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Chris Mitchell

Publications and source records attributed to Chris Mitchell.

15 recordsLinked to original sources
PubMed2006

The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia.

OBJECTIVE: Thiopurine metabolism was investigated in children with acute lymphoblastic leukemia treated in the United Kingdom Medical Research Council trial ALL97. This trial compared the efficacy and toxicity of thioguanine (INN, thioguanine) versus mercaptopurine. METHODS: Consecutive children were randomized to receive thioguanine or mercaptopurine during maintenance chemotherapy. Toxicity data were collected by an adverse event-reporting system with follow-up questionnaires. Red blood cell thiopurine methyltransferase (TPMT) activity and thioguanine nucleotide concentrations were measured by standard techniques. RESULTS: Of the children, 748 were randomized to thioguanine and 744 were randomized to mercaptopurine. There was no difference in the event-free survival rate between the 2 groups (80% and 81%, respectively, at 5 years). Thioguanine was associated with veno-occlusive disease (VOD) of the liver in 95 children, and persistent splenomegaly as a result of portal hypertension developed in 43 children. TPMT activity was significantly lower in the children in whom VOD developed, with a median of 13.4 U (range, 5.8-23 U) compared with 15.2 U (range, 5.3-27) in a control group of 161 leukemia patients in whom VOD did not develop (median difference, 1.8 U; 95% confidence interval, 0.9-2.7 U; P = .0001). TPMT activity in children with persistent splenomegaly was also lower than that in control subjects (median difference, 1.6 U; 95% confidence interval, 0.3-2.8 U; P = .012). There was no difference in red blood cell thioguanine nucleotide concentrations. CONCLUSIONS: Thioguanine was associated with liver damage in 11% of children randomized to thioguanine without an improvement in event-free survival rate. The association of lower TPMT activity with thioguanine-related liver damage could provide a means of identifying at-risk patients.

Adolescent↗
PubMed2006

Effects of preexposure on stimulus discrimination: an investigation of the mechanisms responsible for human perceptual learning.

The effect of preexposure on human perceptual learning was investigated in four experiments. In Experiments 1a and 1b, participants were preexposed to one pair of visual stimuli on an intermixed schedule (AX/BX) and one on a blocked schedule (CX_DX). The ability to discriminate between AX and BX and between CX and DX was then assessed by examining the extent to which key presses assigned to each member of a stimulus pair generalized to the other member (Experiment 1a) and by looking at the accuracy of same-different responses (Experiment 1b). Stimuli were more easily discriminated following intermixed than following blocked preexposure on both the generalization and same-different tasks. This suggests that two stimuli are more perceptually distinct after intermixed preexposure. Experiments 2a and 2b investigated the mechanisms responsible for perceptual learning using same-different tasks. The results support the suggestion that the enhanced discrimination observed after intermixed preexposure is due to increases in the salience of the unique elements.

Discrimination Learning↗
PubMed2005

Improved description of the surface acidity of eta-alumina.

The surface acidity of an activated eta-alumina catalyst has been investigated by examining the interaction of pyridine with the catalyst by a combination of gravimetric and volumetric adsorption isotherms, infrared spectroscopy (diffuse reflectance and transmission), inelastic neutron scattering spectroscopy, temperature-programmed desorption spectroscopy, and gravimetric desorption experiments. From previous work, this surface was considered to contain three types of Lewis acid sites of increasing acidity: weak, medium, and strong. However, this multitechnique approach reveals the presence of an additional type of Lewis acid site. Although the traditional pyridine ring modes about 1580 cm(-1) are consistent with previous studies, temperature-programmed infrared spectroscopy of the surface hydroxyl groups and mass-selective temperature-programmed desorption experiments establish that the medium-strength Lewis acid category can be subdivided into two components. In this way, the surface structure of the activated catalyst is redefined as comprising (i) weak, (ii) medium-weak, (iii) medium-strong and (iv) strong Lewis acid sites. The (O-H) stretching mode of surface hydroxyl groups provides information on the local structure of the distinct sites, and schematic descriptions for these sites are proposed.

Journal Article↗
PubMed2005

GATA1 mutation and trisomy 21 are required only in haematopoietic cells for development of transient myeloproliferative disorder.

