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Biomedical subjects

J Barnett

Publications and source records attributed to J Barnett.

At least 19 recordsLinked to original sources
PubMed2001

Risk perception and experience: hazard personality profiles and individual differences.

The dominance of the "psychometric" paradigm and the consequent emphasis on personality profiles of hazards has resulted in little attention being given to individual variability in risk judgments. This study examines how far differences in experience of risk activities can explain individual variability in risk assessments. A questionnaire study (n = 172) was used to explore the relationships between experience and risk perceptions in relation to 16 risk activities. It was expected that these relationships would differ for voluntary and involuntary activities. Measures of experience included assessments of "impact" and "outcome" valence as well as "frequency." These three aspects of experience each related to risk assessment but their relationship depended on whether the risk experiences were voluntary or not. The results indicate the importance of developing more fine-grained ways of indexing risk experience.

Adolescent↗
PubMed2000

A cytoskeletal basis for wood formation in angiosperm trees: the involvement of microfilaments.

The cortical microfilament (MF) component of the cytoskeleton within axial elements of the secondary vascular system of the angiosperm tree, Aesculus hippocastanum L. (horse-chestnut) was studied using transmission electron microscopy of ultrathin sections and indirect immunofluorescence microscopy of actin in thick sections. As seen by electron microscopy, MF bundles have a net axial orientation within fusiform cambial cells and their secondary vascular derivatives (i.e. in the axial xylem and phloem parenchyma, xylem fibres, vessel and sieve elements, and companion cells). Immunofluorescence studies, however, reveal that this axial orientation can be more accurately described as a helix of extremely high pitch; it is a persistent feature of all axial secondary vascular elements during their development. Helical MF arrays are the only arrangement seen in secondary phloem cells. However, in addition to helices, other MF arrays are seen in secondary xylem cells. For example, fibres possess ellipses of MFs associated with simple-pit formation, and vessel elements possess circular arrays of MFs that associate with the developing inter-vessel bordered pits, ray-vessel contact pits, and with the perforation plate. Linear MF arrays are seen co-oriented with the developing tertiary wall-thickenings in vessel elements. The possible roles of MFs during the cytodifferentiation of secondary vascular cells is discussed, and compared with that of microtubules.

Actin Cytoskeleton↗
PubMed2000

Artificial antigen-presenting cells as a tool to exploit the immune 'synapse'.

Recent progress in molecular medicine has provided important tools to identify antigen-specific T cells. In most cases, the approach is based on oligomeric combinations of recombinant major histocompatibility complex-peptide complexes fixed to various rigid supports available for binding by the T-cell receptor. These tools have greatly increased our insight into mechanisms of immune responses mediated by CD8+ T cells. Examples of the diverse fields of application for this technology include immunization, viral infections and oral tolerance induction.

Antigen Presentation↗
PubMed2000

Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients.

BACKGROUND: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). METHODS: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 micromol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. RESULTS: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. CONCLUSIONS: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.

Adult↗
PubMed2000

Can dietary assessment in general practice target patients with unhealthy diets?

Diet is important in the aetiology and management of many conditions in primary care. Although valid dietary assessment is required for both clinical work and research, no dietary assessment instruments have been validated among patients seen in primary care. A range of simple self-completion dietary assessment questionnaires and established research instruments were compared with an accepted reference standard, a seven-day weighed record, in 111 subjects assessed in a practice nurse-run treatment room. Simple self-completion tools based on food groups and portion sizes perform as well (likelihood ratios for a positive test = 2 to 3) as much more time-consuming instruments. The error in using such instruments is comparable with the error of the standard itself. There is little justification for using time-consuming dietary assessment questionnaires, since simple tools are accurate enough to be clinically useful--to allow practice nurses to target patients for counselling and waste less time on inappropriate counselling--and also useful for research.

Confidence Intervals↗
PubMed2000

Preclinical study of the systemic toxicity and pharmacokinetics of 5-iodo-2-deoxypyrimidinone-2'-deoxyribose as a radiosensitizing prodrug in two, non-rodent animal species: implications for phase I study design.

