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Biomedical subjects

D Roland

Publications and source records attributed to D Roland.

16 recordsLinked to original sources

Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type.

Peroxisomal biogenesis defects include a number of severe neurodevelopmental disorders, among which infantile Refsum disease (IRD) occupies the mildest end of the spectrum. Although high docosahexaenoic acid (DHA) and low phytanic acid diets can correct some of the biochemical defects, they have not consistently altered the progressive course of the disease. We carried out orthotopic liver transplantation (OLT) in a mildly symptomatic 6-month-old infant who was a sibling of a severely neurologically impaired older sister. After transplantation the clinical course of this young child appeared much improved by comparison to her older sister. She walked alone at 4 years, had acceptable social interaction and had a noticeable recovery of audition. After transplantation her biochemical parameters were significantly improved: phytanic acid and very long-chain fatty acid (VLCFA) serum concentrations decreased. Abnormal bile acids disappeared from plasma. Although the OLT did not result in a cure of the disorder, the clinical and biochemical results suggest that OLT should be considered in mildly symptomatic patients.

ATPases Associated with Diverse Cellular Activitie↗

Relief of gastrointestinal symptoms under enzyme replacement therapy [corrected] in patients with Fabry disease.

Gastrointestinal symptoms, including diarrhoea and abdominal pain, are one of the earliest and most frequently reported signs of Fabry disease, a rare X-linked lipid storage disorder. As the disease progresses, renal, cardiac and cerebrovascular complications develop, resulting in more serious symptoms and early mortality. The present study evaluated the effects of enzyme replacement therapy (ERT) with agalsidase alfa on the gastrointestinal symptoms of Fabry disease. Following 6 months of treatment, both the severity ( p < 0.02) and frequency ( p < 0.02) of abdominal pain decreased. For those patients who had received agalsidase alfa for more than 6 months, the observed improvement was generally maintained. This is the first study indicating a significant beneficial effect of ERT on gastrointestinal symptoms in a group of patients treated for Fabry disease.

Abdominal Pain↗

Estimation of bioavailability of DL-methionine hydroxy analogue relative to DL-methionine in layers with exponential and slope-ratio models.

An experiment was conducted using molted hens to estimate the bioavailability of DL-methionine hydroxy analogue-free acid (MHA-FA) relative to DL-methionine (DLM). In this experiment, 5 supplemental levels (0.012, 0.024, 0.036, 0.048, and 0.060%) of DLM or equimolar concentrations of MHA-FA were added to a basal diet containing 14.97% protein and 0.27% methionine. The low protein diet was used to increase the sensitivity of laying hens to methionine deficiency. Feed consumption, egg production, egg mass, and egg weight increased (P < 0.05), and feed conversion decreased (P < 0.05) when DLM or MHA-FA was added to the basal diet for some supplemental methionine levels. There was no difference (P > 0.05) in feed consumption between hens fed DLM and hens fed MHA-FA. Regression analysis showed that the bioavailability of MHA-FA relative to DLM on a molar basis was 88.7% (egg production), 88.0% (egg mass), and 84.6% (egg weight) with the exponential model, and was 89.7% (egg production), 89.6% (egg mass), and 86.8% (egg weight) with the slope-ratio model. The average bioavailability of MHA-FA relative to DLM was 88% on a molar basis.

Animal Feed↗

Effects of pulsed magnetic energy on a microsurgically transferred vessel.

This article reports the findings of a study that attempted to elucidate whether pulsed magnetic energy stimulates neovascularization in vivo, using a microsurgically created arterial loop model in a prospective randomized trial of 108 rats (n = 12/group). Pulsed magnetic energies of 0.1 and 2.0 gauss were applied immediately postoperatively and for 4, 8, and 12 weeks, respectively, with a statistically significant increase in neovascularization among the treated animals compared with control rats. The study provides a starting point for future study and evaluation of the stimulation of angiogenesis with the use of pulsed magnetic energy and suggests a possible use of this modality to increase the quality of revascularized tissue.

Animals↗

Inhibition of LTB4 biosynthesis in situ by CGS 23885, a potent 5-lipoxygenase inhibitor, correlates with its pleural fluid concentrations in an experimentally induced rat pleurisy model.

An intrapleural injection of carrageenan in rats induced LTB4 and LTC4/D4/E4 biosynthesis, exudate formation, and cellular influx in the pleural cavity. An injection of calcium ionophore (A23187, 100 nmol) 16-18 h after carrageenan injection augmented leukotriene biosynthesis and exudate formation, but not cellular influx. The carrageenan-induced pleurisy model modifid by A23187 administration was used to study the oral effect of CGS 23885 (N-hydroxy-N-[(6-phenoxy-2H-1-benzopyran-3-yl)-methyl]urea), a potent 5-lipoxygenase (5-LO) inhibitor, on inflammatory parameters. CGS 23885 dose-dependently (1 to 30 mg/kg) inhibited the enhanced LTB4 and LTC4/D4/E4 (1 to 10 mg/kg) biosynthesis, but had no effect on enhanced exudate formation. An inhibitory effect of CGS 23885 of small magnitude on cellular influx due to carrageenan stimulation was seen at 30 mg/kg. The concentrations of CGS 23885 in the pleural fluid were dose-related, and a positive correlation (r2=0.989) between pleural fluid concentration of LTB4 and CGS 23885 was observed. The results confirm that CGS 23885 is a specific, orally active 5-LO inhibitor which can achieve concentrations in the pleural cavity sufficient to inhibit production of LTB4 and LTC4/D4/E4 in an ongoing inflammatory response.

