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Biomedical subjects

M Manfrini

Publications and source records attributed to M Manfrini.

At least 19 recordsLinked to original sources

Hospital use of decontaminating mats.

Decontaminating mats made of several layers of adhesive sheets (water-based acrylic 6 g/m2) supplemented with a bactericidal agent (3-1 benzoisothiazolin) at a concentration of 25% were placed in the passages providing access to the operating rooms of an orthopaedic service. Contact plates containing tryptone soy agar were used to assess bacterial concentration at specific points in front of and beyond the mats. For trolley passageways two areas were defined: central and lateral paths, corresponding to the areas walked upon by the personnel pushing the trolleys and to the paths covered by the trolley wheels, respectively. In order to exclude a simple mechanical effect, a comparison of bacterial loads at defined sites beyond the mats was carried out in the presence and in the absence of decontaminating mats. Bacterial colony counts in the presence of decontaminating mats were substantially and statistically significantly reduced compared with the absence of mats. The lower mean number of colony-forming units detected at points located beyond the mats parallels this finding; this difference is also statistically significant. We thus conclude that decontaminating mats are potentially useful in decreasing micro-organism carry-over due to personnel or the passage of trolleys into areas at high risk of infection such as operating rooms.

Bacteria↗

Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide.

BACKGROUND: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. PATIENTS AND METHODS: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. RESULTS: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). CONCLUSIONS: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.

Adolescent↗

Mechanical strength of a femoral reconstruction in paediatric oncology: a finite element study.

In 1997 the proximal femur of a four-year-old child affected by a Ewing sarcoma was reconstructed using a massive bone allograft in conjunction with a vascularized fibula autograft. During the first three years of follow-up the reconstruction underwent important morphological changes. The aim of the present study was to evaluate the risk of fracture of the reconstructed proximal femur, once the physiological loads are restored, associated with a short, slow but unprotected level walk. Subject-specific finite element models of the operated femur, and of the intact contralateral one, were generated from a computed tomography exam, taken for routine clinical monitoring at month 33 of follow-up. The material properties were mapped on to the mesh and a loading condition comprising the hip joint reaction and the abductor muscle force was simulated. The risk of fracture was locally estimated, for the operated and intact femur, using the ratio between the bone tissue strength and the predicted Von Mises equivalent stress, taking into account the different behaviours of the bone tissue in tension or compression. The results showed that although the fibula grew dramatically during follow-up, the reconstructed femur had not recovered the whole mechanical strength of a normal femur. The reconstructed femoral neck seemed to be weaker than the contralateral one and hence at a higher fracture risk. However, no region reached the failure limit, so the model predicted no fracture of the femur if a short, slow but unprotected walk were allowed. The model predictions found an indirect clinical validation when the child was allowed to perform short unprotected walks and did not experience any fracture.

Bone Transplantation↗

Local and systemic control in Ewing's sarcoma of the femur treated with chemotherapy, and locally by radiotherapy and/or surgery.

The role of radiotherapy and/or surgery in the local treatment of Ewing's sarcoma has still to be determined. The outcome of Ewing's sarcoma may differ according to its location and a selection bias towards surgery limits the ability to compare methods of local treatment. We have carried out a retrospective review of 91 consecutive patients treated for non-metastatic Ewing's sarcoma of the femur. They received chemotherapy according to four different protocols. The primary lesion was treated by surgery alone (54 patients), surgery and radiotherapy (13) and radiotherapy alone (23). One was treated by chemotherapy alone. At a median follow-up of ten years, 48 patients (53%) remain free from disease, 39 (43%) have relapsed, two (2%) have died from chemotherapeutic toxicity and two (2%) have developed a radio-induced second tumour. The probability of survival without local recurrence was significantly (p = 0.01) higher in patients who were treated by surgery with or without radiotherapy (88%) than for patients who received radiotherapy alone (59%). The five- and ten-year overall survival rates were 64% and 57%, respectively. Patients who were treated by surgery, with or without radiotherapy, had a five- and ten-year overall survival of 64%. Patients who received only radiotherapy had a five- and ten-year survival of 57% and 44%, respectively. Our results indicate that in patients with Ewing's sarcoma of the femur, better local control is achieved by surgical treatment (with or without radiotherapy) compared with the use of radiotherapy alone. Further studies are needed to verify the impact of this strategy on overall survival.

