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Biomedical subjects

R Gibson

Publications and source records attributed to R Gibson.

At least 55 records · Page 3Linked to original sources

Microsurgical excision of a pontomedullary epidermoid cyst with prepontine extension: case report.

We report the case of a patient with a pontomedullary epidermoid cyst extending into the prepontine cistern. The patient presented with a progressive VIth nerve palsy, ataxia, and headache. Magnetic resonance imaging demonstrated a well-defined pontomedullary tumor with a high fat content. We excised the lesion using a microsurgical approach through the floor of the fourth ventricle. Postoperative magnetic resonance imaging confirmed the removal of both intra- and extra-axial components. We discuss the anatomic configuration, radiological appearances, and management of this unusual pathological finding.

Adult↗

Randomised clinical trial of parenteral selenium supplementation in preterm infants.

AIM: To determine whether selenium supplementation of parenteral nutrition with 3 micrograms/kg/day of selenious acid is safe and effective in improving the selenium status of preterm infants. METHODS: Thirty eight preterm infants with mean (SEM) birthweight of 1171 (38) g and gestational age 29 (0.3) weeks were randomly allocated to a non-supplemented (PN-selenium, n = 19) or supplemented (PN+selenium, n = 19) group. The study began at 2.8 (0.2) (range 1-5) days of age. Term breastfed (n = 23) and formula fed (n = 8) infants were used as a reference group. RESULTS: Initially there was no difference between the preterm groups in plasma or erythrocyte selenium or glutathione peroxidase activity. Plasma selenium declined by a mean (SEM) of -13.3 (3.2) micrograms/l from 28 (4) to 16 (3) micrograms/l over the first three weeks in the PN-selenium group, but there was no fall in the supplemented infants and no net change in either group over six weeks. Over six weeks, there was a net decline in erythrocyte selenium of -106 (27) ng/g haemoglobin in the PN-selenium group, but no change in the PN+selenium group, such that at week 6 erythrocyte selenium was lower in the PN-selenium group (401 (17) ng/g haemoglobin) than the PN+selenium group (493 (25) ng/g haemoglobin). Urinary selenium was substantially higher in the PN+selenium group at each week. Initially term and preterm plasma selenium concentrations were similar, but they increased in term breastfed infants (+17 (2) micrograms/l), with both groups of preterm infants having lower plasma selenium concentrations at week 6 compared with term breastfed infants (PN-selenium 22 (3) micrograms/l; PN+selenium 23 (4) micrograms/l and term breastfed 49 (2) micrograms/l). CONCLUSIONS: Selenium supplementation of PN at 3 g/kg/day prevented depletion in newborns, but was inadequate to achieve selenium concentrations equivalent to those of breastfed term infants. Whether higher doses are more effective remains to be determined, particularly in light of the high urinary selenium secretion in supplemented infants. Selenium supplementation of both parenteral nutrition and formulas is recommended, but the optimal form and dose remain unclear.

Analysis of Variance↗

Managed care and chronic care: challenges and opportunities.

As managed care enrolls an increasing proportion of the population, increased attention needs to be paid to the care of persons with chronic conditions. This trend is occurring in the context of medical care in the United States that is deeply rooted in the acute care model of illness. The distinctive character of chronic conditions requires a reorientation of clinical practice and the way in which medical and nonmedical services are organized. Optimal chronic care systems are characterized by the integration of primary and specialty care, integration of medical and nonmedical services, and emphasis on functional status and quality of life. Analyzing enrollment data, beginning chronic disease care improvement efforts, and redesigning key support systems are all targets for HMO action.

Aged↗

Acute portal vein thrombosis after autologous stem cell transplantation.

Three patients developed abdominal pain and abnormal liver enzymes without hyperbilirubinemia, early after autografting for lymphoma. Two had received conditioning therapy with busulfan, cyclophosphamide and continuous infusion etoposide; the other had received busulfan and melphalan. Doppler ultrasound in all cases demonstrated thrombosis of the main portal vein and its branches. In the two patients tested, transient deficiencies in protein C (both cases) and protein S (one case) were observed. One case was chronologically related to anti-fibrinolytic therapy and resolved spontaneously. The other two cases resolved after treatment with low molecular weight heparin. Portal vein thrombosis should be considered in the differential diagnosis of abdominal pain and liver dysfunction after BMT.

Acute Disease↗

Are long-chain polyunsaturated fatty acids essential nutrients in infancy?

