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Biomedical subjects

C Giles

Publications and source records attributed to C Giles.

At least 19 recordsLinked to original sources

Lattice distortion effects on the magnetostructural phase transition of MnAs.

We present a systematic experimental and theoretical study of the first-order phase transition of epitaxially grown MnAs thin films under biaxial tensile stress. Our results give direct information on the dependence of the phase-transition temperature of MnAs films on the lattice parameters. We demonstrate that an increase of the lattice constant in the hexagonal plane raises the phase-transition temperature (T(p)), while an increase of the perpendicular lattice constant lowers T(p). The results of calculations based on density functional theory are in good agreement with the experimental ones. Our findings open exciting prospects for magneto-mechanical devices, where the critical temperature for ferromagnetism can be engineered by external stress.

Journal Article↗

Paclitaxel-containing high-dose chemotherapy for relapsed or refractory testicular germ cell tumours.

High-dose regimes containing etoposide, carboplatin and an oxazaphospharine can salvage 30-40% of patients with relapsed or refractory male germ cell tumours (GCTs). The additional benefit of paclitaxel in such high-dose therapy has not been tested. Between March 1995 and November 2002, 36 male GCT patients were treated with Carbop-EC-T (paclitaxel 75 mg x m(-2), etoposide 450 mg x m(-2), carboplatin AUC 10 on days -7, -5 and -3 and cyclophosphamide 60 mg x kg(-1) on days -5 and -3) followed by peripheral blood stem cell infusion (day 0). The 1-year overall survival rate for all patients is 67% (median follow-up 29 months). For the 24 patients with cisplatin-sensitive disease, the 1-year overall and event-free survivals are 88 and 64%, respectively. For those with cisplatin refractory or absolutely refractory disease, the 1-year overall survival is 25%. In all, 12 patients relapsed at a median duration of 5 months, 11 of whom have died. There were also six treatment-related deaths, five associated with pneumonitis. Pulmonary toxicity has been reported with paclitaxel in other high-dose regimes. Since altering our protocol so that paclitaxel is infused over 24 h with steroid prophylaxis, only one of 18 patients (13 testicular GCTs and five other tumour types) has had a treatment-related death. Our results suggest that Carbop-EC-T may enable a greater proportion of patients with relapsed and refractory GCTs to enter long-term remission.

Adult↗

First experiments on diffraction-enhanced imaging at LNLS.

Diffraction-enhanced images have been obtained using two silicon crystals in a non-dispersive set-up at the XRD2 beamline at the Brazilian Synchrotron Light Laboratory (LNLS). A first asymmetrically cut silicon crystal using the (333) reflection vertically expanded the monochromated beam from 1 mm to 20 mm allowing the imaging of the whole sample without movements. A symmetrically cut Si(333) second crystal was used as a Bragg analyzer. Images of biological samples including human tissue were recorded using a direct-conversion CCD detector resulting in enhancement of the contrast compared with absorption-contrast images.

Brazil↗

High-resolution X-ray diffraction beamline at the LNLS for the study of charge, orbital and magnetic structures.

A high-resolution X-ray diffraction beamline at the Brazilian Synchrotron Light Laboratory (LNLS) has been commissioned for the study of crystalline magnetic materials. The beamline optics is based on a Rh-coated vertical-focusing X-ray mirror and a sagittal-focusing double-crystal monochromator. The primary instrument is a six-circle diffractometer equipped with energy and polarization analysers and a closed-cycle He cryostat. The beamline source is a bending magnet of the 1.37 GeV storage ring of the LNLS, delivering approximately 4 x 10(10) photons s(-1) at 8 keV at the sample position. Resonant and non-resonant scattering are the main techniques used to study charge, orbital and magnetic structures. Examples of magnetic scattering in Ho and NiO single crystals, as well as orbital ordering in manganites thin films, are presented.

Brazil↗

Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age, status at transplant, previous treatment and conditioning regimen. A single-centre experience in 127 patients.

