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Biomedical subjects

G Ward

Publications and source records attributed to G Ward.

At least 55 records · Page 3Linked to original sources
PubMed1996

Artificial rearing of infant rats on milk formula deficient in n-3 essential fatty acids: a rapid method for the production of experimental n-3 deficiency.

Research into the function of docosahexaenoic acid (DHA; 22:6n-3), the predominant polyunsaturated fatty acid (PUFA) in the central nervous system (CNS), is often hindered by the difficulty in obtaining dramatic experimental decreases in DHA in the brain and retina of laboratory rats. In this study, the artificial rearing procedure, whereby infant rats are removed from their mothers, gastrostomized, and fed synthetic formula, was used in an attempt to produce rapid changes in CNS levels of DHA. Female rats were raised, from day 4-5 of life, on one of two formulas-one containing the essential fatty acids of both the n-6 and n-3 series in proportions approximately equal to those of rat milk, and the other containing high levels of 18:2n-6 but very little n-3 fatty acid. At weaning, both groups were given AIN-76A diets modified so that the PUFA content resembled that of the preweaning formula. At eight weeks of age, the n-3-deficient group exhibited decreases of more than 50% in total DHA content in the brain, accompanied by increases in arachidonic acid (AA) (20:4n-6) and, especially, docosapentaenoic acid (22:5n-6). Other artificially-reared rats were mated and their offspring were also maintained on the respective diets. In spite of the fact that they had been reared artificially, the rats mated successfully and reared litters with no obvious abnormalities. At both ten days of age and again at eight weeks, offspring of the n-3-deficient mothers exhibited decreases of more than 90% in total DHA content. Again, the long-chain n-6 PUFA increased proportionately so that total PUFA levels in the brain were not lower. As these differences are greater than those commonly reported, even after 2-3 generations of normal dietary deprivation in rodents, this procedure may be an important tool in the study of the effects of n-3 deficiency on neural development and, subsequently, of the function of DHA in nervous tissue.

Animals↗
PubMed1996

Essential fatty acid uptake and metabolism in the developing rodent brain.

Studies were carried out to determine whether the brain takes up and metabolizes essential fatty acids during early postnatal development in rodents. Rats and mice were dosed with deuterium-labeled linoleic and linolenic acids either by intraperitoneal injection or by gavage. Animals were killed at different times thereafter, and organs were removed. Brains, livers, and blood were analyzed by gas chromatography--negative-ion-mass spectrometry for labeled fatty acids. To determine whether fatty acids were present in the brain apart from cerebral blood, a subset of animals was exsanguinated by perfusion with buffered saline, and the brain was then fractionated into subcellular components. Results demonstrated that the brain took up both labeled essential fatty acids within 8 h from the time of dosing. There was on average a greater uptake of linolenic acid into the cerebellum than into the cerebral cortex during the first 8 d of life in rats. The amount of linoleic acid taken into either region was similar, however. Docosahexaenoic acid intermediates, 20:5n-3 and 22:5n-3, were also found labeled in the brain. Time-course labeling experiments indicated that these intermediates may be converted to 22:6n-3 within the brain. A rise of labeled 22:6n-3 in the brain at 24 h appeared to be due to uptake of this fatty acid from the blood. The amount of labeled 22:6n-3 in the brain continued to increase beyond 24 h, and this did not appear to be correlated with its blood concentration. These results suggest that, during development in the rodent, different regions within the brain may vary in their capacity to synthesize 22:6n-3, and this may be correlated with regional growth rates.

Administration, Oral↗
PubMed1996

Peptide YY receptor in submucosal and myenteric plexus synaptosomes of canine small intestine.

