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M Mercuri

Publications and source records attributed to M Mercuri.

At least 55 records · Page 3Linked to original sources
PubMed2000

Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects.

We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultrasonograph in patients with type 2 diabetes (n = 81; 41 men and 40 women; mean age, 67.1 yr) and nondiabetic subjects (n = 105; 48 men and 57 women; mean age, 65.5 yr) and genotyped for the Leu7Pro polymorphism in prepro-NPY. The frequency of Pro7 in prepro-NPY was 9.9% (8 of 81) in diabetic patients and 14.3% (15 of 105) in control subjects (P = 0.360). The mean common carotid IMT was 1.04 +/- 0.02 mm in nondiabetic subjects without the Leu7Pro polymorphism and 1.14 +/- 0.04 mm in nondiabetic subjects with in (P = 0.156) and 1:18 +/- 0.03 and 1.58 +/- 0.21mm in diabetic patients without and with the Leu7Pro polymorphism (P = 0.004), respectively. In the analysis of covariance of the entire group, the mean common carotid IMT was independently associated with the Leu7Pro polymorphism (F = 5.165; P = 0.024) after adjustment for known risk factors. Thus, the presence of the Pro7 substitution in the prepro-NPY associates with increased carotid atherosclerosis.

Aged↗
PubMed2000

Lipid-altering efficacy and safety of simvastatin 80 mg/day: worldwide long-term experience in patients with hypercholesterolemia.

BACKGROUND AND AIM: Clinical data suggesting that larger decreases in low density lipoprotein cholesterol (LDL-C) result in greater reductions in coronary heart disease events have led to the establishment of aggressive LDL-C targets for the treatment of hypercholesterolemia. In view of this, the efficacy and safety of a new maximum dose of simvastatin, 80 mg, were evaluated in 9 studies involving 2819 hypercholesterolemic patients. This report focuses on the combined results from the 4 main or Pivotal studies in which a total of 1936 patients received simvastatin 40 or 80 mg for 36 to 48 weeks. METHODS AND RESULTS: The Pivotal studies had similar randomized, multicenter, controlled, double-blind, parallel-group designs. Their combined results demonstrated a significant advantage in the LDL-C-lowering effect for the 80 mg dose. At week 24, the mean percentage reductions (95% confidence intervals) from baseline in LDL-C for the 40 and 80 mg groups were -39.8% (-40.9, -38.7) and -45.7% (-46.5, -45.0) respectively (p < 0.001, between groups), and larger reductions in total cholesterol and triglycerides were also observed in the 80 mg group. Both doses were well tolerated. No new or unexpected adverse events were observed and the overall clinical event profiles were similar in the two groups. Clinically significant hepatic transaminase increases (> 3 times the upper limit of normal/ULN) and myopathy (muscle symptoms plus creatine kinase increase > 10 times ULN) occurred infrequently with both doses. Simvastatin 80 mg had a comparable efficacy and safety profile in women and men as well as in non-elderly and elderly patients. CONCLUSIONS: Simvastatin 80 mg provides additional LDL-C and triglyceride reductions compared to the 40 mg dose and has an excellent safety and tolerability profile.

Adolescent↗
PubMed1999

Italian Cooperative Study for the treatment of children and young adults with localized Ewing sarcoma of bone: a preliminary report of 6 years of experience.

BACKGROUND: In 1991, the Italian Association for Pediatric Hematology-Oncology and the National Council of Research (CNR) initiated an Italian Cooperative Study (SE 91-CNR Protocol) with the main objective of improving the overall survival (SUR) and the event free survival (EFS) of children and young adults with localized Ewing sarcoma and primitive neuroectodermal tumors of bone compared with a previous study (IOR/Ew2 Protocol). METHODS: Between November 1991 and November 1997, 165 patients were enrolled in this study, 160 of whom were evaluable. The patients were treated with a multimodal approach characterized by intensified chemotherapy, hyperfractionated and accelerated radiation therapy, and the addition of ifosfamide and etoposide to standard chemotherapy with vincristine, actinomycin-D, doxorubicin, and cyclophosphamide. RESULTS: After a median follow-up of 37 months, 126 of the 160 evaluable patients remained free of disease recurrence. Thirty-one patients developed a disease recurrence (20 with disseminated disease). CONCLUSIONS: The 3-year SUR and EFS rates found in the current study (83.6% and 77.8%, respectively) may be considered satisfactory. Only age at diagnosis < or =14 years and a good histologic response appeared to affect the outcome of patients with localized Ewing sarcoma positively. These results appear to demonstrate the efficacy of the addition of ifosfamide in induction chemotherapy to four-drug standard combination chemotherapy, as confirmed by the improved outcome in terms of 3-year EFS reported in the SE 91-CNR Protocol compared with the IOR/Ew2 Protocol (77.8% vs. 60.7%). In addition, the better outcome also could be explained by the change in treatment strategy with a trend toward the use of more surgery than radiation therapy compared with the authors' previous protocol.

