Search PubMed⌕ Search

Biomedical subjects

D J Taylor

Publications and source records attributed to D J Taylor.

At least 91 records · Page 5Linked to original sources

Reduced cytosolic acidification during exercise suggests defective glycolytic activity in skeletal muscle of patients with Becker muscular dystrophy. An in vivo 31P magnetic resonance spectroscopy study.

Becker muscular dystrophy is an X-linked disorder due to mutations in the dystrophin gene, resulting in reduced size and/or content of dystrophin. The functional role of this subsarcolemma protein and the biochemical mechanisms leading to muscle necrosis in Becker muscular dystrophy are still unknown. In particular, the role of a bioenergetic deficit is still controversial. In this study, we used 31p magnetic resonance spectroscopy (31p-MRS) to investigate skeletal muscle mitochondrial and glycolytic ATP production in vivo in 14 Becker muscular dystrophy patients. Skeletal muscle glycogenolytic ATP production, measured during the first minute of exercise, was similar in patients and controls. On the other hand, during later phases of exercise, skeletal muscle in Becker muscular dystrophy patients was less acidic than in controls, the cytosolic pH at the end of exercise being significantly higher in Becker muscular dystrophy patients. The rate of proton efflux from muscle fibres of Becker muscular dystrophy patients was similar to that of controls, pointing to a deficit in glycolytic lactate production as a cause of higher end-exercise cytosolic pH in patients. The maximum rate of mitochondrial ATP production was similar in muscle of Becker muscular dystrophy patients and controls. The results of this in vivo 31P-MRS study are consistent with reduced glucose availability in dystrophin-deficient muscles.

Acids↗

Increased incidence of apoptosis in non-labour-affected cytotrophoblast cells in term fetal membranes overlying the cervix.

A regional reduction in the cellularity of the cytotrophoblastic and decidual layers occurs in the fetal membranes overlying the cervix in the lower uterine segment prior to labour. Although the mechanism(s) involved are not known it could result from regionally increased apoptosis, the histological manifestation of programmed cell death, or decreased proliferation. Apoptosis was assessed in regionally sampled fetal membranes from women undergoing elective Caesarean section (n = 14) by the presence of apoptotic bodies by light and electron microscopy. Cell proliferation was assessed by immunocytochemical detection of the protein Ki-67. Apoptotic bodies were identified in all regions of the fetal membrane with the highest incidence found within the cytotrophoblast layer. However, this layer in fetal membranes biopsied over the cervix contained significantly more apoptotic bodies (mean +/- SD 0.085 +/- 0.020%) compared to the layer in fetal membranes obtained from the mid-zone (0.020 +/- 0.008%) apoptotic bodies. Isolated Ki-67 positive cells were detected in the cytotrophoblast layer, but no regional differences in their incidence were seen. Fetal membranes also failed to exhibit significant immunoreactivity for BCL-2 but exhibited strong BAX immunoreactivity within the decidual layer. We conclude that the regionally increased incidence of apoptosis in the cytotrophoblastic layer in the membrane overlying the cervix may account for the reduction in its cellularity but not the relative decrease in the decidual layer. Given the consequence of the loss of local function in degrading uterotonins and stabilizing the fetal membrane, the study of the regulation of apoptosis in these cells may have important implications for fetal membrane rupture and parturition.

Amnion↗

Alternatively spliced tenascin-C mRNA isoforms in human fetal membranes.

Tenascin-C is an extracellular matrix glycoprotein whose monomers include eight consecutive fibronectin type III-like repeats, encoded by exons 10-16, and which are subject to alternative splicing. Transcripts containing these exons are expressed during tissue wounding and active tissue remodelling. Human fetal membranes have been proposed to undergo active tissue remodelling as part of the mechanisms leading to their rupture and immunoreactive tenascin-C has been detected in this tissue. Employing reverse transcription-polymerase chain reaction (RT-PCR) and exon-specific primers, products corresponding to multiple splicing events in the alternatively spliced region have now been identified. The overall splicing pattern would indicate that the major transcripts correspond to complete exclusion of the alternatively spliced region; inclusion of only exon 16; and inclusion of exons 10-14 and 16, including or excluding exon 12. The sole site in tenascin-C susceptible to cleavage by matrix metalloproteinases (MMP)-2 and MMP-3 is found within the exon 12 encoded repeat, therefore translation of isoforms which include or exclude exon 12 may produce 'large' tenascins mediating functions ascribed to this form but susceptible or resistant to these MMPs. The demonstration of expression of 'large' tenascin mRNA isoforms supports the concept that fetal membranes at term are a site of active tissue remodelling.

