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Biomedical subjects

Roberto Bellucci

Publications and source records attributed to Roberto Bellucci.

16 recordsLinked to original sources
PubMed2007

Optimizing higher-order aberrations with intraocular lens technology.

PURPOSE OF REVIEW: Aspheric intraocular lens technology has been implemented during the past 5 years, and more and more intraocular lenses with different amounts of asphericity are becoming available. Despite the efficacy in the correction of spherical aberration and the good results on implanted eyes, the theoretical advantages of aspheric intraocular lenses are still controversial. RECENT FINDINGS: All investigations showed the ability of the aspheric intraocular lenses to correct the positive spherical aberration of the cornea, with variable impact on the total eye wavefront but with constant advantages in the optical quality of the eyes as measured by the Modulation Transfer Function, the Point Spread Function, and the contrast sensitivity of implanted patients. Theoretical studies on model eyes underlined some possible limitations of aspheric intraocular lenses, especially sensitivity to decentration. In addition, the actual optical quality in implanted eyes is also affected by light scattering, a parameter missed by simple aberration analysis. SUMMARY: Aspheric intraocular lenses effectively reduce spherical aberration in implanted eyes, with improvement in optical quality over the parent spherical intraocular lens. The advantages for implanted eyes could be limited by decentration, by small pupil diameter, and by reduced media transparency.

Astigmatism↗
PubMed2006

Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis.

A unique characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC) is the presence of high-titer and extremely specific autoantibodies to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Autoantibodies to PDC-E2 antigen have only been detected in patients with disease or in those who subsequently develop PBC. One exception has been a subgroup of patients with multiple myeloma (MM) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received donor lymphocyte infusions (DLIs) after transplantation. These patients developed high-titer antibodies to a variety of myeloma-associated antigens, including PDC-E2, coincident with rejection of myeloma cells in vivo. To examine the specificity of autoantibodies to PDC in these patients, we screened sera from patients with MM, chronic leukemias, monoclonal gammopathy of unknown significance (MGUS), PBC, and healthy donors. Three of 11 patients with MM (27%) and 2 of 6 patients with chronic leukemias (33%) developed anti-PDC-E2 antibodies in association with DLI response; 2 of 12 (17%) patients in the MGUS pretreatment control population also had detectable anti-PDC responses. Interestingly, the epitope specificity of these PDC-E2 autoantibodies was distinctive, suggesting that the mechanisms leading to loss of tolerance in the transplantation patients are distinct from PBC.

Aged↗
PubMed2006

IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo.

IL-2 plays a critical role in the maintenance of CD4+CD25+ FOXP3(+) regulatory T cells (Tregs) in vivo. We examined the effects of IL-2 signaling in human Tregs. In vitro, IL-2 selectively up-regulated the expression of FOXP3 in purified CD4+CD25+ T cells but not in CD4+CD25- cells. This regulation involved the binding of STAT3 and STAT5 proteins to a highly conserved STAT-binding site located in the first intron of the FOXP3 gene. We also examined the effects of low-dose IL-2 treatment in 12 patients with metastatic cancer and 9 patients with chronic myelogenous leukemia after allogeneic hematopoietic stem cell transplantation. Overall, IL-2 treatment resulted in a 1.9 median fold increase in the frequency of CD4+CD25+ cells in peripheral blood as well as a 9.7 median fold increase in FOXP3 expression in CD3+ T cells. CD56+CD3- natural killer (NK) cells also expanded during IL-2 therapy but did not express FOXP3. In vitro treatment of NK cells with 5-aza-2'-deoxycytidine restored the IL-2 signaling pathway leading to FOXP3 expression, suggesting that this gene was constitutively repressed by DNA methylation in these cells. Our findings support the clinical evaluation of low-dose IL-2 to selectively modulate CD4+CD25+ Tregs and increase expression of FOXP3 in vivo.

Antigens, CD↗
PubMed2005

Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation but the immune mechanisms leading to the diverse clinical manifestations of cGVHD remain unknown. In this study, we examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies demonstrated decreased frequency of CD4+CD25+ T cells in patients with cGVHD compared with patients without cGVHD (P < .001) and healthy individuals (P < .001). Gene expression of Treg transcription factor FOXP3 was reduced in cGVHD patients compared with patients without cGVHD (P = .009) or healthy donors (P = .01). T-cell receptor excision circle (TREC) assays for the evaluation of thymus activity revealed fewer TRECs in both transplant groups compared with healthy donors (P < .001 and P = .02, respectively) although no difference was observed between patients with or without cGVHD (P = .13). When tested in functional assays, Tregs from both patient cohorts and healthy individuals mediated equivalent levels of suppression. Collectively, these studies indicate that patients with active cGVHD have reduced frequencies of Tregs but the function of these cells remains normal. These findings support the development of new strategies to increase the number of Tregs following allogeneic hematopoietic stem cell transplantation to prevent or correct cGVHD.

