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Biomedical subjects

K Hughes

Publications and source records attributed to K Hughes.

At least 73 records · Page 4Linked to original sources

Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore.

STUDY OBJECTIVE: To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is at least partly explained by central obesity, insulin resistance, and syndrome X (including possible components). DESIGN: Cross sectional study of the general population. SETTING: Singapore. PARTICIPANTS: Random sample of 961 men and women (Indians, Malays, and Chinese) aged 30 to 69 years. MAIN RESULTS: Fasting serum insulin concentration was correlated directly and strongly with body mass index (BMI), waist-hip ratio (WHR), and abdominal diameter. The fasting insulin concentration was correlated inversely with HDL cholesterol and directly with the fasting triglyceride concentration, blood pressures, plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA), but it was not correlated with LDL cholesterol, apolipoproteins B and A1, lipoprotein(a), (Lp(a)), fibrinogen, factor VIIc, or prothrombin fragment (F)1 + 2. This indicates that the former but not the latter are part of syndrome X. While Malays had the highest BMI, Indians had a higher WHR (men 0.93 and women 0.84) than Malays (men 0.91 and women 0.82) and Chinese (men 0.91 and women 0.82). In addition, Indians had higher fasting insulin values and more glucose intolerance than Malays and Chinese. Indians had lower HDL cholesterol, and higher PAI-1, tPA, and Lp(a), but not higher LDL cholesterol, fasting triglyceride, blood pressures, fibrinogen, factor VIIc, or prothrombin F1 + 2. CONCLUSIONS: Indians are more prone than Malays or Chinese to central obesity with insulin resistance and glucose intolerance and there are no apparent environmental reasons for this in Singapore. As a consequence, Indians develop some but not all of the features of syndrome X. They also have higher Lp(a) values. All this puts Indians at increased risk of atherosclerosis and thrombosis and must be at least part of the explanation for their higher rates of CHD.

Adult↗

Aerosol delivery during continuous nebulization.

BACKGROUND AND OBJECTIVES: Continuous administration of aerosolized beta 2-agonists has been suggested as an effective treatment for severe reversible airways disease. To facilitate continuous therapy and avoid a feed system for small-volume nebulizers (SVNs), a large-volume medication nebulizer (Vortran HEART) was developed. The goal of this study was to determine actual drug delivery of the HEART and conventional SVNs for both adult and pediatric breathing patterns. DESIGN: Output studies were conducted on comparable samples of CIS-US AeroTech II and Hospitak PowerMist SVNs and Vortran HEART large-volume continuous nebulizers. To duplicate clinical aerosol delivery via an aerosol mask, drug particles were inhaled through the mouth of a model of a human face for two test breathing patterns (adult = tidal volume (Vt) of 500 mL, 20 breaths/min, duty cycle of 40%; pediatric = VT of 100 mL, 35 breaths/min, duty cycle of 40%), generated by a ventilator. Radiolabeled particles of saline solution, confirmed to behave identically to albuterol, were collected on absolute filters at the mouth of the face to measure the actual mass of albuterol particles delivered to the airway opening. RESULTS: The AeroTech II and PowerMist SVNs delivered 5.14 and 3.74 mg/h, respectively, for the adult breathing pattern and 2.97 and 2.48 mg/h, respectively, for the pediatric breathing pattern. Drug delivery rates of the HEART were a function of drug concentration and ranged from 0.87 to 3.48 mg/h for the adult breathing pattern. For the pediatric breathing pattern, drug delivery rate was a function of drug concentration and inspired minute ventilation and ranged from 0.41 to 1.83 mg/h. CONCLUSION: Our data demonstrate that drug delivery to the patient, expressed as inhaled mass over time, is similar for continuous nebulization (HEART system) and intermittently filled SVNs. In addition, for all nebulizers, the influence of the pediatric breathing pattern needs to be considered. Continuous nebulization permits the redistribution of health-care personnel and may reduce the costs of therapy.

Adrenergic beta-Agonists↗

Prevalence rates of major and minor electrocardiogram abnormalities in the Singapore general population.

