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Biomedical subjects

I Mackay

Publications and source records attributed to I Mackay.

At least 19 recordsLinked to original sources
PubMed2005

A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease.

CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. OBJECTIVE: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. DESIGN: The study design was a genome-wide screen performed on affected relative pairs with AITD. SETTING: Patients were recruited through hospital endocrinology clinics. PARTICIPANTS: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. INTERVENTION: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. MAIN OUTCOME MEASURE: The study aimed to identify regions of genetic linkage to AITD. RESULTS: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. CONCLUSIONS: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD.

Chromosome Mapping↗
PubMed2005

Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis.

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.

Absorptiometry, Photon↗
PubMed2005

Constant or special observations of inpatients presenting a risk of aggression or violence: nurses' perceptions of the rules of engagement.

In acute psychiatric settings the practice of 'observation' is commonly employed. Increased levels of observation, 'constant' or 'special' are used for those perceived as presenting a 'higher' risk. As an intervention it is used most frequently for those at risk of self-harm or suicide, the practice is also however, used for those thought to present a risk of violent behaviour. In this descriptive study the perceptions of 1st level registered mental nurses (RMNs) gave an account of observation for those perceived to be at risk of violence or aggression and insight into what was considered important and desirable in practice. Unstructured qualitative interviews were conducted with a purposive sample of six RMNs from a psychiatric intensive care unit. Three major categories, Procedure, Role, and Skills emerged which revealed a complex practice far removed from its literal description as merely 'watching'. Six subcategories emerged from the Role. (1) intervening; (2) maintaining the safety of the patient and others; (3) prevention de-escalation and the management of aggression and violence; (4) assessing; (5) communication; and (6) therapy. Skills in these and, experience were thought to IMPACT on the success of the practice. The description of this and the skills involved offer a definition of the 'rules of engagement' which give insight to the practice and the training needs of staff advocated for 'observation'. The acronym IMPACT may be useful in this.

Aggression↗
PubMed2005

Outcomes after placement of colorectal stents.

BACKGROUND: Colonic stents are increasingly used to palliate or alleviate large bowel obstruction in patients with colon cancer and other obstructing lesions in whom a definitive surgical procedure is inappropriate. We report on the outcomes of a large group of patients who underwent deployment of a colon stent in a single institution by a single operator. PATIENTS AND METHODS: This was a retrospective observational cohort study of all patients undergoing colonic stenting between September 1995 and May 2002. Data collected included nature of pathology, type of stent used, procedure morbidity, patient survival and details of any definitive procedures performed after stenting. RESULTS: One hundred and seven patients were evaluated (58 male) with a median age of 75 years (range 36-99 years). A total of 112 stents were successfully deployed (46 as an emergency). Twelve patients had double stents inserted coaxially and overlapping. In 7 patients the stent could not be safely deployed. Eighty-seven patients had colorectal cancer, 13 patients had an extra-luminal malignancy, 5 had diverticular strictures and in 2 patients the pathology was unknown. At last review (May 2002) 18 patients were alive, 82 patients had died and 7 patients had been lost to follow-up. Of those patients who died, the median survival after stenting alone was 6 weeks (range 4 days-36 weeks). Ten patients underwent subsequent definitive surgery. Stent complications included, 2 colonic perforations, 3 stent occlusions and 4 stent migrations. CONCLUSION: Colonic stenting can be used effectively, with acceptable morbidity, to manage patients presenting with large bowel obstruction. In a smaller number of patients colon stents may safely temporize symptoms while definitive surgery is planned.

Adult↗
PubMed2003

miLD and booLD programs for calculation and analysis of corrected linkage disequilibrium.

We describe software which calculates a set of linkage disequilibrium statistics, including multiallelic D' corrected by the bootstrap and permutation. The software also provides a tool for maximum likelihood and least squares estimation and testing of a set of hierarchical hypotheses formulated within the framework of the Malecot model of the decay of linkage disequilibrium with distance. Additionally, the bootstrap approach is used for estimation of the model parameter's confidence intervals and for hypothesis testing. The programs are available from http://www.geneticepi.com/Research/software/software.html

Algorithms↗
PubMed2002

Photochemistry and photophysics of Cr(III) macrocyclic complexes.

