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Biomedical subjects

A Pandolfi

Publications and source records attributed to A Pandolfi.

At least 19 recordsLinked to original sources
PubMed2002

Autologous bone marrow transplantation with negative immunomagnetic purging for aggressive B-cell non-Hodgkin's lymphoma in first complete remission.

To evaluate the effect on survival of negative immunomagnetic purging in aggressive B-cell non-Hodgkin's lymphoma (NHL), 20 patients retrospectively staged according to the age-adjusted International Prognostic Index as high-intermediate (11 patients) or high-risk (9 patients) received autologous bone marrow transplantation (ABMT) in first complete remission (CR1). All patients received six to eight cycles of a F-MACHOP-like protocol as induction treatment and then underwent high-dose chemotherapy (HDC) with a CBV-like regimen. Negative purging included a panel of monoclonal antibodies against B-cell antigens and immunomagnetic beads. The data were compared to a historical control of 18 patients with the same characteristics treated in our institution who received unpurged bone marrow support. The median yield of mononuclear cells (MNC), colony-forming units-granulocyte/macrophage (CFU-GM), and CD34+ cells after purging were 52%, 49%, and 57%, respectively. The median B-cell depletion after negative selection was 1.8 logs. All patients obtained a complete engraftment with no significant differences between the purged and unpurged group. Two toxic deaths (one for each group) were observed and the main extrahematological toxicities were mucositis, vomiting, and diarrhea. The event-free survival (EFS) and overall survival (OS) at 3 years for the whole group of 38 patients were 73% (95% CI: 59-88%) and 81% (95% CI, 68-94%), respectively. The comparison between patients receiving purged marrow and patients receiving unmanipulated marrow indicated no significant survival differences between the two groups both for EFS 84% (95% CI: 67-100%) vs 61% (95%CI: 39-84%) ( P=0.12) and OS 84% (95% CI: 69-100%) vs 71% (95% CI: 50-93%) ( P=0.58). Our report shows that HDC followed by reinfusion of autologous bone marrow can produce long EFS and OS in high-intermediate and high-risk patients with B-cell NHL transplanted in CR1, but was not be able to demonstrate a significant clinical advantage using immunomagnetic purged marrow. However, the use of ex vivo negative purging combined with innovative treatment modalities (peripheral blood stem cell transplant, in vivo administration of monoclonal antibodies) needs to be explored.

Adolescent↗
PubMed2001

Acute hyperglycemia and acute hyperinsulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat.

Decreased plasma fibrinolysis may contribute to accelerated atherothrombosis in diabetes. To observe whether hyperglycemia and hyperinsulinemia, common findings in type 2 diabetes, acutely affect plasma fibrinolysis in vivo, we evaluated plasma fibrinolysis (lysis of fibrin plates, free PAI-1 activity and t-PA activity) in the rat after a hyperglycemic euinsulinemic clamp (n=8), an euglycemic hyperinsulinemic clamp (n=7) or a saline infusion (n=15). Plasma fibrinolytic activity was sharply reduced after both the hyperglycemic and hyperinsulinemic clamps as compared to the respective controls (mean lysis areas on the fibrin plate, 139+/-21 vs. 323+/-30 mm2, p<0.001; 78+/-27 vs. 312+/-27 mm2 p<0.001, respectively). Plasma PAI-1 activity was greater after both hyperglycemic and hyperinsulinemic clamps as compared to saline infusion (6.6+/-2.6 vs. 1.6+/-0.6 IU/ml, p<0.001; 26+/-4 vs. 1.3+/-0.7 IU/ml, p<0.0001, respectively). Plasma t-PA activity was significantly reduced both after the hyperglycemic (0.36+/-0.15 vs. 2.17+/-0.18 IU/ml in controls, p<0.001) and the hyperinsulinemic (0.3+/-0.1 vs. 2.3+/-0.3 IU/ml in control, p<0.001) clamps. These data show that in vivo both acute hyperglycemia and acute hyperinsulinemia can decrease plasma fibrinolytic potential and that this is due to increased plasma PAI-1 and decreased free t-PA activities.

Animals↗
PubMed2001

Costs of high-dose chemotherapy and peripheral blood progenitor cell autograft for breast cancer.

