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Biomedical subjects

D Dallari

Publications and source records attributed to D Dallari.

At least 19 recordsLinked to original sources

Cyclic voltammetry and 1H-NMR of Rhodopseudomonas palustris cytochrome c2. Probing surface charges through anion-binding studies.

The effects of increasing concentrations of Cl-, ClO4-, and HCO3- on the redox potential of Rhodopseudomonas palustris cytochrome c2 indicate that the two polyatomic anions bind specifically to the protein at one site, while chloride simply exerts an ionic atmosphere effect. The change in E degree upon specific anion binding allows us to probe for the influence of surface charges on the redox potential of cytochromes c. The decrease in redox potential at null ionic strength (delta E degree I = 0) due to anion neutralization of one positive surface charge was found to be 23 mV with perchlorate and 33 mV with bicarbonate. These values compare reasonably well with previous theoretical predictions and estimates of the effect of charge alteration on the E degree values in cytochromes c chemically modified or mutated at surface lysines. These delta E degree values, determined on the unmodified protein, are unprecedented for c-type cytochromes. The anion-induced chemical shift changes of the hyperfine-shifted heme 1H-NMR resonances of the oxidized protein yield lower limit values of 53 M-1 and 18 M-1 for the affinity constant for specific HCO3- and ClO4- binding, respectively.

Anions

Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.

Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.

Adolescent

Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy.

Seventeen patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively, the patients received high-dose methotrexate (HD-MTX) and cisplatinum (CPD) (HD-MTX/CPD) and doxorubicin. CPD was delivered intraarterially, the other drugs intravenously. Limb-salvage surgery was performed in 12 instances, and five patients were treated with amputation. Postoperative chemotherapy was tailored according to the grade of chemotherapy-induced necrosis. In 13 cases (86%), the resultant grade of necrosis was greater than 90% (good responders). The mean follow-up interval was 3.5 years with a range of 18 to 78 months. Fourteen patients (82%) remained continuously disease-free, while three patients developed lung metastases. Two of these died because of uncontrolled disease, whereas the third patient is alive and disease-free after metastasectomy. No local recurrences were observed. These results are better than those observed in 215 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not a uniformly lethal tumor as suggested by prior reports. By employing neoadjuvant chemotherapy, a high percentage of patients with TOS can be cured, and in most of them, a limb-sparing surgery is possible and safe.

Amputation, Surgical

Primary chemotherapy and delayed surgery for malignant fibrous histiocytoma of bone in the extremity.

Between March 1983 and September 1988, 22 patients with non-metastatic malignant fibrous histiocytoma MFH of bone of the extremities were treated with two regimens of neo-adjuvant chemotherapy successively activated. Preoperatively, the patients received moderate doses of methotrexate and cisplatinum-Regimen 1- or high dose methotrexate, cisplatinum and adriamycin-Regimen 2. Cisplatinum was delivered intraarteriously, the other drugs intravenously. Limb salvage surgery was performed in 20 patients, and 2 patients were amputated. The surgical margins were adequate (radical or wide) in 18 cases and inadequate (marginal) in 4. The histologic response to chemotherapy was good (90% or more tumor necrosis) in 8 patients. In both regimens postoperative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. At an average follow-up of 40 months (15-70), 15 patients (68%) remained continuously disease-free and 7 relapsed with metastases. No local recurrences were observed. Regimen 2 was slightly more effective than Regimen 1 in terms of good histologic response (5/10 vs 1/12) and continuous disease-free survival (8/10 vs 7/127). The results demonstrate that, as in osteosarcoma, in non-metastatic malignant fibrous histiocytoma of bone in the extremities a high percentage of patients can be cured with neoadjuvant chemotherapy and that in most of them limb sparing surgery is possible and safe.

Adolescent

The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively.