Adult↗
PubMed2005

Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor.

Donor lymphocyte infusions (DLIs) induce effective graft-versus-tumor responses in patients with multiple myeloma who relapse after allogeneic hematopoietic stem-cell transplantation. The graft-versus-myeloma response is presumably mediated primarily by donor T cells, but recent studies have also demonstrated the presence of antibodies specific for a variety of myeloma-associated antigens in patients who achieve complete remission after DLI. One of the B-cell antigens identified in these studies was B-cell maturation antigen (BCMA), a transmembrane receptor of the tumor necrosis factor (TNF) superfamily that is selectively expressed by mature B cells. The present studies were undertaken to characterize the functional significance of antibodies to BCMA in vivo. Using transfected cells expressing BCMA, antibodies in patient serum were found to react with the cell-surface domain of BCMA. Post-DLI patient serum was able to induce complement-mediated lysis and antibody-dependent cellular cytotoxicity (ADCC) of transfected cells and primary myeloma cells expressing BCMA. BCMA antibodies were only found in post-DLI responders and not in other allogeneic transplant patients or healthy donors. These results demonstrate that BCMA is a target of donor B-cell immunity in patients with myeloma who respond to DLI. Antibody responses to cell-surface BCMA may contribute directly to tumor rejection in vivo.

Adult↗
PubMed2005

Visual acuity and contrast sensitivity comparison between Tecnis and AcrySof SA60AT intraocular lenses: A multicenter randomized study.

PURPOSE: To evaluate best corrected visual acuity (BCVA) and photopic and mesopic contrast sensitivity in pseudophakic patients implanted either with the aspheric intraocular lens (IOL) designed to correct for corneal spherical aberration or with a conventional IOL. SETTING: Three surgical centers participated this prospective randomized masked comparative study. METHODS: Thirty eyes of 30 patients after aspheric lens implantation (Pfizer/Pharmacia Tecnis Z9000) were compared with 30 eyes of 30 age-matched patients after conventional lens implantation (Alcon AcrySof SA60AT). Two to three months after surgery, best spectacle corrected distance visual acuity was measured using the Early Treatment Diabetic Retinopathy Study chart. Contrast sensitivity was measured by sinusoidal grating charts for distance at photopic (85 cd/m(2)) and mesopic (6 cd/m(2)) luminance level with optical correction in place. Tested spatial frequencies were 1.5, 3, 6, 12, and 18 cycles per degree (cpd). RESULTS: The mean BCVA was -0.053 +/- 0.044 logMAR in eyes with the aspheric Tecnis IOL and 0.006 +/- 0.059 logMAR in eyes with the conventional AcrySof IOL (P=.0001). Eyes with the aspheric IOL showed better contrast sensitivity at spatial frequencies of 3 cpd (P<.05) and 6, 12, and 18 cpd (P<.01) in photopic and in mesopic conditions. Peak improvement occurred at 18 cpd and was 36% (0.29 log units) in photopic and 54% (0.27 log units) in mesopic conditions. CONCLUSIONS: The aspheric Tecnis IOL yielded better BCVA and better distance contrast sensitivity than the conventional IOL. The differences were clinically significant for higher spatial frequencies. The results give some suggestions for further studies.

Aged↗
PubMed2005

Multifocal intraocular lenses.

PURPOSE OF REVIEW: Multifocal intraocular lenses (IOLs) are growing in popularity among patients and surgeons, and opened the way to refractive lens exchange. Still they are not used routinely in cataract surgery, for reasons probably connected to the frequently observed reduction in contrast sensitivity. Recent papers with clinical study outcomes can help in understanding the advantages and the limits of multifocal IOLs. RECENT FINDINGS: Emerging from every published study, both refractive and diffractive multifocal IOLs usually provide good near visual acuity with distance correction. As many multifocal IOLs are distance-dominant, near vision can be improved by correcting for near the distance focus. The near contrast sensitivity thus obtained is similar to that of monofocal IOLs. Multifocal IOLs have been employed with success in complicated cataract surgery and in trauma cases, with the same outcome as in normal cataract cases. Presbyopic lens exchange remains controversial, with a high success rate in original ametropic eyes, but limited success in original emmetropic eyes. Secondary procedures to improve the refractive outcome are usually of little efficacy in improving patient satisfaction. A new anterior chamber phakic multifocal IOL has been designed to correct presbyopia and small refractive errors. The first clinical results indicate high patient satisfaction, with 7.3% explantation rate. SUMMARY: Multifocal IOLs can be more widely used after cataract surgery, but should be used with caution in almost emmetropic eyes with little or no cataract. Refractive lens exchange with multifocal IOL is especially worthwhile in hyperopic eyes. The new phakic multifocal IOL adds the concept of reversibility to presbyopic lens exchange.

