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Biomedical subjects

J Barnett

Publications and source records attributed to J Barnett.

At least 19 recordsLinked to original sources
PubMed2006

Human Vero cytotoxigenic Escherichia coli (VTEC) O157 infection linked to birds.

Vero cytotoxin-producing Escherichia coli O157 (VTEC O157) infections are a threat to public health. VTEC O157 has been isolated from gulls but evidence of transmission to humans from birds has not been reported. We recount an incident of VTEC O157 infection affecting two sibling children who had no direct contact with farm animals. An outbreak control team was convened to investigate the source of infection, its likely mode of transmission, and to advise on control measures. Human and veterinary samples were examined and the human isolates were found to be identical to an isolate from a sample of bird (rook) faeces. Cattle, rabbit and environmental samples were negative. This report provides evidence that birds may act as intermediaries for human infection with VTEC O157.

Animals↗
PubMed2004

Botulinum toxin injection after biliary sphincterotomy.

BACKGROUND AND STUDY AIMS: Endoscopic biliary sphincterotomy in patients with sphincter of Oddi dysfunction (SOD) is associated with a high risk of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP), which may be secondary to residual pancreatic sphincter hypertension. It was hypothesized that botulinum toxin injection could be used to reduce pancreatic sphincter hypertension temporarily in SOD patients after biliary sphincterotomy, thereby reducing the rate of procedure-induced pancreatitis. PATIENTS AND METHODS: All patients undergoing ERCP with manometry due to a suspected biliary SOD were asked to participate in the study. Patients with elevated basal sphincter pressures were randomly assigned to receive either botulinum toxin or a sham saline injection after biliary sphincterotomy. Fifty units of botulinum toxin were delivered via a sclerotherapy needle in the form of two 25-U injections of 0.25 ml each into the pancreatic sphincter. In patients in the sham arm, 0.50 ml of saline was injected into the duodenal lumen. RESULTS: Between 12 February 1999 and 29 November 2000, a total of 98 patients were referred for ERCP with manometry; 86 consented to participate in the study, and 26 had elevated baseline pressures and underwent random assignment. Twelve received botulinum toxin injection and 14 were randomly assigned to receive the sham injection. A total of six patients in the sham group (43 %) developed procedure-induced pancreatitis, compared with three patients in the botulinum toxin group (25 %; P = 0.34). CONCLUSIONS: Biliary sphincterotomy in patients with sphincter of Oddi dysfunction without pancreatic protection is risky and should no longer be carried out. This study demonstrates that botulinum toxin injection into the residual pancreatic sphincter after biliary sphincterotomy is technically feasible and safe, showing a trend toward a reduced post-ERCP pancreatitis rate in patients with sphincter of Oddi dysfunction. Further studies will need to confirm the validity of these experimental results before this technique can be used routinely.

Acute Disease↗
PubMed2003

Complex chimeras to map ligand binding sites of GPCRs.

Family 1a GPCRs are thought to bind small molecule ligands in a pocket comprising sequences from non-contiguous transmembrane helices. In this study, receptor-ligand binding determinants were defined by building a series of complex chimeras where multiple sequences were exchanged between related G-protein coupled receptors. Regions of P2Y(1), P2Y(2) and BLT(1) predicted to interact with nucleotide and leukotriene ligands were identified and receptors were engineered within their transmembrane helices to transpose the ligand binding site of one receptor on to another receptor. Ligand-induced activation of chimeras was compared with wild-type receptor activation in a yeast reporter gene assay. Binding of ligand to a P2Y(2)/BLT(1) chimera confirmed that the ligand binding determinants of BLT(1) are located in the upper regions of the helices and extracellular loops of this receptor and that they had been successfully transferred to a receptor that normally binds unrelated ligands.

Amino Acid Sequence↗
PubMed2001

Serial regulation of transcriptional regulators in the yeast cell cycle.

