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Biomedical subjects

K Hughes

Publications and source records attributed to K Hughes.

At least 109 records · Page 6Linked to original sources

How much monitoring is needed for basilar skull fractures?

Basilar skull fractures account for approximately 19% of all skull fractures. There have been little data published concerning the need for intensive care monitoring in this injury. We retrospectively studied 259 patients admitted to our trauma center over an 8-year period with a diagnosis of basilar skull fracture. All patients were evaluated with cranial computed tomographic (CT) scans. These patients were admitted to the trauma service, and neurosurgical consultation was obtained in all cases. The diagnosis was made by clinical signs in 207 patients (80%), by CT scan in 47 (18%), and by plain films in 5 (2%). Ninety-two patients (group I) had intracranial pathology in addition to basilar skull fracture. Twenty-one patients in this group underwent craniotomy. In this group, the morbidity and mortality rates were 11% and 7%, respectively. Forty-four patients (group II) had no intracranial pathology and a Glasgow Coma Score (GCS) of less than 13. The morbidity was 2%, and the mortality was 2%. One hundred twenty-three patients (group III) had no intracranial pathology on CT scan and a GCS of 13 or greater. The complication rate in this group was 1%, and there was no neurologically related mortality. Patients who are admitted with a diagnosis of basilar skull fracture and who have a GCS of 13 or greater with no intracranial pathology on CT can be managed without intensive care monitoring.

Adolescent↗

Pterin metabolism in depression: an extension of the amine hypothesis and possible marker of response to ECT.

Urinary excretion of neopterins and biopterins was measured in 23 patients with severe depression before and after receiving electroconvulsive therapy (ECT) and 26 healthy control subjects. Patients with psychotic depression and those responding to ECT had neopterin:biopterin (N:B) ratio significantly higher than controls before commencing ECT and positive therapeutic response was associated with reduction of N:B ratio towards control values. 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 disorders. The N:B ratio may be a marker for certain depressive subtypes and response to ECT.

Adult↗

Corneal arcus and cardiovascular risk factors in Asians in Singapore.

This study was a cross-sectional random survey of the whole of Singapore, based on 2143 subjects (aged 18-69 years, response rate 60.3%). The presence of corneal arcus was determined by a doctor using the naked eye in good light. Cardiovascular risk factors were measured by standardized techniques. The prevalence rates overall of corneal arcus were: 18-29 years (males 0.5%, females 0.3%), 30-49 years (males 18.1%, females 13.3%) and 50-69 years (males 70.7%, females 55.3%). In the 30-49 age group, people with arcus had higher serum low density lipoprotein (LDL) cholesterol concentrations than people without arcus, the mean differences being, males 0.31 mmol/l (P = 0.040) and females 0.62 mmol/l (P less than 0.001) with an increased likelihood of having values greater than 5.5.mmol/l of males 1.8 (95% confidence interval (95% CI): 1.0-3.4) and females 2.6 (95% CI: 1.4-4.8). There were no significant differences for LDL-cholesterol in the 50-69 age group. Arcus was weakly associated with fasting plasma glucose in the 30-49 age group. Arcus was not associated with serum high density lipoprotein (HDL) cholesterol, serum fasting triglyceride, blood pressure and cigarette smoking. It is concluded that while corneal arcus is primarily an age-related change, its formation is accelerated by high serum LDL-cholesterol so that in people under 50 years it is a marker for the condition.

Adolescent↗

Siderophore-specific induction of iron uptake in Pseudomonas aeruginosa.

Pseudomonas aeruginosa has two siderophore-based high-affinity iron-uptake systems utilizing pyoverdin and pyochelin. Using strain IA1, a mutant deficient in production of both siderophores, we have shown that addition of purified siderophore to the growth medium induces expression of specific iron-regulated outer-membrane proteins and increases 55Fe-siderophore transport. Addition of pyoverdin from the parent strain PAO1 or from a clinical strain 0:12 induced expression of an 85 kDa IROMP and increased the rate of 55Fe-pyoverdin transport. Transport rates for 55Fe-PAO1 pyoverdin increased from 1.27 to 3.57 pmol Fe min-1 per 10(9) cells. Addition of purified pyochelin induced expression of a 75 kDa IROMP accompanied with increased 55Fe-pyochelin uptake without affecting 55Fe-pyoverdin transport. 55Fe-pyochelin transport increased from 0.3 to 10.6 pmol min-1 per 10(9) cells. Addition of pyoverdin from the parent strain or a chromatographically distinct pyoverdin caused increased reactivity with an anti-85 kDa mAb in Western blotting, indicating that the same receptor is being induced. These results suggest that P. aeruginosa can respond specifically to the presence of siderophore and moreover that not only can the pyoverdin receptor transport its cognate ferri-pyoverdin but also different ferri-pyoverdins, albeit at a reduced rate.