Humans↗
PubMed2003

Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens.

The ability of donor lymphocyte infusions (DLIs) to induce complete responses (CRs) in patients with relapsed myeloma after allogeneic bone marrow transplantation (BMT) provides clear evidence of an effective graft-versus-myeloma (GVM) response. To identify target antigens of the GVM response, we screened a myeloma cDNA expression library with post-DLI serum from 4 patients with myeloma who achieved CR after DLI and 1 patient who was in CR before DLI. We identified a panel of 13 gene products reactive with post-DLI serum but negative with pre-DLI and pre-BMT serum. Antibodies to these proteins were not detected in the sera of 10 patients who underwent allogeneic BMT without DLI and 5 patients with acute graft-versus-host disease (GVHD). Minimal reactivity with these proteins was detected in the sera of 20 healthy donors and 20 patients with chronic GVHD. In contrast, 5 of these proteins were recognized by more than 1 myeloma DLI responder. Testing of serial serum samples showed an association between antibody response and time of best response after DLI. The expression of these genes was evaluated in primary myeloma cells and in normal plasma cells. This study demonstrates that the GVM response is associated with antibody responses to highly expressed myeloma-associated antigens.

Antibody Formation↗
PubMed2003

Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion.

Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vbeta repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded approximately 10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.

Adult↗
PubMed2003

Possibility of progenitor cell mobilization during the hematological recovery following peripheral blood stem cell autograft.

Twenty-four patients with hematological malignancies were studied during recovery following autografting in order to establish the proportion of patients that show CD34+ cell mobilization and the kinetics of mobilized CD34-positive cells. The patients showed a peak in peripheral blood (PB) CD34+ cells after a median of 14 days (range 12-20) following reinfusion. According to the number of circulating CD34+ cells, two groups could be clearly distinguished: 17 patients (group A) with <10 PB CD34+ cells/microl (median 1.2, range 0-5) and 7 patients (group B) with >10 CD34+ cells/microl (median 51, range 13-123). Compared to group A, patients of group B showed a faster hematological reconstitution of both polymorphonuclear leukocytes >500/microl (12 vs. 15 days) and platelets >50,000/microl (12 vs. 17 days). The expression of the beta1 integrin CD49d was similar in the two groups of patients, while a lower expression of the beta2 integrin CD11a and a greater expression of the L-selectin CD62L were observed in the PB CD34+ cells of group B patients. Both in the PB and in the BM, the number of CFU-GEMM, CFU- GM, CFU-E and BFU-E of group B was significantly greater than that of group A. However, when the clonogenic potential of a single CD34+ cell was evaluated, no major differences in the number of colonies produced per CD34+ cell were found between the two groups.

Adolescent↗
PubMed2002

Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma.

Reconstitution of T-cell immunity after bone marrow transplantation (BMT) is often delayed, resulting in a prolonged period of immunodeficiency. Donor lymphocyte infusion (DLI) has been used to enhance graft-versus-leukemia activity after BMT, but the effects of DLI on immune reconstitution have not been established. We studied 9 patients with multiple myeloma who received myeloablative therapy and T-cell-depleted allogeneic BMT followed 6 months later by infusion of lymphocytes from the same donor. DLI consisted of 3 x 10(7) CD4(+) donor T cells per kilogram obtained after in vitro depletion of CD8(+) cells. Cell surface phenotype of peripheral lymphocytes, T-cell receptor (TCR) V beta repertoire, TCR rearrangement excision circles (TRECs), and hematopoietic chimerism were studied in the first 6 months after BMT and for 1 year after DLI. These studies were also performed in 7 patients who received similar myeloablative therapy and BMT but without DLI. Phenotypic reconstitution of T and natural killer cells was similar in both groups, but patients who received CD4(+) DLI developed increased numbers of CD20(+) B cells. TCR V beta repertoire complexity was decreased at 3 and 6 months after BMT but improved more rapidly in patients who received DLI (P =.01). CD4(+) DLI was also associated with increased numbers of TRECs in CD3(+) T cells (P <.001) and with conversion to complete donor hematopoiesis (P =.05). These results provide evidence that prophylactic infusion of CD4(+) donor lymphocytes 6 months after BMT enhances reconstitution of donor T cells and conversion to donor hematopoiesis as well as promoting antitumor immunity.

Adult↗
PubMed2002

Allogeneic stem cell transplantation for multiple myeloma.

