Novel local anaesthetic analgesic technique for tongue-tie.
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Administration, Topical↗
Biomedical subjects
J Stewart
Publications and source records attributed to J Stewart.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology.
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Antineoplastic Combined Chemotherapy Protocols↗
Restricted access to food, but not sucrose, saccharine, or salt, synchronizes the expression of Period2 protein in the limbic forebrain.
Restricted feeding schedules (RF) in which daily access to food is limited to a few hours each day can entrain the rhythms of expression of circadian clock genes in the brain and periphery in rodents. The critical factors mediating the effect of RF on rhythms of clock gene expression are unknown. Previously, we demonstrated that daytime RF shifts the phase of expression of the clock protein, Period2 (PER2) in the oval nucleus of the bed nucleus of the stria terminalis in rats kept on a 12-h light/dark cycle, and restored the rhythm of PER2 expression in rats housed in constant light. We now report that RF also modifies the rhythms of PER2 expression in the central and basolateral nuclei of the amygdala and in the dentate gyrus, such that all three areas become synchronized, peaking 12 h after the time of food presentation. Daily limited access to sucrose or saccharine in freely fed rats or scheduled access to saline in sodium-deprived rats had no effect on these PER2 rhythms. Thus, it would appear that the rhythms of PER2 in limbic forebrain structures are sensitive to signals that arise from the alleviation of a negative metabolic state associated with scheduled feeding and that access to rewarding substances in the absence of food deprivation or metabolic challenges, per se, is not sufficient to alter the rhythms of PER2 expression in these regions.
Animals↗
Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk.
Prediction of cardiovascular (CV) complications represents the Achilles' heel of end-stage renal disease. Surrogate markers of endothelial dysfunction have been advocated as predictors of CV risk in this cohort of patients. We have recently adapted a noninvasive laser Doppler flowmetry (LDF) functional testing of endothelium-dependent microvascular reactivity and demonstrated that end-stage renal disease patients are characterized by profound alterations in thermal hyperemic responsiveness. We hypothesized that such functional assessment of the cutaneous microcirculation may offer a valid, noninvasive test of the severity of endothelial dysfunction and CV risk. To test this hypothesis, we performed a cross-sectional study, in which we compared LDF measurements to conventional risk factors, and performed a pilot longitudinal study. LDF studies were performed in 70 patients and 33 controls. Framingham and Cardiorisk scores were near equivalent for low-risk patients, but more divergent as risk increased. C reactive protein (CRP) levels and LDF parameters (amplitude of thermal hyperemia (TH), area under the curve of TH) showed significant abnormality in high-risk vs low-risk patients calculated using either Framingham or Cardiorisk scores. Patients who had abnormal LDF parameters showed increased CV mortality, however, had similar risk assessments (Framingham, Cardiorisk, CRP, and homocysteine) to those with unimpaired LDF tracings. In conclusion, LDF parameters of microvascular reactivity offer a sensitive characterization of endothelial dysfunction, which may improve CV risk assessment through incorporation into the Framingham or Cardiorisk algorithm.
Adult↗
Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats.
We investigated the involvement of the adrenal glucocorticoid, corticosterone, in the control of the rhythmic expression of the circadian clock protein, Period2, in forebrain nuclei known to be sensitive to glucocorticoids, stressors and drugs of abuse, the oval nucleus of the bed nucleus of the stria terminalis and the central nucleus of the amygdala. We found previously that the daily rhythm of Period2 in these nuclei is uniquely dependent on the integrity of the adrenal glands (Amir S, Lamont EW, Robinson B, Stewart J (2004) A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci 24:781-790; Lamont EW, Robinson B, Stewart J, Amir S (2005) The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. Proc Natl Acad Sci U S A 102:4180-4184). We now show that, in rats, in the absence of the adrenals, corticosterone replacement via the drinking water, which is associated with daily fluctuations in corticosterone levels, restores the rhythm of Period2 in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. Corticosterone replacement via constant-release pellets has no effect. These results underscore the importance of circadian glucocorticoid signaling in Period2 rhythms in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala and suggest a novel mechanism whereby stressors, drugs of abuse, and other abnormal states that affect the patterns of circulating glucocorticoids can alter the functional output of these nuclei.
Adrenal Cortex↗
Models of total and presumed wildlife sources of fecal coliform bacteria in coastal ponds.
Models that accurately predict fecal coliform bacteria (FCB) concentrations, one of the most widely used measures of estuarine water quality, are needed to improve land use decision-making. Rapidly occurring changes in coastal land uses and the influence on water quality increases the urgency of having improved decision tools. For this study, samples were collected monthly from six coastal ponds, two tidal creeks and four shallow water wells for up to 212 years. These data were used along with other measures of environmental conditions and land classes within each watershed to construct quantitative relationships between combinations of variables and both total and presumed wildlife sources of FCB. Linear regression, bootstrapping and generalized additive modeling that incorporates both linear and nonlinear terms were used. Results of repeated simultaneous sampling on the same tide stage of ponds and downstream estuarine creeks suggest that most FCB come from wildlife and that the ponds effectively remove these bacteria except immediately following heavy rainfall. Predictive models for concentrations of total and presumed wildlife bacteria are provided along with simple measures to estimate watershed boundaries. It is proposed that these tools can be used to minimize impacts on receiving water body quality. The models can be used to test alternative development approaches within coastal watersheds similar to that found in the southeastern USA coastal zone as well as to evaluate specific proposed landscape alterations.