The phosphorescence and photochemical behavior of the macrocyclic complexes (1,4,7,10,13,16-hexaazacyclooctadecane)chromium(III) (Cr([18]-aneN(6))(3+); 1) and (4,4',4''-ethylidynetris(3-azabutan-1-amine)) chromium(III) (Cr(sen)(3+); 2) have been compared to each other and to the complex Cr(en)(3)(3+). For both macrocyclic complexes, phosphorescence from room temperature aqueous solutions is too weak to be observed, contrasting with Cr(en)(3)(3+), though both had somewhat longer 77 K lifetimes than Cr(en)(3)(3+). Phosphorescence lifetimes for these macrocyclics decreased with increasing temperature much faster than for Cr(en)(3)(3+) and a conventional extrapolation based on a fit of reciprocal lifetimes (corrected for the low-temperature contribution) to the Arrhenius equation gave estimated room temperature phosphorescence lifetimes of a few nanoseconds, consistent with the failure to observe room temperature emission. Fitting of the nonlinearity of the data seen in these plots suggested that two high-temperature processes were occurring with estimated activation parameters (E in kJ mol(-1) and A in s(-1)) for Cr([18]-aneN(6))(3+): E(1) = 40, A(1) = 1 x 10(16); E(2) = 24, A(2) = 1 x 10(14): Cr(sen)(3+); E(1) = 45, A(1) = 2 x 10(15); E(2) = 29, A(2) = 7 x 10(11). Cr([18]-aneN(6))(3+) was photochemically inert on irradiation. On irradiation into the lowest quartet ligand field absorption band, Cr(sen)(3+) photolyzes with a quantum yield of 0.098 +/- 0.001 at room temperature. Laser flash photolysis with conductivity detection showed that this photoreaction occurred faster than protonation of the liberated amine ligand at all practical proton concentrations. The quantum yield for irradiation directly into the doublet absorption band of Cr(sen)(3+) was 0.077 +/- 0.003. Photoaquation of Delta-Cr(sen)(3+) led to loss of optical activity and product analysis by capillary electrophoresis showed that both racemic and Delta-Cr(sen)(3+) photoaquate to a single main product, trans-Cr(sen-NH)(H(2)O)(4+). The product stereochemistry is shown to be consistent with predictions based on the angular overlap model for Cr(III) photochemistry, recognizing the additional constraints imposed by the ligand. The abnormally short room temperature solution lifetime of the doublet state is a result of a radiation-less process that competes with other processes depleting the doublet state. However, this doublet-state deactivation process does not lead to photoaquation but competes with BISC and photoaquation via the quartet state, resulting in an unprecedented reduction in photoaquation quantum yield on direct irradiation into the doublet state.

Journal Article↗
PubMed2001

Replication and extension studies of inflammatory bowel disease susceptibility regions confirm linkage to chromosome 6p (IBD3).

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine, commonly diagnosed as either ulcerative colitis (UC) or Crohn's disease (CD). Epidemiological studies have consistently shown that both genetic and environmental factors influence the pathogenesis of IBD. A number of genome scans have been conducted in cohorts of IBD families with affected sibling pairs (ASPs) to identify chromosomal regions that harbour IBD susceptibility genes. Several putative linked loci have been identified, including two loci on chromosomes 16 and 12, IBD1 and IBD2, which have subsequently been replicated by independent region-specific studies. We have conducted both a replication study on another linkage region, chromosome 6p (IBD3), and extension studies on two other regions, chromosomes 3p and 7q. Microsatellite markers across each region were genotyped in 284 IBD ASPs from 234 families. A nonparametric peak multipoint LOD score of 3.0 was observed near D6S291, replicating the previous linkage to chromosome 6p (IBD3). Nominal evidence of linkage was observed at both the 3p and 7q regions.

