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D Donati

Publications and source records attributed to D Donati.

At least 55 records · Page 3Linked to original sources
PubMed2001

Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: results in eleven cases.

Between January 1995 and December 1999, 11 patients with synchronous multifocal osteosarcoma (SMO) received neoadjuvant treatment with high-dose methotrexate, cisplatinum, Adriamycin, and ifosfamide. After primary chemotherapy in 4 patients who had only two bone localizations, it was possible to treat all tumor foci locally. The remaining patients, with more than three bones involved, were treated surgically only in 3 cases at the primary site, while secondary lesions did not receive any treatment. The final results of our study were disappointing. All patients died of the tumor 6 to 24 months after the beginning of treatment (mean 11.9 months). Nevertheless, the survival time of the 4 patients with locally treated lesions was significantly longer than the one of 7 patients in whom the secondary lesions were not locally treated (18.2 vs 9.1 months; P<0.008). It should be noted that those patients simultaneously operated on two sites, the response to chemotherapy of "primary" and "secondary" lesions was always similar. This homogeneity supports the thesis that in synchronous multifocal osteosarcoma the tumors are not multicentric in origin but represent bone-to-bone metastases from a monocentric tumor.

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

Temperament, character, and attachment patterns in borderline personality disorder.

The aim of this study was to assess the specificity of the association between temperamental vulnerability, character deficits, and Borderline personality disorder (BPD), controlling for the effects of attachment patterns. A total of 44 BPD patients were compared with 98 non-BPD patients with other cluster B Personality Disorder (PD) diagnoses, 39 patients with any cluster A or cluster C PD diagnoses, 70 patients with no PD diagnosis, and 206 nonclinical patients. All patients were administered the Temperament and Character Inventory, the Parental Bonding Instrument, and the Attachment Style Questionnaire. Multivariate and univariate tests showed that BPD patients differed significantly from all control groups on Novelty Seeking and Cooperativeness. These differences remained significant when controlling for the effect of attachment.

Adult↗
PubMed2000

Synthesis and SAR of new 5-phenyl-3-ureido-1,5-benzodiazepines as cholecystokinin-B receptor antagonists.

A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.

Animals↗
PubMed2000

Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10.

Because of its immunosuppressive properties, interleukin-10 (IL-10) is thought to play an important role in a number of human disease states, including inflammation, autoimmunity, and transplant rejection. In this study, we demonstrate that introduction of human or viral IL-10 genes into Burkitt's lymphoma cells markedly reduced their ability to grow as subcutaneous (sc) tumors in SCID mice. In vivo assays for angiogenesis revealed an inhibition of the angiogenic capacity of the IL-10-transfected lines. Recombinant human IL-10 abolished and viral IL-10 reduced vascular endothelial growth factor (VEGF)-165-induced neovascularization. Furthermore, IL-10 blocked the VEGF- and fibroblast growth factor (FGF)-2-induced proliferation of microvascular endothelial cells in vitro. The current observations suggest a direct role for IL-10 in the prevention of angiogenesis in human lymphoid malignancies.

Animals↗
PubMed2000

Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses.

Elevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9+/-0.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27+/-0.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40+/-0.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0+/-0.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients.

Adult↗
PubMed2000

Synthesis and pharmacological properties of novel glycine antagonists.

The NMDA receptor is an ionotropic receptor complex widely distributed in the central nervous system and its activation, particularly in hypoxic conditions such as stroke, traumatic head injury and hypoglycemia, results in a massive influx of calcium ions into the post-synaptic neurones, leading to cell death through the activation of several neurotoxic cascades. The NMDA receptor is a unique ionotropic receptor complex because its activation requires the simultaneous binding of glutamate and glycine and selective antagonists at the glycine binding site are endowed with a better side-effect profile than competitive NMDA antagonists. Then, considerable efforts have been devoted to find potent and selective ligands, resulting in the identification of several classes of glycine antagonists. The research at Glaxo Wellcome has been aimed at the identification of novel in vivo active glycine antagonists, and led to the synthesis and pharmacological characterization of a number of novel, potent and systemically active compounds belonging to different chemical classes.

Animals↗
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↗
PubMed2000

Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli.

