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D J Taylor

Publications and source records attributed to D J Taylor.

At least 127 records · Page 7Linked to original sources

The effect of propionyl L-carnitine on skeletal muscle metabolism in renal failure.

The effect of propionyl L-carnitine on skeletal muscle metabolism in chronic renal failure. Carnitine deficiency, resulting in defective oxidative ATP synthesis, has been implicated in the myopathy of chronic renal failure. Using 31P magnetic resonance spectroscopy we examined calf muscle metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g.p.o. daily. Resting phosphocreatine/ATP (4.41 +/- 0.20 [SEM]) decreased to normal control levels on PLC (3.98 +/- 0.14; controls 4.00 +/- 0.06). In contrast, there was no effect of PLC on aerobic and anaerobic metabolism of muscle during or following 2-10 min exercise. The maximal calculated oxidative capacity (Qmax) remained below normal (28 +/- 3 mM/min before and 24 +/- 3 mM/min after PLC; controls 49 +/- 3 mM/min). Qmax correlated positively with hemoglobin concentration ([Hb]) after PLC (p < 0.03). Oxidative capacity assessed by phosphocreatine recovery T significantly improved with PLC administration (0.93 +/- 0.1 to 0.74 +/- 0.08 min) in those patients (n = 6) with [Hb] > 10 g/dl. [Hb] was rate limiting to oxidative metabolism in recovery from exercise but only following treatment with PLC. Patients with anemia or those subjects who use relatively more non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative metabolism did not normalize on PLC suggesting that anemia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.

Adenosine Triphosphate↗

Ageing: effects on oxidative function of skeletal muscle in vivo.

31P magnetic resonance spectroscopy studies were carried out on calf muscle of 144 normal male and female subjects age 20-83 years in order to investigate age-related changes in muscle metabolism. Compared to the young adults (20-29 years), oxidative capacity was higher in the children (6-12 years) and was significantly decreased in the elderly (70-83 years). In the adults, the intracellular pH change during exercise diminished with increasing age, resulting in higher calculated free [ADP] and possibly serving as an adaptive mechanism to stimulate mitochondrial ATP production. Children also had higher pH and [ADP] in exercise, but unlike results from the elderly, this was associated with higher oxidative capacity and more rapid metabolic recovery from exercise.

Adenosine Diphosphate↗

Lack of reproducibility in pregnancy of Korotkoff phase IV as measured by mercury sphygmomanometry.

BACKGROUND: Since hypertensive disorders of pregnancy are common, blood pressure is frequently measured in all pregnant women. Many authorities recommend that Korotkoff phase IV (K4, muffling of sound) is taken as the diastolic identification point measured on mercury sphygmomanometry in pregnancy because of reports that phase V (K5, disappearance of sound) is at or near to zero cuff pressure in some pregnant women. We compared the identification and reproducibility of K4 and K5 by observers unaware of each other's results. METHODS: In the first part of the study, two pairs of observers each took 340 measurements in 85 pregnant women. The second part of the study consisted of 1120 measurements in 80 pregnant and 80 non-pregnant women by five pairs of observers. Measurements were taken simultaneously by sphygmomanometry with a shared cuff and diaphragm; the observers were in separate booths. FINDINGS: K5 was identified in all measurements by both observers and never approached zero. K4 was heard in only 52% of measurements; in 33% of cases it was heard by only one of the pair of observers, so the pair agreed on its detection in only 19% of readings. Visual analogue scores used to assess Korotkoff sound quality indicated that systolic blood pressure was perceived significantly more clearly than diastolic blood pressure (K4 or K5). Even when K4 was heard by both observers, agreement on its value was poor (78% within 5 mm Hg vs 86% for K5, p < 0.05). K4 was heard significantly less often in non-pregnant women (32% of measurements). There was also no consistency in the identification of K4 within individual women. INTERPRETATION: K4 has little value in clinical management because it cannot be reproduced accurately. We recommend that K4 should be replaced by K5 as the measure of diastolic blood pressure in pregnancy.

Blood Pressure↗

Phylogenetics and evolution of the Daphnia longispina group (Crustacea) based on 12S rDNA sequence and allozyme variation.