Adolescent↗
PubMed1999

Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I.

A randomized, blinded, multicenter clinical trial was performed comparing low- and high-dose simvastatin (40 and 80 mg) with comparable doses of atorvastatin (20 and 40 mg) for effects on plasma concentrations of lipoproteins and apolipoprotein A-I over 12 weeks in 842 patients with elevated low-density lipoprotein cholesterol. The 2 agents reduced low-density lipoprotein cholesterol and triglycerides to a comparable degree, but simvastatin raised high-density lipoprotein cholesterol and apolipoprotein A-I more than atorvastatin, suggesting differences in metabolic effects of the 2 agents on plasma lipids and lipoproteins.

Anticholesteremic Agents↗
PubMed1999

Relationship of angiotensin-converting enzyme gene polymorphism to carotid wall thickness in middle-aged men.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50-59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18 +/- 0.30, 1.22 +/- 0.24, and 1.08 +/- 0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.

Carotid Arteries↗
PubMed1999

Stiffness of the aortic wall in hypercholesterolemic children.

Arterial stiffness may be an indicator of early vascular changes signaling the development of vascular disease, while hypercholesterolemia is a well-recognized promoter of atherogenesis. It has been shown that hypercholesterolemic children have a thicker intima-media in the carotid artery than children with normal cholesterol. The aim of this study was to assess the stiffness of the abdominal aorta in children with hypercholesterolemia. Noninvasive imaging evaluation of the aorta was performed in 85 outpatient children (age, 3 to 14 years) with and without high cholesterol levels ((and) 247 mg/dL [6.4 mmol/L], respectively). Ultrasound imaging of the abdominal aorta that allowed diameter measurements was available in 67 children. Using an image-processing workstation, the maximum and minimum internal diameter of the aorta was measured, and the following indices of elastic properties of the abdominal aorta were derived: arterial strain, pressure-strain elastic modulus, and stiffness. No statistical difference for aortic strain, stiffness, and elastic modulus was found in normocholesterolemic compared with hypercholesterolemic children. The effect of age on the elastic modulus was different in the two groups: in normal children, the elastic modulus increased linearly with age (y = -0.020+0.003 x age [months], P<.001), while the high-cholesterol group had a weak increase in this parameter with age (y = 0.118+0.0009 x age, P = .051). The slope of the regression equations (elastic modulus vage) was significantly different in the two groups (t = 2.45, P = .017). The behavior of arterial stiffness with respect to age was similar, y = 0.677+0.018 x age (P = .002) in normocholesterolemic children and y = 2.06+0.00198 x age (P = .66) in hypercholesterolemic children. The slope of the regression equations (stiffness v. age) was significantly different in the two groups (t = 2.37, P = .021). The present study demonstrates an influence of hypercholesterolemia on age-related modification in the elastic properties of the aorta. A remodeling of the aortic wall in hypercholesterolemic children (cholesterolemia >247 mg/dL) could explain the different age-dependent increase in aortic elastic modulus and stiffness.

Adolescent↗
PubMed1999

Associations of risk factors with segment-specific intimal-medial thickness of the extracranial carotid artery.

