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Biomedical subjects

K Bartlett

Publications and source records attributed to K Bartlett.

At least 19 recordsLinked to original sources
PubMed2001

Neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency.

Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency has not yet been introduced in the UK, primarily because of uncertainty about the natural history of the disorder and concerns about the specificity of the screening test. To obtain data on these issues, we did a retrospective study in which we analysed the concentrations of acylcarnitines in stored neonatal blood spots, and reviewed patients with high octanoylcarnitine concentrations at age 7-9 years. The high morbidity and mortality associated with the disorder, and the specificity of acylcarnitine analysis seen in our study support the introduction of screening for MCAD deficiency.

Acyl-CoA Dehydrogenase↗
PubMed2001

Carnitine palmitoyl transferase I and the control of beta-oxidation in heart mitochondria.

Mitochondrial beta-oxidation provides much of the fuel requirements of heart and skeletal muscle despite the malonyl-CoA concentration greatly exceeding the IC(50) of carnitine palmitoyl transferase for malonyl-CoA. To try to explore the relationship between inhibition of carnitine palmitoyl transferase I activity and beta-oxidation flux, we measured the flux control coefficient of carnitine palmitoyl transferase I over beta-oxidation carbon flux in suckling rat heart mitochondria. The flux control coefficient was found to be 0.08 +/- 0.05 and 50% of carnitine palmitoyl transferase I activity could be inhibited before beta-oxidation flux was affected. These observations may help to explain the presence of high rates of beta-oxidation despite the high concentration of malonyl-CoA in rat heart; we hypothesize that although not rate-limiting in vitro, carnitine palmitoyl transferase is rate-limiting in vivo because of the high malonyl-CoA concentration in heart and muscle.

Animals↗
PubMed2001

Carnitine palmitoyl transferase I and the control of myocardial beta-oxidation flux.

Carnitine palmitoyltransferase I is assumed to be rate limiting for beta-oxidation in all tissues. However, the concentration of malonyl-CoA in heart and muscle is high and is enough to completely inhibit beta-oxidation if this assumption is correct. In this review, we consider whether: (i) there is a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity; (ii) the measured malonyl-CoA concentration in the heart is physiologically meaningful; and (iii) carnitine palmitoyltransferase I is rate-limiting for beta-oxidation in the heart.

Acetyl Coenzyme A↗
PubMed2001

Spatial and temporal distribution of airborne Bacillus thuringiensis var. kurstaki during an aerial spray program for gypsy moth eradication.

We measured airborne exposures to the biological insecticide Bacillus thuringiensis var. kurstaki (Btk) during an aerial spray program to eradicate gypsy moths on the west coast of Canada. We aimed to determine whether staying indoors during spraying reduced exposures, to determine the rate of temporal decay of airborne concentrations, and to determine whether drift occurred outside the spray zone. During spraying, the average culturable airborne Btk concentration measured outdoors within the spray zone was 739 colony-forming units (CFU)/m3 of air. Outdoor air concentrations decreased over time, quickly in an initial phase with a half time of 3.3 hr, and then more slowly over the following 9 days, with an overall half-time of about 2.4 days. Inside residences during spraying, average concentrations were initially 2-5 times lower than outdoors, but at 5-6 hr after spraying began, indoor concentrations exceeded those outdoors, with an average of 244 CFU/m3 vs. 77 CFU/m3 outdoors, suggesting that the initial benefits of remaining indoors during spraying may not persist as outside air moves indoors with normal daily activities. There was drift of culturable Btk throughout a 125- to 1,000-meter band outside the spray zone where measurements were made, a consequence of the fine aerosol sizes that remained airborne (count median diameters of 4.3 to 7.2 microm). Btk concentrations outside the spray zone were related to wind speed and direction, but not to distance from the spray zone.

Aerosols↗
PubMed2001

A model for predicting endotoxin concentrations in metalworking fluid sumps in small machine shops.

