Search PubMed⌕ Search

Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 37 records · Page 2Linked to original sources
PubMed2004

Interaction of cocultured decidual endothelial cells and cytotrophoblasts in preeclampsia.

Disturbed cell-cell communication between trophoblasts and the maternal endothelium may be responsible for the deficient endovascular invasion seen in preeclampsia. In vitro studies have been hampered by lack of suitable models to directly examine interactions between these cell types. Using a bilayer coculture model, we examined the effect of decidual endothelial cells on matrix metalloproteinase secretion and the migration of cytotrophoblasts from preeclamptic pregnancies. Cells were incubated on semipermeable membranes in 20% or 2% O(2) with or without the tumor promoter phorbol 12-myristate 13-acetate, which activates matrix metalloproteinase-2 and -9 in endothelial cells. Cytotrophoblasts from preeclamptic pregnancies secreted significantly less matrix metalloproteinase-2 and -9 than their normal counterparts. Although decidual endothelial cells downregulated cytotrophoblast migration in normal pregnancy, this was not observed in cocultures with cytotrophoblasts from preeclamptic pregnancies. In addition, cytotrophoblasts from preeclamptic pregnancies altered phorbol myristate acetate-induced activation of endothelial matrix metalloproteinases. Hypoxia increased cytotrophoblast migration when cells were incubated alone but not in coculture with decidual endothelial cells due to increased adhesion between the two cell types. These results suggest dysfunctional interactive regulation of migration and matrix metalloproteinase secretion in preeclampsia that could result in abnormal endovascular trophoblast invasion of the maternal vasculature.

Cell Communication↗
PubMed2004

Sex-specific antenatal reference growth charts for uncomplicated singleton pregnancies at 15-40 weeks of gestation.

OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all gestational ages. The purpose of this study was to compare female and male fetuses in terms of intrauterine ultrasound growth measurements and to develop gestational-age-related charts based on a computerized perinatal database. METHODS: This was a retrospective study of unselected women in the second and third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data analysis was performed using measurements obtained from a mixed-race population of 4234 women, who underwent 5198 ultrasound examinations. The scans were performed by four trained sonographers, according to a standardized protocol. Routine measurements included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The main end-points were sex- and race-specific differences in fetal biometry, which were also used to estimate fetal weight. RESULTS: The base-line demographic characteristics and risk factors were comparable in female and male fetuses. Significant differences in fetal BPD, HC, AC and estimated fetal weight, but not FL, were seen between male and female fetuses. Centile charts for each of these variables were constructed for both male and female fetuses. CONCLUSIONS: This study suggests that small but consistent sex-related differences in prenatal BPD, HC and AC measurements are established by as early as 15 weeks of gestation. The use of sex-specific nomograms may improve the prenatal assessment of fetal growth as well as the diagnosis of structural abnormalities.

Embryonic and Fetal Development↗
PubMed2004

Clinical impact of first and early second trimester fetal echocardiography on high risk pregnancies.

OBJECTIVE: To evaluate the clinical impact of fetal echocardiography before 16 weeks' gestation on the management of pregnancies with fetuses at risk of congenital heart disease. DESIGN AND SETTING: Observational study in a fetal medicine unit. PARTICIPANTS AND METHODS: 222 consecutive women with high risk pregnancies (230 fetuses) underwent transabdominal fetal echocardiography at a median gestation of 14(+1) weeks. For 10%, transvaginal scans were also performed. Criteria for normal scans were normal sequential segmental analysis, symmetrical four chamber view, normal semilunar valves, arterial outflow tracts, and ductal and aortic arches. Early scans were compared with mid-second trimester fetal echocardiography. Postmortem and postnatal data were added. Adverse pregnancy outcomes were diagnosis of a major cardiac or extracardiac abnormality, chromosomal defects, intrauterine death, or termination of pregnancy. RESULTS: There were 21 abnormal cardiac scans (9%): 14 major structural defects (eight isolated, six with chromosomal or extracardiac abnormalities) in pregnancies resulting in three live births, one intrauterine death, and 10 terminated pregnancies. Seven scans showed asymmetry between right and left sided structures (two isolated, five with chromosomal or extracardiac abnormalities); six of the seven pregnancies were terminated. The scans were normal in 199 cases (87%). Cardiac follow up of 184 of 199 babies (93%) confirmed situs and connections. One case each of pulmonary stenosis and ventricular septal defect requiring postnatal intervention were diagnosed at later scans. In 28 of 199 (14%) babies there was a non-cardiac adverse outcome. First examination was not diagnostic for 10 (4%). CONCLUSION: Early fetal echocardiography in high risk pregnancies was diagnostic in 96%. Abnormal cardiac scans (isolated in 48%, major structural defects in 67%) led to termination of pregnancy in 76%. Most cardiac scans were normal, allowing family reassurance. The high number of adverse outcomes with normal cardiac anatomy stresses the need for a multidisciplinary approach to early fetal echocardiography.