Adolescent↗

Antifungal activity of 5 new synthetic compounds vs. Trichophyton rubrum and Epidermophyton floccosum.

The antifungal activity of five new synthetic compounds was evaluated on two dermatophytes: Epidermophyton floccosum and Trichophyton rubrum. The data showed that the imidazo-pyrazole and pyrazolo-thiazoles were not particularly effective, while the two pyrazole-thiocyanates proved highly active on both fungi. The most active 5-amino-3-methyl-1-phenylpyrazolo-4-thiocyanate was chosen to perform SEM and TEM morphological studies on both fungi. Both SEM and TEM observations revealed interesting alterations on the two dermatophytes, particularly involving the endomembrane system.

Antifungal Agents↗

High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study.

With the intention of starting an international protocol between Italy and Scandinavia on neoadjuvant treatment of extremity osteosarcoma using the four active drugs at maximum doses (doxorubicin 75 mg/m2 pre-operatively, and 90 mg/m2 post-operatively, cisplatin 120 mg/m2, methotrexate 12 g/m2, and ifosfamide 15 g/m2), a single center (the Rizzoli institute) performed a pilot study to closely monitor toxicity, safety, and tumor necrosis. Only 7 patients (10%) had a reduced number of the scheduled cycles. A total of 1,050 of the expected 1,076 cycles (98%) were administered. Delays and dose reduction were minimal, leading to a mean received dose intensity of 89%. Limb salvage surgery was performed in 59 cases (87%), with 6 amputations and 3 rotation plasties. Chemotherapy-induced necrosis higher than 95% was observed in 38 patients (56%). Eleven patients had total necrosis (16%). At a median follow-up of 60 months (range 50-65 months), 53 patients (73%) were continuously disease-free. Six of the relapsed patients were rescued with further treatments leading to an overall survival of 87%. Hematological toxicity was remarkable despite the use of G-CSF and hospitalization due to febrile neutropenia occurred in 25 patients (37%). Platelet transfusions were required in 77 of the 194 episodes of grade 4 thrombocytopenia, but no case of major bleeding was observed. Red blood cell transfusions were necessary in all patients (in 15 cases perioperatively only). Non-hematological toxicity comprised grade 1-2 nephrotoxicity in 3 cases, CNS toxicity in 2 cases, and dilata- tive cardiopathy leading to heart transplantation in 1 case. In conclusion, the pilot study was feasible in the vast majority of cases with toxicity not superior to that of the previous protocols where chemotherapy was given in lower doses. The rate of limb salvage procedures, event-free survival and overall survival seemed to be higher than in previous protocols. On the basis of this study, in March 1997 the Italian and Scandinavian Sarcoma Groups started a new protocol for osteosarcoma of the extremities.

Adolescent↗

Growth and remodelling of the autologous bone transplant used in a pediatric femoral reconstruction.

The aim of the present work was to assess how growth and remodelling changed the morphology of the transplanted fibula used to reconstruct the proximal femur of a 5 year old child affected by a Ewing's sarcoma during the first 3 years of follow-up. The morphological evolution of the transplant was quantitatively assessed on diagnostic images. Special software was developed to perform three-dimensional measurements on computed tomography (CT) datasets, while state-of-the-art image processing software was used for conventional radiography. The measurements were then correlated with the loads expected to act on the hip during the various stages of the rehabilitation protocol. A simple cantilever beam model was used for a gross estimate of the risk of fracture of the transplant. The results of the analysis showed that there is no clear correlation between the morphological changes of the autograft and the hip loading conditions experienced. Apart from a drastic increase in the periosteal radius in the frontal plane, occurring in the first 10 months after the operation, the growth of the transplanted fibula seems well within the ranges of the normal fibular growth. The cantilever beam model suggested that, although the autograft is currently subjected to subcritical stresses. morphological evolution could increase the risk of fracture in the next few years if a normal level of loading were allowed.

Bone Remodeling↗

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↗

Skeletal reconstruction with a free vascularized fibula graft associated to bone allograft after resection of malignant bone tumor of limbs.

