Search PubMed⌕ Search

Biomedical subjects

K Hughes

Publications and source records attributed to K Hughes.

At least 37 records · Page 2Linked to original sources

Health risk assessment of 1,3-butadiene as a Priority Substance in Canada.

1,3-Butadiene was included in the second list of Priority Substances to be assessed under the Canadian Environmental Protection Act. Potential hazards to human health were characterized on the basis of critical examination of available data on health effects in experimental animals and occupationally exposed human populations, as well as information on mode of action. Based on consideration of all relevant data identified as of April 1998, butadiene was considered highly likely to be carcinogenic to humans, and likely to be a somatic and germ cell genotoxicant in humans. In addition, butadiene may also be a reproductive toxicant in humans. Estimates of the potency of butadiene to induce these effects have been derived on the basis of quantitation of observed exposure-response relationships for the purposes of characterization of risk to the general population in Canada exposed to butadiene in the ambient environment.

Animals↗

Microdermabrasion: a clinical and histopathologic study.

BACKGROUND: Microdermabrasion is a widely performed skin rejuvenation procedure. Few studies have examined its efficacy. OBJECTIVE: To evaluate the clinical and histopathologic effects of microdermabrasion. METHODS: Fourteen patients underwent microdermabrasion treatments over 12-14 weeks. Self-rated questionnaires were given before and after the treatment series and were evaluated by a paired t-test. Three of the 14 patients were treated for moderate to severe acne scarring. Acute histologic effects were assessed ex vivo on human abdominal skin. Chronic histopathologic effects were examined in three volunteers who underwent skin biopsies before and after a treatment series on the dorsal forearms. RESULTS: By patient assessment, there was statistically significant improvement in roughness, mottled pigmentation, and overall improvement of skin appearance, but not in rhytides. Acne scarring sometimes improved, but required deeper ablation. Acutely the stratum corneum was homogenized and focally compacted. Chronically there was epidermal hyperplasia, decreased melanization, and some increase in elastin. CONCLUSION: Microdermabrasion improves some aspects of photoaging and select cases of acne scarring.

Abdomen↗

Risk factors and incident coronary heart disease in Chinese, Malay and Asian Indian males: the Singapore Cardiovascular Cohort Study.

OBJECTIVE: This prospective study in Singapore investigated the relationships of established coronary risk factors with incident coronary heart disease (CHD) for Chinese, Malay, and Asian Indian males. SUBJECTS: A cohort (consisting of 2879 males without diagnosed CHD) derived from three previous cross-sectional surveys. METHODS: Individual baseline data were linked to registry databases to obtain the first event of CHD. Hazard ratios (HR) or relative risks for risk factors were calculated using Cox's proportional hazards model with adjustment for age and ethnic group and adjustment for age, ethnic group and all other risk factors (overall adjusted). RESULTS: There were 24,986 person-years of follow-up. The overall adjusted HR with 95% CI are presented here. Asian Indians were at greatest risk of CHD, compared to Chinese (3.0; 2.0-4.8) and Malays (3.4; 1.9-3.3). Individuals with hypertension (2.4; 1.6-2.7) or diabetes (1.7; 1.1-2.7) showed a higher risk of CHD. High low density lipoprotein cholesterol (LDL-C) (1.5; 1.0-2.1), high fasting triglyceride (1.5; 0.9-2.6) and low high density lipoprotein cholesterol (HDL-C) (1.3; 0.9-2.0) showed a lesser but still increased risk. Alcohol intake was protective with non-drinkers having an increased risk of CHD (1.8; 1.0-3.3). Obesity (body mass index > or =30) showed an increased risk (1.8; 0.6-5.4). An increased risk of CHD was found in cigarette smokers of > or =20 pack years (1.5; 0.9-2.5) but not with lesser amounts. CONCLUSIONS: The increased susceptibility of Asian Indian males to CHD has been confirmed in a longitudinal study. All of the examined established risk factors for CHD were found to play important but varying roles in the ethnic groups in Singapore.

Adult↗

Percutaneous intervention for symptomatic vertebral artery stenosis using coronary stents.

