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Biomedical subjects

D J Taylor

Publications and source records attributed to D J Taylor.

At least 73 records · Page 4Linked to original sources

Reactive thrombocytosis after caesarean section and vaginal delivery: implications for maternal thromboembolism and its prevention.

OBJECTIVE: To assess the duration and severity of reactive thrombocytosis after caesarean section and vaginal delivery. DESIGN: A prospective cohort study. SETTING: A large teaching hospital. METHODS: Women admitted for delivery at the Leicester Royal Infirmary were recruited into the study. The platelet count was measured before delivery and postnatally on days 3, 8, 12, 16, 20 and 24. Women who had antepartum haemorrhage, postpartum haemorrhage and those delivered by instrumental delivery were excluded from the study. Sixty-five were recruited, and 45 completed the study, 20 of whom were delivered by a normal vaginal delivery and 25 by caesarean section. A random effects model was used to compare platelet counts within and between the two groups to assess the severity and the timing of reactive thrombocytosis. RESULTS: There were no statistically significant differences in booking and pre-delivery platelet counts between the two groups (mean values 248.4 x 10(9)/L and 245 x 10(9)/L in the normal vaginal group and 269.4 x 10(9)/L and 251.6 x 10(9)/L in the caesarean section group, respectively). Postnatally, a rise in the platelet count was noted in the normal vaginal delivery group, reaching statistically significant peak values, compared with booking and pre-delivery at days 8 and 12 of the postnatal period (mean value 365.8 x 10(9)/L; P < 0.001 and 369.4 x 10(9)/L; P < 0.001 respectively). In the caesarean section group, the platelet count was raised to a statistically significant high value, compared with booking and pre-delivery at day 8 of the postnatal period. The platelet count peaked at days 12 and 16 of the postnatal period (mean value 522.5 x 10(9)/L; P < 0.0001 and 526.5 x 10(9)/L; P < 0.0001, respectively) and remained significantly higher than booking and predelivery values for 24 days after the caesarean section. There was a greater rise in the platelet count in the caesarean section group compared with the vaginal delivery group. The platelet counts in the caesarean section group were significantly higher than these in the normal vaginal delivery group from day 12 to day 24 of the postnatal period. CONCLUSION: A significant rise in platelet count occurred eight to twelve days after normal vaginal delivery and caesarean section. The increase in platelet count continued to rise for 16 days after caesarean section, and it stayed significantly higher for more than 24 days after the delivery.

Cesarean Section↗

Attempted eradication of salmonellosis from a colony of short-tail grey opossums (Monodelphis domestica).

Prior to re-housing a colony of laboratory short-tail grey opossums, the animals were found to harbour salmonella. This paper describes an unsuccessful attempt to eradicate the infection from the colony by means of antibiotic treatment and hygienic measures. A pilot treatment of five animals which received enrofloxacin 10 mg/kg for 5 days appeared to be successful in that no salmonellae were recovered from faeces or organs sampled after treatment. The process was repeated on the whole colony prior to a change of accommodation but 2 animals were found to be still infected, 5 weeks after cessation of treatment.

Animals↗

Unilateral diaphragmatic paralysis following bronchial artery embolization for hemoptysis.

Bronchial artery embolization is an effective treatment for patients with hemoptysis. Serious complications are rare, but may occur if the arterial supply to other structures is compromised. We present a case of unilateral diaphragmatic paralysis following bronchial artery embolization in a patient with cystic fibrosis. We believe that the diaphragmatic paralysis was due to the inadvertent obstruction of the left pericardiacophrenic artery during the embolization procedure, with compromise of the phrenic nerve blood supply. This resulted in a significant loss of lung function in our patient, who did not recover despite the subsequent return of diaphragmatic function.

Adult↗

Very low levels of the mtDNA A3243G mutation associated with mitochondrial dysfunction in vivo.

We studied mitochondrial function in vivo in 2 brothers harboring the mitochondrial DNA A3243G mutation by using magnetic resonance spectroscopy. One brother presented with recurrent strokes and had a mitochondrial respiratory chain complex I defect, with 85% A3243G mutation in his quadriceps. The maximum rate of mitochondrial ATP production in his calf, measured in vivo, was reduced to 21% of the normal mean value. The second brother had mild exercise intolerance, normal muscle histochemistry, and normal respiratory chain activity in vitro. Despite a level of the A3243G mutation of only 5.95% (SD, 4.45; range, 0.7-16.1%) within single muscle fibers from the gastrocnemius muscle, the maximum rate of mitochondrial ATP production in his calf, measured in vivo, was reduced to 35% of the normal mean value. These findings suggest that there may not be a clear genetic threshold level for the expression of the A3243G mutation in skeletal muscle in vivo.

