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C Bernasconi

Publications and source records attributed to C Bernasconi.

At least 91 records · Page 5Linked to original sources
PubMed1995

Chronic myelogenous leukemia and exposure to ionizing radiation--a retrospective study of 443 patients.

Exposure to ionizing radiations (Rx) has been implicated as a causative factor of chronic myelogenous leukemia (CML). We performed a retrospective study of 443 consecutive CML patients, looking for a history of significant exposure to Rx, and evaluated the clinical and hematological characteristics in order to find any difference between radiation-related CML patients and those with de novo CML. We identified 406 patients without known exposure to mutagens (group I) and 37 patients with prior significant exposure to Rx (group II). In comparison to patients of group I, those of group II showed particular clinical and hematological features: significantly lower incidence of bulky splenomegaly (p < 0.05) and hyperleukocytosis (WBC > 100 x 10(9)/l; p < 0.05); significantly higher incidence of anemia (Hb < 10 g/dl; p < 0.01). Patients with radiation-related CML had a significantly better survival than those with de novo CML (median survival 61 months vs 42 months; p < 0.05). In conclusion, this study of a large cohort of CML patients indicates that the subgroup of patients with a history of significant exposure to ionizing radiation has particular clinical and hematological features at onset (lower tumor burden, higher frequency of anemia) and a better survival.

Adolescent↗
PubMed1995

Evaluation of the relatedness of strains of Mycobacterium avium using pulsed-field gel electrophoresis.

The application of molecular techniques to investigate strain relatedness may help define the local epidemiology of Mycobacterium avium infection, and, by identifying false isolates (i.e. neither pathogens nor colonizers) resulting from contamination, may serve as a tool for quality control in the laboratory. For this purpose, isolates from all patients (n = 129) with Mycobacterium avium infections identified over a two-year period were investigated by pulsed-field gel electrophoresis (PFGE). Of 38 PFGE patterns identified, 34 corresponded to unique strains or to isolates present in no more than two or three individuals. One prevalent strain was identified among HIV-infected patients and three patterns were related to culture contamination events. PFGE (i) established the diversity of Mycobacterium avium strains in a community; (ii) identified the existence of a unique strain that may account for one-fifth of Mycobacterium avium isolated from HIV-infected patients locally; (iii) documented the extent and resolution of a suspected pseudo-outbreak; and (iv) uncovered an additional-unsuspected contamination event.

AIDS-Related Opportunistic Infections↗
PubMed1995

Modulation of all-trans retinoid acid pharmacokinetics in acute promyelocytic leukaemia by prolonged interferon-alpha therapy.

Continuous treatment with all-trans retinoid acid (ATRA) induces accelerated drug catabolism which is considered responsible for acquired resistance to ATRA. We studied the effect of interferon-alpha 2a (IFN) on ATRA pharmacokinetics in two patients with acute promyelocytic leukaemia (APL) in complete remission maintained by alternating 15 d of IFN and 15 d of ATRA. Day 15 ATRA levels obtained during IFN+ATRA treatment were significantly higher than those observed in patients maintained on ATRA alone. In one patient IFN was discontinued and day 15 ATRA levels decreased to those observed in patients scheduled for maintenance with ATRA alone. In our two patients IFN substantially reduced the induction of ATRA catabolism, indicating a potential role for IFN in modulating ATRA pharmacokinetics.

Drug Interactions↗
PubMed1995

A novel insertion element from Mycobacterium avium, IS1245, is a specific target for analysis of strain relatedness.

The insertion sequence IS1245 is a novel mycobacterial repetitive element identified in Mycobacterium avium. It encodes a transposase which exhibits a 64% amino acid similarity with IS1081, an insertion element present in the M. tuberculosis complex. The host range of IS1245 appears limited to M. avium as this element was not identified in M. intracellulare or in any other of 18 mycobacteria species tested. When IS1245 was used for restriction fragment length polymorphism (RFLP) analysis, human isolates characteristically presented a high number of copies (median, 16; range, 3 to 27) and a diversity of RFLP patterns comparable to that found by pulsed-field gel electrophoresis. Isolates from nonhuman sources differed both in number of copies and in RFLP pattern diversity: while swine isolates shared the characteristics of human strains, those from several avian sources exhibited a very low copy number of IS1245 and appeared clonal on the basis of RFLP.

Animals↗
PubMed1995

Acute myeloid leukemia and diabetes insipidus: results in 5 patients.

The clinical and hematological characteristics of 5 patients affected with both acute myeloid leukemia (AML) and diabetes insipidus (DI) are described. Banded chromosomal analysis demonstrated monosomy 7 in 2 patients and a complex cytogenetic rearrangement in another. No patient entered complete remission with standard induction chemotherapy. These data confirm that in patients with AML, the association of DI (with or without monosomy 7) is an unfavorable prognostic factor.

