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Biomedical subjects

P Hart

Publications and source records attributed to P Hart.

At least 19 recordsLinked to original sources
PubMed2006

Beta blockers in the management of chronic kidney disease.

The sympathetic nervous system modulates renal function through its receptors namely beta1 (cardiac output and renin release), alpha1 (systemic and renovascular constriction), and beta2 renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to increasing the risk of cardiovascular events as well as increasing renal disease progression. Recent evaluations of drug use in people with CKD shows a remarkably low percentage of patients receiving beta-blockers, especially in more advanced stage CKD when cardiovascular risk is higher. This is in large part due to tolerability of these agents. Moreover, water-soluble beta-blockers such as atenolol and metoprolol are dialyzable and require supplementation to avoid exacerbation of arrhythmias following dialysis. Newer vasodilating beta-blockers have better tolerability and different effects on renal hemodynamics as well as metabolic variables. These effects are related to the relative alpha1-blocking effect of agents such as carvedilol and labetolol, with carvedilol having relatively greater alpha-blocking effects. Few studies evaluate beta-blockers on cardiovascular risk in CKD patients. Studies with carvedilol demonstrate attenuated increases in albuminuria as well as reduction in cardiovascular events in CKD patients with hypertension. This paper reviews the animal and clinical trial data that evaluate beta-blockers in CKD highlighting the vasodilating beta-blockers. It is apparent that greater use of this drug class for blood pressure control would further enhance reduction of risk of heart failure, the most common cause of death in the first year of starting dialysis.

Adrenergic beta-Antagonists↗
PubMed2006

Predicting susceptibility and incubation time of human-to-human transmission of vCJD.

BACKGROUND: Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility. METHODS: Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene. Since the human PrP gene has variation at codon 129, with MM, VV, and MV genotypes, three inbred lines with an identical genetic background were produced to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were inoculated with BSE or vCJD and assessed for clinical and pathological signs of disease. FINDINGS: BSE was transmitted to the bovine line but did not transmit to the human lines. By contrast, vCJD was transmitted to all three human lines with different pathological characteristics for each genotype and a gradation of transmission efficiency from MM to MV to VV. INTERPRETATION: Transmission of BSE to human beings is probably restricted by the presence of a significant species barrier. However, there seems to be a substantially reduced barrier for human-to-human transmission of vCJD. Moreover, all individuals, irrespective of codon-129 genotype, could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue.

Amyloid↗
PubMed2006

The transmissible spongiform encephalopathies: emerging and declining epidemics.

TSEs (transmissible spongiform encephalopathies) are neurodegenerative diseases of various mammalian species, the best known of which include BSE (bovine spongiform encephalopathies) in cattle, CJD (Creutzfeldt-Jakob disease) in humans, scrapie in sheep and CWD (chronic wasting disease) in deer. This review examines the emergence of various TSE strains and their transmission, and discusses disease surveillance and control.

Creutzfeldt-Jakob Syndrome↗
PubMed2003

The natural (baseline) quality of groundwater: a UK pilot study.

Knowledge of the natural baseline quality of groundwaters is an essential prerequisite for understanding pollution and for imposing regulatory limits. The natural baseline of groundwaters may show a range of concentrations depending on aquifer mineralogy, facies changes, flow paths and residence time. The geochemical controls on natural concentrations are discussed and an approach to defining baseline concentrations using geochemical and statistical tools is proposed. The approach is illustrated using a flowline from the Chalk aquifer in Berkshire, UK where aerobic and anaerobic sections of the aquifer are separately considered. The baseline concentrations for some elements are close to atmospheric values whereas others evolve through time-dependent water-rock interaction. Certain solutes (K, NH(4)(+)), often considered contaminants, reach naturally high concentrations due to geochemical controls; transition metal concentrations are generally low, although their concentrations may be modified by redox controls. It is recommended that the baseline approach be incorporated into future management strategies, notably monitoring.

Journal Article↗
PubMed2002

Association of salivary Streptococcus mutans with caries in young children: effect of dental health education on salivary levels.