PYY receptors were characterized and their loci determined in canine small intestine. The density of 125I-labeled peptide tyrosine tyrosine (PYY) binding was highest in myenteric (MY) and submucosal (SUB) plexus fractions enriched in synaptosomes. Two binding sites [high affinity (H) and low affinity (L)] were found in the submucosal synaptosome-enriched membrane: dissociation constant (Kd)H = 7.6 pM, maximal binding capacity (Bmax)H = 28 fmol/mg; KdL = 0.18 nM, BmaxL = 120 fmol/mg protein. The binding of 125I-PYY reached a maximum within 30 min; dissociation was incomplete in the presence of unlabeled PYY. The rate of dissociation was enhanced after exposure of synaptosomes to guanosine 5'-O-(3-thiotriphosphate). Binding of 125I-PYY was completely inhibited by neuropeptide Y (NPY)-(13-36) (in SUB and MY) and by [Leu31,Pro34]NPY (in MY) but only partially by [Leu31,Pro34]NPY in SUB, suggesting the presence of Y2 receptor in SUB and the presence of Y1 and Y2 receptors in MY. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the PYY receptor complex revealed a radioactive band at 70 kDa. The PYY receptors in the canine small intestinal myenteric and submucosal plexus correspond in location to that of PYY in synaptosomes and are coupled with G proteins. Different subtypes are present in different loci.

Animals↗
PubMed1996

Is docosahexaenoic acid necessary in infant formula? Evaluation of high linolenate diets in the neonatal rat.

Neural accretion of docosahexaenoic acid (DHA) is thought to play an important role in the neural development of human infants. The lack of DHA in infant formulas contributes to the lowered neural accretion of DHA observed in formula-fed infants relative to those breast-fed. We hypothesized that lowering the dietary linoleic acid (LA) to alpha-linolenic acid (LNA) ratio may lead to increases in the level of DHA in the developing brain and retina. Lowering the LA to LNA ratio from 10:1 to 1:1 and to 1:12 in the artificially reared (AR) neonatal rat pup resulted in a significant increase in the percentage of brain DHA between AR dietary groups. The brain level of DHA in the AR group fed a 1:12 ratio was similar to that of a dam-reared reference group. However, levels of DHA in the retina of all AR groups were significantly lower than that of the (chow fed) dam-reared group. It appears that LNA may serve as an adequate substrate for the accretion of DHA in the brain, but not the retina of the developing rat. In both the brain and the retina, levels of arachidonic acid in the AR pups fed the 1:1 ratio were similar to that of the dam-reared group. However, levels in the 1:12 group were significantly reduced. The addition of long chain n-3 polyunsaturates such as DHA to infant formula may therefore be necessary for adequate neural DHA accretion and optimal neural development.

Animal Feed↗
PubMed1996

Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity.

Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.

Adult↗
PubMed1996

Low density lipoprotein particle size in hypopituitary adults receiving conventional hormone replacement therapy.

Adults receiving conventional replacement therapy for hypopituitarism are known to have increased cardiovascular mortality. The aim of this study was to assess the lipid profiles of 30 hypopituitary adults compared with 2 case control groups, 1 matched for age, sex, and body mass index (BMI) and the second matched for age and sex only with a BMI representative of the general population. Fasting lipids, lipoproteins, and apoproteins (Apo) were determined by routine methods. Low density lipoprotein (LDL) particle size was determined by nondenaturing gradient gel electrophoresis. LDL size was significantly smaller in the hypopituitary group (25.9 +/- 0.1 nm) than in the BMI-matched (26.2 +/- 0.1 nm; P < 0.05) and standard control (26.3 +/- 0.1 nm; P < 0.01) groups. High density lipoprotein cholesterol levels in the hypopituitary group were significantly lower than those in the BMI-matched control group (1.13 +/- 0.06 vs. 1.34 +/- 0.06 mmol/L; P < 0.05) and the standard control group (1.38 +/- 0.06 mmol/L; P < 0.005). Apo A1 levels were also lower compared with those in the BMI-matched (122 +/- 6 vs. 137 +/- 4 mg/dL; P < 0.05) and the standard (143 +/- 4 mg/dL; P < 0.005) control groups. There was a trend toward higher triglyceride levels when the hypopituitary subjects were compared with the standard control group [1.4 (95% CI, 1.3-2.2) vs. 1.0 (95% CI, 0.9-1.4) mmol/L; P = 0.06]. These differences were more marked in the female subjects studied. No significant differences were noted in total cholesterol, LDL cholesterol, or Apo B levels. We conclude that hypopituitary patients receiving conventional replacement therapy have an atherogenic lipid profile characterized by small dense LDL, decreased high density lipoprotein cholesterol, and increased triglyceride levels, which may contribute to the excess cardiovascular mortality in this group.

