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Biomedical subjects

G Selvaggi

Publications and source records attributed to G Selvaggi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Lymphoplasmacytic hyperplasia (possibly pre-PTLD) has varied expression and appearance in intestinal transplant recipients receiving Campath immunosuppression.

Posttransplant lymphoproliferative disorders (PTLD) are a frequent complication in bowel transplant recipients. Histological changes in PTLD range from expansile lymphoplasmacytic (LP) hyperplasia to frank lymphoma. Small bowel allograft biopsies obtained in the first 250 days posttransplant were retrospectively graded after patients had received induction immunosuppression with either anti-CD52 (Campath) or anti-CD25 (Zenapax) monoclonal antibodies. The biopsies were analyzed with respect to the onset intensity of lymphoplasmacytic infiltrates and presence of in situ EBV hybridization (EBER) positivity. We observed that lymphoplasmacytic infiltrates were a frequent change in all bowel transplant patients over the examined period. Campath-treated patients developed earlier LP infiltrates of mild to moderate intensity between day 1 and 100 posttransplant, thereafter decreasing to mild. No EBER positivity was detected in this group. Zenapax-treated patients presented with LP infiltrates later of mild to moderate intensity through day 100 posttransplant. However, more persistent and intense LP infiltrates was observed after day 101 in this group, including a case of lymphoma and two cases of EBER positivity. We conclude that Campath immunosuppression results in an earlier appearance of LP lesions that are generally less intense than those evident with Zenapax. We attribute these findings to the more profound immunodeficiency and cell targeting following Campath treatment.

Alemtuzumab↗
PubMed2004

Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation.

Surgical principles and techniques derived from organ transplantation surgery can provide novel applications in general surgery. We present an update on our 5-year experience with intestinal autotransplantation and abdominal wall transplantation. Nine patients underwent intestinal or multivisceral transplantation with the addition of 10 abdominal wall grafts to cover the large open areas from previous surgeries. Seven patients underwent near-total abdominal evisceration, ex vivo resection of masses at the base of the mesentery, followed by intestinal autotransplantation; 44% of the abdominal wall graft recipients are alive, but none of the fatalities were related to the graft itself. In two cases the graft had to be removed due to venous thrombosis. Of patients with intestinal autotransplants, 71% are alive with two mortalities due to recurrent metastatic malignancy. In only one case, the intestinal autograft had to be removed because of venous thrombosis. All surviving patients but one are on a regular diet; two are on supplemental enteral feeds. These results show that anastomotic and resection techniques derived from the experience in solid organ transplant can be utilized in complex wound closure, as is the case of abdominal wall transplantation, or resection of large retroperitoneal tumors with intestinal autotransplantation.

Abdominal Wall↗
PubMed2004

Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer.

BACKGROUND: We designed a prospective study to test epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) in resected stage I-IIIA non-small-cell lung cancer (NSCLC) and to correlate overexpression with survival. PATIENTS AND METHODS: EGFR expression was evaluated in 130 consecutive NSCLC patients after radical surgery (60 squamous cell carcinomas, 48 adenocarcinomas, 22 large cell carcinomas: stage I, 41 (31%); stage II, 37 (29%) and stage IIIA, 52 (40%). RESULTS: Overall, 101 of 130 (78%) specimens expressed EGFR, and with a cut-off value of 10% positive cells 48 cases (37%) were classified as positive. At univariate analysis, EGFR was significantly more expressed in stage III (50%) than stage I (20%) and stage II (25%) (P <0.03). No correlation with histotype was found. After a median follow-up of 84 months, both median survival time (18 versus 50 months), 2-year (43% versus 70%) and 5-year (31% versus 46%) survival rates of positive cases were significantly lower than negative ones [P <0.001; hazard ratio 1.96; 95% confidence interval (CI) 1.16-3.30]. At the multivariate analysis, EGFR overexpression and stage emerged as independent factors for cancer-related mortality. CONCLUSION: In patients with radically resected stage I-IIIA NSCLC, EGFR overexpression predicts shorter survival, thus representing a valuable prognostic factor.

Adenocarcinoma↗
PubMed2003

The role of iodine in antisepsis and wound management: a reappraisal.

For more than 150 years, iodine has been used for the prevention of infection and for the treatment of wounds. Nowadays a large amount of published evidence is available and, although it is generally in support of the use of iodine product, it is confused by being a mixture of laboratory, animals and human studies, often using different preparations. This makes interpretation and comparison difficult. After new developments and publications, the role of iodine in antisepsis and in wound management needs to be reevaluated. We mainly focused our review on the following problems: the role of the newly developed formulations of iodine preparations, its antimicrobial activity, the possibility of impairing the wound healing process, the role of iodine in the problem of growing resistance against antibiotics and antiseptics. New formulations seem to keep the same clinical efficacy, avoiding the problem of toxicity; it seems that the antibacterial activity of iodine is superior compared to other products and, in contrast with antibiotics and other antiseptics, it seems to have no resistance problem. It seems that povidone-iodine has all the characteristics to become the first choice antiseptic in wound treatment.