Adult↗
PubMed1994

Analysis of long-term results and prognostic factors among 138 patients with advanced Hodgkin's disease treated with the alternating MOPP/ABVD chemotherapy.

BACKGROUND: A prospective study was conducted to assess (a) the long-term results and toxicity of the alternating MOPP/ABVD regimen in advanced Hodgkin's disease; (b) the prognostic value of pretreatment variables and of drug dose intensity. PATIENTS AND METHODS: A total 138 consecutive patients with advanced Hodgkin's disease entered this study; patient selection included stages IIB (33% of total), IIIB (26%), IV (25%), and stages IIA-IIIA (16%) with bulky disease and pulmonary hilum involvement. The MOPP/ABVD program was delivered in an 8-month program; adjuvant radiotherapy on sites of bulky disease was delivered in 24 patients. RESULTS: Complete remission was obtained in 106 (77%) patients; significant factors for CR in univariate analysis were stage, symptoms, histology, and bone marrow involvement. The five-year relapse-free survival (RFS) was 83%; in a multivariate analysis, histology only correlated with RFS (p = 0.04). The five-year freedom from tumor mortality and overall survival (OS) were 79% and 67%, respectively. An adverse prognostic significance for OS was observed for B symptoms and bone marrow involvement. The median percentage of relative dose intensity (RDI) was as follows: Adriamycin 86, mechlorethamine 85, vincristine 73, vinblastine 84, bleomycin 79, procarbazine 74, dacarbazine 81. No significant association was found between RDI and clinical outcome. No severe pancytopenia or life-threatening complications occurred during therapy. CONCLUSIONS: Alternating MOPP and ABVD cured more than 65% of patients with advanced HD; acute and late toxicity were acceptable. Prognostic analysis defined subgroups with a lower chance of cure which may deserve a more intensive initial therapy.

Adolescent↗
PubMed1993

Molecular approach to identifying route of transmission of tuberculosis in the community.

There is growing concern that tuberculosis is spread in Europe in the way that it is in the USA. We have used DNA "fingerprinting" in a systematic evaluation of tuberculosis cases notified in our community to uncover foci of transmission. An IS6110 probe was used to test all isolates from culture-confirmed tuberculosis cases (163 patients) notified in 1991-92 in the Canton of Berne. In total, 45 patients (27.6%), potentially linked on the basis of restriction fragment length polymorphism, were investigated epidemiologically. The largest group (n = 22) included members of a defined social group (drug addicts, homeless persons, alcoholics), from whom tuberculosis spread to the general population. A key patient developed multidrug-resistant tuberculosis during the surveillance period. This population study showed that (i) extensive transmission of Mycobacterium tuberculosis is now taking place in Europe in the same social setting as in the USA; (ii) there is definite "spillover" to the general population; (iii) the dimensions of the problem cannot be recognised easily by routine public health service activities because of the complexity of the transmission network; and (iv) multidrug-resistant tuberculosis develops in this setting.

Adult↗
PubMed1993

The role of systemic high-dose cytarabine in the treatment of central nervous system leukemia. Clinical results in 46 patients.

BACKGROUND: Given the good penetration of systemic high-dose cytarabine (HDara-C) into the cerebrospinal fluid (CSF), this approach was used to treat patients with central nervous system (CNS) leukemia, either isolated or with concurrent extraneurologic disease (END). METHODS: From 1983 to 1991, 46 adults with CNS involvement were treated with systemic HDara-C: 25 had acute lymphoblastic leukemia (ALL), 15 had high-grade non-Hodgkin lymphoma (NHL), 5 had acute myelogenous leukemia (AML), and 1 had lymphoid blast crisis of chronic myelogenous leukemia. Induction consisted of HDara-C 3 g/m2 every 12 hours, by 3-hour infusion, for 8 doses (30 patients), or 6 doses (16 patients), followed by 4 doses at day 21. RESULTS: Of 46 patients, 29 (63%) achieved complete remission (CR): 15/15 with isolated CNS leukemia, and 14/31 (45%) with CNS and concurrent marrow or lymph node disease. Of 17 patients not meeting CR criteria because of persistent END, 11 showed complete CNS response. The first 10 remitters were consolidated with monthly 4-dose courses of HDara-C. The remaining 19 received postinduction multidrug chemotherapy (including vincristine, doxorubicin, cyclophosphamide, L-asparaginase, etoposide plus intermediate-dose ara-C, mitoxantrone plus HDara-C) and intrathecal methotrexate (MTX) +/- cranial radiation therapy. One patient underwent autologous and one allogeneic bone marrow transplant. Median CR duration was 7 months (range, 2-56+): 8 months for patients with isolated CNS leukemia, and 4 months for those with concurrent END: In only two patients was CNS the primary site of relapse. Three patients with isolated CNS leukemia are disease-free at 23, 40, and 56 months. The main toxicity was myelosuppression. No patient showed dose-limiting neurologic toxicity. CONCLUSIONS: Systemic HDara-C appears effective therapy for CNS leukemia, maximally in cases with isolated CNS involvement. HDara-C may be combined safely with cranial radiation therapy and intrathecal MTX. This approach for CNS leukemia, however, needs to be combined with additional treatments to eradicate residual disease in extraneurologic compartments.