High-dose therapy with autologous stem cell transplantation (ASCT) has become the treatment of choice for symptomatic eligible patients with multiple myeloma (MM). We report our centre experience and analyse retrospectively the prognostic influence of pretransplant characteristics and transplant modalities on response and survival. A total of 127 MM patients (median age: 55.2 years) were transplanted between 1994 and 2001. In all, 69 patients had IgG, 28 IgA, 23 light chain, one IgD and six non secretory MM. At the time of autograft, 6% of patients were in complete remission (CR), 73% in partial remission (PR), 12% showed minor response to previous treatment and 9% had stable or refractory disease. Prior to autograft, 79% of cases had received only one line of chemotherapy and 21% two or more lines. All patients received PBSC support after conditioning with 200 mg/m(2) melphalan alone (100 patients) or melphalan and TBI (27 patients). We evaluated the influence of age (using as cutoff value the ages of 55, 60 and 65 years), type of MM, status pre- and post-ASCT, number of lines of previous regimens, time of ASCT from diagnosis, year of autograft, dose of reinfused CD34+ cells, plasma cell infiltration and beta(2)-microglobulin at diagnosis on overall (OS) and progression-free survivals (PFS) to define patients with better prognosis. Following ASCT, 15% of patients were in CR and 81% in PR, while only two patients progressed. Median OS and PFS from transplantation were 50.4 and 23.5 months, respectively. Median OS from diagnosis was 79.7 months. Transplant-related mortality was 2.3%. Low levels of beta(2)-microglobulin and the achievement of CR post-transplant correlated with longer PFS (P<0.03 and P<0.01, respectively). The median PFS was 36.1, 23.9, 21.1 and 16.4 months for nonsecretory, IgG, IgA and light chain subtypes, respectively. Age was not an important prognostic factor at a cutoff value of 55 or 60 years. We conclude that ASCT is a safe and effective procedure even in resistant cases. The outcome was independent of age, time from diagnosis, previous treatment and conditioning regimen, but there was a tendency for better survival in the nonsecretory patients.

Age Factors↗

Immune neutropenia associated with anti-human neutrophil antigen-2a (NB1) antibodies following unrelated donor stem cell transplantation for chronic myeloid leukaemia: perpetuation by granulocyte colony-stimulating factor.

A case of immune neutropenia following unrelated stem cell transplantation for chronic myeloid leukaemia is described. The neutropenia developed following herpes zoster viral infection and was associated with antibodies to the human neutrophil antigen (HNA)-2a (formerly known as NB1). The neutropenia was prolonged, profound and unresponsive to granulocyte colony-stimulating factor (GCSF). The neutrophil count recovered after GCSF was discontinued. HNA-2a has been reported to be upregulated following GCSF administration. In the present case, it appears that the immune neutropenia may have been perpetuated by GCSF administration.

Adult↗

Post-antibiotic growth suppression of linezolid against Gram-positive bacteria.

The in vitro post-antibiotic effects (PAEs) of eight different concentrations of linezolid against Gram-positive cocci were investigated and the results analysed using the sigmoid E(max) model for mathematically modelling the PAE. Mean maximal linezolid PAEs against strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Streptococcus pneumoniae were 2.2, 1.8, 2.8, 2.0 and 3.0 h, respectively. Resistance to methicillin (for the staphylococci), vancomycin (for the enterococci) and penicillin (for the pneumococci) had no effect on the duration of the PAE. Results of PAE testing support twice-daily dosing of linezolid in humans.

Acetamides↗

CCNU (lomustine), idarubicin and dexamethasone (CIDEX): an effective oral regimen for the treatment of refractory or relapsed myeloma.

We report the results of a non-randomized pilot study of an oral regimen comprising CCNU (lomustine; 25 or 50 mg/m2 on day 1), idarubicin (4-demethoxydaunorubicin) (10 mg/m2 on days 1-3) and dexamethasone (10 mg b.d. on days 1-4) in patients with relapsed or refractory myeloma. Treatment was given every 28 d for a maximum of six courses. Sixty patients were entered of whom 57 were evaluable. Overall response rate (partial or minor response) was 49% with 30% of patients achieving a partial response (50% tumour reduction). Response rates were higher in patients with untested relapse than in those with refractory disease (overall response rates 56% vs. 31%). The major toxicity was neutropenia and the regimen was otherwise well tolerated. The median survival from entry of all patients was 15 months, with 30% of patients alive at 2 years. This regimen represents a useful addition to available treatment options.