Anti-Infective Agents, Local↗
PubMed2001

Temperature-dependent fermi gap opening in the c(6x4)-C60/Ag(100) two-dimensional superstructure.

High-resolution angle-integrated photoemission of one monolayer of C (60) chemisorbed on Ag(100) shows the reversible opening of a gap at the Fermi level at temperatures 25< or =T< or =300 K. The gap reaches a maximum value of approximately 10 meV at T< or =70 K. This finding is the first evidence of an electronic phase transition in C60 monolayers and has implications on the ongoing debate about surface superconductivity in C60-based bulk materials.

Journal Article↗
PubMed2001

Phase II study of high-dose paclitaxel and carboplatin in previously untreated, unresectable non-small cell lung cancer.

INTRODUCTION: This phase II study was designed to assess the activity and tolerability of the carboplatin-paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Sixty patients (15 stage IIIb and 45 stage IV) received paclitaxel 225 mg/ml on day 1, followed by carboplatin AUC 6 mg/ml per minute (Calvert formula) every 3 weeks. Paclitaxel was administered as a 3-h intravenous infusion followed by carboplatin over 30 min, on completion of paclitaxel administration. RESULTS: The combination showed a good safety profile with Grade 4 neutropenia occurring in 31% of patients without any serious infectious episodes requiring hospitalization. Moderate to severe anemia and thrombocytopenia seldom occurred. Sensorimotor peripheral neuropathy (Grade 2-3) and myalgia (Grade 3-4) were documented in 34 and 20% of the patients, respectively. Among 59 evaluable patients, there was one complete response and 26 partial responses for an overall response rate of 46% (95% C.I.: 34-59%). With a minimum follow-up duration of 16.5 months, the median overall survival time is 52 weeks and the 1-year survival rate is 50%. Median duration of response is 20 weeks (range: 4-52) and progression-free survival is 22 weeks (range: 5-77). CONCLUSION: In advanced NSCLC, the combination carboplatin-paclitaxel at doses of AUC 6 mg/ml per minute and 225 mg/ml every 3 weeks, is both active and relatively well-tolerated.

Adult↗
PubMed2001

The effect of twisting on microanastomotic patency of arteries and veins in a rat model.

The authors examined the effect of twisting on the patency of microvascular anastomoses 3 days after surgery. A total of 69 male Wistar rats were divided randomly into four groups. The femoral arteries and veins were dissected for a standard distance. A total of 69 microarteriorrhaphies and 68 microvenorrhaphies were performed at 0 deg and with twist of the vessel ends of 90, 180, and 270 deg. Three-day patency rates for arterial microanastomoses were 100% with a 0-deg twist, 80.9% with a 90-deg twist, 68.4% with a 180-deg twist, and 64.2% with a 270-deg twist. Three-day patency rates for venous microanastomoses were 100% with a 0-deg twist, 85% with a 90-deg twist, 28.5% with a 180-deg twist, and 25% with a 270-deg twist (p = 0.047 for arteries, p = 0.001 for veins). These data are statistically significant. Moreover, assuming the risk of thrombosis to be 1 for microanastomosis without twisting, the odds ratio for the risk of vessel thrombosis for 270-deg twisting (the maximal examined degree of arterial and venous twist in the current study) is 10.08 for arterial anastomosis and 226.85 for venous anastomosis.

Anastomosis, Surgical↗
PubMed2000

A three-week schedule of gemcitabine-cisplatin in advanced non-small-cell lung cancer with two different cisplatin dose levels: a phase II randomized trial.

BACKGROUND: To explore a new schedule of gemcitabine-cisplatin (GP) combination therapy using two different cisplatin doses in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From May to December 1997, 92 chemonaive patients entered the study and 88 (28 with locally advanced and 60 with disseminated NSCLC) were evaluable for response and toxicity (45 in arm A and 43 in arm B). Patients were randomly assigned to arm A or arm B. Gemcitabine 1000 mg/m2 was given on days 1-8 plus cisplatin 100 mg/m2 in arm A and cisplatin 70 mg/m2 in arm B on day 2 of every 21-day cycle. RESULTS: The overall response rates in arms A and B were 42% (95% confidence interval (CI): 27.8%-56.7%) and 47% (95% CI: 31.6%-61.5%), respectively. Median duration of response was 9.7 months (range 1.8 to 30.9 months; 13.1 and 9.5 months for arm A and B, respectively), and median survival was 12 months (range 0.2 to 31.1 months; 15.4 and 11.5 months for arm A and B, respectively). Major WHO grade 3-4 toxicities in arm A vs. arm B included: thrombocytopenia (23% vs. 17% of courses), leukopenia (15%, vs. 4% of courses), anemia (7% vs. 6% of courses), and nausea-vomiting (20% vs. 7% of patients). Grade 1-2 nephrotoxicity occurred in 20% of patients in arm A and in 7% of patients in arm B, with one grade 4 episode in arm A. Six patients discontinued treatment because of toxicities, 5 in arm A and I in arm B. CONCLUSIONS: Results of this trial indicate that both schedules are feasible and active, with a milder toxicity in the arm with the lower cisplatin dose.

