Biomedical subjects

Colin Pritchard

Publications and source records attributed to Colin Pritchard.

At least 19 recordsLinked to original sources

PubMed2006

An analysis of suicide and undetermined deaths in 17 predominantly Islamic countries contrasted with the UK.

BACKGROUND: Suicide is expressly condemned in the Qu'ran, and traditionally few Islamic countries have reported suicide. Undetermined deaths are classified by the World Health Organization (WHO) as Other Violent Deaths (OVD) in ICD-9, or Other External Causes (OEC) in ICD-10. It has been suggested that to avoid under-reporting of suicides, both formal suicide verdicts and OVD should be considered together because OVD may contain 'hidden' suicides. METHOD: The latest WHO mortality data, by age and gender, were analysed and tested by chi2 tests. Levels of suicide and OVD in 17 Islamic countries were examined and contextually compared with UK rates. The regional Islamic cultural differences in Middle Eastern, South Asian, European Islam countries and those of the former Union of Socialist Soviet Republics (FUSSR) were analysed separately to test the hypotheses that there would be no difference between regional suicide and OVD rates per million (pm) and 17 Islamic countries and UK rates. RESULTS: Suicide rates were higher for males than females, and 'older' (65+) higher than 'younger' (15-34) rates in every country reviewed. The rate for Middle Eastern males was 0-36 pm, South Asian 0-12 pm, European 53-177 pm and FUSSR 30-506 pm, with three countries exceeding the UK rate of 116 pm. The Western male average OVD rate was 22 pm; the UK 55 pm rate was highest. Middle Eastern OVD was 1-420 pm, South Asian 0-166 pm, European 1-66 pm and FUSSR 11-361 pm. OVD rates in 10 Islamic countries were considerably higher than the Western average and eight had OVD rates considerably higher than their suicide rates. CONCLUSIONS: Islamic suicide rates varied widely and the high OVD rates, especially the Middle Eastern, may be a repository for hiding culturally unacceptable suicides.

Adolescent↗

PubMed2006

Monitoring left ventricular function in adults receiving anthracycline-containing chemotherapy.

AIMS: To assess prospectively (1) the incidence of early anthracycline-induced cardiotoxicity; (2) the best predictor for identifying individuals at risk of developing functional cardiotoxicity; and (3) the most sensitive standard echocardiographic measure for the detection of anthracycline-induced changes in left ventricular (LV) function. METHODS: Sixty-seven consecutive patients (45 male, mean age 50+/-18 years) requiring doxorubicin-containing chemotherapy were enrolled. Clinical and echocardiographic assessments occurred before they received any anthracycline, after low-dose anthracyclines and 1-3 months after completion of their chemotherapy. RESULTS: Twenty six percent of patients without significant pre-existing cardiac disease developed cardiotoxicity. The parameter that best predicted the development of functional cardiotoxicity was the change in EF between baseline and low dose with an area under the curve of 0.92. The Tei index detected declines in LV function earlier in the course of treatment with anthracyclines and to a greater significance than any other standard echocardiographic measurement but did not predict functional cardiotoxicity. CONCLUSIONS: All patients receiving potential cardiotoxic chemotherapy should be under the care of a cardiologist and have their EF monitored closely.

Adolescent↗

PubMed2006

The contributions of normal variation and genetic background to mammalian gene expression.

BACKGROUND: Qualitative and quantitative variability in gene expression represents the substrate for external conditions to exert selective pressures for natural selection. Current technologies allow for some forms of genetic variation, such as DNA mutations and polymorphisms, to be determined accurately on a comprehensive scale. Other components of variability, such as stochastic events in cellular transcriptional and translational processes, are less well characterized. Although potentially important, the relative contributions of genomic versus epigenetic and stochastic factors to variation in gene expression have not been quantified in mammalian species. RESULTS: In this study we compared microarray-based measures of hepatic transcript abundance levels within and between five different strains of Mus musculus. Within each strain 23% to 44% of all genes exhibited statistically significant differences in expression between genetically identical individuals (positive false discovery rate of 10%). Genes functionally associated with cell growth, cytokine activity, amine metabolism, and ubiquitination were enriched in this group. Genetic divergence between individuals of different strains also contributed to transcript abundance level differences, but to a lesser extent than intra-strain variation, with approximately 3% of all genes exhibiting inter-strain expression differences. CONCLUSION: These results indicate that although DNA sequence fixes boundaries for gene expression variability, there remain considerable latitudes of expression within these genome-defined limits that have the potential to influence phenotypes. The extent of normal or expected natural variability in gene expression may provide an additional level of phenotypic opportunity for natural selection.