AIM: This study aimed to determine the effect of a long-term dental health education (DHE) for mothers with young children on the level of salivary Streptococci mutans (SM) and their association with caries in young children. METHODS: A randomly selected cohort of 228 children born between 1 January and 30 September 1995, in a low socioeconomic high caries suburb of Leeds (UK), was divided into the following groups: A) DHE focused on diet; B) DHE focused on oral hygiene instruction (OHI) using fluoride toothpaste; C) DHE by a combined diet and OHI message. DHE was given using an interview and counselling for at least 15 minutes in each child's home, every three months for the first two years and twice a year in the third year of the study. A fourth group D was given diet and OHI, at home, but once a year only. The children in a fifth group E (control), received no DHE and were never visited, but examined at three years of age only. All children and mothers were examined for caries using the BASCD criteria. The levels of salivary SM were determined by sampling of bacteria from the oral cavity with a 1.8 cm wide wooden spatula, after giving the mother a paraffin pellet to chew for a minute and in children using unstimulated saliva. Bacteria were plated out and counted using image analysis for counting colonies. RESULTS: At three years of age the difference in the level of salivary SM between groups was not statistically significant. However, in group E there was a statistically significant relationship (p<0.05) between salivary SM and caries in children. CONCLUSION: The difference in the level of salivary SM between groups given various programs of dental health education was not statistically significant. There was a statistically significant (p<0.05) relationship between salivary MS and caries in children.

Clinical Trial↗
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

Visualization of secreted Hrp and Avr proteins along the Hrp pilus during type III secretion in Erwinia amylovora and Pseudomonas syringae.

Pili are required for protein and/or DNA transfer from bacteria to recipient plant or bacterial cells, based on genetic evidence. However, it has never been shown directly that the effector proteins or DNA are localized along or inside the pili in situ. Failure to visualize an association of effector proteins/DNA with pili is the central issue in the debate regarding the exact function of pili in protein and DNA transfer. In this study, a newly developed in situ immunogold labelling procedure enabled visualization of the specific localization of type III effector proteins of Erwinia amylovora and Pseudomonas syringae pv. tomato along the Hrp pilus, but not along the flagellum or randomly in the intercellular space. In contrast, PelE, a pectate lyase secreted via the type II protein secretion system, was not associated with the Hrp pilus. These results provide direct evidence that type III secretion occurs only at the site of Hrp pilus assembly and that the Hrp pilus guides the transfer of effector proteins outside the bacterial cell, favouring the 'conduit/guiding filament' model.

Animals↗
PubMed2001

Acute fatty liver of pregnancy associated with short-chain acyl-coenzyme A dehydrogenase deficiency.

There is a correlation between pregnancy complications such as acute fatty liver of pregnancy and long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency. We diagnosed another fatty acid beta-oxidation defect, short-chain acyl-coenzyme A dehydrogenase deficiency, in an infant when evaluating him because his mother had acute fatty liver of pregnancy. Other beta-oxidation defects, in addition to LCHAD deficiency, should be considered in children born after pregnancies complicated by liver disease.

Adult↗
PubMed2001

Immunogold labeling of Hrp pili of Pseudomonas syringae pv. tomato assembled in minimal medium and in planta.

Hypersensitive reaction and pathogenicity (hrp) genes are required for Pseudomonas syringae pv. tomato (Pst) DC3000 to cause disease in susceptible tomato and Arabidopsis thaliana plants and to elicit the hypersensitive response in resistant plants. The hrp genes encode a type III protein secretion system known as the Hrp system, which in Pst DC3000 secretes HrpA, HrpZ, HrpW, and AvrPto and assembles a surface appendage, named the Hrp pilus, in hrp-gene-inducing minimal medium. HrpA has been suggested to be the Hrp pilus structural protein on the basis of copurification and mutational analyses. In this study, we show that an antibody against HrpA efficiently labeled Hrp pili, whereas antibodies against HrpW and HrpZ did not. Immunogold labeling of bacteria-infected Arabidopsis thaliana leaf tissue with an Hrp pilus antibody revealed a characteristic lineup of gold particles around bacteria and/or at the bacterium-plant contact site. These results confirm that HrpA is the major structural protein of the Hrp pilus and provide evidence that Hrp pili are assembled in vitro and in planta.

Agar↗
PubMed2001

Frequency of celiac disease in individuals with Down syndrome in the United States.

Ninety-three individuals with Down syndrome (DS) were screened to investigate the prevalence of celiac disease (CD) in the United States. Five of the 93 individuals were antiendomysial antibody (EMA) positive. Of the 5 who tested positive for EMA, 4 were biopsied, 1 refused biopsy. Three of the 4 individuals biopsied manifested changes of CD on small bowel biopsy. This gives a frequency of 3.2% of confirmed CD in our DS individuals and suggests the need for periodic screening for celiac disease in this population.

