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Biomedical subjects

C Hall

Publications and source records attributed to C Hall.

At least 19 recordsLinked to original sources
PubMed2006

Studies of the SIM1 gene in relation to human obesity and obesity-related traits.

OBJECTIVE: The single-minded 1 (SIM1) is a basic helix-loop-helix transcription factor, which plays a critical role in the development of the paraventricular nucleus (PVN) of the hypothalamus. SIM1-deficient mice have a hypocellular PVN and are severely obese with increased food intake. DESIGN: We examined whether variants in the SIM1 gene might be associated with severe early-onset obesity in humans. Two hundred and seventy-seven subjects with hyperphagia and severe, early-onset obesity were screened. Association studies with common single-nucleotide polymorphisms (SNPs) in the SIM1 gene were performed in two population-based cohorts. RESULTS: One novel missense mutation, I128T, was found in one obese subject and not in 192 controls. However, the variant did not co-segregate with obesity in the family. Four SNPs, IVS4+83GA, P352T, A371V and T653T, were also identified. The two common SNPs, P352T and A371V, which are in complete linkage disequilibrium, were genotyped in 981 subjects from a population-based cohort, the Ely Study. An allele frequency of 0.13 was observed. Male subjects carrying the P352T/A371V haplotype were found to have a slightly higher body mass index (BMI; P=0.038). Female subjects homozygous for the haplotype gained more weight over a period of 4.5 and 10 years (P=0.003 and P=0.02, respectively). The association studies were repeated in another population-based cohort, the European Prospective Investigation into Cancer and Nutrition (EPIC) - Norfolk Study with 4869 subjects successfully genotyped. Male subjects homozygous for the P352T/A371V haplotype had slightly higher BMI (P=0.04). CONCLUSION: Mutations in SIM1 are not commonly found in humans with severe early-onset obesity. The relationship between the common variants in SIM1 with BMI and body weight gain deserves further exploration in other populations.

Basic Helix-Loop-Helix Proteins↗
PubMed2006

Period and cohort dynamics in fertility norms at the onset of the demographic transition in Kenya 1978-1998.

A characteristic of African pre-transitional fertility regimes is large ideal family size. This has been used to support claims of cultural entrenchment of high fertility. Yet in Kenya fertility rates have fallen. In this paper this fall is explored in relation to trends in fertility norms and attitudes using four sequential cross-sectional surveys spanning the fertility transition in Kenya (1978, 1984, 1989 and 1998). The most rapid fall in the reported ideal family size occurred between 1984 and 1989, whilst the most rapid fall in the total fertility rate occurred 5 to 10 years later, between 1989 and 1998. Thus these data, spanning the fertility transition in Kenya, support the traditional demographic model that demand for fertility limitation drives fertility decline. These data also suggest that the decline in fertility norms over time was partly a period effect, as the reported ideal family size was seen to fall simultaneously in all age cohorts, and partly a cohort effect, as older age cohorts reporting higher ideal family sizes were replaced by younger cohorts reporting lower ideal family sizes. These data also suggest that a new fertility norm of four children may have developed by 1989 and continued until 1998. This is consistent with, and perhaps could have been used to predict, the stall in the Kenyan fertility decline after 1998.

Adolescent↗
PubMed2006

Wavelet-based feature extraction applied to small-angle x-ray scattering patterns from breast tissue: a tool for differentiating between tissue types.

This paper reports on the application of wavelet decomposition to small-angle x-ray scattering (SAXS) patterns from human breast tissue produced by a synchrotron source. The pixel intensities of SAXS patterns of normal, benign and malignant tissue types were transformed into wavelet coefficients. Statistical analysis found significant differences between the wavelet coefficients describing the patterns produced by different tissue types. These differences were then correlated with position in the image and have been linked to the supra-molecular structural changes that occur in breast tissue in the presence of disease. Specifically, results indicate that there are significant differences between healthy and diseased tissues in the wavelet coefficients that describe the peaks produced by the axial d-spacing of collagen. These differences suggest that a useful classification tool could be based upon the spectral information within the axial peaks.

Algorithms↗
PubMed2006

Leisure activities and the risk of amnestic mild cognitive impairment in the elderly.