The aim of the study was to analyze the real cost of single or tandem high-dose chemotherapy (HDC) and peripheral blood progenitor cell autologous transplant (PBPCT) in patients with breast cancer. We analyzed the costs of 40 PBPCT performed in 20 patients. Tandem transplant was planned for each patient. Resources used and direct costs were identified for each patient. The study was carried out using the hospital perspective and monetary values were reported in 1999 Euro. The mean cost of whole procedure for single transplant was 20,816.63 Euro, while the mean cost of tandem transplant was 38,770.83 Euro. The cost distribution in the two groups was similar: the most expensive phase of procedure was the supportive phase post transplant (about 60% of total cost), with the categories of cost most represented being professional fees (about 28%) and pharmacy (about 35%). Awaiting more convincing trials of the clinical advantage of HDC in breast cancer, our analytical evaluation of transplant costs for different therapeutic options, single or tandem, permits identification of the most expensive categories in order to intervene for cost savings.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Plasminogen activator inhibitor type 1 is increased in the arterial wall of type II diabetic subjects.

Plasma plasminogen activator inhibitor type 1 (PAI-1) increases in diabetes, and this might contribute to decreased fibrinolysis and accelerated atherosclerosis. Increased PAI-1 levels in the vessel wall could decrease local fibrinolysis and elevate thrombus formation and the unfavorable evolution of atherosclerotic plaques. High glucose increases PAI-1 synthesis in arterial wall cells in culture, and aortic wall PAI-1 levels have been found to be elevated in diabetic animals. However, arterial wall PAI-1 levels have not been investigated in diabetic subjects. Therefore, the aim of this study was to determine the effect of diabetes on PAI-1 levels in the arterial wall. Blood samples and small tissue specimens from the mammary artery were obtained from 11 diabetic and 10 nondiabetic subjects who underwent coronary artery bypass graft surgery. PAI-1 antigen localization in the arterial wall was obtained by immunohistochemistry and was read by laser scanning confocal microscopy; plasma fibrinolytic activity was measured by lysis of fibrin plates; and PAI-1 activity was assessed by a chromogenic method. PAI-1-related immunofluorescence was increased in the arterial wall of diabetic patients, whereas plasma fibrinolysis was reduced. These data provide evidence that diabetes is associated with increased PAI-1 in the arterial wall. This might be an important factor for increased cardiovascular risk and unfavorable plaque evolution in diabetes.

Aged↗
PubMed2000

Relationship between patient practice-oriented knowledge and metabolic control in intensively treated Type 1 diabetic patients: results of the validation of the Knowledge and Practices Diabetes Questionnaire.

AIMS: To validate a newly developed questionnaire for the measurement of patients' knowledge and practices, with particular attention to its ability in predicting HbA1c levels. RESEARCH DESIGN AND METHODS: The Knowledge and Practices Diabetes Questionnaire (KPDQ) is a questionnaire composed of two scales, investigating patient knowledge and practices. Twenty-two questions, 12 dealing with patients' knowledge and 10 relative to patients' practices, were initially identified. Factor analysis and reliability analysis were used to validate the questionnaire. The ability of the two scales in predicting metabolic control was then evaluated. The questionnaire was administered to a population of Type 1 diabetic subjects intensively treated and regularly attending the diabetes outpatient clinic of Pescara General Hospital. The mean of all HbA1c measurements performed after patients were taken in charge by the clinic was used as an indicator of metabolic control. RESULTS: Out of 133 Type 1 patients identified, 77 (58 %) filled in the questionnaire. Respondents had a mean age (+/- SD) of 37 +/- 13 years and a mean diabetes duration of 13 +/- 9 years. The application of factor and reliability analyses led to the definition of two final scales composed of 10 (Knowledge Score, KS) and 5 items (Practice Score, PS), respectively. Item-scale correlation was > or = 0.40 for all the items investigated. Cronbach's alpha coefficient exceeded the value of 0.70 for both scales. The mean number of HbA1c determinations during a median period of observation of 4 years was of 11 +/- 5. The mean HbA1c value for the whole population was of 7.0% +/- 1.4, while the proportion of patients with values < or = 7.0% was of 57%. After adjusting for clinical and patient-related characteristics, the KS was the only independent predictor of metabolic control. Patients in the lowest quartile of the KS showed a more than 20-fold increased risk of having mean HbA1c values > or = 7.0% as opposed to those in the highest quartile (odds ratio, OR=23.3;p=0.009). No association emerged between metabolic control and PS. CONCLUSIONS: The KPDQ presents excellent psychometric properties. The KS also shows a very impressive association with the mean HbA1c values over a period of 4 years. These findings are particularly remarkable in that many studies have failed in documenting such a relationship. The KS can thus be considered as a quick and efficient screening tool to be used in an ambulatory setting to monitor the level of practice-oriented knowledge of patients with Type 1 diabetes as well as to identify those subjects who need individualized educational interventions.

Adult↗
PubMed1996

Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture.

