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Biomedical subjects

R Gibson

Publications and source records attributed to R Gibson.

At least 19 recordsLinked to original sources
PubMed2001

Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: results of a phase I multi-center study.

Cystic fibrosis (CF) is characterized by defective cystic fibrosis transmembrane regulator (CFTR) expression and function, associated with abnormal ion transport and mucociliary clearance, and clinical lung disease. Triphosphate nucleotides such as uridine-5'-triphosphate (UTP) and INS 365, may be useful for CF through actions, mediated via P2Y(2) extracellular receptors, on chloride and liquid secretion, and ciliary beat frequency. INS 365 may offer chemical stability advantages over UTP. In a randomized, double-blind, multicenter phase I study, we studied the safety and maximally tolerated dose of escalating, single doses of aerosolized INS 365, in adult and pediatric patients with mild to moderate CF lung disease (FEV(1) > or = 45% predicted). In four successive dose cohorts of adult patients (n = 12 per cohort, age > or = 18 years) and four successive pediatric dose cohorts (n = 12 per cohort, age 5-12 years), patients were randomized 3:1 active/placebo (0.9% saline) to evaluate doses of 20, 40, 80, and 100 mg INS 365 delivered by nebulizer (Pari Star ). Sputum was collected pre- and post-dosing to obtain preliminary results on clinical efficacy. After each dose cohort, a Data Safety Monitoring Committee (DSMC) reviewed the data. Forty-eight adult and 36 pediatric patients completed the protocol (up to 100 mg for adults, 80 mg for pediatric patients). The predominant adverse events were cough, wheezing, chest tightness, and a decrease in FEV(1) (occurring in 8/48 adults, and 5/36 pediatric patients), which occurred predominantly in the 80-mg and 100-mg dose cohorts. Though a few adult patients had a tendency to increase sputum production, there was little consistent effect noted on sputum production in this acute, single-dose study. The data suggest that aerosolized INS 365 is safe when delivered at single doses of up to 40 mg in adults and children with CF, but that higher doses are unlikely to be tolerated.

Adolescent↗
PubMed2001

Effects of combination therapy with PTH and 17beta-estradiol on long bones of female mice.

Parathyroid hormone (PTH) is thought to increase trabecular bone mass in postmenopausal women by stimulating osteoblast function. A similar action may contribute to estrogen's protective effect on the skeleton, which we have explored in female mice, in which estrogen induces an exaggerated osteogenic response. In the present investigation, we used this model to determine whether an interaction exists between stimulatory effects of PTH and estrogen on osteoblast function in cancellous bone. An initial dose response study was performed where PTH (hPTH, 1-38) was administered to ten-week-old intact female mice by daily sc injection for 28 days, at doses of 1, 10, 100 microg/kg. In a subsequent study, intact female mice were given PTH and/or 17beta-estradiol (E2) 10 and 40 microg/kg/day respectively. Femoral BMD was assessed by peripheral DXA (PIXImus), and histomorphometry was performed to analyse changes in cancellous and cortical bone. PTH caused a small gain in femoral BMD, and increased the extent of periosteal bone formation surfaces, but had relatively little effect on other skeletal parameters when given alone. As previously found, E2 produced a large increase in femoral BMD, stimulated cancellous and endocortical bone formation, but inhibited periosteal bone formation. In mice treated with combination therapy, a greater increase in femoral BMD was observed compared to that following treatment with either agent alone. No differences in indices of cancellous bone were found between animals treated with E2 compared to the combination group. However, cortical area and periosteal bone formation rate were significantly greater in the latter group. We conclude that PTH and E2 exert an additive effect on bone mass in long bones of female mice, possibly reflecting an ability of PTH to oppose E2-induced suppression of periosteal bone formation.

Absorptiometry, Photon↗
PubMed2001

Incorporation of alpha-linolenic acid and linoleic acid into human respiratory epithelial cell lines.

