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Biomedical subjects

A Millward

Publications and source records attributed to A Millward.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence and clinical implications of the inter-arm blood pressure difference: A systematic review.

A blood pressure (BP) difference between arms was first reported over 100 years ago. Knowledge of its prevalence and relevance to the accurate measurement of BP remains poor. Current hypertension guidelines do not emphasise it. The objectives of this study were to establish the best estimate of prevalence of the inter-arm difference (IAD) in the population, to consider its implications for accurate BP measurement and treatment, and to discuss its aetiology and potential as a risk marker for cardiovascular disease. Systematic literature review was carried out. The data sources were Medline EMBASE and CINAHL databases, and Index of Theses. Studies reporting prevalence rates of IAD were retrieved and considered for inclusion against explicit methodological criteria. Point prevalence rates were extracted and weighted mean prevalence rates calculated. The main outcome measures were weighted mean prevalences of systolic IAD > or =10 and > or =20 mm Hg and of diastolic IAD > or =10 mm Hg. Thirty-one studies were identified. Most had methodological weaknesses; only four met the inclusion criteria. Pooled prevalences of the IAD from these four studies were 19.6% systolic > or =10 mm Hg (95% CI 18.0-21.3%), 4.2% systolic > or =20 mm Hg (95% CI 3.4-5.1%) and 8.1% diastolic > or =10 mm Hg (95%CI 6.9-9.2%). In conclusion, an IAD is present in a substantial number of patients and should be looked for whenever diagnosis and treatment depend on accurate measurements of BP. The importance of an IAD should be better emphasised in current hypertension management guidelines. There is evidence associating an IAD with peripheral vascular disease, raising the possibility that its presence may predict cardiovascular events.

Algorithms↗
PubMed2004

Polymorphisms of chemokine and chemokine receptor genes in Type 1 diabetes mellitus and its complications.

Cytokines and chemokines have been implicated in the pathogenesis of Type 1 diabetes mellitus (T1DM) and its microvascular complications. Recently, genetic variants of monocyte chemotactic protein-1 (MCP-1), CC-chemokine receptor 2 (CCR2), CC-chemokine receptor 5 (CCR5) genes have been identified. The aim was to investigate whether genetic variants of the MCP-1 G(-2518)A, CCR2B 64I, CCR5 G(59029)A, and CCR5 Delta32 are associated with T1DM and its microvascular complications. Two hundred and sixty patients with T1DM with and without diabetic microvascular complications, and 104 normal controls were recruited for this study. Genotypes of the MCP-1 G(-2518)A, CCR2B 64I, CCR5 G(59029)A, and CCR5 delta32 were performed by polymerase chain reaction followed by digestion with appropriate restriction endonucleases. Frequencies of the MCP-1 A(-2518) allele (74.6% vs. 63.5%, p < 0.003) and A/A genotype (54.5% vs. 34.6%, p < 0.001, Pc = 0.002) were significantly higher in patients with T1DM compared with normal controls. CCR5 G(59029) was slightly increased in the patients with microvascular complications compared with the uncomplicated (21.4% vs. 10%, p < 0.03, Pc = ns). The frequency of haplotype G/G/W was slightly increased in the patients with diabetic complications compared to the uncomplicated (39.6% vs. 28.8%, p < 0.02, Pc = ns). These results suggest that polymorphisms of the MCP-1, CCR2 and CCR5 genes may be associated with T1DM and its complications.

Adolescent↗
PubMed2003

Functional differences between the susceptibility Z-2/C-106 and protective Z+2/T-106 promoter region polymorphisms of the aldose reductase gene may account for the association with diabetic microvascular complications.

Studies have shown that polymorphisms located at positions -106 and approximately -2100 base pairs (5'ALR2) in the regulatory region of the aldose reductase gene are associated with susceptibility to microvascular complications in patients with diabetes. The aim was to investigate the functional roles of these susceptibility alleles using an in vitro gene reporter assay. Susceptibility, neutral and protective 5'ALR2/-106 alleles were transfected into HepG2 cells and exposed to excess D-glucose (D-glucose at final concentrations 14 or 28 mmol/l). Transcriptional activities were determined using a dual luciferase reporter gene assay. The "susceptibility alleles" Z-2 with C-106 had the highest transcriptional activity when compared with the "protective" combination of Z+2 with C-106 alleles (58.7+/-9.9 vs. 10.1+/-0.7; P<0.0001). Those constructs with either the Z or Z-2 in combination with the C-106 allele had significantly higher transcriptional activities when compared to those with the T-106 allele (Z/C-106, 37.4+/-5.4 vs. Z/T-106 7.7+/-1.6, P<0.003; Z-2/C-106, 58.7+/-9.9 vs. Z-2/T-106 10.9+/-0.6, P<0.0001). These results demonstrate that the Z-2/C-106 haplotype is associated with elevated transcriptional activity of the aldose reductase gene. This in turn may explain the role of these polymorphisms in the susceptibility to diabetic microvascular complications.