Hyperglycaemia and hyperinsulinaemia have both been related to accelerated atherosclerosis in non-insulin-dependent diabetes mellitus (NIDDM). Plasma fibrinolytic potential is reduced in NIDDM and it is known that glucose and insulin can modulate plasminogen activator inhibitor (PAI-1) and tissue-plasminogen activator (t-PA) secretion and can therefore regulate local fibrinolysis. Vascular smooth muscle cells (vSMC) play an important role in the development of atherosclerotic lesions; however, the role of insulin and glucose in regulating PAI-1 and t-PA production in vSMC is presently not known. Therefore, we cultured arterial vSMC explanted from human umbilical cords and exposed them to increasing concentrations of glucose (5, 12, 20, 27, 35 mmol/l) or insulin (0.1, 0.5, 1, 10 nmol/l) in a serum free medium. After 24 h, PAI-1 and t-PA antigens and activity were evaluated in the culture medium; in cells exposed to 20 mmol/l glucose and to 0.5 nmol/l insulin PAI-1 gene expression was also evaluated. An increase in PAI-1 antigen was observed at each glucose concentration (by 138, 169, 251 and 357% as compared to 5 mmol/l glucose) which was paralleled by an increase in PAI-1 activity. t-PA concentration was also increased by glucose but its activity was sharply reduced. An increase in PAI-1 antigen was detected at each insulin level (by 121, 128, 156 and 300% as compared to no insulin). PAI-1 activity was slightly increased at the lowest insulin concentrations but markedly increased by 10 nmol/l insulin. t-PA antigen was also increased by insulin; however, its activity was markedly reduced at each concentration. As compared to control cells, PAI-1 mRNA was increased by 2.5 and 2.0 fold by 20 mmol/l glucose and 0.5 nmol/l insulin, respectively. We conclude that in human vSMC both glucose and insulin can affect the fibrinolytic balance so as to reduce fibrinolytic potential. This might contribute to decreased local fibrinolysis and thereby might accelerate the atherothrombotic process in NIDDM subjects.

Antibodies, Monoclonal↗
PubMed1996

Surfactant protein A-producing cells in human fetal lung are good targets for recombinant adenovirus-mediated gene transfer.

Local delivery of Escherichia coli beta-galactosidase gene (beta-gal) to surfactant protein-A (SP-A)-producing cells by a replication-defective recombinant adenovirus (AdCMV.beta-gal) was tested in human 8-12-wk-old fetal lung explants cultured in Waymouth's medium. In contrast to uninfected explants, direct addition of 0.8-1.6 x 10(6) plaque-forming units of AdCMV.beta-gal resulted in beta-galactosidase (beta-Gal)-specific staining of the pulmonary epithelium. SP-A localization by indirect immunofluorescence showed positive specific staining of the beta-Gal+ lung epithelial cells, demonstrating that recombinant-defective adenoviruses efficiently transfer reporter genes to fetal lung SP-A+ cells. The reporter gene expression in SPA+ cells persisted for more than 1 mo. No apparent alteration of morphology, phenotype, and growth was observed. The in vitro human lung model described may be useful for testing DNA constructs for vector-mediated gene therapy, as an approach to the treatment of congenital defects and neonatal disorders, such as respiratory distress syndrome and bronchopulmonary dysplasia.

Adenoviruses, Human↗
PubMed1993

A phase I safety study of doxifluridine and interferon-alpha-2a in patients with advanced neoplastic disease.

AIMS AND BACKGROUND: Doxifluridine (RO 21-9738, 5'-dFUR) is a fluoropyrimidine derivative with proven antitumor activity in different experimental models. On the basis of experimental evidence, several clinical trials have been carried out to define the optimal 5'-dFUR dose and route of administration. In general, the maximum monthly dose of 5'-dFUR was 36-38 g. According to these clinical data, we explored the feasibility of a combination of 5'-dFUR and interferon-alpha-2a (IFN-alpha-2a). The aim of the protocol was to confirm the maximum tolerated dose (MTD) of the drug in combination with a settled dose of IFN alpha 2a. METHODS: An open-label phase I study with intravenous 5'-dFUR was carried out in 12 patients with a histologically proven diagnosis of advanced gastrointestinal or breast cancer refractory to previous conventional hormone-chemotherapy. Escalating doses of 5'-dFUR were administered as a 2-h intravenous infusion, once a week for at least 4 weeks in groups of 3 patients. IFN-alpha-2a was administered as an intramuscular injection of 3 MU 3 times a week for 4 consecutive weeks. Physical and laboratory parameters were assessed at baseline and then weekly until the end of treatment. RESULTS: The treatment with 5'-dFUR was stopped at 5 g/m2, since this level corresponded to the maximum monthly dosage reported in the literature (36-38 g). No severe toxicity was recorded up to this drug level. CONCLUSIONS: The combination of 5'-dFUR plus IFN-alpha-2a was well tolerated at the level of 5 g/m2. Although the MTD was not reached, it can be stated that the dosage administered in this study could be explored in a larger trial.

