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Biomedical subjects

C Messina

Publications and source records attributed to C Messina.

At least 73 records · Page 4Linked to original sources
PubMed1996

Extracorporeal photochemotherapy for the treatment of graft-versus-host disease.

Photopheresis is an extracorporeal photochemotherapy (ECP) used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system; then, reinfused to the host. Because skin exposure to 8-MOP and UVA (PUVA) has been shown to improve cutaneous GVHD, we evaluated in a pilot study, if ECP might be beneficial for patients with GVHD unresponsive to conventional protocols. In this study, we enrolled 9 children or young adults, with acute (no = 1) or chronic extensive GVHD (no. = 8). A significant improvement was observed in three of the 5 patients with scleroderma-like lesions and in one patient with severe liver involvement. Karnofsky performance score improved from 30-50% to 90% in the 4 responders. The better control of GVHD in these patients allowed a reduction of the immunosuppressive therapy that was, finally, discontinued in two. No significant side effects were observed during ECP. Our results suggest that ECP is a nonaggressive treatment that may benefit patients with c-GVHD unresponsive to standard immunosuppressive therapies.

Adolescent↗
PubMed1995

Localization of vinculin and talin at perineurial cells of human sural nerve.

Immunolocalization of spectrin, vinculin, talin, desmin and titin was investigated in human sural nerve. No binding for spectrin and titin was seen in any structure of the nerve. Antibody against desmin immunostained sporadic epineurial vessels only. Endoneurial and epineurial vessels were intensely positive for vinculin and talin. We found expression of vinculin and talin at the perineurial cells, using immunocytochemistry and gold immunoelectron microscopy. Since vinculin and talin are known to be involved in cell-cell and cell-extracellular matrix transmembrane connections, we propose that they, possibly together with other cytoskeletal proteins, may be implicated in the permeability barrier property of the perineurium. In pathological conditions, perineurium plays an as yet unknown role. Future studies are needed to investigate expression of vinculin and talin in neuropathies.

Adolescent↗
PubMed1995

High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study.

We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m2 over 4 d) combined with fractionated total body irradiation (F-TBI) (200 cGy x 2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8.5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. Of the 46 patients who underwent AlloBMT, 33 had isolated or combined marrow relapse and 13 isolated extramedullary relapse. Of the 29 patients given ABMT, 23 had preBMT isolated or combined marrow relapse and six isolated extramedullary relapse. 44/75 patients are alive and in CR at a median follow-up of 35 months (range 10-90 months). Seven children given AlloBMT (15.8%) and two given ABMT (7%) died from transplant-related causes. No major early organ toxicity, including vincristine-related toxicity, was recorded. The overall 3-year EFS estimate (95% CL) was 53.8% (42-66%): in particular, 58.2% (40-76%) for AlloBMT and 27.6% (9-46%) for ABMT patients who experienced a marrow relapse before transplant. The overall 3-year relapse rate estimate (95% CL) was 39.2% (27-51%): in particular, 30.1% (12-49%) in the AlloBMT group and 72% (54-91%) in the ABMT group (P < 0.01) who presented a preBMT isolated or combined marrow relapse. We conclude that the conditioning regimen with high-dose vincristine combined with cyclophosphamide and F-TBI is feasible and promising, although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies.

Adolescent↗
PubMed1995

Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.

PURPOSE: To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. PATIENTS: Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) were patients with an RI > or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. RESULTS: Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. CONCLUSION: Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.

Adolescent↗
PubMed1995

Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.

PURPOSE: To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS: All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS: In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION: Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.

Adolescent↗
PubMed1994

Independent expression of p55 and p75 interleukin-2 receptors (IL-2R) during intravenous or subcutaneous administration of recombinant interleukin-2 (rIL-2) by T-lymphocytes and natural killer cells.

BACKGROUND: The effects of immunotherapy with recombinant interleukin-2 (rIL-2) on peripheral blood lymphocytes have been a matter of debate. In this study the authors addressed the issue of the biologic effects of two different schedules of rIL-2 administration (i.e., continuous intravenous infusion versus subcutaneous injection) on the expression of the p55 and p75 chains of interleukin-2 receptor (IL-2R). METHODS: Sixteen patients were studied: 6 patients with a previous diagnosis of acute leukemia entered the study at least +60 days (+63(-)+144 days) after autologous bone marrow transplantation and were treated with continuous rIL-2 infusion; 10 patients with advanced metastatic renal cancer were treated with subcutaneous rIL-2 therapy. In both groups of patients, therapy consisted of two cycles of 5-day rIL-2, and immunologic evaluation was performed two days after completion of the second cycle. RESULTS: Intravenous treatment was associated with a marked increase in CD56+ natural killer (NK) cells expressing the p75 but lacking the p55 IL-2R; however, the absolute number of CD3+ lymphocytes was unchanged, and they showed a low or absent expression of the p55 and negativity for the p75 IL-2R. After subcutaneous rIL-2 therapy, a slight increase in the percentage of NK cells expressing only the p75 IL-2R was shown. CD3+ lymphocytes still retained the p75 IL-2R negative phenotype, however, with a significant increase (> 15%) in p55 IL-2R expression. The absolute number of CD3+ lymphocytes was also significantly increased. Functional tests on the purified CD3+ population indicate that these cells exhibited low values of cytotoxic and proliferative activities in vitro. CONCLUSIONS: The authors' data point out that subcutaneous administration of rIL-2 during a 2-week period is associated with a marked increase in T-cells that bear the low affinity p55 IL-2R. These findings could be relevant considering the independent role of lymphokine modulation mediated by the p55 and p75 IL-2R on T- and NK cells.