Adult↗
PubMed1999

Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer.

INTRODUCTION: This phase I study was designed to establish the maximum tolerated dose (MTD) of the carboplatin paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. PATIENTS AND METHODS: Fifty patients (one stage IIIa, 31 stage IIIb and 18 stage IV) were sequentially assigned to one of 14 treatment groups in which paclitaxel and carboplatin were administered in doses ranging from 130 to 235 mg/m2 and from 230 to 375 mg/m2 , respectively. Paclitaxel was administered as a 3-h intravenous infusion using non-polyvinylchloride tubing and connectors. The carboplatin infusion, over 30 min, was administered at the completion of the paclitaxel infusion. RESULTS: The MTD for the combination has been reached at 235 mg/m2 of paclitaxel and at 375 mg/m2 of carboplatin. The combination shows a good safety profile with very few and brief episodes of neutropenia without any infectious episodes. At the doses tested thrombocytopenia did not occur at all. Among 47 assessable patients there was one complete response and 17 partial responses for an overall response rate of 38%. There has been a tendency to a dose-response relationship for the combination with only six partial responses (27%) reported in 22 patients who received paclitaxel at doses < or = 195 mg/m2 and carboplatin at doses < 350 mg/m2 and 12 partial responses in 25 patients (48%) receiving paclitaxel > 195 mg/m2 and carboplatin > or = 350 mg/m2, respectively. The median event-free survival time is 33 weeks (range, 4-156 +). With a minimum follow up duration of 57 weeks the median overall survival time is 51.81 weeks (range, 7-162 +) and the 1-year survival rate is 49%. CONCLUSION: In advanced NSCLC the carboplatin-paclitaxel combination can be safely administered at the doses of 375 and 225 mg/m2 every 4 weeks, it appears to be active and well tolerated.

Adolescent↗
PubMed1999

Multidrug resistance in non-small-cell lung cancer.

Resistance to cytotoxic drugs is an important cause of treatment failure. The causes are complex and may be determined by a combination of the tumour characteristics, such as the proportion of resting cells, adequacy of blood supply, and specific cellular mechanisms, as in the multidrug resistance phenotype. In lung cancer four types of multidrug resistance have been defined on the basis of the cellular drug targets involved, i.e., classical multidrug resistance (MDR), non-P-glycoprotein MDR (also called MRP), atypical MDR (mediated through altered expression of topoisomerases II) and lung resistance-related protein. In lung cancer the role of the different forms of multidrug resistance is complex and only partially understood.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: A phase II trial.

PURPOSE: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m(2) once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.

Adult↗
PubMed1999

Carboplatin and paclitaxel in non-small cell lung cancer: the role of amifostine.

Lung cancer remains the leading cause of cancer deaths in industrialized countries. Efforts toward the development of new cytotoxic drugs and more active combination regimens for non-small cell lung cancer (NSCLC) are ongoing. Nevertheless, specific targeting of malignant cells poses a major challenge; toxicities of normal tissues continue to be dose limiting. Cytoprotective agents, such as amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), that can shield normal tissues from cytotoxic effects are now the subject of intense clinical investigation. Amifostine has been shown to selectively protect normal tissues when used in combination with a large number of chemotherapeutic agents, including cisplatin, carboplatin, and paclitaxel. The addition of amifostine to paclitaxel or carboplatin has been shown to reduce the dose-limiting toxicities associated with each chemotherapeutic agent. However, now the combination regimen of carboplatin/paclitaxel is commonly used in NSCLC. To improve the tolerance of this regimen, a large, phase III, multicenter, randomized trial has been initiated that compares carboplatin/paclitaxel with or without amifostine in patients with locally advanced and metastatic NSCLC. The main objective is to evaluate the impact of amifostine on myelotoxicity and neurotoxicity. The addition of cytoprotective agents such as amifostine to other active NSCLC regimens may also reduce overall toxicity and improve the therapeutic index.

