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Biomedical subjects

G Cimino

Publications and source records attributed to G Cimino.

At least 37 records · Page 2Linked to original sources
PubMed2001

Lymphadenectomy in well differentiated thyroid carcinoma.

In this review, the authors analyze, in relation to the data collected in other literature, the indications and the type of surgical procedure to perform on the neck lymph nodes in cases of differentiated thyroid carcinoma. The authors stress the fact that the surgical procedure must be determined according to the stage in which the diagnosis and prognostic factors are formed and in relation to the natural history of these tumors.

Humans↗
PubMed2001

Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia.

The NUP98/RAP1GDS1 (NRG) is a new fusion gene, originating from the t(4;11)(q21;p15) translocation, that characterizes a subset of T-cell acute lymphoblastic leukemia (T-ALL). In this study we analyzed 43 T-ALL patients for the expression of this new molecular marker using a reverse transcription-polymerase chain reaction (RT-PCR) system, which is more sensitive and specific than cytogenetics alone, confirming that NRG-positive ALLs are infrequent, accounting for approximately 5% of cases.

Chromosomes, Human, Pair 11↗
PubMed2000

Chemical ecology of the Antarctic nudibranch Bathydoris hodgsoni Eliot, 1907: defensive role and origin of its natural products.

A variety of Antarctic marine invertebrates contains secondary metabolites that may provide defense against potential predators. However, only in a few cases have tissues, extracts or isolated compounds of these invertebrates been tested against sympatric predators. The Antarctic nudibranch Bathydoris hodgsoni Eliot, 1907 contains hodgsonal, a compound only present in the external body (mantle tissues), which may protect the slugs from predators. To test this defensive hypothesis for hodgsonal, we carried out a series of experiments using the sympatric omnivorous seastar Odontaster validus Koehler, 1906 as a potential predator. Our experiments revealed that natural concentrations of hodgsonal elicit significant feeding deterrent responses in O. validus. Furthermore, hodgsonal is probably biosynthesized de novo by the nudibranch, since it was not detected in the viscera (as it should be in the case of a dietary compound), its concentration in the mantle (0.05-0.15% dry mass) is quite constant in individuals from different localities and depths, and its sequestration from a particular dietary source is unlikely because B. hodgsoni is an omnivorous feeder.

Journal Article↗
PubMed2000

A prospective study of residual-disease monitoring of the ALL1/AF4 transcript in patients with t(4;11) acute lymphoblastic leukemia.

Twenty-five patients (22 adults and 3 infants) with ALL1/AF4-positive acute lymphoblastic leukemia (ALL) were prospectively monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) between January 1992 and July 1999. After high-dose induction and consolidation chemotherapy without bone marrow transplantation, all patients had a complete hematologic remission. Using nested RT-PCR (sensitivity 10(-4)), we observed conversion to PCR negativity in 11 (44%) of the patients. Thirteen of the 14 patients who did not have a molecular remission had a relapse at a median time of 4 months (range, 1 - 20 months). Of the 11 patients who had a conversion to PCR negativity, 5 reconverted to PCR positivity within 1 to 14 months. These 5 patients all progressed to hematologic relapse after 2, 3, 4, 4, and 7 months, respectively. Of the remaining 6 patients, 4 are in persistent hematologic and molecular remission at 12, 14, 88, and 96 months, whereas 2 are early in their follow-up. Actuarial probabilities of relapse and overall survival were 100% and 0% at 14 and 24 months and 67% and 43% at 96 and 100 months, respectively, in patients who had persistent RT-PCR positivity and in those who had a molecular remission. For both relapse and survival, the differences observed between the two groups were significant (P =.003 and P <.005, respectively). This study, which represents the first prospective analysis of residual-disease monitoring carried out in a substantial series of patients with t(4;11)-positive ALL, emphasizes the clinical relevance of RT-PCR-based methods to monitor minimal residual disease in this leukemia subset. (Blood. 2000;95:96-101)

Adult↗
PubMed2000

Scalarane and homoscalarane compounds from the nudibranchs Glossodoris sedna and Glossodoris dalli: chemical and biological properties.