Echocardiography, Doppler, Color↗
PubMed2003

N-acetyl-L-cysteine prevents DNA damage induced by UVA, UVB and visible radiation in human fibroblasts.

The thiol N-acetyl-L-cysteine (NAC) is a source of cysteine for the synthesis of the endogenous antioxidant glutathione (GSH) which is depleted by ultraviolet radiation. It is also associated with the scavenging of reactive oxygen species (ROS). In this study the effects of NAC were examined in cultured human fibroblasts during prolonged exposure to ultraviolet B (UVB), ultraviolet A (UVA) and visible irradiation (280-700 nm), delivered by a 150 W xenon-arc lamp. The alkaline comet assay was used to assess the DNA damage in individual cells. It was found that incubating skin and lung fibroblasts at 37 degrees C for 1 h with an optimal 6 mM NAC supplement prior to light exposure, significantly reduced the level of DNA damage in both cell types, however, the skin fibroblasts were less sensitive to xenon-arc lamp irradiation than lung fibroblasts. NAC incubation resulted in an initial delay in DNA damage when the cells were irradiated. There was also a significant reduction in the overall levels of DNA damage observed with continued irradiation. NAC significantly reduced the DNA damage produced in lung fibroblasts depleted of normal GSH protection by the glutamylcysteinyl synthetase inhibitor, L-buthionine-[S,R]-sulfoximine. Although the specific mechanism of NAC protection has not yet been elucidated, these results support the hypothesis that NAC may protect the cells directly, by scavenging ROS induced by UVA and visible radiation, and indirectly by donating cysteine for GSH synthesis.

Acetylcysteine↗
PubMed2003

Arteriovenous malformation of the uterus associated with secondary postpartum hemorrhage.

We present the case of a young woman with persistent secondary postpartum hemorrhage. Transvaginal imaging demonstrated an irregular pulsatile lesion in the anterior myometrium. Color Doppler analysis revealed the presence of abnormal vessels consistent with an arteriovenous malformation. Typically this vascular abnormality had a turbulent pattern of arterial and venous flow with high peak velocities and low resistance. The patient was treated with selective arterial embolization leading to a full recovery.

Adult↗
PubMed2003

Intraobserver and interobserver variability of ovarian volume, gray-scale and color flow indices obtained using transvaginal three-dimensional power Doppler ultrasonography.

OBJECTIVE: To assess intraobserver and interobserver variability in ovarian volume and gray-scale and color flow index measurements using transvaginal, three-dimensional, power Doppler ultrasonography. METHODS: Eleven women (22 ovaries) were examined on day 8 of controlled ovarian hyperstimulation therapy, which was part of their in vitro fertilization treatment protocol. The patients were examined twice by the first observer and once by the second observer. The acquired volume datasets were analyzed using the VOCAL imaging program, enabling the assessment of ovarian volume, vascularization index (VI), flow index (FI), vascularization flow index (VFI) and mean grayness (MG). For these parameters the intraclass (intra-CC) and interclass (inter-CC) correlation coefficients, within-observer and between-observers repeatability coefficient (r) and limits of agreement were calculated. RESULTS: Both intraobserver and interobserver repeatability of ovarian volume measurements were considered very good with an intra-CC value of 1.00 and inter-CC value of 0.99, respectively. Also VI, FI, VFI and MG measurements were repeatable by a single observer, the intra-CC ranging from 0.82 to 0.91. The interobserver reproducibility was also good for VI, VFI and MG measurements (inter-CC values 0.73, 0.70 and 0.81, respectively), but for FI measurements the reproducibility was poor (inter-CC = 0.29, r = 7.87). CONCLUSIONS: In general, the intraobserver reproducibility was better than interobserver reproducibility for all parameters. The volume assessments were reproducible both by one observer and by two separate observers. The intraobserver and interobserver variabilities were acceptable for VI, VFI and MG, whereas for FI the interobserver reproducibility was poor. Our results suggest that measurement of gray-scale and color Doppler flow indices is reproducible thus allowing them to be used in clinical practice and research.

