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Biomedical subjects

C Bruce

Publications and source records attributed to C Bruce.

At least 19 recordsLinked to original sources
PubMed2006

Menstrual cycle-dependent changes of Toll-like receptors in endometrium.

BACKGROUND: Rapid innate immune defences against infection usually involve the recognition of invading pathogens by specific pattern recognition receptors recently attributed to the family of Toll-like receptors (TLRs). Reports from our laboratory and others have demonstrated the existence of TLRs 1-6 in the female reproductive tract. However, little has been done to identify TLRs 7-10 in the female reproductive tract, particularly in the uterus. Also little information exists regarding variation in TLRs in the female reproductive tract during the menstrual cycle. METHOD: The distribution of TLR7-10 protein was detected by immunostaining in timed endometrial biopsies from normal women. RT-PCR was used to show the existence of TLR1-10 genes in endometrial tissue and real-time PCR analysis to investigate the relative expression of these genes during the menstrual cycle in normal human endometrium. RESULTS: TLR7-10 proteins were detected in endometrial epithelium and stroma. TLR1-10 genes were expressed in human endometrial tissue, and the mean relative expression of TLR2-6, 9 and 10 genes was significantly higher during the secretory phase compared with other phases of the menstrual cycle. CONCLUSIONS: TLR7-10 localization is not limited to endometrial epithelium but is also present in the stroma of the endometrial tissue. Endometrial TLR2-6, 9 and 10 genes are cyclically expressed during the menstrual cycle.

Adult↗
PubMed2006

Is secondary radiological follow-up of infants with a family history of developmental dysplasia of the hip necessary?

The practice of regular radiological follow-up of infants with a positive family history of developmental dysplasia of the hip is based on the widespread belief that primary acetabular dysplasia is a genetic disorder which can occur in the absence of frank subluxation or dislocation. We reviewed all infants who were involved in our screening programme for developmental dysplasia of the hip, between November 2002 and January 2004, and who had a normal clinical and ultrasound examination of the hip at six to eight weeks of age, but who, because of a family history of developmental dysplasia of the hip, had undergone further radiography after an interval of 6 to 12 months. The radiographs of 89 infants were analysed for signs of late dysplasia of the hip and assessed independently by three observers to allow for variability of measurement. There were 11 infants (11%) lost to follow-up. All the patients had normal radiographs at the final follow-up and none required any intervention. We therefore question the need for routine radiological follow-up of infants with a positive family history of developmental dysplasia of the hip, but who are normal on clinical examination and assessment by ultrasound screening when six to eight weeks old.

Acetabulum↗
PubMed2005

Characterization of Toll-like receptors in the female reproductive tract in humans.

BACKGROUND: Rapid innate immune defences against infection involve the recognition of invading pathogens by specific pattern recognition receptors recently attributed to the family of Toll-like receptors (TLR). Little is known about the in vivo protein expression or distribution of TLR in the female reproductive tract in humans. It is likely that TLR distribution in the female reproductive tract reflects the immunological tolerance to the commensal organisms in lower parts of the tract (vagina, ectocervix and, partially, endocervix) and the intolerance to commensal microbial flora in the upper tract (the uterus and uterine tubes). METHODS: Using immunohistochemistry techniques, distribution of TLR1-6 was studied in surgical sections from the vagina, ecto- and endocervix, endometrium and uterine tubes, obtained from patients undergoing abdominal hysterectomy for benign gynaecological conditions. RESULTS: TLR1, 2, 3, 5 and 6 were present in the epithelia of different regions of female reproductive tract. However, TLR4 was only present in the endocervix, endometrium and uterine tubes and absent in vagina and ectocervix. In addition, a secretory form of TLR4 seems to be produced by the endocervical glands. CONCLUSION: TLR4 may play an important role in modulation of immunological tolerance in the lower parts of the female reproductive tract, and in host defence against ascending infection.

Adult↗
PubMed2005

Differential effects of fluticasone and montelukast on allergen-induced asthma.

Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 microg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P <0.05 for Mont vs placebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P <0.05 for FP vs placebo and FP vs Mont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P <0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients.

Acetates↗
PubMed2004

Early periprosthetic femoral bone remodelling using different bearing material combinations in total hip arthroplasties: a prospective randomised study.