Animals↗

PubMed2006

Increased expression of osteopontin contributes to the progression of prostate cancer.

Osteopontin is a secreted glycosylated phosphoprotein known to be involved in numerous physiologic functions and associated with the late stages of various cancers. We used preneoplastic and neoplastic mouse models of prostate cancer to determine the onset of elevated expression of osteopontin in the development of this disease. Osteopontin alterations occurred early in the disease with dysregulated expression observed in lesions of low-grade prostatic intraepithelial neoplasia (PIN). Over time, osteopontin expressing dysplastic cells seemed to increase in number in high-grade PIN and increased further in adenocarcinoma, and in metastasis, almost all of the cancer cells immunohistochemically stained positive for osteopontin overexpression. We examined the biological properties of human prostate cancer cell lines LNCaP and PC-3, in which osteopontin overexpression was achieved via lentiviral gene transduction. Evidence was obtained that osteopontin could contribute to a proliferative advantage in both cell types, although more significantly in LNCaP than PC-3. Osteopontin also influenced their in vitro invasive ability, and again, most strikingly in the weakly oncogenic LNCaP. Furthermore, excess osteopontin induced the LNCaP cells to acquire a strong intravasation potential in vivo in the chicken embryo chorioallantoic membrane assay for blood vessel penetration. These results establish a correlation between an increased gradient of osteopontin expression throughout the stages of murine prostate cancer, beginning from the preneoplastic lesions to distant metastases that suggests a proliferative and invasive advantages to those prostate tumor cells overexpressing osteopontin. Together, these findings support a strategy designed to target osteopontin in the context of prostate cancer therapy.

Adenocarcinoma↗

PubMed2006

The Tei index identifies a differential effect on left and right ventricular function with low-dose anthracycline chemotherapy.

OBJECTIVE: We sought to study the relative effect on left ventricular (LV) and right ventricular (RV) function of low-dose anthracycline-containing chemotherapy regimes. METHODS: A total of 23 patients (mean age 48 +/- 20 years) underwent echocardiographic examinations before any anthracycline had been administered and then after low-dose anthracycline (doxorubicin 50-125 mg/m2). The Tei index was used to compare the relative effects on RV and LV function. RESULTS: Anthracycline administration was significantly associated with an increase in the LV Tei index (0.38 +/- 0.12 vs 0.46 +/- 0.16, P = .02). There was no significant change in the RV Tei index (0.19 +/- 0.10 vs 0.20 +/- 0.10, P = .72). Comparing the relative effect on global LV and RV function the change in LV Tei was significantly greater than the change in RV Tei (0.07 +/- 0.13 vs 0.01 +/- 0.09, P = .044). CONCLUSIONS: Low-dose anthracycline administration has a significant negative impact on LV function but does not affect RV function.

Adolescent↗

PubMed2006

Suicide in the major Western countries 2000-2002: the violent deaths of September 11, 2001.

Following the September 11th 2001 atrocity, Western Government policies focused more on 'defense,' which undermines Government's commitment to reducing suicide. Annual US and major Western countries suicides were compared with '9/11' deaths to highlight the extent of mortality associated with mental disorder, homicide and road deaths are reviewed for contrast. The 3,074 fatalities of 9/11 are set against the US three year annual average 29,691 suicides, 17,077 homicides and 47,775 road deaths, thus every two weeks more US citizens died violently than on 9/11. In the majority of countries, there were more suicides than 9/11 victims, with suicides exceeding the 9/11 atrocity 18 times in Russia, nine in Japan and the US and three times in France and Germany. Annual suicides compared with terrorist violence should inform policy.

Australia↗

PubMed2005

Changing patterns of suicide in a poor, rural county over the 20th century: a comparison with national trends.

Rural suicide rates have been shown to be disproportionately high in several countries. This study compares suicide rates in Cornwall with the rest of England and Wales over a 90-year period (1911-2001). Age and sex standardised mortality ratios were calculated for suicide and undetermined death for Cornwall standardised to England and Wales. From 1911 until the start of the Second World War, suicide rates were lower in Cornwall than England and Wales. Since the 1960s suicide rates in Cornwall have risen significantly above England and Wales. We have shown that the suicide rate in a poor, rural area has increased disproportionately compared to England and Wales over the last 35 years. This change has occurred in both sexes. Prior to this period the suicide rate was lower or about the same as that in England and Wales.