Trisomy 21 [Down's syndrome (DS)] and mutations in transcription factor GATA1 predispose neonates to a transient myeloproliferative disorder (TMD) and/or acute megakaryocytic leukaemia (AMKL). The role of trisomy 21 in their pathogenesis is unclear. We previously reported two rare neonates without DS who had TMD, one of whom progressed to AMKL. Trisomy 21 was detected only in blood cells at presentation with TMD/AMKL and disappeared with disease resolution. We now show that the blood cells at presentation of TMD harboured GATA1 genomic DNA mutations, suggesting a requirement for trisomy 21 in haematopoietic cells, rather than other cell types, for development of TMD/AMKL.

Base Sequence↗
PubMed2005

Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: results of the Medical Research Council ALL 97 trial.

We report on the outcome of children with Philadelphia positive acute lymphoblastic leukaemia (Ph+ ALL) treated on the UK Medical Research Council (MRC) trial for childhood ALL, MRC ALL 97, between January 1997 and June 2002. Forty-two (2.3%) patients were Ph+. Nineteen (45%) had <25% blasts in bone marrow (BM) within the first 2 weeks of treatment and were defined as a good response group (GRG), the others as a poor response group (PRG). Thirty-six (86%) achieved first complete remission (CR1) at the end of induction, of which 28 underwent BM transplantation (BMT). The median follow-up was 42 months (range, 21-84). The 3-year event-free survival (EFS; 52%, 95% CI, 36-66%) was a considerable improvement on the previous MRC UKALL XI trial (27%). EFS for the GRG and PRG were 68% (43-84%) and 39% (18-59%), respectively (P = 0.03); presenting white cell count <50 x 10(9)/l (P = 0.02) was predictive for overall survival. Changes in the MRC ALL97 trial within the study period resulted in some Ph+ ALL receiving daunorubicin and either prednisolone or dexamethasone during induction. Though the use of daunorubicin during induction was not a prospective study question, EFS was significantly better for those whose induction included this drug (P = 0.02). Steroid randomization was not stratified for Ph+ ALL patients and was not predictive for EFS. BMT in CR1 appeared to reduce the risk of a subsequent BM relapse. These results show significant improvement on previous MRC trials; future therapeutic strategies should include early intensive therapy and BMT in CR1.

Adolescent↗
PubMed2005

Acquired distinctiveness and equivalence in human discrimination learning: evidence for an attentional process.

In a first stage of training, participants learned to associate four visual cues (two different colors and two different shapes) with verbal labels. For Group S, one label was applied to both colors and another to both shapes; for Group D, one label was applied to one color and one shape, and the other label to the other cues. When subsequently required to learn a task in which a given motor response was required to one of the colors and one of the shapes, and a different response to the other color and the other shape, Group D learned more readily than Group S. The task was designed so that the associations formed during the first stage of training could not generate differential transfer to the second stage. The results are consistent, however, with the proposal that training in which similar cues are followed by different outcomes will engage a learning process that boosts the attention paid to features that distinguish these cues.

Association Learning↗
PubMed2003

The role of biopsy in the diagnosis of renal tumors of childhood: Results of the UKCCSG Wilms tumor study 3.

BACKGROUND: The United Kingdom Children's Cancer Study Group (UKCCSG) Wilms Tumor Study 3 has adopted preoperative chemotherapy for Wilms tumors (WT), but required prechemotherapy biopsy for histologic diagnosis. The aims of this review were to assess the usefulness and safety of prechemotherapy biopsy and to compare histologic features of WT before and after chemotherapy. PROCEDURE: There were 286 eligible patients but only 241 biopsies and 226 nephrectomy case slides were submitted for panel review. The presence of different histologic components of WT before and after chemo therapy was retrospectively assessed. RESULTS: Among the 241 cases, the biopsy material in 9 (4%) was not diagnostic, in 28 (12%) that were clinically and radiologically consistent with WT, the biopsy revealed tumors other than WT, and in the remaining 204 (85%) WT was confirmed. Of 188 WT suitable cases, blastema was found in 89% of tumors at biopsy, but in only 50% at nephrectomy; the remainder were either completely necrotic (17%) or showed only epithelial and/or stromal elements (33%). Of 182 children who had percutaneous cutting needle biopsy (PCNB), a fall in haemoglobin (20% of cases) and local pain (19%) were the most common complications. One child required emergency nephrectomy due to massive intratumoral bleeding, another had tumor rupture and subsequently died, and a third developed a needle track recurrence 8 months after the biopsy. CONCLUSIONS: A number of renal tumors (12%) can have the correct histologic diagnosis made by PCNB. Preoperative chemo therapy markedly decrease in the number of samples with preserved blastema. The morbidity associated with PCNB is small. Needle biopsy of any renal mass prior to initiation of chemotherapy is recommended.