Chromosome Mapping↗
PubMed1999

Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43). UK Prospective Diabetes Study (UKPDS) Group.

AIMS/HYPOTHESIS: Juvenile-onset, insulin-dependent diabetes is associated with islet cell antibodies and with specific "high-risk" HLA-DRB1 and HLA-DQB1 genotypes. Patients with Type II (non-insulin-dependent) diabetes mellitus can have islet-related antibodies, but the genotypic associations at different ages of onset have not been evaluated. Our aim was to determine (i) the prevalence of DRB1 and DQB1 genotypes in patients at diagnosis of Type II diabetes at different ages from 25 to 65 years compared with the general population, and (ii) whether the presence of islet cell antibodies (ICA) or glutamic acid decarboxylase antibodies (GADA) or both by age is associated with different DRB1 and DQB1 genotypes. METHODS: The antibodies to islet cells and those to glutamic acid decarboxylase were measured in 1712 white Caucasian diabetic subjects at diagnosis of diabetes and they were genotyped for HLA DRB1*03 and DRB1*04 and the high-risk DRB1*04-DQB1* 0302 haplotype. To assess over-representation of high-risk alleles for Type I (insulin-dependent) diabetes mellitus, the prevalence of high-risk alleles in diabetic patients was expressed relative to the prevalence of low-risk alleles, non-DR3/non-DR4, that provided a reference denominator in both the diabetic patients and in 200 non-diabetic control subjects. The prevalence of ICA or GADA or both in patients with different HLA genotypes was assessed in those diagnosed in four age groups, 25-34 years, 35-44 years, 45-54 years and 55-65 years. RESULTS: In Type II diabetic patients presenting at ages 25-34, 35-44 and 45-54 years, there was an increased prevalence of DR3/DR4 compared with the general population with approximately 6.5-fold, 2.9-fold, 2.1-fold over-representation, respectively (p < 0.0001, < 0.01, < 0.05) but this was not found in those aged 55-65 years old. In the group aged 25-34 years, 32 % of patients with ICA or GADA or both had DRB1*03/DRB1*04-DQB1*0302 compared with 10% in those aged 55-65 years and expected 3% prevalence. Conversely, only 14% of those aged 25-34 years with antibodies had non-DR3/non-DR4, compared with 35 % in those aged 55-65 years. There was thus pronounced age heterogeneity in DRB1 and DQB1 predisposition to Type II diabetes. The antibodies displaced DRB1 or DQB1 genotypes in the multivariate model for requiring insulin therapy by 6 years of follow-up. CONCLUSION/HYPOTHESIS: The age of presentation of Type I diabetes in adulthood was in part dependent on the DRB1/DQB1 genotype. Islet cell antibodies and glutamic acid decarboxylase antibodies were strongly associated with DRB1*03/DRB1*04-DQB1*0302 in early adulthood but showed little relation with specific HLA genotypes after the age of 55 years.

Adult↗
PubMed1999

Crucial points at diagnosis. Type 2 diabetes or slow type 1 diabetes.

Two major types of diabetes have been recognized since the late 1930s. However, in recent times there have been major changes in classification and understanding of these types, including improved knowledge of maturity-onset diabetes in the young, with the identification of mutations relating to impaired insulin secretion and the recognition of slow-onset type 1 diabetes in adults now designated as latent autoimmune diabetes in adults (LADA). A major problem area in diabetes classification concerns cases of slowly progressive forms of type 1 and type 2 diabetes, particularly in adults aged 25-50 years. This is a more contemporary problem because cases of type 2 diabetes are presenting at an increasingly younger age. In the landmark U.K. Prospective Diabetes Study of type 2 diabetes, islet cell antibodies (ICAs) and antibodies to glutamic acid decarboxylase (anti-GAD) were measured at diagnosis in 3,672 patients. The overall proportion with ICAs was 6%, and anti-GADs was 10%. These subjects clearly had type 1 diabetes or LADA by both phenotypic and genotypic features. The presence of auto antibodies correlated particularly with a younger age and phenotypic features consistent with type 1 diabetes (e.g., early age at diagnosis, lower BMI, and reduced beta-cell function). Overall, of patients requiring insulin by 6 years, 38% were anti-GAD+ at baseline compared with 5.3% of those not on insulin at 6 years. Antibodies to GAD indicate an underlying autoimmune process and have a high positive predictive value for type 1 diabetes and future insulin dependency in adults.