OBJECTIVE: To study the influence of leisure activity participation on risk of development of amnestic mild cognitive impairment (aMCI). METHODS: The authors examined the relationship between baseline level of participation in leisure activities and risk of aMCI in a prospective cohort of 437 community-residing subjects older than 75 years, initially free of dementia or aMCI, using Cox analysis adjusted for age, sex, education, and chronic illnesses. The authors derived Cognitive and Physical Activity Scales based on frequency of participation in individual activities. RESULTS: Over a median follow-up of 5.6 years, 58 subjects had development of aMCI. A one-point increase on the Cognitive (hazard ratio [HR] 0.95, 95% CI 0.91 to 0.99) but not Physical Activities Scale (HR 0.97, 95% CI 0.93 to 1.01) was associated with lower risk of aMCI. Subjects with Cognitive Activity scores in the highest (HR 0.46, 95% CI 0.24 to 0.91) and middle thirds (HR 0.52, 95% CI 0.29 to 0.96) had a lower risk of aMCI compared with subjects in the lowest third. The association persisted even after excluding subjects who converted to dementia within 2 years of meeting criteria for aMCI. CONCLUSIONS: Cognitive activity participation is associated with lower risk of development of amnestic mild cognitive impairment, even after excluding individuals at early stages of dementia.

Aged↗
PubMed2006

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure.

BACKGROUND: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. METHODS: Sixteen men and four women aged 63.0+/-10.4 (mean+/-S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. RESULTS: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables CONCLUSION: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

Cardiac Output, Low↗
PubMed2006

A comparison of endoscopic and microscopic removal of wax: a randomised clinical trial.

OBJECTIVES: Using a microscope to achieve a view of the canal during dewaxing is the most commonly performed method of dewaxing in secondary care, but an endoscope can also be used. We set out to compare endoscopic and microscopic dewaxing. DESIGN: Randomised clinical trial. SETTING: Otolaryngology Outpatient Department. PARTICIPANTS: One hundred participants selected sequentially from patients requiring dewaxing of their ears to allow examination of the tympanic membrane. Patients with external or middle ear pathology were excluded. METHODS: Patients were randomly assigned to have dewaxing performed using microinstruments aided by vision with a microscope or an endoscope. All participants who were entered the study completed the study. MAIN OUTCOME MEASURES: Levels of pain and discomfort experienced by the participants were assessed by a visual analogue scale (VAS). Difficulty of performing the dewaxing indicated by the endoscopist using a VAS. The length of time taken to perform the dewaxing was also recorded. RESULTS: Endoscopic dewaxing was less uncomfortable than microscopic dewaxing for patients (VAS median values 5 and 25 respectively; P < 0.002) as well as less painful (VAS median values 3.5 and 10 respectively; P < 0.075). Endoscopic dewaxing was easier to perform than microscopic dewaxing (VAS median values for difficulty were 9 and 20 respectively; P < 0.005) and took less time (mean time for endoscopic dewaxing was 1.8 min versus 3.3 min for microscopic dewaxing (P < 0.001). Ninety-one per cent of ears could be dewaxed with a Jobson-Horne probe or wax hook. CONCLUSIONS: The cost of an operating microscope suitable for use with dewaxing is approximately 10 times that of a suitable endoscope, dewaxing is a cheaper alternative to microscopic dewaxing that has benefits for the patient and clinician.

Adolescent↗
PubMed2005

Spatially resolved measurement of rock core porosity.

Density weighted, centric scan, Conical SPRITE MRI techniques are applied in the current work for local porosity measurements in fluid saturated porous media. The methodology is tested on a series of sandstone core samples. These samples vary in both porosity and degree of local heterogeneity due to bedding plane structure. The MRI porosity measurement is in good agreement with traditional gravimetric measurements of porosity. Spatially resolved porosity measurements reveal significant porosity variation in some samples. This novel MRI technique should have applications to the characterization of local porosity in a wide variety of porous media.

Journal Article↗
PubMed2005

Considerable differences between methods for plasma D-dimer in the diagnosis of venous thrombosis: increased positive prediction using elevated discriminatory limits.