The sensitivity of myeloma cells to high dose chemotherapy has led to the use of allogeneic hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disease. In addition to providing more effective chemotherapy, the transplantation of allogeneic stem cells also initiates the development of an allogeneic immune response directed against residual myeloma cells. Direct evidence for a graft vs. myeloma (GVM) effect is provided by the ability of donor lymphocyte infusion (DLI) to induce significant responses in 30-50% of patients with myeloma who have relapsed after allogeneic HSCT. Nevertheless, allogeneic stem cell transplantation is also associated with a high incidence of transplant related toxicities, including regimen-related toxicities, graft vs. host disease (GVHD) and opportunistic infections. DLI has been shown to enhance immune reconstitution after allogeneic HSCT in addition to inducing a GVM response. Current efforts are directed at reducing the toxicities associated with allogeneic HSCT, identification of the target antigens of GVM and the development of new strategies to selectively enhance the immune response to myeloma cells.

Graft vs Tumor Effect↗
PubMedDate not supplied

Long-term follow-up after transscleral diode laser photocoagulation in refractory glaucoma.

BACKGROUND AND OBJECTIVE: Patients affected by glaucoma refractory to medical or surgical treatment are difficult to treat. The aim of this study was to evaluate the long-term effect of contact transscleral diode laser cyclophotocoagulation (DLPC) on intraocular pressure (IOP) and on visual acuity of these patients. PATIENTS AND METHODS: One hundred and twenty eyes of 107 patients suffering from refractory glaucoma and treated with DLPC were followed at the Eye Clinic of Verona University for an average of 26 +/- 8 months. Mean age was 57 +/- 26 years. IOP, visual acuity, and ocular complications were analyzed. RESULTS: A total of 207 treatments were given. More than one treatment was given in 55 eyes (45.8%). Mean pretreatment IOP was 30.4 +/- 3.1 mm Hg. At the last follow-up, mean IOP was 20.3 +/- 1.8 mm Hg. Mean total medications were reduced from 4.5 +/- 0.5 to 2.3 +/- 0.3. No serious complications occurred in the 207 treatments. Visual acuity remained stable in 66 eyes (55%), improved in 25 eyes (20.8%), and decreased in 29 eyes (24.2%). CONCLUSIONS: DLPC was effective in lowering IOP in eyes with refractory glaucoma. It also served to reduce the number of antiglaucoma medications, thus improving both the quality of life of the patients and their compliance to therapy. This procedure is relatively safe, very fast and easy to learn. However, careful attention is required to determine the exact position of the ciliary body in malformative glaucoma. Multiple treatments may be required to control IOP.

Administration, Topical↗
PubMedDate not supplied

Comparison of wavefront aberrations and optical quality of eyes implanted with five different intraocular lenses.

PURPOSE: We compared corneal and total higher order wavefront aberrations in 25 pseudophakic eyes implanted with five different types of intraocular lenses to obtain an objective evaluation of the optical quality of these pseudophakic eyes. Five IOLs per type were studied. METHODS: Implanted lenses were the Pharmacia Tecnis Z9000 with negative spherical aberration, Pharmacia 911 Edge, Alcon Acrysof SA60AT and MA60BM, and Allergan Sensar AR40e. Eyes were examined using the Topcon KR-9000PW topographer/aberrometer, which obtains simultaneous coaxial measurements of corneal and ocular aberrations, and displays the calculated Point Spread Function (PSF) and Modulation Transfer Function (MTF). RESULTS: Corneal spherical aberration was positive in all tested eyes. For a 4-mm optical zone, ocular spherical aberration was 0.0054+/-0.0172 microm root-mean-square (RMS) in eyes implanted with the Tecnis lens, and was 0.0562 to 0.0974 microm RMS in eyes implanted with the four other conventional IOLs. A myopic refractive shift with mydriasis of -0.08 D occurred with the Tecnis IOL; it was -0.57 to -0.90 D with the conventional IOLs. Coma did not show a substantial reduction with any of the IOLs. Total wavefront aberrations showed nonsignificant reduction with the Tecnis lens. The PSF and the MTF also showed nonsignificant improvements over conventional IOLs. CONCLUSIONS: The optical quality of pseudophakic eyes can be measured in vivo by aberrometers. Different IOLs resulted in measurably different outcomes. In this preliminary study, compensation of the spherical aberration observed with the Tecnis lens confirmed the theoretical predictions associated with this lens and resulted in no myopic shift in refraction with mydriasis.

Aged↗
PubMedDate not supplied

Reverse flap dissection for glaucoma surgery.

A modified reverse dissection of scleral flaps for glaucoma surgery is described. A conventional square or rectangular flap is designed with deep scleral incisions, the two radial incisions crossing the limbus. A horizontal tunnel is created parallel to the limbus within the peripheral cornea, joining the two radial incisions. This tunnel is then enlarged toward the sclera, gradually dissecting the whole scleral flap. This centrifugal cutting is opposite to the common centripetal cutting employed for scleral flaps. Advantages over conventional dissection include more precise dissection within the limbal area, smoother surfaces, and reduction of disturbing bleeding.

Dissection↗