The present study was performed to test the hypothesis that different bearing materials have an impact on femoral bone remodelling within the first year after a total hip arthroplasty. A total of 225 patients with osteoarthrosis of the hip or avascular necrosis of the femoral head were included in this randomised prospective study. All patients had an identical hybrid total hip arthroplasty (cemented BiMetric stem and cementless RingLoc acetabular cup) except for the bearing materials: polyethylene-on-zirconia (n = 78), CoCr-on-CoCr (n = 71), or alumina-on-alumina (n = 76). Bone mineral density (BMD) was measured with Dual-energy X-ray absorptiometry (DEXA) in seven Gruen zones adjacent to the femoral implant. The DEXA scan was performed within one week after surgery and was repeated one year postoperatively. There was no significant difference in periprosthetic BMD change between the three groups. After twelve months the relative BMD decrease was highest in the proximal part of the femur, - 6.2% in the greater trochanter region and - 12.7% in the lesser trochanter region. In the distal zones the relative BMD decrease was -5.3, -4.2, -2.1, -2.3, and -5.6%, respectively. The use of different bearing materials had no significant impact on femoral bone remodelling adjacent to the cemented hip stem within one year after surgery.

Aged↗
PubMed2004

Infections in neurosurgical patients admitted to the intensive care unit at the University Hospital of the West Indies.

Patients admitted to the Intensive Care Unit (ICU) are at risk of developing life-threatening nosocomial infections, especially with organisms resistant to commonly used antibiotics. Neurosurgical patients are particularly vulnerable because of the serious nature of their illness, the frequency of associated trauma and the presence of invasive devices. Of 120 neurosurgical patients admitted to the ICU of the University Hospital of the West Indies (UHWI) between September 1995 and December 1999, the records of 73 patients were available for analysis. All had prophylactic antibiotics. Twenty-one of these 73 patients (28.8%) developed 22 infections after a mean of five days in the ICU: nine with chest infection, seven with urinary tract infection, four with central nervous system (CNS) infection and one each with wound and skin infection. This is an incidence of 11.6/1000 patient-days. The responsible organisms included Pseudomonas (7/21), Acinetobacter (3/21), E. coli 2/21, Enterobacter (2/21), and Klebsiella (2/21), and one each with Staphylococcus aureus, methicillin resistant Staphylococcus aureus, coagulase negative Staphylococcus, group D Streptococcus and bacteroides (1/21). Infection was significantly related to length of hospital stay, length of ICU stay, duration of intubation, duration of ventilation and the presence of diabetes mellitus. All patients who had surgery after ICU admission developed infection, seven with chest infection, two with urinary tract infection, two with CNS and one with skin infection. The three patients who were admitted with intracranial infections all developed other infections. Infected patients had a significantly longer hospital stay. Five patients died, none directly attributable to infection, while 55 (75.5%) made a good recovery. The problem of ICU infection may be expected to escalate with the increased use of intensive care, increasingly more complex surgical procedures and the growing problem of antibiotic resistance. Since infection is related to the length of ICU stay, earlier discharge of neurosurgical patients to an appropriately staffed high dependency unit is likely to result in reduction of the infection rate. Reinforcement of infection control strategies within the ICU may be expected to further minimize the infection rate.

Adolescent↗
PubMed2003

Health and stress in Australian interns.

Over a 3-year period, interns completed questionnaires on self-reported health and stress during their orientation week at the beginning of the year, during mid year, and at the end of the first year. Interns experienced increased levels of stress and ill health in the middle of the year as compared with the start and end of the year (chi2=11.9, P=0.003 and chi2=20.4, P<0.001, respectively). Despite workplace reform for junior doctors, this study suggests that interns still feel overburdened with work expectations and this is having a negative effect on their health.

Adult↗
PubMed2002

Caffeine decreases exhaled nitric oxide.