A series of homoscalarane and scalarane compounds (2-7) have been isolated from two distinct species of Pacific Glossodoris nudibranchs. The structure and elucidation of the relative stereochemistry of the new metabolites 2 and 3 were obtained by spectroscopic methods. Compound 2 was ichthyotoxic at 0.1 ppm against Gambusia affinis and showed moderate activity (IC(50) 18 microM) to inhibit mammalian phospholipase A(2).

Animals↗
PubMed2000

HLA class I in acute promyelocytic leukemia (APL): possible correlation with clinical outcome.

The majority of patients with acute promyelocytic leukemia (APL) possess either a bcr1 or a bcr3 type fusion between PML and RARalpha genes. The junction sequences may possibly be a target for immune response and influence susceptibility to the disease. In this case, HLA class I allele frequencies would be different between bcr1 and bcr3 patients. To test this hypothesis, we typed 102 APL patients for HLA-A, -B and -Cw alleles. The A*1, A*30, B*51, B*41, Cw*0602, and Cw*1701 alleles showed a different distribution between bcr1 and bcr3 patients, but in no case was this statistically significant after correction for the number of comparisons or was confirmed in an independent panel. Moreover, no difference was detected between bcr1 and bcr3 when HLA alleles were grouped according to their peptide binding specificities. Comparing HLA frequencies, clinical features at diagnosis and clinical outcome of the 64 patients homogeneously treated with all-trans retinoic acid and idarubicin (AIDA protocol) we observed a statistically significant association between HLA-B*13 and risk of relapse by univariate and multivariate regression analysis. Should this finding be confirmed in larger future studies, this observation would be of outmost importance in identifying patients at high risk of relapse in which more aggressive consolidation therapies should be used.

Adult↗
PubMed2000

Idarubicin intensified BUCY2 regimen in allogeneic unmanipulated transplant for high-risk hematological malignancies.

Twenty-nine consecutive patients with high-risk hematological malignancy aged from 3 to 58 years underwent an unmanipulated graft from an HLA-identical sibling after an irradiation-free preparative regimen consisting of idarubicin (IDA), 21 mg/m2/day administered by continuous infusion on days -12 and -11, followed by busulphan (BU), 4 mg/kg/day orally from day -7 to -4, and cyclophosphamide (CY), 60 mg/kg/day intravenously on days -3 and -2 (IDA-BUCY2). Most clinically relevant extra-hematological regimen-related toxicities consisted of stomatitis observed in all subjects and hemorrhagic cystitis occurred in five cases (17%) within 100 days after transplant. Six patients (21%) developed a grade 2 acute graft-versus-host disease (GVHD) and three (10%) a grade 3 or 4; extensive chronic GVHD was assessed in nine of 22 (41%) evaluable patients. So far, 12 patients have died and 17 are alive, 16 of whom disease-free, 5-41 months after transplant (median, 15 months). The causes of death were related to GVHD in three patients, to sepsis in one and to disease recurrence in the remaining eight. At present, only one of nine relapsed patients is alive. For all patients the actuarial probability of survival (OS) at 1 and 2 years +/- standard error (s.e.) was 63 +/- 9% and 52 +/- 10%, respectively. The actuarial probabilities of disease-free survival (DFS), relapse and transplant-related mortality (TRM) at both 1 and 2 years +/- s.e. were 53 +/- 9%, 35 +/- 9% and 16 +/- 7%, respectively. These results are encouraging but not substantially different from those obtained in 28 patients with malignancy in advanced phase transplanted after the standard BUCY2 regimen, who had an actuarial probability of OS, DFS, relapse and TRM projected at 10 years +/- s.e. of 54 +/- 10%, 57 +/- 9%, 36 +/- 9% and 11 +/- 6%, respectively. Although the retrospective comparison between the two groups does not seem to show any advantage in the use of the IDA intensified regimen, only a prospective randomized trial could answer this question.

Adolescent↗
PubMed2000

t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia.

Two cases of T acute lymphoblastic leukaemia (T-ALL) with an identical t(4;11)(q21;p15) translocation were identified within a prospective study on the biological and clinical features of adult ALL patients enrolled into the therapeutic protocol ALL0496 of the GIMEMA Italian Group. In both cases, the molecular characterization showed an involvement of the NUP98 gene on 11p15 which rearranges with the RAP1GDS1 gene on 4q21. The morphological and immunological features of the leukaemic cells, as well as the clinical behaviour and response to induction therapy, were the same in both patients. Based on the available data, the t(4;11)(q21;p15) translocation involving the NUP98-RAP1GDS1 fusion gene emerges as a new highly specific genetic abnormality that characterizes a subset of T-ALL.

