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Biomedical subjects

P Strada

Publications and source records attributed to P Strada.

At least 19 recordsLinked to original sources

Catastrophic relapse of Evans syndrome five years after allogeneic BMT notwithstanding full donor chimerism. Terminal hemolytic-uremic syndrome.

A patient with severe Evans syndrome received an allo-BMT from his HLA-identical sister on November, 2000. Full marrow and blood donor chimerism were achieved only after 5 donor lymphocyte infusions (DLI), and coincided with complete clinical remission and disappearence of auto-antibodies. Five years later, hemolytic anemia recurred with rapid increase of serum bilirubin to over 50 mg%: he responded to combined therapy, but died on day +17 from admission of an acute hemolytic uremic syndrome (HUS). All circulating blood cells, including erythrocytes, were 100% donor. Ex vivo cultured and expanded T and B cells from the peripheral blood were also 100% donor. The supernatants from B cell cultures, containing either IgM or IgG, did not react with a panel of erythrocytes. Thus in this typical autoimmune disease with a predominant B cell pathogenesis the donor immune system resulted "innocent of autoimmunity". The persistence of long-lived recipient autoreactive plasma-cell lines in survival niches, still producing autoantibodies, may be hypothesized for this and similar cases. The postulated graft-versus-autoimmunity (GVA) effect was apparently not sufficient to eradicate autoimmunity in this patient.

Adolescent↗

Prevalence of DRB1*01 and DRB1*04 alleles in a group of patients with rheumatoid arthritis living in Liguria.

A major component of genetic susceptibility to rheumatoid arthritis (RA) appears to be explained by inheritance of HLA-DRB1 alleles. Multiple HLA-DRB1 alleles (DRB1*0401, *0404, *0405, *0408, *0101, *102, *1001 and *1402) encoding a shared epitope at amino acid positions 70-74 are associated with susceptibility to RA. There is ethnic variation in the clinical expression of RA and in both the frequency and type of HLA-DRB1 alleles carrying the shared epitope. We evaluated the prevalence of the alleles of HLA-DRB1 locus encoding for SE in 42 outpatients with RA attending the Rheumatology Center of the University of Genoa, Bruzzone Institute, and living in Liguria. A control group was composed of Italian marrow donors. DNA genotyping was performed using a low-resolution polymerase chain reaction technique for characterization of the families of HLA-DRB1 alleles for each of the 42 patients studied. Subsequently, subjects with *01 and *04 haplotype were tested with high-resolution HLA-DRB 1 typing to characterize the *01 and *04 alleles. No statistically significant differences were found in the prevalence of RA-associated single alleles *01 and *04 in the study group or in the control group. In contrast, the sum of susceptibility *04 alleles studied by resolution typing was strongly related to RA in the study group in comparison with the control group.

Adult↗

Left ventricular thrombi: changes in size and in platelet deposition during treatment with indobufen and ticlopidine.

This study was designed to evaluate whether indobufen and ticlopidine can induce changes in the size of left ventricular thrombi and variations in the deposition of platelets on thrombus surface. Forty-seven patients with left ventricular thrombosis, who were not treated with antithrombotic drugs, were prospectively evaluated with 111In-oxine platelet imaging and two-dimensional echocardiography. The first scintigraphic examination was negative in 15 of the 47 patients with left ventricular thrombosis, thus they were excluded from further evaluation. The remaining 32 patients with evidence of labeled platelet deposition on the thrombus were divided into three groups. Group 1 comprises 11 patients treated with different doses of ticlopidine: 6 with 250 mg/day, and 5 with 500 mg/day. Group 2 comprises 12 patients who received 400 mg/day of indobufen. Group 3 comprises 9 patients who were not treated with antithrombotic drugs. All 32 patients underwent repeated 111In-oxine platelet imaging and echocardiography 40 +/- 11 days after the first examination. During treatment with ticlopidine, deposition of labeled platelets on the thrombus became absent in 2 patients (500 mg/day), and reduced in 5 (2 treated with 250 and 3 with 500 mg/day). A decrease of platelet deposition on the thrombus was also observed in 5 of the 12 patients receiving indobufen and in only 1 of 9 controls. With regard to thrombus dimensions, 1 patient treated with ticlopidine showed a decrease in thrombus size associated with a reduction of the scintigraphic activity. In conclusion, a decrease of the platelet uptake on the thrombus surface, without significant changes in the size, was detected in most patients during treatment with indobufen and ticlopidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography↗

Mixed chimerism after allogeneic marrow transplantation for leukaemia: correlation with dose of total body irradiation and graft-versus-host disease.

Fifty-four patients allografted for leukaemia were evaluated at various intervals after bone marrow transplantation for the presence of host haemopoiesis using red blood cell and cytogenetic markers. Out of 40 patients in remission, 10 showed functional host and donor haemopoiesis (mixed chimerism), whereas in the other 30 (complete chimerism) host haemopoiesis was never detected. Seven of the 14 evaluable patients who relapsed showed the reappearance of host haemopoiesis at the time of relapse. Analysis of the dose of total body irradiation (TBI) indicated that patients who achieved mixed chimerism, whether or not they relapsed, had received significantly lower doses than those with complete chimerism. However, some patients with complete chimerism had received a TBI dose equivalent to the dose received by those with mixed chimerism, suggesting that the TBI dose is not the only factor determining the reappearance of host haemopoiesis. The data on chimerism and relapse suggest that there is heterogeneity in radiosensitivity between normal marrow cells and leukaemic cells, and also within the different types of leukaemia. The incidence/severity of acute and chronic graft-versus-host-disease (GVHD) was significantly higher in patients with complete chimerism than in mixed chimeras, suggesting that mixed chimerism may play a role in the development of tolerance. Alternatively the absence of GVHD (i.e. tolerance) may be responsible for the persistence of host haemopoietic cells.