Adult↗
PubMed1993

A phase I-II study of oral doxifluridine plus radiotherapy in radiosensitive tumors of the pelvic region.

AIMS AND BACKGROUND: Fluoropyrimidines have shown synergic effects in combination with radiotherapy in several tumor types. Doxifluridine is a novel 5-fluorouracil (5-FU) prodrug which is transformed into 5-FU in neoplastic tissue. This would imply enhancement of radiotherapy by 5-FU in neoplastic tissue, where the drug is concentrated higher than in surrounding healthy tissues. METHODS: A phase I-II study was carried out on 10 patients with radiosensitive tumors of the pelvic area (4 uterine carcinomas). Escalating doses of oral doxifluridine were administered in combination with standard radiotherapy to assess the efficacy and toxicity profile of the combined treatment. The 9 evaluable patients (3 groups of 3 patients each) received oral doxifluridine, at daily doses of 500, 750, or 1000 mg, for 6 consecutive weeks in combination with a standard (1.8-2.0 Gy) dose of radiotherapy. Assessment of physical and laboratory parameters was made at baseline, then weekly up to the end of the treatment and at follow-up. RESULTS: At the final evaluation, one patient with a diagnosis of uterine carcinoma showed a complete response that lasted 10 weeks. One patient had a partial response, and 7 patients had no change. The most frequent adverse events were gastrointestinal: 27 episodes of mild to moderate nausea/vomiting and diarrhea. Three patients complained of severe diarrhea of 5-7 days duration: all patients spontaneously recovered. There were no significant changes in laboratory or clinical parameters, and no serious toxicity requiring reduction or interruption of the radiotherapy. CONCLUSIONS: The maximum tolerated dose of oral doxifluridine in combination with standard radiotherpay was assessed at 1000 mg/patient/day (equivalent to 36-38 g monthly, previously reported as mTD in phase I studies).

Administration, Oral↗
PubMed1993

A new diagnostic aid for natural family planning.

INTRODUCTION: We have studied the use-effectiveness of salivary ferning as a diagnostic testing aid to natural family planning. We used PG/53, a pocket microscope. MATERIALS AND METHODS: Use of natural family planning methods was studied in 32 women who used the new technology PG/53 to detect the fertile period. By this means the women observed their menstrual cycles and other markers of fertility, such as basal body temperature and appearance of cervical mucus. RESULTS: Of the 32 women participating in this research, 28 women had a good salivary test with positive ferning by the microscope in the same period as other markers of fertility. In 4 cycles the ferning was uninterpretable as there was no correspondence with the cycle phase. Ferning began 1-2 days before cervical mucus appearance, and lasted a mean of 6.2 days. Ferning occurred, on average, 7.2 days before the first day of temperature shift. CONCLUSIONS: There is a direct correlation between salivary ferning and fertile period. Salivary ferning may be used as a new parameter to aid women to detect the fertile period in combination with other symptothermal methods of ovulation detection. We now need further research in order to improve the use-effectiveness of salivary ferning.

Body Temperature↗
PubMed1993

Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats.

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4-6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, DL-buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC50 of 10(-4) M, after 48-72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10(-4) M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.

Aging↗
PubMed1993

Progenitor cells purging: negative selection.

Disease relapse after autologous bone marrow transplantation (ABMT) may arise from residual tumor in the recipient and/or from cancer cells that are reinfused. The aim of purging by negative selection is to remove tumor cells from the marrow without adversely affecting the engraftment potential of the normal cell. We report the results of a study on fifty-six patients (pts) with non Hodgkin's lymphoma or acute leukemia submitted to ABMT after immunomagnetobead (IMB) purging (11 pts), Maphosphamide purging (31 pts) and no purging (14 pts). The IBM procedure involved one incubation of 3 monoclonal antibodies (CD10, CD19 and CD22) and two incubations with magnetic beads (Dynabeads M-450). The median recovery of mononuclear cells and CFU-GM was 40% and 45% after IMB purging and 84% and 5% after Maphosphamide purging respectively. The rate of leukocyte, neutrophils and platelets recovery following ABMT was similar in the three groups of pts, although platelet recovery was slow in patients received graft purged with Maphosphamide. Our study confirms the clinical feasibility of the IMB procedure, but only randomized studies will be able to definitely address the question of the clinical utility of purging.

