Biomedical subjects

S Christie

Publications and source records attributed to S Christie.

At least 19 recordsLinked to original sources

PubMed2005

Analysis of renal service provision in south and mid Wales.

OBJECTIVES: This paper estimates point prevalence of renal replacement therapy (RRT) utilization within population strata defined by geography and deprivation in south and mid Wales. It investigates spatial accessibility of main and satellite renal units by comparing population and patient numbers within bands of travel time. STUDY DESIGN: Prevalence study based on patient registers. METHODS: From a list of patient and renal unit locations, geocoded at the level of unit postcodes, and electoral division-level denominator population data, we calculated RRT point prevalence for the 16 unitary authorities in the study area, fifths of small area deprivation, and three bands of travel time from the nearest main renal unit and any (main or satellite) unit. RESULTS: Overall point prevalence was 633 per million population (pmp) and this varied from 256 to 780 pmp across unitary authorities. RRT prevalence was lower in more deprived areas. Sixty-nine percent of the population and 73% of patients lived within 30 min of a main renal unit. Eighty-four percent of the population and 88% of patients lived within 30 min of a main or satellite renal unit. CONCLUSIONS: The provision of satellite renal units has significantly improved spatial accessibility of RRT services. However, a substantial proportion of the population remains geographically distant from renal units. This has important implications for planning of future provision of RRT, given the inverse relationship between RRT acceptance and travel time, and the impact on quality of life of patients who travel frequently to renal units.

Geography↗

PubMed2004

Disrupted in Schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondria.

DISC1 is disrupted by a chromosomal translocation cosegregating with schizophrenia and recurrent major depression in a large Scottish family and has also been reported as a potential susceptibility locus in independent populations. We reveal a widespread and complex pattern of DISC1 expression, with at least five forms of Disrupted in Schizophrenia 1 DISC1 detectable. Mitochondria are the predominant site of DISC1 expression with additional nuclear, cytoplasmic, and actin-associated locations evident. Although the subcellular targeting of DISC1 is clearly complex, the association with mitochondria is of interest as many mitochondrial deficits have been reported in schizophrenia and other neuropsychiatric illnesses. Moreover, of the many cellular functions performed by mitochondria, their role in oxidative phosphorylation, calcium homeostasis, and apoptosis may hold particular relevance for the neuronal disturbances believed to be involved in the pathogenesis of schizophrenia.

Actins↗

PubMed2004

Flavonoid supplement improves leg health and reduces fluid retention in pre-menopausal women in a double-blind, placebo-controlled study.

Flavonoid extracts derived from plant foods have been shown to benefit certain types of fluid retention. However, no studies have investigated these compounds for use in premenstrual fluid retention, a complaint common among women with otherwise normal menstrual cycles. Therefore, we conducted a double-blind, placebo-controlled, pilot study into the effect of a daily flavonoid extract (Colladeen, 320 mg oligomeric procyanidins) on premenstrual fluid retention. Fluid retention was assessed at baseline and throughout 4 menstrual cycles of the intervention using validated questionnaires. Leg girth was also measured at baseline and at the end of the study. Thirty subjects completed the study (n = 18 active treatment; n = 12 placebo). Although no significant changes in leg girth measurements were noted, there was a significant improvement in subjective "leg health" scores after flavonoid treatment compared to placebo (p = 0.013). Furthermore, this was accompanied by an improvement in reported premenstrual fluid retention nearing significance (p = 0.066). We conclude that flavonoids supplements may provide a new therapeutic direction to counter premenstrual fluid retention and improve leg health. A larger study is now warranted.

Adult↗

PubMed2004

Multiple sclerosis gender issues: clinical practices of women neurologists.

Substantially more women than men develop multiple sclerosis (MS), but information about the effects of MS and gender-specific issues such as pregnancy, breastfeeding, menstruation and hormone use is lacking. A survey study of neurologists' practice patterns was undertaken to elicit information about gender-specific topics and the use of disease-modifying MS therapies (DMT) including the interferons and glatiramer acetate (GA). A total of 147 surveys were returned. Half of respondents require patients to discontinue DMT during pregnancy, while 35% encourage discontinuation. Among those who allow patients to continue therapy, half consider GA to be safer during pregnancy than the interferons. Nearly 86% of respondents do not use DMT in patients who are breastfeeding. Among the 11% who actually prescribe during breastfeeding, most recommend GA. Neurologists generally leave the decision to breastfeed up to patients, and most refer patients to obstetrician/gynaecologists for counselling about contraception or hormone replacement therapy. The survey results described here provide insight into how neurologists manage reproductive health issues among women with MS.

Breast Feeding↗

PubMed2003

Clinical assessment of a generic DNA amplification assay for the identification of respiratory adenovirus infections.