BACKGROUND: Caffeine is known to inhibit phosphodiesterases, to mobilise intracellular calcium, and to act as an antagonist at adenosine receptors, all of which can potentially alter nitric oxide (NO) production. It was therefore hypothesised that caffeine may alter exhaled NO (eNO) levels. METHODS: In a randomised, single blind, crossover manner, 12 normal subjects consumed either (1) coffee and a placebo capsule, (2) decaffeinated coffee and a capsule of 200 mg caffeine, or (3) decaffeinated coffee and a placebo capsule. Serum caffeine levels were measured at baseline and 1 hour later. Exhaled NO levels were also measured at baseline and each hour for 4 hours. RESULTS: A significant percentage fall in mean (SE) eNO from baseline was seen 1 hour after either caffeinated coffee or a caffeine capsule when compared with placebo (13.5 (4.0)%, p=0.009 and 19.0 (3.8)%, p=0.001, respectively). CONCLUSION: Caffeine causes a significant decrease in eNO which will need to be considered when designing trials to measure eNO levels. The mechanism may be via adenosine receptor antagonism or by altering levels of cGMP.

Adult↗
PubMed2001

Effect of ecNOS polymorphisms and coronary artery disease upon exhaled nitric oxide.

Exhaled nitric oxide (eNO) is thought to arise principally from the airway epithelium. NO regulates smooth muscle tone, and abnormal activity of NO synthase has been implicated in coronary artery disease (CAD). Polymorphisms of endothelial constitutive NO synthase (ecNOS) may affect NO generation and be associated with CAD. It was hypothesised that a polymorphism, such as the ecNOS intron 4 polymorphism (ecNOS4a), affects the levels of eNO via airway epithelial NOS. eNO levels were measured in 53 patients with ischaemic chest pain who had previously been genotyped for ecNOS polymorphisms, with sample enrichment for the ecNOS4a allele. Subjects were also assessed for two other ecNOS polymorphisms (T-786C substitution in the promoter region, and G5557T in exon 7), variably associated with vascular disease. Those homozygous for the 'a' allele (ecNOS4a/a) had a lower mean eNO (9.0 ppb) than those who were heterozygous (ecNOS4a/b, 13.6 ppb), who in turn had a lower level than those homozygous for the wild-type ecNOS4b/b (16.1 ppb). No association of eNO levels was found with the other polymorphisms. Levels of eNO remained significantly lower in the ecNOSa/a subjects than in the ecNOSa/b and ecNOSb/b subjects, even when controlled for angiographic CAD, and smoking habit. In addition, all subjects with CAD had a significantly lower mean eNO (12.1 ppb) than subjects without angiographic CAD (19.9 ppb). In this selected population low levels of eNO were thus associated with presence of the ecNOS4a allele and also with CAD.

Administration, Oral↗
PubMed2001

Effect of peer led programme for asthma education in adolescents: cluster randomised controlled trial.

OBJECTIVE: To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma. DESIGN: Cluster randomised controlled trial. SETTING: Six high schools in rural Australia. PARTICIPANTS: 272 students with recent wheeze, recruited from a cohort of 1515 students from two school years (mean age 12.5 and 15.5 years); 251 (92.3%) completed the study. INTERVENTION: A structured education programme for peers comprising three steps (the "Triple A Program"). MAIN OUTCOME MEASURES: Quality of life, school absenteeism, asthma attacks, and lung function. RESULTS: When adjusted for year and sex, mean total quality of life scores showed significant improvement in the intervention than control group. Clinically important improvement in quality of life (>0.5 units) occurred in 25% of students with asthma in the intervention group compared with 12% in the control group (P=0.01). The number needed to treat was 8 (95% confidence interval 4.5 to 35.7). The effect of the intervention was greatest in students in year 10 and in females. Significant improvements occurred in the activities domain (41% v 28%) and in the emotions domain (39% v 19%) in males in the intervention group. School absenteeism significantly decreased in the intervention group only. Asthma attacks at school increased in the control group only. CONCLUSION: The triple A programme leads to a clinically relevant improvement in quality of life and related morbidity in students with asthma. Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in adolescents.

Absenteeism↗
PubMed2001

Nasal and exhaled nitric oxide in response to occupational latex exposure.

