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Biomedical subjects

G Leone

Publications and source records attributed to G Leone.

At least 253 records · Page 14Linked to original sources

Ventilation-perfusion mismatching as prognostic factor of respiratory failure after pulmonary resection.

This paper reports the results of a retrospective study undertaken to assess the reliability of regional ventilation-perfusion pulmonary scanning in predicting the remaining respiratory function (pFEV1), and the early and long-term outcome of 33 patients with chronic airways disease, submitted to pulmonary resection at the 1st Department of Surgery. All patients had been diagnosed as resectable with the traditional tools and had a traditional pFEV1 (tpFEV1) greater than 800 ml. All pFEV1 were re-calculated (npFEV1) with our new formula which also includes as lost for function all lung areas not to be resected with V/Q mismatching. Normal perfusion and ventilation distribution was found in 24.2% of patients in the lesion area and in 33.3% in the remaining pulmonary areas. An impairment of perfusion was observed in the lesion area in 72.7% of patients, in the remaining areas in 48.4%. An impairment of ventilation was observed in the same regions in 66.6% and 48.5% of patients, respectively. Abnormality in ventilation/perfusion matching occurred in the lesion area in 15.2% of cases, in the ipsilateral lung areas in 18.2%, in the contralateral lung in 48.4% of cases. In predicting postoperative FEV1, and early and long-term mortality among our resectable patients, the tpFEV1 showed an accuracy of 91%, an index of resectability of 93.7%, of unresectability of 0%. Our npFEV1 reached an accuracy of 94.4%, an index of resectability of 100% and an index of unresectability of 66.7%.

Adolescent↗

Renal cell carcinoma in adolescents. A case report and review of the literature.

Renal cell carcinoma is rare in adolescents. Observation of a 16-year-old girl with a clear-cell carcinoma prompted us to review 372 published cases in adolescents. The tumor affects the sexes indifferently and has no side predominance. The incidence is higher in white races. The most frequent presenting sign is a palpable mass (52.7%). X-ray films typically show renal calcifications (25%). The most common histotype is the clear cell carcinoma (76.8%) and at diagnosis 59.5% of these tumors already extended beyond the kidney. The overall 5-year actuarial survival rate is 60.4%.

Adolescent↗

[Update on deep thrombophlebitis and pulmonary thromboembolism].

Pulmonary thromboembolism, a frequent complication in deep vein thrombosis, is still a pathology with a high rate of mortality and morbidity. The authors underline that this pathology is particularly frequent after some types of surgery and in subjects with primary or secondary risk factors. The paper analysis the pathogenesis of deep-vein thrombosis and the physiopathology of pulmonary embolism. The authors then outline the current management in terms of the diagnosis, prophylaxis, and medical and surgical therapy of this pathology.

Humans↗

E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity.

Numerous experiments have defined a critical role for the G1 cyclins and associated kinases in allowing a normal progression of cells from a quiescent state, through G1, and into S phase. We now demonstrate that G1 cyclin-dependent kinase activity is critical for the accumulation of E2F activity late in G1. Moreover, E2F-1 overexpression can overcome a G1 arrest caused by the inhibition of G1 cyclin-dependent kinase activity, consistent with E2F activation being an important consequence of the action of G1 cyclins. E2F-1 also overcomes a G1 block caused by gamma irradiation and leads to an apparent complete replication of the cellular genome and entry into mitosis. This E2F-1-mediated induction of S phase and mitosis is not accompanied by the rise in either cyclin D-associated kinase activity or cdk2 activity that is normally observed during the G1 phase of the cell cycle. We conclude that one key function for G1 cyclin-dependent kinase activity is the activation of E2F-1, that the accumulation of E2F activity may be sufficient to allow initiation and completion of S phase, but that additional events, including G1 cyclin kinase activity, are likely necessary for a normal proliferative event.

Blotting, Western↗

Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia.

The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S-2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u-PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.

Adolescent↗

Quercetin inhibits the growth of leukemic progenitors and induces the expression of transforming growth factor-beta 1 in these cells.

We previously showed that quercetin (3,3',4',5,7 pentahydroxyflavone) inhibits in a dose-dependent manner the growth of acute leukemias and is able to enhance the antiproliferative activity of cytosine arabinoside. We show here that quercetin inhibits the clonogenic activity of 20 of 22 acute leukemias (AL; 4 M1-AML, 3 M2-AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL). In the present report, we show that the induction of transforming growth factor-beta 1 (TGF-beta 1) in leukemic blasts is one of the growth-inhibitory mechanisms of quercetin in these cells. This observation was supported by the following data. (1) Quercetin-sensitive leukemic blasts, when treated with quercetin, secrete large amounts of TGF-beta 1 in the medium and show positivity for TGF-beta 1-immunoreactive material in the cytoplasm. (2) At a concentration of 8 mumol/L, antisense TGF-beta 1 oligonucleotides prevent the growth-inhibitory action of quercetin. (3) Anti-TGF-beta 1 neutralizing monoclonal antibodies can prevent almost completely the growth-inhibitory activity of quercetin. The analysis of quercetin-resistant cases confirmed as well the central role of TGF-beta 1 in the growth-inhibitory activity of quercetin. In conclusion, quercetin can act as a cytostatic agent for leukemic cells by modulating the production of TGF-beta 1.