Acute Disease↗
PubMed1994

Ataxia, mental deterioration, epilepsy in a family with dominant enamel hypoplasia: a variant of Kohlschütter-Tönz syndrome?

We describe 3 sibs, their father, and paternal grandfather with amelogenesis imperfecta. In 2 sibs and the father the defect is associated with a neurological syndrome which has a wide range of phenotypic variability. The proposita has ataxia, EEG abnormalities, moderate dementia, and enamel hypoplasia. This case and the affected relatives are discussed in relation to Kohlschütter-Tönz syndrome and neuroectodermal diseases. The syndrome described here, characterized by the association of a genetic enamel defect and neurological impairment, may be of considerable interest in advancing genetic and clinical knowledge on ectodermal tissues and their development.

Abnormalities, Multiple↗
PubMed1994

Reliability among neurologists in the severity assessment of blepharospasm and oromandibular dystonia: a multicenter study.

The reliability of a scale of 0 to 4 (where 0 is normal) in rating the severity of blepharospasm (BS) and oromandibular dystonia (OMD) was evaluated by the concordance among six neurologists from different neurological institutions. As expressed by k index, interobserver agreement was moderate either for BS or for OMD according to the Landis classification. Neurologists showed different rating attitude toward BS and OMD. In fact, the category analysis showed that raters were inclined to overestimate BS and to underestimate OMD. The familiarity with dystonia influenced reliability more than the length of professional experience in neurology. In fact, when examiners were subdivided into subgroups (each of three raters) according to the former criteria, the level of interobserver agreement increased significantly. Almost perfect agreement was obtained in intrarater comparisons. These results may be of value with regard to the conduct of multicenter epidemiologic and clinical studies on focal dystonias.

Adult↗
PubMed1994

Immunocytochemistry of muscle cytoskeletal proteins in acid maltase deficiency.

Immunocytochemistry of dystrophin, spectrin, vinculin (sarcolemma-specific proteins), and desmin (an intermediate filament protein) were investigated in 5 patients with acid maltase deficiency (AMD). One patient had infant onset, 2 had childhood onset, and 2 had adult onset. All had a vacuolar myopathy with autophagic vacuoles containing glycogen and cytoplasmic degradation products. Dystrophin, spectrin, and vinculin were localized at the sarcolemma as in normal muscle fibers. Within the cytoplasm of many fibers, immunoreactivity for the three proteins was seen as single or multiple spots or as circular structures, which most likely corresponded to the limiting membrane of vacuoles. Desmin was overexpressed at the periphery of some vacuoles. It is plausible that, before exocytosis occurs, sarcolemma-specific proteins appear within the vacuole membrane. Vacuole immunolabeling frequently occurred in the patients with childhood and adult onset AMD, but very rarely occurred in the case with infant onset. We hypothesize that a reduced exocytosis rate might explain the infrequent vacuole immunolabeling and the early onset of the infant form of the disease.

Adult↗
PubMed1994

Muscle phosphoglycerate mutase (PGAM) deficiency in the first Caucasian patient: biochemistry, muscle culture and 31P-MR spectroscopy.

Muscle phosphoglycerate mutase (PGAM) deficiency has been so far identified in only six patients, five of these being African Americans. We report the results of clinical, morphological, biochemical, muscle culture and 31P-MR spectroscopy studies in the first Caucasian patient with muscle PGAM deficiency. A 23-year-old man had a 10-year history of cramps after physical exertion with one episode of pigmenturia. Neurological examination and EMG study were normal. ECG and echocardiography revealed hypertrophy of the interventricular septum and slight dilation of the left chambers of the heart. Muscle biopsy revealed increased glycogen content and some accumulation of mitochondria. Muscle PGAM activity was markedly decreased (6.5% and 9.7% of control value in two different biopsies). Citrate synthase and other mitochondrial respiratory chain enzyme activities were much higher than normal. In contrast to the marked decrease of PGAM activity observed in muscle biopsy, total enzyme activity in the patient's aneural muscle culture was normal, being represented exclusively by BB isoenzyme. The deficiency of PGAM-MM isoenzyme was reproduced in the patient's innervated muscle culture. Muscle 31P-MR spectroscopy showed accumulation of phosphomonoesters only on fast "glycolytic" exercise. On "aerobic" exercise, Vmax, calculated from the work-energy cost transfer function, showed an increase consistent with the morphological and biochemical evidence of mitochondrial proliferation. This might represent a sort of compensatory aerobic effort in an attempt to restore muscle power.

