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Biomedical subjects

G Perona

Publications and source records attributed to G Perona.

At least 19 recordsLinked to original sources

Third metacarpal bone mineral density assessment in the standing horse by dual X-ray absorptiometry: suitability, precision and accuracy.

Bone mineral density (BMD) is correlated to mechanical properties of bone. In the horse, dual energy X-ray absorptiometry (DXA) has yet only been performed ex-vivo, but a new portable DXA device would be ideal for in-vivo BMD measurement. We explored field suitability, precision and accuracy of this device for in-vivo third metacarpal density assessment. Precision was analysed by calculating measurement variation under repeated measurement tests with (reproducibility) and without (repeatability) limb repositioning. Repeatability and reproducibility were tested ex-vivo, at the same time that intra- and inter-operator reproducibility were assessed in-vivo. In order to test accuracy, bone mineral content (BMC) of several bone samples determined by DXA and ashing were compared. Repeatability was 1.47% and reproducibility 1.69% ex-vivo. In-vivo reproducibility varied between 2.91 and 4.06% for intra-operator test and between 3.13 and 5.53% for inter-operator test. BMC measured by DXA and ash weight were highly correlated (R2>0.99). In conclusion, under described conditions this DXA device is usable, accurate and precise. Its sensitiveness reaches 8.23% in an individual longitudinal monitoring. Using the third metacarpal bone as an example, we have shown that this device is suitable for experimental or clinical monitoring.

Absorptiometry, Photon↗

Effect of dietary clenbuterol and cimaterol on muscle composition, beta-adrenergic and androgen receptor concentrations in broiler chickens.

Illegal dietary supplementation with beta(2)-agonists has been shown to increase protein deposition and decrease fat accretion in domestic animals. In poultry the metabolic and endocrine responses to beta(2)-agonists are not fully elucidated. In this trial the effects of dietary clenbuterol (1 p.p.m.) and cimaterol (1 p.p.m.) on muscle composition and endocrine response of male broiler chickens were studied. Dietary clenbuterol induced a slight, but in general not significant, improvement of zootechnical performances and carcass yields. Chemical composition of muscle was not influenced by dietary treatments, even if a slight improvement of protein content was observed in treated groups. No effects on fatty acid composition of meat were detected. Both clenbuterol and cimaterol treatments caused a downregulation in testicular androgen receptors and in pulmonary, cardiac and central nervous system beta-adrenergic receptors.

Adrenergic beta-Agonists↗

Transplantation potential of peripheral whole blood primed by VACOP-B chemotherapy plus filgrastim (r-metHuG-CSF) in patients with aggressive non-Hodgkin's lumphoma.

Large volumes of peripheral blood need to be processed to obtain sufficient stem cells for hematopoietic rescue after myeloablation, and more than one leukapheresis is necessary in most patients. We conceived the feasibility of harvesting sufficient numbers of hematopoietic cells from the whole blood, obtainable by venaepunctures, of patients treated with a standard dose chemotherapy regimen for high-grade non-Hodgkin's lymphoma. We evaluated the kinetics of mobilization, amount and quality of hematopoietic cells released into circulation during VACOB-B chemotherapy (which consists of a 12-week program), and G-CSF in 6 patients with aggressive non-Hodgkin's lymphoma. The median number of granulocyte-macrophage colony-forming cells (GM-CFC) x 10(3)/ml of blood (range), were 1.9 (0.3-8), and 1.16 (0.2-3.2) after the 7th and 11th weekly dose of drugs, respectively, showing an increase of 19- and 12-fold over patients' prechemotherapy values and of 53- and 33-fold over normal controls (p < 0.001). The median number of CD34+ cells x 10(3)/ml of blood (range), at the 7th and 11th cycle, was 135 (53.7-240.9) and 79.8 (69-173.5), respectively, showing an increase of 10- and 13-fold over patients prechemotherapy values (p < or = 0.04) and of 300- and 179-fold over normal controls (p < or = 0.001). Long-term culture initiating cells (LTC-IC) were released into circulation together with hematopoietic progenitors. We estimated that 1 liter of peripheral blood could yield on average 1.8 x 10(6)/kg CD34+ cells and 2 x 10(4)/kg GM-CFC with LTC-IC frequency comparable to a bone marrow harvest. These figures may be considered sufficient for hematopoietic rescue after myeloablation or hematopoietic support after high-dose chemotherapy.