Bone Marrow↗

Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella infection.

A case of Brucella septicemia presenting at the onset as a severe microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome (severe epistaxis, gross hematuria, and skin purpura) is reported. A hemogram showed severe thrombocytopenia, anemia, and leukopenia. Bone marrow morphology showed the typical features associated with Brucella infection: numerous histiocytes with signs of activation, multiple granulomata, giant cells, and hemophagocytosis. After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and he is alive and well 1 year later with disappearance of all hematological abnormalities.

Adult↗

Is there an effect of weightlessness on mental rotation of three-dimensional objects?

We studied the performance of eight cosmonauts in a mental rotation paradigm with simultaneously presented perspective views of three-dimensional objects. The cosmonauts were tested successively on earth, in microgravity aboard the Russian MIR station and again on earth. Their performance was compared to performance of a control group of five subjects tested on earth on the same dates. We particularly tried to disambiguate the effect of microgravity, procedural bias and practice. Our results show that the microgravity did not alter the mental rotation process. The performance of cosmonauts increased with practice, similarly to the performance of control group's subjects suggesting that the weightlessness did not impair implicit learning as well. Finally, we propose an explanation of previous contradictory results.

Adult↗

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↗

Independence of bilateral symmetry detection from a gravitational reference frame.

Data were collected during three orbital flights aboard the Russian MIR space station from eight cosmonauts tested on a bilateral symmetry detection task. It is known that on earth subjects' performance is significantly superior for a vertical or horizontal than for an obliquely oriented axis of symmetry, giving a so-called oblique effect. The present results show that this oblique effect did not disappear in microgravity. They confirm that the detection of visual symmetry is not tied to a gravitational reference frame. An unexpected result of the experiments was that practice reduced the reaction time for detection of asymmetrical patterns below that for symmetrical patterns. This result suggests the presence of two separate detection processes. The detection of symmetry, being useful for the efficient encoding of visual information, is well developed in naive subjects. Extensive practice on a symmetry-detection task, however, increases the efficacy of the asymmetry-detection process.

Adult↗

Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%, with complete response in 62%: 63% in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 86% of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and 1 severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduced clinical toxicity in comparison to the standard doxorubicin-containing CHOP regimen in patients with intermediate-grade non-Hodgkin's lymphoma.

Adult↗

Hemostatic disorders associated with arterial hypertension and peripheral arterial disease.

To study a possible hypercoagulability in vascular disease, in 22 patients with essential hypertension and in 13 patients with obliterative arteriopathies of the lower limbs we measured the levels of plasma thrombomodulin (TM), plasma and urine beta-thromboglobulin (beta-TG), plasma D-dimer (DD) and plasminogen activator-inhibitor (PAI-1) and compared to the values obtained from 10 healthy volunteers. The values observed in hypertensive patients show only PAI-1 levels significantly higher. All the parameters were found to be significantly increased in vasculopathic patients. These data confirm that in vasculopathic patients endothelium damage, platelet activation, impaired fibrinolytic potential and increase of fibrin turnover, occur. On the other hand, in the hypertensive patients, at first stages of the disease, we have found only an increase of PAI-1 plasma levels documenting impaired fibrinolytic potential.

Adult↗

Chemotherapy and recombinant human granulocyte colony-stimulating factor primed donor leukocyte infusion for treatment of relapse after allogeneic bone marrow transplantation.

Two patients affected by acute leukemia relapsed 10 and 12 months respectively after allogeneic bone marrow transplantation. They were treated with aggressive chemotherapy and then infused with HLA-identical donor leukocytes (DLI) collected after recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration. A total of 5.6 and 6.3 x 10(6)/kg CD34+ cells, 2.7 and 3.0 x 10(4)/kg CFU-GM, 4.7 and 4.4 x 10(8)/kg MNC, 4.6 and 3.9 x 10(9)/kg PMN respectively were infused. Both patients achieved complete remission (CR) and complete chimerism was re-established. One patient developed grade IV acute graft-versus-host disease of the liver requiring immunosuppression and he died in CR from disseminated aspergillosis, 7 months after chemotherapy; one patient is alive in relapse 12 months after treatment.

Acute Disease↗