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Biomedical subjects

F Miraldi

Publications and source records attributed to F Miraldi.

51 records · Page 3Linked to original sources

Localization of GD2-specific monoclonal antibody 3F8 in human osteosarcoma.

3F8 is a murine IgG3 monoclonal antibody specific for the antigen disialoganglioside GD2. Immunofluorescence staining showed strong binding of 3F8 to 15 of 17 human osteosarcomas, including primary and metastatic tumors. The targeting potentials of the native monoclonal antibody (3F8) and the F(ab')2 fragment (p-3F8) were tested in BALB/c athymic nude mice xenografted with human osteosarcomas. After radiolabeling with iodine using the chloramine T method, both 3F8 and p-3F8 retained immunoreactivities. The irrelevant IgG3 antibody TIB114 and its F(ab')2 fragment were used as negative controls. A Ewing's sarcoma xenograft, which was low in GD2 antigen, was also studied for comparison. Mice were sacrificed 1 day and 4 days after i.v. antibody injection. 3F8 and p-3F8 showed preferential accumulation in osteosarcoma over normal tissues with tumor:nontumor ratios of 2.7-58:1 and 1.4-82:1, respectively, on Day 1. These ratios improved to 10-163:1 and 6.0-75:1 on Day 4. The intact antibody 3F8 showed selective tumor uptake with a much higher percentage of injected dose per g than the fragment p-3F8 and exhibited a longer tissue half-life than p-3F8. These data indicate that anti-GD2 monoclonal antibodies may be useful for imaging and targeted therapy of human osteogenic sarcoma. The F(ab')2 fragment has the advantage of achieving favorable tumor:nontumor ratios sooner after antibody injection while the intact antibody shows better retention by tumor tissues.

Animals↗

Targeting of ganglioside GD2 monoclonal antibody to neuroblastoma.

The biodistribution of 3F8, and IgG3 murine monoclonal antibody (MoAb) specific for the disialoganglioside GD2, was studied in nude mice xenografted with human neuroblastoma (NB). 3F8 conjugated to radioactive iodine and injected intravenously localized selectively to seven human NB when compared with Ewing's sarcoma and Hela cell xenograft controls. Uptake in NB was shown to be specific for MoAb 3F8 when contrasted with pooled mouse IgG or irrelevant IgG3 MoAb controls. Both small (50 mg) and large tumors greater than 2 g) showed radiolocalization. The percent injected dose uptake per gram tumor ranged from 8 to 50% and was inversely correlated with tumor size. Optimal tumor to normal tissue ratios were reached by 24-48 hr. There was no abnormal uptake in the reticuloendothelial system and the MoAb did not cross the blood-brain barrier. Based on the kinetics of the amount of radioactivity deposited in tissues, the relative radiation dose to normal organs was estimated to be 1% to 20% of the tumor dose. The MoAb 3F8 is useful for targeting radioactivity to human NB in vivo and the nude mice xenograft model may allow optimization of parameters that influence such biodistribution.

Animals↗

Potential of NMR and PET for determining tumor metabolism.

The basic principles underlying nuclear magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) are explained. Examples of work relating to tumor metabolism are given and some of the important findings of clinical interest are presented. The future prospects of both systems are explored.

Brain Neoplasms↗

Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice.

The antibody 3F8, an IgG3 murine monoclonal antibody (MoAb) against disialoganglioside GD2, could target iodine-131 (131I) to established subcutaneous human neuroblastoma (NB) xenografts in BALB/c nude mice. 131I-radiolabeled MoAb (0.125-1 mCi) was injected iv. Tumor radioactivity over time was calculated from scintigraphy, and radiation dose to individual tumors was calculated. Tumor shrinkage occurred only with 131I-labeled 3F8, but not with nonradioactive 3F8 or radiolabeled irrelevant antibody. While the tumor of the control mice enlarged by tenfold, the treated tumor showed over 95% shrinkage by 12 days. Both the rate of shrinkage and duration of tumor response were dose dependent. Calculated doses of more than 10,000 rad could be achieved. Only those tumors that received more than 4,200 rad were completely ablated without recurrence. Recurrent tumors were not antigen negative or radioresistant. These results confirmed the prediction based on imaging studies that human NB xenografts could be effectively eradicated with the use of 131I-labeled MoAb 3F8 with tolerable toxicities.

