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1.  Intra-tumour genetic heterogeneity and poor chemoradiotherapy response in cervical cancer 
British Journal of Cancer  2010;104(2):361-368.
Background:
Intra-tumour genetic heterogeneity has been reported in both leukaemias and solid tumours and is implicated in the development of drug resistance in CML and AML. The role of genetic heterogeneity in drug response in solid tumours is unknown.
Methods:
To investigate intra-tumour genetic heterogeneity and chemoradiation response in advanced cervical cancer, we analysed 10 cases treated on the CTCR-CE01 clinical study. Core biopsies for molecular profiling were taken from four quadrants of the cervix pre-treatment, and weeks 2 and 5 of treatment. Biopsies were scored for cellularity and profiled using Agilent 180k human whole genome CGH arrays. We compared genomic profiles from 69 cores from 10 patients to test for genetic heterogeneity and treatment effects at weeks 0, 2 and 5 of treatment.
Results:
Three patients had two or more distinct genetic subpopulations pre-treatment. Subpopulations within each tumour showed differential responses to chemoradiotherapy. In two cases, there was selection for a single intrinsically resistant subpopulation that persisted at detectable levels after 5 weeks of chemoradiotherapy. Phylogenetic analysis reconstructed the order in which genomic rearrangements occurred in the carcinogenesis of these tumours and confirmed gain of 3q and loss of 11q as early events in cervical cancer progression.
Conclusion:
Selection effects from chemoradiotherapy cause dynamic changes in genetic subpopulations in advanced cervical cancers, which may explain disease persistence and subsequent relapse. Significant genetic heterogeneity in advanced cervical cancers may therefore be predictive of poor outcome.
doi:10.1038/sj.bjc.6605971
PMCID: PMC3031882  PMID: 21063398
heterogeneity; cervical cancer; chemoradiotherapy; array CGH; selection
2.  Occupational injury in a fishmonger with a macular rash, hepatosplenomegaly and pancytopenia 
Journal of Clinical Pathology  2006;59(9):993-994.
A 47‐year‐old fishmonger presented with a history of weight loss and lethargy. On investigation he was found to have myeloma. He presented again before follow up, with a 3‐day history of fever and a maculopapular rash. He was admitted to the haematology ward and treated with broad‐spectrum antibiotics. Blood cultures were found to be positive for Erysipelothrix rhusiopathiae. Penicillin treatment was given, and he made a good recovery. The importance of occupational illness in an already immunocompromised patient and of taking a proper social and occupational history from patients on admission is illustrated through this case.
doi:10.1136/jcp.2005.030221
PMCID: PMC1860486  PMID: 16935976
3.  Radiation treatment waiting times for breast cancer patients in Manitoba, 2001 and 2005 
Current Oncology  2009;16(5):58-64.
Introduction
Our study examined the wait time from ready-to-treat to radiation therapy for cohorts of breast cancer patients requiring adjuvant radiation therapy in 2001 and in 2005 after the implementation of strategies to reduce wait times for radiation treatment. We also examined the overall time from diagnosis to radiation treatment and whether distance from the cancer treatment centre or month of referral had an effect on wait times.
Methods
This population-based retrospective study looked at representative samples of women newly diagnosed with breast cancer in 2001 and 2005. Patients who required radiation treatment to the breast or chest wall were followed from first contact to the start of radiation treatment.
Results
Time from ready-to-treat to first radiation treatment was significantly reduced for patients in 2005 as compared with 2001, regardless of whether chemotherapy was administered before radiation treatment. Time from diagnosis to radiation treatment was not different by year for those who received radiation only. Time from diagnosis to chemotherapy was significantly longer in 2005. No effect of month of diagnosis on wait times was observed.
Interpretation
A significant improvement in the median wait time from ready-to-treat to first radiation treatment was noted from 2001 to 2005. This improvement may be attributable to measures taken to reduce such waits. However, we observed an increase in the median time from diagnosis to referral and from referral to consultation with medical or radiation oncology (or both), so that the overall time from diagnosis to radiation treatment was not different. Although specific intervals related to radiation treatment delivery were improved, the entire trajectory of breast cancer care experienced by patients needs to be considered.