Although members of the crustacean genus Daphnia have been the target of much research, there is little understanding of the group's evolutionary history. We addressed this gap by inferring a phylogeny for one of the major species groups (longispina) using nucleotide sequence variation of a 525-bp segment of the mitochondrial 12S rDNA and allozyme variation at 21 loci. We identified the major lineages and their relationships, assessed the phylogenetic utility of the few morphological characters in the group, and examined Daphnia phylogeography. Nuclear and mtDNA phylogenies were generally concordant in recognizing the same four species complexes. An exception was the position of Daphnia galeata mendotae. The allozyme tree paired this species with the Daphnia rosea lineage, whereas the mtDNA trees grouped D. g. mendotae with Daphnia galeata galeata. This discordance was consistent with the reticulate evolution of nuclear genes supporting the hypothesis that D. g. mendotae represents a case of homoploid hybrid speciation. Striking morphological stasis in the longispina group was evidenced by its very limited morphological divergence over an estimated 100 MY, and by the unusual transitional saturation of the conservative 12S rRNA gene within a species group. Phylogenetic inference also provided evidence that similarities in cephalic crest shape likely resulted from convergent or parallel evolution among species. Endemism at the continental level was indicated for previously cosmopolitan species, but the estimated times of these divisions were inconsistent with vicariance events suggesting recent dispersal among continents. A significant role for divergent selection in new habitats during speciation was suggested by the neighboringly sympatric distributions of four sister species pairs over broad geographic areas.

Alleles↗

Diurnal blood pressure difference in the assessment of preeclampsia.

OBJECTIVE: To evaluate diurnal variation in blood pressure (BP) in normal gravidas and those with preeclampsia, using ambulatory BP monitoring. METHODS: A cross-sectional comparative observational study was performed in three teaching hospital maternity units. Twenty-four normotensive and 24 preeclamptic women who were similar in age, weight, and mean duration of gestation (35 weeks) were studied. Diurnal variation and BP measurement were assessed using ambulatory BP monitors validated for use in pregnancy and for which normal reference ranges for pregnancy have been derived. RESULTS: At night, the BP fall was less in preeclamptic women than in normotensive women. The day-night BP difference decreased as average BP rose (diastolic gradient = -0.54 [95% confidence interval (CI) -0.77 to -0.31], systolic gradient = -0.36 [95% CI -0.58 to -0.14], where gradient denotes a unit increase in BP leading to an increase or decrease in the day-night difference). CONCLUSION: The decrease in day-night BP difference observed in preeclampsia is inversely related to average BP. This blunting of the day-night BP difference may be a useful adjunctive measure of disease severity in preeclampsia.

Adolescent↗

Hypertension in pregnancy: which method of blood pressure measurement is most predictive of outcome?

OBJECTIVE: To determine the clinical effectiveness of blood pressure (BP) measurement using conventional sphygmomanometry in the antenatal clinic and obstetric day unit compared with automated BP monitoring at home. METHODS: The study population consisted of 109 nulliparous white women with BPs of at least 140 or 90 mmHg at the antenatal clinic after 20 weeks' gestation, who underwent obstetric day unit and 24-hour automated BP monitoring on the same day. Automated measurement was obtained every half hour for 24 hours using a commercially available device that had been previously validated in pregnancy. RESULTS: At the traditional BP cutoff point (140/90 mmHg), the relative risk for subsequent development of adverse obstetric outcome was greatest for automated BP measurement: The relationships between outcome and automated diastolic BP were all statistically significant: proteinuria (P = .034), preterm delivery (P < .001), birth weight below the tenth percentile (P = .001), admission to the special care neonatal unit (P = .001), and cesarean delivery (P = .007). CONCLUSION: Automated BP measurement appears to improve the identification of patients who are at high risk of poor obstetric outcome. Automated BP measurement is worthy of further evaluation as an antenatal screening and diagnostic test.

Adolescent↗

Efficacy of balloon angioplasty of the superficial femoral artery and popliteal artery in the relief of leg ischemia.

PURPOSE: To assess the efficacy of balloon angioplasty in the superficial femoral artery (SFA) and popliteal artery for relief of lower-limb claudication and critical ischemia. METHODS: All patients who underwent SFA or popliteal balloon angioplasty at the Royal Adelaide Hospital between January 1989 and September 1994 were reviewed. Risk factors, indications, angiographic variables, and complications were assessed. Outcome was expressed in life-table form as patency, limb survival, and patient survival rates. RESULTS: One hundred seventy-six patients (96 men, 80 women) who underwent 200 balloon angioplasty procedures were monitored for a mean of 25 months. Seventy-four percent of procedures were for claudication relief and 26% for critical ischemia. The cumulative patency rate at 24 months for all cases was 46%. The limb salvage rate was 95%, and the patient survival rate was 91% at 24 months. CONCLUSION: Percutaneous transluminal angioplasty of the SFA and popliteal arteries is commonly used to treat claudication and critical ischemia but is associated with a high initial failure rate and poor patency at 24 months. Balloon angioplasty is not recommended to treat claudication.