Blood Flow Velocity↗
PubMed2003

Results from an ultrasound-based familial ovarian cancer screening clinic: a 10-year observational study.

OBJECTIVES: To assess the use of transvaginal sonography as a screening test for familial ovarian cancer and, secondarily, to determine the value of a family history of malignant disease and the potential role of serum CA 125 levels in the screening procedure. METHODS: Two thousand five hundred self-referred women were studied at the Ovarian Screening Clinic at King's College Hospital, London. These symptom-free women with at least one close relative who had developed ovarian cancer were studied prospectively. Each woman was scanned for the presence of a persistent ovarian lesion and a sample of peripheral blood was taken for the retrospective analysis of serum CA 125. Women with a positive screen result were referred for surgical investigations; those with a negative result but considered to be at high risk were rescreened. The main outcome measures were findings at surgery, the histological classification of ovarian lesions, and cancer reported at follow-up. RESULTS: The women were aged 17 to 78 (mean, 48) years; 65% were premenopausal, 26% were postmenopausal and 9% had undergone hysterectomy. Seven hundred and thirty-eight women (29.5%) had a family history of multiple site cancers and 279 (11.2%) reported cancer specific to the ovary. There were 4231 screenings (2500 first screens, 998 second screens and 733 third or higher order screens). One hundred and four screens gave a positive result (2.5%); 11 cancers were detected (seven (64%) at stage I, four of which were of borderline malignancy). One additional cancer was reported within 12 months of the last scan and classified as a false-negative screen result. Eight cancers (including two peritoneal) were reported at follow-up (> 1-9 years after the last scan). All these women presented at an advanced stage (stage III). Fifteen of 20 cancers occurred in premenopausal women. The overall sensitivity of ultrasound screening was 92% (95% confidence interval, 76-100); the specificity was 97.8%. The prior odds of any woman having a screen-detectable ovarian malignancy during the study period were 1 : 207. The posterior odds subsequent to a positive screen result were 1 : 8.5 (1 : 12.7 at Screen 1; 1 : 3.7 at Screen 2; 1 : 3.0 at subsequent screens); the value was 1 : 11.4 for women with one family relative with ovarian cancer and 1 : 5.0 for women with the site-specific ovarian cancer syndrome. The prior use of a decision level for serum CA 125 >or= 20 U/mL would have reduced the number of women undergoing sonography by 78%; seven of the 12 cancers (58%) would have been detected (63% of all stage I disease, 75% of invasive stage I disease). An alternative cut-off value of 35 U/mL would have resulted in a detection rate of 33%. CONCLUSIONS: Transvaginal sonography can effectively detect intraovarian cancer and tumors of borderline malignancy in women with a family history of the disease. Screening efficacy is related to the type of family history. The level of serum CA 125 can be used to select women for sonography, but the detection rate for early cancers would be reduced.

Adolescent↗
PubMed2003

Reduced and standard target concentration tacrolimus with sirolimus in renal allograft recipients.

We report 6-month results of renal allograft recipients enrolled in seven Australian centers as part of a worldwide, multicenter, randomized, open-label, concentration-controlled trial comparing standard tacrolimus (sTAC) with reduced tacrolimus (rTAC) both with sirolimus (SRL) and steroids. Patients were randomized 1:1 to either rTAC (n = 33) with a target maintenance concentration of SRL of 8 to 15 ng/mL and TAC of 3 to 7 ng/mL, or sTAC (n = 31) with SRL target of 5 to 10 ng/mL and TAC of 8 to 12 ng/mL. Antibody induction was prohibited. Adult recipients of a first or second cadaveric or non-HLA-identical living donor renal graft were eligible for enrollment. Recipients with a panel-reactive antibody level of >50% and recipients of regrafts who had lost their first graft from rejection within the first 6 months were ineligible. The groups were compared for graft function, incidence of rejection, and patient and graft survival at 6 months. There were no differences in demographics. There were 30% and 29% discontinuations in the rTAC and sTAC groups mainly due to adverse events in the first month. The 6-month patient and graft survival by intention-to-treat analysis was 94% and 91% for rTAC and 100% and 97% for sTAC (P = NS), respectively. Incidence and severity of biopsy-proven acute rejection was not different between the two groups, being 21% for rTAC and 19% for sTAC. The mean serum creatinine was 121 micromol/L and 148 micromol/L for rTAC and sTAC groups (P =.09), respectively. Glomerular filtration rate (GFR) was 68 mL/min and 62 mL/min (P =.23), respectively. Adverse events, infections, and antihypertensive and antilipidemic agent usage were similar. Of interest is that the overall incidence of thrombotic microangiopathy was 14%. These results support the safety and efficacy of SRL + TAC. Reduced TAC is associated with a trend toward improved renal function.