Adult↗

High serum levels of pro-matrix metalloproteinase-3 are associated with greater radiographic damage and the presence of the shared epitope in patients with rheumatoid arthritis.

OBJECTIVE: To determine if there is a relationship between serum pro-matrix metalloproteinase-3 (proMMP-3) levels and radiographic damage in rheumatoid arthritis (RA), and to investigate whether high levels are associated with presence of the HLA-DRB1 shared epitope (SE). METHODS: Serum proMMP-3 levels were measured by ELISA on 45 RA patients with early disease and 292 with established disease. Early RA was arbitrarily defined as disease duration <3 years. Clinical and laboratory measures of disease activity and severity were obtained. Radiographic damage was assessed by scoring radiographs of the hands and feet using the method of Larsen. HLA-DRB1 typing was performed by sequence-specific oligonucleotide probing. Data were analyzed by multiple regression analysis. RESULTS: In all patients, there was a correlation (r = 0.318, p<0.0001) between serum proMMP-3 levels and Larsen scores. Other correlations were found with Health Assessment Questionnaire score (r = 0.261, p<0.0001) and C-reactive protein (CRP) (r = 0.357, p<0.0001) levels. ProMMP-3 levels were significantly higher in SE+/+ patients than in those completely lacking the SE, with the highest levels in patients carrying an HLA-DRI+/DR4+ phenotype. The greatest difference in proMMP-3 levels between SE+/+ and SE-/- patients was in those with a disease duration <3 years (381.6 vs. 71.7 ng/ml; p = 0.02). CONCLUSION: Our data indicate that there is a significant relationship between radiographic damage and serum levels of proMMP-3. As well, higher circulating levels of proMMP-3 are found in patients positive for the SE, particularly in early RA, and this may partly explain the association between the SE and more erosive disease.

Adult↗

Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy.

We studied in vivo muscle energy metabolism in patients with Huntington's disease (HD) and dentatorubropallidoluysian atrophy (DRPLA) using 31P magnetic resonance spectroscopy (MRS). Twelve gene-positive HP patients (4 presymptomatic patients) and 2 gene-positive DRPLA patients (1 presymptomatic patient) were studied. 31P-MRS at rest showed a reduced phosphocreatine-to-inorganic phosphate ratio in the symptomatic HD patients and DRPLA patient. Muscle adenosine triphosphate/(phosphocreatine + inorganic phosphate) at rest was significantly reduced in both groups of symptomatic and presymptomatic HD subjects and was below the normal range in the 2 DRPLA subjects. During recovery from exercise, the maximum rate of mitochondrial adenosine triphosphate production was reduced by 44% in symptomatic HD patients and by 35% in presymptomatic HD carriers. The maximum rate of mitochondrial adenosine triphosphate production in muscle was also reduced by around 46% in the 2 DRPLA subjects. Our findings show that HD and DRPLA share a deficit of in vivo mitochondrial oxidative metabolism, supporting a role for mitochondrial dysfunction as a factor involved in the pathogenesis of these polyglutamine repeat-mediated neurodegenerative disorders. The identification of 31P-MRS abnormalities may offer a surrogate biochemical marker by which to study disease progression and the effects of treatment in HD and DRPLA.

Adenosine Triphosphate↗

Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia.

Friedreich ataxia (FRDA), the most common of the inherited ataxias, is an autosomal recessive degenerative disorder, characterized clinically by onset before the age of 25 of progressive gait and limb ataxia, absence of deep tendon reflexes, extensor plantar responses, and loss of position and vibration sense in the lower limbs. FRDA is caused by a GAA triplet expansion in the first intron of the FRDA gene on chromosome 9q13 in 97% of patients. The FRDA gene encodes a widely expressed 210-aa protein, frataxin, which is located in mitochondria and is severely reduced in FRDA patients. Frataxin function is still unknown but the knockout of the yeast frataxin homologue gene (YFH1) showed a severe defect of mitochondrial respiration and loss of mtDNA associated with elevated intramitochondrial iron. Here we report in vivo evidence of impaired mitochondrial respiration in skeletal muscle of FRDA patients. Using phosphorus magnetic resonance spectroscopy we demonstrated a maximum rate of muscle mitochondrial ATP production (V(max)) below the normal range in all 12 FRDA patients and a strong negative correlation between mitochondrial V(max) and the number of GAA repeats in the smaller allele. Our results show that FRDA is a nuclear-encoded mitochondrial disorder affecting oxidative phosphorylation and give a rationale for treatments aimed to improve mitochondrial function in this condition.