Adolescent↗
PubMed2000

Myeloperoxidase gene expression in non-infant pro-B acute lymphoblastic leukaemia with or without ALL1/AF4 transcript.

In this study, we examined myeloperoxidase (MPO) gene expression in a series of 31 non-infant pro-B acute lymphoblastic leukaemia (ALL) patients that included 16 cases with the t(4;11) translocation and/or the resultant ALL1/AF4 chimaeric gene. Sixteen out of 31 cases (51%) were MPO mRNA positive/enzyme negative. MPO mRNA was detected in nine out of 16 (56%) and seven out of 15 (47%) patients with and without the ALL1/AF4 fusion transcript respectively. The comparative study between MPO mRNA positive and negative cases showed statistically significant differences with regard to age and white blood cell (WBC) count, and was 39.5 years vs. 26.3 years (P = 0.016) and 71.4 x 10(9)/l vs. 157.8 x 10(9)/l (P = 0.046) in the MPO mRNA positive and negative groups respectively. The correlation analysis between MPO mRNA expression, age, WBC count and leukaemic relapse according to the presence/absence of the ALL1/AF4 fusion showed that the statistically significant differences observed in the whole group were related mostly to the ALL1/AF4-positive ALL patients. In fact, in this latter group, the mean WBC count and patients' age were 85 +/- 79 x 10(9)/l vs. 289.8 +/- 102 x 10(9)/l (P = 0.0005) and 44.8 +/- 15.3 years vs. 26.7 +/- 13.7 years (P = 0.01) in patients with and without MPO mRNA expression respectively. It appears, therefore, that the assessment of MPO mRNA expression enables a further dissection of leukaemia heterogeneity in apparently homogeneous genetic/immunophenotypic ALL subsets.

Adolescent↗
PubMed2000

Unmanipulated peripheral blood stem cell autograft in chronic lymphocytic leukemia: clinical findings and biological monitoring.

BACKGROUND AND OBJECTIVES: To investigate the feasibility of peripheral blood stem cell (PBSC) transplantion in patients with high-risk chronic lymphocytic leukemia (CLL) in remission after fludarabine therapy, the clinical impact of minimal residual disease (MRD) monitoring and the immunologic reconstitution after transplantation. DESIGN AND METHODS: Twenty CLL patients, in clinical complete remission (CR) after fludarabine, were offered an unmanipulated PBSC transplant and were longitudinally monitored for MRD and immunologic reconstitution. RESULTS: Due to unsatisfactory PBSC collection, 4 patients received bone marrow cells. All patients engrafted. Two patients died, one due to infection and one because of another neoplasia. Thirteen patients are at present in clinical CR after a median follow-up of 17 months and 18 patients are alive with a survival probability of 0.87 (+/-0.04) at 52 months after transplant. Fifteen patients had a molecular remission. Three of them showed a molecular relapse 16-28 months after autograft, followed by a clinical relapse 10-16 months later. Three of the four patients who remained persistently rearranged could be revaluated over time and showed an immunologic relapse 11-26 months after transplant; two of these had a clinical relapse 12 and 7 months later. A marked and persistent impairment of both the B- and T-immunologic compartments was recorded in the horizontal follow-up. INTERPRETATION AND CONCLUSIONS: Unmanipulated PBSC autograft is a feasible procedure that produces prolonged molecular remissions in high-risk CLL patients. Persistence or reappearance of a molecular signal after engraftment is predictive of subsequent immunologic and clinical CLL recurrence. The long -lasting impairment of the host immune repertoire after fludarabine followed by autograft has to be taken into account in the patients' management.

Adult↗
PubMed2000

[Otoneurological findings in a case of congenital central hypoventilation syndrome (Ondine's curse)].

The authors report a case of congenital central hypoventilation syndrome (CCHS) studied from the otoneurological point of view. Emphasis is placed on the numerous alterations in the electronystagmograph and auditory potentials. The results obtained confirm the hypothesis that such patients are subject to CNS alterations, suggesting that the disease pathogenesis derives from an alteration in the mechanism of central chemoreceptor stimuli integration.