Bacterial Outer Membrane Proteins↗

The pyocin Sa receptor of Pseudomonas aeruginosa is associated with ferripyoverdin uptake.

We have used Tn5 mutagenesis to obtain a mutant resistant to pyocin Sa. When grown in iron-deficient succinate medium this mutant lacked an 85-kDa iron-regulated outer membrane protein (IROMP), and expression of a 75-kDa IROMP was increased compared with that in the parent strain. The mutant was deficient in pyoverdin biosynthesis and showed a 95% decrease in transport of ferripyoverdin purified from the parent strain, suggesting that the 85-kDa IROMP is the specific receptor for ferripyoverdin and pyocin Sa. The mutant compensated for the deficiency in pyoverdin biosynthesis and transport by exhibiting a fourfold increase in ferripyochelin transport. The low-level transport of ferripyoverdin in the Sa-resistant mutant, which extended to heterologous pyoverdins from other strains, suggests that Pseudomonas aeruginosa has a second ferripyoverdin uptake system of lower affinity and broader specificity.

Bacterial Outer Membrane Proteins↗

Activation of protein kinase C increases phosphorylation of the L-myc trans-activator domain at a GSK-3 target site.

The L-myc protein migrates as three distinct differentially phosphorylated bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This phosphorylation can be rapidly increased either by treatment with the protein kinase C (PKC) activator phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or by inhibition of serine/threonine protein phosphatases with okadaic acid. In vitro mutagenesis and phosphoamino acid analyses define the N-terminal serine residues 38 and 42 of L-myc as critical targets for the PKC-dependent phosphorylation. These are the exclusive sites of phosphorylation in the N-terminal third of the L-myc protein, and can be phosphorylated in vitro by glycogen synthase kinase 3 beta (GSK-3 beta). A mutant L-myc protein in which these serines have been replaced by alanine residues does not show heterogeneous electrophoretic migration or hyperphosphorylation in response to PKC activation, and is not a substrate for GSK-3 beta in vitro. Similar potential phosphorylation sites are present in c-myc and N-myc in a highly conserved region thought to represent a transcriptional activation domain. We suggest that N-terminal phosphorylation of the L-myc protein is a means of rapid regulation of this oncoprotein, possibly mediated in vivo by the action of GSK-3.

Calcium-Calmodulin-Dependent Protein Kinases↗

Cell-cycle associated transcriptional regulation of ribonucleotide reductase in L1210 leukemia cells and drug-resistant variants.

Previous studies from this laboratory have shown that the steady-state levels of the mRNA for the non-heme iron (NHI) subunit of ribonucleotide reductase were markedly elevated in hydroxyurea-resistant L1210 cell lines with minimal changes in the mRNA levels for the effector-binding (EB) subunit. In the present study, wild-type L1210 cells and their drug-resistant variants [hydroxyurea-resistant (HU-7); deoxyadenosine-resistant (Y-8); and deoxyadenosine/pyrazoloimidazole-resistant (ED2)] were synchronized by EGTA treatment in the G0/G1-phase of the cell cycle. Upon the addition of CaCl2, the cells reentered the cell cycle. The steady-state levels and the transcriptional rates of the mRNAs for the EB subunit and glyceraldehyde-3-phosphate dehydrogenase were measured and found to be similar in the drug-resistant variants compared to the wild-type cells. While the steady-state level of the mRNA for the NHI subunit was increased 35-fold in the HU-7 cell line, the transcription rate was increased only 7-fold. The increase in the transcription rate did not account for the large increase in the steady-state level. These data indicate that the increased steady-state level of the mRNA for the NHI subunit in the HU-7 L1210 cell line was not due to cell-cycle differences and that post-transcriptional processing and/or stability may play a role as well.

Animals↗

Prevalence of antibodies to spotted fever group rickettsiae in dogs from southeastern Australia.

