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Biomedical subjects

C Mitchell

Publications and source records attributed to C Mitchell.

At least 19 recordsLinked to original sources
PubMed2007

Influence of 4- and 6-color flow cytometers and acquisition/analysis softwares on the determination of lymphocyte subsets in HIV infection.

BACKGROUND AND OBJECTIVES: Lymphocyte immunophenotyping provides valuable information for the diagnosis and monitoring of patients with cellular immunodeficiencies, such as HIV/AIDS. In this study, we have assessed the influence of 4-color and 6-color flow cytometers, and respective analytical softwares on the enumeration of lymphocytes in HIV infected individuals. METHODS: The expression of various cell surface markers on lymphocytes was measured from the EDTA blood of 66 HIV infected patients on the FACSCalibur (4-color) and FACSCanto (6-color) flow cytometers. Percentage of lymphocytes expressing a particular cell surface marker was analyzed on FACSCalibur using the Cell Quest Pro software (v 5.2), while the analysis on FACSCanto was done using FACSCanto (v 1.0.3) and FACSDiva (v 4.1) softwares respectively. RESULTS: The data shows significantly higher mean CD3 T-cell counts on FACSCalibur, Cell Quest Pro (1,864 +/- 1,044 cells/microl) as compared to FACSCanto (1,840 +/- 1,040 cells/microl) (P < 0.05). The CD4 T-cell counts were also higher on FACSCalibur, Cell Quest Pro (885 +/- 770 cells/microl), and FACSDiva (892 +/- 773 cells/microl) versus FACSCanto (867 +/- 767 cells/microl) (P < 0.05). FACSCalibur, Cell Quest Pro, and FACSDiva showed similar values except for CD8 T-lymphocytes where FACSDiva had significantly lower values (P < 0.05). The B-cell counts were unaffected when either of the instruments or softwares were used, while the natural killer (NK) cells (CD16 + 56 positive cells) showed similar trend like CD3 and CD4 counts with significant differences in the mean cell counts between FACSCalibur, Cell Quest Pro (240 +/- 165 cells/microl), and FACSDiva (238 +/- 163 cells/microl) versus FACSCanto with higher NK cell counts (260 +/- 176 cells/microl). CONCLUSIONS: The enumeration of lymphocyte subsets was comparable between FACSCalibur, Cell Quest Pro, and FACSDiva, based analysis and it was significantly different than FACSCanto software based analysis. Our observations suggest that FACSDiva software should be preferred over the FACSCanto software for immunophenotyping on FACSCanto flow cytometer and the laboratories should report the instrument and software used for the specimen analysis while reporting immunophenotyping results.

Antigens, Surface↗
PubMed2006

Rectal adenocarcinoma following cranio-spinal radiotherapy for cerebellar medulloblastoma.

The authors present a case of a 16-year-old female diagnosed with rectal adenocarcinoma 10 years after receiving cranio-spinal radiotherapy for a cerebellar medulloblastoma. While the risk of a second malignancy is recognised to be increased in children previously treated with radiotherapy, rectal adenocarcinoma is a rare presentation. A child presenting with symptoms of weight loss and a change in bowel habit in a patient who has previously received radiotherapy should alert practitioners to the possibility of a colorectal malignancy.

Adenocarcinoma↗
PubMed2005

Perinatal and reproductive factors: a report on haematological malignancies from the UKCCS.