Alternative Splicing↗

The role of observer error in antenatal dipstick proteinuria analysis.

OBJECTIVE: To determine the role of inter-observer error and the influence of training upon dipstick urine analysis. DESIGN: A two phase observational and training study. METHODS: Five standard solutions of serum albumin were used to test the accuracy of midwives and nursing auxiliaries involved in dipstick urine analysis at a maternity hospital. The standard solutions were chosen such that they should have resulted in negative (n = 2) and positive (n = 3) dipstick test results, respectively. SETTING: A teaching maternity hospital and academic department of obstetrics and gynaecology. PARTICIPANTS: Twenty midwives, 20 nursing auxiliaries and nine laboratory technicians. RESULTS: For the two nonproteinuric solutions, a higher false positive rate was observed for nursing auxiliaries (40% and 55%), compared with midwives (5% and 30%) (P = 0.020 and P = 0.20, respectively). Before training, laboratory technicians recorded high false positive rates (67% and 89%), but after training these were reduced to 0% and 22% (P = 0.25 and P = 0.023, respectively). Both nursing auxiliaries and midwives recorded false negative rates of between 10% and 45% for the three proteinuric solutions. CONCLUSIONS: Observer error may be reduced by assigning midwives to urine dipstick analysis or by the implementation of directed training. Classification of pre-eclampsia or other hypertensive diseases of pregnancy on the basis of the presence and degree of proteinuria should be confirmed with a 24-hour quantitative protein collection.

False Negative Reactions↗

The Calgary Conjoint Nursing Program. Part I: Spirit of collaboration.

On January 26, 1993, a small but significant gathering in Calgary celebrated the government's approval of the Calgary Conjoint Nursing Program. In attendance were faculty and staff of the nursing education programs of the Foothills Hospital School of Nursing, Mount Royal College and the University of Calgary, as well as senior administrators from each of those sites, practising nurses and a member of Alberta's Legislative Assembly. The group was celebrating the culmination of six years of working together toward the realization of a co-operative, collaborative baccalaureate nursing education program.

Alberta↗

The Calgary Conjoint Nursing Program. Part II: Successful political action.

When three calgary institutions decided to develop a collaborative nursing program to prepare for the transition to baccalaureate nursing education by the year 2000, the planners found that they had to overcome a broad range of political and institutional hurdles. Faculty from Mount Royal College, Foothills Hospital School of Nursing and the University of Calgary spent six years developing the curriculum and planning for the implementation of the Calgary Conjoint Nursing Program (CCNP). (See The Calgary Conjoint Nursing Program, Part I: Spirit of Collaboration, in the March 1999 issue of this journal.)

Alberta↗

The relative accuracy of sequential same-arm and simultaneous opposite-arm measurements for the intra-arterial validation of blood pressure monitors.

OBJECTIVE: To compare the results of simultaneous opposite-arm and sequential same-arm intra-arterial validation of automated blood pressure monitors. DESIGN: Intra-arterial blood pressure measurements were compared with blood pressure measurements obtained using conventional sphygmomanometry and two automated blood pressure monitors (the Dinamap XL and the SpaceLabs Scout) using a methodology based on the protocol published by the Association for the Advancement of Medical Instrumentation (AAMI) for the intra-arterial validation of automated monitors. METHODS: Thirteen women with radial arterial lines were recruited from the obstetric intensive care unit at Groote Schuur Hospital, Cape Town. For each woman, intra-arterial blood pressure measurements were compared with those obtained by mercury sphygmomanometry and by using the two automated blood pressure monitors with both a sequential same-arm protocol and a simultaneous opposite-arm protocol. The mean and SD of the differences was calculated for each protocol and the results were compared using Student s t test. RESULTS: The differences between the 'means of the differences' for these two protocols never differed by more than 2 mmHg. For individuals the differences between data obtained using the two methodologies were up to 32 mmHg for mercury sphygmomanometry and 18 mmHg for the automated monitors. The differences between the SD of the differences were all less than 3 mmHg except for that of systolic blood pressure obtained by mercury sphygmomanometry, which was 7 mmHg CONCLUSIONS: The results of this study show that a sequential same-arm and a simultaneous opposite-arm comparison of intra-arterial and indirect blood pressure measurements yield similar results.

