Search PubMed⌕ Search

Biomedical subjects

R Marra

Publications and source records attributed to R Marra.

At least 19 recordsLinked to original sources
PubMed2000

Effects of compounds acting on GABA(B) receptors in the pentylenetetrazole kindling model of epilepsy in mice.

The involvement of GABA(B) receptors in the behavioural and epileptic electrocortical discharges occurring in chemical kindling induced by repeated treatments with a subconvulsant dose of pentylenetetrazole (25 mg/kg i.p.) has been investigated in CD1 mice. Behavioural and electrocorticographic epileptic seizures following kindling induced by pentylenetetrazole (25 mg/kg i.p.) were attenuated or completely antagonized in a dose-dependent manner by the GABA(B) receptor agonist R-baclofen (2 and 6 mg/kg) whilst the GABA(B) receptor antagonist 3-amino-propyl-diethoxy-methyl-phosphinic acid (CGP 35348, 25, 50 or 100 mg/kg) and 3-[1-(S)-(3, 4-dichloro-phenyl-ethyl]amino-2-(S)-hydroxy-propyl-benzyl-phosphinic acid (CGP 55845A, 10 or 20 mg/kg) produced a more rapid development of kindling and an increase in behavioural and electrocorticographic epileptic changes. In addition, all GABA(B) receptor antagonists were able to induce an increase in Fos and Jun protein expression in pentylenetetrazole (25 mg/kg i.p.) treated mice whilst the GABA(B) receptor agonist R-baclofen (2 or 6 mg/kg) attenuated the expression of Fos and Jun protein, at cortical and limbic structures. In order to study the persistence of changes induced by pentylenetetrazole kindling, different groups of mice were rechallenged with a kindling stimulus 15 or 30 days after withdrawal from the last injection of vehicle+pentylenetetrazole, R-baclofen+pentylenetetrazole or GABA(B) receptor antagonists+pentylenetetrazole. The groups receiving GABA(B) receptor antagonists+pentylenetetrazole showed a higher incidence of seizures following the kindling stimulus than mice receiving vehicle+pentylenetetrazole whilst animals treated with R-baclofen were protected from the kindling stimulus. The different effects observed following repeated treatment with the GABA(B) receptor agonist and antagonist used revealed that GABA(B) receptors are able to affect the development of the epileptic kindling state induced by pentylenetetrazole.

Animals↗
PubMed2000

MiCMA: an alternative treatment for refractory or recurrent Hodgkin's disease.

BACKGROUND: We determined the response rate to MiCMA (mitoxantrone, carboplatinum, methylprednisolone and aracytin) in a group of 29 patients with Hodgkin's disease (HD) and poor prognostic factors either resistant to first line or relapsing after conventional chemotherapy and subsequently evaluated the role of autologous stem-cell transplantation (ASCT) in these patients after MiCMA. PATIENTS AND METHODS: The treatment was intended as a brief tumor debulking program before ASCT. Twenty-nine patients with primary refractory HD or relapsed HD were submitted to two courses of MiCMA (mitoxantrone 10 mg/m2 day 1; carboplatinum 100 mg/m2 days 1-4; aracytin 2 g/m2 day 5; methylprednisolone 500 mg/m2 days 1-5) and subsequently evaluated for response. Those with responding or stable disease, received one or two other courses of MiCMA followed by ASCT. RESULTS: There were 10 complete responses (34% CR), 15 partial responses (52% PR) and 4 treatment failures with disease progression (14% PD). In total there were 25 evaluable responses out of 29 patients (86% CR + PR). Myelosuppression was the main toxicity of this treatment. At this time 20 patients (69%) are alive with a median follow-up of 26.5 months (7-100), 13 patients in CR (45%), 8 patients died, 7 of them from disease progression and one due to multi-organ failure, one patient is lost to follow-up. All but one of the patients who achieved CR after MiCMA are alive. Only the number of extranodal sites was found to predict a poor response to MiCMA. CONCLUSIONS: A short pre-transplantation treatment with MiCMA is an effective tumor debulking approach in patients with refractory or relapsed HD.

Adolescent↗
PubMed2000

Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.

PURPOSE: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. PATIENTS AND METHODS: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). RESULTS: In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). CONCLUSION: Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.

Adult↗
PubMed1999

The role of antithrombin III in the perioperative management of the patient with unstable angina.