Adolescent↗
PubMed1991

A technique for isolation of bone marrow cells using hydroxyethyl starch (HES) sedimentation agent.

Various methods have been investigated to concentrate hemopoietic stem cells before in vitro treatment and cryopreservation. Each procedure requires various degrees of cell manipulation; moreover, the extent of purification of the stem cell fraction depends on the further use of bone marrow. Fifty four bone marrows were treated with hydroxyethyl starch (HES) to isolate the mononuclear cell population. The manipulation with HES permitted to concentrate marrow stem cells in a small volume with removal of unwanted granulocytes, red blood cells and the donor isohemagglutinins in the major ABH incompatibility. We describe here a manual method which permits the transfusion of a very few number of red cells without depletion of progenitor cells and thus delay of engraftment.

Blood Group Incompatibility↗
PubMed1991

Immunomagnetic purging procedure for autologous bone marrow transplantation in lymphoid malignancies.

In this report we describe the use of the immunomagnetic depletion of tumor cells from harvested bone marrow in two patients with acute lymphoblastic leukemia. The immunomagnetic procedure of purging involved one incubation of the marrow cells with a mixture of 4 monoclonal antibodies which bind to antigens of CD10 (ALB2), CD19 (HD37), CD20 (B1) and CD22 (HD39). Two incubations with magnetic beads (Dynabeads M-450) covered with antimouse antibodies followed by magnetic separation were performed. The bead/target B cell ratio was 50:1. After purging the recovery of mononuclear cells was 56% and 40%, while the recovery of CFU-GM was 45% and 38% respectively. Both patients engrafted rapidly without serious complications. One patient relapsed 4 months after transplant, the other remains in complete remission after 5 months. Our results confirm that the use of immunomagnetic beads is a simple, safe and reproducible technique to remove tumor cells before ABMT in patients with B malignancies using a broad mixture of MoAbs. However only a randomized trial using autologous marrow purged or not will clarify the effective clinical value of the procedure.

Adolescent↗
PubMed1989

Increased plasma levels of platelet-derived growth factor activity in patients with progressive systemic sclerosis.

We measured mitogenic activity of whole blood serum and platelet-poor plasma-derived serum of a group of 10 patients with progressive systemic sclerosis and of 8 controls. Mitogenic activity of plasma-derived serum was greater in patients than in controls, in the absence of other signs of platelet activation. This increased activity was inhibited by specific antibodies, anti-platelet derived growth factor, suggesting that circulating levels of platelet-derived growth factor may be present in progressive systemic sclerosis patients. Platelet-derived growth factor, released either by platelets or by monocytes, might play a role in the pathogenesis of scleroderma.

Biological Assay↗
PubMedDate not supplied

Dose-finding study of 5'-deoxy-5-fluorouridine in combination with fixed doses of cisplatin and L-folinic acid for the treatment of advanced or recurrent squamous cell carcinoma of the head and neck.

In order to assess the maximum tolerated dose of 5'-deoxy-5-fluorouridine (5dFUR) combined with a cisplatin (20 mg/m2 i.v.) and L-folinic acid (100 mg/m2 i.v.), 5-day schedule 19 consecutive chemotherapy-naive patients affected by advanced or recurrent carcinoma of the head and neck were entered in this phase I trial. Doses of 5dFUR were escalated from a starting level of 2,000 mg/m2/day up to 3,000 and 5,000 mg/m2/day. At the latter step the dose-limiting acute toxicities were stomatitis and diarrhea, which were of WHO grade 3-4 and occurred in 3 and 1 out of 4 evaluated patients, respectively. Other grade 3 acute toxicities were leukopenia, anemia, renal impairment, and neurologic symptoms, observed in 1 patient each. Furthermore, one possibly treatment-related death was registered among patients entered in the highest dose level. Eleven out of 19 patients (58%; 95% CI:34-80%) showed a complete (2 cases) or partial (9 cases) response to this treatment, regardless of the 5dFUR dosage employed. From our results we may define the maximum tolerated dose of 5dFUR to be associated with cisplatin and L-folin acid used in this trial as 3,000 mg/m2/day x 5 days. Assessment of the real activity of this combination chemotherapy deserves further studies.

Aged↗
PubMedDate not supplied

Docetaxel and epirubicin plus G-CSF as mobilizing treatment to support high-dose chemotherapy in breast cancer.

BACKGROUND: In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC). PATIENTS AND METHODS: Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis. RESULTS: The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed. CONCLUSIONS: Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.

Adult↗