Arteries↗

Genetic amniocentesis: gestation-specific pregnancy outcome and comparison of outcome following early and traditional amniocentesis.

Amniocentesis remains the most common prenatal diagnostic invasive procedure for fetal karyotyping. During counselling prior to this procedure miscarriage rates are often quoted as a single figure. In this review of 2924 amniocenteses, we report that miscarriage rates vary with the gestational age at which the procedure is performed. The total miscarriage rate was 1.0 per cent after early amniocenteses (11 + 0-14 + 6 weeks) and 1.2 per cent after traditional mid-trimester amniocenteses (15 + 0-18 + 6 weeks). The rate was greatest (3.1 per cent) for amniocenteses performed after 18 + 6 weeks' gestation. The cumulative miscarriage risk increased from 0.03 per cent one week after the procedure to plateau at 1.1 per cent five weeks after the procedure. The preterm and still-birth rates following amniocenteses were similar in early and traditional mid-trimester amniocenteses but were significantly higher when amniocenteses were performed after 19 weeks' gestation. Although the incidence of talipes equinovarus was higher after early amniocentesis compared with traditional mid-trimester amniocenteses (1.4 per cent versus 0.2 per cent), none of the affected infants required corrective surgery. We conclude that counselling for this procedure should be tailored to each unit's unintended fetal loss rate based on cumulative rates. Such figures should be available to parents to assist them in their decision-making.

Adult↗

Changes in biochemical markers of joint tissue metabolism in a randomized controlled trial of glucocorticoid in early rheumatoid arthritis.

OBJECTIVE: To determine the effects of low-dose prednisolone on joint tissue metabolism in early rheumatoid arthritis (RA). METHODS: In addition to a range of biochemical markers of cartilage, bone and synovial tissue turnover, levels of pro-matrix metalloproteinase 3 (pro-MMP-3), pro-MMP-1, and cytidine deaminase (CD) were measured in serum from 79 of 128 patients with early RA who took part in the Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study. Serum concentrations of joint tissue metabolites on treatment and off treatment were compared using Student's t-test. RESULTS: Levels of the keratan sulfate epitope, 5D4, and glycosaminoglycan (GAG) were similar on and off treatment. However, the levels of synovium-derived markers, hyaluronate (HA) and N-propeptide of type III procollagen (PIIINP), were reduced by 23.9% (P < 0.01) and 25.2% (P < 0.001), respectively, during treatment with prednisolone. Serum osteocalcin (OC) was reduced by 25.8% (P < 0.001), while the levels of CD and pro-MMP-3 increased by 31.2% (P < 0.01) and 53.7% (P < 0.001) during prednisolone treatment compared with the off-treatment period. CONCLUSION: Low-dose prednisolone had no significant effect on markers of cartilage turnover (GAG, 5D4) in early RA, suggesting that early erosions do not involve cartilage surfaces. The reduction in the markers of bone turnover (OC) and synovial tissue turnover (HA and PIIINP) support the general view that prednisolone reduces synovitis and suppresses bone turnover.

Adult↗

Automated, ambulatory, or conventional blood pressure measurement in pregnancy: which is the better predictor of severe hypertension?

OBJECTIVES: Our purpose was to investigate the benefit, if any, of automated blood pressure monitoring over obstetric day unit conventional blood pressure measurement in the assessment of hypertensive pregnancies. STUDY DESIGN: A prospective, observational study was carried out in two large teaching hospitals. Three hundred and forty-eight women with a confirmed clinic blood pressure of at least 140/90 mm Hg were recruited. Conventional blood pressure measurements (< or =5) were obtained on the day unit and simultaneously an ambulatory blood pressure monitor was applied for 24 hours. The predictive ability of day unit assessment (blood pressure > 140/90 mm Hg) and automated blood pressure monitoring (blood pressure > 130/85 mm Hg) was compared. Principal outcome measures included the occurrence of severe hypertension (> 160/110 mm Hg) and proteinuria (> 500 mg or 2+) within (a) 2 weeks and (b) the remainder of the pregnancy. Thompson's method was used to compare sensitivity and specificity of the day unit blood pressure and automated blood pressure monitoring. RESULTS: Three hundred and forty-eight women were recruited to the study. The comparison between automated blood pressure monitoring and conventional blood pressure measurement for both sensitivity and specificity for systolic and diastolic blood pressure revealed increased sensitivity and decreased specificity with automated blood pressure monitoring for all principal outcomes except development of proteinuria for systolic blood pressure. Sensitivity for the outcomes was increased with automated blood pressure monitoring by between 14% and 27% for systolic blood pressure and between 7% and 39% for diastolic blood pressure, with the greatest improvement seen for the development of severe hypertension within 2 weeks of assessment. CONCLUSIONS: In the assessment of hypertensive pregnancies, automated blood pressure measurement was a significantly better predictor (compared with conventional day unit assessment) for the development of severe hypertension within 2 weeks of assessment for both systolic and diastolic blood pressure.