The relationship between dose-intensity and outcome was retrospectively analyzed in 125 patients with osteosarcoma of the extremities treated at our institution with neoadjuvant chemotherapy between 1986 and 1988. Before surgery, chemotherapy was performed with high-dose methotrexate (HDMTX) i.v. followed by cisplatinum (CDP) i.a. and adriamycin (ADM) i.v. Postoperative chemotherapy was tailored according to the necrosis induced by preoperative treatment. Patients who were "good responders" had 31-weeks of chemotherapy with the same drugs utilized preoperatively, while "poor responder" patients received a longer treatment (40 weeks) in which ifosfamide and etoposide (VP-16) were added to HDMTX, CDP and ADM. At a median follow-up of 2 years (1-3 years) 100 patients (80%) remained continuously disease-free and 25 patients relapsed: 24 with lung metastases and 1 with local recurrence. According to the real dose-intensity received, calculated as a percentage of the dose intensity projected by the protocol, the continuously disease-free survival was 87% in the 82 patients who received 80% or more of the scheduled dose-intensity and only 65% for the 43 patients who received less than 80% of the projected dose-intensity. This difference is highly significant (P less than 0.01). These results suggest that in neoadjuvant chemotherapy of osteosarcoma the real dose-intensity delivered is a determinant of treatment outcome and therefore every effort should be made to avoid reductions of doses and delays of cycles of chemotherapy in these patients.

Adolescent

Neoadjuvant chemotherapy for localized Ewing's sarcoma of the extremities: preliminary results of a protocol which uses surgery (alone or followed by radiotherapy) for local control.

From June 1983 to December 1985, thirty-eight patients with localized Ewing's sarcoma of the extremities were treated with a protocol that consisted of an initial nine week period of polychemotherapy (vincristine, adriamycin and cyclophosphamide) followed by local therapy and additional chemotherapy (vincristine, adriamycin, cyclophosphamide and dactinomycin) for one year. As local treatment all patients were offered surgery; thirty-two accepted and six refused. These six patients were locally treated with radiotherapy alone (50 Gy). In the remaining patients an amputation was performed in one case and a resection in thirty-one. In resected patients when a wide margin was achieved (24 cases) no further local treatment was performed; when it was marginal (5 cases) or intralesional (2 cases) radiotherapy at lower doses (40 Gy) followed. At mean follow-up of thirty-seven months the percentage of continuously disease-free patients was 50% for those treated with radiotherapy, 76% with surgery, and 85% with surgery and radiotherapy. Eight patients developed metastatic disease and two patients had local recurrence and metastases. The local recurrences were seen in one patient locally treated with surgery and in one locally treated with radiotherapy. Nine major local complications were observed: three in patients treated with radiotherapy, five in patients treated with surgery, and one in a patient treated with surgery and radiotherapy. These results indicate that after induction chemotherapy conservative surgery is possible in almost all cases of Ewing's sarcoma of the extremities and that such treatment is better than radiotherapy alone as local therapy.

Adolescent

Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for telangiectatic osteogenic sarcoma of the extremities.

Twelve patients with telangiectatic osteogenic sarcoma (TOS) of the extremities were treated with neoadjuvant chemotherapy, according to two different protocols. Preoperatively the patients received high-dose methotrexate(HD-MTX)/cisplatinum(CPD) or HD-MTX/CPD/adriamycin(ADM). CPD was delivered intra-arterially, the other drugs intravenously. Limb salvage surgery was performed in eight instances and four patients underwent amputation. Post operative chemotherapy was tailored according to the grade of necrosis determined by preoperative treatment on the primary tumor. In ten cases (83%) the grade of necrosis resulted higher than 95%. The mean length of follow-up was 3.5 years with a range of 18 to 72 months. Ten patients (83%) remained continuously disease-free, while two patients developed lung metastases and died of uncontrolled disease. No local recurrences were observed. These results are better than those observed in 167 contemporary cases of conventional osteosarcoma treated with the same protocols. This study confirms that TOS is not always a lethal tumor as suggested by prior reports. Employing neoadjuvant chemotherapy a high percentage of patients with TOS can be cured and in most of them, limb sparing surgery is possible and safe.

Adolescent

Metastatic patterns in osteosarcoma.

The clinical courses of 193 patients with high-grade, non-metastatic osteosarcoma were reviewed to ascertain the evolution of the natural history of the disease. All patients had the primary lesion in the extremities and were treated at the Rizzoli Orthopaedic Institute between 1976 and 1982 with surgery alone (30 cases) or surgery plus adjuvant chemotherapy (163 cases). All patients were regularly followed at our Institute. One hundred and fourteen patients, of which 27 were treated with surgery alone and 87 treated with adjuvant chemotherapy, developed overt metastatic disease. No differences were found concerning the sites of the first relapse which, for approximately 90% of cases, were lungs in both groups. However, in the group of patients treated with adjuvant chemotherapy the development of overt metastatic disease, as compared to non-adjuvant patients, was delayed with time (13 vs 8 months) and the number of metastatic nodules in the lung at first relapse was reduced. This alteration in metastatic pattern due to adjuvant chemotherapy is important because it allows surgical resection of pulmonary metastases in a larger number of patients (51% vs 29%).