Adult↗

Effects of sodium selenite on in vitro interactions between platelets and endothelial cells.

Selenium is an essential component of glutathione peroxidase enzymes, which protect cells against peroxidation and control concentrations of intracellular proxides. Since selenium deficiency is associated with an increased incidence of arterial thrombosis, we studied the effect of selenium on in vitro interactions between platelets and endothelial cells. Platelets from normal volunteers on a diet with (PLTSe+) or without (PLTSe-) selenium supplementation and human umbilical vein endothelial cells cultured in medium alone (ECSe-) or supplemented with Se (ECSe+) were used. The effect of in vivo administration or in vitro supplementation of selenium on platelet function was investigated in an aggregometry model designed for studying the interactions between platelets and endothelial cells using ADP and arachidonic acid as agonists. We observed that: (1) selenium-dependent glutathione peroxidase enzyme activity increased in both PLTSe+ and ECSe+, being about fivefold higher in the former; (2) platelet aggregation was inhibited by Se+ cells; (3) Se+ cells released less thromboxane B(2) (PLTSe+) and more 6-keto-prostaglandin F(1alpha) (ECSe+) than Se- cells; (4) when ECSe+ were treated with acetylsalicylic acid, the inhibitory effect of selenium on platelet aggregation disappeared; (5) the concentration of nitric oxide metabolites in Se+ culture media did not differ from that in Se- media. We suggest that an antithrombotic effect on the interactions between platelets and endothelial cells can be induced by stimulating glutathione peroxidase enzymes with selenium via a mechanism that is blocked by acetylsalicylic acid and is apparently unrelated to the biosynthesis of nitric oxide metabolites.

6-Ketoprostaglandin F1 alpha↗

Invasive aspergillosis in neutropenic patients: rapid neutrophil recovery is a risk factor for severe pulmonary complications.

BACKGROUND: In invasive aspergillosis, the duration of neutropenia is an accepted risk factor, and recovery from neutropenia is generally associated with a favourable outcome. However, the rapidity of granulocyte recovery may rarely be associated with adverse sequelae. The purpose of this study was to define the relationship between neutrophil (polymorphonuclear, PMN) recovery after chemotherapy-induced bone marrow aplasia and the occurrence of severe pulmonary complications (haemoptysis, pneumothorax and death) in patients with haematological malignancies who developed invasive fungal pneumonias. METHODS: Twenty consecutive patients were retrospectively studied; eight of them had developed pulmonary events between 5 and 11 days after neutrophil recovery that followed deep neutropenia (PMN < 100 microL-1). RESULTS: Five patients had haemoptysis (one of these also had pneumothorax) and three had pneumothorax. According to the multiplicative logistic model, the odds of occurrence of a pulmonary event increased significantly with increasing PMN count on the fifth day (P < 0.001). Five of the eight patients who had pulmonary complications died. Also, the risk of death was larger in the presence of rapid neutrophil recovery, although the difference was not statistically significant (P = 0.111). Analysis of clinical and laboratory data showed that the risk of pulmonary complications significantly increased when the neutrophil concentration was > 4500 microL-1 on day 5 after deep granulocyte neutropenia (PMN < 100 microL-1). There was no correlation between pulmonary complications, dosage of amphotericin B and deaths. CONCLUSION: The occurrence of life-threatening complications in patients with invasive fungal pneumonia is closely related to rapid PMN recovery.

Adolescent↗

The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy.