Animals↗

The effect of mAs variation upon computed tomography image quality as evaluated by in vivo and in vitro studies.

The effect of different mAs settings on computed tomobraphy (CT) image quality was evaluated by a clinical study and phantom studies. In the clinical portion of this study, a number of CT images, obtained at various mAs settings, were reviewed by experienced CT interpreters. From these same images, graphs were charted of the root-mean-standard deviation (RMSD) vs. body size; there appeared to be a linear relationship between noise, as measured by RMSD, and body size. A performance phantom was used to evaluate the effect of the different mAs settings on resolution. There was some loss in low contrast resolution at 6 and 20 mAs; however, the resolution was identical at 40 and 100 mAs.

Humans↗

Grading liposarcomas with PET using [18F]FDG.

Five patients with liposarcomas of the thigh were studied using positron emission tomography (PET) with [18F]2-deoxy-2-fluoroglucose (FDG). There were three low-grade tumors (all National Cancer Institute Grade 1 myxoid liposarcomas) and two high-grade tumors (both pleomorphic liposarcomas, Grades 2 and 3). The low-grade liposarcomas were easily identified with an average dose uptake ratio (DUR) of 1.38 +/- 0.045 (mean +/- SD). The high-grade lesions were more avid for FDG with a mean DUR of 2.45 +/- 0.24. There was a significant difference (p = 0.004) in the DUR for the two groups and the histological grade of malignancy was highly correlated with the DUR for FDG (Rho = 0.89). These findings suggest that FDG-PET may be useful for distinguishing between low-grade and high-grade liposarcomas.

Deoxyglucose↗

Mid-term outcome of surgical coronary ostial plasty: our experience.

The conventional coronary artery bypass procedure that uses venous or arterial conduit for isolated critical stenosis of the left main coronary artery (LMCA) restores a less physiological perfusion of the myocardium and uses an appreciable length of bypass material. Coronary ostial plasty has been described as an alternative surgical technique in proximal obstructive coronary artery disease without calcifications. Here we report 23 patients (15 males and 8 females aged 37-78 years; mean age 57 years) who underwent surgical ostial plasty. Ostial reconstruction with fresh pericardial patch was performed in all patients: 15 patients with LMCA stenosis, 6 patients with right coronary (RC) ostial stenosis, and 2 patients with both RC artery and LMCA stenosis. In seven cases, coronary artery bypass grafting was added for contralateral distal stenosis with a total of five arterial conduits and six venous grafts. One patient died; the ostial plasty and grafts were patent at necropsy. Thallium-201 myocardial scintigraphy under stress at 30 days to 6 months after operation demonstrated good myocardial perfusion in 21 of 22 patients. Coronary angiography at follow-up (49 +/- 8 months) demonstrated good surgical ostial plasty results in 21 of 22 patients and good coronary flow in 19 of 22 patients; angiographic study at mid-term follow-up revealed only one failure of the surgical ostial plasty technique associated with venous graft obstruction. In 2 other patients CABG failure due to venous graft obstruction (1 patient) or distal stenotic lesions of the left coronary artery (1 patient) was noted. The overall successful outcome of the surgical ostial plasty was 22 of 23. We believe that surgical angioplasty of the coronary ostia may be used in the presence of proximal noncalcified obstructive lesions as an alternative technique, which offers a more physiological revascularization; it also spares grafting material and allows subsequent percutaneous transluminal angioplasty or coronary artery bypass surgery.

Adult↗

Total arterial myocardial revascularization using new composite graft techniques for internal mammary and/or radial arteries conduits.

