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G Papa

Publications and source records attributed to G Papa.

At least 19 recordsLinked to original sources
PubMed1998

Delayed hypersensitivity to diclofenac: a report on two cases.

BACKGROUND: Although skin reactions have been reported during use of diclofenac, a nonsteroidal anti-inflammatory drug, immunopathogenic mechanisms have been demonstrated in only a few cases. METHODS: We administered skin and patch tests to two subjects who had developed maculopapular rashes respectively 48 and 72 hours after initiation of treatment with diclofenac. RESULTS: In both cases, prick and intradermal tests with the drug were negative at 20 minutes, but 24 hours later an erythematous infiltrate had appeared at the intradermal test site. Patch tests with diclofenac were also positive at 48 and 72 hours. CONCLUSIONS: The features of both these cases are suggestive of delayed hypersensitivity to diclofenac. Delayed-reading intradermal and patch tests may be a simple and effective means of diagnosing reactions of this type.

Aged↗
PubMed1997

A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group.

The safety and efficacy of filgrastim as an adjunct to acute myeloid leukemia (AML) induction and consolidation therapy was assessed in this prospective double-blind, randomized, placebo-controlled, multicenter trial. A total of 521 consecutive de novo AML patients aged 16 or more years were randomized to receive filgrastim (5 microg/kg/d subcutaneously) or placebo after standard induction as well as consolidation chemotherapy. Blinded study drug was given from 24 hours after chemotherapy until the absolute neutrophil count was >/=1.0 x 10(9)/L for 3 consecutive days. The overall complete remission rate was 68%. After a median follow-up of 24 months (range 5 to 40) the median disease-free survival was 10 months (95% confidence interval [CI], 8.7 to 10.8) and the median overall survival was 13 months (95%CI, 12.2 to 14.6). These did not differ between treatment groups. Patients receiving filgrastim experienced neutrophil recovery 5 days earlier after induction 1 than those receiving placebo (P < .0001). This was accompanied by reductions in the duration of fever (7 v 8.5 days; P = .009), parenteral antibiotic use (15 v 18.5 days; P = .0001), and hospitalization (20 v 25 days; P = .0001). Similar reductions were seen after induction 2 and the consolidation courses. There was a significant reduction in the number of patients requiring systemic antifungal therapy in the filgrastim group during induction treatment (34% v 43%; P = .04). In conclusion, filgrastim is safe in that it had no negative impact on the prognosis of the AML patients. In addition, it effectively reduced the duration of neutropenia, leading to significant clinical benefits by reducing the duration of fever; requirement for parenteral anti-infectives, specifically amphotericin B; and the duration of hospitalization.

Adolescent↗
PubMed1997

Minimally differentiated acute myeloid leukemia (AML-M0): comparison of 25 cases with other French-American-British subtypes.

We compared the immunophenotypic and karyotypic features of 25 cases of minimally differentiated acute myeloid leukemia (AML-M0) with those of 247 cases comprising all AML French-American-British (FAB) classification. Myeloperoxidase (MPO) was detectable with a specific monoclonal antibody in all cases of AML-M0, whereas CD13 and CD33 were both negative in 4 of the 25 cases. Thus, anti-MPO reliably detects minimal myeloid differentiation in AML-M0. CD34 and terminal deoxynucleotidyl transferase (TdT) were more frequently expressed in AML-M0 (96% and 68% of the cases, respectively) than in the other FAB subsets (P < .001 for both). By contrast, GP-170 and CD7 were less frequently expressed in AML-M0 than in FAB classes such as M1, M4, and M5 (P = .02 and .003, respectively). A total of 80% of AML-M0 cases carried lymphoid markers (including TdT), and 48% showed a coordinate positivity for two or more of them. CD2, CD5, CD10, and CD19 were expressed in a similar fashion among the different FAB groups, whereas CD4 expression was significantly more frequent in AML-M0, AML-M4, and AML-M5 (P = .014). AML-M0 was characterized by a more frequent occurrence of complex karyotypes. In addition, approximately 20% of cases had TdT positivity, complex karyotypes, and anomalies of chromosome 5 and/or 7, a pattern not observed in the other FAB subsets. Finally, 80% of anomalies of chromosome 5 and/or 7 in AML-M0 were comprised within complex karyotypes, whereas only 13% of the remaining FAB cases carried this feature. In summary, AML-M0 frequently expresses immunophenotypic and karyotypic aspects that are likely to identify a "stem cell" pattern.