Adult↗
PubMed1994

Expression of cytoskeleton proteins in central core disease.

Despite advances in genetics the pathogenesis of central core disease (CCD) is still unknown. We studied muscles from 5 CCD patients by immunocytochemistry using monoclonal antibodies against various cytoskeletal proteins (dystrophin, spectrin, vinculin, desmin, vimentin, myosin heavy chain (MHC) of developmental, neonatal, adult slow and fast types). Dystrophin, spectrin and vinculin immunoreactivity was localized only at sarcolemma as in normal muscle. Vimentin was not present in myofibers. Only sporadic fibers were positive for developmental and neonatal MHC isoforms in adult CCD muscles. A 4-month-old patient had 5% of neonatal MHC-immunoreactive fibers, a finding similar to that of age-matched normal muscle. Desmin intermediate filaments were overexpressed in many core-fibers in extra-core regions, reduced or absent at cores, and greatly increased at the periphery of some cores. Moreover, irregular desmin-positive spots were seen within some cores. On the contrary, in neurogenic muscle atrophy patients, target lesions had increased desmin. These features indicate a possible role of desmin in the pathogenesis of cores, although we do not know if primary or secondary. In addition, they suggest that: (i) cores and targets may be manifestations of different processes; (ii) it is likely that core-fibers are not denervated fibers.

Adolescent↗
PubMed1994

Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia in remission: first choice for isolated extramedullary relapse?

Between May 1984 and May 1992, 75 children 3-19 (median 9) years of age underwent autologous marrow transplant. Clinical data were obtained from the BMT Registry of the AIEOP (Italian Association of Pediatric Hemato/Oncology). Fifty-six children were transplanted after marrow +/- other site(s) relapse and 19 after an isolated extramedullary relapse. The transplant preparative regimens varied according to the center performing the transplant. Seven patients (9%) died of transplant-related complications. Forty-four (58.6%) of 75 patients relapsed again following autologous BMT. The 5-year DFS was 27.8%. An isolated extramedullary relapse was the only variable that statistically influenced DFS. In this retrospective study, autologous BMT for patients with ALL in second CR following marrow relapse did not offer an encouraging result (13% probability of DFS at 5 years), whereas autologous BMT following an (early) isolated extramedullary relapse resulted in nearly 70% DFS. Autologous BMT may be appropriate for this latter group of patients.

Adolescent↗
PubMed1994

Cytomegalovirus interstitial pneumonia in autologous bone marrow transplant recipients. Infectious Disease Working Party of the European Group for Bone Marrow Transplantation.

CMV pneumonia is rare following ABMT. No information has been presented concerning risk factors or outcome of antiviral therapy. Information concerning CMV pneumonia after ABMT was collected from bone marrow transplant centers in Europe. Twenty-one patients who fulfilled the diagnostic criteria of CMV pneumonia were reported. Eighteen of these patients were reported from centers who also reported the total number of ABMT performed. The CMV pneumonia frequency among 2252 reported ABMT patients was 0.8%, and this varied from 0% to 8.6% between different centers. Survival for > 30 days from diagnosis of pneumonia was 43%. Three patients suffered relapses, which were fatal, giving a total survival of 28%. Patients treated with or without TBI had a survival of 18% and 50%, respectively. Among patients given ganciclovir or foscarnet with or without intravenous immune globulin, survival at 30 days was 50% and total survival 28%. There was no difference in survival with or without the addition of intravenous immune globulin. CMV pneumonia is an infrequent but serious complication of ABMT.

Adolescent↗
PubMed1993

Cardiovascular autonomic dysfunction in multiple sclerosis is likely related to brainstem lesions.

Impairment of cardiovascular autonomic reflexes has been described in multiple sclerosis (MS), and believed reflecting dysfunction of reflex pathways located within the central nervous system. A battery of cardiovascular autonomic tests were performed in 40 patients with definite MS: R-R interval variation test, deep breathing, Valsalva manoeuvre, blood pressure and heart rate responses to standing, sustained handgrip. The results were evaluated by Bayesian analysis, a pattern recognition technique. The patients had also magnetic resonance imaging (MRI) of brain and in 19 subjects of cervical spinal cord. Deep breathing test and sustained handgrip test produced most frequently abnormal results (17.5% and 40%, respectively). However, only 4 patients (10% had two or more tests abnormal, with a very variable pattern. Evaluation by Bayesian analysis revealed 7 patients (17.5%) with definite autonomic dysfunction. A correlation was found between the confidence level obtained by Bayesian analysis, as index of autonomic function, and the Kurtzke brainstem FS score (r = 0.43, P < 0.01). There was a significant association between presence of autonomic dysfunction and clinical (P < 0.02) and MRI (P < 0.005) evidence of brainstem lesions.

Adult↗