The United Kingdom Childhood Cancer Study was designed to examine the potential aetiological role of a range of perinatal and reproductive factors. Our use of clinical records permitted a more exact characterisation of reproductive events than is possible in investigations that rely on self-reporting; and the increased specificity with which antecedent events were measured produced more precise risk estimates, albeit ones based on progressively smaller numbers. Information on the conduct of this component of the study and results for 1485 children with haematological malignancies and 4864 controls are presented. The 'find' rate for obstetric records was high at 86% for cases, with 81% having information on both matched controls. Associations were seen for severe hyperemesis (Odds Ratio=3.6, 95%Confidence Interval=1.3-10.1, for all leukaemias), polyhydramnios (OR=4.0, 95%CI=1.5-10.3, for acute myeloid leukaemia (AML)), anaemia (haemoglobin <10 g, OR=2.6, 95%CI=1.7-4.1, for AML), and pre-eclampsia (OR=1.7, 95%CI=1.1-2.7, for non-Hodgkin's lymphoma). Babies who developed leukaemia were heavier at birth (>4000 g, OR=1.2, 95%CI=1.0-1.4), as were their older siblings (>4000 g, OR=1.4, 95%1.0-1.9). Mothers' whose children developed common B-cell precursor acute lymphoblastic leukaemia (ALL) were more likely to have had a previous molar pregnancy (OR=5.2, 95%CI=1.9-14.7). Gender-specific analysis revealed that findings often differed markedly for boys and girls; and, in common with other reports, strong associations with Down's syndrome were seen for both ALL and AML.

Acute Disease↗
PubMed2005

Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults.

BACKGROUND: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. AIM: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. METHODS: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. RESULTS: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV(1)) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 microg (three of 11, 73%) compared to 2000 microg or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). CONCLUSIONS: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.

Administration, Inhalation↗
PubMed2005

Gastrointestinal stromal tumour treated with neoadjuvant imatinib.

This report describes a case of unresectable primary gastrointestinal stromal tumour (GIST) treated with imatinib on a neoadjuvant basis, before subsequent successful surgical resection. After six months of imatinib, computed tomography and positron emission tomography imaging demonstrated a significant size reduction and complete metabolic response to treatment, rendering the tumour resectable. Mutational analysis showed an activating KIT mutation in exon 11. The pathological appearance of the resected tumour was heterogeneous with extensive necrosis, cystic and myxoid change, extensive hypocellularity, and patchy foci of residual viable tumour. The implications for this management option of radiological, pathological, and molecular assessment are discussed.

Aged↗
PubMed2005

An evaluation of the Child Perceptions Questionnaire in the UK.

OBJECTIVE: To assess the reliability and validity of the Child Perceptions Questionnaire (CPQ11-14), an oral health related quality of life measure for 11-14 year old children, for use in the UK. BASIC RESEARCH DESIGN: Cross-sectional questionnaire and clinical analytical study. CLINICAL SETTING: Orthodontic and paediatric dentistry clinics at a dental hospital and one general dental practice. PARTICIPANTS: Eighty-nine children between 11 and 14 years of age attending for an examination. MAIN OUTCOMES MEASURES: The children were invited to complete the CPQ11-14, global oral health and impact on life overall ratings. Clinical data on caries status, malocclusion and presence of dental opacities and gingivitis were collected. CPQ11-14 was summarised as the total score (sum of the item codes) and the number of impacts reported often or every day. RESULTS: The Cronbach's alpha for the total scale was 0.87 and ranged from 0.59 to 0.83 for the subscales indicating acceptable internal consistency. The intraclass correlation coefficient on repeated application of the measure was 0.83 (95% CI = 0.76-0.90) suggesting almost perfect agreement. Summary measures of CPQ11-14 correlated with the global oral health rating indicating acceptable criterion validity. Impact on life overall was related to all summary measures of CPQ11-14. Number of impacts correlated with the total number of missing teeth and missing teeth due to caries. No other relationships between clinical and CPQ11-14 data were apparent. CONCLUSION: The CPQ11-14 shows acceptable reliability, criterion and construct validity in relation to life overall. Relationships with clinical data were more tenuous. If this measure is to be used to compare the impacts of oral diseases in similar settings in the UK a large sample will be required.

Adolescent↗
PubMed2004

Sediments, nutrients and pesticide residues in event flow conditions in streams of the Mackay Whitsunday Region, Australia.