Adaptor Proteins, Signal Transducing↗

Temporal organization of fetal behavior from 24-weeks gestation onwards in normal and complicated pregnancies.

Developmental aspects of behavioral organization were investigated in 29 healthy fetuses from 24-weeks gestation onwards: (a) short-term association between body (GM) and eye (EM) movements; (b) linkage of pairs of the three state variables [fetal heart rate pattern (FHRP), GM, and EM]; and (c) sequence of change of state variables during transitions. Linkage and sequence were also studied in complicated pregnancies. Short-term association between GM and EM was well established after 28 weeks. Linkage of state variables improved considerably after 32-34 weeks. FHRP was the first variable to change during synchronized transitions from 1F to 2F between 28-39 weeks, and the last variable during 2F to 1F transitions between 32-39 weeks. Although clear developmental patterns could be recognized, the interfetal variability was such that identification of the abnormal fetus is still difficult. Only transitions were significantly different in growth-restricted fetuses, as they showed no specific sequence of change. Assessing the temporal organization of fetal behavior seems, therefore, until now, not of great clinical value.

Adult↗

Gene conversion and evolution of daphniid hemoglobins (Crustacea, cladocera).

The extracellular hemoglobins of cladocerans derive from the aggregation of 12 two-domain globin subunits that are apparently encoded by four genes. This study establishes that at least some of these genes occur as a tandem array in both Daphnia magna and Daphnia exilis. The genes share a uniform structure; a bridge intron separates two globin domains which each include three exons and two introns. Introns are small, averaging just 77 bp, but a longer sequence (2.2-3.2 kb) separates adjacent globin genes. A survey of structural diversity in globin genes from other daphniids revealed three independent cases of intron loss, but exon lengths were identical, excepting a 3-bp insertion in exon 5 of Simocephalus. Heterogeneity in the extent of nucleotide divergence was marked among exons, largely as a result of the pronounced diversification of the terminal exon. This variation reflected, in part, varying exposure to concerted evolution. Conversion events were frequent in exons 1-4 but were absent from exons 5 and 6. Because of this difference, the results of phylogenetic analyses were strongly affected by the sequences employed in this construction. Phylogenies based on total nucleotide divergence in exons 1-4 revealed affinities among all genes isolated from a single species, reflecting the impact of gene conversion events. In contrast, phylogenies based on total nucleotide divergence in exons 5 and 6 revealed affinities among orthologous genes from different taxa.

Amino Acid Substitution↗

Measurement and characterization of cockroach allergens detected during normal domestic activity.

BACKGROUND: Cockroach allergen is recognized as a causal factor for asthma. However, airborne cockroach allergen has not been detected in undisturbed conditions, and therefore the behavior and properties of airborne cockroach allergen have been poorly characterized. A new aeroallergen sampling method and sensitive system of immunoassay have been used to examine cockroach allergen exposure. OBJECTIVE: Our purpose was to measure and characterize airborne cockroach allergens during normal domestic exposure in the homes of Sydney, Australia. METHODS: Air sampling with Institute of Occupational Medicine, Edinburgh (IOM) samplers was performed in the living rooms of 10 houses during low- and no-disturbance environments. In addition, inhaled particles were collected by each home occupant during low domestic exposure with use of intra-nasal samplers that impact particles onto an adhesive surface. The particles collected on the IOMs and the intra-nasal samplers were immunostained with Bla g 1 monoclonal antibodies. Particle size, morphologic characteristics, and the relative Bla g 1 content of particles were estimated. Reservoir dust samples from the kitchen, living room, and bedroom were assayed by an ELISA. Two forms of repeatability of IOM air sampling were examined. The first measure tested the repeatability of 2 IOM samples collected simultaneously in the same room during low- and no-disturbance activities. The second measure examined the repeatability of IOM sampling over time on 10 consecutive days. RESULTS: Bla g 1 was detected in reservoir dust samples taken from all homes (geometric mean 1.5 U/g, range 0.2-9.4 U/g). Inhaled particles containing Bla g 1 were detected during 1 hour of intra-nasal sampling in 8 of 10 homes during low disturbance. Cockroach particles were detected on all of the IOM samples collected for both 4-hour low-disturbance and overnight no-disturbance sampling environments. Particles containing Bla g 1 collected with the IOM samplers during low disturbance ranged in size from 3 to 350 microm. These particles are amorphous and irregular in shape, and a majority of the large particles were described as flakes (flat, transparent particles) and fibers (threadlike). A relationship was demonstrated between the allergen content of cockroach particles and their particle size. The larger particles elute more Bla g 1. The coefficient of repeatability for measurements made during low and no disturbance was 3.62 and 2.09, respectively. For measurements repeated over time at the same site, the coefficient of repeatability was 2.61. This represents the fold range within which 95% of pairs of measurements made at an interval of 1 day would be expected to lie. CONCLUSIONS: Airborne cockroach allergen is present in both undisturbed and low-disturbance environments in homes with relatively low reservoir levels of Bla g 1. In agreement with previous reports, airborne particles containing cockroach allergen (Bla g 1) are mainly associated with particles >10 microm. These particles are amorphous and irregular in shape and can be described as flakes and fibers.