PURPOSE: The identification of prognostic factors in patients with nonmetastatic Ewing's sarcoma could allow the use of risk-adapted therapeutic strategies of treatment. PATIENTS AND METHODS: Data on 359 patients with nonmetastatic Ewing's sarcoma of bone treated at a single institution between January 1979 and April 1995 were retrospectively considered. The influence of clinical, hematologic, therapeutic, and histologic parameters on event-free survival was assessed. RESULTS: By univariate analysis, the following features were found to be associated with a poor prognosis: male sex (P <.02), age older than 12 years (P <.006), fever (P <.0001), anemia (P <.0025), high serum lactate dehydrogenase (LDH) level (P <.0001), axial location (P <.04), radiation therapy only for local control (P <.009), type of chemotherapy regimen (P <.0001), and poor chemotherapy-induced necrosis (P <.001). After multivariate analysis, the adverse independent prognostic factors were male sex (P <.04), age older than 12 years (P <.001), fever (P <.0002), anemia (P <.02), high serum LDH level (P <.0003), axial location (P <.02), and type of chemotherapy regimen (P <.0003). When the multivariate analysis was restricted to surgically treated patients, the adverse independent prognostic factors were poor chemotherapy-induced necrosis (P <.0001), fever (P <.015), anemia (P <.02), and high serum LDH level (P <.025). CONCLUSION: The prognosis in cases of nonmetastatic Ewing's sarcoma is influenced by many different clinical and hematologic variables, all of which are to be considered when patients are being stratified according to the risk of relapse. In surgically treated patients, the most important prognostic factor is chemotherapy-induced necrosis.

Adolescent↗
PubMed2000

Neoadjuvant chemotherapy for peripheral malignant neuroectodermal tumor of bone: recent experience at the istituto rizzoli.

PURPOSE: The results achieved in 44 patients with nonmetastatic peripheral neuroectodermal tumor (PNET) of bone treated with neoadjuvant chemotherapy are reported. PATIENTS AND METHODS: A six-drug regimen of chemotherapy (vincristine, doxorubicin, dactinomycin, cyclophosphamide, ifosfamide, and etoposide) was administered to all patients. Local treatment consisted of surgery in 20 patients, surgery followed by radiotherapy in 13, and radiotherapy only in 11. RESULTS: At a mean follow-up of 4.5 years (range, 2 to 7 years), 23 patients (52%) remain event-free, 20 have relapsed (45%), and one has died of chemotherapy-related toxicity. The 5-year event-free survival and overall survival were 54.2% and 62.7%, respectively. To assess the prognostic significance of neural differentiation in the family of Ewing's sarcoma, these results have been compared with the outcomes of 138 concomitant patients with typical Ewing's sarcoma (TES) who were treated according to the same protocol. Of these, 103 (75%) remained continuously event-free, 34 (24%) relapsed, and one died of chemotherapy-related toxicity. It follows that PNET patients treated with this chemotherapy regimen have a significantly worse prognosis than typical ES patients (5-year event-free survival, 54.2% v 70.6%, P <.012; 5-year overall survival, 62.7% v 78.3%, P <.002). CONCLUSION: The authors conclude that studies into new adjuvant therapy for Ewing's sarcoma modulated according to risk of relapse should also consider neural differentiation as a risk factor.

Adolescent↗
PubMed2000

A psychometric study of DSM-IV passive-aggressive (negativistic) personality disorder criteria.

The passive-aggressive (negativistic) personality disorder (PAPD) is one of the most controversial personality disorders. In order to assess DSM-IV PAPD psychometric properties and comorbidity pattern in a mixed psychiatric sample, 379 consecutively admitted in- and outpatients were administered SCID-II, Version 2.0. Confirmatory factor analysis showed that DSM-IV PAPD is a unidimensional construct with adequate internal consistency (K-R 20 = .85). A strong, specific association (odds ratio = 10.38, 95% CI = 4.83-22.30) was observed between DSM-IV PAPD and narcissistic personality disorder (NPD). Confirmatory factor analysis showed that DSM-IV PAPD should be considered as a subtype of a broader narcissistic disorder.

Adult↗
PubMed2000

Muscle performance about the knee joint in patients who had distal femoral replacement after resection of a bone tumor. An objective study with use of gait analysis.