We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil, a source of docosahexaenoic acid (DHA, 22:6 omega 3), to infant formula. Healthy, term infants were randomised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed. Breastfed term infants were enrolled as a reference group. Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6, 16, and 30 weeks of age. Visual evoked potential (VEP) acuity was determined at 16 and 30 weeks. VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age (p < 0.001 and p < 0.01). Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants (p < 0.001). Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested. A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods (< 16 weeks) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula. Erythrocyte arachidonic acid (20:4 omega 6) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks (p < 0.001), although no adverse effects were noted, with growth of all infants being similar. DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity. Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be elucidated.

Adult↗

Phosphorylation modulates catalytic function and regulation in the cAMP-dependent protein kinase.

Site-directed mutagenesis was used to remove a critical phosphorylation site, Thr-197, near the active site of the catalytic subunit of cAMP-dependent protein kinase. This residue is present in a number of protein kinases, and its phosphorylation largely influences catalytic activity. We changed Thr-197 to aspartic acid and alanine and measured the effects of these substitutions on the kinetic mechanism and inhibitor affinities. The mutants were expressed as the free catalytic subunit and as soluble fusion proteins of glutathione-S-transferase. The values for KATP and Kpeptide for all three mutants are raised by approximately 2 orders of magnitude relative to the wild-type enzyme. Viscosometric measurements indicate that elevations in Kpeptide are the result of reduced rates for phosphoryl transfer and not reduced substrate affinities. This implies that the loop that contains the phosphothreonine, the activation loop, does not reduce access to the substrate site as proposed for the inactive forms of cdk2 kinase [DeBont, H. L., et al. (1993) Nature 363, 595-602] and MAP kinase [Zhang, F., et al. (1994) Nature 367, 704-711]. The mutants associate slowly with the wild-type regulatory subunit, although the cAMP-free wild-type regulatory subunit inhibits the mutants stoichiometrically. A mutant regulatory subunit that binds cAMP poorly and rapidly inhibits the wild-type catalytic subunit does not inhibit the mutant proteins. These data suggest that the phosphothreonine region serves as a docking surface for the regulatory subunit in the holoenzyme complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Biochemical folate, B12, and iron status of a group of pregnant adolescents accessed through the public health system in southern Ontario.

PURPOSE: This study was designed to estimate the prevalence of biochemical iron, folate, and vitamin B12 depletion among a group of Canadian pregnant adolescents accessed through the Public Health system. Further, the impact of prenatal supplement use, chronologic age, gynecologic age, living arrangement, main source of income, postpartum custody plan, time of entry into prenatal care, and cigarette smoking on laboratory indices of the three nutrients were determined. METHODS: Fifty-eight adolescents (14.5-19.0 years) were interviewed and blood samples were collected at 36 +/- 2 wk gestation. RESULTS: Thirteen (22%) of the pregnant adolescents had anemia (hemoglobin < 110 g/L) and forty-five (78%) had depleted iron stores (plasma ferritin < 26.6 pmol/L or 12.0 micrograms/L). Twenty-five subjects had plasma B12 values in the sub-optimal range (< 148 pmol/L). Five of the 16 adolescents who infrequently or never consumed a folate-containing supplement had suboptimal erythrocyte folate values. Twenty-four percent of the subjects had hypersegmented neutrophils and of these, all and 71% of subjects had plasma ferritin and B12 concentrations in the suboptimal range, respectively. Self-reported folic acid and B12 supplement intakes were correlated with the corresponding blood values for these nutrients. In contrast, supplement iron use was only weakly, or not at all associated with biochemical indices of iron status. CONCLUSIONS: Data from the present study indicate that plasma B12 and ferritin levels are low in a group of pregnant adolescents. These low values appear to be associated with a high prevalence of hypersegmented neutrophils. Prenatal supplement use appears to reduce the risk of low folate and B12 blood values but not biochemical iron status.

Adolescent↗

Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation.

The fatty acid composition of breast milk from 23 breast-feeding women was serially assessed by capillary gas chromatography from the 6th to the 30th wk of lactation. The proportions of total n-3 and n-6 fatty acids were unchanged with time, although some significant differences were noted for individual polyunsaturated fatty acids (PUFAs). Of the n-3 PUFAs, only docosahexaenoic acid (DHA, 22:6n-3) concentrations changed, decreasing between 6 and 16 wk from 0.26 +/- 0.13% to 0.21 +/- 0.13% of total fatty acids but remaining at this proportion until 30 wk. Of the n-6 PUFAs, 18:3, 20:3, 20:4, and 22:5 all showed reductions with time. Compared with concentrations observed in a 1981 study, linoleic acid was higher (14% compared with 11% of total fatty acids), whereas the concentration of DHA was lower (0.21% compared with 0.32% of total fatty acids), possibly reflecting a general change in the diets of Australian women.