Four analytical methods for plasma D-dimer have been compared in a group of 82 consecutive patients with suspected venous thrombosis, 22 of whom subsequently received a positive clinical diagnosis. Differences in diagnostic power between methods were observed. In three of the four methods tested, the use of elevated discriminatory limits (rather than conventional 95-percentile upper reference limits) resulted in stronger positive predictive values for thromboembolism. We suggest that this approach may result in better diagnostic performance of the D-dimer method.

Adult↗
PubMed2005

The immunogenicity of a conformationally restricted peptide mimetic of meningococcal lipooligosaccharide.

Life-threatening meningitis and septicaemia caused by Neisseria meningitidis are a public health priority, and their prevention by vaccination is a major objective. Meningococcal capsular polysaccharide-based vaccines are effective against the major invasive serogroups, except for serogroup B, the capsule of which mimics human polysaccharides and is poorly immunogenic. An alternative vaccine candidate that has the potential to offer cross-protection against antigenically diverse meningococci is the lipooligosaccharide (LOS). The structurally constrained peptide mimetic, C22, of a bactericidal antibody epitope within LOS was previously shown to elicit cross-reactive antibodies to meningococcal LOS when complexed to NeutrAvidintrade mark as a carrier protein. The immunogenicity of this antigen in H-2(d) (BALB/c) and H-2(k) (C3H/HeN) haplotype mice was further investigated. Anti-LOS immunoglobulin G (IgG) antibody titres increased with the vaccine dose and correlated with the anti-C22 peptide antibody titres in both haplotypes. Antigen-stimulated Th1/Th2 cytokine secretion by splenocytes and antibody isotypes indicated a Th2-type immune response with IgG1 antibodies and a low titre of IgG2b. There was no serum bactericidal activity observed against the meningococcus.

Animals↗
PubMed2004

Novel p21-activated kinase-dependent protrusions characteristically formed at the edge of transformed cells.

During long-term culture, certain lines become neoplastic while accumulating changes in cell shape. Early and late cell populations have characteristic shape phenotypes that have been quantified by computerized assay. Phenotypes are determined from variables describing three-dimensional aspects of the subcellular distribution of mass. The features of cells can be recognized by use of latent factors, which are theoretical variables based on the covariance of the primary variables. Factor #7 represented a cell edge feature different from filopodia. We studied the morphological characteristics and morphogenesis of the feature. Brief exposure of cells from rat tracheal epithelium to phorbol 12-myristate 13-acetate (PMA) enhanced #7 values. The time to reach maximal #7 values was prolonged if PMA was administered with calcium ionophore or lysophosphatidic acid (LPA). Factor #7 was elevated during periods of ruffling suppression and stress fiber reorganization. Cells showing high #7 values were examined by scanning electron microscopy (SEM) and found to exhibit strap-shaped and cupola-shaped projections. Because RhoA regulates stress fiber formation, we sought to perturb #7 features by introducing dominant-acting negative and positive constructs of RhoA, RhoA-N19, and RhoA-V14. Neither affected #7 values. Although overexpression of the kinase inhibitory domain of p21-activated kinase 1 (PAK) had no effect on #7 values, they were affected by overexpression of a domain binding PAK-interacting guanine nucleotide exchange factor (PIX). Because a PAK-PIX complex is implicated in the remodeling of focal complexes (FCs) and recycling of PAK to the cytoplasm, the results implicate a component of FCs in the formation of #7 features. The data suggested that feature formation is driven by activated Cdc42-binding kinase (ACK) and Rac. Moreover, they suggested that the #7 protrusions are neurite-like structures and that their development involves FC regulation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Development of neuronal sensitivity to toxins in cerebrospinal fluid from HIV-type 1-infected individuals.