BACKGROUND: There is very limited experience with percutaneous treatment of symptomatic vertebral artery disease. Angioplasty and stenting for vertebral artery stenosis are still evolving and have generally been performed for asymptomatic disease. We performed vertebral artery stenting in 12 patients with vertebrobasilar transient ischemic attacks and present our short- and intermediate-term results. METHODS: A total of 12 lesions affecting the vertebral artery were treated by coronary stent placement. The mean age was 72 +/- 8 years and 83% were males (10 males, 2 females). Baseline characteristics included hypertension (11/12); hypercholesterolemia (8/12); coronary artery disease (8/12); and diabetes (5/12). Mean lesion length was 8.6 +/- 2.7 mm, mean calipered stenosis was 78 +/- 8%, and mean arterial diameter was 4.1 +/- 0.3 mm. All patients were symptomatic, fulfilling our criteria for vertebral artery angioplasty. All patients were followed for at least 6 months after treatment. RESULTS: All 12 lesions were successfully stented, with a mean residual stenosis of 11 +/- 6%. Clinical follow-up showed resolution or improvement of symptoms in all patients. One patient had symptomatic restenosis seven months after the initial procedure requiring repeat angioplasty. CONCLUSIONS: Stent placement for symptomatic stenosis involving the vertebral artery is safe and effective for alleviating symptoms of vertebrobasilar ischemia. Coronary stents appear to be well suited to treat atherosclerotic lesions of the vertebral artery.

Aged↗

Self-expanding stents for carotid interventions: comparison of nitinol versus stainless-steel stents.

BACKGROUND: Angioplasty and stenting are becoming increasingly accepted techniques for the treatment of carotid stenosis. However, the optimal stent for carotid intervention is not known. METHODS: We compared the short- and intermediate-term results of carotid stenting using either nitinol or stainless-steel self-expanding stents in 178 high surgical risk patients undergoing carotid stenting at our institution. Of these 178 patients, eighty-nine received stainless-steel stents and 89 received nitinol stents. The groups were similar with respect to age, gender, diabetes, hypertension, left ventricular function, and symptom status. There were more patients with contralateral carotid occlusion in the nitinol stent group. Independent neurological evaluation was performed in all patients pre- and post-carotid stenting. RESULTS: At 6 months, there was a similar incidence of stroke (3.3% versus 2.2%) in the stainless-steel group and nitinol stent group, respectively. There was higher 6-month mortality noted in the stainless-steel stent group, but there were no neurological deaths in either group. CONCLUSIONS: In a single-center patient cohort with similar baseline characteristics, patients receiving nitinol stents and stainless-steel stents had similar neurological outcomes.

Aged↗

Socio-demographic correlates of screening intention for colorectal cancer.

OBJECTIVE: To assess the relationship between socio-demographic factors and screening intention for colorectal cancer (CRC). METHODS: A cross-sectional survey of a random sample of 884 Queenslanders aged 40-80 years was conducted using a computer-assisted telephone interviewing system. The factors measured included socio-demographic characteristics, personal history of CRC, knowledge of others with CRC and perceived symptom status. Chi-squared and Monte Carlo estimates of Fisher Exact Tests were performed to determine the associations between socio-demographic factors and screening intention. In multivariate analyses, multinomial logistic regression (MNLR) was utilised to examine potential determinants of screening intention. RESULTS: 77.5% (95% CI 74.0%-80.7%) of the respondents indicated their intention to participate in CRC screening if it were recommended by their doctor or health authorities. The likelihood ratio chi-squared tests in the MNLR analyses show that age (chi(df = 6)2 = 15.0; p = 0.02), education (chi(df = 8)2 = 19.4; p = 0.01), perceived symptom status (chi(df = 4)2 = 22.9; p = 0.00), sex (chi(df = 2)2 = 4.5; p = 0.11), income (chi(df = 14)2 = 19.6; p = 0.14) and personal history of CRC (chi(df = 2)2 = 4.3; p = 0.12) were potential determinants of screening intention. Other socio-demographic factors, including country of birth, private health insurance status, Socio-economic Index for Areas, and Rural and Remote Areas Classification codes, were not associated with screening intention. CONCLUSIONS AND IMPLICATIONS: The results indicate that a variety of socio-demographic factors are associated with screening intention and need to be considered in the future development of a population-based screening program for CRC.

Adult↗

Effects of topiramate on kainate- and domoate-activated [14C]guanidinium ion flux through GluR6 channels in transfected BHK cells using Cytostar-T scintillating microplates.