Adult

The effectiveness of chemotherapy in localized malignant fibrous histiocytoma (MFH) of bone: the Rizzoli Institute experience with 66 patients treated with surgery alone or surgery + adjuvant or neoadjuvant chemotherapy.

Between January, 1974 and July, 1985 66 patients with non-metastatic malignant fibrous histiocytoma (MFH) of bone in the estremities were surgically treated with amputation (34 cases) or resection (32 cases) according to the extension of the tumor. With the exception of 3 patients, who had severe medical contraindications to the chemotherapeutic drugs, all the patients were offered, in addition to the surgery, adjuvant chemotherapy (patients treated before 1983) or neoadjuvant chemotherapy (patients treated after 1983). 33 patients accepted, while 30 wanted to be treated with surgery alone. At median follow-up of 7 years (3-14) 25 patients remained continuously disease-free and 41 relapsed (27 with metastatic disease, 1 with local recurrence and 13 with both metastases and local recurrence). The percentage of patients who remained continuously disease-free was 12.1% (4:33) in the group of patients treated with surgery alone and 63.5% (21:33) in the group treated with surgery plus adjuvant or neoadjuvant chemotherapy. Although the two groups of patients were not completely superimposable (the patients treated with surgery alone were older and more often the MFH arose in pre-existing bone lesions) these results seem to suggest the usefulness of adjuvant and neoadjuvant chemotherapy for this tumor.

Adolescent

Neoadjuvant chemotherapy in the treatment of osteosarcoma of the extremities: preliminary results in 131 cases treated preoperatively with methotrexate and cisdiamminoplatinum.

The results of 131 cases of classic non-metastatic osteosarcoma of the extremities treated with preoperative chemotherapy, surgery and postoperative chemotherapy are reported. Preoperatively, the patients were given Methotrexate (MTX) intravenously (high and average doses) and Cisplatinum (CDP) intraarterially. For postoperative chemotherapy, the drugs and treatment protocols were based on the degree of necrosis observed (good, fair, poor). Conservative surgery was performed in 73% of the cases and amputation in 27%. At an average 30 month follow-up (9-48 months) 59.5% of the patients had remained disease-free, 37.5% had developed metastases, and 3% had developed local recurrence. The percentage of disease-free patients was higher for those treated with high doses of MTX (68% vs. 51%) and for those in whom preoperative chemotherapy had induced good necrosis (75% vs. 44%). Neither the age or sex of the patients, nor the site of the tumor or type of surgery performed influenced prognosis.

Antineoplastic Combined Chemotherapy Protocols

Prognostic value of serum alkaline phosphatase in osteosarcoma.

In 163 patients with osteosarcoma of the extremities treated with adjuvant chemotherapy, serum alkaline phosphatase (SAP) levels were evaluated before treatment and successively closely monitored in an attempt to determine whether serum levels of this enzyme had clinical value in predicting the course of the disease. Of 121 patients with elevated preoperative SAP levels, 78 (64%) recurred. Of 42 patients with normal preoperative SAP levels, only 8 (19%) recurred (P less than 0.00001). Of the 140 patients locally treated with amputation, SAP returned to normal values in 77 patients; 46 of these (59%) relapsed. Of the 21 patients whose SAP remained elevated after amputation, all but 2 relapsed (90%). Among 119 patients with normal postoperative values of SAP, at the time of relapse SAP resulted elevated in 22 of 41 patients (53%). These data confirm that in osteosarcoma, preoperative SAP levels have a definite value in establishing the prognosis and that posttreatment follow-up examination should include SAP determination, since persistent elevated or increasing values herald the appearance of a recurrence.

Adolescent

Prognostic significance of serum lactic acid dehydrogenase in Ewing's tumor of bone.

Pretreatment serum lactic acid dehydrogenase (LDH) levels were examined in 82 patients with Ewing's tumor of bone (23 metastatic and 59 localized). The percentage of patients with increased serum LDH levels was significantly higher in the metastatic group than in the group of patients with localized disease (87 vs. 45%). After treatment with combined therapy, in this latter group the recurrence rate was significantly higher in patients with elevated serum LDH levels at admission than in those with normal serum LDH levels (50 vs. 9%). Of the 16 patients with localized disease who relapsed, 13 (81%) had elevated serum LDH levels at the time of recurrence. These results indicate that in Ewing's tumor serum LDH levels may serve as useful prognostic markers and could be valuable in monitoring the effectiveness of combined therapy.