A cross-sectional survey on the general population was carried out in Singapore, with each of the 2143 persons (Chinese, Malays and Indians) aged 18 to 69 years having a 12-lead resting electrocardiogram (ECG). The tracings were coded according to the Minnesota Code with major abnormalities being Q wave changes (1-1 and 1-2), complete atrio-ventricular (A-V) block (6-1), and left bundle branch block (7-1) and minor abnormalities being lesser Q wave changes (1-3), ST depression of at least 1 mm (4-1), and T wave inversion of at least 1 mm (5-1 and 5-2). In all age groups the prevalence rates of any major abnormality were higher in males than females. In the age-adjusted 18-69 age group the prevalence rates in males and females were 2.0% and 0.5% respectively (P = 0.001). The prevalence rates of any minor abnormality (without any major abnormality) were higher in females than males in all age groups and in the age-adjusted 18-69 age group the prevalence rates in males and females were 3.5% and 5.4% respectively (P = 0.027). The prevalence rates of any minor abnormality (without any major abnormality) in the 18-29 age group in males and females were 2.2% and 4.7% respectively, indicating that these proportions of the population have minor abnormalities as a normal physiological variant. It is estimated in the 50-69 age group that 33.8% of males and 50.0% of females with any minor abnormality (without any major abnormality) have these changes as a normal physiological variant.

Adult↗

Screening for and treatment of hypercholesterolaemia--a review.

The screening for and treatment of hypercholesterolaemia is still a complex and controversial issue. As hypercholesterolaemia is a major risk factor for coronary heart disease (CHD), there was initially much enthusiasm for mass screening with intervention recommended for persons with serum cholesterol levels > or = 6.5 mmol/L. However, trials of treatment of hypercholesterolaemia using lipid lowering drugs showed overall benefit (i.e. reduced all-cause mortality) only for persons with pre-existing CHD (secondary prevention) or other major risk factors. For this and other reasons (e.g. cost effectiveness) screening for hypercholesterolaemia has been recommended for persons with CHD or major risk factors (family history of premature coronary heart disease, cigarette smoking, hypertension, and diabetes mellitus). Recent trials with statins have shown greater benefit than with other lipid lowering drugs, confirming the benefits of secondary prevention. In addition, one trial has shown overall benefit after 5 years for middle-aged hypercholesterolaemic males without a previous myocardial infarction, raising the possibility of mass screening. However, longer follow-up of a number of trials of primary prevention including on persons without risk factors together with a full assessment of the local situation with regards to hypercholesterolaemia is needed before mass screening can be recommended.

Adult↗

Hypercholesterolaemia and its treatment in Singapore with implications for screening.

The National University of Singapore Heart Study is a cross-sectional survey of the whole of Singapore from 1993 to 1995 with a random sample of 961 persons aged 30 to 69 years (response rate 71.2%). Serum lipids were measured enzymatically on an autoanalyser (Ektachem, kodak). Hypercholesterolaemia was diagnosed if the person was on lipid lowering drugs or had a serum cholesterol > or = 6.5 mmol/L (250 mg/dL). Results for the 40 to 64 age group are presented. The proportion and number in Singapore with hypercholesterolaemia were high, 23.7% and 186,544 persons respectively. However, they declined with the additional requirement of coronary heart disease (CHD) or risk factors (i.e. cigarette smoking, hypertension or diabetes mellitus), and were small if only hypercholesterolaemic persons with CHD were included, 1.6% and 13,126 persons respectively. For both genders, the proportions on drugs increased with the added options of CHD or risk factors, so that for persons with hypercholesterolaemia and CHD the proportion on drugs was very high i.e. 84.0%. However, 11.2% of persons with only hypercholesterolaemia (i.e. without CHD or other risk factors) had been prescribed drugs. The main conclusions were:1) The use of different criteria for the screening and treatment of hypercholesterolaemia would involve large differences in the number of Singaporeans on lipid lowering drugs and this should be considered when deciding policy and 2) Medical practitioners currently to some extent do consider the presence of CHD or other risk factors when prescribing lipid lowering drugs for hypercholesterolaemia.

Adult↗

Promoting sugar-free medicines: parents' views.