PMCID: PMC2768502  PMID: 19862362
Breast cancer; radiation; wait times
4.  Changing perceptions of weight in Great Britain: comparison of two population surveys 
Objectives To examine changes in public perceptions of overweight in Great Britain over an eight year period.
Design Comparison of data on self perceived weight from population surveys in 1999 and 2007.
Setting Household surveys of two representative samples in Great Britain.
Participants 853 men and 944 women in 1999, and 847 men and 989 women in 2007.
Main outcome measures Participants were asked to report their weight and height and classify their body size on a scale from “very underweight” to “obese.”
Results Self reported weights increased dramatically over time, but the weight at which people perceived themselves to be overweight also rose significantly. In 1999, 81% of overweight participants correctly identified themselves as overweight compared with 75% in 2007, demonstrating a decrease in sensitivity in the self diagnosis of overweight.
Conclusions Despite media and health campaigns aiming to raise awareness of healthy weight, increasing numbers of overweight people fail to recognise that their weight is a cause for concern. This makes it less likely that they will see calls for weight control as personally relevant.
doi:10.1136/bmj.a494
PMCID: PMC2500200  PMID: 18617488
5.  Duplication 2 (q11.2-q21): a previously unreported abnormality 
Journal of Medical Genetics  1995;32(10):825-826.
A 7 year old boy is described with moderate learning disability, facial dysmorphism, and a de novo duplication of chromosome 2 (q11.2-q21). There are few published reports of proximal 2q duplication, and none reporting direct de novo duplication for this exact region.
Images
PMCID: PMC1051712  PMID: 8558566
6.  Prospective evaluation of cell kinetics in head and neck squamous carcinoma: the relationship to tumour factors and survival. 
British Journal of Cancer  1994;69(4):717-720.
Tumour growth rates were measured in 105 patients using in vivo incorporation of bromodeoxyuridine (BrdU) and investigated for any relationship to tumour factors or survival. The median labelling index (LI) was 8.7%, the duration of S-phase (Ts) was 14 h and the potential doubling time (Tpot) was 5.9 days. The labelling index in aneuploid tumours was significantly higher than that in diploid tumours. However the total labelling index (TLI) did not differ significantly between aneuploid and diploid tumours, and so it would seem likely that the difference in LI is due to the dilutional effect of benign tissue upon the calculation of LI in diploid tumours. The total labelling index, duration of S-phase and potential doubling time were not related to the tumour factors examined (site, T stage, N stage, stage grouping). Interim survival analysis was carried out and there was no difference in survival between those patients with high values for TLI, Ts, and Tpot and those with low values.
PMCID: PMC1968830  PMID: 8142259
8.  Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry. 
British Journal of Cancer  1992;65(5):698-702.
The cell kinetics of 82 squamous cell carcinomas of the head and neck were studied by in vivo administration of the thymidine analogue, bromodeoxyuridine (BrdUrd). Ploidy, BrdUrd labelling index (LI), duration of S-phase (Ts), potential doubling time (Tpot) and S-phase fraction (SPF) were measured by flow cytometry on 50 microns paraffin embedded sections. The range of values obtained compared well with other in vivo cell kinetic studies of head and neck cancer. Aneuploid tumours had a significantly higher BrdUrd labelling index and SPF, and a short Tpot than diploid tumours. To validate the use of 50 microns sections for measuring cell kinetic parameters by flow cytometry a comparison of values obtained by 50 microns sections and small blocks of tissue was made. No significant difference was found between the two methods. Reproducibility of values between two consecutive thick sections was also good. We conclude that reproducible cell kinetic measurements can be made in tumour samples using 50 microns sections of BrdUrd labelled tissue.
PMCID: PMC1977390  PMID: 1586597
9.  Admissions to mental handicap hospitals. 
BMJ : British Medical Journal  1991;303(6805):787.
PMCID: PMC1671022  PMID: 1932957
11.  Ploidy as a prognostic indicator in end stage squamous cell carcinoma of the head and neck region treated with cisplatinum. 