Adolescent↗

PubMed2005

Comparison of suicide in people aged 65-74 and 75+ by gender in England and Wales and the major Western countries 1979-1999.

BACKGROUND: The factors most strongly associated with suicide are age and gender--more men than women, and, more people over 65 kill themselves. As a number of Governments have targets to reduce suicide levels we compare elderly suicide rates over a 20-year period in England and Wales. And the major Western countries focusing upon age and gender. METHOD: WHO mortality data were used to calculate three-year average General Population Suicide Rates (GPSR) for 1979-1981 to 1997-1999 and rates of people aged 65-74 and 75+ suicide by gender to provide ratios of change and a statistical comparison of England and Wales and the Major Western countries over the period. RESULTS: Male GSPR: '65-74' suicide ratios fell significantly in six countries and in three for the '75+'. Female GSPR: '65-74' suicide ratios fell in every country except Spain. Proportionately, there were more suicides in the over 65s in countries with an 'extended family' tradition, Spain, Italy, Germany, France and Japan, than in the five 'secular' countries. England and Wales male '65-74' suicide fell significantly more than Canada, France, Germany, Italy, Japan, Spain, Netherlands and the USA, and did significantly better than the other countries for all female senior citizen suicides. CONCLUSION: Suicide of the over-65s has improved in seven countries, especially in England and Wales, who had the greatest proportional reduction, which reflects well upon the psycho-geriatric and community services. However, in all countries, male 65-74 rates did not match the female out so extra efforts are needed to improve male rates.

Age Distribution↗

PubMed2005

Differential suicide rates in typologies of child sex offenders in a 6-year consecutive cohort of male suicides.

Earlier research identified 3 typologies of Child Sex Offenders [CSO] with high rates of suicide. To test this finding suicide rates of 3 types of CSO were compared in a 6-year cohort of regional suicides. All male suicides were identified from Coroners" inquest files and CSO data drawn from police records to calculate CSO suicide rates. The results show that suicide in "Multi-criminal" CSO is 12 times higher than the general population but not statistically significantly. Two significant results were "Sex Only" CSO suicides were 183 times the general population and 15 times the Multi-criminal CSO rates, with no suicides amongst the Violent CSO's. Implications for suicide prevention and child protection are presented.

Adult↗

PubMed2004

Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation.

Bone and bone marrow are closely aligned physiologic compartments, suggesting that these tissues may represent a single functional unit with a common bone marrow progenitor that gives rise to both osteoblasts and hematopoietic cells. Although reports of multilineage engraftment by a single marrow-derived stem cell support this idea, more recent evidence has challenged claims of stem cell transdifferentiation and therefore the existence of a multipotent hematopoietic/osteogenic progenitor cell. Using a repopulation assay in mice, we show here that gene-marked, transplantable marrow cells from the plastic-nonadherent population can generate both functional osteoblasts/osteocytes and hematopoietic cells. Fluorescent in situ hybridization for the X and Y chromosomes and karyotype analysis of cultured osteoblasts confirmed the donor origin of these cells and excluded their generation by a fusion process. Molecular analysis demonstrated a common retroviral integration site in clonogenic hematopoietic cells and osteoprogenitors from each of seven animals studied, establishing a shared clonal origin for these ostensibly independent cell types. Our findings indicate that the bone marrow contains a primitive cell able to generate both the hematopoietic and osteocytic lineages. Its isolation and characterization may suggest novel treatments for genetic bone diseases and bone injuries.

Animals↗

PubMed2004

'Coalition-In-Iraq' countries 'internal' civil violent deaths compared to the USA 'external' violence of September 11th 2001.

BACKGROUND: The atrocity of 9/11 exemplified 'external' caused civil violent deaths, which have major policy implications for the countries contributing armed forces to the 'Coalition-In-Iraq' [C.I.I]. C.I.I Government's resources for perennial 'internal' violent deaths (suicide, homicide and road), are likely to be threatened by alternative priorities. C.I.I 'internal' deaths are compared with those of 9/11 to provide information to determine relative risks. MATERIAL/METHODS: To uniformly compare mortality between countries we utilise the most recent WHO mortality data, taking the latest three years 1997-1999 and calculating an average annual number and rate of 'internal' deaths in each country, these are compared with the 9/11 fatalities, calculating a proportional ratio, as an indicator of differential damage to families and society. RESULTS: USA 'external' deaths were 3,074 people and annual average suicides were 30,966. Total 'internal' deaths exceeded 'external' more than 30 times. Every fortnight there are more USA 'internal' violent deaths than on 9/11. Except Australia and Bulgaria, every country had more suicides than died on 9/11. Apart from Bulgaria, total 'internal' deaths exceeded the 'external' toll in all other CAI countries- by 14 times in Japan; 6 in Republic of Korea, 4 in Italy, 3 in Spain and the UK, twice in Canada and 1.5 times in Australia. CONCLUSIONS: The extent of 'internal' civil violent deaths, such as suicide, highlight the perennial pressures upon psychiatric services and the need to defend resources at a time of competing priorities.