Chemoreceptor Cells↗
PubMed1999

New minor diterpenoid diacylglycerols from the skin of the nudibranch anisodoris fontaini

The Patagonian dorid nudibranch Anisodoris fontaini contains in its mantle a series of isocopalane diterpenoid diacylglycerols. Five new minor metabolites, anisodorins 1-5 (1-5), along with the already reported 6 and 7, have been isolated and chemically characterized. The structure and the relative stereochemistries have been determined by spectroscopic means, while the absolute stereochemistries for 2-5 are suggested to be the same as for the biogenetically related major compounds 6 and 7. Synthesis of the enantiomer (8) of anisodorin 1 confirmed the proposed structure and absolute stereochemistry.

Journal Article↗
PubMed1999

Volvatellin, caulerpenyne-related product from the sacoglossan volvatella sp

Volvatellin (4) is a highly unstable terpene isolated from the extracts of the Indian opisthobranch mollusk Volvatella sp. The structure and the relative stereochemistry of 4 were determined by NMR methods. The paper also describes a hypothetical biosynthesis of 4 starting from the alga-derived caulerpenyne.

Journal Article↗
PubMed1999

Three new butenolide lipids from the caribbean gorgonian pterogorgia anceps

Three novel fatty acid derivatives (1-3), containing one or two butenolide moieties, were isolated from the Caribbean gorgonian Pterogorgia anceps and chemically characterized by spectroscopic methods and comparison with known compounds. The new molecules were structurally related to ancepsenolide (4), a typical metabolite from Pterogorgia species, which was not detected in this collection of P. anceps.

Journal Article↗
PubMed1999

Umbilical cord blood transplant from unrelated HLA-mismatched donors in children with high risk leukemia.

In the last 3 years, 14 children with high-risk leukemia (11 ALL, 2 AML and 1 CML) underwent cord blood transplantation from unrelated HLA-mismatched donors at a median of 99 days from the start of search. Eight patients were transplanted in second CR, one in accelerated phase, three at relapse and two patients in first CR. Conditioning regimen (fractionated TBI, etoposide, CY and anti-lymphocyte serum) and prophylaxis of GVHD (CsA and 6-methylprednisolone) were identical for all patients. Neutrophils >0.5x10(9)/l were reached at a median of 33 days from transplant, but in four cases we observed an autologous hematopoietic reconstitution (three spontaneous, one after autologous BM rescue). Acute and chronic GVHD were observed in 10/14 and 3/8 evaluable cases, respectively. Three patients died of transplant-related toxicity and three patients relapsed. The probabilities of event-free, disease-free and overall survival were 50, 53 and 64%, respectively. Cord blood transplant from HLA-mismatched unrelated donor is a valid option for the treatment of children with high-risk leukemia. With our eligibility criteria, conditioning regimen and prophylaxis of graft-versus-host disease, the main obstacles to successful transplant were represented by graft failure and fatal acute GVHD.

Adolescent↗
PubMed1999

Outpatient management of acute promyelocytic leukemia after consolidation chemotherapy.

The feasibility and safety of outpatient management of acute promyelocytic leukemia (APL) during the aplastic phase after intensive consolidation chemotherapy, the incidence and types of complications requiring readmission to hospital, and the number of hospital days spared by this policy have been prospectively evaluated. After chemotherapy administration, patients were evaluated on an ambulatory basis. In the event of any complication they referred to the Emergency Unit (EU) of our Department dedicated to outpatients with hematologic diseases. Forty patients with APL observed over a 4 year period were eligible for intensive chemotherapy. After the achievement of complete remission they received a total of 104 consolidation courses and in 98 instances they were followed on an ambulatory basis. There were 41 cases (42%) of rehospitalization for fever (40 cases) or severe anemia (one case). Only one patient died due to a brain hemorrhage. Streptococcus viridans was the organism most frequently isolated from blood. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 87% of the cases and made possible early discharge in 28% of the cases to continue the antibiotic therapy on an outpatient setting. Patients were managed out of the hospital for 76% of the post-consolidation neutropenia period. Thanks to the availability of an EU specifically dedicated to outpatients with hematologic diseases, out-hospital management of APL patients after consolidation therapy appeared to be safe, well accepted, potentially cost-saving, and contributed to saving the risk of developing severe nosocomial infections.

Adult↗