BACKGROUND: The treatment of a malignant bone tumor in the distal aspect of the femur often requires great sacrifice of bone and muscle. The extent of quadriceps removal has been reported to influence the long-term functional efficiency of a patient's gait. The objective of the present study was to determine gait function as it relates to the residual quadriceps strength and to the specific component or components of the quadriceps removed in patients treated with total knee replacement because of a malignant bone tumor in the distal aspect of the femur. METHODS: Sixteen patients were evaluated after implantation of a modular hinged cementless knee prosthesis. The patients were assigned to two groups on the basis of the different components of the quadriceps muscle that were resected. Group 1 consisted of five patients who had removal of the vastus medialis and the vastus intermedius and two who had removal of the vastus medialis only. Group 2 consisted of nine patients who had removal of the vastus lateralis and the vastus intermedius. Residual muscular strength about the treated knee was measured by voluntary maximum contraction isometric testing. Foot-ground reaction forces, kinematic and kinetic findings, and electromyographic activity during free-speed walking were recorded. RESULTS: The kinematic study showed that the patients in Group 1 tended to have a stiff-knee gait during stance, whereas those in Group 2 (in which the vastus medialis was spared) had a more regular flexion-extension knee pattern. Electromyographic findings showed that a higher percentage of patients in Group 1 had reduced or absent rectus femoris activity during the loading response. Compared with the contralateral side, knee-extension strength in the treated limb was decreased in both groups. However, there were no significant differences between the groups with respect to the pattern of strength loss. CONCLUSIONS: Good gait function can be achieved in patients with a distal femoral tumor that is treated with distal femoral resection, partial excision of the quadriceps, and total knee arthroplasty with insertion of a hinged prosthesis. Patients in whom the vastus lateralis and vastus intermedius were removed had better gait performance and a more physiological knee-loading pattern than did patients in whom the vastus medialis was removed.

Adult↗
PubMed2000

Human herpesvirus 6 infection in autologous bone marrow transplant recipients: a prospective study.

After primary infection in early life, human herpesvirus 6 (HHV-6) remains latent in the body and may reactivate in subjects with poor immune status. A 180-day longitudinal study of HHV-6 infection was carried out in 23 autologous bone marrow transplant recipients to evaluate reactivation of HHV-6; two of these patients underwent a double transplant. The patients were monitored prospectively for HHV-6 DNA in peripheral blood mononuclear cells (PBMC) by hot start nested PCR. Positive samples were typed by the enzymatic restriction protocol. Positive plasma samples were also tested for HHV-6 DNA. Antibodies against HHV-6 were measured by immunofluorescence. Five and two out of 23 patients had intermittent and persistent positivity to HHV-6 DNA in PBMCs, respectively; four patients carried variant B, and the other three patients both A and B. None of the respective plasma samples were positive. Two patients were positive for HHV-6 antibodies. Since the significance of HHV-6 DNA in PBMCs is unclear, these findings do not necessarily indicate active infection but may be due to mild immunosuppression in autologous BMT recipients.

Antibodies, Viral↗
PubMed2000

Recent developments in glycine antagonists.

This paper covers the relevant scientific and patent literature published in the last two years concerning different classes of glycine antagonists and their potential application to therapeutic targets. Many of the molecules described here are approaching the final stages of clinical studies.

Animals↗
PubMed1999

CD40 cross-linking enhances the immunogenicity of Burkitt's-lymphoma cell lines.