BACKGROUND AND PURPOSE: It is generally assumed that risk factors affect extracranial carotid intimal-medial thickness similarly among all arterial segments. This assumption underlies use of single segments or walls of segments as outcome variables for risk factor studies and clinical trials. However, if the impact of risk factors was unequal for various segments or circumferentially asymmetrical within segments, then inferences drawn from a single segment or wall might not be generalizable; furthermore, since individual segments and walls have unique histological characteristics and are differentially exposed to turbulent flow, risk factor relationships with a particular segment or wall may provide inferences regarding pathogenesis of atherosclerosis. METHODS: We evaluated associations of risk factors with intimal-medial thickness at the near and far walls of the common carotid artery, bifurcation, and internal carotid artery in 280 individuals older than 45 years equally divided between coronary artery disease cases and controls and between men and women. RESULTS: The patterns of differences in mean intimal-medial thickness among segments vary, depending on age, history of hypertension, body mass index in women, and coronary (case-control) status. The asymmetry of disease depended on blood glucose concentrations, prior history of diabetes, smoking, and coronary status. Sex, postmenopausal status, LDL cholesterol, systolic blood pressure, and history of myocardial infarction all had statistically significant relationships with intimal-medial thickness that were fairly homogeneous among arterial sites. CONCLUSIONS: Focus on an individual segments or walls of the extracranial carotid arteries may lead to overestimation or underestimation of associations of risk factors with extracranial carotid intimal-medial thickness.

Aged↗
PubMed1999

[Surgical treatment of pulmonary metastases of osteosarcoma. Apropos of 206 operated cases].

Two hundred and six patients were operated for lung metastases from osteosarcoma over a period of 7 years. The operative mortality was 0.3%. The actuarial survival for the overall population was 78% at one year. 50% at two years, 40% at three years and 34% at five years. The most significant prognostic factors (p < 0.01) were the number of metastases, the duration of the free interval and the degree of differentiation. Sex, age, site and type of resection of osteosarcoma or the metastases did not have any influence on prognosis. Surgical resection of lung metastases currently constitutes an essential part of the multidisciplinary management of osteosarcoma.

Adolescent↗
PubMed1998

Neoadjuvant chemotherapy for Ewing's sarcoma of bone: no benefit observed after adding ifosfamide and etoposide to vincristine, actinomycin, cyclophosphamide, and doxorubicin in the maintenance phase--results of two sequential studies.

BACKGROUND: Ifosfamide (IF) alone or combined with etoposide (ET) was reported to be effective in the treatment of patients with Ewing's sarcoma who relapsed after treatment with the VACA regimen, which consisted of vincristine (VC), actinomycin (AC), cyclophosphamide (CP), and doxorubicin (AD). The purpose of this article is to report the results achieved in a new neoadjuvant protocol in which IF and ET were added to the conventional VACA regimen and administered to patients with localized disease. METHODS: In this study, eighty-two patients were treated between May 1988 and October 1991. Chemotherapy consisted of two induction cycles of VC/CP/AD followed by alternating cycles of VC/AD/CP, VC/IF/AC, IF/ET, and VC/CP/AC after local treatment. Twenty-two patients (27%) were treated with surgery only, 22 (27%) underwent surgery followed by radiation therapy, and 38 (46%) received radiotherapy only. RESULTS: At a median follow-up of 6.7 years (range, 4-9 years), 43 patients (52%) remained continuously disease free, and 39 relapsed (34 with metastases, 4 with local recurrence and metastases, and 1 with a local recurrence). These results were similar to those obtained at the same institute in a previous neoadjuvant study (March 1983 and April 1988) that included 108 patients treated with the conventional 4-drug regimen. The 5-year disease free and overall survival in the current study were 54% and 59%, respectively, and in the first study were 50% and 56%, respectively. CONCLUSIONS: The comparison of these two sequential studies, although not randomized, referred to homogeneous groups of patients observed at the same institution who were treated by the same medical team. No advantage was observed when IF and ET were added to the VACA regimen.

Adolescent↗
PubMed1998

[Not Available].

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Journal Article↗
PubMed1998

Magnitude of alimentary lipemia is related to intima-media thickness of the common carotid artery in middle-aged men.

Fat intake leads to generation of potentially atherogenic triglyceride-rich lipoproteins (TRL). To investigate the relationship between early atherosclerotic changes and accumulation of hepatic and intestinal TRL after oral fat intake, an estimate of the intima-media thickness (IMT) was made using ultrasound of the common carotid artery, and postprandial TRL was quantified during a standardized oral fat tolerance test in 30 healthy normo- and hypertriglyceridemic middle-aged men. At base line the expected positive association between the LDL cholesterol level and the IMT of the common carotid artery was observed (r = 0.53, P<0.01). In addition, postprandial plasma triglycerides, in particular those measured late (6 h) after intake of the test meal, correlated positively with the IMT (r = 0.44, P<0.05). Of note, this latter correlation was independent of both the LDL cholesterol and the fasting plasma triglyceride concentrations. In a multivariate analysis, 39% of the total variability for the common carotid IMT were explained by age, LDL cholesterol and the postprandial triglyceride level. In univariate analysis, few statistically significant relations were found between common carotid IMT and postprandial levels of chylomicron remnants, VLDL and VLDL remnants of different particle size, the latter determined by specific measurements of ApoB-48 and ApoB-100 in subfractions of TRL. Therefore, in healthy middle-aged men, elevated postprandial triglyceride levels might identify a metabolic state related to early atherosclerosis.