Adult↗
PubMed2003

Vaccine and skin testing properties of two avirulent Mycobacterium bovis mutants with and without an additional esat-6 mutation.

SETTING: Molecular techniques are now available to develop new live tuberculosis vaccines by producing avirulent strains of the Mycobacterium tuberculosis complex with known genes deleted. OBJECTIVES: Determine if removal of esat-6 from new live tuberculosis vaccines with known attenuating mutations affects their vaccine efficacy and if it could enable the development of discriminating diagnostic tests. DESIGN: Remove the esat-6 gene by allelic exchange from two illegitimate mutants of Mycobacterium bovis that had previously been shown to have similar vaccine efficacy to BCG in a guinea pig vaccination model. Determine the effect this removal has on virulence, vaccine efficacy and skin test reactivity in guinea pigs. RESULTS: Two double knockout strains of M. bovis were produced and their virulence and vaccine efficacy were compared to their parent strains. Removal of the esat-6 gene had no significant effect on vaccine efficacy. In skin tests, animals inoculated with the double knockout strains reacted to PPD but not ESAT-6, whereas those inoculated with the parent strains had similar skin test reactivity to both PPD and esat-6. CONCLUSION: Removal of esat-6 from new live tuberculosis vaccine candidates has no significant effect on vaccine properties but does enable the use of skin tests to distinguish between vaccination and infection.

Animals↗
PubMed2003

Combination immunomodulatory therapy with cyclosporine and azathioprine in corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of outcome.

BACKGROUND: Cyclosporine is a fungal metabolite and a powerful immunosuppressant. While response to intravenous steroids in severe ulcerative colitis is in excess of 60%, the remainder of patients are left with the options of curative panproctocolectomy or administration of intravenous rescue therapy with cyclosporine. There have been conflicting reports on the efficacy of intravenous cyclosporine in acute ulcerative colitis, and there are serious concerns about potential toxicity and opportunistic infections such as Pneumocystis carnii pneumonia. There are also concerns about early relapse and colectomy following cyclosporine rescue. To date there has been a paucity of data available to help guide the gastroenterologist in the use of cyclosporine and the maintenance of remission once achieved. METHODS: Between 1994 and 2001, a total of sixteen patients who had received intravenous cyclosporine for acute exacerbation of their known UC (seven females, nine males, mean age 33 years) whose records were available for analysis. All patients were refractory to intravenous methylprednisolone (60 mg/24 h). Patients who responded to cyclosporine were discharged on a regimen of oral cyclosporine, oral steroids oral azathioprine and 5-aminosalicylate. RESULTS: Median disease duration was 5.4 years (range 0.9-25 years). All sixteen patients were initially treated with cyclosporine at a dose of 4 mg/kg/day. Nine patients were started on oral azathioprine (median dose 1.8 mg/kg). Seven patients underwent surgery (panproctocolectomy), although none had surgery after 6 months. Comparisons were made between patients with <7 days and >7 days intravenous steroid. Other parameters analysed were stool frequency at 3 days and CRP at 3 days. There were no significant differences between these groups. Median bowel frequency at day 3 was higher in patients who finally underwent surgery. At 3 years follow-up, 56% of the sixteen patients had avoided surgery by using azathioprine immunosuppression. CONCLUSION: The initial response rate to intravenous cyclosporine was high (69%). Side effects were documented in the majority of patients, but none of the patients had to discontinue treatment on account of these. Azathioprine has a useful role in maintaining the remission achieved by i.v. cyclosporine for acute ulcerative colitis patients. More than half the patients will avoid colectomy long-term when using triple immunosuppressive therapy including azathioprine adding support for its relative safety and another role for its use.

Administration, Oral↗
PubMed2003

Transcription profile of brewery yeast under fermentation conditions.

