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C Bernasconi

Publications and source records attributed to C Bernasconi.

At least 19 recordsLinked to original sources

Comparison of three different media for the detection of E. coli and coliforms in water.

The European Drinking Water Directive defines reference methods for the enumeration of microbiological parameters in drinking water. The method to be used for Escherichia coli and coliforms is the membrane filtration technique on Lactose TTC agar with Tergitol 7. Many technical drawbacks of the procedure, as well as its limitations regarding the recent taxonomy of coliforms, make it necessary to evaluate alternative methods. Two alternative assays, a chromogenic media (m-ColiBlu24) and a defined substrate technology-DST test (Colilert 18/Quanty Tray) were compared with the ISO standard with attention to the phenotypic characteristic of the isolates. Results showed that the ISO method failed to detect an important percentage of coliforms and E. coli while m-ColiBlu24 and Colilert 18 provided results in a shorter time allowing the simultaneous detection of E. coli and coliforms with no further confirmation steps.

Culture Media↗

Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution.

The impact of clinical parameters, International Prognostic Scoring System (IPSS) scores/cytogenetic categories, and some single cytogenetic defects on overall survival (OS) and time to myelodysplastic syndromes (MDS)/AML progression (progression-free interval (PFI)) was evaluated in 331 MDS patients. Statistical analysis demonstrated that OS and PFI were significantly affected by all these parameters. Since single 7q- showed a better survival than the poor IPSS cytogenetic category (P=0.009), it was considered as a new prognostic entity ('modified IPSS categories'). In multivariate analysis OS was significantly influenced by age, marrow blast cell percentage, number of cytopenias and either modified or standard IPSS cytogenetic categories; hazard ratios for MDS/AML progression were influenced by all the former, except for age and cytopenias. Multivariate analysis of del(7)(q31q35) confirmed the results of univariate analysis, but the Akaike Information Criterion showed no difference in evaluating OS and PFI between the modified and standard IPSS cytogenetic grouping. In conclusion, (i) chromosome defects as grouped by IPSS and blast cell percentage are the most relevant parameters for predicting OS and PFI; (ii) the prognostic power of the IPSS cytogenetic grouping is not ameliorated by the introduction of del(7)(q31q35) as a new entity; (iii) complex karyotypes have a prognostic value independent of blast cell percentage.

Aged↗

Is FISH a relevant prognostic tool in myelodysplastic syndromes with a normal chromosome pattern on conventional cytogenetics? A study on 57 patients.

Conventional cytogenetics (CC) at clinical diagnosis shows a normal karyotype in 40-60% of de novo myelodysplastic syndromes (MDSs). Fluorescence in situ hybridization (FISH) might detect occult aberrations in these patients. Therefore, we have used FISH to check 57 MDS patients who were karyo-typically normal on CC. At clinical diagnosis, FISH revealed a clonal abnormality in 18-28% interphase cells from nine patients, five of whom also presented the same defect on metaphase FISH. In five out of nine patients, the occult defect effected a change in the international prognostic scoring system (IPSS). An abnormal FISH pattern was significantly correlated with marrow blast cell percentage (P<10(-3)) and IPSS (P<10(-3)). Patients with an occult abnormality showed an overall survival and event-free survival significantly inferior in comparison to those of patients with normal FISH (P<10(-3), P<10(-3)). Death and AML progression were 15- and eight-fold more frequent in FISH abnormal patients. In conclusion, occult defects (1) are revealed in about 15% of CC normal MDS patients, (2) are overlooked by CC either because of the poor quality of metaphases or their submicroscopic nature, (3) are clinically relevant as they may cause a change in the IPSS category and may identify a fraction of CC normal patients with an unfavorable clinical outcome.

Adult↗

Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea.

ET is a chronic myeloproliferative disorder rarely evolving into AML, sometimes preceded by a myelodysplastic syndrome (MDS). Such transformations mostly occur in patients treated with radiophosphorous ((32)P) or alkylating agents, especially busulfan. Recently, concern has also arisen about the long-term safety of hydroxyurea (HU). Pipobroman (PI), a well tolerated and simple to use drug, constitutes a valid alternative to those cytoreductive treatments. The present study reports on 155 ET patients treated at our institution from 1985 to 1995, and monitored until December 2000. A good control of thrombocytosis was achieved with PI as the only treatment in 106 patients and with HU in 23 patients. Twenty-six patients received no treatment. After a median follow-up of 104 months, seven patients (four treated with HU, and three with PI) developed AML whereas one patient treated with PI developed MDS. A significant difference in progression-free survival was observed between HU- and PI-treated patients (P = 0.004). A short-arm deletion of chromosome 17 was most frequently detected in HU-treated patients, while a long-arm trisomy of chromosome 1 and a monosomy 7q were seen in PI-treated patients. No TP53 mutation was discovered in the six patients studied (two HU-treated and four PI-treated). We conclude that these cytogenetic abnormalities are not linked to the natural history of the disease, but rather that they might be induced by the cytoreductive treatment.