Adolescent↗
PubMed2000

Conversion from tacrolimus to cyclosporin in stable renal transplant patients: safety, metabolic changes, and pharmacokinetic comparison.

BACKGROUND: Conversion from tacrolimus to cyclosporin has not previously been reported as routine clinical practice, but only as indicated by rejection or adverse effects. METHODS: The safety and metabolic outcome of elective conversion from tacrolimus to cyclosporin was examined in 19 recipients of cadaver renal transplants. Conversion was performed in stable patients at 3-6 months after transplantation. RESULTS: Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0.65-1) mmol/liter (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/liter (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporin (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration postdose (Cmax), minimum concentration postdose (Cmin), time to maximum concentration (Tmax). CONCLUSION: This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporin-based immunosuppression in stable patients after renal transplantation. This conversion was performed without early immunological hazard, but there was a small rise in blood cholesterol levels after conversion. Pharmacokinetic studies showed cyclosporin in the form of Neoral showed less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.

Adult↗
PubMed2000

Conversion from tacrolimus to cyclosporine in stable renal transplant patients: safety, metabolic changes, and pharmacokinetic comparison.

BACKGROUND: Although conversion between tacrolimus and cyclosporine has been performed when indicated for rejection or adverse effects, the safety and metabolic outcome of elective conversion from tacrolimus to cyclosporine has not previously been examined. METHODS: Conversion from tacrolimus to cyclosporine was performed in 19 recipients of cadaver renal transplants at 3-6 months after transplantation. Pharmacokinetic profiles and biochemical studies were performed three times, in steady state, before, and after conversion. RESULTS: Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0.65-1) mmol/L (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/L (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporine (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration after dose (Cmax), minimum concentration after dose (Cmin), and time to maximum concentration (Tmax). CONCLUSION: This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporine-based immunosuppression in stable patients after renal transplantation. This conversion was performed without early immunological hazard, but there was a small rise in blood cholesterol levels after conversion. Pharmacokinetic studies showed that cyclosporine in the form of Neoral exhibited less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.

Adult↗
PubMed2000

Acylcarnitines in plasma and blood spots of patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase defiency.

The acylcarnitines in plasma and blood spots of 23 patients with proven deficiency of long-chain 3-hydroxyacylcoenzyme A dehydrogenase were reviewed. Long-chain 3-hydroxyacylcarnitines of C14:1, C14, C16 and C18:1 chain length, and long-chain acylcarnitines of C12, C14:1, C14, C16, C18:2 and C18:1 chain length were elevated. Acetylcarnitine was decreased. In plasma, elevation of hydroxy-C18:1 acylcarnitine over the 95th centile of controls, in combination with an elevation of two of the three acylcarnitines C14, C14:1 and hydroxy-C16, identified over 85% of patients with high specificity (less than 0.1% false positive rate). High endogenous levels of long-chain acylcarnitines in normal erythrocytes reduced the diagnostic specificity in blood spots compared with plasma samples. The results were also diagnostic in asymptomatic patients, and were not influenced by genotype. Treatment with diet low in fat and high in medium-chain triglyceride decreased all disease-specific acylcarnitines, often to normal, suggesting that this assay is useful in treatment monitoring.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

Laboratory findings associated with thrombophilia are not more common in inflammatory bowel disease.

Thromboembolic disease (TED) has been recognized as a complication of inflammatory bowel disease (IBD) since the 1930s (Bargen & Barker 1936). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency is unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously, when the disease is in clinical remission (Talbot et al. 1986; Jackson et al. 1997). Studies looking at the prevalence of specific thrombophilic states such as Antithrombin III deficiency (Jackson et al. 1997; Lake, Stauffer & Stuart 1978; Cianco et al. 1996; Ghosh et al. 1983), Factor V Leiden mutation (APC Resistance) (Jackson et al. 1997; Probert et al. 1997; Ardizzone et al. 1998; Liebman et al. 1998), anticardiolipin antibodies (Ciancio et al. 1996), Protein C (Wyshock, Caldwell & Crowley 1988; Korsten & Reis 1992) and Protein S deficiencies (Jorens et al. 1990; Aadland et al. 1992) in IBD have been contradictory or equivocal. We had previously found that IBD patients with a history of TED are not more likely to have a laboratory thrombophilic abnormality than those with uncomplicated disease. We also demonstrated that the prevalence of heterogenous laboratory thrombophilic abnormalities (usually minor) in all IBD patients may be as high as 60%, much higher than the recognized prevalence of TED (Lim, Jones & Gould 1996). We wondered how this would compare with the healthy non-IBD population. We have therefore explored the prevalence of such thrombophilic abnormalities in a group of IBD patients who had no history of TED and compared them with healthy age and sex matched controls.