BACKGROUND: To evaluate the effectiveness of intraoperative administration of antithrombin III (AT III) to improve anticoagulation and preserve the hemostatic mechanisms during cardiopulmonary bypass (CPB) in patients with unstable angina under heparin treatment. METHODS: We divided 22 patients, scheduled for coronary artery bypass grafting, into two groups. Group A (11 patients) received 3000 International Units (IU) of AT III concentrates plus heparin before aortic cannulation. Group B (11 patients) received only heparin. Blood drainage, allogeneic blood transfusions, and intraoperative activated coagulation time were recorded. Also, AT III, thrombin-antithrombin complex (TAT), fragment 1.2 (F 1.2), and D-dimers were measured during the operation and the first postoperative day. RESULTS: Group A patients had fewer transfusions and had less chest-tube drainage. In group A, AT III levels increased after AT III concentrates administration and were always higher than in group B. In group B, F 1.2 and TAT increased significantly more after CPB and at the end of operation. Differences in D-dimers between the groups were not significant. CONCLUSIONS: Intraoperative administration of AT III concentrates allowed adequate anticoagulation during CPB and attenuated the coagulative cascade activation and the consequent consumptive coagulopathy.

Angina, Unstable↗
PubMed1999

Multiple paraneoplastic diseases associated with thymoma.

Here we report a patient with a lymphoepithelial thymoma who developed in chronological sequence limbic encephalitis, neuromyotonia and myasthenia gravis. The patient presented with limbic encephalitis associated with an invasive thymoma and improved after surgery and cytotoxic therapy. Two months after thymectomy, neuromyotonia associated with hyperhidrosis and mild motor neuropathy occurred and the patient was given plasma-exchange and prednisone therapy. Five months later he developed mild generalised myasthenia gravis. Anti-acetylcholine receptor antibodies, previously repeatedly negative, were found positive at the onset of clinical signs of myasthenia gravis.

Adult↗
PubMed1998

Anaplastic large cell lymphoma Hodgkin's-like: a randomized trial of ABVD versus MACOP-B with and without radiation therapy.

During the last few years, morphological, immunohistochemical, and genetic findings have placed anaplastic large cell lymphoma (ALCL) as a distinct clinicopathologic entity, and several reports have focused on the existence of different subtypes of the tumor. Particular attention has been paid to the ALCL-Hodgkin's-like (HL) subtype, which seems to be on the border between Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL). From September 1994 to July 1997, during the course of an Italian multicentric trial, 40 ALCL-HLs were randomized to receive as front-line chemotherapy MACOP-B (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin-a third-generation HG-NHL regimen) or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine-a scheme specific for HD). All patients with bulky disease in the mediastinum at diagnosis underwent local radiotherapy after the chemotherapeutic program. Complete response (CR) was achieved in 17 of the 19 (90%) patients who were treated with MACOP-B, and in 19 of the 21 (91%) patients who were administered ABVD. The probability of relapse-free survival, projected at 32 months, was 94% for the MACOP-B subset and 91% for the ABVD subset. The majority of patients with mediastinal bulky disease obtained CR (evaluated with 67Ga single photon emission computed tomography [SPECT]) after their radiotherapy. The present study suggests that ALCL-HL, in line with its borderline status, responds in an equivalent way to third-generation chemotherapy for HG-NHL and to conventional HD treatment in terms of both CR and relapse-free survival rates. However, as to the latter, a longer follow-up period may be needed before stating the absolute equivalence of the two regimens used.

Adolescent↗
PubMed1997

A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.

OBJECTIVES: To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS: Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS: Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION: Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.

Adult↗
PubMed1997

The role of bronchoalveolar lavage in the microbiological diagnosis of pneumonia in patients with haematological malignancies.

In the aetiological diagnosis of pulmonary infections in patients affected by haematological malignancies we evaluated the utility of bronchoalveolar lavage (BAL). One hundred and twenty-seven BAL were performed in 119 patients. In our series, we identified the agent of pneumonia in 53.5% of episodes with the best results in aspergillosis, very common in these patients. The previous empirical anti-infective treatment was modified in 14 episodes (11%). The procedure was generally well tolerated and only one patient bled. We maintain that BAL is a useful diagnostic tool for detecting the agents of pulmonary infections in patients with haematological malignancies, especially when the routine microbiological procedures fail, and it also represents a good alternative to more invasive procedures.

Adolescent↗
PubMed1995

Intrathecal chemotherapy for treatment of overt meningeal leukemia: comparison between intraventricular and traditional intralumbar route.