Apolipoprotein B-100↗
PubMed1998

The value of imaging in the diagnosis and treatment of bone tumors.

The authors report their experience in the diagnosis of bone tumors at the Rizzoli Institute of Bologna. The main imaging techniques used to this purpose are conventional radiography, CT, MRI, and isotope bone scan. Angiography is rarely used. Conventional radiography is the examination of choice and is sufficient in several benign lesions not requiring treatment. Supplementary imaging studies are usually needed when radiographic findings are questionable and/or the lesion requires treatment. When a biopsy is required, it should be carried out after a complete imaging work-up, which sometimes allows a correct prebiopsy diagnosis, indicates the biopsy modality, approach and site, and is also mandatory to stage the tumor, plan the surgical approach and technique, and show in the finest details the occult tumor spread. CT best shows mineralized tissues and pulmonary metastases. It is also frequently used as a guide for needle biopsies. MRI beautifully shows the different tissues and compartments and it is particularly sensitive in depicting fat. Moreover, it can be repeated many times, even in pregnant women, because it needs no ionizing radiations and iodinated contrast; it is also free of artifacts in the patients with orthopedic devices which are usually nonferromagnetic. However, the execution of an adequate MRI requires experience and knowledge of bone pathologic conditions. Bone scan helps in detecting any 'active' area in the bone. It can be thus useful to depict lesion quiescence or activity and to stage any tumor which can metastasize to the skeleton. Bone scan is also helpful to show bone lesions when they are not visible on plain radiographs and indicates the tumor response to preoperative chemotherapy. Angiography is helpful when a preoperative selective embolization is needed, or when complex vertebral surgery or vascular surgery are planned. The bad outcome of bone tumors often depends on incomplete, inadequate or misinterpretated imaging findings.

Adolescent↗
PubMed1998

Neoadjuvant chemotherapy for extremity osteosarcoma--preliminary results of the Rizzoli's 4th study.

A neoadjuvant chemotherapy protocol (1/93-1/95) for extremity osteosarcoma preoperatively using high-dose methotrexate (HDMTX) as single agent per cycle and three different combinations of other drugs (CDP/IFO,CDP/ADM,IFO/ADM) is reported. The four drugs were used postoperatively as single agents. Treatment was uniform, but suspended earlier if total necrosis was attained. An improvement was found in the results of the previous study using only IFO postoperatively, with 16/119 patients (97%) avoiding amputation, and 38 (32%) attaining complete necrosis. At a 3-year (2-4 years) mean follow-up, 92 patients (76%) remained continuously disease-free, 2 died of chemotherapy-related toxicity and 25 suffered relapse. Projected 3-year DFS also improved (75% vs. 60%; p = 0.04). Despite limb salvage, local recurrences (6.3%) and infections were few, although postoperative chemotherapy was restarted within a week. Therefore, until new effective drugs are found, expertise in using the four known drugs may improve cure rate and help to avoid amputation in almost all patients.

Adolescent↗
PubMed1998

Predictive factors of histological response to primary chemotherapy in Ewing's sarcoma.

Clinicopathologic variables associated with a good histological response to primary chemotherapy in Ewing's sarcoma are identified. The histological response to preoperative chemotherapy in 243 cases of Ewing's sarcoma treated with neoadjuvant chemotherapy was analyzed in relation to different clinicopathological features (sex and age of the patients, tumor size, serum lactate dehydrogenase (LDH) levels, tumor site) and to the type and schedule of anticancer drugs delivered preoperatively according to three consecutive chemotherapy regimens. A higher rate of good responses was achieved with the use of ifosfamide and dactinomycin in addition to a conventional three-drug VAC regimen, suggesting that these drugs should be included from the beginning in neoadjuvant regimens for the treatment of Ewing's sarcoma. The analysis of event-free survival in 158 patients with a 4-year minimum follow-up confirmed that histological response to preoperative chemotherapy is a reliable predictor of outcome in Ewing's sarcoma.