British Journal of Cancer  1990;61(5):759-762.
We measured tumour cellular DNA in 102 patients entered into two phase III trials of chemotherapy for end stage squamous carcinoma of the head and neck. The median survival of untreated patients with aneuploid tumours was 55 days compared with 224 days for patients treated with cisplatinum. This difference was highly significant. In contrast the median survival of untreated patients with diploid tumours was 74 days compared with 118 days for treated patients. Although this difference is statistically significant, the increased survival of 6 weeks is of no clinical benefit compared with the prolongation of survival of 6 months in patients with aneuploid tumours. Multivariate analysis showed that the significant predictors of survival were Karnofsky status, response to chemotherapy and ploidy.
PMCID: PMC1971589  PMID: 2337512
12.  Abuse of mentally handicapped adults. 
BMJ : British Medical Journal  1990;300(6718):193.
PMCID: PMC1662191  PMID: 2105809
13.  Abuse of mentally handicapped adults. 
BMJ : British Medical Journal  1989;299(6695):392.
PMCID: PMC1837210  PMID: 2506986
14.  Behaviour of effector cells, synovial fluids, and sera from rheumatoid arthritis patients in antibody-dependent cell-mediated cytotoxicity. 
Annals of the Rheumatic Diseases  1979;38(3):252-256.
Antibody-dependent cell-mediated cytotoxicity (ADCC) was examined in patients with rheumatoid arthritis (RA). The cytotoxicity of peripheral blood leucocytes from patients with RA was similar to that found in normal persons, whereas ADCC was less effective in RA synovial fluid cells. It is possible that the activity in these cells is lower because of immune complexes and other factors being absorbed from the synovial fluid itself. Although patients' sera had little effect on normal peripheral blood leucocytes, synovial fluid from RA patients was markedly inhibitory in ADCC. The degree of inhibition correlated significantly with the clinical status of the patients.
PMCID: PMC1000447  PMID: 485583
15.  Factors influencing in vitro production of colony-stimulating factor by mononuclear leukocytes from humans. 
The purpose of this study was to identify factors that influence the production of colony-stimulating factor by leukocytes of humans. The use of nonadherent light-density bone marrow cells is semisolid agar cultures to assay the concentrations of colony-stimulating factor in the supernatant of monocyte and mononuclear leukocyte cultures made it possible to distinguish between colony-stimulating factor, which stimulates colony-forming cells directly, and monocyte-dependent stimulating activity, which acts indirectly, by increasing the monocyte production of colony-stimulating factor. Colony-stimulating factor was not detectable in the cytosol of monocytes; that detected in culture must, therefore, have been newly synthesized. Synthesis was enhanced independently by heat-inactivated human serum and by semipurified serum fractions enriched with monocyte-dependent stimulating activity. The kinetics of the production of colony-stimulating factor in the presence and absence of monocyte-dependent stimulating activity indicated that the latter facilitated monocyte production of the former. Factors released from neutrophils were shown to reduce the production of colony-stimulating factor and thr proliferation of colony-forming cells and thus may provide a feedback control mechanism limiting the proliferation of neutrophils.
PMCID: PMC1704294  PMID: 316353
16.  Action of inhibitor released from neutrophils and leukemic blast cells. 
The concept that polymorphonuclear leukocytes, or neutrophils, play a role in feedback control of granulopoiesis has been supported by the finding in bone marrow culture studies that mature neutrophils inhibited formation of granulocytic colonies. The study described in this paper was done to investigate the mechanisms involved. With the use of a modified assay it was found that mature neutrophils released factors that reduced the proliferation of colony-forming cells in cultures stimulated by cell-free colony-stimulating factor. In myeloproliferative and myelodysplastic disorders the amount of inhibitor released by the neutrophils varied greatly. Leukemic blast cells also released inhibitor, and in some cases the amount released per cell was greater than the amount released from normal mature neutrophils. The inhibitory factors released from the neutrophils differed from those previously described in the literature in terms of mode of action and apparent molecular size.
PMCID: PMC1818928  PMID: 312135

Results 1-16 (16)