BACKGROUND: A long-standing concern among dental health professionals has been about the harmful effects of sugered medicines on teeth, especially in children who regularly take such medications. AIM: To investigate parental attitudes, perceptions, and motivations to sugar-free medicines so that an effective promotional campaign could be mounted. METHOD: A qualitative, focus group approach was used to gather data. RESULTS: These show the dominant influence of the doctor over the patient/parent, and the bearing this has on the prescribing of sugar-free medicines. CONCLUSION: This study highlights the scope for sugar-free medicine promotion for prescribed and over-the-counter products, and the polarizing of attitudes to the use of sugar-free medicines based on social class.

Attitude to Health↗

Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.

The Drosophila gene product Wingless (Wg) is a secreted glycoprotein and a member of the Wnt gene family. Genetic analysis of Drosophila epidermal development has defined a putative paracrine Wg signalling pathway involving the zeste-white 3/shaggy (zw3/sgg) gene product. Although putative components of Wg- (and by inference Wnt-) mediated signalling pathways have been identified by genetic analysis, the biochemical significance of most factors remains unproven. Here we show that in mouse 10T1/2 fibroblasts the activity of glycogen synthase kinase-3 (GSK-3), the murine homologue of Zw3/Sgg, is inactivated by Wg. This occurs through a signalling pathway that is distinct from insulin-mediated regulation of GSK-3 in that Wg signalling to GSK-3 is insensitive to wortmannin. Additionally, Wg-induced inactivation of GSK-3 is sensitive to both the protein kinase C (PKC) inhibitor Ro31-8220 and prolonged pre-treatment of 10T1/2 fibroblasts with phorbol ester. These findings provide the first biochemical evidence in support of the genetically defined pathway from Wg to Zw3/Sgg, and suggest a previously uncharacterized role for a PKC upstream of GSK-3/Zw3 during Wnt/Wg signal transduction.

Androstadienes↗

The lambda sign at 10-14 weeks of gestation as a predictor of chorionicity in twin pregnancies.

Chorionicity was prospectively determined in 369 twin pregnancies by ultrasound at 10-14 weeks of gestation. Pregnancies were classified as monochorionic if there was a single placental mass in the absence of the lambda sign at the inter-twin membrane-placental junction, and dichorionic if there was a single placental mass but the lambda sign was present, or the placentas were not adjacent to each other. In 81 (22%) cases, the pregnancies were classified as monochorionic and in 288 (78%) as dichorionic. Pregnancy outcome was available in 279 cases and all 63 of these pregnancies classified as monochorionic resulted in the delivery of same-sex twins. Similarly, all 100 different-sex pairs were correctly classified as dichorionic. These findings demonstrate the high reliability of ultrasound examination at 10-14 weeks of gestation in determining chorionicity in twin pregnancies.

Adult↗

Experimental study of allogeneically vascularized prefabricated flaps.

The authors fashioned vascularized island flaps using cryopreserved allogeneic vascular bundles as the vascular pedicles in rabbits. Auricular vessels of 8 cm in length were harvested and cryopreserved in liquid nitrogen for 30 days. The allovascular bundles were anastomosed into the recipients' native auricular vessels. Dorsal flaps (6 x 6 cm) in the recipient were raised on the implanted allovascular bundle. Eight days later, the flaps were elevated as vascular island flaps nourished by the allovascular bundle. Computed microangiography demonstrated the anastomoses between the vasculatures of the implanted vessels and the recipient sites 8 days after vascular implantation in the dorsal flap. Flap survival estimation, which was done 1 week after flap elevation, showed flap viability. Allogeneic vascular bundles proved their potential utility as vascular pedicles of autologous tissue transfer.

Anastomosis, Surgical↗

Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period.

Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.

Amino Acid Sequence↗

Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation.