Adult↗
PubMed1996

Microregional blood flow in murine and human tumours assessed using laser Doppler microprobes.

A multichannel laser Doppler system has been used to measure microregional fluctuations in perfusion in the HT29 human tumour xenograft and in patients with advanced malignant disease. A comparison is made with previously obtained data for the SaF, a transplantable murine tumour. The 300 microns diameter probes recorded fluctuations in erythrocyte flux in tumour microregions with an estimated volume of 10(-2) mm3. Of the 66 human tumour microregions sampled, 26% showed a change in erythrocyte flux by a factor of 2 or more over the 60 min measurement period, compared with 37% of HT29 and 48% of SaF microregions. In each of the studies more than 50% of changes were completed within 20 min, although slower changes were more common in the human tumours than in the experimental systems. Within the 1 h monitoring period at least 30% of the changes were reversed (human tumours 30%, HT29 45%, SaF 31%). These findings demonstrate that microregional changes in erythrocyte flux, consistent with transient, perfusion-driven changes in oxygenation, are a feature of human malignancies as well as experimental transplanted tumours.

Aged↗
PubMed1995

Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liver disease.

OBJECTIVE: Increased serum GH concentrations and GH responses to a variety of stimuli have been reported in patients with chronic liver disease (CLD). We investigated the pulsatile pattern of endogenous GH release and GH-binding protein (GHBP) and insulin-like growth factor-I (IGF-I) diurnal profiles in adults with cirrhosis, in comparison with healthy, matched control subjects. DESIGN: Case-control, cross-sectional. PATIENTS: Seven patients with biopsy proven cirrhosis, and sex, age, height, weight and oestrogen status matched controls. MEASUREMENTS: Serum immunoreactive GH concentrations in samples collected at 20-minute intervals for 24 hours were analysed using a multi-parameter deconvolution method to simultaneously resolve endogenous GH secretory and disappearance rates. Diurnal patterns of GHBP (specific immunoprecipitation method) and serum IGF-I (RIA after acid-ethanol extraction) were assessed. RESULTS: The mean daily GH secretion rate in patients with CLD was increased (210 +/- 93 vs 100 +/- 55 mU/I/day; P = 0.025), and GH disappearance half-time was prolonged (43 +/- 10 vs 24 +/- 9 min; P = 0.006) compared to controls. Detectable GH secretory bursts were more frequent in patients with CLD (10 +/- 1 vs 6 +/- 3/day; P = 0.038), but of similar mean mass (21 +/- 10 vs 17 +/- 8 mU/I) compared to controls. In patients with CLD, mean serum GHBP was slightly lower (63 +/- 36 vs 71 +/- 14% pooled control; P > 0.1). Fasting serum IGF-I concentrations (after size-exclusion HPLC) were lower in the patients with CLD (13 +/- 5 vs 21 +/- 2 nmol/l; P < 0.0001). Multiple regression analysis showed that GH secretion rate was increased in patients with CLD with higher Child's classifications (R2 = 0.86; P = 0.002) and with lower serum IGF-I concentrations measured after HPLC (R2 = 0.11; P = 0.044). CONCLUSIONS: Adults with chronic liver disease have (1) increased total daily GH secretion rates, which appear to be influenced by disease severity and diminished serum IGF-I-mediated negative feedback; (2) markedly impaired endogenous GH clearance, possibly reflecting changes in hepatic GH-receptor status; and (3) GHBP levels which do not correlate with GH kinetics or serum IGF-I concentrations.