Animals↗
Factors affecting the monetary return from programmes for synchronising oestrus in dairy cows with gonadotrophin-releasing hormone and prostaglandin F2alpha.
Synchronisation, using a combination of gonadotrophin-releasing hormone and prostaglandin F2alpha injections, is commonly used to control the reproductive cycle of dairy cows. A simple model that could predict the monetary return from synchronisation would be a valuable tool in determining whether it would be worthwhile. This study used data from three controlled clinical trials to investigate the effects of six factors (interval between calving and synchronisation, 21-day submission rate, number of cows synchronised, average age, pregnancy rate of non-synchronised cows and season) on the return from synchronisation. The results suggests that the herd's submission and pregnancy rates, the time between calving and synchronisation, and the number of cows synchronised can all significantly affect the return from synchronisation, but only time since calving significantly affected the return in all three trials. They also suggest that there is no simple linear relationship between these factors and the return from synchronisation.
Age Factors↗
Association of APOE e4 and cerebrovascular pathology in traumatic brain injury.
BACKGROUND: Previous studies have found the e4 allele of the apolipoprotein E gene (APOE e4) is associated with an unfavourable outcome after head injury, but this has not been related to specific pathological features. OBJECTIVES: This study tested the postulate that head injured patients with APOE e4, amounting to approximately a third of the population, are selectively predisposed to one or more of the different pathological features that constitute the response to traumatic brain injury (TBI), and that this underlies the association of APOE e4 with poor clinical outcome. METHODS: Included in the study were 239 fatal cases of TBI (1987-1999) for which APOE genotypes were determined from archival tissue. For each case, specific pathological features of trauma were recorded by researchers blinded to the APOE e4 status. Of the 239 cases examined, 83 (35%) were APOE e4 carriers and 156 (65%) were non-carriers. RESULTS: Possession of APOE e4 was associated with a greater incidence of moderate or severe contusions (42% v 30% for carriers versus e4 non-carriers; p = 0.05) and there was a trend towards a greater incidence of severe ischaemic brain damage (54% v 42%; p = 0.08). Significant differences were not noted between the other pathological features examined. CONCLUSIONS: Possession of APOE e4 is associated with a greater incidence of moderate/severe contusional injury and severe ischaemic brain damage in fatal cases of TBI. This may be relevant to the relatively poor outcome from traumatic brain injury in patients with APOE e4 identified in clinical studies.
Adolescent↗
Novel functional association of serine palmitoyltransferase subunit 1-A peptide in sphingolipid metabolism with cytochrome P4501A1 transactivation and proliferative capacity of the human Glioma LN18 brain tumor cell line.
Some chemical modulators of cytochrome P4501A1, Cyp1A1, expression also perturb the activity of serine palmitoyltransferase, SPT, a heterodimeric protein responsible for catalyzing the first reaction in sphingolipid biosynthesis. The effect of altered SPT activity on Cyp1A1 expression has generally been attributed to changes in the composition of bioactive sphingolipids, generated downstream in the SPT metabolic pathway, but the precise mechanism remains poorly defined. A generally accepted model for chemical-induced transactivation of the Cyp1A1 gene involves intracellular signaling mediated by proteins including the arylhydrocarbon receptor, AhR, whose interaction with the 90 kilo Dalton heat shock protein, Hsp90, is essential for maintaining a high affinity ligandbinding receptor conformation. Because ligand-induced Cyp1A1 expression is important in the bioactivation of environmentally relevant compounds to genotoxic derivatives capable of perturbing cellular processes, binding to Hsp90 represents an important regulatory point in the cytotoxicity process. In the present study, based on evidence that indicates subunit 1 of serine palmitoyltransferase, SPT1, interacts with Hsp90, both ligand-induced Cyp1A1 transactivation and capacity for proliferation were evaluated using the wild type Glioma LN18 human brain cancer cell line and its recombinant counterparts expressing green fluorescent SPT1 fusion proteins. Exposure to the prototypical Cyp1A1 inducer, 3-methylcholanthrene, 3-MC, resulted in the translocation of SPT1 from a primarily cytoplasmic domain to sites of focal adhesion complexes. Immunolabel for Hsp90, which was dispersed throughout the cell, became primarily cytoplasmic, while the distribution of AhR remained unaffected. When compared to the wild type, cells transfected with recombinant SPT1-GFP vectors had significantly attenuated levels of 3-MC-induced Cyp1A1 mRNA, as determined by quantitative reverse transcription PCR. Although all the Glioma cell lines exhibited mitogenic proliferative response in dose response assay with the potent Cyp1A1 inducers 3-MC, 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and benzo [k] fluoranthene, BKF, only the recombinant cell line designated - 75SPT1-GFP, which was transfected with a mutant deletion of SPT1, retained its proliferative capacity at the highest PAH doses used in this study. The results suggest that overexpressing SPT1 as a green fluorescent fusion protein has a modulating effect on the transactivation of Cyp1A1. This is possibly due to SPT1 interacting with Hsp90 to modulate AhR-Hsp90 interaction, and altering downstream events such as in downregulating the transactivation and metabolic activity of Cyp1A1. This is supported by the fact that the -75SPT1-GFP recombinant cell line, with much lower capacity for Cyp1A1 induction, exhibited sustained mitogenic response to high doses of AhR ligands, but not the Cyp1A1 inducible wild type. Conceivably, the effect mediated by SPT1 on the AhR signaling pathway is an important underlying factor contributing to variability in Cyp1A1 gene expression and consequently, cytotoxic response to environmentally relevant compounds that pose risk to human health.