Epstein-Barr-virus (EBV)-positive Burkitt's-lymphoma (BL) cell lines are not recognized by EBV-specific T cells, due to their non-immunogenic phenotype and restricted expression of latent EBV genes. We tested whether triggering of CD40 can alter the phenotype of the tumor cells with regard to: (i) expression of surface markers, (ii) expression of viral antigens, (iii) presentation of endogenous antigens to MHC-class-1 restricted cytotoxic T lymphocytes (CTLs), (iv) stimulatory capacity in allogeneic mixed-lymphocyte cultures (MLCs), (v) sensitivity to natural-killer (NK)-cell-mediated lysis. Co-culture of EBV-positive BL cells with CD40-ligand-transfected L cells induced up-regulation of CD54 and CD80 but did not affect the expression of viral genes. In spite of significant up-regulation of TAP1 and TAP2, and increased expression of MHC class 1, the BL cells remained unable to present endogenously expressed viral antigens to EBV-specific CTL. However, the up-regulation of adhesion and co-stimulatory molecules was associated with increased stimulatory capacity in MLC and enhanced sensitivity to NK cells. These findings indicate that, while inducing only a modest phenotype shift, cross-linking of CD40 under physiologic conditions may selectively enhance the sensitivity of BL cells to anti-tumor immune responses.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Intravenous itasetron: establishing the effective dose range for the prophylactic control of acute emesis in cancer patients undergoing high-dose cisplatin chemotherapy.

Nausea and vomiting induced by chemotherapy are a major cause of distress to patients and reduce compliance with potentially beneficial treatment. Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist with potent antiemetic properties. It is more potent than ondansetron in animal models and in early clinical studies it demonstrates a long half-life and does not undergo hepatic biotransformation before elimination. The aim of this open, uncontrolled study was to establish the effective dose range of itasetron hydrochloride given intravenously (i.v.) to patients due to receive high-dose cisplatin chemotherapy (50-120 mg/m2) for the first time. Thirty-nine patients were enrolled in the trial and received a single i.v. infusion of itasetron hydrochloride at a dose of 17-280 microg/kg body weight before commencing the cisplatin infusion (median dose 90-110 mg/m2). Antiemetic protection was demonstrated by doses in the range of 35-280 microg/kg. The 17 microg/kg dose was not effective. Treatment failure (>5 emetic episodes/24 hours) was reported in only six (16%) of the 38 evaluable patients over all treatment groups. Adverse events were generally mild or moderate and of a similar type and incidence to those of current 5-HT3 antagonists. Physicians' and patients' assessments of efficacy and tolerability of itasetron hydrochloride were similar, the majority rating the treatment as 'good' or 'very good'. In conclusion, itasetron hydrochloride is effective in the dose range 35-280 microg/kg in preventing cisplatin-induced emesis. Taken together with results from a larger dose-finding study, a dose corresponding to 35 microg/kg (equivalent to 2.5 mg itasetron, calculated as free base) has been pursued in Phase III studies with the i.v. formulation.

Acute Disease↗
PubMed1999

Production of platelet-activating factor in patients with sepsis-associated acute renal failure.

BACKGROUND: Studies in experimental animals have suggested that platelet-activating factor (PAF) is a mediator of sepsis-associated acute renal failure (ARF). In the present study we have evaluated whether an increased concentration of PAF within circulation or urine of septic patients correlated with the worsening of renal function. METHODS: The concentration of PAF and selected cytokines (TNF, IL-1, IL-6, IL-8) was evaluated in blood and urine of 12 patients with septic shock and ARF for 4 consecutive days. RESULTS: The data obtained indicate that blood and urinary concentrations of PAF and of IL-1, IL-6 and IL-8 were significantly higher in septic patients than in controls subjects and in patients with chronic renal failure. The concentration of TNF was significantly increased only in urine. A significantly positive correlation was found among blood concentration of PAF and heart rate (r = 0.4193, P < 0.017), serum creatinine (r = 0.3671, P < 0.038), serum IL-6 (r = 0.5475, P < 0.005) and urine excretion of IL-8 (r = 0.3984, P < 0.044), whereas a negative correlation was present with the number of circulating platelets (r = -0.4285, P < 0.018). Moreover, a positive correlation among the concentration of PAF in urine and the serum concentration of IL-6 (r = 0.5654, P < 0.006) and urine excretion of IL-6 (r = 0.6589, P < 0.0008) and IL-8 (r = 0.6371, P < 0.0004) were found. CONCLUSIONS: These results demonstrate in humans during ARF associated with septic shock the production of PAF, a mediator that has been previously implicated in the pathogenesis of experimental endotoxin-induced shock and renal injury. The observation that blood and urinary concentrations of PAF correlated with some of the clinical and laboratory parameters related to the severity of ARF and sepsis suggests that PAF may contribute to the development of renal injury in septic patients.

Acute Kidney Injury↗