BACKGROUND: Despite advances in the treatment of acute lymphoblastic leukemia (ALL), overt meningeal leukemia remains a dire condition. The role of intraventricular chemotherapy (IVC) in its treatment is still a matter for debate. Data suggesting benefit from it have been countered by statements of concern regarding the potential complications associated with its use. This report details our results from using IVC. PATIENTS AND METHODS: We compared two groups of adult patients with ALL at their first meningeal involvement. Twelve of them were submitted to ILC and 9 to IVC. RESULTS: Our data showed that IVC yielded a higher rate of complete response (88% vs. 33%) and a lower incidence of second CNS relapse than did ILC (none vs. 50%). Even though there were more long-term disease-free survivors (33% vs. 8%) among the IVC patients, the difference in median event-free survival was not significant (120 vs. 80 weeks; p = 0.66). IVC was associated with a longer overall survival (p = 0.005) and CNS remission time (p = 0.046). Two cases refractory to ILC were later fully responsive to IVC. There were 22% device-related and 11% drug-related complications. CONCLUSIONS: The results are promising, but the small series does not allow for any definite conclusion. In our opinion, the hazards inherent in the placement and operation of the device do not outweight the benefits of IVC for the treatment of overt meningeal leukemia and should not preclude its use. Accurate neurosurgical technique, meticulous care in drug administration and experience with this form of therapy can all contribute to minimizing complications so that full advantage can be taken of IVC's potential.

Adolescent↗
PubMed1994

Sequential peripheral blood progenitor cell transplantation after mobilization with salvage chemotherapy and G-CSF in patients with resistant lymphoma.

We enrolled 18 patients affected by refractory or relapsed lymphoma (HD, NHL) in a two-step protocol that included salvage chemotherapy with mitoxantrone, carboplatinum, methylprednisolone, and cytosine arabinoside (MiCMA) plus G-CSF (5 micrograms/kg/day), peripheral blood progenitor cell (PBPC) collection, and subsequent transplantation after BUCY2 regimen. After MiCMA chemotherapy, four patients (22%) achieved complete response, eight patients (44%) obtained a partial response, and six showed progression of disease (PD). Fourteen out of 18 patients (78%) were considered eligible for PBPC transplantation. Three patients with complete response refused PBPCT; they are currently in continuous complete remission (CCR) at 15, 13, and 15 months, respectively. One patient has been recently transplanted but is too early to be evaluated. Ten patients so far completed the study, eight of whom are currently alive in CR, with a median follow-up of 7.5 months (range 2-13). Hematologic reconstitution was very rapid with a median time to achieve WBC > 1 x 10(9)/L, PMN > 0.5 x 10(9)/L, platelets > 50 x 10(9)/L and > 100 x 10(9)/L of 13 (range 9-15), 12 (range 9-14), 10 (range 0-22), and 14 (range 5-49) days, respectively. Our protocol is highly effective as a salvage treatment, while permitting PBPC collection after G-CSF administration. Hemopoietic reconstitution after transplantation of PBPCs collected with this procedure is complete, rapid, and sustained.

Adolescent↗
PubMed1994

Prevalence of obesity in young adults with acute lymphoblastic leukemia.

We studied the hormonal pattern of nine patients with acute lymphoblastic leukemia. The patients were treated with standard therapeutic regimens. They were overweight by a mean of 52% at the end of the consolidation treatment, and this persisted after a follow-up of 2 years. The only endocrine alteration observed was a moderate decrease in serum testosterone levels in male patients. The other parameters studied were in the normal range. We conclude that prolonged treatment with high doses of corticosteroids, which have a depressive effect on metabolism, was responsible for the obesity.

Adolescent↗
PubMed1993

Granuloblastic masses in the breast: report of two cases.

Two patients with granuloblastic masses of the breast, onsetting at diagnosis and as first relapse site of acute myeloid leukemia are reported. The first case had been diagnosed initially as a carcinoma, and the patient underwent bilateral mastectomy. Acute leukemia was only revealed by histology of the surgical specimen. In the second case a second neoplasia, occurring during acute leukemia, was suspected: a fine needle aspirate of the breast mass showed a leukemic infiltrate. Involvement of breast during acute myeloid leukemia is a rare event and, in our experience, of bad prognostic significance. Mammary glands may be a sanctuary for leukemic cells, contributing to unresponsiveness to chemotherapeutic agents.

Acute Disease↗