Adult↗
PubMed1995

Assessing patients with HIV-associated dementia.

HIV-associated dementia may pose communication challenges to healthcare staff. It is essential to obtain an accurate assessment of the confusion in order to achieve a baseline from which to evaluate a patient. It is important to communicate in a way that conveys worth and value to the patient. The expertise of the multidisciplinary team should be drawn on when working with such patients.

AIDS Dementia Complex↗
PubMed1994

Effects of breathing a normoxic helium mixture on exercise tolerance of patients with cystic fibrosis.

Breathing helium-oxygen (He-O2) mixtures of 20.9% O2/79.1% He has been shown to increase exercise ventilation and peak oxygen uptake in healthy subjects. The improved exercise performance is thought to be due to the reduced density of He-O2 compared to air and the resulting increases in ventilation. Patients with cystic fibrosis (CF) frequently have abnormal pulmonary function test results, low exercise ventilations and diminished exercise tolerance. This led to the hypothesis that in CF the exercise tolerance of patients might improve when breathing He-O2. To test this hypothesis, 11 patients with CF or mild to severe airway obstruction performed spirometry and progressive maximal exercise tests while breathing air or He-O2. The He-O2 mixture significantly increased (P < 0.05) forced expiratory volume in 1 sec (FEV1) by 8.2%, peak expired flow by 39%, and maximal voluntary ventilation (MVV) by 17.9% compared to air, while forced vital capacity (FVC) and forced mid-expiratory flow rate (FEF25-75%) were unchanged by breathing He-O2. Ventilation and oxygen uptake at matched submaximal power outputs were not increased while breathing He-O2, nor were peak exercise ventilation (VEpeak) or peak exercise oxygen uptake (VO2peak). Estimated hemoglobin saturation and total exercise time were also unchanged during He-O2 breathing. However, there was a trend for the subjects with the better FEV1 to increase VO2peak. Increases in VO2peak when breathing He-O2 and air were correlated (r = 0.67, P < 0.05) with the percent of predicted FEV1 values. Still, in the 11 patients as a group, breathing He-O2 did not significantly improve VO2peak, VEpeak, or exercise tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Investigating severe and fatal asthma.

BACKGROUND: Severe asthma continues to present a major therapeutic problem despite advances in our understanding of the disease. Innovative ideas for investigating the underlying causes and treatment of severe asthma are few, and many patients still become dependent on oral steroids. We describe two separate studies: first, a prospective investigation measuring the responses of persons with severe asthma to an allergen-free environment; second, a retrospective analysis of factors associated with eight fatalities and one near fatality caused by asthma exacerbations. METHODS: In the prospective study 17 persons with severe asthma were admitted to a hospital clinical research unit containing an allergen-free room for steroid dose reduction. Peak flow measurements, treatment requirements, and evidence of infection were followed up. In the retrospective study, the cases of nine patients who had been evaluated for asthma and who subsequently died during an asthma attack were reviewed; where possible allergen levels in their house dust and specific IgE antibodies to common indoor allergens were measured. RESULTS: Analysis of the patients in the prospective study revealed two categories of responses to steroid dose reduction: (1) asthmatic persons who either maintained or improved peak flow values on steroid reduction; these patients were predominantly allergic to indoor allergens; (2) asthmatic persons whose condition deteriorated; these patients were unable to tolerate reduction in steroid dose. The second group included persons with sensitization to fungal antigens who had asthmatic exacerbations in association with culture-documented fungal colonization. The retrospective study revealed that in five of the eight fatalities caused by asthma, exposure to a relevant allergen had occurred at home before death. CONCLUSION: Some steroid-dependent persons with severe asthma are allergic to inhalant allergens and may benefit from avoiding allergens. In some cases there is no evidence that antigen exposure from diet, inhalants, fungal infections, or sinusitis is relevant to their disease. However, persons with severe asthma include individuals infected with and sensitized to fungal antigens. The results suggest that cases of severe asthma should be investigated to identify treatable causes.