We have demonstrated previously an improved therapeutic index for oral 5-iodo-2-deoxypyrimidinone-2'-deoxyribose (IPdR) compared with oral and continuous infusion of 5-iodo-2'-deoxyuridine (IUdR) as a radiosensitizing agent using three different human tumor xenografts in athymic mice. IPdR is a prodrug that is efficiently converted to IUdR by a hepatic aldehyde oxidase, resulting in high IPdR and IUdR plasma levels in mice for > or =1 h after p.o. IPdR. Athymic mice tolerated oral IPdR at up to 1500 mg/kg/day given four times per day for 6-14 days without significant systemic toxicities. In anticipation of an investigational new drug application for the first clinical Phase I and pharmacology study of oral IPdR in humans, we studied the drug pharmacokinetics and host toxicities in two non-rodent, animal species. For the IPdR systemic toxicity and toxicology study, twenty-four male or female ferrets were randomly assigned to four IPdR dosage groups receiving 0, 15, 150, and 1500 mg/kg/day by oral gavage x 14 days prior to sacrifice on study day 15. All ferrets survived the 14-day treatment. Ferrets receiving 1500 mg/kg/day showed observable systemic toxicities with diarrhea, emesis, weight loss, and decreased motor activity beginning at days 5-8 of the 14-day schedule. Overall, both male and female ferrets receiving IPdR at 1500 mg/kg/day experienced significant weight loss (9 and 19%, respectively) compared with controls after the 14-day treatment. No weight loss or other systemic toxicities were observed in other IPdR dosage groups. Grossly, no anatomical lesions were noted at complete necropsy, although liver weights were increased in both male and female ferrets in the two higher IPdR dosage groups. Histologically, IPdR-treated animals showed dose-dependent microscopic changes in liver consisting of minimal to moderate cytoplasmic vacuolation of hepatocytes, which either occurred in the periportal area (high dosage group) or diffusely throughout the liver (lower dosage groups). Female ferrets in the highest IPdR dose group also showed decreased kidney and uterus weights at autopsy without any associated histological changes. No histological changes were found in central nervous system tissues. No significant abnormalities in blood cell counts, liver function tests, kidney function tests, or urinalysis were noted. Hepatic aldehyde oxidase activity was decreased to approximately 50 and 30% of control ferrets in the two higher IPdR dosage groups, respectively, after the 14-day treatment period. The % IUdR-DNA incorporation in ferret bone marrow at the completion of IPdR treatment was < or =0.05% in the two lower dosage groups and approximately 2% in the 1500 mg/kg/day dosage group. The % IUdR-DNA in normal liver was < or =0.05% in all IPdR dosage groups. In a pharmacokinetic study in four Rhesus monkeys, we determined the plasma concentrations of IPdR after a single i.v. bolus of 50 mg/kg over 20 min. Using a two-compartment model to fit the plasma pharmacokinetic data, we found that IPdR was cleared in these non-human primates in a biexponential manner with an initial rapid distributive phase (mean T1/2alpha = 6.5 min), followed by an elimination phase with a mean T1/2 of 63 min. The mean maximum plasma concentration of IPdR was 124+/-43 microM with a mean total body clearance of 1.75+/-0.95 l/h/kg. IPdR was below detection (<0.5 microM) in the cerebrospinal fluid. We conclude that there are dose-limiting systemic toxicities to a 14-day schedule of p.o. IPdR at 1500 mg/kg/day in ferrets that were not found previously in athymic mice. However, no significant hematological, biochemical, or histopathological changes were found. Hepatic aldehyde oxidase activity was reduced in a dose-dependent in ferret liver, suggesting partial enzyme saturation by this IPdR schedule. The plasma pharmacokinetic profile in Rhesus monkeys showing biexponential clearance is similar to our published data in athymic mice. These data are being applied

Aldehyde Oxidoreductases↗
PubMed1999

Treatment of lesions of osteomyelitis in the hind flippers of six grey seals (Halichoerus grypus).

Six rescued grey seal (Halichoerus grypus) pups had traumatic injuries to their hind flippers; three had osteomyelitis without fractures, one had a single fracture and associated osteomyelitis, and two had multiple compound fractures and large open wounds. The medical and surgical methods used to treat these lesions are described. A proprietary waterproof covering appeared to be a better method for dressing the wounds than conventional bandaging.

Animals↗
PubMed1999

A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis.