AIMS: Yeast strains, used in the brewing industry, experience distinctive physiological conditions. During a brewing fermentation, yeast are exposed to anaerobic conditions, high pressure, high specific gravity and low temperatures. The purpose of this study was to examine the global gene expression profile of yeast subjected to brewing stress. METHODS AND RESULTS: We have carried out a microarray analysis of a typical brewer's yeast during the course of an 8-day fermentation in 15 degrees P wort. We used the probes derived from Saccharomyces cerevisiae genomic DNA on the chip and RNA isolated from three stages of brewing. This analysis shows a high level of expression of genes involved in fatty acid and ergosterol biosynthesis early in fermentation. Furthermore, genes involved in respiration and mitochondrial protein synthesis also show higher levels of expression. CONCLUSIONS: Surprisingly, we observed a complete repression of many stress response genes and genes involved in protein synthesis throughout the 8-day period compared with that at the start of fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: This microarray data set provides an analysis of gene expression under brewing fermentation conditions. The data provide an insight into the various metabolic processes altered or activated by brewing conditions of growth. This study leads to future experiments whereby selective alterations in brewing conditions could be introduced to take advantage of the changing transcript profile to improve the quality of the brew.

Anaerobiosis↗
PubMed2003

In vitro migration of cytotrophoblasts through a decidual endothelial cell monolayer: the role of matrix metalloproteinases.

Deficient trophoblast invasion is a major feature of pre-eclampsia. In vitro studies suggest that in normal pregnancy, maternal cells may play a role in controlling trophoblast invasion, although the exact nature of the regulatory interactions between these cells is not fully understood. To examine the effect of maternal-placental cell interactions on matrix metalloproteinase (MMP) secretion and endovascular cytotrophoblast migration in normal pregnancy and in pre-eclampsia, we performed co-culture experiments using cytotrophoblasts from normal pregnancies, together with decidual endothelial cells from both normal and preeclamptic pregnancies. Cells were incubated on semi-permeable membranes with or without phorbol 12-myristate 13-acetate (PMA). Results showed that third trimester cytotrophoblasts are migratory under basal conditions and display a different MMP profile from decidual endothelial cells. Co-culture did not damage either cell type and resulted in reduced latent MMP-9 secretion and reduced cytotrophoblast migration. Although PMA upregulated MMPs in decidual endothelial cells, it had no effect on cytotrophoblast MMP secretion. PMA, however, reduced cytotrophoblast migration. Pre-eclamptic decidual endothelial cells showed reduced MMP-1 secretion, but overall were not different in co-culture from normal endothelial cells. This study demonstrates the effectiveness of a bilayer co-culture model to study maternal-foetal cell interactions and provides evidence that maternal cells may contribute to the control of endovascular cytotrophoblast invasion.

Adult↗
PubMed2003

A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD), toxicity profile and response rate of the oral 5-fluorouracil prodrug UFT (tegafur/uracil) and leucovorin (LV) in combination with irinotecan in patients with advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic colorectal adenocarcinoma received first-line chemotherapy comprising UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1 to 14, with escalating doses of irinotecan (200-300 mg/m(2)) administered intravenously on day 1 of a three-weekly cycle. Eligibility criteria were standard. The MTD was defined as the dose at which >33% of six patients experienced a dose-limiting toxicity (DLT) during cycle 1. RESULTS: A total of 32 patients were studied. Initially, six patients were treated at each of the irinotecan dose levels (200, 250 and 300 mg/m(2)) combined with UFT 250 mg/m(2)/day and LV 90 mg/day. DLTs consisting of grade 3 or 4 diarrhoea and febrile neutropenia were observed in one of 20 patients at 250 mg/m(2) and three of six patients at the 300 mg/m(2) irinotecan dose level. Having defined the MTD, the 250 mg/m(2) dose level was established as the recommended dose (RD) and expanded to 20 patients in whom treatment was generally well tolerated. The overall response rate was 19%, with five patients having a partial response (PR) and 18 stable disease (SD) out of 32 response-evaluable patients. CONCLUSION: UFT and LV can be safely combined with irinotecan. The RDs for future studies are UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1-14, with irinotecan 250 mg/m(2) administered on day 1, every 3 weeks. This combination is well tolerated and active. Further investigation of UFT and LV in combination with irinotecan is warranted in patients with colorectal cancer.

Adenocarcinoma↗
PubMed2003

A subtle governance: 'soft' medical leadership in English primary care.