OBJECTIVE: To determine the prevalence of increased fetal nuchal translucency thickness in twin pregnancies and to evaluate screening for trisomy 21 by a combination of translucency thickness and maternal age. DESIGN: Prospective screening study at 10 to 14 weeks of gestation. SETTING: Fetal Medicine Centre. POPULATION: 22,518 self-selected pregnant women at 10 to 14 weeks of gestation, including 21,477 singleton and 448 twin pregnancies with live fetuses. METHODS: Fetal nuchal translucency thickness was measured by ultrasound examination at 10-14 weeks. Sensitivity and false positive rates of screening for trisomy 21 by a combination of fetal nuchal translucency thickness and maternal age were calculated. MAIN OUTCOME MEASURES: Prevalence of increased nuchal translucency thickness and detection of trisomy 21. RESULTS: In the 448 twin pregnancies the nuchal translucency thickness was above the 95th centile of the normal range (for crown-rump length in singletons) in 65/896 fetuses (7.3%), including 7/8 (88%) with trisomy 21. Increased translucency was also present in four fetuses with other chromosomal abnormalities. In the chromosomally normal twin pregnancies the prevalence of increased nuchal translucency was higher in fetuses from monochorionic (8.4%; 16/190) than in those with dichorionic pregnancies (5.4%; 37/688). The minimum estimated risk for trisomy 21, based on maternal age and fetal nuchal translucency thickness, was 1 in 300 in 19.5% (175/896) of the twins including all eight of those with trisomy 21. CONCLUSIONS: In twin pregnancies the sensitivity of fetal nuchal translucency thickness in screening for trisomy 21 is similar to that in singleton pregnancies, but the specificity is lower because translucency is also increased in chromosomally normal monochorionic twin pregnancies.

Adult↗

Melorheostosis of the foot: a case report and review of the literature.

As seen in the case presented, melorheostosis is a bony dysplasia showing irregular wavy lines of hyperostotic bone. Clinically, patients present variably, ranging from incidental radiographic discovery of the syndrome to severe deformities and pain. Subsequently, diagnosis is often delayed or missed. Treatment is usually symptomatic, although surgical correction of deformities is often pursued. Unfortunately, these surgeries may be complicated with frequent vascular problems and deformities usually recur. Thus, treatment of melorheostosis should be individualized based on the patient's lifestyle, progression of disease and age.

Foot Deformities, Acquired↗

The role of pterins in depression and the effects of antidepressive therapy.

Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.

Adult↗

Direct sequencing of PCR amplified pig PrP genes.

The protein coding regions of the PrP genes of six pigs were sequenced directly from PCR-amplified genomic DNA. All six sequences were identical. The gene encodes a protein of 257 amino acids and shows an overall similarity of 77 to 88% with the PrP sequences from other mammalian species. The significance of amino acids unique to the pig PrP are discussed.

Amino Acid Sequence↗

Approach to health risk determination for metals and their compounds under the Canadian Environmental Protection Act.

The Canadian Environmental Protection Act (CEPA) authorizes the Ministers of the Environment and of Health in Canada to investigate a wide variety of substances that may contaminate the environment and cause adverse effects on the environment and/or on human health. Under the Act, assessments have been completed for 44 environmental contaminants on the first Priority Substances List, including four metals and their compounds. The principles developed for the assessment of risk to human health for priority substances under CEPA are outlined, with specific emphasis on the metals. These include general aspects such as estimation of total exposure from all media, the development of exposure potency indices for carcinogens in lieu of low-dose risk estimates, and incorporation of toxicokinetic and toxicodynamic data, where available, to modify traditionally adopted uncertainty factors for development of tolerable intakes, or concentrations, for nonneoplastic effects. Aspects of the approach to human health risk assessment more specific to the metals considered under CEPA (i.e., arsenic, cadmium, chromium, and nickel) and implications for the subsequent strategic options process are also addressed, including the extent to which various chemical forms could be assessed (i.e., speciation) and essentiality.

Adolescent↗

Speciation in health risk assessments of metals: evaluation of effects associated with forms present in the environment.

Because metals occur in various forms in the environment, speciation is an issue which must be addressed in regulatory health risk assessment programs. The manner in which speciation was addressed in a federal program in Canada is discussed in this article. Under the Canadian Environmental Protection Act, four metals, including arsenic, cadmium, chromium, and nickel, and their compounds were assessed as priority substances to determine the risk to human health associated with exposure to levels present in the general environment in Canada. The extent to which the speciation of these metals could be considered in these assessments was largely determined by the nature of available data. Very few data were identified on speciation in environmental media to which humans are exposed. Based on available data on health effects, it was possible to conduct assessments on only one form each of arsenic and cadmium (i.e., inorganic arsenic and inorganic cadmium), two forms of chromium (trivalent and hexavalent), and four forms of inorganic nickel (oxidic, sulfidic, soluble, and metallic.

Canada↗