PURPOSE: This study was undertaken to test the hypothesis that topiramate (TPM) exerts a negative modulatory effect on some types of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)/kainate receptors by binding to the site at which protein kinase A (PKA) phosphorylates the receptor-channel complex. METHODS: The effect of TPM on kainate- or domoate-induced [14C]guanidinium ion flux through iGluR6 channels expressed in baby hamster kidney (BHK) cells was evaluated. Because the hypothesis predicts that TPM will bind only in the dephosphorylated state, a variety of experimental conditions were used to either promote or impede the phosphorylation of the receptor-channel complex. These included the use of dibutyryl cyclic adenosine monophosphate (cAMP) and forskolin to activate PKA, H-9 and H-89 to inhibit PKA, and okadaic acid to inhibit protein phosphatases. RESULTS: Kainate (1 microM) induced a gradual accumulation of [14C]guanidinium into the cells that plateaued approximately 30 min after initiation of the reaction, whereas domoate (0.1 microM) caused a rapid accumulation into the cells that peaked within 5 min; thereafter, the amount of [14C]guanidinium in the cells declined gradually. Topiramate, at 0.1 and 100 microM, did not significantly affect the [14C]guanidinium accumulation under any of the experimental conditions used. CONCLUSIONS: The results of this study are not consistent with the hypothesis tested. However, the results must be interpreted cautiously because iGluR6 receptors expressed in the BHK cells and the functional state of proteins that regulate AMPA/receptors (e.g., PSD-95) may not be sufficiently similar to the receptors and functional state in neurons to serve as a true test of the hypothesis.

Animals↗

Homocysteine, folate, vitamin B12, and cardiovascular risk in Indians, Malays, and Chinese in Singapore.

OBJECTIVE: To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is partly attributable to differences in blood concentrations of homocysteine, and related blood concentrations of folate and vitamin B12. DESIGN: Cross sectional study of the general population. SETTING: Singapore. PARTICIPANTS: Random sample of 726 fasting subjects aged 30 to 69 years. MAIN RESULTS: Mean plasma total homocysteine concentrations did not show significant ethnic differences; values were Indians (men 16.2 and women 11.5 mumol/l), Malays (men 15.0 and women 12.5 mumol/l), and Chinese (men 15.3 and women 12.2 mumol/l). Similarly, the proportions with high plasma homocysteine (> 14.0 mumol/l) showed no important ethnic differences being, Indians (men 60.0 and women 21.9%), Malays (men 53.9 and women 37.8%), and Chinese (men 56.6 and women 30.6%). Mean plasma folate concentrations were lower in Indians (men 8.7 and women 10.9 nmol/l) and Malays (men 8.5 and women 10.8 nmol/l), than Chinese (men 9.7 and women 13.8 nmol/l). Similarly, the proportions with low plasma folate (< 6.8 nmol/l) were higher in Indians (men 44.9 and women 36.6%) and Malays (men 45.3 and women 24.5%) than Chinese (men 31.4 and women 12.6%). Mean plasma vitamin B12 concentrations were lowest in Indians (men 352.5 and women 350.7 pmol/l), then Chinese (men 371.1 and women 373.7 pmol/l), and then Malays (men 430.5 and women 486.0 pmol/l). CONCLUSION: While there were ethnic differences for plasma folate and vitamin B12 (in particular lower levels in Indians), there was no evidence that homocysteine plays any part in the differential ethnic risk from CHD in Singapore and in particular the increased susceptibility of Indians to the disease.

Adult↗

Development of a high throughput scintillation proximity assay for hepatitis C virus NS3 protease that reduces the proportion of competitive inhibitors identified.

A screening assay has been developed for hepatitis C virus (HCV) NS3 protease using the scintillation proximity assay (SPA) technology. The sequence of the peptide substrate used was taken from the site cleaved by the enzyme in the mature nonstructural protein of HCV. The peptide was biotinylated at the N-terminus and tritiated at the C-terminus so that a decrease in signal was detected as a result of enzyme activity. IC(50) values were calculated for the cleaved product, and it was shown that the value obtained was dependent on the substrate concentration used. The effect of substrate concentration on the inhibition of HCV NS3 protease was further highlighted in a mock screening assay, using colored natural product samples, in which the hit rate was altered by a change in substrate concentration. An increase in substrate concentration reduced the proportion of competitive inhibitors identified. This study highlighted the importance of optimizing the components used in SPA assays in order to obtain an assay format valid for high throughput screening.

Binding, Competitive↗

Developing a tool to measure holistic practice: a missing dimension in outcomes measurement within complementary therapies.