Adolescent↗
PubMed1997

Long-term tolerability of nimesulide and acetaminophen in nonsteroidal antiinflammatory drug-intolerant patients.

BACKGROUND: Oral challenges are used to identify alternative nonsteroidal antiinflammatory drugs (NSAIDs) for patients who react adversely to drugs of this class, but challenge conditions often differ from those in which the drug will actually be used. OBJECTIVE: To determine whether the results of oral challenges with nimesulide or acetaminophen, using cumulative administration of a single therapeutic dose while the patient is in good health, can predict the response to multiple doses of the drug during future illness. METHODS: Follow-up interviews were conducted with 248 NSAID-intolerant subjects who had tolerated oral challenges with nimesulide and/or acetaminophen 1 to 3 years earlier. We analyzed the adverse reaction rate in light of the febrile/non-febrile nature of the condition treated and the number of doses consumed. RESULTS: Nimesulide was tolerated by 115/122 (94.2%) of the patients who had tried it; acetaminophen by 71/75 (94.6%). A total of 8/159 (5%) patients had experienced reactions (seven urticarial and one asthmatic) to one or both drugs. Intolerance was unrelated to the nature of the condition treated or the number of doses administered, but all four patients who failed to tolerate acetaminophen and 3/7 of those who reacted to nimesulide had histories of chronic urticaria. CONCLUSIONS: Oral challenges can reliably predict long-term NSAID tolerability in patients with previous adverse reactions to other drugs of this class, except for patients with chronic urticaria.

Acetaminophen↗
PubMed1997

Aminopenicillin allergy.

Eight two children with histories of maculopapular or urticarial rashes during aminopenicillin treatment underwent skin tests, patch tests, radioallergosorbent assays and, in some cases, oral challenges. Hypersensitivity was diagnosed in eight (9.8%): immediate in four with urticarial reactions and delayed (that is cell mediated) in four with maculopapular rashes. In 49 children (38 with maculopapular eruptions, 11 with urticarial/angiooedematous reactions), negative allergologic findings were confirmed using oral challenges with the suspected drug. Maculopapular rashes may reflect delayed hypersensitivity to aminopenicillins, which can be diagnosed on the basis of late intradermal reactions and/or patch test positivity. The allergen panel must include the suspected aminopenicillin itself, as many cases are side chain specific. Most patients with urticarial reactions (more typical of immediate hypersensitivity) will also react to penicilloyl polylysine and minor determinant mixture. The time elapsed between the reaction and testing must be considered if negative results emerge, because IgE mediated sensitivity (unlike cell mediated forms) declines in the absence of antigen exposure.

Algorithms↗
PubMed1997

P-glycoprotein expression in de novo acute myeloid leukemia.

Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive; on the other hand, most patients with t(8;21) or t(15;17) were MDR negative. Rh123 accumulation studies showed a significant decrease of mean fluorescence intensities both in C219 and in JSB1 positive cases in comparison with PGP negative ones (P < 0.001). A significant decrease of remission induction rates (CR) was highlighted both between C219+ and C219- and between JSB1+ and JSB1- cases (32.1% v 62.1% and 32.6% v 73.8%, respectively, with P < 0.0001). The overall survival and the remission duration (CCR) were significantly shorter both in C219+ and in JSB1+ patients with no relationship to age. Furthermore, a higher rate of early relapses was noted among MDR+ when compared with MDR- patients both for C219+ and JSB1+ cases. The combination (C219- JSB1+) identified a subset of patients with an intermediate prognosis. On multivariate analysis, C219 and JSB1 were confirmed to be independent prognostic factors for achievement of CR, overall survival and CCR. In conclusion, the assessment of MDR phenotype by flow cytometry is a crucial prognostic factor of treatment outcome in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia.

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis.

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.

Humans↗
PubMed1996

In vitro inhibitory activity of citreoviridin against HIV-1 and an HIV-associated opportunist: Candida albicans.

Citreoviridin, a mycotoxin produced by some molds of the genera Penicillium and Aspergillus, inhibits the growth of bacteria of the Bacillus genus. Since significant information was not available on the effects of citreoviridin on eukaryotic cells and viruses, this molecule was tested on CD4+ T-lymphoid cell lines, on HIV-1 and on Candida albicans, which sometimes complicates HIV-infection. Antiviral activity was detected in H9 HTLV IIIB cells, a clone chronically infected by HIV-1. Citreoviridin reduced p24 in the supernatant of H9 HTLV IIIB in a dose-dependent manner with a pharmacological selectivity index of 2.6. In C. albicans, the effects of the mold-derivative were evaluated on some parameters associated with pathogenicity and virulence: cellular proliferation, germ tube production, expression of heat shock mannoproteins, release of proteases and phospholipases. At a 12.5 microM dose, citreoviridin showed a marked inhibitory effect on all parameters analyzed. As regards the mechanism of action, it is possible to hypothesize that the effects of citreoviridin may be due to a reduction of protein synthesis, since it inhibited the replication of HIV-1 at post-integrational stages and reduced the intracellular RNA and protein content in C. albicans.