Air Pollution, Indoor↗

Quantitative analysis of fetal general movements: methodological considerations.

OBJECTIVES: We studied the effects of gestational age and various smoothing procedures on four incidence parameters of fetal general movement, to evaluate reported variation in previous studies and to establish the optimal way of smoothing. SUBJECTS AND METHODS: General movements were studied longitudinally between 24 and 40 weeks of gestation in 29 healthy fetuses. The number of movement bursts per hour, burst duration, onset-onset interval between successive bursts (OOI) and the percentage incidence were analysed in detail. RESULTS: Advancing gestation was characterised by a proportional increase in OOI's lasting > 60 s and a decreased number of bursts, whereas burst duration remained relatively stable (unsmoothed data). Smoothing resulted in an exaggerated decrease in the number of bursts and in increases in burst duration, OOI and percentage incidence. These changes occurred in a gestational age specific manner and could largely explain the variation in results between previous studies. CONCLUSIONS: The temporal patterning of fetal general movements undergoes developmental change, as shown by differential effects of smoothing between mid and late pregnancy. A smoothing procedure is to be preferred which includes short intervals (1-3 s) between the elements composing a burst, since small changes in movement generation can still be recognised this way.

Adult↗

Demographic characteristics in adult paternity for first births to adolescents under 15 years of age.

PURPOSE: To examine parental demographic characteristics by adult (> or = 20 years at baby's conception) and teenage (< 20 years at baby's conception) paternity in births to very young adolescents (< 15 years at baby's conception). METHODS: This was a population-based, retrospective cohort analysis of all 12,317 very young adolescent mothers residing in California with a first singleton live birth during 1993-1995. Risks for adult, compared to teenage, paternity were evaluated using multivariate logistic regression. RESULTS: Adult fathers, responsible for 26.7% of births to very young adolescents, were a mean of 8.8 years older than the mother. The risk factors for adult compared to adolescent paternity were as follows: father's educational attainment of at least 3 years below that considered adequate for his age [adjusted odds ratio (AOR) = 8.34], father's (AOR = 2.46) or mother's (AOR = 1.36) educational attainment 1-2 years below that considered adequate for their age, mother's birthplace outside the United States (AOR = 3.12), and father's Hispanic ethnicity (AOR = 1.60) or African-American race (AOR = 1.50). CONCLUSIONS: Adult fathers were responsible for over one quarter of the births in our study. Adolescent pregnancy prevention focusing on younger adolescents must programmatically address adult paternity. Variations in adult paternity patterns across cultural groups suggest that we need further study of the role that cultural beliefs and practices play in very young adolescent pregnancy.

Adolescent↗

Phase I trial of the selective mitochondrial toxin MKT077 in chemo-resistant solid tumours.