METHODS: In British Columbia, Canada, nineteen small machine shops which used water-based metalworking fluids (MWF) were examined. One bulk MWF sample was taken from each independent sump (N=140) and tested for endotoxin using the Limulus Amoebocyte Lysate assay. Factors that might influence the MWF sump endotoxin concentration were investigated using mixed effect multiple regression modelling to control for repeated measures within shops. RESULTS: The geometric mean (GM) endotoxin concentration was 6791 EU/ml. Contamination of MWF with tramp oil, MWF pH, MWF temperature, and MWF type were significant predictors of sump fluid endotoxin concentration (model P=0.0001, ordinary least squares R(2) =0.36). Concentrations of endotoxin in sump fluids were increased by MWF contamination with tramp oils such as hydraulic oils, preservative oils, spindle oils, slidway lubricants, gear lubricants, and greases (model predicted GM=17400 EU/ml vs. 1600 EU/ml without tramp oil). Concentrations were also elevated where pH was lower than 8.5 (predicted GM=10600, vs 3600 EU/ml for pH 8.5 to 9.5), where soluble fluids were used (predicted GM=11800 vs. 2800 EU/ml for synthetic fluids), and where sump fluid temperatures were higher (predicted GM=2600 EU/ml at 11 degrees C vs. 21500 EU/ml at 32 degrees C). The within-shop correlation of sump bulk fluid endotoxin concentrations was 38%. CONCLUSIONS: Minimizing tramp oil contamination, using synthetic fluids, and monitoring pH and temperature would be valuable tools for controlling endotoxin contamination in MWF sumps. In addition, since there was correlation within-shop, contamination of one sump in a shop may suggest changing the fluids in all.

Endotoxins↗
PubMed2000

The measurement of volatile constituents in Foray 48B, an insecticide prepared from Bacillus thuringiensis var. kurstaki.

Foray 48B, an insecticide prepared from Bacillus thuringiensis var. kurstaki (Btk), has been used for many years to combat infestations of Gypsy moths. Foray 48B also contains a large number of 'inert ingredients' which are not disclosed by the manufacturer. Gypsy moths usually enter the country through marine- and airports in close proximity to urban areas, which consequently need to be sprayed. The population affected often demands more detailed information than what is available including the potential presence of volatile organic agents which could be released during spraying, posing a potential health hazard. Four different methods were investigated using GC/mass spectrometry regarding their ability to capture volatile agents associated with Foray 48B. It was found that solid phase micro-extraction was most efficient in capturing volatile agents from the head-space of Foray 48B. Separate trials using 95:5% ethanol/isopropanol mixture and toluene in an impinger configuration were much less efficient. Standard techniques using activated charcoal tubes in the laboratory setting as well as in a field trial did not capture any compounds. It was concluded that the volatile agents associated with Foray 48B did not appear to constitute a significant health hazard and no one agent was a likely candidate to serve as a tracer for Foray 48B exposure.

Bacillus thuringiensis↗
PubMed2000

Plasma coenzyme Q(10) in children and adolescents undergoing doxorubicin therapy.

The objective of this study was to test the hypothesis that doxorubicin treatment for cancer in childhood and adolescence causes a dose-related decrease in the concentration of plasma coenzyme Q(10). The concentration of plasma coenzyme Q(10) was measured before and after administration of doxorubicin in six patients, and before and after chemotherapy in six patients undergoing treatments that did not include doxorubicin. There was a significant increase in the concentration of plasma coenzyme Q(10) in post-treatment samples compared to pre-treatment samples in patients treated with doxorubicin (P=0.008; n=32), whereas there were no significant changes in plasma coenzyme Q(10) concentrations in patients treated with chemotherapy that did not include doxorubicin. (P=0.770; n=30). We hypothesise that the increase in plasma coenzyme Q(10) that was observed in patients undergoing doxorubicin treatment is due to release of coenzyme Q(10) from apoptotic or necrotic cardiac tissue. We conclude that the cardiotoxicity due to doxorubicin therapy does not involve acute myocardial depletion of coenzyme Q(10).

Adolescent↗
PubMed2000

The mitochondrial trifunctional protein: centre of a beta-oxidation metabolon?