Anemia is a frequent complication of multiple myeloma, becoming chronic in patients who are resistant to chemotherapy. This randomized, parallel, controlled multicenter study (71 patients receiving concomitant chemotherapy) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy. Forty patients were treated with subcutaneous epoetin alfa (150 IU/kg per dose, increasing to 300 IU/kg per dose, every 3 weeks) for 6 months, and 31 entered a control group. The epoetin alfa group had a significantly (P < or = 0.001) greater percentage of patients (75% vs. 21%) with increases in hemoglobin levels and/or reduced transfusion requirements. In 44 non pre-transfused patients (20 controls, 24 in the epoetin alfa group), the mean increase in hemoglobin was significantly (P < or = 0.0001) greater in the epoetin alfa group (+2.1 vs. -0.2 g/dl). Increases in hematocrit and red blood cells were also significantly (P < or = 0.0001) greater in epoetin alfa-treated patients, with corresponding reductions in transfusion requirement. In the 27 pre-transfused patients (11 controls, 16 in the epoetin alfa group), there was a trend towards reduced transfusional need in epoetin alfa-treated patients. Thus, in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused.

Aged↗

Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin.

On the basis of a previous experience suggesting that daunorubicin dose in induction was an independent prognostic factor in adult ALL, we designed a chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin (270 mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol was otherwise conventional: induction and post-remission therapy were followed by chemo-radio prophylaxis of the central nervous system (CNS) and periodical reinductions over a 3-year maintenance period. Sixty consecutive patients (male 42, female 18, median age 34 years, range 14-71; B-lineage, 35; T-lineage, 25; Ph' and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for treatment outcome. Complete remissions were 56 (93%), one patient had refractory disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom were Ph'+. Median time to relapse was 11 months (range 3-47); 68% of relapses occurred within 12 months from CR. No CNS relapses were observed. After a median follow-up of 44 months (1-100), 33/60 (55%) patients remain event-free; 23/60 (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63 months; range 38-100). These results suggest that increasing DNM dosage in induction is one of the possible approaches to improve the outcome of adult ALL by decreasing the relapse occurrence.

Adolescent↗

Regulation of the proliferative potential of cord blood long-term culture-initiating cells (LTC-IC) by different stromal cell lines: implications for LTC-IC measurement.

BACKGROUND AND OBJECTIVE: Long-term culture-initiating cells (LTC-IC) are the best available approximation to an in vitro assay of stem cells in humans although they still represent a heterogeneous population in terms of proliferative capacity and sensitivity to different growth factors. Human umbilical cord blood (CB) is rich in hemopoietic progenitor cells, as measured by clonogenic assays and contains stem cells capable of reconstituting the marrow after ablation in clinical transplantation. We evaluated the influence of culture conditions on the in vitro behavior of LTC-IC from CB. DESIGN AND METHODS: LTC-IC were evaluated in long-term cultures, comparing two types of murine stromal cell lines: M2-10B4 and M2-10B4 transfected with cDNAs for human G-CSF and IL-3. RESULTS: Two and five fold higher numbers of terminally differentiated cells were produced during nine weeks of culture of CB mononuclear or CD34+ cells respectively, in cultures containing a M2-10B4 IL-3 G-CSF cell line compared to cultures containing the parental cell line. Likewise, a higher number of colony-forming cells (CFC) were detected in the supernatant of cultures with the transfected cell line. In contrast, the number of CFC generated within the stromal layer, after 5 or 9 weeks of culture, was significantly higher in cultures on M2-10B4 cells than those on M2-10B4 IL-3 G-CSF. INTERPRETATION AND CONCLUSIONS: Our results show that the proliferative capacity of CB LTC-IC can be strongly influenced by culture conditions and that the frequency of LTC-IC estimated using these cell lines as stromal support is not identical.

Cell Communication↗

Eighty-one percent event-free survival in advanced Burkitt's lymphoma/leukemia: no differences in outcome between pediatric and adult patients treated with the same intensive pediatric protocol.