Aldehyde Reductase↗
PubMed2001

Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom.

Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations, from Finland and Germany. We have studied CAPN10 in white subjects of British/Irish ancestry, using both family-based and case-control studies. In 743 sib pairs, there was no evidence of linkage at the CAPN10 locus, which thereby excluded it as a diabetes-susceptibility gene, with an overall sib recurrence risk, lambda(S), of 1.25. We examined four single-nucleotide polymorphisms (SNP-44, -43, -19, and -63) previously either associated with type 2 diabetes or implicated in transcriptional regulation of calpain-10 expression. We did not find any association between SNP-43, -19, and -63, either individually or as part of the previously described risk haplotypes. We did, however, observe significantly increased (P=.033) transmission of the less common C allele at SNP-44, to affected offspring in parents-offspring trios (odds ratio 1.6). An independent U.K. case-control study and a small discordant-sib study did not show significant association individually. In a combined analysis of all U.K. studies (P=.015) and in combination with a Mexican American study (P=.004), the C allele at SNP-44 is associated with type 2 diabetes. Sequencing of the coding region of CAPN10 in a group of U.K. subjects revealed four coding polymorphisms-L34V, T504A, R555C, and V666I. The T504A polymorphism was in perfect linkage disequilibrium with the diabetes-associated C allele at SNP-44, suggesting that the synthesis of a mutant protein and/or altered transcriptional regulation could contribute to diabetes risk. In conclusion, we were not able to replicate the association of the specific calpain-10 alleles identified by Horikawa et al. but suggest that other alleles at this locus may increase type 2 diabetes risk in the U.K. population.

Alleles↗
PubMed2001

Community care in practice: social work in primary health care.

This paper examines the establishment of social work within primary health care settings in Great Britain, following the passage of the National Health Service and Community Care Act in 1990. Although the improvement of relationships between social workers and primary health care teams has been promoted for a number of years, the advent of formal policies for community care has made this a priority for both social services and health. This paper presents interim findings from the evaluation of three pilot projects in Nottinghamshire, Great Britain. These findings are analysed from three linked perspectives. The first is the extent to which structures and organisations have worked effectively together to promote the location of social workers within health care settings. The second is the impact of professional and cultural factors on the work of the social worker in these settings. The third is the effect of interpersonal relationships on the success of the project. The paper will conclude that there is significant learning from each of these perspectives which can be applied to the future location of social workers to primary health care.

Community Health Services↗
PubMed2000

A CA repeat polymorphism of the IFN-gamma gene is associated with susceptibility to type 1 diabetes.

Recent studies have shown that loci outside the HLA region are involved in determining susceptibility to type 1 diabetes. Polymorphisms in the coding and noncoding regions of the genes encoding cytokines may be involved in modulating the immune response to self and nonself antigens. There is increasing evidence that an imbalance and disruption of the Thl and Th2 T cell subsets play a key role in the development of experimental and clinical type 1 diabetes. The aim of this study was to investigate the frequency of a CA dinucleotide repeat polymorphism in the interferon-gamma (IFN-gamma) gene (IFNG) and a C(-590)T polymorphism of the interleukin-4 (IL-4) gene in 236 Caucasoid patients with type 1 diabetes. There was a highly significant increase in the 3/3 IFNG genotype in the patients compared with normal healthy controls (34.3% vs. 13.5%, p<0.0001) as well as a significant increase in allele 3 of the IFNG locus in the patients compared with controls (51.9% vs. 31.7%, p<0.00001). In contrast, no significant differences were found in the frequency of the C(-590)T IL-4 polymorphism between patients and controls. These results suggest that polymorphisms of the IFNG gene may modify the function of this proinflammatory mediator and the response to pancreatic islet beta cells.

Adolescent↗
PubMed2000

Polymorphisms of the aldose reductase gene and susceptibility to retinopathy in type 1 diabetes mellitus.