Adult↗

CD34+-selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome.

Thirty-six patients with multiple myeloma (23 PR1, nine PR2, four stable disease) were entered into a pilot study evaluating the use of CD34+-selected peripheral blood progenitor cell transplantation (PBPCT) following high-dose melphalan alone or high-dose melphalan and total body irradiation. Peripheral blood progenitor cells (PBPCs) were mobilized with cyclophosphamide and granulocyte colony stimulating factor (G-CSF). CD34+ selection using the Cellpro Ceprate-SC system was performed in 22 cases with an adequate yield in 20. 10 patients failed to mobilize sufficient cells to permit selection and in four cases selection was not performed for other reasons. 16 patients therefore received unselected PBPC. Tumour cell contamination was evaluated by IgH gene fingerprinting (fpPCR). Harvested PBPC were fpPCR positive in 13/20 CD34+-selected cases and remained positive after selection in seven. Harvested PBPC were studied in 9/16 patients receiving unselected cells; fpPCR was positive in five and negative in four. There was no difference in event-free survival (EFS) between the CD34+-selected group and the unselected group (median 21 and 26 months, respectively, P=ns). The CD34+-selection process therefore reduced contamination but did not eliminate it completely, and in this small non-randomized study there was no apparent clinical benefit of CD34+ selection.

Adult↗

Nanosecond-resolved XMCD on ID24 at the ESRF to investigate the element-selective dynamics of magnetization switching of Gd-Co amorphous thin film.

The one-bunch filling mode of the ESRF is combined with a microcoil to generate a pulsed-magnetic-field pump phased with respect to the probe that is given by the bunch of photons emitted each turn (357 kHz). Nanosecond-resolved X-ray magnetic circular dichroism (XMCD) is carried out. Besides the microcoil, the two other key-elements are the energy-dispersive XAS spectrometer, which yields parallel data acquisition, and the diamond-based quarter-wave plate, which tunes the helicity of the photon alternatively left and right.

Journal Article↗

A versatile X-ray diffraction station at LNLS (Brazil).

Versatility was a major consideration in the project to provide an X-ray diffraction station at LNLS. At least two techniques are possible at the station: powder diffraction and multiple single-crystal diffraction. A two-crystal monochromator based on monolithic elastic translators, developed at LNLS, with sagittal focusing by the second crystal, allows 10 mrad of a >/=2 keV monochromatic beam to be used on the diffractometer. The station is equipped with a fast scintillation detector, imaging plates, a high-energy-resolution pin-diode detector, an ionization chamber and a high-angular-resolution soller slit. The data collection and control hardware and software were also developed at LNLS. The theta-2theta goniometry for powder diffraction on this 1 m-diameter diffractometer is based on commercial rotation tables. The multiple single-crystal goniometry is realized by an independent elastic axis driven by differential micrometers for both high- and low-resolution angular movements. At least four independent axes can be positioned as necessary on the diffractometer table. Powder diffractograms and double-crystal rocking curves collected with the synchrotron beam show the expected quality.

Journal Article↗

High-dose therapy including carboplatin adjusted for renal function in patients with relapsed or refractory germ cell tumour: outcome and prognostic factors.

Thirty-one consecutive patients with relapsed or refractory GCT received an HDT schedule including carboplatin, the dose of which was adjusted to measured glomerular filtration rate. There was one HDT-associated death (3%), due to acute renal failure. The 3-year probability of overall and disease-free survival for 21 patients with primary refractory disease or responsive relapse was 60% and 42%, respectively, while none of ten patients with refractory relapse have survived disease free.

Carboplatin↗

A randomized study of VAD therapy with either concurrent or maintenance interferon in patients with newly diagnosed multiple myeloma.