Recent epidemiologic data suggests that Rickettsia australis, the cause of Queensland tick typhus, is present in southeastern Australia. In order to further confirm this observation, a canine serosurvey was undertaken to determine if naturally occurring antibodies were present in pet and farm dogs from this newly-recognized endemic area. Thirty-five of 312 surveyed dogs (11.2%) had indirect immunofluorescent antibody titers of 1:64 or greater against R. australis antigen. Positive control sera were obtained from two dogs experimentally inoculated with R. australis. One of these dogs was serially sampled and a rickettsemia could not be documented. None of 26 control sera obtained from dogs from South Australia, New Zealand, western Victoria, or North Carolina had antibody titers greater than or equal to 1:64. These results suggest that spotted fever group rickettsiae are present in Southeastern Australia.

Animals↗

Cardiovascular diseases in Chinese, Malays, and Indians in Singapore. I. Differences in mortality.

STUDY OBJECTIVE: The aim of the study was to analyse differences in mortality from the main cardiovascular diseases (ischaemic heart disease, hypertensive disease, and cerebrovascular disease) among Chinese, Malays, and Indians in Singapore. DESIGN: The study was a survey using national death registration data in Singapore for the five years 1980 to 1984. The underlying cause of death, coded according to the ninth revision of the International Classification of Diseases, was taken for the analyses. SETTING: The study was confined to the independent island state of Singapore, population 2.53 million (Chinese 76.5%, Malays 14.8%, Indians 6.4%, Others 2.3%). Death registration is thought to be complete. SUBJECTS: All registered deaths in the age range 30-69 years during the study period were analysed by ethnic group. MEASUREMENT AND MAIN RESULTS: Indians had higher mortality from ischaemic heart disease than the other ethnic groups in both sexes, with age-standardised relative risks of Indian v Chinese (males 3.8, females 3.4), Indian v Malay (males 1.9, females 1.6), and Malay v Chinese (males 2.0, females 2.2). The excess mortality in Indians declined with age. For hypertensive disease Malays had the highest mortality, with age-standardised relative risks of Malay v Chinese (males 3.4, females 4.4), Malay v Indian (males 2.0, females 2.5), and Indian v Chinese (males 1.6, females 1.6). For cerebrovascular disease there was little ethnic difference except for lower rates in Chinese females, with age-standardised relative risks of Malay v Chinese (males 1.1, females 1.9), Malay v Indian (males 1.0, females 1.1), and Indian v Chinese (males 1.1, females 1.7). CONCLUSIONS: There are significant differences in mortality from the three main cardiovascular diseases in the different ethnic groups in Singapore.

Adult↗

Cardiovascular diseases in Chinese, Malays, and Indians in Singapore. II. Differences in risk factor levels.

STUDY OBJECTIVE: The aim of the study was to examine cardiovascular risk factors to see how these might explain differences in cardiovascular disease mortality among Chinese, Malays, and Indians in the Republic of Singapore. DESIGN: The study was a population based cross sectional survey. Stratified systematic sampling of census districts, reticulated units, and houses was used. The proportions of Malay and Indian households were increased to improve statistical efficiency, since about 75% of the population is Chinese. SETTING: Subjects were recruited from all parts of the Republic of Singapore. SUBJECTS: 2143 subjects aged 18 to 69 years were recruited (representing 60.3% of persons approached). There were no differences in response rate between the sexes and ethnic groups. MEASUREMENTS AND MAIN RESULTS: Data on cardiovascular risk factors were collected by questionnaire. Measurements were made of blood pressure, serum cholesterol, low and high density lipoprotein cholesterol, fasting triglycerides and plasma glucose. In males the age adjusted cigarette smoking rate was higher in Malays (53.3%) than in Chinese (37.4%) or Indians (44.5%). In both sexes, Malays had higher age adjusted mean systolic blood pressure: males 124.6 mm Hg v 121.2 mm Hg (Chinese) and 121.2 mm Hg (Indians); females 122.8 mm Hg v 117.3 mm Hg (Chinese) and 118.4 mm Hg (Indians). Serum cholesterol, low density lipoprotein cholesterol and triglyceride showed no ethnic differences. Mean high density lipoprotein cholesterol in males (age adjusted) was lower in Indians (0.69 mmol/litre) than in Chinese (0.87 mmol/litre) and Malays (0.82 mmol/litre); in females the mean value of 0.95 mmol/litre in Indians was lower than in Chinese (1.05 mmol/litre) and Malays (1.03 mmol/litre). Rank prevalence of diabetes for males was Indians (highest), Malays and then Chinese; for females it was Malays, Indians, Chinese. CONCLUSIONS: The higher mortality from ischaemic heart disease found in Indians in Singapore cannot be explained by the major risk factors of cigarette smoking, blood pressure and serum cholesterol; lower high density lipoprotein cholesterol and higher rates of diabetes may be part of the explanation. The higher systolic blood pressures in Malays may explain their higher hypertensive disease mortality.