Amifostine↗
PubMed1998

Fourier transform infrared microspectroscopy detects changes in protein secondary structure associated with desiccation tolerance in developing maize embryos

Isolated immature maize (Zea mays L.) embryos have been shown to acquire tolerance to rapid drying between 22 and 25 d after pollination (DAP) and to slow drying from 18 DAP onward. To investigate adaptations in protein profile in association with the acquisition of desiccation tolerance in isolated, immature maize embryos, we applied in situ Fourier transform infrared microspectroscopy. In fresh, viable, 20- and 25-DAP embryo axes, the shapes of the different amide-I bands were identical, and this was maintained after flash drying. On rapid drying, the 20-DAP axes had a reduced relative proportion of alpha-helical protein structure and lost viability. Rapidly dried 25-DAP embryos germinated (74%) and had a protein profile similar to the fresh control axes. On slow drying, the alpha-helical contribution in both the 20- and 25-DAP embryo axes increased compared with that in the fresh control axes, and survival of desiccation was high. The protein profile in dry, mature axes resembled that after slow drying of the immature axes. Rapid drying resulted in an almost complete loss of membrane integrity in the 20-DAP embryo axes and much less so in the 25-DAP axes. After slow drying, low plasma membrane permeability ensued in both the 20- and 25-DAP axes. We conclude that slow drying of excised, immature embryos leads to an increased proportion of alpha-helical protein structures in their axes, which coincides with additional tolerance of desiccation stress.

Journal Article↗
PubMed1998

Gemcitabine as second-line treatment for relapsing or refractory advanced non-small cell lung cancer: a phase II trial.

We investigated the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. From November 1995 to October 1997, 83 patients (73 men and 10 women) with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m2 on a weekly x 3 every 4 weeks schedule. Responses were assessed every two treatment courses. The median age of the patients was 63 years. Eastern Cooperative Oncology Group performance status was 0-1 in 62 patients; 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and I stage IIIA). Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well-tolerated: leukopenia and thrombocytopenia World Health Organization grade 2-3 occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients and peripheral edema was observed in 5% of patients. Nausea and vomiting were present in 16% of patients. In this study, gemcitabine showed significant activity in a patient population usually associated with poor prognosis. This finding suggests a possible role for gemcitabine as second-line treatment in patients who have recurring disease or who have failed a platinum-containing regimen, and in the absence of significant toxicity.

Adult↗
PubMed1997

Human islet allografts in patients with type 2 diabetes undergoing liver transplantation.

BACKGROUND: Most patients with cirrhosis have insulin resistance and impaired glucose tolerance, and 20% eventually develop diabetes. Although diabetes in this setting may be reversible after orthotopic liver transplantation (OLTx), immunosuppressive agents administered after transplantation could exacerbate this disease. We report the results of the first pilot trial of islet cell transplantation (ICTx) in patients with diabetes undergoing OLTx. METHODS: Five patients with diabetes and liver cirrhosis underwent OLTx and ICTx. Donor bone marrow cells were also infused to enhance the acceptance of the graft. We identified seven patients who received only OLTx and donor bone marrow cells as historical controls. RESULTS: Preliminary results suggest that ICTx in conjunction with OLTx may improve glucose metabolism (insulin requirement, hemoglobin A1c) in patients with liver cirrhosis. However, there was virtually no change in pre- and posttransplant basal C-peptide levels in the recipients of OLTx + ICTx. CONCLUSIONS: We are planning to further evaluate the effect of OLTx with or without ICTx in a randomized prospective trial, using euglycemic insulin clamp studies.

Adolescent↗
PubMed1997

High-dose donor bone marrow infusions to enhance allograft survival: the effect of timing.

BACKGROUND: The development of strategies to enhance survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advance in posttransplant patient care. The aim of this clinical trial was to determine the effect of timing and dose of peripheral donor bone marrow cell (DBMC) infusion on graft and patient survival after liver transplantation. METHODS: DBMC, obtained from vertebral bodies, were administered in 101 recipients of liver allografts (OLTX). There were 107 patients for whom DBMC could not be obtained; they received OLTX alone (controls). A total of 5 x 10(8)/kg DBMC were infused at day 0 (group 1; n=9); at days 0 and 11 (group 2; n=26); or at days 5 and 11 (group 3; n=26). In group 4 (n=40), patients received up to five infusions of 2 x 10(8)/kg DBMC at days 5, 14, 21, 28, and 90 after OLTX. RESULTS: When the results from patients receiving two or more DBMC infusions (groups 2, 3, and 4) are considered, both patient and graft survival were significantly improved compared with the control group (P=0.02 and P=0.01, respectively). In groups 3 and 4, 88.5% and 95% of patients were alive with mean follow-up of 536 and 265 days, respectively, compared with 77.6% of patients in the control group (average follow-up of 452 days) (P=0.02). Graft survival was also significantly improved in groups 3 (88.5%) and 4 (92.5%), compared with the controls (72%) (P=0.007). CONCLUSIONS: The results suggest that dose and timing of DBMC infusions may be important variables affecting allograft survival. A randomized prospective trial is now in progress to compare group 3 DBMC infusion protocol with controls receiving OLTX alone.

Adult↗