Adult↗
PubMed2000

The utility of the Digi-walker step counter to assess daily physical activity patterns.

PURPOSE: The Digi-Walker step counter is a promising and cost-effective tool to measure physical activity under free-living conditions. Two specific studies were conducted to evaluate the number of steps required to meet current physical activity guidelines. METHODS: Thirty-one adults (17 men, 14 women) served as participants. In study 1, we determined the number of steps to complete a mile under two different conditions and three paces. In study 2, we conducted a field trial to examine the relationship between daily step counts and other indices of physical activity. Participants in this study wore a Digi-Walker for 2 consecutive weeks and completed the 7-d physical activity recall (PAR) after each week. RESULTS: In study 1, there were no differences in step counts by site, but steps were inversely related to pace, with values ranging from 1330 to 1996. Individual step counts at a specific pace were negatively correlated with height, weight, leg length, and stride length and were positively correlated with body fatness. In study 2, participants had average daily step counts of 11,603 when structured vigorous activity was included and 8265 when only light and moderate activity were measured. Modest correlations were found between step counts and estimated energy expenditure. Similar correlations were observed when step counts were related to minutes of activity per day and minutes of sitting per day. CONCLUSIONS: Pedometers provide a useful indicator of daily step counts but variability in activity patterns make it difficult to establish step count guidelines that correspond with other public health guidelines.

Activities of Daily Living↗
PubMed1998

Preventing Groupthink Revisited: Evaluating and Reforming Groups in Government.

This article critically examines Janis's recommendations for preventing groupthink in high-level policymaking. It puts forward three models of small group functioning in government, each of which highlights different dimensions of collegial policymaking and distinct criteria for evaluating group performance. Each model also inspires different proposals for groupthink prevention and improvement of group performance in general. Proposals for designing and managing high-level groups in government need to take into account these multiple perspectives. Furthermore, their proponents should be aware of the institutionalized and competitive context in which political decision groups operate. Evaluations of their performance and proposals for reforming them are inevitably tied up in this process. This has important implications for the feasibility of recommendations set forth by small group analysts. The article concludes with an agenda for increasing the policy relevance and practical feasibility of research on political decision groups. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Acute and subacute changes in the ultrasound measurements of the calcaneus following intense exercise.

The amount of exercise necessary to cause bone structural change in humans is unknown. We examined whether a single bout of intense exercise in vivo leads to acute and subacute changes in the physical properties of bone as measured by ultrasound. It was hypothesized that structural changes such as accumulation of fatigue microdamage would result in a decrease in velocity of sound (VOS) and broadband ultrasound attenuation (BUA) across the calcaneus. We performed a prospective cohort study in 111 (97 M, 14 F) entrants of the 1996 Melbourne marathon (42.3 km) and 28 (10 M, 18 F) nonrunning controls. Runners had a mean (SD) age of 45.3 +/- 11.4 years (range 20-75), had completed 15.2 +/- 17.3 prior marathons (0-88), and had been running regularly for 14.2 +/- 9.2 years (0.25-50). An ultrasound densitometer (Cuba Clinical, McCue) was used to measure VOS and BUA across the right calcaneus. Runners were tested on three occasions: 1-3 days prior to, immediately after (<2 hours), and 5-6 days following the marathon. Seventy-three (66%) runners presented for all three measurements. Controls were tested on three occasions with the same time intervals as the runners. BUA values in the runners were significantly elevated by 5.0% immediately after the marathon but returned to baseline levels by the third test session (P = 0. 0001). Changes in BUA values in the controls were not significant and all were less than 0.7% (P = 0.88). Age was a significant independent predictor of the BUA change between test 1 and test 2 in the runners (beta = 0.2094; SE = 0.0917; P = 0.03). VOS measurements were not significantly different across the three testing sessions in both the runners (P = 0.07) and the controls (P = 0.33). Therefore, ultrasound measurements of BUA and VOS did not detect evidence of lasting structural change in the calcaneus following a marathon.

Adult↗