Adult↗
PubMed1998

Primary ciliary dyskinesia: diagnosis and standards of care.

Primary ciliary dyskinesia (PCD) is characterized by disease of the upper and lower respiratory tract, in association with visceral mirror image arrangement in 50% of cases, due to abnormal structure and/or function of cilia. The purpose of this paper is to review the clinical features, diagnosis and management of PCD. Presentations include neonatal respiratory distress, recurrent lower respiratory tract infection, chronic rhinosinusitis and male infertility. PCD enters the differential diagnosis of bronchiectasis, atypical asthma, and unusually severe upper airway disease. Diagnosis is by a cascade of investigations, starting with the saccharin test in patients older than 10 yrs; ciliary beat frequency and pattern on light microscopy; and electron microscopy to assess ciliary morphology and orientation. It is important not to confuse primary and secondary ciliary abnormalities. Nasal nitric oxide is low in PCD, and this measurement shows promise as a screening test for PCD. Diagnosis is important, in order to prevent the development of bronchiectasis and to avoid any unnecessary otorhinolaryngological procedures. Regular follow-up is essential, and management should be multidisciplinary, with input from centres with a special interest in PCD, having access to paediatric and adult chest physicians, otolaryngologists and audiological physicians, physiotherapists, counselling services and fertility clinics. The prognosis is good, but morbidity can be considerable if PCD is incorrectly managed.

Adult↗
PubMed1998

Perennial rhinitis.

Explore the source record for details and available documents.

Adrenal Cortex Hormones↗
PubMed1996

HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus.

The differential antibody response to glutamic acid decarboxylase (anti-GAD) and to islet cell cytoplasm (ICA) according to HLA-DR and DQ genotypes were examined in 28 Spanish patients with Type I diabetes mellitus (11.1 +/- 10.4 year diabetes duration) and their 41 first degree non-diabetic relatives. Anti-GAD was detected by radioimmunoprecipitation and ICA by indirect immunofluorescence and HLA-DR/DQ alleles were assigned by PCR and sequence specific oligonucleotide probes. The frequency in patients of positivity for ICA was 7.1% and of anti-GAD+ 64.3%, and in relatives, the frequency of ICA+ was 4.9%, and anti-GAD+ 9.8%. Concurrent positivity for ICA and anti-GAD existed in only one patient, and in none of the relatives. We confirm for a Spanish population the high frequency of risk genotypes for Type I, involving DR3, DR4 and DQB1*0302 (DQ8) which were present in 26 of 28 (93%) patients and 32 of 41 (78%) relatives. The most frequent genotypes were DR3/DQB1*0201/DQA1*0501-DR4/DQB1*0302/DQA1*0301( 9 patients, 32%; 6 relatives, 15%), DR3/DQB1*0201/ DQA1*0501-DR3/DQB1*0201/DQA1*0501 (5 patients, 18%; 7 relatives, 17%) and DE3/DQB1*0201/DQA1*0501-DR1/ DQB1*0501/DQA1*0101(5 patients, 18%; 1 relative, 2%). Positivity for anti-GAD or for ICA did not correlate with gender, or age at onset or duration of DM. The distribution of high risk HLA genotypes were similar regardless the anti-GAD or anti-ICA status either in patients or in their relatives.

Adolescent↗
PubMed1995

Charing Cross CT protocol for endoscopic sinus surgery.

The Charing Cross computerized tomography protocol for imaging the paranasal sinuses uses 2 mm thick slices with table increments of 8 mm: 10 to 12 coronal and two axial images are produced. These provide the necessary information for diagnosis of chronic rhinosinusitis and safe endoscopic sinus surgery. The technique is quicker and cheaper than previously described protocols and exposes the lens of the eye to less radiation.