AIDS-Related Opportunistic Infections↗
PubMed1996

High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study.

PURPOSE: To evaluate, in a prospective multicentric study, the efficacy of a conventional salvage chemotherapy (dexamethasone, cisplatin, and cytarabine [DHAP]) versus high-dose chemotherapy (carmustine, etoposide, cytarabine, and cyclophosphamide [BEAC]) followed by autologous bone marrow transplantation (ABMT) in patients with aggressive non-Hodgkin's lymphoma (NHL) in clinical partial response (PR) after two thirds of a conventional front-line therapy. PATIENTS AND METHODS: From August 1988 to August 1991, 286 patients with aggressive NHL were randomized in seven Italian institutions to receive fluorouracil, methotrexate, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as front-line therapy. Of the 286 patients enrolled onto the trial, 77 (27%) were considered in PR after two thirds of the front-line therapy, and 49 of 77 (64%) were randomized: 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT. RESULTS: The response after second-line treatment was as follows: in the DHAP group, four patients (15%) achieved a complete remission (CR), 12 (44%) remained in stable PR, and 11 (41%) showed progressive disease; in the ABMT group, three patients (14%) obtained a CR, 18 (82%) obtained a stable PR, and one (4%) progressed, with an overall response (CR + stable PR) of 59% and 96% (P < .001) in the DHAP and ABMT groups, respectively. The overall survival was 59% versus 73% and the progression-free survival (PFS) was 52% versus 73% in the DHAP and ABMT groups, respectively (P, not significant). The toxicity was mild, particularly in the ABMT group, and no treatment-related deaths occurred in either group. CONCLUSION: Because of the small number of patients randomized, we were unable to determine whether ABMT or a standard salvage regimen (DHAP) is superior for PR patients. However, we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients.

Adolescent↗
PubMed1996

Allergic respiratory diseases and environmental pollution: experience in the printing/paper-manufacturing industry.

Several studies have shown a correlation between airborne pollutants and respiratory disorders. To determine whether professional exposure to industrial pollution might represent a risk factor for allergic respiratory diseases, we administered allergologic tests to 275 workers employed in a paper-making/printing factory and to a control population composed of 160 office workers from the same urban area. All subjects were evaluated on the basis of personal and family histories, the results of prick tests with common airborne allergens, specific serum IgE levels, pulmonary function test, and standard chest radiography. The percentage of subjects with allergies in the factory-worker group (67/275; 24.4%) was significantly higher than that observed among the office workers (20/160; 12.5%) (chi-square test: 8.17; P < 0.01). Of the 67 factory workers with allergies, 94% had histories of daily exposure to aliphatic hydrocarbons. The results of this study indicate that exposure to the latter type of industrial pollutants is associated with a significantly higher prevalence of allergic respiratory diseases.

Adult↗
PubMed1995

Cytogenetic analysis is non-informative for assessing the remission rate in chronic myeloid leukemia (CML) patients on interferon-alpha (IFN-alpha) therapy.

Cytogenetic analysis is considered pivotal for assessing the remission rate in CML patients on IFN therapy. On the basis of general agreement, at least 25 metaphases should be analyzed in each case. The main limitations to this approach are: 1) the small number of analyzable metaphases generally found in cytogenetic preparations from IFN-alpha-treated patients; and 2) the inability of this technique for scoring interphase cells. We compared the results of cytogenetic analysis and double-color FISH detection of bcr/abl genes fusion in 13 CML patients on IFN-alpha therapy (marrow sampling for cytogenetic and FISH analysis was carried out after 12 months in all patients and repeated after 18 months of IFN therapy in patients 4, 6, and 8). In five specimens, 20 to 25 cells were evaluable for cytogenetic examination, in another five no analyzable metaphases were scored, and in the remaining six samples two to 14 cells could be analyzed. With FISH detection at least 100 cells were easily scored in each specimen (mean number, 175). Comparing the results carried out with the two methods in different samples it emerged that cytogenetic analysis led to improper conclusions as regards the rate of Ph positivity, even in those patients where 20-25 metaphases were analyzed. Although many more cases have to be studied to establish the role of FISH analysis in Ph-positive patients, we are of the opinion that cytogenetic analysis is unfit for easily and accurately assessing the actual quality of remission in IFN-treated subjects.