Genome-wide location analysis was used to determine how the yeast cell cycle gene expression program is regulated by each of the nine known cell cycle transcriptional activators. We found that cell cycle transcriptional activators that function during one stage of the cell cycle regulate transcriptional activators that function during the next stage. This serial regulation of transcriptional activators forms a connected regulatory network that is itself a cycle. Our results also reveal how the nine transcriptional regulators coordinately regulate global gene expression and diverse stage-specific functions to produce a continuous cycle of cellular events. This information forms the foundation for a complete map of the transcriptional regulatory network that controls the cell cycle.

Cell Cycle↗
PubMed2001

Zebrafish E-cadherin: expression during early embryogenesis and regulation during brain development.

Zebrafish E-cadherin (cdh1) cell adhesion molecule cDNAs were cloned. We investigated spatial and temporal expression of cdh1 during early embryogenesis. Expression was observed in blastomeres, the anterior mesoderm during gastrulation, and developing epithelial structures. In the developing nervous system, cdh1 was detected at the pharyngula stage (24 hpf) in the midbrain-hindbrain boundary (MHB). Developmental regulation of MHB formation involves wnt1 and pax2.1. wnt1 expression preceded cdh1 expression during MHB formation, and cdh1 expression in the MHB was dependent on normal development of this structure.

Animals↗
PubMed2001

Human jejunal permeability of two polar drugs: cimetidine and ranitidine.

PURPOSE: To determine the human jejunal permeability of cimetidine and ranitidine using a regional jejunal perfusion approach, and to integrate such determinations with previous efforts to establish a baseline correlation between permeability and fraction dose absorbed in humans for soluble drugs. METHODS: A sterile multi-channel perfusion tube, Loc-I-Gut, was inserted orally and positioned in the proximal region of the jejunum. A solution containing cimetidine or ranitidine and phenylalanine, propranolol, PEG 400, and PEG 4000 was perfused through a 10 cm jejunal segment in 6 and 8 subjects, respectively. RESULTS: The mean Peff (+/- se) of cimetidine and ranitidine averaged over both phases were 0.30 (0.045) and 0.27 (0.062) x 10(-4) cm/s, respectively, and the differences between the two were found to be statistically insignificant. The mean permeabilities for propranolol, phenylalanine, and PEG 400 averaged over both phases and studies were 3.88 (0.72), 3.36 (0.50), and 0.56 (0.08) x 10(-4) cm/s, respectively. The differences in permeability for a given marker were not significant between phases or between the two studies. CONCLUSIONS: The 10-fold lower permeabilities found for cimetidine and ranitidine in this study, compared to propranolol and phenylalanine, appear to be consistent with their less than complete absorption in humans.

Adolescent↗
PubMed2001

First cut, then blend: an electrocautery technique affecting bleeding at sphincterotomy.

BACKGROUND AND STUDY AIMS: The use of pure cut electrocautery current for endoscopic sphincterotomy lowers pancreatitis rates following endoscopic retrograde cholangiopancreatography (ERCP), but at the expense of greater localized bleeding which partially obscures the endoscopic view. We hypothesized that localized bleeding could be decreased by using blended current at the end of the sphincterotomy, without losing the benefit associated with pure cut current of lower post-ERCP pancreatitis benefit. PATIENTS AND METHODS: Patients undergoing sphincterotomy were randomly allocated to receive pure cut current alone or a sequential combination of pure cut then blended current. In the sequential combination patients, the first 75 - 80 % of the sphincterotomy was done using pure cut current at 30 W and the remainder completed at a blend 2 setting (pure cut plus coagulation current), also at 30 W. RESULTS: 142 patients were enrolled in the study. No statistical difference was noted between the two groups in the rates of overall pancreatitis or bleeding requiring transfusion. When comparing visible bleeding rates (more than a few drops), we found that there was significantly more bleeding (P < 0.05) in the pure cut group (31/75, 41 %) at the time of sphincterotomy compared with the sequential combination group (16/67, 23 %). CONCLUSIONS: A sequential combination of pure cut and blended current for sphincterotomy caused less visible bleeding than pure cut alone. This occurred without a change in the rate of post-ERCP pancreatitis.

Acute Disease↗
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↗