Adult↗

Newborn acid-base status and umbilical cord morphology.

OBJECTIVE: To assess the relation between umbilical cord morphology and intrapartum fetal status and umbilical cord blood gases at birth. METHODS: In a prospective study of 134 consecutive newborns and their umbilical cords, relations were investigated between umbilical cord morphologic characteristics (umbilical cord length, number of vascular coils, coiling index, and vessel length index) and intrapartum fetal heart rate (FHR) decelerations, color of amniotic fluid, operative delivery for suspected fetal acidosis, umbilical vessel blood gases, and acid-base status. RESULTS: Statistically significant linear correlations were found between umbilical venous pH and the umbilical cord length (r = 0.30; 95% confidence interval [CI] 0.13, 0.46; P < .001), number of vascular coils (r = 0.27; 95% CI 0.10, 0.43; P = .001), coiling index (r = 0.15; 95% CI 0, 0.33; P = .05), and vessel length index (r = 0.30; 95% CI 0.13, 0.46; P < .001). Statistically significant negative linear correlations were found between the umbilical venous partial pressure of carbon dioxide (PCO2) and cord length (r = -0.34, 95% CI -0.49, -0.17; P < .001), number of vascular coils (r = -0.30, 95% CI -0.46, -0.13; P < .001), coiling index (r = -0.17, 95% CI -0.34, 0; P = .03), and vessel length index (r = -0.34, 95% CI -0.49, -0.17; P < .001). The umbilical artery pH was related to vessel length index and to the number of umbilical vascular coils (r = 0.17, 95% CI 0.03, 0.36; P = .04 and r = 0.17, 95% CI 0.02, 0.35; P = .047, respectively). No relation was found between umbilical cord indices and intrapartum FHR decelerations, meconium staining of the amniotic fluid, or mode of delivery. Placental weight also correlated with umbilical cord length and vessel length index (95% CI 0.15, 0.46; P < .001 and 95% CI 0.05, 0.38; P = .01, respectively), but not with the number of umbilical cord coils or the coiling index. CONCLUSION: Umbilical venous pH and PCO2 and umbilical artery pH are related to umbilical cord morphology. Associated variations in placental morphology or placental blood flow affecting maternal-fetal gas exchange may explain these findings.

Acid-Base Equilibrium↗

Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle.

It has been shown previously that some patients with chronic fatigue syndrome show an abnormal increase in plasma lactate following a short period of moderate exercise, in the sub-anaerobic threshold exercise test (SATET). This cannot be explained satisfactorily by the effects of 'inactivity' or 'deconditioning', and patients with abnormal lactate responses to exercise (SATET +ve) have been found to have significantly fewer Type 1 muscle fibres in quadriceps biopsies than SATET -ve patients. We performed phosphorus magnetic resonance spectroscopy on forearm muscles of 10 SATET +ve patients, 9 SATET -ve patients and 13 sedentary volunteers. There were no differences in resting spectra between these groups but at the end of exercise, intracellular pH in the SATET +ve patients was significantly lower than in both the SATET -ve cases and controls (P < 0.03), and the SATET +ve patients also showed a significantly lower ATP synthesis rate during recovery (P < 0.01), indicating impaired mitochondrial oxidative phosphorylation. These observations support other evidence which indicates that chronic fatigue syndrome is a heterogeneous disorder, and confirms the view that some chronic fatigue syndrome patients have a peripheral component to their fatigue.

Adenosine Diphosphate↗

Normal in vivo skeletal muscle oxidative metabolism in sporadic inclusion body myositis assessed by 31P-magnetic resonance spectroscopy.

Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance spectroscopy to assess in vivo skeletal muscle mitochondrial function in the calf muscles of 12 patients with definite s-IBM. Eleven patients showed multiple mitochondrial DNA deletions in skeletal muscle and 67% showed ragged red fibres and/or cytochrome c oxidase-negative fibres. T1-weighted MR images showed increased signal intensity in the calf muscle of all patients except one. The involvement of calf muscle was confirmed by 31P magnetic resonance spectroscopy of resting muscle, which disclosed abnormalities in metabolite ratios in all patients. However, muscle oxidative metabolism assessed during recovery from exercise was normal in patients with s-IBM, as maximum rates of mitochondrial ATP production and post-exercise ADP recovery rates were within the normal range in all cases. We conclude that muscle mitochondrial abnormalities are a secondary process and unlikely to play a significant role in the pathogenesis of s-IBM.

Adenosine Diphosphate↗

The origin and evolution of variable-region helices in V4 and V7 of the small-subunit ribosomal RNA of branchiopod crustaceans.

We sequenced the V4 and V7 regions of the small-subunit ribosomal RNA (SSU rRNA) from 38 species of branchiopod crustaceans (e.g., Artemia, Daphnia, Triops) representing all eight extant orders. Ancestral large-bodied taxa in the orders Anostraca, Notostraca, Laevicaudata, and Spinicaudata (limnadiids and cyzicids) possess the typical secondary structure in these regions, whereas the spinicaudatan Cyclestheria and all of the cladocerans (Anomopoda, Ctenopoda, Onychopoda, and Haplopoda) possess three unique helices. Although the lengths and primary sequences of the distal ends of these helices are extremely variable, their locations, secondary structures, and primary sequences at the proximal end are conserved, indicating that they are homologous. This evidence supports the classical view that Cladocera is a monophyletic group and that the cyclestheriids are transitional between spinicaudatans and cladocerans. The single origin and persistence since the Permian of the unique cladoceran helices suggests that births and deaths of variable region helices have been rare. The broad range of sequence divergences observed among the cladoceran helices permitted us to make inferences about their evolution. Although their proximal ends are very GC-biased, there is a significant negative correlation between length and GC content due to an increasing proportion of U at their distal ends. Slippage-like processes occurring at unpaired nucleotides or bulges, which are very U-biased, are associated with both helix origin and runaway length expansion. The overall GC contents and lengths of V4 and V7 are highly correlated. More surprisingly, the lengths of these SSU rRNA variable regions are also highly correlated with the length of the large-subunit rRNA expansion segment, D2, indicating that mechanisms affecting length variation do so both across single genes and across genes in the rRNA gene family.

Animals↗

Uterine surveillance of asymptomatic postmenopausal women taking tamoxifen.

The aim of this study was to assess the ability of transvaginal sonography (TVS) and office hysteroscopy with sharp curettage to characterize the morphological changes in the uteri of asymptomatic postmenopausal women taking long-term tamoxifen for breast cancer. The overall acceptability of a single-visit screening clinic for these women was also evaluated. Fifty-eight women were recruited from patients undergoing regular follow-up at the Leicester Royal Infirmary for breast cancer. A single-visit clinic was acceptable to 94.8% of these women. Transvaginal sonography detected endometrial thickness of greater than 5 mm in 84.5% of cases, but there was no relationship between total tamoxifen exposure and endometrial thickness. Transvaginal sonography also detected uterine lesions such as fibroids and endometrial cysts in 34.5% of cases. Hysteroscopy detected the latter uterine lesions in 53.4% of cases, with three cases (5.2%) of endometrial polyps also being identified in these women. Sharp curettage sampling of the endometrium produced specimens sufficient for diagnosis in 84.5% of cases; 70.7% of specimens were reported as showing types of 'quiescent' endometrium with 13.8% of specimens showing 'active' endometrium. In the latter group, there was a case of complex hyperplasia detected and also a case with granulomatous endometritis. For each histopathological diagnosis identified, there was a wide range of endometrial thickness recorded by TVS. A single-visit screening clinic involving TVS and hysteroscopy with sharp curettage was acceptable to asymptomatic women taking tamoxifen. However, hysteroscopy was more effective than TVS in detecting endometrial lesions such as polyps, fibroids and cystic areas. Although TVS detected endometrial thickness greater than 5 mm in the majority of cases, there were no malignancies detected and, for each histopathological classification, there was a wide range of endometrial thickness associated. Thus, the isolated use of TVS is insufficient for screening the endometria of these women.

Curettage↗