This randomized study was designed to determine whether response to VAD chemotherapy could be prolonged by using rh alpha-2b-interferon (IFN) at a dose of 3 mU three times per week, either concurrently with VAD (VIC) or as maintenance after completion of VAD (VIF). Maintenance IFN was given for 9 months in order for the duration of IFN therapy to be similar in both groups. 72 patients were randomized between December 1988 and August 1993. The majority of patients had poor prognostic features. The objective response rate was similar in each arm, 78% in VIF and 77% in VIC. Of the 56 responders, 33 have relapsed, three died in remission, and 18 proceeded to high-dose therapy, withdrew for other reasons or were lost to follow-up and were censored from analysis at the relevant time point. Only two patients remain in remission (both in partial remission). Median PFS was 15 months for both VIF and VIC, compared with 16.5 months for a historic control group treated with VAD alone (n.s.). The estimated median survival in VIF was 43 months and in VIC 22 months, compared with 45 months in the historic controls (n.s.). These findings indicate that neither maintenance nor concurrent IFN prolongs response to VAD.

Antineoplastic Combined Chemotherapy Protocols↗

When to harvest peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood.

PURPOSE: To evaluate whether the CD34+ yield from a single peripheral-blood stem-cell (PBSC) harvest could be predicted by measurement of the patient's circulating WBC and CD34+ cell concentrations on the day before harvest. PATIENTS AND METHODS: Thirty-nine patients with hematologic or nonhematologic malignancy underwent 41 stem-cell mobilization episodes with cytotoxic chemotherapy and/or granulocyte colony-stimulating factor (G-CSF), and a total of 63 leukapheresis procedures were performed. Peripheral-blood samples were analyzed for WBC and CD34+ cell concentration both on the day before and the day of leukapheresis. RESULTS: The median WBC and CD34+ concentrations on the day preceding leukapheresis were 10.0 x 10(9)/L (range, 0.4 to 44.4) and 24.9 x 10(6)/L (range, 0.1 to 349.4), respectively. On the day of harvest, the corresponding figures were 15.1 x 10(9)/L (range, 1.5 to 52.6) and 29.3 x 10(6)/L (range, 0.1 to 543.1), respectively. The median CD34+ cell number collected in a single leukapheresis was 2.6 x 10(6)/kg body weight (range, 0.1 to 26.1). Both the preceding day (r = .84, P < .001) and harvest day (r = .95, P < .001) CD34+ circulating concentrations correlated significantly with the number of CD34+ cells per kilogram collected at leukapheresis. The correlation between CD34+ cells per kilogram collected and harvest day WBC count was also significant (r = .43, P <.001), but with the preceding day WBC count was nonsignificant. CONCLUSION: The number of CD34+ cells harvested in a single leukapheresis can be predicted by measurement of the preceding day peripheral-blood circulating CD34+ concentration, and on the basis of these data a table of probable CD34+ cell yield has been constructed. This correlation may facilitate the efficient organization of leukapheresis procedures.

Antigens, CD34↗

Characterization of two hybrid C4 allotypes (C4A*12 and C4B*3) by electrophoretic, serological and restriction fragment length polymorphism analyses.

Informative pedigree analysis of two rare C4 allotypes is reported. One proband was C4A deficient as a consequence of having one haplotype with a deleted C4A gene, and the second haplotype with two C4B genes--one encoding the common C4B*1 and one encoding a unique hybrid gene product C4B*3. C4B*3 had approximately normal C4B hemolytic activity, a single alpha-chain of MR 94,000 by SDS-PAGE but was positive for Rg:1,2 by hemagglutination inhibition (HAI) and for Rg:1 by Western blotting. The hybrid nature was confirmed by RFLP analysis with a Rg:1-associated fragment by Eco0109 digestion but no C4A-associated fragments by N1aIV digestion were identified. A gene conversion at Locus I which included just the C4 isotype region could explain the structure of C4B*3. The second pedigree had a Rodgers negative C4A*12 allotype. This C4A gene, which segregated with a single 7.0 kb TaqI fragment, encoded a C4A alpha-chain, which was negative for Rg:1 epitope. The affected haplotype lacked the Rg:1-associated fragment by Eco0109 digestion yet had the C4A specific N1aIV digestion fragment. These studies successfully employed RFLP analyses to confirm serologic and electrophoretic observations.

Adolescent↗