Animal and human studies designed to examine the effects of alpha-linolenic acid (ALA) and linoleic acid (LA) supplementation on the fatty acid composition of plasma and tissues have demonstrated a marked difference in incorporation into phospholipids of these 18-carbon precursors of the long-chain polyunsaturates. Whereas tissue phospholipid levels are linearly related to dietary ALA and LA, the levels of tissue LA can be 10-fold higher than tissue ALA even when dietary levels are equivalent. There is some dispute whether this disparity is due to ALA being more rapidly metabolized to its products or substantially oxidized by the liver, or whether LA but not ALA is readily incorporated into cellular phospholipids. We examined the level of incorporation of polyunsaturated fatty acids into human respiratory epithelial cell lines (A549, 16HBE) by determining the dose-dependent incorporation of ALA and LA as free fatty acid (5-150 microg FFA/mL). Cell membrane phospholipid ALA and LA were both increased up to approximately 20-30% total fatty acids, with a concomitant decrease predominantly in monounsaturated membrane fatty acids, before significant toxicity was observed (50 microg/mL). Our data support the concept that rather than any inherent inability by human cells to incorporate ALA into membrane phospholipids, the lack of ALA content in human and animal tissues in vivo is due to the rapid metabolism or oxidation of this fatty acid in the liver.

Arachidonic Acid↗
PubMed2001

Environmental enrichment: effects on spatial memory and hippocampal CREB immunoreactivity.

Environmental enrichment has been shown to improve performance in tests of spatial memory, induce neurogenesis in the hippocampus, enhance survival of newly formed granule cells, and inhibit spontaneous apoptosis. Although neuroplasticity of the mammalian brain declines with age, recent evidence suggests that the adult brain exhibits significant plasticity in response to environmental stimulation. The present study was designed to evaluate the effect of environmental enrichment on spatial memory and on immunoreactivity to cAMP response element binding protein (CREB) from the hippocampus. C57/BL/6 mice were trained in a Morris water maze after exposure to an enriched environment, either from 35 to 94 days or from 100 to 159 days of age. Hippocampal tissue from representative animals was later analyzed by Western blot for CREB immunoreactivity. Results indicate that environmental enrichment (particularly during the earlier period) improved performance on the Morris water maze and tended to increase immunoreactivity to CREB in the hippocampus. Social interaction by itself did not result in significant differences in navigational performance. Results with regard to social interaction and CREB immunoreactivity were mixed. Results are discussed in terms of evaluating the construct of enrichment, the correlation of CREB transcription and behavior change, and the importance of the developmental period for enrichment.

Animals↗
PubMed2001

Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis.

OBJECTIVES: To assess the serum and lower respiratory tract tobramycin concentrations (C(T)) produced by a single dose of tobramycin for inhalation delivered by a nebulizer and a compressor in patients with cystic fibrosis (CF) 6 months to 6 years of age. STUDY DESIGN: We performed a dose escalation study of serum C(T) measured before and 0.5, 1, 2, and 4 hours after a single dose of inhaled tobramycin, either 180 mg (10 patients) or 300 mg (19 patients). In a separate group of 12 patients, epithelial lining fluid (ELF) C(T) was measured by bronchoalveolar lavage 30 to 45 minutes after a 300-mg dose. RESULTS: A 180-mg dose of inhaled tobramycin produced a mean peak serum C(T) of 0.5 microg/mL (SD 0.4; range, <0.2 to 1.4 microg/mL). A 300-mg dose produced a mean peak serum C(T) of 0.6 microg/mL (SD 0.5; range, <0.2 to 1.2 microg/mL). These peak values are well below the accepted maximum trough concentration with parenteral dosing (2 microg/mL). The target ELF C(T) was 20 microg/mL, 10-fold greater than the minimal inhibitory concentration for most Pseudomonas aeruginosa isolates from very young patients with CF (2 microg/mL). Mean ELF C(T) was 90 microg/mL (SD 54; range, 16 to 204 microg/mL) and exceeded the target concentration in 11 patients. CONCLUSION: In patients with CF ages 6 months to 6 years, a single 300-mg dose of inhaled tobramycin appears to produce safe peak serum concentrations and drug concentrations in the bactericidal range in the lower respiratory tract.