BACKGROUND: respiratory adenoviruses are common, often resulting in serious sporadic and epidemic infections and impaired immunity can dramatically increase their severity. They are now thought capable of establishing latency. Diagnosis by culture is slow while direct antigen detection by immunofluorescence lacks sensitivity. Molecular diagnosis can be both rapid and sensitive but the genetic heterogeneity of adenoviruses poses problems. OBJECTIVES: to design a generic adenovirus nested polymerase chain amplification assay designed to be capable of detecting all respiratory adenoviruses. This was achieved through optimised thermal cycling and the development of a generic degenerate primer set targeting the adenovirus hexon gene. STUDY DESIGN: this was a cross-sectional study on 172 respiratory specimens from hospital-based patients, and one from a general practice, in Northern Ireland. A comparison was made between the amplification assay, virus culture and immunofluorescence. RESULTS: the nested polymerase chain reaction (nPCR) assay had a generic capacity for adenovirus detection and an analytical sensitivity of 6.4x10(2) copies/ml. Using an expanded gold standard (defined as a true positive or a true negative where a specimen was positive or negative by at least two of the study assays, respectively), PCR had a clinical sensitivity and specificity of 46/46 (100%) and 15/126 (91.3%), respectively. Patients with acute respiratory adenovirus infections were more likely to be male (chi(2), p=0.005) and to present with a fever (chi(2), p=0.02) than patients diagnosed with another respiratory virus. Co-infection was identified in 12/172 patients. CONCLUSIONS: the nested amplification assay proved highly sensitive in both the analytical and clinical settings for the detection of respiratory adenovirus infections.

Adenovirus Infections, Human↗

PubMed2001

Truncation of WT1 results in downregulation of cyclin G1 and IGFBP-4 expression.

Mutations in the WT1 gene are found in a subset of Wilms' tumours and in certain other disorders such as Denys-Drash syndrome. The WT1 gene product is a zinc finger transcription factor for which many target genes have been suggested. Here we utilise gene targeting to generate cells containing only truncated forms of WT1, in which the DNA-binding region is disrupted. Examination of gene expression in these cells using cDNA macroarrays suggests two novel WT1 transcriptional targets, cyclin G1 (Ccng1), and insulin-like growth factor binding protein 4 (Igfbp4).

Antineoplastic Agents↗

PubMed2001

Flavonoids--a new direction for the treatment of fluid retention?

Flavonoid extracts are important for the health of the micro-blood vessel network and are clinically exploited in this way by medical herbalists and physicians in mainland Europe. In the present review, we provide preliminary evidence that suggests that plant flavonoid extracts from dietary sources facilitate the repair of vessel damage responsible for 'small blood vessel permeability'. Correction of this pathophysiological abnormality is known to lead to a reduction in symptoms of diffuse benign fluid retention including swollen limbs, fingers, breasts and the tissue surrounding the eye area. There is currently little orthodox treatment for this type of fluid retention except diuretics which are not without side effects and fail to address the underlying cause of the disorder. This paper marshals available data including some preliminary studies that suggest that detailed scientific study of this clinical area and its treatment through flavonoid intervention is warranted.

Anthocyanins↗

PubMed2001

Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia.

Two overlapping and antiparallel genes on chromosome 1, Disrupted In Schizophrenia 1 and 2 (DISC1 and DISC2), are disrupted by a (1;11)(q42.1;q14.3) translocation which segregates with schizophrenia through at least four generations of a large Scottish family. Consequently, these genes are worthy of further investigation as candidate genes potentially involved in the aetiology of major psychiatric illness. We have constructed a contiguous clone map of PACs and cosmids extending across at least 400 kb of the chromosome 1 translocation breakpoint region and this has provided the basis for examination of the genomic structure of DISC1. The gene consists of thirteen exons, estimated to extend across at least 300 kb of DNA. The antisense gene DISC2 overlaps with exon 9. Exon 11 contains an alternative splice site that removes 66 nucleotides from the open reading frame. The final intron of DISC1 belongs to the rare AT-AC class of introns. We have also mapped marker DIS251 in close proximity to DISC1, localising the gene within a critical region identified by several independent studies. Information regarding the structure of the DISC1 gene will facilitate assessment of its involvement in the aetiology of major mental illness in psychotic individuals unrelated to carriers of the translocation.

Cell Line↗

PubMed2001

A study of fructo oligosaccharides in the prevention of travellers' diarrhoea.