The trifunctional enzyme comprises three consecutive steps in the mitochondrial beta-oxidation of long-chain acyl-CoA esters: 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase. Deficiencies in either 3-hydroxyacyl-CoA dehydrogenase activity, or all three activities, are important causes of human disease. The dehydrogenase and thiolase have a requirement for NAD+ and CoA respectively, whose levels are conserved within the mitochondrion and thus provide possible means for control and regulation of beta-oxidation. Using analysis of the intact CoA ester intermediates produced by the complex, we have examined the sensitivity of the complex to NAD+/NADH and acetyl-CoA. We consider the evidence for channelling within the trifunctional protein and propose a model for a beta-oxidation 'metabolon'.

Amino Acid Sequence↗
PubMed2000

Preliminary report on the results of the second phase of a round- robin endotoxin assay study using cotton dust.

In an on-going endotoxin assay study, a two-part interlaboratory endotoxin assay study has been completed. The purpose of the study was to compare the variation in assay results between different laboratories, and, if the variation was high, to see if a common protocol would reduce the variation. In both parts of the study, membrane filters laden with the same approximate amount and type of cotton dust were sent for analysis to laboratories that "routinely" perform endotoxin analyses. First, each of these laboratories performed the analysis using the methodology common to its laboratory. In the second part of the study, membrane filters with cotton dust were again sent to the same laboratories where the analyses were performed as before but with a common extraction protocol. The preliminary results from the first phase of the study have been collected and showed that intra-laboratory variations were small, but large and significant interlaboratory variation was observed. The results were reported elsewhere. The preliminary results from the second part of the study consisting of the data currently collected are presented here. Again, intra-laboratory variations were small, but, also again, large and significant inter-laboratory variation was observed. However, in this part of the study, the range between the highest and lowest average results was narrower than in the first part of the study. Influence of the assay kit type was examined. The variation within assay kit type was small but significant differences in results were observed between assay kit types. The findings suggest that endotoxin concentration in samples can be ranked within laboratories, but not necessarily between laboratories. However, some of the variation between laboratories has been reduced by a common extraction protocol which suggests the possibility of further standardization that may lead to better comparability between laboratories.

Air Pollution, Indoor↗
PubMed2000

Effect of oral antibiotics on intestinal production of propionic acid.

BACKGROUND: Propionic acid derived from colonic bacterial fermentation contributes substantially to overall propionate load in children with disorders of propionate metabolism, and its reduction is important for adequate metabolic control. AIMS: To evaluate the in vitro and in vivo effects of antibiotic treatment on propionate production by colonic bacteria, and plasma propionate concentrations in a child with propionic acidaemia. METHODS: In vitro fermentation techniques were used to study the effects of addition of antibiotics (metronidazole, clindamycin, erythromycin, and vancomycin) on net faecal production of short chain fatty acids including propionic acid. Courses of oral antibiotics of 7 days duration were used to assess the in vivo effects on faecal propionate production and metabolic control including plasma propionate concentrations. RESULTS: Metronidazole produced the largest and most consistent reduction (77-84%) in the production in vitro of propionate from faecal homogenates. Oral administration of metronidazole reduced faecal propionate production by 43% within 24 hours of treatment; a 7 day course virtually eliminated it for the next 3 weeks. These reductions were accompanied by substantially lowered plasma propionate concentrations during the same period. CONCLUSIONS: Intermittent courses of oral metronidazole might be as effective as continuous treatment in reducing gut propionate production in children with disorders of propionate metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Intermediates of myocardial mitochondrial beta-oxidation: possible channelling of NADH and of CoA esters.