Adolescent

The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs.

The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.

Adolescent

Bone scan in the evaluation of cementless hip prostheses.

The authors report the data obtained in a bone scan study conducted in 15 patients with cementless total hip arthroplasty. The study was conducted a minimum of 6 months and a maximum of 46 months postsurgery. Contrary to what occurs for cemented prostheses, we used bone scan not as a diagnostic aid for complications, but in order to evaluate the osteogenetic response of the bone to a cementless prosthetic implant. Zonal bone scan high uptake revealed specific areas of overloading, or, when localized in the para-articular region, they anticipated the presence of ossifications before they became visible radiographically. Bone scan was also useful in monitoring the incorporation and remodelling phases of the auto and/or homoplastic bone grafts used.

Aged

The role of surgery in the treatment of localized Ewing's sarcoma.

This study includes 193 patients affected with localized Ewing's sarcoma and treated at the Rizzoli Orthopaedic Institute between April 1972 and May 1988. It is the purpose of this study to evaluate the efficacy of surgical treatment with regard to the prognosis of patients affected with E.S. and to define its indications as well as its limits as compared with radiotherapy. Ninety patients were treated surgically: 13 underwent amputation (localization of the disease in the leg and foot), 4 underwent debulking, 48 had resection of the tumor without any reconstruction (expendable bones), while for 25 other patients resection of the tumor required alloplastic or allograft replacement. In cases of E.S. localized in the pelvis and spine, surgery did not obtain improvement in prognosis. In the other sites, the percentage of disease-free patients increased from 57% to 72% in cases where surgery +/- radiotherapy was used instead of radiotherapy alone, while the percentage of local recurrences decreased from 18% to 5.5%, respectively. As for functional results, the highest incidence of excellent to good scores was obtained with surgery associated with radiotherapy (69%). The incidence of complications was only slightly different for the two groups.

Amputation, Surgical

An evaluation of the "in vivo" and "in vitro" biological reaction and mechanical features of carbon fibre composites.

Tissue reaction to an epoxy resin-carbon fibre composite was tested "in vivo" and "in vitro" in order to evaluate this material as an alternative to metal alloys for clinical use in orthopaedic surgery. While the "in vitro" tests suggest a mild toxic effect of the composite on cells, good biocompatibility "in vivo" was observed when debris are not generated. The mechanical tests compared the composite and stainless steel plates, confirming the expected values for static strength and elastic modulus, revealing, however, the formation of long needles of carbon fibre following breakage of the plate.

Animals

Anatomical ceramic arthroplasty (AN.C.A.): preliminary experience with a new cementless prosthesis.

The study reports the results obtained in 100 hips operated with a new cementless arthroplasty (AN.C.A.) characterized by the anatomical shape of a stem coated with Al2O3 and by a spherical acetabulum in ceramic-titanium, stabilized to the acetabulum first by screwing of the titanium ring and then by bony ingrowth in the cupola covered with porous ceramic. The patients were followed-up after an average of 17.4 months (+/- 8 SD). The patients were clinically evaluated using on the Merle d'Aubigné system, with the following average values +/- SD: pain 5.51 +/- 1, walking 5.01 +/- 1.1, and range of motion 5.38 +/- 0.9. The radiographic stabilization of the prosthesis (considering the worst results of the acetabulum and/or of the stem) was bony (BS) in 83% of the case and fibrous (FS) in 11%; 6 cases (5 acetabulums and 1 stem) showed signs of radiographic instability. Of these, 2 were submitted to further surgery to substitute the acetabulum. Two other patients were also submitted to a second operation: 1 involved substitution of the fractured ceramic head, and the other involved substitution of the stem in a patient with progressive coxalgia and no radiographic signs of loosening. The method of radiographic evaluation was significantly correlated with pain (p = 0.0001) and with walking (p = 0.0095). Instead, there were no significant correlations between stabilization of the prosthesis and precision of the femoral fit (press-fit) of the stem, age, evaluation of preoperative mineralization of the bone, and length of the stem. 8% of the cases presented important radiographic signs of stress-shielding; while 16% presented hypertrophy of the femoral cortex. These radiographic findings were not correlated to clinical ones.

Adult