In many countries governments are recruiting the medical profession into a more active, transparent regulation of clinical practice. Consequently the medical profession adapts the ways it regulates itself and its relationship to health system managers changes. This paper uses empirical research in English Primary Care Groups (PCGs) and Primary Care Trusts (PCTs) to assess the value of Courpasson's concept of soft bureaucracy as a conceptualisation of these changes. Clinical governance in PCGs and PCTs displays important parallels with governance in soft bureaucracies, but the concept of soft bureaucracy requires modification to make it more applicable to general practice. In English primary care, governance over rank-and-file doctors is exercised by local professional leaders rather than general managers, harnessing their colleagues' perception of threats to professional autonomy and self-regulation rather than fears of competition as the means of 'soft coercion'.

Attitude of Health Personnel↗
PubMed2003

Impact of a newly opened prison on an accident and emergency department.

OBJECTIVE: To determine the impact of a newly opened prison on an accident and emergency (A&E) department. METHOD: A new category B prison opened in April 1999, the first privately run prison in Scotland and the third largest in population. All prisoners referred to the A&E department for treatment were identified prospectively during the first year after the opening of the prison. RESULTS: 99 prisoners and four members of staff attended during the one year period. Ages ranged from 18-64 years with a mean age of 29.8 years. Presentations were as a result of deliberate self harm (22%), injury after violence (18%), sports injury (15%), surgical condition (15%), medical illness (13%), accidental injury (9%), ENT problem (2%), and miscellaneous (6%). Thirty seven prisoners (35.6%) were admitted to the hospital. Further review at outpatient clinics was arranged for 15 prisoners. One prisoner died, the result of suicide by hanging. The remaining prisoners were returned to the prison for further management by the prison medical and nursing team. Twelve prisoners re-attended a total of 37 times, ranging from twice to a maximum of eight visits. Some 42.3% of attendances were during "working hours" (09.00-17.00) and 57.7% attended "out of hours" (17.00-09.00). Twenty four referrals (23.1%) were deemed inappropriate by the prison medical team on retrospective review. Sixteen of these occurred "out of hours". Forty one prisoners (39.4%) were known to have a history of injecting drug misuse. Including re-attenders, 59 presentations (56.7%) to the A&E department had a history of injecting drug misuse. Of these 41 prisoners, 11 (26.8%) were hepatitis C positive, with eight of these having a positive polymerase chain reaction test. No prisoners had HIV and only one prisoner was hepatitis B positive. CONCLUSION: The opening of the prison resulted in only a slight increase in the workload of the A&E department. A significant proportion of prisoners were admitted to the hospital highlighting the practical and logistical problems of managing people restrained and in custody. Most cases can be safely referred back to the prison. Increased input is required from the prison medical team when dealing with deliberate self harm, frequent attenders, and "out of hours" referrals. All A&E staff must be aware of the increased risk of hepatitis C infection when dealing with a confined prison population.

Adolescent↗
PubMed2003

The prevalence of haemochromatosis gene mutations in the West of Scotland and their relation to ischaemic heart disease.

OBJECTIVES: Excess iron stores have been postulated to enhance the risk of ischaemic heart disease. This study aims to determine whether the two major mutations of the haemochromatosis (HFE) gene (C282Y and H63D) are associated with ischaemic heart disease (IHD) or myocardial infarction (MI). DESIGN: Cross sectional case-control study. SETTING: The geographical area studied by the MONICA (monitoring trends and determinants in cardiovascular disease) heart attack register for North Glasgow in Scotland, UK. PATIENTS: 1009 control subjects chosen at random from general practitioner registers were studied. Additionally, 924 subjects who had survived a first MI sustained between 1985 and 1992 were identified from the MONICA register. MAIN OUTCOME MEASURES: C282Y and H63D mutations, previous MI, and presence or absence of IHD. RESULTS: Mutant gene prevalences in the whole control population were as follows: C282Y: homozygote 0.9%, heterozygote 17.7%; H63D: homozygote 2.1%, heterozygote 25.5%; and compound heterozygote: 2.4%. Analysis by chi(2) test and logistic regression analysis did not identify any significant difference in genotype prevalence between normal control, IHD control, and MI survivor groups. CONCLUSIONS: The C282Y homozygote and heterozygote prevalences are among the highest reported worldwide. No association between IHD or MI and HFE genotype was identified. However, these results need to be interpreted in the light of the cross sectional case-control nature of the study.

Aged↗