Adult↗

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.

Adolescent↗

How appropriate are commercially available human milk fortifiers?

A preliminary investigation was made into the effectiveness of two breastmilk fortifiers on the Australian market (FM-85 [Nestlé, Vevey, Switzerland] and Enfamil Human Milk Fortifier [EHMF; Mead Johnson, Evansville, IN, USA]). Infants < 1800 g and < 34 weeks gestation at birth, who were receiving breast milk, were randomized to receive either of the fortifiers (n = 14 for FM-85, n = 10 for EHMF), until a weight of 2 kg was reached. Infants not receiving breast milk (n = 9) were fed a preterm formula (Prenan, Nestlé). The two fortifier groups were similar in most parameters examined: (i) weight gain (17.9 +/- 3.0 vs 17.4 +/- 3.5 g/kg per day); (ii) head circumference growth (1.02 +/- 0.28 vs 1.03 +/- 0.25 cm/week); (iii) arm muscle area growth (32.6 +/- 20.0 vs 33.5 +/- 13.7 mm2/week); (iv) arm fat area growth (14.0 +/- 8.7 mm2/week); (v) plasma calcium (2.52 +/- 0.08 vs 2.58 +/- 0.15 mmol/L); (vi) plasma phosphate (2.02 +/- 0.21 vs 2.13 +/- 0.32 mmol/L); (vii) plasma copper (5.28 +/- 2.83 vs 5.66 +/- 3.07 mumol/L); and (vii) plasma zinc (13.3 +/- 5.5 vs 15.8 +/- 9.2 mumol/L). The FM-85 group had a higher alkaline phosphatase level (355 +/- 110 vs 231 +/- 70 iu/L) than the EHMF group; however, no values were outside the normal range. The Prenan group had a higher rate of weight gain (23.6 +/- 3.3 g/kg per day) and higher arm fat area growth rate (25.2 +/- 7.6 mm2/week) than the fortifier groups while all other parameters were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Evaluation of risks for non-Hodgkin's lymphoma by occupation and industry exposures from a case-control study.

The etiology of non-Hodgkin's lymphoma (NHL) is not well understood. To develop hypotheses on causes of this tumor, data from a population-based case-control interview study of 1,867 white men (622 cases and 1,245 controls) in Iowa and Minnesota conducted during 1980-1983 were examined. Subjects, or their next of kin, were interviewed to obtain information on agricultural exposures, work history, medical conditions, and family history. This analysis focuses on risks of NHL by occupation, by industry, and by selected exposures. Although many comparisons were made, few significant associations were observed. Small numbers and limitations in exposure assessment, however, would tend to reduce opportunities to detect associations. The strongest finding was with various occupations that work in metals and metal products. The analysis by exposure estimates also uncovered a significant association with metals, but risks did not increase with estimated intensity of exposure. Slightly elevated risks were also noted among persons employed as painters and construction workers, agricultural and forestry workers, printers and typesetters, funeral directors and embalmers, and dry cleaners. Although the overall risks for benzene and other solvents were small, they increased slightly with level of assigned exposure. Although some associations may be due to chance, several of these occupations and industries have been linked to lymphoma in other investigations and deserve further attention.

Adult↗

Effects of diabetes on the activity and content of the branched-chain alpha-ketoacid dehydrogenase complex in liver.

Severe ketotic diabetes induced in rats by streptozotocin resulted in a reduction in activity of the hepatic branched-chain alpha-ketoacid dehydrogenase complex, regardless of whether activity was expressed on the basis of liver wet weight, total liver, liver protein, or liver DNA. A decrease in enzyme specific activity (units of enzyme activity per mg of enzyme protein) was found responsible for the reduction in measurable enzyme activity of the complex. Insulin treatment reversed the decrease in enzyme specific activity. Treatment of tissue extracts with phosphoprotein phosphatase had no effect, indicating that activity of the complex was decreased by some mechanism other than reversible phosphorylation. Specific protein components of the complex were also not found reduced by the diabetic state. Induction of severe ketotic diabetes in rats previously fed a low-protein diet resulted in activation of the enzyme as a consequence of dephosphorylation. Nevertheless, the specific activity of the dephosphorylated enzyme of diabetic, low-protein-fed rats was decreased relative to that of control, low-protein-fed animals. Reconstitution studies with tissue extracts fortified with the purified E1 component indicate that severe diabetes induces a defect in this component of the hepatic branched-chain alpha-ketoacid dehydrogenase complex.