Administration, Inhalation↗
PubMed2001

Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum.

The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.

Amino Acid Sequence↗
PubMed2001

Some nemerteans (Nemertea) from Queensland and the Great Barrier Reef, Australia.

Three species of marine nemerteans described and illustrated from Queensland and the Great Barrier Reef, Australia, include one new genus and two new species: these are the monostiliferous hoplonemerteans Thallasionemertes leucocephala gen. et sp. nov. and Correanemertes polyophthalma sp. nov. A new colour variety of the heteronemertean Micrura callima is also reported, this species previously only being known from Rottnest Island, Western Australia. A key for the field identification of the marine nemerteans recorded from coastal Queensland and the Great Barrier Reef is provided.

Animals↗
PubMed2000

Evidence of a chronic systemic cause of instability of atherosclerotic plaques.

BACKGROUND: Major thrombotic and embolic complications of atherosclerosis are closely associated with irregularity and rupture of atheromatous plaques in both the carotid and coronary arteries. Plaque instability is partly determined by local factors, but systemic factors, such as infection, autoimmunity, or genes, may also be important. If plaque stability is influenced by systemic factors that are present in only a proportion of patients, some individuals should be more prone to rupture of plaques than others--ie, irregular plaques should occur in multiple vascular beds in some individuals more frequently than would be expected by chance alone. METHODS: We studied 5393 carotid bifurcation angiograms from 3007 patients with a recently symptomatic carotid stenosis. We assessed the extent to which plaque-surface irregularity at the symptomatic carotid artery was associated with irregularity at a distant site, the contralateral carotid artery, and the extent to which plaque irregularity at these sites was associated with previous myocardial infarction or subsequent non-stroke vascular death (due mainly to coronary-artery disease). FINDINGS: Patients with plaque-surface irregularity (n=1897) in the symptomatic carotid artery were more likely than those with smooth plaque (n=110) to have irregularity in the contralateral carotid artery (odds ratio 2.21 [95% CI 1.62-3.01], p<0.001). Patients with irregular plaques in both arteries were more likely to have had a previous myocardial infarction than patients with smooth plaques (hazard ratio 1.82 [1.23-2.64], p<0.001), and were more likely to have a non-stroke vascular death on follow-up (hazard ratio 1.67 [1.15-2.44], p=0.007). However, there was no difference in the risk of non-vascular death (hazard ratio 0.92 [0.57-1.45], p=0.5). These associations were not explicable on the basis of differences in traditional vascular risk factors. INTERPRETATION: These data suggest that some individuals have a systemic predisposition to irregularity and rupture of atherosclerotic plaques that is independent of traditional vascular risk factors. This finding supports the hypothesis that other systemic factors are important in the cause of plaque instability.

Angiography↗
PubMed2000

Utilization of docosahexaenoic acid from intravenous egg yolk phospholipid.

Docosahexaenoic acid (DHA, 22:6n-3) is provided directly to human premature infants during parenteral nutrition from the egg yolk fraction of an intravenous fat emulsion. This study aimed to determine whether the high egg yolk phospholipid content of Intralipid 10% (IL 10%, Pharmacia, Uppsala, Sweden) relative to the standard emulsion Intralipid 20% (IL 20%, Pharmacia) could be a strategy to increase the delivery of DHA to the developing brain. Male, Large White piglets were randomly selected from sows 3 d after birth. Piglets were assigned to receive a 9-d continuous intravenous infusion commencing 5 d after birth of either Intralipid (IL) 10%, IL 20%, or Lipofundin S 20% (LFS; B. Braun, Melsungen, Germany). There were four piglets in each treatment group. IL 10% provides twice as much DHA as IL 20%, while LFS provides no DHA. Protein and other nutrients were provided enterally using a low-fat milk formula. After 9 d, animals were killed, and the fatty acid compositions of blood, liver, and cerebral cortex were analyzed. IL 10% infusion approximately doubled the amount of plasma phospholipid DHA (microg/mL of plasma) in comparison to IL 20%. However, red blood cells, liver, and cerebral cortex phospholipid DHA levels were indistinguishable between these two groups. LFS was associated with reduced levels of DHA in plasma, red blood cell and liver phospholipids in comparison to IL 20%. We conclude that infusion of additional phospholipid is an ineffective strategy for increasing DHA delivery to piglet tissues. This may be due to the formation of inert phospholipid particles in plasma. The data do not support the concept of using IL 10% as a means of providing additional DHA to premature human infants.