Despite the wide and continuing debate over the relevance of particular research methods to evaluate complementary therapies, less attention has been given to what outcome criteria and measures to use and/or whether these have a sufficient breadth in perspective. While complementary and alternative medicine researchers have paid heed to the importance of measuring the subjective experience of therapy users, they have left unmeasured the notion of holism, in particular, the measurement of the effect of the interaction between therapist and therapy user, and its underlying philosophy of health and healing. This paper reports on an exploratory, qualitative study aimed at developing a measure of holism and holistic practice. It draws out some key features requiring measurement and provides insight into the emerging measure. Further development work is needed before the measure can be used within research or routine practice.

Complementary Therapies↗

Incidence of ischaemic heart disease and stroke in Chinese, Malays and Indians in Singapore: Singapore Cardiovascular Cohort Study.

INTRODUCTION: This is the first prospective cohort study in Singapore to describe the incidence of ischaemic heart disease (IHD) and stroke among Chinese, Malays and Asian Indians. MATERIALS AND METHODS: The Singapore Cardiovascular Cohort Study is a longitudinal follow-up study on a general population cohort of 5920 persons drawn from 3 previous cross-sectional surveys. Morbidity and mortality from IHD and stroke were ascertained by record linkage using a unique identification number with the death registry, Singapore Myocardial Infarct Registry and in-patient discharge databases. RESULTS: There were 193 first IHD events and 97 first strokes during 52,806 person-years of observation. The overall incidence of IHD was 3.8/1000 person-years and that of stroke was 1.8/1000 person-years. In both males and females, Indians had the highest IHD incidence, followed by Malays and then Chinese. For males after adjusting for age, Indians were 2.78 times (95% CI 1.86, 4.17; P < 0.0001) and 2.28 times (95% CI 1.34, 3.88; P = 0.002) more likely to get IHD than Chinese and Malays respectively. For females after adjusting for age, Indians were 1.97 times (95% CI 1.07, 3.63; P = 0.03) and 1.37 times (95% CI 0.67, 2.80; P = 0.39) more likely to get IHD than Chinese and Malays respectively. For stroke, male Chinese and Indians had higher incidence than Malays (though not statistically significant). However, in females, Malays had the highest incidence of stroke, being 2.57 times (95% CI 1.31, 5.05; P = 0.008) more likely to get stroke than Chinese after adjustment for age. CONCLUSIONS: This prospective study of both mortality and morbidity has confirmed the higher risk of IHD in Indians. It has also found that Malay females have a higher incidence of stroke, which deserves further study because of its potential public health importance.

Adult↗

The antibody response of cattle infected with bovine immunodeficiency virus to peptides of the viral transmembrane protein.

The development of the antibody response to peptides of the transmembrane glycoprotein of bovine immunodeficiency virus (BIV) was followed over a period of 50 weeks in six cattle experimentally infected with the BIV(FL112) isolate. Antibody was detected by an enzyme immunoassay using either a linear or a cyclized peptide with structural features common to an immunodominant region of other lentiviruses. The assay was specific for BIV, detecting antibody in bovine sera to BIV(FL112) or BIV(R29) but not to six other common viruses of cattle. Antibody was present in the sera of all cattle inoculated with BIV(FL112) within 4 weeks of infection, peaked between 10 and 30 weeks and persisted in most cattle during the 50 weeks of observation. These features indicate that this assay may be useful in identifying cattle infected with other strains of BIV in the field.

Amino Acid Sequence↗

Early versus delayed repair of facial fractures in the multiply injured patient.