Chronic Disease↗
PubMed1994

Antibodies to type II collagen in human serum: storage effects and role of IgM antiidiotype in regulation.

OBJECTIVE: To investigate the observation that IgG reactivity to human denatured type II collagen (denatured CII) is increased in normal human serum stored at 4 degrees C compared to serum stored at -20 degrees C. METHODS: Reactivity was measured by ELISA, and the effect of heating was also assessed. Serum was separated on affinity columns and mixing experiments were performed with the resultant fractions to test for inhibitory or enhancing effects. RESULTS: There is a storage labile and heat labile inhibitor in the IgG depleted fraction of serum stored at -20 degrees C from healthy subjects, and an inhibitor is present in some pooled human IgM preparations which reduces the reactivity of antibody to human CII in serum from both healthy subjects and patients with rheumatoid arthritis. CONCLUSIONS: Storage conditions and heat significantly affect IgG antibodies to denatured CII but not antibodies to other antigens. These effects may be mediated by the presence of an IgM antiidiotype against the IgG antibody to denatured CII.

Antibodies, Anti-Idiotypic↗
PubMed1993

Baseline plasma fibrinolysis and its correlation with clinical manifestations in patients with Raynaud's phenomenon.

OBJECTIVES: (1) To assess if patients with various forms of Raynaud's phenomenon (RP) have abnormal plasma fibrinolysis that may contribute to diminished digital blood flow; (2) to assess whether patients with RP with evidence of endothelial damage have abnormal plasma fibrinolysis; (3) to determine the clinical relevance of abnormalities, if any, in plasma fibrinolysis in patients with RP. METHODS: One hundred and sixty eight patients with significant RP were studied--46 had primary Raynaud's disease (RD), 32 had suspected Raynaud's syndrome secondary to an undifferentiated connective tissue disorder (undifferentiated CTD), 25 had Raynaud's syndrome associated with atherosclerosis (athero RS), and 65 had an underlying connective tissue disease (CTD RS). All attended in the morning after a low fat light breakfast. After a clinical history was obtained, venous blood samples were collected without stasis for assays of plasma fibrinolysis and factor VIII von Willebrand factor antigen (fVIII vWF Ag). Results were compared with those obtained from normal subjects matched for sex and age. As patients with athero RS were significantly older than the other patients with Raynaud's phenomenon, two groups of control subjects were recruited--namely, 'old' and 'young' control subjects. RESULTS: Patients with CTD RS and athero RS had higher concentrations of fVIII vWF Ag (CTD RS median 174.5 range (45-370)% v 100 (38-202)%, p < 0.001; athero RS 182-5 (100-240)% v 100 (50-158)%, p < 0.001). Both had raised fibrinogen (CTD RS 3.25 (1.9-6.8) g/l v 2.4 (1.2-4.2) g/l, p < 0.001; athero RS 3.4 (2.2-6.2) g/l v 2.5 (1.8-3.9) g/l, p < 0.001) and both had diminished fibrinolysis with reduced plasminogen activator activity (CTD RS 79.5 (31-72) mm2 v 92 (37-197) mm2, p < 0.04; athero RS 73 (45-125) mm2 v 98 (41-197) mm2, p < 0.03). Patients with CTD RS also had raised plasminogen activity (3.3 (2.3-5.8) cU/ml v 2.9 (1.5-5.4) cU/ml, p < 0.001). On the contrary, patients with primary RD and undifferentiated CTD had normal fibrinogen and plasma fibrinolysis. Within each patient group, no significant differences in any of the measured variables were found between those who had RP all year and those who had RP in the winter only, those with RP of the hands only and of hands and feet, or those with and without digital ulcers. CONCLUSION: Diminished plasma fibrinolysis is found in patients likely to have endothelial damage (CTD RS and athero RS). These changes are probably a consequence rather than a cause of the disease.

Arteriosclerosis↗