Adolescent↗
PubMed1998

Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy.

Between September 1986 and September 1991, 44 patients with lung metastases originating from an osteosarcoma of an extremity were treated with: primary chemotherapy, simultaneous resection of primary and metastatic lesions (when feasible), and then further chemotherapy. After primary chemotherapy, lung metastases disappeared in 5 patients, whereas in 11 patients they remained surgically unresectable. All 16 patients received local treatment of the primary tumor only. In the remaining 28 patients simultaneous surgical treatment of the primary and the metastatic tumor was performed. The removal of metastatic lesions was complete in 25 and incomplete in 3 patients. With a median follow-up of 8 years (5.5-10.8) all 14 patients who never achieved a tumor-free status died. Of the 30 patients who achieved remission 5 (17%) remained continuously free of disease and 25 developed new metastases, associated with local recurrence in 4 cases. The 5-year overall survival for all 44 patients of the study was 14%, and the 5-year disease-free survival for the 30 patients who reached remission was 17%. These results are significantly worse than those achieved with the same chemotherapy protocol in 144 contemporary patients with localized disease at presentation (73% disease-free and 79% overall survival). We conclude that, despite aggressive chemotherapy which is successful in patients with localized disease, the prognosis remains very poor for patients with osteosarcoma of the extremities with lung metastases at presentation, and justifies the use of novel therapies.

Adolescent↗
PubMed1998

Ifosfamide and actinomycin-D, added in the induction phase to vincristine, cyclophosphamide and doxorubicin, improve histologic response and prognosis in patients with non metastatic Ewing's sarcoma of the extremity.

The role of ifosfamide as first-line chemotherapy treatment of non metastatic Ewing's sarcoma of the extremity is still under discussion. The purpose of this paper is to report the results achieved in a neoadjuvant protocol (REN-3) in which ifosfamide, added to the conventional VACA regimen, was employed since the induction phase. Induction chemotherapy consisted of vincristine, cyclophosphamide, doxorubicin, actinomycin-D and ifosfamide. After local treatment, patients received the drugs used in the induction phase and etoposide. Between November 1991 and November 1994, 61 patients with non metastatic Ewing's sarcoma of the extremity were treated. Forty-nine patients underwent surgery and 73.5% of them had a good histologic response. At a median follow-up of 60 months (range 32-76), 48 patients (79%) remained continuously disease-free. The 5-year event-free and overall survival were 77% and 87%, respectively. These results were significantly better both in terms of histologic response or event-free and overall survival than those obtained in 58 patients with non metastatic Ewing's sarcoma of the extremity treated in a previous protocol (REN-2) in which the same drugs were used, but ifosfamide was employed only in the maintenance phase. The present study suggests the importance of early use of ifosfamide in the treatment of patients with non metastatic Ewing's sarcoma of the extremity.

Adolescent↗
PubMed1998

Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.

PURPOSE: In osteosarcoma of the extremity, a strong correlation between chemotherapy-induced necrosis and prognosis has been reported. The aim of this study was to investigate the possible factors that influence histologic response to primary chemotherapy. PATIENTS AND METHODS: In 272 patients with high-grade osteosarcoma of the extremity preoperatively treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and doxorubicin (ADM), the histologic response to chemotherapy was evaluated and graded as complete (no viable tumor cells) or incomplete (persistence of viable tumor cells). Several factors, such as metastatic disease to the lung at diagnosis, sex, age, site and tumor volume, histologic subtype, serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate (MTX) pharmacokinetics were investigated to test their predictive significance on histologic response. RESULTS: Fifty-one patients with localized disease (20.6%) and none of the 25 patients with metastatic disease at presentation had a complete histologic response (P = .006). After multivariate analysis, performed on patients with localized disease only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were proven to be significant predictive factors of histologic response. A complete response was seen in 28.8% of patients with 700 micromol/L or greater MTX serum levels and in 9.9% of those patients with lower levels (P = .001). The chondroblastic subtype was less responsive (6.1% of complete response), compared with the osteoblastic (16.3%), fibroblastic (33.3%), and telangiectatic (42.3%). CONCLUSION: Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.

Adolescent↗