Cause of Death↗

PubMed2004

Comparison of cohorts of elective and emergency neurosurgical patients: psychosocial outcomes of acoustic neuroma and aneurysmal sub arachnoid hemorrhage patients and carers.

OBJECTIVES: To compare the psychosocial outcomes of cohorts of elective [Acoustic Neuroma (AN)] and emergency [Aneu-rysmal Sub Arachnoid Hemorrhage (ASAH)] Neurosurgical patients and carers. METHODS: The standardized Wessex Patient Carer Questionnaire was designed with patients and carers and provided psychosocial and economic outcome data following elective or emergency surgery. Clinical data on size of tumor and size of bleed, respectively, were extracted from Consultant notes. RESULTS: Both cohorts were generally satisfied with neurosurgical in-patient care but both suffered high-economic costs and were predominately very dissatisfied with community care. There were significant psychosocial differences between elective and emergency patients, and despite greater relative physical disability among elective patients, it was the emergency cohort who had worse psychosocial outcomes. CONCLUSIONS: Despite many common psychosocial features, the differences between the cohorts were mainly psychological rather than physiological, because of greater 'post-traumatic-stress-reaction' in the emergency cohort, indicating the need for appropriate psychosocial care immediately after neurosurgery to reduce unnecessary distress and costs to patients, carers, and community.

Caregivers↗

PubMed2004

Cost-benefit analysis of an integrated approach to reduce psychosocial trauma following neurosurgery compared with standard care: two-year prospective comparative study of enhanced specialist liaison nurse service for aneurysmal subarachnoid hemorrhage (ASAH) patients and carers.

BACKGROUND: Dysfunctional psychosocial stress often follows standard treatment for aneurysmal subarachnoid hemorrhage (ASAH). An enhanced Specialist Liaison Nurse (SLN) service sought to reduce this stress in a 2-year comparative prospective study, and was designed to determine if such a service would be cost-effective? METHOD: Clinical data based on consultant notes, included Glasgow Coma Scale (GCS) and high-risk bleed score. Psychosocial outcomes used a standardized patient/carer designed questionnaire to compare outcomes of the SLN cohort (n = 184) with retrospective 18/12 control ASAH cohort (n = 142). Costs-benefits analysis identified savings in reduced need for subsequent medical care, time-off-work, and contributions to the economy. RESULTS: The cohorts were socio-clinically well matched; 54% aged less than 55 years, 83% were middle-class and 32% had children still in school; 65% of SLN patients had high risk bleeds, and 81% were Grade 1 and 2 on the G.C.S. The SLN patients and carers had statistically significantly reduced psychosocial trauma compared to controls, with early and easy accessibility being the key to success of SLN. Net savings of $280,000 per annum at 2003 prices, from reduced time-off work, re-admissions and saved medical time. Prospectively, more than $3.03 million is added to the national economy by the 80% of employed patients returning to work. CONCLUSIONS: We conclude that an integrated ASAH treatment yields major psychosocial and economic benefits. Dysfunctional stress after an ASAH is not inevitable in the majority of patients. High-technology neurosurgery is not just a public cost but also improves and saves lives and generates revenue.

Adult↗

PubMed2003

Expressed sequence tag profiling identifies developmental and anatomic partitioning of gene expression in the mouse prostate.

BACKGROUND: The prostate gland is an organ with highly specialized functional attributes that serves to enhance the fertility of mammalian species. Much of the information pertaining to normal and pathological conditions affecting the prostate has been obtained through extensive developmental, biochemical and genetic analyses of rodent species. Although important insights can be obtained through detailed anatomical and histological assessments of mouse and rat models, further mechanistic explanations are greatly aided through studies of gene and protein expression. RESULTS: In this article we characterize the repertoire of genes expressed in the normal developing mouse prostate through the analysis of 50,562 expressed sequence tags derived from 14 mouse prostate cDNA libraries. Sequence assemblies and annotations identified 15,009 unique transcriptional units of which more than 600 represent high quality assemblies without corresponding annotations in public gene expression databases. Quantitative analyses demonstrate distinct anatomical and developmental partitioning of prostate gene expression. This finding may assist in the interpretation of comparative studies between human and mouse and guide the development of new transgenic murine disease models. The identification of several novel genes is reported, including a new member of the beta-defensin gene family with prostate-restricted expression. CONCLUSIONS: These findings suggest a potential role for the prostate as a defensive barrier for entry of pathogens into the genitourinary tract and, further, serve to emphasize the utility of the continued evaluation of transcriptomes from a diverse repertoire of tissues and cell types.