Adult rat heart mitochondria were isolated and incubated with [U-14C]hexadecanoyl-CoA or unlabelled hexadecanoyl-CoA. The accumulating CoA and carnitine esters and [NAD+]/[NADH] ratio were measured by HPLC or tandem mass spectrometry. Despite minimal changes in the intramitochondrial [NAD+]/[NADH] ratio, 2, 3-unsaturated and 3-hydroxyacyl esters were observed as well as saturated acyl-CoA and acylcarnitine esters. In addition to acetylcarnitine, significant amounts of butyryl-, hexanoyl-, octanoyl- and decanoylcarnitines were detected and measured. Rat myocardial beta-oxidation is subject to control at the level of 3-hydroxyacyl-CoA dehydrogenase but this control is not due to a simple lack of oxidised NAD. We hypothesise a pool of NAD in contact between the trifunctional protein of beta-oxidation and complex I of the respiratory chain, the turnover of which is responsible for some of the control of beta-oxidation flux. In addition, short- and medium-chain acylcarnitine esters were detected whereas only small amounts of long-chain acylcarnitines were present. This may imply the presence of a mitochondrial carnitine octanoyl transferase or may reflect channelling of long-chain CoA esters so that they are not available for carnitine palmitoyl transferase II activity.

Animals↗
PubMed1999

Tandem mass spectrometry--the potential.

We summarize the current status of the use of tandem mass spectrometry for the detection of inherited metabolic disorders and the investigation of the pathophysiology of these conditions. We also indicate some of the more recent developments of this technology that have potential diagnostic applications.

Humans↗
PubMed1999

Wheat antigen content of inhalable dust in bakeries: modeling and an inter-study comparison.

The purposes of this study were (a) to compare wheat antigen content of inhalable bakery dust in Canada and the Netherlands and, (b) to evaluate the validity of dust exposure measurement as a surrogate of specific antigen exposure. Wheat antigen exposure data from the studies of Canadian and Dutch bakeries were used to explore the correlation between dust and antigen levels, and identify factors explaining variability of the antigen content of bakery dust. Direct comparison and pooling of the data were possible because the same antigen assay was used in both studies. Wheat antigen exposure samples totaling 544 were available, all originating from personal full-shift monitoring of bakery workers. The wheat antigen content of bakery dust varied greatly between the two studies and with different products within each study. Bakery dust from the Canadian study had a much higher wheat antigen content. Therefore, the interstudy difference in the wheat antigen content of bakery dust was by far the most significant in undermining the validity of the use of dust levels as a surrogate measures of wheat antigen exposure. The production of croissants, wheat bread and buns, puff pastry, bagels, and cinnamon buns was associated with increased wheat antigen content of bakery dust, while in rye bread production, bakery dust with less wheat antigen content was emitted. Although we can, in part, account for the pattern of variability in the wheat antigen content of bakery dust (explaining 49% of it), we concluded that the effort involved in modeling it accurately would probably exceed that expended in direct measurement of the antigen level. Therefore, for the exposure assessments carried out for the purpose of managing occupational risks of aeroallergen exposure in bakeries, we recommend the use of analytical techniques that can directly measure antigen exposure.

Antigens↗
PubMed1999

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting. To examine whether these different phenotypes are due to differences in the VLCAD genotype, we investigated 58 different mutations in 55 unrelated patients representing all known clinical phenotypes and correlated the mutation type with the clinical phenotype. Our results show a clear relationship between the nature of the mutation and the severity of disease. Patients with the severe childhood phenotype have mutations that result in no residual enzyme activity, whereas patients with the milder childhood and adult phenotypes have mutations that may result in residual enzyme activity. This clear genotype-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1999

Endotoxin exposure among softwood lumber mill workers in the Canadian province of British Columbia.

An increased prevalence of respiratory problems among softwood lumber mill workers has been observed in a number of studies. These workers are potentially exposed to a variety of respiratory hazards including wood dust, abietic or other resin acids, monoterpenes, and fungi, as well as endotoxins. The objectives of this study were to determine if lumber mill workers were exposed to hazardous levels of airborne endotoxin and to identify the factors contributing to high exposures. Personal endotoxin samples (n = 216) were collected in four lumber mills in the Canadian province of British Columbia. The mean personal exposure concentration was 2.09 ng/m.(3) and 9% of the samples were above 5 ng/m.(3). Factors related to the personal endotoxin exposure were type of job, use of compressed air, the percentage of time spent in a booth or cab during a shift, and dust concentration. Log storage practices were also suspected of playing a role. The levels of exposure observed in this study were low compared to the levels reported for populations with respiratory problems attributed to endotoxins.

Air Microbiology↗