PURPOSE: Aldose reductase (ALR2) is the first and rate-limiting enzyme of the polyol pathway and is involved in the pathogenesis of diabetic retinopathy. Polymorphisms of the ALR2 gene are associated with susceptibility to diabetic retinopathy in Chinese and Japanese patients with type 2 diabetes. There are no reports investigating these polymorphisms in white patients with type 1 diabetes from either Western Europe or North America. A CA dinucleotide repeat polymorphism (5'ALR2; located at -2100 bp) as well as a novel C(106)T polymorphism was investigated in 229 white patients with type 1 diabetes, with or without retinopathy. METHODS: The DNA was typed for these polymorphisms using conventional polymerase chain reaction techniques. RESULTS: There was a highly significant increase in the frequency of the Z-2 5'ALR2 allele and Z-2/X (where X is not Z+2) genotype in patients with diabetic retinopathy (n = 159) compared with those without who had diabetes of 20 years' duration (uncomplicated, n = 70; chi(2) = 17.0, P < 0.0001). There was a similar decrease in the Z+2/Y genotype (where Y is not Z-2; chi(2) = 30.1, P < 0.000,001) in the patients with retinopathy compared with the uncomplicated diabetes group. The C/Z-2 C(-106)T/5' ALR2 haplotype was found in 33.3% of the patients with retinopathy and 8.7% of the patients with uncomplicated diabetes. CONCLUSIONS: These results confirm previous studies in other populations and in type 2 diabetes showing that polymorphisms in the promoter region of the ALR2 gene are associated with susceptibility to diabetic retinopathy.

Adolescent↗
PubMed1999

Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes.

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic beta cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) when heterozygous. We studied the role of IPF-1 in Caucasian diabetic and nondiabetic subjects from the United Kingdom. Three novel IPF-1 missense mutations (C18R, D76N, and R197H) were identified in patients with type 2 diabetes. Functional analyses of these mutations demonstrated decreased binding activity to the human insulin gene promoter and reduced activation of the insulin gene in response to hyperglycemia in the human beta-cell line Nes2y. These mutations are present in 1% of the population and predisposed the subject to type 2 diabetes with a relative risk of 3.0. They were not highly penetrant MODY mutations, as there were nondiabetic mutation carriers 25-53 years of age. We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation.

Adult↗
PubMed1998

Susceptibility to diabetic neuropathy in patients with insulin dependent diabetes mellitus is associated with a polymorphism at the 5' end of the aldose reductase gene.

OBJECTIVES: There is evidence that the polyol pathway is involved in the pathogenesis of diabetic neuropathy. Aldose reductase (ALR2) is the first and rate limiting enzyme of this pathway and recent studies have suggested that polymorphisms in and around the gene are associated with the development of diabetic microvascular disease. The aim was to examine the role of ALR2 in the susceptibility to diabetic neuropathy in patients with insulin dependent diabetes mellitus (IDDM). METHODS: One hundred and fifty nine British white patients with IDDM and 102 normal healthy controls were studied using the polymerase chain reaction to test for a highly polymorphic microsatellite marker 2.1 kilobase (kb) upstream of the initiation site of the ALR2 gene. RESULTS: Seven alleles were detected (Z-6, Z-4, Z-2, Z, Z+2, Z+4, and Z+6). There was a highly significant decrease in the frequency of the Z+2 allele in those patients with overt neuropathy compared with those with no neuropathy after 20 years duration of diabetes (14.1% v 38.2%, chi2 =17.3, p<0.00001). A similar difference was also found between the neuropathy group and those patients who have had diabetes for < five years with no overt neuropathy (14.1% v 30.2%, chi2=9.0, p<0.0025). The neuropathy group also had a significant decrease in the frequency of the Z/Z+2 genotype compared with those patients who have no neuropathy after 20 years duration of diabetes (14.0% v 44.7%, chi2=13.0, p<0.0005). CONCLUSION: These results suggest that the aldose reductase gene is intimately involved in the pathogenesis of diabetic neuropathy.

Adult↗
PubMed1997

Continuous monitoring of salivary flow rate and pH at the surface of the dentition following consumption of acidic beverages.

Use of a splint-mounted flexible pH electrode has allowed reliable continuous monitoring of pH at the surface of the dentition whilst still enabling subjects to drink normally. pH was monitored at the palatal upper left central incisor and upper right first permanent molar sites after drinking 1% (w/v) citric acid. A maximal decrease in pH to values of 2-3 was observed after 1 min followed by a slower recovery which was above pH 5.5 within 2 min at the former site and in 4-5 min at the latter site. A sharp rise in parotid saliva flow rate was seen at 1 min after drinking the same concentration of citric acid by glass, straw or feeder cup, which returned to resting levels within 6 min although the fall-off of flow rate was slower with the feeder cup. Thus, after dietary acid intake the pH at the surface of the dentition is below the critical pH for enamel dissolution for shorter periods than previously suggested, which is probably a reflection of salivary neutralisation and washing.