BACKGROUND: MKT077 is a rhodacyanine dye analogue which preferentially accumulates in tumour cell mitochondria. It is cytotoxic to a range of tumours. In this phase I study, MKT077 was administered as a five-day infusion once every three weeks. PATIENTS AND METHODS: Ten patients, median age 59 (38-70) years, with advanced solid cancers were treated at three dose levels: 30, 40 and 50 mg/m2/day for a total of 18 cycles. 31Phosphorus magnetic resonance spectroscopy (MRS) was used to evaluate the effect of MKT077 on skeletal muscle mitochondrial function. RESULTS: The predominant toxicity was recurrent reversible functional renal impairment (grade 2, two patients). One patient with renal cancer attained stable disease and the remainder progressive disease. There were no MRS changes in the first or second treatment cycles but one patient received 11 treatment cycles and developed changes consistent with a mitochondrial myopathy. Mean values for all pharmacokinetic parameters were at sub micromolar levels and did not exceed IC50 values (> or = 1 microM). CONCLUSIONS: Because of the renal toxicity, and animal studies showing MKT077 causes eventual irreversible renal toxicity, further recruitment was halted. The study shows, however, that it is feasible to target mitochondria with rhodacyanine analogues, if drugs with higher therapeutic indices could be developed.

Adult↗

Subtribe-specific monoclonal antibodies to Lolium perenne.

BACKGROUND AND OBJECTIVES: The ability to measure personal exposure to airborne grass pollen is important in the understanding of allergic diseases. Visual identification is time consuming and it is difficult to distinguish between many grass pollens morphologically. Although grass pollens share common allergenic determinants, we attempted to produce monoclonal antibodies that would distinguish between species, tribes and subfamilies of grasses which would allow immunodetection of pollens. METHODS: Monoclonal antibodies raised against Lolium perenne were screened for specificity against an extended panel of grass pollen extracts using standard ELISA techniques and a novel particle blotting assay using whole pollen grains. RESULTS: Antibodies showing specificity ranging from subfamily to part-tribe specificity were raised. The most specific monoclonal antibodies (numbers 4, 13 and 17) had reactivity to Lolium perenne and Festuca elatior but displayed little cross-reactivity to Phalaris arundinaceae and the rest of the Poeae tribe when tested by ELISA and no detectable cross-reaction when tested with particle blotting. CONCLUSION: Monoclonal antibodies that are functionally specific to only two grasses can be produced and used to discriminate between related grass species.

Allergens↗

The use of digital cameras in a mobile retinal screening environment.

AIMS: To assess how successfully digital camera technology might be incorporated into a mobile screening environment. METHODS: One hundred and ninety-seven people had their fundi photographed using a Topcon/Imagenet digital system and 534 using a Canon CR5/Ris-Lite system in addition to concurrent 45 degrees CR4NM Polaroid photography. One hundred and eighteen randomly selected patients were also sent for 7 field stereo photography as a gold standard. An acceptability questionnaire was answered by a random sample of those photographed. RESULTS: For the detection of any retinopathy, digital pictures had a sensitivity of 0.74 (95% confidence interval (CI) 0.68-0.80) whilst Polaroid was 0.72 (95% CI 0.66-0.78) and for referable retinopathy digital pictures had a sensitivity of 0.85 (95% CI 0.80-0.90) and Polaroid was 0.90 (95% CI 0.86-0.94). A concurrent ophthalmoscopic evaluation improved the sensitivity to 0.92 (95% CI 0.86-0.98) for detection of any retinopathy whilst the sensitivity at the referral level was improved to 0.95 (95% CI 0.91-0.99). Twenty-nine of 176 respondents experienced flash discomfort with the Polaroid system with only four of 154 describing 'some' discomfort from the digital systems which have a lower flash power (10 W vs. 300 W) and a faster recovery time. CONCLUSIONS: This study indicates that digital systems are a feasible and acceptable alternative to Polaroid-based cameras for use in a mobile environment.

Adult↗

Noninferiority testing in crossover trials with correlated binary outcomes and small event proportions with applications to the analysis of condom failure data.

Regulatory agencies may require demonstrating a new therapy or device as noninferior to an existing method. For example, a new condom type must demonstrate noninferiority to existing latex condoms before consideration as an equivalent method of pregnancy prevention. Studies designed to assess condom effectiveness typically measure experimental and standard condom failure in a crossover trial, resulting in unbalanced correlated binary outcomes with low event proportions. We used simulations to evaluate the test size of a simple population average approach to noninferiority testing with the small event proportions, intracluster correlations, and sample sizes frequently found in condom studies. Results emphasize the importance of considering test accuracy when designing any study.

Binomial Distribution↗