Adult↗

Human fetal kidney morphometry during gestation and the relationship between weight, kidney morphometry and plasma active renin concentration at birth.

1. This study was designed to examine the changes in kidney morphometry during gestation in fetuses that were either appropriate or small for gestational age and the relationship between umbilical vein plasma active renin and kidney morphometry. 2. Serial ultrasound measurements of various morphometric and renal indices were performed in a cohort of 87 singleton fetuses from 22 to 38 weeks gestation. Blood was collected from the umbilical vein at delivery and active renin was measured from the plasma based on angiotensinogen I generated during incubation with plasma and ox renin substrate. 3. Growth in the longitudinal plane of fetal kidneys was similar in the small- and appropriate-for-gestational age groups; however, growth in the anterio-posterior, transverse and circumference planes of the kidneys was significantly slower in the small-for-gestational-age group after 26 weeks gestation. Differences in growth rate in the two groups were most marked between 26 and 34 weeks and persisted until delivery when the anterior-posterior diameter was significantly larger (P < 0.00001) in the appropriate-for-gestational-age group (26.1 +/- 2.5 mm compared with 19.8 +/- 2.6 mm). The mean umbilical vein active plasma renin concentration at delivery was significantly higher (P < 0.05) in the small-for-gestation-age group (274.4 +/- 32.9 mu-units/ml plasma) than in the appropriate-for-gestational-age group (164.9 +/- 28.3 mu-units/ml plasma). In addition, there were statistically significant inverse correlations between renin concentration and birthweight (r = -0.55, P < 0.001) and between renin concentration and kidney anterior-posterior diameter (r = -0.67, P < 0.001). 4. Fetal renal growth was slower in small than in appropriate-for-gestational-age fetuses. The period of 26-34 weeks gestation was that during which maximum fetal renal growth occurred. Umbilical vein plasma renin levels were higher in small-for-gestational-age fetuses. The findings of slow fetal renal growth rate and associated high renin concentrations seen in small-for-gestational-age fetuses could be implicated in an irreversible reno-vascular pathology leading to adult hypertension. We suggest that 26 to 34 weeks could be the "critical period' during which the insult that leads to in-utero programming for the development of adult hypertension occurs.

Birth Weight↗

Application of ultrasonic transit time flowmetry to the measurement of umbilical vein blood flow at caesarean section.

OBJECTIVES: To determine the applicability of ultrasonic transit time flowmetry to the measurement at caesarean section of umbilical vein blood flow rate and to examine the relationship between flow rates and birthweight for gestational age. DESIGN: Umbilical vein blood flow was measured at caesarean section using a transonic time flow probe on a loop of the umbilical cord in 33 appropriate and 21 small for gestational age fetuses. RESULTS: The mean (SD) umbilical vein blood flow in the 54 fetuses was 78.4 (23.1) ml kg-1 min-1. There was a linear relation between umbilical vein blood flow measured by ultrasonic transit time flowmetry and birthweight (r = 0.63, P < 0.0001). The mean umbilical vein blood flow in appropriate for gestational age fetuses [90 (18) ml kg-1 min-1] was greater than that in the small for gestational age group [66 (23) ml kg-1 min-1], P < 0.04). CONCLUSIONS: Umbilical vein blood flow measurements obtained by the ultrasonic transit time flowmetry technique are simple to perform and compare well with reported values obtained by the Doppler ultrasound technique (when vessel diameter is greater than 4 mm). Umbilical venous blood flow rate is significantly lower in small for gestational age fetuses.

Birth Weight↗

Fetal fibronectin in cervicovaginal secretions as a predictor of preterm birth.