BACKGROUND: Latex sensitivity is an increasing problem among health-care workers. Allergic responses are associated with changes in nitric oxide (NO) generation and the changes secondary to latex have not been described. METHODS: A total of 22 subjects comprising equal numbers of control volunteers and subjects with self-reported latex sensitivity were recruited to undergo latex skin prick testing. Symptom scores, exhaled nitric oxide (eNO), and nasal nitric oxide (nNO) were studied 1) before and after a controlled latex challenge (n=16), and 2) at the beginning and end of the working week, during exposure to latex (n=18). RESULTS: Latex challenge caused a significant fall in nNO levels in latex-sensitive subjects, compared to normal control subjects (P=0.04). eNO levels also decreased in the latex-sensitive subjects after latex challenge, but to a lesser degree. There were no significant differences between the beginning and end of the working week in terms of eNO or nNO in either group, although symptom scores showed a nonsignificant increase in latex-sensitive subjects. CONCLUSION: Fall in nasal NO after latex challenge is associated with reported symptomatic latex sensitivity, and this corresponds to latex skin prick test positivity. Neither nNO nor eNO showed a clear relationship to routine workplace exposure.

Adult↗
PubMed2001

Supporting Partners of People with Aphasia in Relationships and Cconversation (SPPARC).

This paper reviews new theoretical and practical developments in working with partners of people with aphasia and describes the development of a clinician's resource entitled 'SPPARC: Supporting Partners of People with Aphasia in Relationships and Conversation'. It focuses particularly on one part of that resource: the SPPARC Conversation Training Programme, which adapts conversation analysis for clinical use. The paper describes the stages involved in assessing and working on conversation in everyday life.

Aphasia↗
PubMed2001

The development of a self-directed and peer-based clinical training programme.

A reflective learning approach for clinical training with final year students is described. The training programme aims to promote the development of independent and reflective practitioners. The theories and ideas that have influenced the structure of the programme are described and an outline of the programme is provided. The views of students who have participated in the process are discussed. Most students were positive about their experiences, but some problems were reported. Suggestions for improving the supervisory process are considered.

Consumer Behavior↗
PubMed2000

Receptors and lipid transfer proteins in HDL metabolism.

It is believed that HDL exerts its anti-atherogenic effects through the process of delivering cholesterol from peripheral tissues back to the liver for removal from the body (i.e., reverse cholesterol transport). The metabolic life cycle of HDL lipid and apolipoproteins during reverse cholesterol transport involves both its modification in plasma by lipid transfer proteins and the clearance from plasma of HDL lipid and protein mediated by hepatic cell surface proteins. We review recent work from our laboratory that focuses on specific metabolic steps in reverse cholesterol transport and the results of altering these steps on plasma HDL levels and atherosclerosis. Recently, SR-BI was shown to be an authentic HDL receptor mediating the selective uptake of HDL lipids into cells without degradation of HDL proteins. We discuss the evidence for additional receptor activity mediating HDL protein catabolism in the liver from studies in obese (ob/ob) mice, which have markedly increased HDL due to a defect in hepatic catabolism of apoA-I and apoA-II. In addition, we review recent findings that phospholipid transfer protein deficiency in mice results in markedly reduced HDL levels. Lastly, we highlight our findings that overexpression of SR-BI in LDL receptor-deficient mice results in decreased atherosclerosis.

Animals↗
PubMed2000

Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins.

Phospholipid transfer protein gene knock-out (Pltp KO) mice have defective transfer of very low density lipoprotein (VLDL) phospholipids into high density lipoprotein (HDL) and markedly decreased HDL levels (Jiang et al. 1999. J. Clin. Invest. 103: 907-914). These animals also accumulated VLDL- and LDL-sized lipoproteins on a high saturated fat diet. The goals of this study were to further characterize the abnormal lipoproteins of Pltp KO mice and to determine the mechanisms responsible for low HDL levels. A lipoprotein fraction enriched in lamellar structures was isolated from the low density lipoprotein (LDL) region and was shown to be phospholipid- and free cholesterol-rich and to have apoA-IV (55%) and apoE (25%) as major apolipoproteins. The lamellar lipoproteins accumulating in these mice probably represent surface material derived from triglyceride-rich lipoproteins (TRL). The HDL was found to be protein-rich (primarily apoA-I) and specifically depleted in phosphatidylcholine (PC) (28% in wild-type mice (WT) vs. 15% in Pltp KO mice, P < 0.001). Unexpectedly, turnover studies using autologous HDL revealed a profound 4-fold increase in the catabolism of HDL protein and cholesteryl ester in Pltp KO mice compared to wild-type, with minor differences in synthesis rates. In contrast, injection of WT mouse HDL into Pltp KO mice showed only a 2-fold increase in fractional catabolism. Reminiscent of the defect in Tangier disease, the failure of transfer of PC from TRL into the HDL fraction results in dramatic hypercatabolism of HDL. These results suggest that defective phospholipid transfer from TRL into HDL, arising from decreased lipolysis or decreased PLTP activity, could lead to hypoalphalipoproteinemia characterized by hypercatabolism of HDL protein. lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins.