3-Hydroxybutyric Acid↗

Effects of a fish oil rich diet on hyperoxic lung damage in mice.

Mice were fed a chow diet plus 10% cellulose, 10% fish oil or 10% sunflower oil for 3 weeks, then exposed to 100% oxygen for 75 h. Large changes in lung fatty acid composition occurred, but this did not affect hyperoxic lung damage nor levels of thiobarbituric acid reactive substances or myeloperoxidase in lungs of mice following exposure to hyperoxia. Thus there is no evidence that the ingestion of large quantities of fish oil increased the susceptibility to the oxidative stress induced by hyperoxia.

Animals↗

Thoracic outlet syndromes and magnetic resonance imaging.

The thoracic outlet syndromes encompass the diverse clinical entities affecting the branchial plexus or subclavian artery including cervical ribs or bands. Thoracic outlet syndrome are often difficult to diagnose on existing clinical and electrophysiological criteria and new diagnostic methods are necessary. This study reports our experience with magnetic resonance imaging (MRI) of the brachial plexus in 20 patients with suspected thoracic outlet syndrome. The distribution of pain and sensory disturbance varied widely, weakness and wasting usually affected C8/T1 innervated muscles, and electrophysiology showed combinations of reduced sensory nerve action potentials from the fourth and fifth digits, and prolonged F-responses or tendon reflex latencies. The MRI study was interpreted blind. Deviation of the brachial plexus was recorded in 19 out of the 24 symptomatic sides (sensitivity 79%). Absence of distortion was correctly identified in 14 out of 16 asymptomatic sides (specificity 87.5%). The false positive rate was 9.5%. Magnetic resonance imaging demonstrated all seven cervical ribs visible on plain cervical spine radiographs. Magnetic resonance imaging also showed a band-like structure extending from the C7 transverse process in 25 out of 33 sides; similar structures were detected in three out of 18 sides in control subjects. These MRI bands often underlay the brachial plexus distortion observed in our patients. We also observed instances of plexus distortion by post-traumatic callus of the first rib, and by a hypertrophied serratus anterior muscle. If they did not demonstrate a cervical rib, plain cervical spine radiographs had no value in predicting brachial plexus distortion. We believe MRI to be of potential value in the diagnosis of thoracic outlet syndrome by: (i) demonstrating deviation or distortion of nerves or blood vessels; (ii) suggesting the presence of radiographically invisible bands; (iii) disclosing other causes of thoracic outlet syndrome apart from ribs or bands.

Adult↗

A new autosomal recessive anomaly mimicking Fanconi's anaemia phenotype.

A family in which three siblings born to related parents all manifested clinical abnormalities characteristic of Fanconi's anaemia (microcephaly, short stature, slow growth, beak nose, micrognathia, skin dyspigmentation and forearm and thumb dysplasia in 2/3) is reported. All five family members had normal spontaneous chromosome breakage, a normal response to diepoxybutane and mitomycin C, and were fully informative for linkage with four DNA markers from chromosome 20q12-13.3 with no evidence for linkage. It is concluded that abnormalities typical for Fanconi's anaemia are inherited as an autosomal recessive without the defect responsible for increased chromosomal fragility and independently from the genes so far identified as being responsible for Fanconi's anaemia.

Abnormalities, Multiple↗

A single administration of LFA-1 antibody confers prolonged allograft survival.

C57BL/6 (B6) thyroid gland transplanted to the left kidney capsule of an allogeneic (BALB/c) host was typically rejected in 14 days. A single administration of 500 micrograms of an antibody to the adhesion molecule, leucocyte function-associated antigen (LFA-1, CD11a), prevented all thyroid allograft rejection for at least 70 days. Fifty percent of the treated recipients retained intact allografts for 470 days. However, the same treatment with anti-CD11a could not protect a sensitized BALB/c mouse from rejecting a second B6 thyroid allograft. Production of donor-specific alloantibodies elicited by allograft rejection was also inhibited in this system. In this transplant model, the Ab therapy is more efficacious than that of FK506, administered daily for 14 days at 15 mg/kg. These results demonstrate the remarkable effect of an anti-LFA-1 antibody in promotion of allograft survival.

Animals↗