OBJECTIVE: To determine whether fetal fibronectin detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labour is a predictor for preterm birth. DESIGN: A blind prospective observational study. SETTING: A teaching hospital. PARTICIPANTS: One hundred and forty-one women presenting to the delivery suite between 24 and 37 weeks of gestation (112 were between 24 and 34 weeks of gestation) with symptoms suggestive of preterm labour, with intact membranes and cervical dilation of < 2 cm. INTERVENTION: Specimens of cervicovaginal secretions were collected from the ectocervix and posterior fornix. Fetal fibronectin levels were measured by an ELISA and samples were considered positive if the level of fetal fibronectin present was > or = 0.05 microgram/ml. MAIN OUTCOME MEASURES: Gestation at birth and sampling-birth interval. RESULTS: The preterm birth (before 37 weeks of gestation) rate in the population studied was 19.1%. Fetal fibronectin predicted preterm birth with sensitivity of 63%, specificity of 95.6%, positive predictive value of 77.3%, and negative predictive value of 91.6%. Analysis of the data from women at less than 34 weeks of gestation showed similar results. A negative test accurately excluded (97.9%) the chance of subsequent birth during the three weeks interval following sampling. CONCLUSIONS: The presence of fetal fibronectin in the cervicovaginal secretions of women admitted with symptoms suggestive of preterm labour indicates a significant risk for subsequent preterm birth. The absence of fetal fibronectin in this group is a very strong indication that subsequent preterm birth is unlikely to occur. Fetal fibronectin test, if combined with clinical findings, has a potentially important role in clinical management of women with symptoms suggestive of preterm labour.

Adult↗

Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers.

OBJECTIVE: To examine the effect of a relatively low dose of creatine on skeletal muscle metabolism and oxygen supply in a group of training athletes. METHODS: 31P magnetic resonance and near-infrared spectroscopy were used to study calf muscle metabolism in a group of 10 female members of a university swimming team. Studies were performed before and after a six week period of training during which they took either 2 g creatine daily or placebo. Calf muscle metabolism and creatine/choline ratios were studied in resting muscle, during plantar flexion exercise (10-15 min), and during recovery from exercise. RESULTS: There was no effect of creatine on metabolite ratios at rest or on metabolism during exercise and recovery from exercise. Muscle oxygen supply and exercise performance were not improved by creatine if compared to placebo treated subjects. CONCLUSIONS: Oral creatine supplementation at 2 g daily has no effect on muscle creatine concentration, muscle oxygen supply or muscle aerobic or anaerobic metabolism during endurance exercise.

Administration, Oral↗

Magnetic resonance spectroscopy in congenital heart disease.

OBJECTIVE: To determine the feasibility of studying myocardial and skeletal muscle bioenergetics using 31P magnetic resonance spectroscopy (MRS) in babies and young children with congenital heart disease. SUBJECTS: 16 control subjects aged 5 months to 24 years and 18 patients with CHD, aged 7 months to 23 years, of whom 11 had cyanotic CHD, five had cardiac failure, and two had had a Senning procedure. DESIGN: 31P MRS was carried out using a 1.9 Tesla horizontal 65 cm bore whole body magnet to study the myocardium in 10 patients and skeletal muscle (gastrocnemius) in 14 patients, eight of whom were exercised, together with appropriate controls. RESULTS: In hypoxaemic patients, in skeletal muscle at rest intracellular pH (pHi) was abnormally high [7.06 (SEM 0.04) v 7.04 (0.05), P < 0.01] and showed a positive correlation with haemoglobin (P < 0.03). On exercise, hypoxaemic patients fatigued more quickly but end-exercise pHi and phosphocreatine recovery were normal, implying that an equivalent but smaller amount of work had been performed. End-exercise ADP concentration was lower. On recovery, the initial rate of phosphocreatine resynthesis was low. Skeletal muscle bioenergetics were within normal limits in those in heart failure. In the myocardium, the phosphocreatine/ATP ratio was similar in controls and hypoxaemic subjects, but low in those in heart failure. CONCLUSIONS: In heart failure, the myocardial phosphocreatine/ATP ratio was reduced, as in adults, while resting skeletal muscle studies were normal. By contrast, hypoxaemic children had normal myocardial bioenergetics, but showed skeletal muscle alkalinity, and energy reserves were more readily depleted on exercise. On recovery, the initially slow phosphocreatine resynthesis rate reflects a low rate of mitochondrial ATP synthesis, probably due to an inadequate oxygen supply. 31P MRS offers a safe, non-invasive method of studying myocardial and skeletal muscle bioenergetics in children as young as 5 months.

Adenosine Triphosphate↗

Changes in energy metabolism of calf muscle in patients with intermittent claudication assessed by 31P magnetic resonance spectroscopy: a phase II open study.