BACKGROUND: Total arterial myocardial revascularization (TAMR) is feasible because of the excellent long-term patency of the arterial conduits. We present five new surgical configurations for TAMR. METHODS: Between December 1998 and July 1999, 34 patients with triple vessel disease underwent TAMR. All patients were in CCS III or IV. Sketelonized internal mammary arteries (IMAs) were used. The surgical techniques for TAMR consisted of Y or T composite grafts constructed between the in situ RIMA and free LIMA graft or radial artery (RA) conduit in three different configurations. Other techniques uses included a T graft constructed between the RA conduit and free LIMA graft in two configurations. Twenty-six (76%) patients underwent contrast-enhanced TTE color Doppler before and after adenosine provocative test, and seven (20%) patients had postoperative coronary angiography. RESULTS: Overall, 144 anastomoses (average number per patient, 4.2) were completed. One (2.9%) patient undergoing an inverted T graft technique died on postoperative day 2. Another patient (2.9%) undergoing the right Y graft technique using IMAs and RA suffered perioperative AMI due to RA conduit vasospasm. Contrast-enhanced TTE color Doppler before and after the adenosine provocative test and at 1 week postoperation revealed a coronary flow reserve (CFR) of 2.1 +/- 0.2 in the LIMA stem, and in the RIMA stem, a CFR of 2.3 +/- 0.3 (P < 0.007). In one patient undergoing the right Y graft technique using IMAs, we found only anomalous flow dynamic parameters of RIMA, suggesting a partial graft closure. The angiographic examination revealed a free LIMA graft closure. At 6 +/- 2.4 months after operation 33 patients were alive and free of angina. The IMAs stem evaluation by TTE color Doppler at follow-up revealed a 2.45 +/- 0.1 mm LIMA diameter and 2.6 +/- 0.2 mm RIMA diameter, which was more than early postoperative data of P < 0.001 and P < 0.007, respectively. CONCLUSION: These data indicate that TAMR in young patients perhaps offers a better postoperative outcome and perhaps should be part of the surgical armamentarium. These techniques apply the "nontouch" principle and should be taken into consideration in patients with a heavily calcified aorta. Contrast-enhanced TTE color Doppler is a safe, accurate, and noninvasive test, which allows assessment of IMA patency and CFR evaluation. The flow reserve of the IMAs seems to be adequate for multiple coronary anastomoses.

Coronary Angiography↗

[Significance of health education in schools. Strategy for the prevention of cardiovascular diseases].

Cardiovascular diseases are the first cause of death in our Country. They mainly manifests in adult age but it is the result of initiated lesions since the young age and imputable often to errors of behaviours and to non appropriate styles of life. The knowledges related to the prevention of some illnesses, allows a reduction of the incidence of these, a reduction of the mortality, with consequent reduction of the health and social costs related to the care and to the rehabilitation. In our educational system, unlike what happens in the most greater part of the other European countries, these themes are only partially present and however treated in sporadic and insufficient way. For these raisons Pronto Cuore onlus Association has decided to start, in collaboration with the Regione Lazio, a project of health education to the high schools students considering that a more informed population has a longer expectancy of life and a better life quality. This job wants to underline the necessity to undertake a health education program to teach and inform students and teachers: to recognize some factors of risk as principal causes of cardiovascular diseases; to change life style; to recognize critical situations and behaviours to be adopted.

Cardiovascular Diseases↗

Assessment of the effects of ciprofloxacin and nalidixic acid on cerebral blood flow and metabolism in healthy subjects by positron emission tomography.

STUDY OBJECTIVES: The mechanism by which the fluorinated quinolones produce central nervous system effects is unknown. Using positron emission tomography (PET), we evaluated the effects of two quinolones on brain blood flow as well as on oxygen and glucose metabolism. These determinations were done in conjunction with ophthalmologic and neuro-ophthalmologic testing. DESIGN: Randomized, double-blind, placebo-controlled, 7-day course of ciprofloxacin 750 mg (C750) or 500 mg (C500) every 12 hours, or nalidixic acid (NA) 1 g every 6 hours. POPULATION: Twenty-four healthy male volunteers, six in each treatment arm. RESULTS: [table: see text] CONCLUSIONS: Compared with baseline values, NA significantly reduced brain glucose uptake, whereas C500, C750, and placebo produced no detectable effect. No compound significantly altered brain blood flow or oxygen metabolism compared with baseline or other treatments. No significant effect on electroretinographic, electro-oculographic, or other neuro-ophthalmologic tests was observed.

Adolescent↗