BACKGROUND: Advanced Burkitt's lymphoma (BL) has an extremely poor prognosis in adults. With a previous protocol including CNS prophylaxis, 40% of our adult patients achieved CR and only 13% became long survivors. In 1988, following this poor experience, we adopted a very intensive pediatric-derived protocol. PATIENTS AND METHODS: Twenty-one consecutive patients, 8 adults (median age 35, stage III: 1; IV: 7; leukemias: 6) and 13 children (median age 10, state III: 8; IV: 5; leukemias: 4) were treated with the same protocol (POG 8617), based on alternate two-phase cycles with sequential high-dose CTX, VCR, ADM + CNS chemoprophylaxis (phase A) and HD MTX + HiDAC (phase B). Adults received 6 cycles, children 8; i.t. prophylaxis in phase B was omitted in adults. RESULTS: Twenty of 21 (95%) patients achieved CR (adults 100%, children 92%). Two patients died early; 2 relapsed at 4 and 9 months. With a median follow-up of 28 months (4-96), 17 patients (81%) are event free (adults 75%, children 85%). Severe infections affected 62% of adults and 15% of children. CONCLUSIONS: (1) The prognosis of adult advanced BL definitely improved with this intensive protocol. (2) There were no differences in outcome between adults and children. (3) Outcome of lymphoma and leukemia was similar. (4) Severe infections occurred frequently in adults. This intensive pediatric protocol requires a careful supportive therapy.

Adolescent↗

Radiographic evaluation of the effect of orthodontic retraction on the root of the maxillary canine.

OBJECTIVES: To evaluate possible apical root resorption following orthodontic retraction of the maxillary canine quantitatively and qualitatively. METHODS: Twenty maxillary canines in 12 patients were retracted using a prefabricated orthodontic spring. Twenty non-treated mandibular canines from the same patients served as controls. Standardized radiographs were taken of all upper and lower canines before (T0) and after (T2) retraction. Root length and tooth length were measured on the radiographs at T0 and T2, and the root length/tooth length ratio was calculated. Ten orthodontists assessed blind the root apex of the pairs of radiographs taken at T0 and T2 for resorption. Digital subtraction was performed between the pairs of radiographs taken at T0 and T2 and the mean density and the standard deviation of the grey shades of the root apex calculated. RESULTS: There were no significant differences between root length/tooth length ratio at T0 and T2 for either the maxillary (p = 0.45) or the mandibular canines (p = 0.79). There was considerable variation between observers judgements of root resorption: nine out of ten observers agreed that a resorption had taken place in only one tooth. There were no significant differences between the mean density values in the subtraction images of the upper and lower canines (p = 0.3). CONCLUSIONS: Quantitative assessment with conventional and subtraction radiography failed to demonstrate root resorption in the maxillary canines. Root resorption could be shown qualitatively in only one tooth. The standardized orthodontic force system used for canine retraction appeared to cause no resorption, or only a small degree of resorption of no clinical relevance.

Adult↗

Correlation between clinical features and circulating levels of soluble intercellular adhesion molecule-1 in Hodgkin's disease.

Previous reports have suggested soluble intercellular adhesion molecule-1 as a marker of disease activity in Hodgkin's disease. In the present study we investigated serum levels of intercellular adhesion molecule-1 at diagnosis in 104 patients with Hodgkin's disease and in 77 of these patients following the achievement of complete remission (within 12 months of diagnosis). Mean serum levels at diagnosis were significantly higher in patients than in controls (P < 0.0001) and were related to advanced stages of disease (P = < 0.0001), presence of "B" symptoms (P < 0.0001), abnormality of laboratory indexes (P < 0.0001), erythrocyte sedimentation rate values (r = 0.41, P < 0.0001) and serum levels of soluble interleukin-2 receptor alpha chain (r = 0.51, P < 0.0001). Mean values in complete remission were significantly lower than at diagnosis (P = 0.003). Lower mean values at diagnosis were detected in 30 patients with advanced disease who attained complete remission, compared with 6 patients who failed to attain complete remission with standard treatment. We conclude that in Hodgkin's disease, high serum levels of soluble intercellular adhesion molecule-1 are detectable at presentation and strictly correlate with some clinical features. Response to treatment is paralleled by reduced serum levels. Larger prospective studies are needed to evaluate the possible prognostic significance of serum levels of soluble intercellular adhesion molecule-1 at diagnosis.