Energy status and metabolism in skeletal muscle of nine patients with peripheral arterial disease and suffering from intermittent claudication were evaluated using 31phosphorus magnetic resonance spectroscopy (MRS) before and after treatment for 3 months with propionyl-L-carnitine (PLC; 2 g/day p.o.). Maximum walking distance (MWD) was assessed on a standard treadmill (4 km/h, zero incline). For the group as a whole 31P MRS results did not change significantly with PLC. Although MWD increased by a mean of 36%, this change did not reach significance. However, when these variables were assessed with respect to the change in MWD, there were significant differences between those who increased MWD by > 30% (responders, R; n = 5) and those who did not (nonresponders, NR; n = 4). Compared with pretreatment values, during exercise the decrease in muscle pH in R relative to the decrease in phosphocreatine was less after PLC (p = 0.04). After exercise there was a significant inverse correlation between the changes in recovery half-time (t1/2) for phosphocreatine and in MWD (r = -0.91, p = 0.01). With PLC, Vmax increased in R (p = 0.04), but not in NR. For the patient group as a whole, the changes in Vmax and MWD correlated positively (r = 0.90, p = 0.01). This study helps to identify the changes in muscle metabolism that correlate with changes in exercise performance, and may accompany treatment with PLC.

Adenosine Diphosphate↗

Skeletal muscle metabolism before and after gemfibrozil treatment in dialysed patients with chronic renal failure.

Patients with chronic renal failure appear at greater risk for skeletal muscle side effects from the fibric acid group of lipid lowering agents. In order to determine whether sub-clinical defects of skeletal muscle metabolism can be detected in dyslipidaemic dialysis-dependent patients receiving fibrates. we studied nine patients before and after three months of gemfibrozil therapy (300-600 mg daily). Aerobic and anaerobic metabolism of the right calf muscle was examined at rest and during exercise using 31P magnetic resonance spectroscopy. Near infra-red spectroscopy was used to assess skeletal muscle re-oxygenation following ischaemic exercise of the arm. Following gemfibrozil treatment plasma triglycerides fell significantly 3.0 +/- 0.5 mM (SEM) to 1.5 +/- 0.2 mM. Gemfibrozil did not affect the established metabolic defects that exist in the skeletal muscle of the dialysed patient. Skeletal muscle re-oxygenation was not significantly lower in renal failure and was not altered by gemfibrozil. Gemfibrozil (600 mg daily) significantly improved the lipid profile of chronic renal failure and was not associated with clinical or bioenergetic impairment of skeletal muscle metabolism.

Adult↗

Assessment of mitochondrial function and control in normal and diseased states.

Mitochondrial function in muscle in vivo can be quantitatively evaluated using 31-phosphorus nuclear magnetic resonance. In resting muscle, the concentrations of ions (e.g. H+, Na+) and two of the major bioenergetic components (inorganic phosphate and creatine) are determined by regulated transcellular transport processes. During recovery after exercise the kinetics and control of mitochondrial ATP synthesis can be established. During exercise the relative contributions to ATP synthesis of phosphocreatine (using creatine kinase), anaerobic glycogenolysis and oxidative phosphorylation are dissected and have been shown to change with time. The consequences of mitochondrial lesions and dysfunctions on these processes have been summarised.

Adenosine Triphosphate↗

Skeletal muscle mitochondrial dysfunction in alternating hemiplegia of childhood.

Alternating hemiplegia of childhood is an uncommon disease characterized by repeated, transient attacks of hemiplegia. Its pathophysiology is uncertain, but attention recently has focused on possible mitochondrial abnormalities. Using 31P magnetic resonance spectroscopy, we studied gastrocnemius muscle in 5 patients with alternating hemiplegia, aged 8 to 30 (mean, 18) years, at rest and during incremental aerobic exercise and recovery. There were no significant differences in resting muscle between patients and a control group aged 7 to 42 (mean, 19) years. Exercise performance was grossly impaired in the patients, the mean duration being 30% of normal. The total change in pH during exercise was somewhat less than in control subjects, while the changes in phosphocreatine concentration and intracellular ADP were similar. Thus the average overall rate of fall of phosphocreatine concentration during exercise was three-fold greater than in control subjects. However, the initial rate of ATP turnover at the start of exercise (a measure of muscle mass and efficiency) was not abnormal. During recovery, both the initial rate of phosphocreatine resynthesis and the calculated mitochondrial capacity were reduced by about 35%. This mitochondrial defect probably explains most of the abnormalities seen during exercise.

Adolescent↗