Acute Disease↗

DNA immunization of mice against the VP1 capsid protein of coxsackievirus B4.

The protective activity of a DNA plasmid encoding the immunodominant capsid protein VP1 of coxsackievirus B4 (CBV-4) was studied in BALB/c mice. The plasmid pCI-B4-1-c - which gave the highest expression level of VP1 in cultured monkey and human cells - was chosen for immunization. Two injections of pCI-B4-1-c (1 month apart) into the regenerating mouse muscle tissue induced a specific antibody response to CBV-4, as shown by immunoenzyme and neutralization assays. Upon challenge with live CBV-4, the mortality rate of mice vaccinated with the recombinant plasmid was significantly reduced (21% versus >58%) as compared with that of mice that had been either nontreated or injected with a control plasmid devoid of the insert. The VP1-based vaccine, however, did not provide complete protection as - after virus challenge - moderate viraemia occurred together with modest plasma elevations of pathogenesis-related enzymes (amylase and creatine kinase). Yet, immunofluorescence of the small intestine and heart did confirm the protective effect of the VP1-encoding vaccine. In order to obtain a more complete protection against CBV-4, it may be beneficial to immunize mice with combinations of separate DNA plasmids encoding not only VP1 but also the VP2 and VP3 capsid proteins.

Animals↗

Consolidation treatment with autologous peripheral blood progenitor cell transplantation in acute myeloid leukemia: a single center experience.

Several trials have suggested that intensive post-remission therapy may prolong the duration of complete remission (CR) in acute myeloid leukemia (AML). The purpose of this study was to evaluate the feasibility and the efficacy of high-dose cytarabine (HiDAC) consolidation chemotherapy followed by high-dose therapy and autologous infusion of peripheral blood progenitor cells (PBPC) mobilized by G-CSF in adult patients with AML in first CR. Fifteen consecutive AML patients underwent HiDAC consolidation chemotherapy, used as a method of in vivo purging, followed by G-CSF for the purpose of autologous PBPC collection. Eleven patients collected a median of 6.9x10(8)/kg peripheral blood mononuclear cells (MNC) (range 2.9-23) and a median of 6.67x10(6)/kg CD34+ cells (range 1.8-33.5) with a median of two aphereses (range 1-3). Two patients did not mobilize and two obtained an inadequate number of progenitor cells. The 11 patients with adequate collections received myeloablative chemotherapy followed by the infusion of PBPC. The median number of days to recover neutrophils and platelets was 12 and 13, respectively. After a median follow-up of 28.7 months (range 17.2-43.4), five out of 11 patients who underwent PBPC transplantation are still in CR, five have died in first relapse and one is alive in CR after relapse treated with salvage therapy and second PBPC infusion. These results demonstrate that HiDAC consolidation chemotherapy followed by autologous PBPC transplantation is a feasible procedure with minimal toxicity. Randomized studies should be performed to evaluate whether this form of consolidation may produce a significant improvement in leukemia-free survival.

Acute Disease↗

Thiotepa and fludarabine (TT-FLUDA) as conditioning regimen in poor candidates for conventional allogeneic hemopoietic stem cell transplant.

Standard conditioning for allogeneic bone marrow transplantation induces high transplant-related mortality (TRM) in patients with a poor performance status. Less intensive regimens have been tested to reduce the TRM; our purpose was to evaluate the feasibility and tolerability of a new combination: thiotepa and fludarabine (TT-FLUDA). Six patients received 5 mg thiotepa/kg daily from day -8 to -7 and 25 mg fludarabine/m2 daily from day -6 to -2 followed by an allogeneic peripheral blood progenitor cell infusion; three of these patients with signs of overt leukemia received 18 mg idarubicin/m2 i.v. at day -12. Graft-versus-host-disease (GVHD) prophylaxis was performed i.v. with 1 mg cyclosporine A/kg per day from day -5 to the day of marrow engraftment, then 6 mg/kg per day orally up to day +100, and 10 mg methotrexate/m2 at day +1, and 8 mg/m2 at days +3, +6, and +11. Chimerism was studied with fluorescent in situ hybridization for sex chromosomes (XY-FISH) and minisatellite polymerase chain reaction (PCR) at days +30, +100, +180, and +360. Engraftment was achieved in all cases with complete donor chimerism in all but one patient who had refractory acute leukemia. No major toxicity was noticed; only one patient died at day +51 of acute GVHD because of early cyclosporine A discontinuation. One patient with refractory non-Hodgkin's lymphoma (NHL) had a testicular relapse at day +180. Three patients (one with mantle cell lymphoma, two with acute myeloid leukemia) are still in continuous complete remission (CR) with complete donor chimerism at days +180, +210, and +450, respectively. TT-FLUDA seems to be well tolerated, allowing engraftment and stable donor chimerism in patients who are poor candidates for conventional conditioning regimens.