Chromosome Aberrations↗
PubMed1995

Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.

BACKGROUND: Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission. METHODS: After induction treatment with daunorubicin and cytarabine, patients who had a complete remission received a first course of intensive consolidation chemotherapy, combining intermediate-dose cytarabine and amsacrine. Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation; the others were randomly assigned to undergo autologous bone marrow transplantation (with unpurged bone marrow) or a second course of intensive chemotherapy, combining high-dose cytarabine and daunorubicin. Comparisons were made on the basis of the intention to treat. RESULTS: A total of 623 patients had a complete remission; 168 were assigned to undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to one of the other two groups. Of these patients, 343 completed the treatment assignment: 144 in the allogeneic-transplantation group, 95 in the autologous-transplantation group, and 104 in the intensive-chemotherapy group. The relapse rate was highest in the intensive-chemotherapy group and lowest in the allogeneic-transplantation group, whereas the mortality rate was highest after allogeneic transplantation and lowest after intensive chemotherapy. The projected rate of disease-free survival at four years was 55 percent for allogeneic transplantation, 48 percent for autologous transplantation, and 30 percent for intensive chemotherapy. However, the overall survival after complete remission was similar in the three groups, since more patients who relapsed after a second course of intensive chemotherapy had a response to subsequent autologous bone marrow transplantation. Other differences were also observed, especially with regard to hematopoietic recovery (it occurred later after autologous transplantation) and the duration of hospitalization (it was longer with bone marrow transplantation). CONCLUSIONS: Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin. Transplantation soon after a relapse or during a second complete remission might also be appropriate.

Adolescent↗
PubMed1995

First report of t(8;21)(q22;q22) in a case of de novo acute monoblastic leukemia.

Here we describe the case of a 30-year-old man with a diagnosis of de novo acute monoblastic leukemia (FAB M5a), whose karyotype analysis revealed the presence of the translocation (8;21)(q22;q22) as the sole chromosome anomaly. In spite of the rather good prognosis patients suffering from acute leukemia and carrying this translocation are supposed to have, our patient had a very poor outcome, including an early relapse resistant to any treatment and meningeal localization. Death occurred within 5 months from diagnosis. To our knowledge this is the first report of t(8;21)(q22;q22) in de novo acute monoblastic leukemia.

Adult↗
PubMed1995

Trisomy 4 as the sole karyotypic anomaly in acute biphenotypic leukemia with B lineage markers and in acute minimally differentiated myeloid leukemia (M0).

Trisomy 4 is a recently defined chromosomal aberration in acute leukemia. The first reports suggested that this cytogenetic anomaly belongs to the M4 leukemia subtype of the FAB classification, but recent reports have described this alteration in a wider spectrum of leukemia subtypes. Here we report two cases of trisomy 4 as the sole chromosome anomaly: one was observed in a patient with acute biphenotypic leukemia with B-lineage markers and the second in a patient diagnosed with acute minimally differentiated myeloid leukemia (M0) with myelodysplastic features. To our knowledge these are, respectively, the first and second reports of trisomy 4 as the sole chromosomal anomaly in these leukemia subtypes.

Acute Disease↗
PubMed1995

Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: studies with blasts of leukaemic patients.

BACKGROUND: A clinical pilot study performed by our group showed that dacarbazine can induce a marked reduction of blast cells in patients with acute myelogenous leukaemia (AML). Leukaemic blasts (LB) from responsive patients showed low levels of O6-alkylguanine-DNA alkyltransferase (OGAT). DESIGN: An in vitro study was performed to evaluate OGAT levels and sensitivity to temozolomide (a triazene compound that spontaneously decomposes into the active metabolite of dacarbazine) in a relatively large number of LB samples. RESULTS: OGAT levels varied widely among the LB of different patients, with a mean value higher in acute lymphoblastic leukaemias than in AML. About 25% of LB obtained from patients with AML showed low OGAT activity, in the range corresponding to that observed in leukaemic patients responsive to dacarbazine in vivo. A reasonable inverse correlation was found between OGAT levels and LB sensitivity to temozolomide. CONCLUSIONS: Triazenes could have a therapeutic potential in human leukaemias. Moreover, OGAT determination could provide rapid and reliable information about a patient's susceptibility to these antitumor agents.

Adolescent↗