Bone Marrow Transplantation↗

Competition between recipient and donor cells after bone marrow transplantation for chronic myeloid leukaemia.

The cytogenetic and clinical course of three patients allografted for Ph positive chronic myeloid leukaemia are reported. All patients had a peculiar pattern of relapse. Two out of three patients had donor marrow graft pretreated with monoclonal antibody for graft versus host prevention. The cytogenetic relapse was invariably associated with major morphological changes in the marrow indicating that these were also haematological relapses. However, no changes in the peripheral blood count were observed. When relapse occurred in these patients, Ph positive marrow metaphases and host red blood cells ranged from 75% to 100% of the total cell population: thereafter they spontaneously reverted to complete chimaerism. Therefore the presence of leukaemic cells even in considerable amount was not sufficient, per se, to prevail over normal marrow. In addition these observations indicate that relapse was not associated with elimination of the graft: while haemopoiesis was entirely of recipient origin the donor normal stem cells were present and vital although functionally silent. These data suggest that, although TBI remains the more effective tool for eradicating the majority of leukaemic cells, haemopoietic competition between host and donor marrow may have a major impact on leukaemic relapse.

Acute Disease↗

Activity of left ventricular thrombi of different ages. Assessment with indium-oxine platelet imaging and cross-sectional echocardiography.

To evaluate the possible relation between the age of intracardiac thrombi and the presence and degree of their activity, 29 patients with left ventricular thrombi that developed after an anterior myocardial infarction were evaluated by means of 111In-oxine autologous platelet imaging. None of the patients was treated with anticoagulants or platelet inhibitors during either the acute phase of infarction or the follow-up. The time of appearance and the shape of left ventricular thrombi were assessed by serial cross-sectional echocardiograms, obtained within 24 hours of onset of the chest pain, every 24 hours until the fifth day, every 48 hours until the 15th day, and then every month for a follow-up of 1 to 17 months (mean: 8 months). At the time of the scintigraphic examination, left ventricular thrombi were aged 1 month in 9 patients, and 2 to 14 months in the remaining 20 patients. 111In-oxine imaging with autologous platelets was obtained in all patients at 4, 24, 48 and 72 hours, in the sagittal, 30 degrees and 45 degrees left anterior oblique projections. In 25 patients the degree of haematological activity of the thrombi was evaluated by dividing the values of thrombus activity/background activity, obtained at 4, 24, 48 and 72 hours, respectively, by the value observed at 4 hours (uptake index). Scintigraphic imaging showed the presence of an active thrombus in every patient. In the 9 patients with recent thrombi, the uptake index was significantly greater than in subjects with older ones (P less than 0.01). Hence, in patients with anterior myocardial infarction, untreated with anticoagulants or platelet inhibitors, haematologically active thrombi can be observed even more than one year after their appearance. The uptake of platelets on the surface of thrombi is greater in recent left ventricular thrombi than in older ones.

Adult↗

Bone marrow transplantation for severe aplastic anemia. A report of 9 cases.

9 patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation (BMT). 5 were conditioned with cyclophosphamide and received and HLA-identical graft (4 patients) or a mismatched graft (1 patient): 1 rejected the graft on day 30 and died on day 34 during conditioning for a second transplant; 1 died on day 15 with acute and severe graft versus host disease (GvHD) in the absence of haemopoietic engraftment; 3 are alive and complete chimeras at 1,069, 490 and 332 days after transplantation. GvHD developed in 4 patients and was treated successfully in 3 with high dose methylprednisolone and/or antilymphocytic globulin (ALG). 4 patients were conditioned with ALG and received bone marrow from a haploidentical sibling or parent: 1 patient was refractory; 3 patients showed evidence of hematologic reconstitution, but 2 of these required a second course of ALG. 3 patients in this group are alive between 60 and 490 days; 1 patient died on day 121 of HBSAg-negative acute hepatitis.

Adolescent↗

Effect of (-)eburnamonine, papaverine and UDP-glucose on cerebral energy state during and after experimental hypoxia and ischaemia in beagle dog.

The effect of (-)eburnamonine, papaverine and UDP-glucose intracarotid perfusion has been evaluated in the brain of beagle dogs during various conditions of cerebral damage (hypoxia, hypoxia plus incomplete ischaemia, hypoxia plus complete ischaemia), and after 3, 15 or 30 min of the post-hypoxic recovery and recirculation. The behaviour of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), of the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge potential of the brain were evaluated in the motor area of the cerebral cortex. The different pharmacological effects of (-)eburnamonine, papaverine and UDP-glucose are discussed with regard to the biochemical changes taking place during the physiopathological conditions tested.

Adenosine Diphosphate↗