Adolescent↗
PubMed1993

beta-Casomorphin-immunoreactivity in the brain stem of the human infant.

Using a peptide extraction procedure, reversed phase high performance liquid chromatography, and a radioimmunoassay that utilized an antibody raised specifically against human beta-casomorphin-8 (BC8), BC-immunoreactivity (BCIR) was detected in rostrocaudally increasing levels in nineteen microscopically distinct and functionally relevant areas of mesencephalon, pons cerebri, and medulla oblongata of eight infants. On the basis of the methodology used, it can be concluded, that the BCIR present in their brain stem was due to BC8 and/or to some of its congeners. Data in the literature together with those of this study indicate that beta-casomorphins could be transported by specific mechanisms from the blood into the brain stem and that they could play a role in the central regulation of various physiological phenomena.

Blood-Brain Barrier↗
PubMed1992

A major oligomeric fibroblast proteoglycan identified as a novel large form of type-XII collagen.

Cultured chick embryo skin fibroblasts release a major component with a native molecular mass of about 1 MDa, which resolves into three polypeptide bands of about 300, 350 and 600 kDa upon reduction. We report here the purification of this oligomeric protein and show, by means of polyclonal and monoclonal antibodies, that its three polypeptide constituents are closely related. The 600-kDa polypeptide is likely to be a dimer of two smaller subunits which are cross-linked by non-reducible bonds. By electron microscopy, isolated oligomeric molecules exhibit a novel cruciform structure with a large central globular domain. One arm has the shape of a thin rod about 70 nm in length. The three other arms are thicker, longer (90 nm) and flexible, and carry a prominent double globule at their distal ends. Collagenase treatment of the oligomeric fibroblast protein yields two resistant fragments of about 270 kDa and 320 kDa. The intact 350-kDa and 600-kDa (but not the 300-kDa) polypeptides are chondroitinase sensitive and labeled by metabolic incorporation of [35S]sulfate; collagenase treatment does not remove any [35S] sulfate. Hence, the intact fibroblast protein has glycosaminoglycan chains attached to its non-collagenous domain. Three amino acid sequences obtained from chymotryptic fragments of the fibroblast protein correspond to sequences predicted for chick type-XII collagen from its full-length cDNA [Yamagata, M., Yamada, K. M., Yamada, S. S., Shinomura, T., Tanaka, H., Nishida, Y., Obara, M. & Kimata, K. (1991) J. Cell Biol. 115, 209-221]. However, the novel fibroblast protein described here differs significantly from previously isolated forms of type-XII collagen: its subunits are larger by one third, and it is a proteoglycan.

Amino Acid Sequence↗
PubMed1992

Early intensification followed by allo-BMT or auto-BMT or a second intensification in adult ALL: a randomized multicenter study.

In January 1987 we started a multicenter study in order to evaluate in adult ALL patients the results of an intensive chemotherapy effected early after CR, and to compare the efficacy of allogeneic BMT vs autologous BMT vs prolonged intensive chemotherapy in the attempt to eradicate minimal residual leukemia. To September 1990 ninety-six patients entered this study; of the 87 evaluable for induction 25 were at low risk and 62 at high risk; 67 (77%) achieved CR by an induction chemotherapy including vincristine, adriamycin, cyclophosphamide, dexamethasone. Fifty-six out of 67 remitters were enrolled for the early intensification, which consisted of HDAra-C+amsacrine (or IDAra-C+mitoxantrone) followed by vincristine+adriamycin+cyclophosphamide and etoposide+Ara-C. During the early intensification an unexpectedly high number of relapses (10/56) was observed, showing that very intensive treatment with myelosuppressive agents is not useful at this point of the post-remission therapy. One patient suffered toxic death. Out of 45 patients who completed the early intensification 16 had a related well-matched donor and were selected for allogeneic BMT (performed in 11); of the remaining 29 patients, 14 were randomized for autologous BMT (performed in 9) and 15 for a second intensification. The overall DFS at 3 years is 35%. The high number of early relapses makes it difficult to draw conclusions from the comparison of the three eradication modalities. The best results, although without statistical significance, were obtained after allogeneic BMT; in high-risk patients this procedure should be effected as soon as possible after attainment of CR. Autologous BMT and prolonged intensive chemotherapy gave results similar to each other; both were sometimes followed by delayed relapses.

Adolescent↗