Animals↗

Computed tomography of thoracic aortic trauma.

During a 63-month period, 28 consecutive patients suspicious for injury of the thoracic aorta were examined by computed tomography (CT). Twelve aortic ruptures were evidenced; pseudoaneurysm and mediastinal haematoma in close contact with the aorta were present in 12 patients, marginal lucency in 9, marginal irregularity in 8 and intimal flap in 6. CT was falsely negative in 1 patient with injury of the left subclavian artery. Angiography and surgery confirmed the diagnosis in 7 patients, and surgery alone in 5 patients. CT had a sensitivity of 92% and a specificity of 100%. The need for angiography was obviated in 67% of patients. A radiologist with experience in trauma management, CT and angiography should perform both examinations.

Accidents, Traffic↗

Abnormal temporal patterns of glucose tolerance in obesity: relationship to sleep-related growth hormone secretion and circadian cortisol rhythmicity.

To define the chronobiology of glucose tolerance and insulin secretion in obesity, nine obese men and nine lean men were studied during constant glucose infusion for 53 h, including 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples were collected at 20-min intervals to assay glucose, insulin, C-peptide, cortisol, and GH. Sleep was polygraphically monitored. Abnormal temporal profiles of glucose regulation were observed during wakefulness and sleep in obese subjects. During daytime hours, the normal profile of glucose tolerance was reversed, as an improvement, rather than a deterioration, was observed from morning to late evening. This reversal of the daytime pattern appeared to be caused by a dual defect in glucose regulation during the previous night. Indeed, during early sleep, GH secretion was markedly reduced, and the nocturnal rises of glucose and insulin secretion were dampened. During late sleep, obese subjects failed to suppress insulin secretion and plasma glucose, resulting in high morning levels. Comparisons of metabolic and hormonal patterns during nocturnal and daytime sleep suggest that the failure to suppress insulin secretion in late sleep may reflect a relative insensitivity of the beta-cell to acute inhibitory effects of cortisol in addition to insulin resistance.

Adult↗

Ultrasonographically detectable ring structure in avian (Gallus gallus) egg yolks.

After a preliminary finding of ultrasonographically detectable ring structure within the yolk of avian eggs, a study was initiated to investigate these properties. Ultrasonographically detectable alternating hyperechoic and hypoechoic rings within the egg yolk were found to be consistent but variability occurred in ring numbers, thickness, and clarity. Rings were best seen at two days post oviposition and were not affected by refrigeration or heating of the yolks. The usefulness of rings in experimental studies of yolk content of lipoprotein is postulated.

Animals↗

Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.

To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone.

Adult↗

Life-sustaining treatment. A prospective study of patients with DNR orders in a teaching hospital.

We conducted a prospective survey of attending, resident, and intern physicians who had written a "do not resuscitate" (DNR) order for 93 patients in their care. After writing a DNR order, 11% of respondents would still use chest compression if their patient experienced a cardiopulmonary arrest. Many physicians did not plan to withdraw therapy except intensive care, but most physicians planned to withhold a spectrum of life-sustaining therapies, from hemodialysis (86%) to intravenous fluids (21%). Attending and house-staff physicians generally agreed on whether to withdraw a given therapy or not but frequently disagreed on whether to withhold a therapy or not. After patient discharge or death, 88 charts were reviewed. None of the 88 patients was coded. Physicians initiated 68 life sustaining therapies in 43 patients and discontinued 64 therapies in 34 patients; there was no change in management in 31 patients. We conclude that individual physicians interpret the DNR order differently. These orders often are associated with the discontinuation or noninitiation of life-sustaining therapies other than emergency CPR.

Adult↗

Hemolysis of chicken erythrocytes by t-butyl hydroperoxide and protection by plasma.

Chicken erythrocytes treated with 100-microM t-butyl hydroperoxide (t-BHP) were more than 80% hemolyzed in 2 h and more than 90% hemolyzed after 4 h of incubation. Autologous plasma retarded the rate of hemolysis of chicken red cells produced by t-BHP. Dialysis of chicken plasma resulted in a marked decrease in the ability of plasma to protect erythrocytes from hemolysis by t-BHP. Low molecular weight components of plasma such as uric acid are hypothesized to account for much of the dialyzable material that protects red cells from hemolysis.

Animals↗