Biopsy, Needle↗
PubMed2003

Acquired equivalence and distinctiveness in human discrimination learning: evidence for associative mediation.

In the first stage of Experiments 1-3, subjects learned to associate different geometrical figures with colors or with verbal labels. Performance in Stage 2, in which the figures signaled which of 2 motor responses should be performed, was superior in subjects required to make the same response to figures that had shared the same Stage 1 associate. A third stage of testing showed that the events used as associates in Stage 1 were capable of evoking the motor response trained in Stage 2, an outcome predicted by an associative interpretation of such transfer effects. Experiment 4 provided evidence that the relevant associations can be effective in controlling motor responding even when subjects report an antagonistic relationship between events.

Adolescent↗
PubMed2003

Intraocular relapse of childhood acute lymphoblastic leukaemia.

Relapse of childhood acute lymphoblastic leukaemia (ALL) involving the eye is a rare but challenging problem. Twenty cases occurred in patients treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia XI and ALL97 trials between 1991 and 2001, representing 2.2% of ALL relapses. Seventeen occurred as a first relapse, either in isolation or combined with relapse at another site, and three occurred as a second relapse. All patients with intraocular disease at first relapse were treated with both chemotherapy and radiotherapy, but the doses and protocols used varied. Eleven of these 17 patients are alive and in complete remission with a median follow up of 4 years 2 months from relapse. All 11 children that were treated with a full chemotherapy relapse protocol, together with local radiotherapy have survived. Patients treated with chemotherapy of shorter duration and intensity, despite radiotherapy and/or bone marrow transplantation, did poorly with only one survivor, currently in chronic relapse. Consequently, we suggest that children with eye relapse of ALL be treated with an intensive relapse chemotherapy protocol with local ocular radiotherapy, whether the relapse occurs in isolation or in combination with relapse at another site.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

A GP's duty.

Explore the source record for details and available documents.

Accreditation↗
PubMed2002

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PURPOSE: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. METHODS AND MATERIALS: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. RESULTS: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. CONCLUSION: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Aged↗
PubMed2002

Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the U.K. cancer cytogenetics group and the U.K. Children's Cancer Study Group.

BACKGROUND: Tumor genetic features reported to correlate with adverse outcome in Wilms tumor include karyotype complexity, losses of material from the short arm of chromosome 1 and from the long arms of chromosomes 11, 16 and 22 and gain of material from the long arm of chromosome 1. This study sought to test these associations in a large series of tumors studied by cytogenetic analysis. Identification of markers associated with elevated risk of relapse and fatal outcome could allow more effective treatment stratification at presentation. PROCEDURE: Thirteen member laboratories of the U.K. Cancer Cytogenetics Group provided results from a 12-year period. Karyotype abnormalities were correlated with clinical data (age, tumor stage, and histology) and outcome data provided by the central register of the U.K. Children's Cancer Study Group. RESULTS: Of 127 abnormal karyotypes, 78 included a reputedly "poor prognosis" feature. Univariate survival analysis showed no significant adverse effect for karyotype complexity, 1p loss or 11q loss. The poor outcome of cases with 16q loss was of borderline significance, but this effect was restricted to those tumors with unbalanced translocation der(16)t(1q;16q). The association between relapse risk and gain of 1q material was not significant. Only monosomy 22 was a significant marker of poor outcome in univariate analysis (13 cases showing 50% relapse free survival at 5 years compared to 79% survival for the remaining 114 cases, P = 0.02). In multivariate analysis, significant independent predictors of poor outcome were 1q gain (Hazard Ratio 3.4), stage IV disease (HR 5.0), and monosomy 22 (HR 5.9). CONCLUSIONS: Loss of chromosome 22 identifies high risk Wilms tumors. The prognostic significance of 1q gain, 16q loss and unbalanced translocation der(16)t(1q;16q) is unresolved and warrants further investigation.

Adolescent↗
PubMed2002

HIV prevalence in a gold mining camp in the Amazon region, Guyana.

The prevalence of HIV infection among men in a gold mining camp in the Amazon region of Guyana was 6.5%. This high percentage of HIV infection provides a reservoir for the virus in this region, warranting immediate public health intervention to curb its spread. As malaria is endemic in the Amazon Basin (>30,000 cases/year), the impact of coinfection may be substantial.

Adult↗