OBJECTIVE: A double-blind, multicenter, randomized trial was conducted to compare the side effects and efficacy of domperidone and metoclopramide in symptomatic diabetic gastroparesis. METHODS: Ninety-three insulin-dependent diabetes patients with a > or = 3-month history of gastroparesis symptoms were recruited; 48 received domperidone 2 x 10-mg tablets 4 times daily, and 45 received metoclopramide 1 x 10-mg tablet + 1 placebo tablet 4 times daily. Nausea, vomiting, bloating/distension, and early satiety were evaluated for severity after 2 and 4 wk. Adverse central nervous system (CNS) effects of somnolence, akathisia, asthenia, anxiety, depression, and reduced mental acuity were elicited and graded for severity at 2 and 4 wk. RESULTS: Domperidone and metoclopramide were equally effective in alleviating symptoms of diabetic gastroparesis. Elicited adverse CNS effects were more severe and more common with metoclopramide. Somnolence was acknowledged by 49% of patients (mean severity score, 1.03) after 4 wk of metoclopramide compared with 29% of patients (mean severity score, 0.49) after 4 wk of domperidone (incidence, p = 0.02; severity; p = 0.03). A reduction in mental acuity was acknowledged by 33% of patients (mean severity score, 0.62) after 4 wk of metoclopramide, compared with 20% of patients (mean severity score, 0.27) after 4 wk of domperidone (incidence, p = 0.04; severity, p = 0.04). Akathisia, asthenia, anxiety, and depression were also acknowledged less often, and at a lower severity, after 4 wk of domperidone, although these differences were not statistically significant. CONCLUSIONS: Domperidone and metoclopramide effectively reduce the symptoms of diabetic gastroparesis; CNS side effects are more pronounced with metoclopramide.

Adult↗
PubMed1999

The validity of dietary assessment in general practice.

OBJECTIVE: To validate a range of dietary assessment instruments in general practice. METHODS: Using a randomised block design, brief assessment instruments and more complex conventional dietary assessment tools were compared with an accepted "relative" standard--a seven day weighed dietary record. The standard was checked using biomarkers, and by performing test-retest reliability in additional subjects (n = 29). OUTCOMES: Agreement with weighed record. Percentage agreement with weighed record, rank correlation from scatter plot, rank correlation from Bland-Altman plot. Reliability of the weighed record. SETTING: Practice nurse treatment room in a single suburban general practice. SUBJECTS: Patients with risk factors for cardiovascular disease (n = 61) or age/sex stratified general population group (n = 50). RESULTS: Brief self completion dietary assessment tools based on food groups caten during a week show reasonable agreement with the relative standard. For % energy from fat and saturated fat, non-starch polysaccharide, grams of fruit and vegetables and starchy foods consumed the range of agreement with the standard was: median % difference -6% to 12%, rank correlation 0.5 to 0.6. This agreement is of a similar order to the reliability of the weighed record, as good as or better than test standard agreement for more time consuming instruments, and compares favourably with research instruments validated in other settings. Under-reporting of energy intake was common (40%) and more likely if subjects were obese (body mass idex (BMI) > or = 30 60% under-reported; BMI < 30 29%, p < 0.001). CONCLUSION: Under-reporting of absolute energy intake is common, particularly among obese patients. Simple self assessment tools based on food groups, designed for practice nurse dietary assessment, show acceptable agreement with a standard, and suggest such tools are sufficiently accurate for clinical work, research, and possibly population dietary monitoring.

Adolescent↗
PubMed1998

Effects of feeding Lunaria oil rich in nervonic and erucic acids on the fatty acid compositions of sphingomyelins from erythrocytes, liver, and brain of the quaking mouse mutant.

Feeding an oil from Lunaria biennis rich in 22:1n-9 and 24:1n-9 to homozygous quaking (qk.qk) mice caused a large increase in the percentage of 24:1n-9 and corresponding decreases in the percentage of 24:0 and 22:0 in sphingomyelins from liver, erythrocytes, and milk. Brain sphingomyelin from 2-wk-old qk.qk pups born to qk.qk mothers maintained on the Lunaria oil had essentially normal percentage of 24:1n-9 and 18:0, in contrast to pups born to mothers maintained on a control oil rich in 18:1n-9 whose brain sphingomyelin had a markedly reduced percentage of 24:1n-9 and an increased percentage of 18:0. After 2 wk and up to and beyond weaning, the qk.qk pups from Lunaria-fed mothers weaned on to the Lunaria diet had a markedly decreased percentage of 24:1n-9 in their brain sphingomyelin, accompanied by an increased percentage of 18:0, as compared to heterozygous quaking mice. However, the percentage of 24:1n-9 in brain sphingomyelin in qk.qk pups weaned on to the Lunaria diet continued throughout this period (2-8 wk postbirth) to be significantly higher than in qk.qk pups weaned on to the control diet. We conclude that dietary 24:1n-9 influences the fatty acid composition of brain sphingomyelin in qk.qk mice, but only via the mother in pre- or early postnatal animals. We further consider that the dietary effects may be elicited mainly in the sphingomyelin of nonmyelinated brain cells, and that the nervonic acid in myelin sphingomyelin may be formed mainly by chain elongation in oligodendrocytes from shorter chain fatty acid precursors.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Low- versus high-dose azithromycin triple therapy for Helicobacter pylori infection.

BACKGROUND: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection. METHODS: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary. RESULTS: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects. CONCLUSIONS: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

Adult↗