Adolescent↗

Transbronchial biopsy in the diagnosis of pulmonary infiltrates in immunocompromised patients.

Bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) frequently are performed in the investigation of immunocompromised patients with lung disorders. The risk-benefit ratio of TBB currently is debated, since several authors have found that the less invasive BAL may provide as much information as TBB, with the avoidance of some biopsy-related side effects. We retrospectively evaluated 157 instances of bronchoscopy carried out on 142 immunocompromised patients, with both BAL and TBB performed in every case. Immunosuppressant conditions were HIV infection (79), hematologic malignancies (36), and antirejection therapy in renal transplant recipients (27). Transbronchial biopsy provided a diagnostic yield significantly higher than that obtained by BAL in all categories investigated; diagnostic rates were 77.3% for TBB and 47.6% for BAL (p < 0.001) in patients with HIV infection, 55 and 20% (p < 0.001) in patients with hematologic malignancies, and 57.5 and 27.2% (p < 0.001) in renal transplant recipients. Looking at the whole series, the diagnostic rates of TBB and BAL were 67.5 and 36.3%, respectively (p < 0.001), with a total additional yield of 33% provided by TBB, while in only 2% of cases BAL gave rise to diagnostic information not achieved by TBB. Considering that side effects followed TBB at a negligible rate (2.5%), we believe that TBB should be routinely carried out in these patients once the diagnostic strategy has been oriented to bronchoscopy.

Adolescent↗

T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura.

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disease, characterized by isolated thrombocytopenia and the absence of megakaryocytes in bone marrow. Recent studies suggest that this syndrome is due to diverse etiologies. Humoral or cellular mediated suppression has been alternately demonstrated using an in vitro colony assay for megakaryocytic progenitor cells (colony forming units megakaryocyte, [CFU-meg]). We studied a patient affected by AATP, who was not responsive to conventional therapy, but did respond to antilymphocyte globulin. The immunological characterization of marrow lymphocytes showed a marked increase of T activated suppressor cells (CD8+/DR+). Low density bone marrow mononuclear nonadherent cells (MNAC) from the patient, either in aplastic phase or in remission phase, were plated in plasma clot either directly or after T cell depletion (T-dep MNACs). Co-cultures with normal marrow cells were performed using either T lymphocytes from a normal volunteer donor or patient T lymphocytes. In some experiments we added autologous serum instead of fetal calf serum (FCS). In standard conditions, we observed increased colony formation, which was more evident in remission phase and especially significant after T cell depletion. The T lymphocytes from patient marrow did not modify the number of CFU-meg when co-cultured with allogeneic cells. These results indicate that an immune-mediated mechanism could be responsible for this case of AATP, and that the T cell subset CD8+/DR+ is capable of exerting suppression on megakaryocyte differentiation. This suppressive effect seems restricted to patient cells, suggesting a specific auto-sensitization.

Adult↗

Early lymphoid blastic crisis following major karyotypic conversion in a chronic myeloid leukemia patient treated with interferon-alpha.

A major karyotypic conversion following interferon-alpha treatment delays or prevents blastic crisis in patients with chronic myeloid leukemia. We report here a 12-year-old boy with Ph1+ chronic myeloid leukemia who, after achieving a major karyotypic conversion following 12 months interferon-alpha treatment, developed an early lymphoid blastic transformation 7 months later while still under interferon-alpha therapy. A number of possible explanations for this quite unexpected event are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Postoperative chemotherapy increases the disease-free survival rate in primary gastric lymphomas stage IE and IIE.

