Biomedical subjects
Publications and source records attributed to R Vanacore.
We describe a case of polyradiculoneuropathy (PRN) following living donor kidney transplantation, without clinical evidence of preexisting infection. In this study plasma exchange treatment resulted 6 days later in improvement in extremity weakness and paresthesias in the upper and lower extremities. Total neurological recovery was obtained 3 months after the onset of symptoms.
BACKGROUND: Originally introduced for cutaneous T-cell lymphomas and autoimmune diseases, extracorporeal photopheresis (ECP) has been proven effective to reverse allograft rejection. The aim of the present work was to show the results of a single-center experience with ECP for the treatment of biopsy-proven rejection in selected liver transplant (LT) recipients. PATIENTS AND METHODS: A retrospective review of five LT patients (M:F=4:1; median age 51 years) undergoing ECP for biopsy-proven allograft rejection between January 1996 and December 2003. In this period 476 LT were performed on 441 patients. RESULTS: The indications for LT were three cases of HCV-related cirrhosis, complicated by hepatocellular carcinoma in two; one HBV-HDV-alcoholic cirrhosis; and one fulminant HBV hepatitis. All patients received calcineurin-inhibitor (CNI)-based immunosuppression with induction using anti-IL2R monoclonal antibodies. Indications for ECP were: ductopenic rejection in one patient with HCV recurrence; steroid-resistant acute rejection in two; acute rejection in a major ABO-mismatched liver graft; and one acute rejection in a patient with a proven allergy to steroids. The median interval from LT to inception of ECP was 43 days. The median number of ECP sessions per patient was 20. During the course of ECP, two patients tested positive for CMV antigenemia, associated in one case with bacterial pneumonia. All patients tolerated ECP and there were no procedure-related complications. At a median follow-up of 7.9 months after start of ECP, neither rejection relapses nor HCV/HBV recurrences have been observed. Three patients are off ECP with complete reversal and low-dose immunosuppression. Two patients are still receiving ECP with full-dose immunosuppression: one has achieved normal liver function but ECP is indicated due to a major ABO-incompatible liver graft, while the other patient's liver functions have not yet returned to baseline values.
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BACKGROUND: As single agents, both paclitaxel and epirubicin in combination with cytokines can mobilize peripheral blood progenitor cells (PBPCs). The authors have demonstrated previously that the combination of epirubicin and paclitaxel is very active against metastatic breast carcinoma and tolerated by patients. METHODS: Twenty-one patients with metastatic breast carcinoma received epirubicin 90 mg/m2 in combination with paclitaxel 200 mg/m2 given as a 3-hour infusion, and granulocyte-colony stimulating factor (G-CSF) starting 24 hours after chemotherapy to mobilize PBPCs. An immunophenotypic analysis for CD3, CD4, CD8, CD 19, CD33, CD34, and CD38 antigen expression was performed on apheresis products. Eighteen patients underwent high dose chemotherapy and were engrafted with PBPCs primed with paclitaxel, epirubicin, and G-CSF. RESULTS: The median number of circulating CD34+ cells at peak was 70/microL; in the patients less heavily pretreated, it was 106.7/microL. The mean number of CD34+, CD34+/CD33-, and CD34+/CD38- cells/kg collected per apheresis was 6.3 x 10(6), 2.0 x 10(6), and 0.18 x 10(6), respectively. The mean number of CD34+ cells/kg per apheresis was 7.8 x 10(6) when the preleukapheresis CD34+ cell count was more than 50/microL and 0.9 x 10(6) when the CD34+ cell count was less than 50/microL. The mean number of CD3+, CD4+, and CD8+ cells/kg collected per apheresis was 90 x 10(6), 50 x 10(6), and 30 x 10(6), respectively. CONCLUSIONS: Epirubicin plus paclitaxel in combination with G-CSF mobilizes PBPCs, including more primitive progenitors capable of supporting myeloablative treatment. Moreover, the mononuclear cells collected in this study contained high levels of cytotoxic effector cells suitable for ex vivo manipulation to augment the antitumor effect.