The Mackay Whitsunday region covers 9000 km(2) in northeastern Australia. A study of diffuse pollutants during high flow events was conducted in coastal streams in this region. Sampling was conducted in the Pioneer River catchment during a high flow event in February 2002 and in Gooseponds Creek, Sandy Creek and Carmila Creek in March 2003. Concentrations of five herbicides; atrazine (1.3 microg l(-1)), diuron (8.5 microg l(-1)), 2,4-D (0.4 microg l(-1)), hexazinone (0.3 microg l(-1)) and ametryn (0.3 microg l(-1)) and high concentrations of nutrients (total nitrogen 1.14 mg l(-1), total phosphorus 0.20 mg l(-1)) and suspended sediments (620 mg l(-1)) were measured at Dumbleton Weir on the lower reaches of the Pioneer River. Drinking water guidelines for atrazine and 2,4-D were exceeded at Dumbleton Weir, low reliability trigger values for ecosystem protection for diuron were exceeded at three sites and primary industry guidelines for irrigation levels of diuron were also exceeded at Dumbleton Weir. Similar concentrations were found in the three smaller streams measured in 2003. Herbicides and fertilisers used in sugarcane cultivation were identified as the most likely major source of the herbicide residues and nutrients found.

Agriculture↗
PubMed2004

Indicators of biofilm development and activity in constructed wetlands microcosms.

Methods to measure protein, exopolysaccharide, viable cell number and INT reduction activity were tested on biofilm growing in a wastewater batch reactor. They were shown to be meaningful indicators of biofilm growth and correlated well with each other. Protein, exopolysaccharide, viable cells and INT reduction rates increased linearly over time. Viable cell number exhibited strong linear correlations with protein (R2= 0.98) and exopolysaccharide (R2= 0.99) while INT reduction rate was somewhat less well correlated (R2= 0.90). Our results indicate production rates of 0.91 x 10(-7) microg EPS per viable cell and 1.0 x 10(-7) microg protein per viable cell. Protein and polysaccharide specific INT reduction rates decreased by approximately 50%, whereas viable cell specific INT reduction rates decreased by 65% and the protein to polysaccharide ratio stayed relatively constant at between 1.1 and 1.2 as the biofilm developed. Measurement of protein, polysaccharide, viable cells and INT reduction rate at depth within the bioreactor showed that they were concentrated in the top 1cm of the influent end of the reactor and each decreased to a base level within 4.5 cm of the inlet. Protein to polysaccharide ratios increased with depth in the reactor and the specific INT reduction rates were maximal at 4.5 cm depth. The results indicate that the biomass can take upwards of 100 days to stabilize during batch (fill and draw) operation of subsurface wetlands and that the relative ratios of biomass components remain relatively constant during biofilm growth. Also, it appears that filtration of suspended solids results in biomass concentration at the inlet to the wetland.

Biofilms↗
PubMed2003

Older age is an adverse prognostic factor in stage I, favorable histology Wilms' tumor treated with vincristine monochemotherapy: a study by the United Kingdom Children's Cancer Study Group, Wilm's Tumor Working Group.

PURPOSE: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms' tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. PATIENTS AND METHODS: During two consecutive trials of the United Kingdom Children's Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms' tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. RESULTS: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P =.001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P =.01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P =.66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). CONCLUSION: Treatment for stage I FH Wilms' tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms' tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.

Adolescent↗
PubMed2003

Measurements of the shear Alfvén wave dispersion for finite perpendicular wave number.

Measurements of the dispersion relation for shear Alfvén waves as a function of the perpendicular wave number are reported for the regime in which V(A) approximately V(Te). By measuring the parallel phase velocity of the waves, the measurements can be compared directly to theoretical predictions of the dispersion relation for a parameter regime in which particle kinetic effects become important. The comparison shows that the best agreement between theory and experiment is achieved when a fully complex, warm plasma dispersion relation is used.

Journal Article↗
PubMed2003

Formoterol (Foradil) and medium-high doses of inhaled corticosteroids are more effective than high doses of corticosteroids in moderate-to-severe asthma.