BACKGROUND: Prebiotic carbohydrates selectively stimulate the growth of bifidobacteria and lactobacilli in the human colon. These bacteria form part of the gut's inherent defence against invading pathogens. AIM: To test the effectiveness of fructo oligosaccharides in preventing travellers' diarrhoea. METHODS: A total of 244 healthy subjects, travelling to high and medium risk destinations for travellers' diarrhoea, took part in a randomized, double-blind, placebo-controlled study. The protocol comprised a preliminary week for recording bowel habit by diary, a 2-week pre-holiday period with the diary and consumption of 10 g of fructo oligosaccharides or placebo daily, followed by a 2-week holiday with continuation of treatment and diary. A post-study questionnaire was completed by all subjects on their return to the UK. RESULTS: The consumption of fructo oligosaccharides led to a small (6%; P < 0.02) increase in stool frequency in the pre-holiday period and gave a significantly better sense of 'well-being' during the holiday, although subjects reported more flatulence. There were non-significant decreases in episodes of diarrhoea with 20% on placebo and 11% on fructo oligosaccharides recording episodes in the post-study questionnaire (P=0.08) and 46% placebo, 38% fructo oligosaccharides recording episodes in the diary (P > 0.1). No change in bowel frequency, consistency or stool size was recorded. CONCLUSION: Travel to high risk areas increases diarrhoea. Fructo oligosaccharides alone are not sufficient to prevent this, although do have some benefits for the subjects.

Bifidobacterium↗

PubMed2001

A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates.

Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.

Adult↗

PubMed2000

Chromosomal location and genomic structure of the human translin-associated factor X gene (TRAX; TSNAX) revealed by intergenic splicing to DISC1, a gene disrupted by a translocation segregating with schizophrenia.

Two candidate genes, DISC1 and DISC2 on chromosome 1, are disrupted by a translocation that segregates with major psychiatric illness. Several DISC1 transcripts contain TRAX (HGMW-approved symbol TSNAX) sequence at the 5' end. These transcripts initiate at the 5' end of TRAX and terminate at the final exon of DISC1. Five species of transcript resulting from intergenic splicing have been identified; one encodes a novel TRAX/DISC1 fusion protein. The remaining four transcripts are bicistronic and encode a series of novel truncated isoforms of TRAX and DISC1. Demonstration that the various TRAX/DISC1 transcripts are translated awaits further experimentation. As a consequence of the observation of intergenic splicing, the human TRAX gene has been mapped at least 35 kb proximal to DISC1 and within approximately 150-250 kb of the translocation breakpoint at 1q42.1. The TRAX gene consists of six exons with a putative CpG island at the 5' end. Four major transcripts are produced from this gene, of which the smallest, at 2.7 kb, had previously been identified.

Bacterial Outer Membrane Proteins↗

PubMed2000

Disruption of two novel genes by a translocation co-segregating with schizophrenia.

A balanced (1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related psychiatric disorders in a large Scottish family (maximum LOD = 6.0). We hypothesize that the translocation is the causative event and that it directly disrupts gene function. We previously reported a dearth of genes in the breakpoint region of chromosome 11 and it is therefore unlikely that the expression of any genes on this chromosome has been affected by the translocation. By contrast, the corresponding region on chromosome 1 is gene dense and, not one, but two novel genes are directly disrupted by the translocation. These genes have been provisionally named Disrupted-In-Schizophrenia 1 and 2 ( DISC1 and DISC2 ). DISC1 encodes a large protein with no significant sequence homology to other known proteins. It is predicted to consist of a globular N-terminal domain(s) and helical C-terminal domain which has the potential to form a coiled-coil by interaction with another, as yet, unidentified protein(s). Similar structures are thought to be present in a variety of unrelated proteins that are known to function in the nervous system. The putative structure of the protein encoded by DISC1 is therefore compatible with a role in the nervous system. DISC2 apparently specifies a non-coding RNA molecule that is antisense to DISC1, an arrangement that has been observed at other loci where it is thought that the antisense RNA is involved in regulating expression of the sense gene. Altogether, these observations indicate that DISC1 and DISC2 should be considered formal candidate genes for susceptibility to psychiatric illness.

3' Untranslated Regions↗

PubMed1999

A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome.

The Wilms tumor-suppressor gene, WT1, plays a key role in urogenital development, and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma, leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The analysis of diseases linked specifically with WT1 mutations, such as Denys-Drash syndrome (DDS), can provide valuable insight concerning the role of WT1 in development and disease. DDS is a rare childhood disease characterized by a nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and/or Wilms tumor (WT). DDS patients are constitutionally heterozygous for exonic point mutations in WT1, which include mutations predicted to truncate the protein within the C-terminal zinc finger (ZF) region. We report that heterozygosity for a targeted murine Wt1 allele, Wt1(tmT396), which truncates ZF3 at codon 396, induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice. Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event, implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice. However, the mutant WT1(tmT396) protein accounted for only 5% of WT1 in both heterozygous embryonic stem cells and the WT. This has implications regarding the mechanism by which the mutant allele exerts its effect.

Animals↗

PubMed1999

Transforming growth factor-beta1: a possible signal molecule for posthemorrhagic hydrocephalus?