Adolescent↗
PubMed1997

Polymorphism in the 5'-end of the aldose reductase gene is strongly associated with the development of diabetic nephropathy in type I diabetes.

Recent studies suggest that the gene encoding aldose reductase (ALR2), the enzyme that converts glucose to sorbitol, may confer susceptibility to microvascular disease. DNA from 275 British Caucasian patients with type I diabetes and 102 normal healthy control patients were typed for a (CA)n dinucleotide repeat polymorphic marker in the 5'-region of the ALR2 gene using polymorase chain reaction (PCR). A highly significant decrease in the frequency of the Z+2 allele was found in patients with nephropathy (nephropathy group) compared with those with no complications after a 20-year duration of diabetes (uncomplicated group) (12.7 vs. 38.2%, respectively, chi2 = 18.6, P < 0.00001); this was accompanied by an increase in the Z-2 allele in the nephropathy group (32.0 vs. 12.7% in the uncomplicated group). The nephropathy group also had a significant decrease in the Z/Z+2 genotype compared with the uncomplicated patients (10.7 vs. 44.7%, chi2 = 16.0, P < 0.0001) and an increased frequency of the Z/Z-2 genotype. There was no significant association with diabetic retinopathy. These results demonstrate that the ALR2 gene may play a role in susceptibility to diabetic nephropathy; individuals with the Z+2 allele are more than seven times less likely to develop diabetic renal disease than those without this marker. This marker may prove valuable in screening for patients with diabetic nephropathy at diagnosis of diabetes.

Aldehyde Reductase↗
PubMed1995

In vitro techniques for erosive lesion formation and examination in dental enamel.

An in vitro experimental model has been developed for erosive lesion formation in dental enamel which can mimic in vivo conditions at the tooth surface. The features of this model provide a very reproducible method of producing erosive lesions in several teeth under identical conditions which can be varied to allow examination of a number of different parameters. A replica impression technique has also been developed for subsequent non-destructive microscopic examination of the lesions and comparison with in vivo lesions.

Acrylic Resins↗
PubMed1994

The distribution and severity of tooth wear and the relationship between erosion and dietary constituents in a group of children.

There is very little published information on the severity of tooth wear in children. The current investigation involved clinical examination of 101 children and an assessment of their dietary habits. Evidence of tooth wear was found in over 80% of maxillary incisor teeth, and 30% of primary molar teeth had some dentine exposed. There were 21 children who were regarded as having 'mild' erosion, 45 'moderate' erosion and 35 'severe' erosion. There were highly statistically significant differences between the three groups in relation to drinking habits; the mean number of carbonated drinks consumed per week by children in the 'mild', 'moderate' and 'severe' erosion groups was 3.9, 5.8 and 13.9 respectively, of fruit drinks 10.3, 16.4 and 18.3, and of all fruit-based drinks 17.9, 27.1 and 39.0. There were also highly significant differences in those having a fruit-based drink at bed-time; 14% in the 'mild' erosion group, 32% in the 'moderate' and 60% in the 'severe' group. Although fresh fruit and yoghurt consumption followed the same trend, this did not reveal statistically significant differences. It is important to identify children who exhibit clinical evidence of erosion so that advice can be given about consumption of acidic dietary constituents.

Adolescent↗
PubMed1994

Analysis of the peripheral T-cell receptor V beta repertoire in newly diagnosed patients with type I diabetes.

Type I diabetes is an autoimmune disease characterised by a marked activation of peripheral T cells around the time of clinical diagnosis. Studies of T-cell antigen receptor V beta (TCRBV) gene usage in type I diabetes have been conflicting. Using a semi-quantitative polymerase chain reaction technique and flow cytometry we have investigated the TCRBV gene usage of 13 newly diagnosed patients with type I diabetes and 11 normal healthy controls. No preferential TCRBV gene usage was found between patients and controls even after matching for HLA-DR3 and/or -DR4. In addition, no significant differences in TCRBV gene usage were found between sequential samples taken over a period of up to 7 months following diagnosis. These results suggest that the TCR repertoire of these patients is heterogeneous and it is unlikely that a single 'pathogenic' T-cell clone is dominant at the clinical onset of the disease.

Adult↗