Multiple sclerosis (MS) is postulated to be an immunopathologically mediated disease. This concept is supported by the finding of abnormally distributed peripheral blood T-cell subsets and a decreased T-suppressor function. Thirty-seven MS patients have been selected according to the criteria for definite MS. Fluorescein- or phycoerythrin-conjugated monoclonal antibodies have been used to define different lymphocyte subsets: CD4+, CD5+, CD8+, CD19+, CD38+, CD45RA+, CD4+CD45RA+, CD19+CD5+, CD8+CD38+. In relapsing-remitting (RR)-MS patients a significantly decreased percentage of CD19+ cells and in progressive MS patients a significantly increased percentage of CD19+CD5+ cells have been found. During a relapse in RR-MS, a significantly decreased percentage of CD4+CD45RA+ cells and a significantly increased percentage of CD8+CD38+ cells have been observed. Moreover, in RR-MS patients a significantly increased percentage of CD38+ cells and significantly high IgM amounts have been found. The increased percentage of CD19+CD5+ and CD38+ cells (together with high IgM levels) and the reduced percentage of CD4+CD45RA+ lymphocytes could be related to an activation of both cellular and humoral immune response in acute MS.
Flow cytometry represents an interesting methodological approach to human neutrophil function assessment and to the study of neutrophil biology. Several aspects of neutrophil activation can be evaluated by means of such technology: phagocytosis, respiratory burst, surface markers, modifications in intracellular pH, actin polymerization, membrane potential, aggregation. Neutrophil flow cytometric evaluation is suitable for whole blood evaluation and has been shown to be very specific and sensitive. In particular, whole blood methods have been developed in order to investigate phagocytosis, hydrogen peroxide production, and surface markers expression (integrins, receptors for the Fc fragment of IgG, selectins, etc.). Other aspects of neutrophil activation have to be investigated by using purified neutrophils.
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The effects of interferon-alpha (IFN-alpha) on clinical and serologic manifestations of mixed cryoglobulinemia (MC) were investigated by randomized, crossover-controlled trial in 26 patients. The trial alternated 6 months with and 6 months without IFN-alpha therapy (2 x 10(6) IU daily for a month, then every other day for 5 months). In 22 patients, pretreatment steroid dosage remained unchanged during the study. Six patients dropped out (three because of side effects), whereas another 20 patients experienced a significant improvement of purpura (P < .02) and serum transaminases (P < .005) during IFN-alpha treatment. The presence of clinical improvement was supported by the outcome measurements of several immunologic parameters. In particular, serum cryoglobulins were significantly reduced (P < .04) during IFN-alpha therapy. A rebound phenomenon of clinical and serologic parameters was observed after IFN-alpha discontinuation. In addition, no variations were recorded during 6 months without therapy. Hepatitis C virus (HCV) RNA was detected in 91% (20/22) of our MC patients; in 2/13 cases HCV RNA was no longer detectable in serum samples after IFN-alpha therapy. Thus, IFN-alpha could be considered as treatment for MC in patients with HCV seropositivity.
To confirm the positive results of a preliminary trial, 26 patients with mixed cryoglobulinaemia were enrolled in a controlled, randomised, crossover trial with interferon alfa-2b. A significant improvement was seen in the purpura score and alanine aminotransferase activities during six months' treatment, and was associated with a significant decrease in cryocrit and a returning to normal of the lymphocyte CD4/CD8 ratio (in eight of nine patients). No significant variations were seen during the six month period without interferon. Only six patients withdrew from treatment, three because of side effects and three because of poor compliance.
Antibody response to antigen A60 (a mycobacterial antigen) was evaluated in ELISA in 18 HIV+ subjects with clinical and cultural evidences of mycobacterial infections, in 10 HIV+ subjects without Mycobacterial infections and in 22 healthy donors. We found higher levels of specific IgG in the HIV+ patients with Mycobacterial infections (mean 179.2 +/- 83 U) compared to the values of the donors (mean 92.5 +/- 35.5 U: p < 0.01). This test may be useful in the diagnosis of tuberculosis, but it needs clinical validation.