Adult↗

[Simple techniques for the internal stabilization of fractures and luxations in the sacrococcygeal region of cats and dogs].

Two useful techniques for the repair of caudal sacral fractures and sacrococcygeal fractures/luxations are described. Pre- and postoperative clinical, neurological and radiological findings in 16 operated animals (13 cats and 3 dogs) were compared with findings in 17 (13 cats and 4 dogs) conservatively treated animals. In the surgically treated patients follow up findings were characterized by absence of hyperesthesia and a higher number of animals with recovered tail function. The authors suggest the use of these techniques in cases of caudal sacral fractures or sacrococcygeal fractures/luxations.

Animals↗

Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups.

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count </= 10 x 10(9)/L, platelet count > 40 x 10(9)/L), intermediate-risk (WBC count </= 10 x 10(9)/L, platelets </= 40 x 10(9)/L), and high-risk (WBC count > 10 x 10(9)/L) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (Blood. 2000;96:1247-1253)

Adolescent↗

Bi-directional interactions between visual areas in the awake behaving cat.

The study of the cooperativity among cortical areas is essential to our understanding of brain functioning. Here we investigated the relative contributions of top-down and bottom-up directed interactions between area 17 and area 7 of the cat visual system. Bipolar local field potentials were recorded while the animals performed a go/no-go task or were in a quiet resting state. The data were analyzed by applying measures of interaction based on the Wiener-Granger causality concept. We found that during the visual task top-down directed interactions were of a similar magnitude as the bottom-up component. Second, interareal couplings tended to increase in conditions requiring a discriminative effort. Third, during behaviors not dominated by visual processing non-directed interactions increased.

Animals↗

Trisomy 11 and a complex t(11;11;22) in a patient with acute myelomonocytic leukemia (AML-M4) following myelodysplasia (MDS): a cytogenetic study of a mechanism of leukemogenesis.

We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with +11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.

Aged↗

Pulmonary toxicity following carmustine-based preparative regimens and autologous peripheral blood progenitor cell transplantation in hematological malignancies.

Sixty-five patients with hematological malignancies (25 multiple myeloma, 18 Hodgkin's disease, 22 non-Hodgkin's lymphomas) who received a carmustine-based regimen followed by autologous PBPC transplantation, were studied retrospectively to evaluate the incidence of post-transplant non-infective pulmonary complications (NIPCs), risk factors predictive of NIPCs, and response to steroids. Carmustine (BCNU) given i.v. at a dose of 600 mg/m2 was combined with etoposide and cyclophosphamide in 40 patients (BCV regimen) and with etoposide and melphalan in 25 patients (BEM regimen). Seventeen of 65 patients (26%) had one episode of NIPCs. The median time to NIPCs was 90 days (52-289). Factors that increased the risk of developing NIPCs on multivariate analysis were female sex (P < 0. 001) and BCV regimen (P < 0.05). All patients with NIPCs received prednisone at a dose of 1 mg/kg body weight for 10 days then tapered by 5 mg every two days; complete response to steroids was achieved in 15 of 17 patients; one unresponsive patient died of interstitial pneumonia. BCNU given at the dose of 600 mg/m2 is well tolerated when associated with melphalan and etoposide. In females and in patients receiving BCNU with cyclophosphamide, a BCNU dose reduction may be advisable. Bone Marrow Transplantation (2000) 25, 309-313.

Adolescent↗

Blood stem cell collections in multiple myeloma: definition of a scoring system.

The purpose of the study was to identify factors that could predict good yields of peripheral blood stem cells (PBSC) in multiple myeloma (MM). Fifty-one MM patients, nine with refractory disease and 42 in plateau phase, were mobilized with high-dose cyclophosphamide (HD-Cy) at 4 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/day. Clinical and laboratory parameters at the time of mobilization were analyzed for correlations with the number of CD34+ cells collected, with the colony-forming unit granulocyte-macrophage (CFU-GM) count, and the mononuclear cell (MNC) count. In univariate analysis, low WBC count, low platelet count, prior exposure to melphalan, and an interval >6 months from the start of treatment correlated with poor yields of CD34+ cells. Low platelet count, prior exposure to melphalan or to radiotherapy, and an interval >6 months from the start of treatment were associated with a low CFU-GM count. On the basis of these data, we defined a scoring system able to predict the yield of the mobilizing procedure. According to this system, the presence of more than one risk factor (low WBC and platelet counts, prior exposure to melphalan, interval from first chemotherapy >6 months) was predictive of insufficient collections when a conventional combination of mobilizing measures are used.

Adult↗