This double-blind, randomised, multi-centre, parallel-group study compared the effect of adding Foradil (formoterol fumarate) to existing medium-high doses of inhaled corticosteroids (ICS) with that of doubling the dose of ICS in patients with sub-optimally controlled asthma. After a run-in period, 203 patients with moderate-to-severe asthma who remained symptomatic despite treatment with 500 microg beclomethasone twice daily, were randomised to receive either 12 microg formoterol twice daily (Foradil Aerolizer), Novartis) in addition to beclomethasone 500 microg twice daily, or beclomethasone 1000 microg twice daily and placebo for 12 weeks. The primary efficacy variable was mean morning pre-medication peak expiratory flow (PEF) during the last seven days of treatment. The difference in PEF between treatments was 27.78 l/min in favour of the formoterol/beclomethasone combination (95% CI 13.42, 42.14 l/min, p=0.0002, intention-to-treat population). Significant differences in the urinary cortisol/creatinine ratio between treatment groups at 12 weeks (p=0.001) indicated suppression of the hypothalamic-pituitary-adrenal axis in the patients on beclomethasone 1000 microg twice daily. The addition of formoterol 12 microg twice daily to beclomethasone in patients with asthma who were poorly controlled with beclomethasone 500 microg twice daily was more effective than doubling the ICS dose and resulted in less suppression of the hypothalamic-pituitary-adrenal axis.

Administration, Inhalation↗
PubMed2003

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases.

This study identifies multiple copies of the AML1 gene on a duplicated chromosome 21, dup(21), as a recurrent abnormality in acute lymphoblastic leukemia (ALL). Clusters of AML1 signals were visible at interphase by fluorescence in situ hybridization (FISH). In metaphase, they appeared tandemly duplicated on marker chromosomes of five distinct morphological types: large or small acrocentrics, metacentrics, submetacentrics or rings. The markers comprised only chromosome 21 material. Karyotypes were near-diploid and, besides dup(21), no other established chromosomal changes were observed. A total of 20 patients, 1.5 and <0.5% among consecutive series of childhood and adult ALL respectively, showed this phenomenon. Their median age was 9 years, white cell counts were low and all had a pre-B/common immunophenotype. Although this series is not the first report of this abnormality, it is the largest, permitting a detailed description of the variety of morphological forms that duplicated chromosome 21 can assume.

Adolescent↗
PubMed2002

A pilot study of short-course intensive multiagent chemotherapy in metastatic and axial skeletal osteosarcoma.

BACKGROUND: This pilot study was undertaken to assess the feasibility, toxicity and response to short-course multiagent chemotherapy followed by high-dose chemotherapy (HDC) in patients with poor prognosis osteosarcoma. PATIENTS AND METHODS: A total of 30 patients entered the study. Chemotherapy consisted of four blocks of multiagent chemotherapy administered sequentially over a short period in a dose-intensive manner. This therapy was followed by HDC which consisted of carboplatin at an AUC8 x 3 days, etoposide 400 mg/m(2) x 3 days and cyclophosphamide 60 mg/kg x 2 days. RESULTS: A total of 227 cycles of chemotherapy were administered. The main toxicity (for blocks 1-4) was haematological. There were two treatment-related deaths: one post HDC due to sepsis and one during surgery. High-dose chemotherapy was administered to 11 patients (10 with extremity tumours and only one with a pelvic tumour). Twenty-seven patients underwent surgery to the primary. Histological response was assessed in 23 patients. Seven patients (30%) had >90% necrosis. Eight patients underwent pulmonary metastatectomy. The median survival time for the whole group was 16 months. The 2- and 3-year survival rates were 50% and 21% for those with extremity tumours and 19% and 13% for those with axial skeletal tumours. CONCLUSIONS: Dose-intensive multiagent chemotherapy though feasible in the group of patients with extremity tumours did not significantly improve the treatment outcome compared with conventional relapse therapy. Inferior survival rates in the axial skeletal group are attributed to less intensive treatment and poor local tumour control.

Adolescent↗