The "in vitro" effect of different concentrations of polyclonal human immunoglobulins for intravenous use (IVIG) on cultured T-lymphocyte response to phytohemagglutinin (PHA) was evaluated. Four dilutions of IVIG corresponding with the "in vitro" doses currently employed in therapy have been tested by the effect on PHA stimulated cultures. The dilution of IVIG corresponding with a low therapeutical dose gives a higher statistically significant stimulating effect. The results obtained in our work agree with previous studies performed on activated B-cells. We can suppose the immunoglobulins may control the T-lymphocyte activation either by a direct link with a specific Fc-receptor expressed on the surface of activated T-cell or by affecting the cytokines release from monocyte cells.
Recent research has demonstrated that CD5+ B lymphocytes have an important role in autoimmune and rheumatic diseases. In a case of juvenile rheumatoid arthritis (JRA), we observed the behavior of these cells and other subpopulations of T lymphocytes of peripheral blood before and after therapy with thymopentin (TP5). All the lymphocyte subpopulations returned to normal range, except the CD5+ B cells, where the percentage remained abnormally high (60%). These data suggest that CD5+ B cells can be a useful monitoring index and confirm their important role in the pathogenesis of juvenile rheumatoid arthritis.
FcRIII (CD16) expression on neutrophils from 17 patients with chronic myeloid leukemia (CML) was studied by flow cytometry using monoclonal antibodies. A variable proportion of CD16-negative neutrophils were found both in CML patients in chronic phase (3 out of 8 patients) and in CML patients in hematological remission (3 out of 9 patients). Neutrophils with reduced FcRIII expression showed more defective chemiluminescence and phagocytosis than neutrophils with normal FcRIII expression. Circulating myeloid cells from three patients in chronic phase, showing a normal percentage of CD16-positive neutrophils, were isolated and fractionated by discontinuous Percoll gradients. This study showed that CD16 appears at the stage of metamyelocyte, that band cells and segmented neutrophils display an identical pattern of membrane FcRIII, and that the fluorescence intensity shown by metamyelocytes is different from that displayed by more mature cells. The association between low FcRIII expression and function abnormality could be suggestive of a defect in CML neutrophil maturation.
We investigated subsets of peripheral immunologic cells in 12 drug-free patients affected by major depression according to DSM-III-R criteria, and who had recent evidence of somatic diseases. They were compared with 10 drug-free depressives, with 10 patients with panic disorder, and with 12 healthy volunteers, all without somatic disease. The immune subsets were measured by flow cytometry. The results showed that both groups of depressives had the same abnormalities in immune cells compared with the healthy volunteers or the panic disorder patients; in particular they presented a lower number of CD3+, CD8+ and HLA-DR+. The patients with panic attacks did not differ from healthy controls, except for CD4+ cells which were significantly lowered, even in comparison with the depressive groups. These data, although preliminary and in a small sample, suggest that some immune parameters may be influenced by the presence of a major psychiatric disorder.
Six subjects (4 female, 2 male), aged from 16 to 25 years, presented with allergic rhinitis to Dermatophagoides mites and received SIT by the sub-cutaneous route with delayed-release alpha fraction Bayropharm at the standard doses. Diagnosis was based on clinical history, skin tests and measurement of specific IgE at 0, 3, 9, and 12 months, by the fluoro-enzymatic technique (FAST). For comparison, in a reference group (n = 20) the IgE varied between 0.32 and 0.11 IU/ml for D1 and 0.31 to 0.09 IU/ml for D2. The eight patients had specific IgE titres of D1 = 0.96, D2 = 0.99. For these authors, the FAST technique used for the measurement of specific IgE, although less sensitive than the RIA technique of RAST, gives a good evaluation of SIT.