Over the last twenty years, progress in diagnosis and in adjuvant therapy in the field of malignant bone tumor treatment has allowed for development of limb-saving surgical techniques after oncological excision. In this context, the use of vascularized fibula for transplantation represents an important instrument in the reconstruction of bone, either with or without allografts.Moreover, in pediatric cases, the vascularized transplant of the proximal fibula with its open physis allows for an adequate reconstruction of the bone loss and the possibility of conserving the growth potential of the segment. The purpose of this article is to illustrate the various reconstructive possibilities that the use of the combined graft technique (VFT plus allograft) offers in the treatment of large-scale bone loss. In our department from 1988 to 2000, 142 vascularized fibula transplants were performed in oncological cases. Surgical reconstruction was carried out on the tibia in 70 cases, on the femur in 40, on the humerus in 26 and on the radius in 6. Combined graft intercalary reconstructions were 92. In 22 pediatric cases the fibula was transplanted, including the proximal growing epiphysis in the graft; in two of these cases massive allograft was associated to the VFG. Because of its biological properties, the grafted vascularized fibula allowed for fast bone fusion at the level of the osteotomy. It has also demonstrated a tendency of progressive hypertrophy and osteointegration with the allograft, when used. In 22 pediatric cases, the fibula graft with the proximal epiphysis maintained its ability to grow. Unsuccessful outcomes caused by vascular, mechanical, or septic failure were equal to 8.2 %. The fibula graft in the reconstruction of bone loss secondary to oncological excision is a trustworthy and versatile technique.

Adolescent↗

Dynamic contrast enhanced magnetic resonance imaging subtraction in evaluating osteosarcoma response to chemotherapy.

PURPOSE: To evaluate the results of a new technique of dynamic contrast enhanced Magnetic Resonance (MR) imaging subtraction in the assessment of osteosarcoma response to chemotherapy. METHODS: 24 patients with high grade osteosarcoma, treated with preoperative neo-adjuvant chemotherapy, underwent MR at high field strength (1.5 T). Both unenhanced conventional SE T1- and T2-weighted sequences in the coronal and axial plane and dynamic Gd-DTPA-enhanced SE T1-weighted sequences in the coronal plane were performed. Image postprocessing included subtraction of unenhanced image from enhanced images (arbitrary called "angiographic subtraction") and subtraction of each enhanced image from the last-enhanced image (arbitrary called "pathologic area" subtraction). The early enhancing areas detected in the angiographic subtraction and the pathologic areas detected in the pathologic area subtraction were correlated with histopathological findings on histological macrosections obtained from the resected specimen. The sensitivity, specificity, accuracy, positive and negative predictive value of both the subtraction techniques were calculated. RESULTS: The early enhancing areas of angiographic subtraction were related not only to viable tumor but also to the host reactions such as flogosis and granulation tissue. The pathologic areas detected at the pathologic area subtraction correlated in most cases with viable tumor, while in 3 cases they did not correspond to viable tumor tissue and in 1 case a small area of residual viable tumor was missed. In assessing response to chemotherapy, pathologic areas subtraction had an accuracy of 95% (specificity: 100%, sensitivity: 93%, PPV: 100%, NPV: 88%), whereas angiographic subtraction had an accuracy of 79% (specificity: 37%, sensitivity: 100%, PPV: 76%, NPV: 100%). CONCLUSIONS: Pathologic area subtraction may be a useful technique for assessing the response of osteosarcoma to chemotherapy and for detecting residual viable tumor tissue.

Adolescent↗

Pyrazolo-triazoles as light activable DNA cleaving agents.

In view of the continuous interest in new DNA cleaving compounds, both for the development of new therapeutic agents and for the possible use as reagents in nucleic acids research, a few pyrazolo[3,4-d][1,2,3]triazole derivatives have been obtained and investigated for their antiproliferative activity and capability to cleave DNA, after light-activation. A possible in situ activation, i.e. in neoplastic tissues, of less cytotoxic derivatives, may lead to potential antitumor compounds endowed with high therapeutic indexes.

Antineoplastic Agents↗

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↗

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↗

Synthesis of a novel series of imidazo[4,5-c]pyrazole derivatives and their evaluation as herbicidal agents.