We describe 53 patients with primary gastric non-Hodgkin's lymphoma (38 stage IE,15 stage IIE) treated with surgery as a primary procedure. According to the Working Formulation, 13 cases had low, 21 had intermediate and 19 had high grade malignancy. 34 patients considered at high risk received postoperative polychemotherapy. The overall 10-year disease-related survival is 91%. Median follow-up is 52 months. 7 patients relapsed (13%). The 10-year disease-free survival rate of the 19 patients initially treated with surgery is 60%, as compared with 92% in the patients who also received chemotherapy (P = 0.004). However, overall survival did not differ between the two groups, since two-thirds of the patients who relapsed after surgery alone were rescued with chemotherapy. Stage, age, sex and histology did not correlate with survival. In our experience, surgery was an adequate first step procedure; the addition of chemotherapy significantly reduced relapses and increased the disease-free survival rate in patients with unfavourable prognostic factors.

Adult↗

Increased in vitro neutrophil adherence in a case of chronic idiopathic neutropenia.

In this report we describe a patient with persistent neutropenia whose neutrophils showed increased adhesion in a microplate assay. In three separate assays, from 12.5% to 13.7% of the patient's blood neutrophils exhibited spontaneous (unstimulated) adhesion to fetal bovine serum-coated microplate wells, much higher than adhesion of cells from healthy controls (1.9% +/- 2.5 SD, n = 20). The difference of spontaneous adhesion between the patient's and control neutrophils was even higher when cells from a skin-window exudate were examined (patient: 42.1-100% adhesion; control: 3.6% +/- 3.5 SD, n = 20). Over 80% inhibition of the increased adhesion was produced by the 60.3 anti-CD 18 monoclonal antibody, suggesting an involvement of beta 2-integrins.

Antigens, CD↗

Relationship between Daunorubicin dosage delivered during induction therapy and outcome in adult acute lymphoblastic leukemia.

The long-term results of a therapeutic regimen for adult acute lymphoblastic leukemia (ALL) have been analysed with the main purpose to evaluate the impact of Daunorubicin (DNM) dosage given during the induction. The files of 86 consecutive adult ALL patients treated in our institution between 1974 and 1988 were reviewed. They received the same induction regimen based on Vincristine, DNM and Prednisone, consolidation with L-Asparaginase, central nervous system prophylaxis, and 3-year maintenance with 6-mercaptopurine and Methotrexate with periodic cycles of reinduction. We analysed the overall and disease-free survival (DFS) in relation to various prognostic factors, focusing on the dosage of DNM actually received during the induction period. Complete remission (CR) was achieved in 68 (79%) patients and the overall DFS was of 32 months (median follow-up 37 months); 22 patients (25.6%) are off-therapy and disease-free. The actual dosage of DNM received during induction turned out to be an independent DFS prognostic factor. In fact, patients who received more or less than 175 mg/sqm in induction had a median DFS of 44 and 12 months, respectively (p = 0.05). The plateau of DFS in the two groups was 44% and 21%, respectively. Similar data were found analyzing the dose-intensity (mg/sqm/week) of DNM given in induction. Our data suggest that the actual dosage of DNM given in induction plays a role in the long term DFS of adult ALL.

Adolescent↗

Plasma selenium and glutathione peroxidase activities in individuals living in the Veneto region of Italy.

In order to assess the Se status in individuals living in the Veneto region, a series of related measurements was performed. These included plasma selenium by PIXE and glutathione-peroxidase (GSH-Px) activities in plasma, red blood cells and platelets. Individuals were either normals or people suffering from various liver diseases. Moreover, an oral supplement of sodium selenite was given to 13 patients suffering from stable chronic renal failure (CRF) in parallel to 26 normals: data on plasma GSH-Px and on serum creatinine and creatinine clearance were collected either before or after supplementation. Results were in support of a relatively low selenium status: mean +/- SD plasma Se values of normals (0.82 +/- 0.17mumol/L, n = 82) were comparable to data observed in European regions where Se deficiency was already known. Even lower values were observed in those with liver diseases. Among enzyme activities, the distribution of the data of platelet GSH-Px was in further support of low Se status in the evaluated individuals. After Se supplementation, both normals and CRF patients showed a significant increase in the creatinine clearance, reflecting an improvement of the glomerular filtration rate. We suggest that more extensive surveys of the Se status should be carried out in Italy; moreover, Se supplementation may be advisable in individuals affected with moderate impairment of renal function.

Administration, Oral↗