Adrenal Cortex Hormones↗
PubMed1994

Testing theories of language processing: an empirical investigation of the on-line lexical decision task.

On-line lexical decision has been used to test major theoretical hypotheses about language comprehension. Contrary to several current models, A. Sharkey and N. Sharkey (1992) found that a word in a sentence did not give facilitation to an immediately following, highly associated test item. In this article it is shown that such facilitation can be obtained. Other theories have proposed that syntactic processes supply antecedents for implicit anaphors. In using a test item that was an associate of the antecedent of the anaphor, the authors were unable to replicate previous findings of facilitation at but not before the site of the anaphor. Across 9 experiments, obtaining facilitation depended on the choice of control condition. This dependency raises questions about previous on-line lexical decision results that have been used to support the immediacy of syntactic processing.

Cognition↗
PubMed1994

Simple procedures can markedly enhance automated immunoassay performance.

Theoretically, optimal performance for an immunoassay system is achieved when both the interassay and within-run precisions are identical. Using the Ciba Corning ACS:180 automated immunoassay system, the authors made two simple changes to the operating procedures that allowed near-optimal analytic performance (as assessed with the interassay coefficient of variation determined by the protocol of the National Committee for Clinical Laboratory Standards) for four of six hormones: thyroid-stimulating hormone, luteinizing hormone, prolactin, and human chorionic gonadotropin. At low hormone concentrations, the 20% interassay coefficients of variation for the hormones assayed were as follows: free tetraiodothyronine, 1.74 pM; thyroid-stimulating hormone, .033 mIU/L; luteinizing hormone, .21 U/L; follicle-stimulating hormone, .69 U/L; prolactin, 5.03 mU/L; and human chorionic gonadotropin, 1.52 mU/L. The operational enhancements improved the analytic performance of the assay for all hormones assessed compared with the performance of previously used isotopic immunoassays.

Autoanalysis↗
PubMed1994

Familial testicular carcinoma: in search of genetic triggers.

Two cases of testicular tumours in non-twin brothers of a cancer-prone family are described. Cytogenetic studies of these two patients and human leucocyte antigen (HLA) typing of the family failed to identify any genetic defects. The authors propose using linkage analysis for further genetic studies but would require additional families for this to be performed.

Adult↗
PubMed1993

Effects of ridogrel on the prostacyclin-thromboxane ratio in nulliparous third trimester-pregnant rhesus monkeys.

The effects of ridogrel, a thromboxane synthetase inhibitor and endoperoxide receptor antagonist, were studied in twelve pregnant, nulliparous Rhesus monkeys (Macaca mulatta) during the last trimester of pregnancy. Ridogrel was administered intravenously in two groups of animals (n = 6), at either 0.1 mg/kg or 1.0 mg/kg. Ultrasonic assessment of the fetuses during and after the infusion period revealed no obvious changes in fetal condition. Both dosages reduced serum thromboxane levels 30 minutes after administration, 96.6% and 99.6% suppression, 0.1 mg/kg and 1.0 mg/kg, respectively (P < 0.0001), while the 1.0 mg/kg dose produced continued suppression for 24 hours (78% suppression, P < 0.0001) and was lower than the 0.1 mg/kg 24 hour value (P < 0.008). Prostacyclin levels increased to 340% and 472% of baseline values, 0.1 mg/kg and 1.0 mg/kg, respectively at 30 minutes and to 928% and 255% of baseline at 24 and 48 hours after treatment in the 1.0 mg/kg group (P < 0.0003). Ridogrel caused no changes in maternal or neonatal outcome. The potential for the use of this compound for the treatment of preeclampsia is discussed.

6-Ketoprostaglandin F1 alpha↗