HIV infection of the immature nervous system generally results in a rapid progression of neurological disease that cannot easily be explained by the severity of encephalitis, viral burden, systemic immune deficiency, or developmental changes in utero. Rather than the viral infection dictating disease progression, we explored the possibility that immature neurons might be particularly sensitive to toxins secreted in response to HIV. Primary cultures of rat cortical neurons were exposed to toxic cerebrospinal fluid (CSF) from HIV-infected individuals (CSF(tox)) and evaluated for changes in intracellular calcium and cell death. CSF(tox) had no detectable effect on early neurite outgrowth, calcium regulation, or cell death during the first few days in culture. Starting at Day 4, delayed increases in intracellular calcium appeared in response to CSF(tox). The magnitude of the delayed calcium rise and cell death increased with the age of the culture and correlated with the appearance of synaptophysin immunoreactive varicosities. A similar gradual development of sensitivity was seen during exposure of feline neurons to toxins generated by choroid plexus macrophages after exposure to feline immunodeficiency virus. The possibility that toxin sensitivity is dependent on the presence of synaptic activity is consistent with the rapid pathogenesis in the CNS seen during the first postnatal year. Emerging synaptic activity coupled with other factors such as high metabolic demand in the young nervous system may combine to increase the likelihood of calcium overload and neuronal dysfunction in response to HIV-associated toxins.

Animals↗
PubMed2004

8-isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP-1 macrophages, resulting in long-lived foam cells.

BACKGROUND: Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8-isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F(2)-isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8-isoprostane to modulate oxidized (ox)LDL-induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation. METHODS AND RESULTS: 8-isoprostane (10 micro M) augmented the oxLDL-induced (20 micro g mL(-1)) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and protein level], assessed by RT-PCR and Western blotting, respectively. Moreover, 8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving both mitochondrial-protective and caspase-suppressive mechanisms. Along with these changes, 8-isoprostane increased the oxLDL-induced gene expression of matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity. CONCLUSIONS: We show that 8-isoprostane increases foam cell formation at least partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells, inducing long-lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8-isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization.

Apoptosis↗
PubMed2004

A methodology using subjective and objective measures to compare plaque inhibition by toothpastes.

OBJECTIVES: Plaque scoring usually employs subjective indices. The aim was to compare plaque inhibition of three toothpastes using two objective and one subjective measures of plaque. MATERIAL AND METHODS: Formulations were: (1) an experimental anti-plaque paste (test); (2) an experimental paste (minus active or negative control); and (3) a proprietary anti-plaque toothpaste product (positive control). The study was a blind, randomised crossover design using a 4-day, no tooth brushing, plaque regrowth model and involving 22 healthy subjects. After baseline plaque removal, subjects rinsed twice a day with slurries of the allocated paste. On day 5, plaque was scored by index, wet weight and optical density of extracted disclosing solution from the plaque (stain intensity). RESULTS: All data showed the same pattern. There were highly significant subject and treatment effects but not period effects. The positive control was highly significantly more effective in plaque control than the test and minus active experimental formulations, which in turn were not significantly different from each other. There were strong and significant correlations between pairs of scoring methods particularly wet weight and stain intensity. CONCLUSION: The use of objective methods of plaque alongside conventional subjective indices provided convincing evidence for increased discriminatory power in a study comparing plaque inhibition by toothpastes.

Adult↗
PubMed2004

Sustained oral health improvement and use of toothbrushes and dentifrice by previous users of traditional materials in a rural population in Andhra Pradesh, India.

AIM: To follow-up, one year later, a double-blind, randomised study, which investigated the effect of regular brushing with dentifrices on the oral health of an economically disadvantaged rural population in Andhra Pradesh, India who were primarily users of traditional materials. SUBJECTS: 150 of the original study population. METHOD: Examination to determine whether the improvements in oral health status and oral health behaviour (use of toothbrush and dentifrice), being unsupported, had been sustained since completion of the original study. RESULTS: Data analysis showed sustained, statistically significant improvements in gingival health as measured by gingival bleeding and plaque indices (GBI and PI) comparing users and non-users of toothbrushes and dentifrice in the original study (PI: p = 0.04; GBI: p = 0.03) and sustained use of toothbrushes and dentifrice by 60% of the subjects at follow-up one year later. CONCLUSIONS: This study shows a beneficial effect on oral hygiene indices following the introduction of toothbrushes and dentifrices to a community using traditional oral hygiene materials and sustainability of use of these materials with motivation and support. It may therefore be concluded that it is feasible to achieve significant use of conventional toothbrushes and toothpastes, with consequent major and sustained improvements in plaque control and gingival health in a disadvantaged population hitherto often considered as not amenable to conventional oral hygiene for cultural or economic reasons.