Animals↗
PubMed2000

Photolytic degradation of florasulam on soil and in water.

The rate and pathway of degradation in the presence of light for the triazolopyrimidine herbicide florasulam was determined on soil and in aqueous systems. Florasulam was exposed to natural sunlight for up to 32 days; solar irradiance was measured with either chemical actinometers or by radiometry. The quantum yield for direct photodegradation in a sterile, buffered aqueous solution was determined to be 0.096; an analogous quantum yield for the sum of direct and indirect photodegradation on soil was 0.245. The quantum yields were used to estimate half-lives due to photodegradation as a function of season and temperature. Estimated half-lives due to photodegradation in summer at 40 degrees N latitude were 14 days on soil and 36 days in sterile, buffered water. Photodegradation was much faster in a natural water system, with a measured half-life of 3.3 days in summer at 51.5 degrees N latitude, indicating that indirect photolytic processes will be important contributors to photodegradation of florasulam in aqueous environments.

Herbicides↗
PubMed2000

Effects of massage in acute and critical care.

This is a discussion of the results of a systematic review of 22 articles examining the effect of massage on relaxation, comfort, and sleep. The most consistent effect of massage was reduction in anxiety. Eight of 10 original research studies reported that massage significantly decreased anxiety or perception of tension. Seven of 10 studies found that massage produced physiologic relaxation, as indicated by significant changes in the expected direction in one or more physiologic indicators. In the three studies in which the effect of massage on discomfort was investigated, it was found to be effective in reducing pain. In only three studies was the effect of massage on sleep examined. The methods for measuring sleep were unclear in two of the studies, and results were inconclusive in the other. Further research is needed to investigate the effect of massage on discomfort and promoting sleep.

Acute Disease↗
PubMed2000

Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. On behalf of the European Carotid Surgery Trialists' Collaborative Group.

BACKGROUND AND PURPOSE: The risk of ischemic stroke distal to an atherothrombotic carotid stenosis increases with the degree of stenosis. The main mechanism of stroke is thought to be embolism from fissured or ruptured plaque, but there are few published data on the relationship between plaque morphology and severity of stenosis and their independent effects on the risk of ischemic stroke. We sought to determine the interrelation between plaque surface morphology, degree of carotid stenosis, and the risk of ipsilateral ischemic stroke. METHODS: Severity of stenosis and plaque surface morphology were assessed on angiograms of the symptomatic carotid artery in 3007 patients in the European Carotid Surgery Trial and were related to baseline clinical characteristics, pathological characteristics of plaques examined at endarterectomy, and the risks of carotid territory ipsilateral ischemic stroke and other vascular events on follow-up. RESULTS: The early risk of ipsilateral ischemic stroke on medical treatment was closely related to the degree of carotid stenosis. However, the initial degree of carotid stenosis was not predictive of strokes occurring >2 years after randomization. Angiographic plaque surface irregularity and plaque surface thrombus at endarterectomy increased in frequency as the degree of stenosis increased (both P<0.0001). However, the degree of stenosis was still predictive of the 2-year risk of stroke on medical treatment after correction for plaque surface irregularity. Angiographic plaque surface irregularity was an independent predictor of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis (hazard ratio=1.80; 95% CI, 1. 14 to 2.83; P=0.01). This relationship was maintained when the analysis was confined to strokes occurring >2 years after randomization (hazard ratio=2.75; 95% CI, 1.30 to 5.80; P=0.01). Neither the degree of stenosis nor plaque surface irregularity was predictive of the "background" stroke risk after endarterectomy or the risk of nonstroke vascular events. CONCLUSIONS: Angiographic plaque surface irregularity is associated with an increased risk of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis. The increase in stroke risk with degree of stenosis is partly accounted for by the parallel increase in plaque surface irregularity and thrombus formation, but the degree of narrowing of the vessel lumen is still an independent predictor of ischemic stroke within 2 years of presentation.