Amino Acid Sequence↗

PubMed2003

Alternative splicing of Pax3 produces a transcriptionally inactive protein.

Pax3, a member of the paired-class homeodomain family of transcription factors, plays an important role in embryonic development of neurepithelium and mesenchyme-derived tissues in the mouse and is an early marker for myogenic differentiation. In the present work we identify an alternative splicing event for endogenous Pax3 in primary mouse myoblasts. The resulting splice variant arises through the utilization of a previously unreported splice donor consensus sequence present at the junction between exons 7 and 8 in the Pax3 sequence. The use of this splice donor site in conjunction with the splice acceptor site present between intron 8 and exon 9 results in the deletion of exon 8 and removes a majority of the Pax3 transcriptional activation domain. Consistent with this fact, we demonstrate that the alternatively spliced form of Pax3 is transcriptionally inactive and that the presence of this isoform can effectively inhibit the activity of the full-length protein.

3T3 Cells↗

PubMed2003

Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer.

The murine Pten prostate cancer model described in this study recapitulates the disease progression seen in humans: initiation of prostate cancer with prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma, and subsequent metastasis with defined kinetics. Furthermore, while Pten null prostate cancers regress after androgen ablation, they are capable of proliferating in the absence of androgen. Global assessment of molecular changes caused by homozygous Pten deletion identified key genes known to be relevant to human prostate cancer, including those "signature" genes associated with human cancer metastasis. This murine prostate cancer model provides a unique tool for both exploring the molecular mechanism underlying prostate cancer and for development of new targeted therapies.

Animals↗

PubMed2002

Isolation and characterization of the murine prostate short-chain dehydrogenase/reductase 1 (Psdr1) gene, a new member of the short-chain steroid dehydrogenase/reductase family.

We report the isolation and characterization of a complementary DNA (cDNA) encoding a novel member of the short-chain dehydrogenase/reductase (SDR) gene family that we have designated murine prostate short-chain dehydrogenase/reductase 1 (Psdr1). Psdr1 was cloned as a 3.2 kbp transcript from mouse testis cDNA based on the sequence of the recently described androgen-regulated human PSDR1 gene (Cancer Res. 61 (2001) 1611). The putative protein encoded by Psdr1 consists of 316 amino acids with 85% identity to human PSDR1. A search against the BLOCKS database of conserved protein motifs indicates that Psdr1 retains features essential for SDR function. Northern analyses demonstrate that Psdr1 is highly expressed in the murine testis and liver and exhibits several isoforms. Cloning and sequence analysis of the putative Psdr1 promoter region identified motifs with homology to the consensus androgen response element and progesterone response element. The Psdr1 gene was mapped to mouse chromosome 12q31-34, which has synteny with the human PSDR1 chromosomal location (14q23-24.3). Together, these data describe a new member of the SDR gene family that may be involved in the tissue-specific metabolism of retinoids or steroid hormones.

Amino Acid Sequence↗

PubMed2002

The human (PEDB) and mouse (mPEDB) Prostate Expression Databases.

The Prostate Expression Databases (PEDB and mPEDB) are online resources designed to allow researchers to access and analyze gene expression information derived from the human and murine prostate, respectively. Human PEDB archives more than 84 000 Expressed Sequence Tags (ESTs) from 38 prostate cDNA libraries in a curated relational database that provides detailed library information including tissue source, library construction methods, sequence diversity and sequence abundance. The differential expression of each EST species can be viewed across all libraries using a Virtual Expression Analysis Tool (VEAT), a graphical user interface written in Java for intra- and inter-library sequence comparisons. Recent enhancements to PEDB include (i) the development of a murine prostate expression database, mPEDB, that complements the human gene expression information in PEDB, (ii) the assembly of a non-redundant sequence set or 'prostate unigene' that represents the diversity of gene expression in the prostate, and (iii) an expanded search tool that supports both text-based and BLAST queries. PEDB and mPEDB are accessible via the World Wide Web at http://www.pedb.org and http://www.mpedb.org.

Animals↗