimated to account for 10% to 20% of patients with dyslipidemia. This study assessed the lipid-altering efficacy and tolerability of simvastatin 40 and 80 mg/day as monotherapy. One hundred thirty patients (62 women [48%], 24 [16%] with type 2 diabetes mellitus, mean age 53 years) with mixed hyperlipidemia (baseline low-density lipoprotein [LDL] cholesterol 156 mg/dl [mean], and triglycerides 391 mg/dl [median) were randomized in a multicenter, double-masked, placebo-controlled, 3-period, 22-week, balanced crossover study, and received placebo, and simvastatin 40 and 80 mg/day each for 6 weeks. Compared with placebo, simvastatin produced significant (p <0.01) and dose-dependent changes in all lipid and lipoprotein parameters (LDL cholesterol 2.1%, -28.9%, and -35.5%; triglycerides -3.5%, -27.8%, and -33.0%; high-density lipoprotein cholesterol 3.3%, 13.1%, and 15. 7%; apolipoprotein B 3.8%, -23.1%, and -30.6%; and apolipoprotein A-I 4.0%, 8.2%, and 10.5% with placebo, and simvastatin 40 and 80 mg/day, respectively). The changes were consistent in patients with diabetes mellitus. One patient taking simvastatin 80 mg/day had an asymptomatic and reversible increase in hepatic transaminases 3 times above the upper limit of normal. Simvastatin 40 and 80 mg/day is effective in patients with mixed hyperlipidemia across the entire lipid and lipoprotein profile. The reductions in LDL cholesterol and triglycerides are large, significant, and dose dependent. The increase in high-density lipoprotein cholesterol was greater than that observed in patients with hypercholesterolemia, and appears dose dependent.

Adult↗
PubMed2000

Lipid-altering efficacy and safety of simvastatin 80 mg/day: long-term experience in a large group of patients with hypercholesterolemia. World Wide Expanded Dose Simvastatin Study Group.

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol promote the development of atherosclerosis and coronary heart disease. HYPOTHESIS: Simvastatin 80 mg/day will be more effective than simvastatin 40 mg/day at reducing LDL cholesterol and will be well tolerated. METHODS: Two similar, randomized, multicenter, controlled, double-blind, parallel-group, 48-week studies were performed to evaluate the long-term lipid-altering efficacy and safety of simvastatin 80 mg/day in patients with hypercholesterolemia. One study conducted in the US enrolled patients meeting the National Cholesterol Education Program (NCEP) LDL cholesterol criteria for pharmacologic treatment. In the other multinational study, patients with LDL cholesterol levels > or = 4.2 mmol/l were enrolled. At 20 centers in the US and 19 countries world-wide, 1,105 hypercholesterolemic patients, while on a lipid-lowering diet, were randomly assigned at a ratio of 2:3 to receive simvastatin 40 mg (n = 436) or 80 mg (n = 669) once daily for 24 weeks. Those patients completing an initial 24-week base study were enrolled in a 24-week blinded extension. Patients who had started on the 80 mg dose in the base study continued on the same dose in the extension, while those who had started on the 40 mg dose were rerandomized at a 1:1 ratio to simvastatin 40 or 80 mg in the extension. RESULTS: There was a significant advantage in the LDL cholesterol-lowering effect of the 80 mg dose compared with that of the 40 mg dose, which was maintained over the 48 weeks of treatment. The mean percentage reductions (95% confidence intervals) from baseline in LDL cholesterol for the 40 and 80 mg groups were 41% (42, 39) and 47% (48, 46), respectively, for the 24-week base study, and 41% (43, 39) and 46% (47, 45), respectively, after 48 weeks of treatment (p < 0.001 between groups). Larger reductions in total cholesterol and triglycerides were also observed with the 80 mg dose compared with the 40 mg dose at Weeks 24 and 48. Both doses were well tolerated, with close to 95% of patients enrolled completing the entire 48 weeks of treatment. Myopathy (muscle symptoms plus creatine kinase increase > 10 fold upper limit of normal) and clinically significant hepatic transaminase increases (> 3 times the upper limit of normal) occurred infrequently with both doses. There was no significant difference between the groups in the number of patients with such increases, although there were more cases for both with the 80 mg dose. CONCLUSIONS: Compared with the 40 mg dose, simvastatin 80 mg produced greater reductions in LDL cholesterol, total cholesterol, and triglycerides. Both doses were well tolerated.

Adult↗
PubMed2000

Massive bone allograft reconstruction in high-grade osteosarcoma.

From 1986 to 1994, 112 bone allograft reconstructions were performed in patients with high-grade osteosarcoma in whom neoadjuvant chemotherapy was administered. The allograft reconstruction was used in arthrodesis in 44 cases (41 knees, three ankles), as an intercalary graft in 39 (28 femurs, 11 tibias), as an osteoarticular graft in 22 (three proximal and/or distal humeri, six distal femurs, 13 proximal tibias), and as an allograft and prosthesis composite in seven (two proximal humeri, one proximal femurs, four proximal tibias). In 20 patients an autologous vascularized fibula was used to augment the allograft. Functional results were excellent or good in 74% of the patients after the primary surgery, and in 83% of the patients after secondary surgery. Complications include delayed union (49%) and fracture (27%), although there were no cases of deep infection. The incidence of delayed union, but not infection or fracture, was increased by the use of chemotherapy.

Adolescent↗