Aged↗
PubMed1999

Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori.

Helicobacter pylori, one of the most common bacterial pathogens of humans, colonizes the gastric mucosa, where it appears to persist throughout the host's life unless the patient is treated. Colonization induces chronic gastric inflammation which can progress to a variety of diseases, ranging in severity from superficial gastritis and peptic ulcer to gastric cancer and mucosal-associated lymphoma. Strain-specific genetic diversity has been proposed to be involved in the organism's ability to cause different diseases or even be beneficial to the infected host and to participate in the lifelong chronicity of infection. Here we compare the complete genomic sequences of two unrelated H. pylori isolates. This is, to our knowledge, the first such genomic comparison. H. pylori was believed to exhibit a large degree of genomic and allelic diversity, but we find that the overall genomic organization, gene order and predicted proteomes (sets of proteins encoded by the genomes) of the two strains are quite similar. Between 6 to 7% of the genes are specific to each strain, with almost half of these genes being clustered in a single hypervariable region.

Duodenal Ulcer↗
PubMed1999

Premature infants fed mothers' milk to 6 months corrected age demonstrate adequate growth and zinc status in the first year.

The objective of this investigation was to describe zinc status to 12 months corrected age in premature infants fed their mother's milk in relation to nutritional management in hospital and post-hospital discharge. Twenty-five premature infants fed their mother's milk in hospital were randomized to receive either a multi-nutrient fortifier (MNF), providing protein, calcium, phosphorus and zinc (MM + MNF) or calcium and phosphorus alone (MM + CaGP). Twelve preterm infants fed a preterm formula (PTF) served as a comparison group. At 35 weeks post-menstrual age zinc retention was determined using the stable isotope tracer 70Zn. After hospital discharge infants in MM + MNF and MM + CaGP were designated to a mother's milk-feeding group to 6 months corrected age (Post-MM) or formula feeding group (Post-FF) based on parental choice of feeding practice. Anthropometry was performed at term, three, 6 and 12 months corrected age. At 6 and 12 months corrected age a hair sample was obtained to determine hair zinc concentrations. Preterm infants receiving supplemental zinc in hospital, as MNF, had significantly greater zinc retention in hospital compared to MM + CaGP but not greater hair zinc concentrations at 6 or 12 months corrected age. Despite significantly lower zinc intakes to 6 months corrected age, Post-MM had significantly greater hair zinc concentrations at 6 months compared to PTF (median[25-75th percentile]: 146[106-190] versus 85[54-91] microg/g, P < 0.05). Hair zinc in Post-FF (124[77-163] microg/g) was lower than Post-MM, but this was not significant (P = 0.09). Only in Post-MM were hair zinc concentrations above the median of reference values from term born infants at 12 months corrected age. Mean values of weight, length and head circumference of the preterm infants in Post-MM, Post-FF and PTF groups were between the 3rd and 97th percentiles derived from WHO reference growth standards for mother's milk-fed term infants. Our findings suggest that supplemental zinc either in hospital or post-hospital discharge does not appear to be required for preterm infants fed their mother's milk.

Analysis of Variance↗
PubMed1999

Low recall of local television health care news segment topics, sponsors and program names.

In an effort to examine the effectiveness of hospitals' sponsoring of local broadcast news health care segments, viewer recall of information presented in news reports, the program name of the reports, and the names of the hospital sponsors of those reports were analyzed. Despite the fact that telephone survey respondents said they place a higher value on televised health care information than they do for other mass media, recall was found to be generally poor. A majority of respondents could not name the topic of the televised health news report they had viewed, the program name or the program sponsor.

Adolescent↗