Adolescent↗

Diabetes mellitus and its chronic complications in Singapore: an increasing healthcare problem.

We studied the prevalence of diabetes mellitus in Singapore and compared it to the study conducted ten years previously. A rise in prevalence rates from 2.0% to 4.7% was demonstrated. Impaired glucose tolerance (IGT) was studied for the first time, and a prevalence rate of 0.9% was found. Findings on chronic complications of diabetes were also reported. A high frequency of coronary heart disease and hypertension were detected in both diabetic and IGT subjects. Obesity and hyperlipidaemia were identified as important risk factors. This study demonstrates the scope and impact of diabetes mellitus as a major healthcare problem in Singapore. Strategies directed at prevention and control of this disease needs to be implemented so as to check its rising trend.

Adolescent↗

A simplified anatomical approach to thin section, high resolution CT of the ear and facial nerve.

The pathological processes involving the ear require, for their accurate interpretation, a thorough but nevertheless working anatomical approach. An understanding of this complex, three dimensional anatomy of the ear, including the facial nerve, is the key to accurate diagnosis. This article reflects a simplified anatomical approach and demonstrates that computerised tomography is an admirable substitute for routine pluri-directional tomographic evaluation of the ear.

Cochlea↗

Physical activity in Chinese, Malays and Indians in Singapore.

A population based survey has measured levels of physical activity by questionnaire in persons aged 18 to 69 years in Singapore. Levels of physical activity were classified into high, medium and low based on activity in leisure and at work. The only ethnic difference was that for males a higher proportion were classified as "high" activity in Malays (24.8%) than Chinese (16.0%) and Indians (18.1%). For the overall 18 to 69 age group, it was found that for males, the proportions in the "low" category were Chinese 80%, Malays 70% and Indians 75% while for females it was 95% in all three ethnic groups. As physical activity of sufficient intensity is important in disease prevention and health promotion, more needs to be done on educating the public in Singapore about the benefits of regular exercise.

Adolescent↗

Alcohol consumption in Chinese, Malays and Indians in Singapore.

A population based survey has measured alcohol consumption by questionnaire in persons aged 18 to 69 years in Singapore. The majority were "occasional/none" drinkers, being males (Chinese 87%, Malays 99% and Indians 80%) and females (Chinese 98%, Malays 100% and Indians 100%). "Heavy" consumption was uncommon in males (Chinese 0.6%, Malays 0% and Indians 1.3%) and absent in females, while "heavy/moderate" drinking was males (Chinese 5.7%, Malays 0.5% and Indians 3.8%) and females (Chinese 0.3%, Malays 0% and Indians 0%). For males, "light" drinking was highest in Indians (15.9%), then Chinese (7.8%) and then Malays (0.5%). This survey indicates that alcohol consumption is not yet a major public health problem in Singapore.

Adolescent↗

Obesity and body mass indices in Chinese, Malays and Indians in Singapore.

A population based cross-sectional survey has measured body mass indices (BMIs) in Singapore and compared their means and the proportions who are overweight and obese amongst Chinese, Malays and Indians. For males there was little ethnic differences; for the 18-69 age group, the age-adjusted mean BMIs being Chinese 22.3, Malays 23.1 and Indians 22.5. However for females, Malays and Indians were considerably more obese than Chinese; for the 18-69 age group the age-adjusted mean BMIs in Malays (25.1) and Indians (24.6) were significantly greater (p less than 0.001) than in Chinese (22.2). The proportions categorised as overweight or obese (BMI equal to or more than 26 in males and 25 in females) were males (Chinese 16.7%, Malays 22.4%, and Indians 14.0%) and females (Chinese 21.2%, Malays 51.5%, and Indians 42.0%). Health education on the harmful effects of obesity should be targeted especially on Malay and Indian females.

Adolescent↗