Posthemorrhagic hydrocephalus remains a complication of preterm birth for which we lack a clear understanding and a curative therapy. Transforming growth factor beta (TGF-beta) is a cytokine that upregulates the production by fibroblasts of extracellular matrix proteins. We hypothesized that TGF-beta might be released into cerebrospinal fluid (CSF) after intraventricular hemorrhage and play a role in posthemorrhagic hydrocephalus. Total TGF-beta1 and TGF-beta2 were measured by immunoassay in CSF samples from 12 normal preterm infants, nine preterm infants with transient posthemorrhagic ventricular dilation, and 10 infants who subsequently developed permanent hydrocephalus. Five infants received intraventricular tissue plasminogen activator, and two infants were treated by drainage irrigation and fibrinolytic therapy. Median TGF-beta1 in normal CSF was 0.495 ng/mL. In infants with transient posthemorrhagic ventricular dilation, median initial CSF TGF-beta1 was 2.1 ng/mL. Infants who subsequently had permanent hydrocephalus had median initial CSF TGF-beta1, 9.7 ng/mL (differences between groups p < 0.01). Intraventricular recombinant tissue plasminogen activator was followed by a rise in CSF TGF-beta1 (p = 0.0007). Drainage irrigation and fibrinolytic therapy was followed by a fall in CSF TGF-beta1. TGF-beta2 was detected in CSF and showed similar trends, but the CSF concentration of TGF-beta1 was more than 20 times higher. These findings support the hypothesis that TGF-beta1 is released into CSF after intraventricular hemorrhage and may play an important part in hydrocephalus. The results help to explain the failure of intraventricular fibrinolytic therapy.

Cerebral Ventricles↗

PubMed1998

Primary care. Toil and trouble.

Establishing PCGs will represent a huge change even in areas with well-developed primary care. The inclusion of nurses in PCGs is likely to prove problematic. The new groups will need to achieve high-profile early successes in order to maintain credibility. There is little evidence that fewer managers will be required.

Contract Services↗

PubMed1998

A long-range restriction map across 3 Mb of the chromosome 11 breakpoint region of a translocation linked to schizophrenia: localization of the breakpoint and the search for neighbouring genes.

A balanced t(1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related mental illness in a single large Scottish pedigree. We have constructed a long-range restriction map covering at least 3 Mb of the chromosome 11 breakpoint region and conducted searches for genes whose expression could be altered by the translocation, resulting in schizophrenia. Novel transcribed sequences of unknown function clustered around putative CpG islands, located approximately 500 kb and 700 kb above the breakpoint, represent the only evidence to date for expressed genes within the mapped region.

Cells, Cultured↗

PubMed1998

The burden of infectious disease in New Zealand.

New Zealand mortality records for the years 1980 to 1993 were analysed to estimate the aggregate burden of infectious disease using a recoding of ICD-9 codes to identify deaths with infectious aetiology. The recoding scheme was modified from one developed by US CDC, which used expert panels to assign ICD codes to categories dependent on the proportion of the code attributable to infection. ICD-9 Chapter One ('Infectious and parasitic diseases') accounted for only 0.7% of total deaths. Following recoding, this proportion increased tenfold, with 6.9% of deaths attributable to infectious disease. This proportion was stable or declined only slowly between 1980 and 1993. While rates varied by age, gender and ethnicity, the results indicate that infectious disease still accounts for a substantial proportion of the burden of disease in New Zealand.

Adolescent↗

PubMed1997

Novel transcribed sequences neighbouring a translocation breakpoint associated with schizophrenia.

A 1.3Mb chromosome 11-specific yeast artificial chromosome (YAC) that spans a t(1;11) translocation breakpoint associated with major psychosis has been used to enrich cDNAs that are encoded within it and expressed in the human foetal brain. Database analysis of the selected fragments led to the identification of 54 clones matching alpha-tubulin, 4 fragments matching two anonymous human expressed sequence tags (ESTs) and 8 fragments giving no database matches. The clones matching alpha-tubulin led to the identification of a novel alpha-tubulin locus located approximately 250 kb proximal to the translocation breakpoint. Extensive sequence and expression analysis of this locus suggests that this is a processed pseudogene, although a long open reading frame is maintained and the possibility that an abnormally acting protein may be expressed in a highly tissue or developmental specific manner cannot be discounted. The novel cDNA fragments map up to 700 kb proximal to the translocation breakpoint and are associated with potential CpG islands. Reverse transcriptase polymerase chain reaction (RT-PCR) expression analysis and high resolution genomic mapping suggest that they may comprise up to three novel genes. No major disruption of the identified fragments could be detected in the genomic DNA of translocation carriers. The psychosis associated with this translocation may therefore be due to position effects on the transcription of these genes or an involvement of translocated chromosome 1 sequences.

Chromosomes, Artificial, Yeast↗