The management of facial fractures in the polytrauma patient requires the coordination of multiple surgical disciplines to optimize the functional and cosmetic outcome while minimizing overall morbidity and mortality. Although the plastic surgery literature historically advocates the early repair of facial fractures, the risk of general anesthesia in patients with associated injuries sometimes makes early repair unsafe. We compared early operative repair versus delayed operative repair of facial fractures in multitrauma patients. We specifically examined wound infection, overall complication rate, total length of hospital stay, days in the Intensive Care Unit (ICU), and days on the ventilator in the two groups. A 5-year (1991-1996) retrospective study of multitrauma patients with associated facial fractures was undertaken at an urban community hospital. We had a total of 82 patients, who were divided into three groups. Thirty-three patients did not have operative repair of the facial fractures during the initial admission and were followed by the plastic surgery service on an outpatient basis. These patients will not be discussed further. Seven patients underwent early operative repair, which was defined as repair within 48 hours of admission (group I). Forty-two patients had delayed operative repair, defined as repair more than 48 hours after admission (group II). The reasons for delayed repair included: excessive soft tissue swelling (16), intracranial injuries (12), unstable medical condition (8), and coordination of procedures with other services (6). Of the 49 patients who underwent operative repair, 43 were involved in motor vehicle accidents, 3 were injured by a fall from a height, 2 were involved in auto-pedestrian accidents, and 1 was a victim of assault. Forty-eight of the 49 patients were initially admitted to the ICU. Cumulative associated injuries were as follows: closed head injury (38), extremity fracture (21), blunt chest injuries (11), intra-abdominal injuries (5), vertebral column injuries (7), and ocular injuries (2). The average Injury Severity Score for Group I was 17.3 and for Group II, 18.1. In group I, there were no deaths, there were no wound infections, and the complication rate was 14.3 per cent. The average total number of days spent on the ventilator was 3.0, the average total number of days spent in the ICU was 5.0, and the average total hospital stay was 16.0 days. In group II, there were no deaths, the wound infection rate was 5 per cent, and the overall complication rate was 21 per cent. The average total number of days spent on the ventilator was 3.3, the average total number of days spent in the ICU was 5.8, and the average total days in the hospital was 14.8. Our results indicate that in a similar cohort of multitrauma patients, delayed repair did not increase length of ICU stay or hospital stay. The wound infection rate was negligible, and the complication rate was similar in the two groups. We conclude that a delay in repair of facial fractures in the critically ill patient has an acceptably low complication rate and may be advantageous in decreasing operative risk and minimizing cost by coordinating multiple procedures with various surgical subspecialties.

Adolescent↗

Head-out immersion in the non-human primate: a model of cardiovascular deconditioning during microgravity.

BACKGROUND: Orthostatic intolerance is a common complication associated with spaceflight. It has been speculated that this is due to changes in blood volume and alterations in cardiovascular reflexes. The objective of the current study was to develop a model that would allow us to study the cardiovascular system and the regulation of blood volume during short-term microgravity exposure in the primate with the intent of eventually being able to elucidate those factors responsible for the orthostatic intolerance. HYPOTHESIS: Head-out water immersion in the conscious non-human primate simulates the cardiovascular and volume regulatory responses observed in astronauts during exposure to microgravity. METHODS: Four monkeys were chronically instrumented for measuring BP and heart rate and then conditioned to the primate restraint chair. They were then subjected to 72 h of head-out water immersion (two immersions in three monkeys and one immersion in the fourth) in order to simulate the cardiovascular and renal effects of the microgravity environment. RESULTS: During the immersion, there was an increase in arterial BP (ABP) and central venous pressure (CVP) and a reflex decrease in heart rate (HR). Urine flow (UV) increased and water intake decreased, producing a negative water balance. This was not associated with an alteration in food intake. CVP and UV decreased following de-immersion. There was also resetting of the arterial baroreflex control of HR. Significant tachycardia occurred after the immersion that was associated with a decrease in ABP. CONCLUSION: These results are similar to those observed in astronauts during and after spaceflight, suggesting that head-out water immersion of the non-human primate provides a good model for studying cardiovascular and renal adaptations to spaceflight.

Animals↗

Calmodulin dependence of NFkappaB activation.

The NFkappaB family of transcription factors is regulated by inhibitory IkappaB proteins. A diversity of stimuli leads to the phosphorylation and subsequent degradation of IkappaB, releasing NFkappaB to act on its target genes. Calmodulin (CaM) is a key regulator of numerous cellular processes and is the predominant intracellular receptor for Ca2+ signals. Here we report that several CaM antagonists inhibit the activation of NFkappaB, and that this is due to the prevention of inducible IkappaB phosphorylation. Our results suggest that CaM is involved in the phosphorylation of IkappaB, a finding that may help in elucidating the mechanism of this critical step of NFkappaB activation.

Animals↗

The role of the public in water fluoridation: public health champions or anti-fluoridation freedom fighters?

OBJECTIVE: Using the opportunity of pretesting a leaflet for the general public on water fluoridation, their views were also sought on the issue as a whole. DESIGN: Qualitative research using focus group discussions led by an experienced moderator. SETTING: Among the general public living in north east England. SUBJECTS: Members of the public living in both fluoridated and non-fluoridated areas in three age bands (20-35, 36-50 and 50+) and by social class. RESULTS: The study found: the low priority given to dental health; how emotive the subject of water is; the variable knowledge of fluoride in relation to dental and general health; and the desire for information if new water fluoridation schemes are planned. CONCLUSIONS: The research confirmed public support for water fluoridation but highlighted the place of public health professionals in championing water fluoridation because of public apathy.

Adult↗

Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore.

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.

Arteriosclerosis↗