Adolescent↗
PubMed2004

An unusual presentation of group B streptococcal sepsis.

This paper describes the devastating outcome of a neonate who presented with severe late onset group B beta-haemolytic streptococcal (GBS) disease. There were extensive infarcts of the brain and gangrene of the toes. The purpose of this report is to alert healthcare workers of the unusual presentation and that fatal late onset group B beta-haemolytic streptococcal disease may occur despite early and effective management.

Cellulitis↗
PubMed2003

Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine.

OBJECTIVES: The purpose of this study was to assess the effects of amlodipine on neurohormones and oxidative stress in nonischemic cardiomyopathy, and determine the relationship between baseline and posttreatment levels of these markers with survival. BACKGROUND: Neurohormones and oxidative stress are important in the pathophysiology of heart failure. Calcium-channel blockers are associated with poor outcomes in patients with heart failure, in part due to neurohormonal activation. In contrast, amlodipine, a second-generation dihydropyridine, has a more favorable clinical profile. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation 2 (PRAISE-2) trial, a subset of 181 patients with nonischemic cardiomyopathy were randomized to amlodipine (10 mg/day) or placebo. Blood samples were evaluated at baseline, 2 weeks and 26 weeks for norepinephrine, epinephrine, angiotensin II, dopamine, N-terminal pro-atrial natriuretic peptide (Nt-pro-ANP), brain natriuretic peptide (BNP), adrenolutin and malondialdehyde. RESULTS: There was no difference in levels of neurohormones or oxidative stress markers between the amlodipine and placebo groups at the different times. Both Nt-pro-ANP and BNP decreased at 2 weeks and at 26 weeks. Baseline Nt-pro-ANP correlated with survival in multivariate analysis (P =.001). A strong relationship was found between a reduction in BNP at 26 weeks and survival, with a hazard ratio of 0.153 (95% CI 0.051-0.461, P =.017). No relationship was found between markers of oxidative stress and survival. CONCLUSIONS: We conclude that amlodipine does not affect circulating neurohormones and oxidative stress markers in patients with nonischemic cardiomyopathy treated with angiotensin-converting enzyme inhibitors, digoxin and diuretics. In addition, low circulating Nt-pro-ANP and a reduction in BNP over time confers a good prognosis.

Amlodipine↗
PubMed2003

The effect of a toothpaste containing 2% zinc citrate and 0.3% Triclosan on bacterial viability and plaque growth in vivo compared to a toothpaste containing 0.3% Triclosan and 2% copolymer.

OBJECTIVE: To compare the antimicrobial efficacy and effect on plaque growth of a new silica-based fluoride toothpaste containing 2% zinc citrate/ 0.3% Triclosan with a silica-based fluoride toothpaste containing 0.3% Triclosan/2% copolymer. METHODS: In Study 1, plaque was collected after one week's use of each toothpaste and assessed for bacterial viability, live/ dead ratio and microbial membrane integrity. In study 2, plaque was measured immediately and 18 hours after a single brushing with the specified toothpastes. RESULTS: The 2% zinc citrate/0.3% Triclosan formulation significantly reduced the total number of viable aerobic and anaerobic bacteria (p = 0.0223 and p = 0.0443 respectively) compared to the 0.3% Triclosan/2% copolymer formulation. Both toothpastes increased the bacterial membrane permeability significantly. However, the proportion of live bacteria for the 2% zinc citrate/0.3% Triclosan product was significantly reduced (p < 0.05). Study 2 showed significantly less plaque growth 18 hours after using the 2% zinc citrate/0.3% Triclosan toothpaste compared to the 0.3% Triclosan/2% copolymer toothpaste (p < 0.01). CONCLUSION: Regular use of a fluoride toothpaste containing 2% zinc citrate and 0.3% Triclosan, significantly reduced the viability of plaque bacteria compared to a fluoride toothpaste containing 0.3% Triclosan/ 2% copolymer 12 hours after brushing. In addition, a clinical plaque growth study confirmed that this anti-microbial efficacy leads to a significant reduction in plaque growth.

Adult↗