Ever changing problems in agricultural weed control require periodic introduction of new herbicides. Imidazo[4,5-c]pyrazoles, which were considered of interest as potential herbicides, were synthesized and examined for the pre-emergence, post-emergence, and post-transplant control of weeds in rice against broadleaf and grass weed species. The data obtained suggest that some imidazo[4,5-c]pyrazoles have potential herbicidal activity against a wide range of weeds, with 5-methyl, 5-thiomethyl, and 5-unsubstituted derivatives being the most effective. No herbicidal activity was observed in the 5-methylsulfonylimidazo[4,5-c]pyrazole and imidazo[4,5-c]pyrazolone series.

Arabidopsis↗

Intraepiphyseal resection of the proximal tibia and its impact on lower limb growth.

From 1989 through 1996, 10 children affected by high grade bone tumors of the proximal tibia underwent an intraepiphyseal intercalary resection. The residual epiphyseal bone segment measured less than 2 cm in thickness in all cases and reconstruction always was performed using the combination of a vascularized fibular autograft and a massive bone allograft. The proximal epiphyseal osteosynthesis was fixed by small fragment screws. The aim of this study was to report the growth pattern of the residual proximal tibial epiphysis and to evaluate any possible lower limb discrepancy and/or deformity after the end of skeletal maturity. At current followup six patients were available for the final evaluation. Radiographic documentation included computed tomography scan of both knees before surgery, a panoramic radiographic view and a computed tomography scan of both lower limbs after the end of skeletal growth. The length of both femurs and tibias, the size of the tibial plateau and of the opposite distal femur, and any possible deformity of femur or tibia were measured and compared with the preoperative data. No patient had a limb length discrepancy greater than 3.5 cm. In all cases the ipsilateral femur had a valgus deformity of the hip develop. In two patients this deformity was associated with an elongation of the femur, partially compensating for the shortening of the tibia. The tibial plateau close to reconstruction grew less than the contralateral one (range 2%-8%) but maintained its normal relationship with the distal femur. None of these patients reported any restriction in recreational activities. They could walk, run, and jump. Their functional result according the International Society of Limb Salvage functional grading system was satisfactory in all cases.

Bone Neoplasms↗

Synthesis and biological evaluation of a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles and pyrazolo[3,4-d]oxazoles.

In view of the biological relevance of triazole-based heterocyclic structures as antifungal, antiviral, and antitumor agents, we have synthesized a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles (2e-h, 2j, 4b) which we evaluated for their cytostatic and antiviral (HIV-1 included) activity and for their capability to inhibit the multiplication of various human pathogenic fungi and bacteria. Moreover, the biological activities of a few compounds, namely pyrazolo[3,4-d]oxazoles (3a-e) and pyrazolo[3,4-d]-1,2,3-triazoles (2a-d, 4a, 5), previously obtained by us but not investigated for their biological activity, were also studied. Only compounds 3a-e were endowed with a significative antiproliferative activity on the human lymphoblastoid cell line MT-4 cells. All pyrazole derivatives proved ineffective in protecting cell cultures against the HIV-1-induced cytopathogenicity, and none of the compounds was active against the bacteria and fungi tested.

Anti-Bacterial Agents↗

[Not Available].

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Journal Article↗

Free vascularized growth-plate transfer after bone tumor resection in children.

Limb-salvage surgery is the standard care for most malignant tumors affecting the extremities, and a vascularized fibula transfer is probably the most popular microsurgical option to reconstruct long-bone defects. Skeletal reconstruction after bone-tumor resection involving the metepiphysis of a growing child can be successfully achieved with a vascularized fibula graft incorporating the proximal physis and active growth plate. Such a procedure has been utilized in 12 children under the age of 10 years who had malignant bone tumors located in the upper limb (3 in the distal radius, 9 in the proximal humerus). The follow-up ranged between 4 years and 3 months. Ten grafts were supplied by the anterior tibial artery, and two by the peroneal artery. The average growth rate of the grafts based on the former artery has been more than 1 cm per year, ranging between 0.75 and 1.33 cm. The authors describe a modified operative technique and discuss the clinical results of the procedure which offers a satisfactory skeletal reconstruction and prevents future limb-size discrepancy.

Bone Neoplasms↗