Animals↗
PubMed2000

Inhibition of cholesteryl ester transfer protein by substituted dithiobisnicotinic acid dimethyl ester: involvement Of a critical cysteine.

SC-71952, a substituted analog of dithiobisnicotinic acid dimethyl ester, was identified as a potent inhibitor of cholesteryl ester transfer protein (CETP). When tested in an in vitro assay, the concentration of SC-71952 required for half-maximal inhibition was 1 microm. The potency of SC-71952 was enhanced 200-fold by preincubation of the inhibitor with CETP, and was decreased 50-fold by treatment with dithiothreitol. Analogs of SC-71952 that did not contain a disulfide linkage were less potent, did not display time dependency, and were not affected by dithiothreitol treatment. Kinetic and biochemical characterization of the inhibitory process of CETP by SC-71952 suggested that the inhibitor initially binds rapidly and reversibly to a hydrophobic site on CETP. With time, the bound inhibitor irreversibly inactivates CETP, presumably by reacting with one of the free cysteines of CETP. Liquid chromatography/mass spectroscopy (LC/MS) analyses of tryptic digests of untreated or SC-71952-inactivated CETP was used to identify which cysteine(s) were potentially involved in the time-dependent, irreversible component of inactivation by the inhibitor. One disulfide bond, Cys143-Cys184, was unaffected by treatment with the inhibitor. Inactivation of CETP by SC-71952 correlated with a progressive decrease in the abundance of free Cys-13 and Cys-333. Conversion of Cys-13 to alanine had no effect on the rapid reversible component of inactivation by SC-71952. However, it abolished the time-dependent enhancement in potency seen with the inhibitor when using wild-type CETP. These data indicate that Cys-13 is critical for the irreversible inactivation of CETP by SC-71952 and provides support for the structural model that places Cys-13 near the neutral lipid-binding site of CETP.

Amino Acid Substitution↗
PubMed1999

Amniotic fluid insulin levels identify the fetus at risk of neonatal hypoglycaemia.

AIMS: To investigate the use of amniotic fluid insulin (AFI) as a predictor of neonatal morbidity in the macrosomic newborn of the diabetic mother, in view of the fact that raised AFI levels are a marker for fetal hyperinsulinaemia. METHODS: AFI was measured by radioimmunoassay in a group of pregnant diabetic women (n = 63) with normal (n = 41) or accelerated fetal growth (n = 22). RESULTS: Using log transformed data, liquor insulin was found to be significantly higher in pregnant women with Type 1 and Type 2 diabetes mellitus (17.6 mU/l; 95% confidence interval (CI) 11.7-26.4) compared with women with gestational diabetes mellitus (GDM) (8.2 mU/l; 95% CI 4.8-13.8, P = 0.02) or impaired glucose tolerance (IGT) (6.2mU/l; 95% CI 4.9-8.0, P = 0.0001). In the group with macrosomic fetuses (birth weight > 90th centile for gestational age), there was a significantly higher incidence of elective Caesarean section (CS) and emergency CS (12/22) compared to those with appropriate for gestational age (AGA) fetal weights (birth weight > 10th and < 90th centiles for gestational age) (9/41, P = 0.009). There was no significant correlation between raised AFI and macrosomia except in the Type 1 diabetic women, in whom the AGA group mean was 13.2 mU/l (95% CI 7.4-23.3), and 34.6mU/l (95% CI 17.5-68.4 P = 0.022) in macrosomia. In the latter group, hypoglycaemia requiring treatment was significantly more common in the macrosomic hyperinsulinaemic neonates (8/13), compared to normoinsulinaemic neonates in the same group (0/9, P = 0.005). CONCLUSIONS: Identification of the hyperinsulinaemic fetus before delivery might allow the intensification of maternal insulin therapy leading to a reduction in incidence and severity of diabetic fetopathy. Pregnancy with a normoinsulinaemic fetus could be allowed to continue to the onset of spontaneous labour, which might result in a lower CS rate.

Amniocentesis↗