Base Sequence↗
Family practice-friendly guidelines. Anti-infective guidelines (1994-2005).
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Anti-Infective Agents↗
Amphetamine induces dendritic growth in ventral tegmental area dopaminergic neurons in vivo via basic fibroblast growth factor.
Dopaminergic neurons of the ventral tegmental area are implicated in the physiology of reward, and long-lasting changes in their function induced by exposure to psychostimulant drugs are related to the pathophysiology of drug abuse. It is not known, however, whether such changes are accompanied by morphological changes in these neurons. We characterized and labeled cells in slices containing the ventral tegmental area using whole-cell electrophysiological methods. Injections of saline or amphetamine were given to rats on postnatal days 10, 12 and 14 and individual neurons were examined one to four weeks later. We show that repeated exposure to amphetamine induces substantial dendritic growth of ventral tegmental area dopaminergic neurons in vivo. Furthermore, we show, by immuno-neutralization of endogenous basic fibroblast growth factor, that the amphetamine-induced increase in astrocytic basic fibroblast growth factor in the ventral tegmental area is essential for these morphological changes. We propose that the amphetamine-induced elaboration of the dendritic arbor of dopaminergic neurons leads to their increased excitability and contributes to compulsive drug-seeking and relapse.
Amphetamine↗
Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control.
As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.
Adolescent↗
Daily restricted feeding rescues a rhythm of period2 expression in the arrhythmic suprachiasmatic nucleus.
Second only to light, daily restricted feeding schedules can entrain circadian rhythms in mammals [Neurosci Biobehav Rev 4 (1980) 119; J Biol Rhythms 17 (2002) 284]. Contrary to light, however, such feeding schedules have been found not to affect the master circadian clock in the suprachiasmatic nucleus (SCN) [Genes Dev 14 (2000) 2950; Eur J Neurosci 13 (2001) 1190]. Here, we show that in rats that are arrhythmic as a consequence of prolonged housing in constant light, a daily restricted feeding schedule not only restores behavioral rhythmicity, as previously shown [Physiol Behav 53 (1993) 509], but in addition, induces a rhythm of the clock protein, Period2 in the SCN. These findings challenge the idea that the SCN is invulnerable to feeding schedules and call for a reevaluation of the role of the SCN clock in the circadian effects of such schedules.
Analysis of Variance↗
Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus.
Neonatal ventral hippocampal (nVH) lesions in rats result in adult onset of a number of behavioral and cognitive abnormalities analogous to those seen in schizophrenia, including hyperresponsiveness to stress and psychostimulants and deficits in working memory, sensorimotor gating and social interaction. Molecular and neurochemical alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of nVH-lesioned animals suggest developmental reorganization of these structures following neonatal lesions. To determine whether nVH lesions lead to neuronal morphological changes, we investigated the effect of nVH lesion on dendritic structure and spine density of pyramidal neurons of the PFC and medium spiny neurons of the NAcc. Bilateral ibotenic acid-induced lesion of the VH was made in Sprague-Dawley pups at postnatal day 7 (P7); and at P70, neuronal morphology was quantified by modified Golgi-Cox staining. The results show that length of basilar dendrites and branching and the density of dendritic spines on layer 3 pyramidal neurons were significantly decreased in rats with nVH lesions. Medium spiny neurons from the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. The data, comparable to those observed in the PFC of schizophrenic patients, suggest that developmental loss of excitatory projections from the VH may lead to altered neuronal plasticity in the PFC and the NAcc that may contribute to the behavioral changes in these animals.
Age Factors↗
A review of UK housing policy: ideology and public health.
OBJECTIVES: The aim of this paper is to review UK public health policy, with a specific reference to housing as a key health determinant, since its inception in the Victorian era to contemporary times. REVIEW: This paper reviews the role of social and private housing policy in the development of the UK public health movement, tracing its initial medical routes through to the current socio-economic model of public health. The paper establishes five distinct ideologically and philosophically driven eras, placing public health and housing within liberal (Victorian era), state interventionist (post World War 1; post World War 2), neoliberal (post 1979) and "Third Way" (post 1997) models, showing the political perspective of policy interventions and overviewing their impact on public health. The paper particularly focuses on the contemporary model of public health since the Acheson Report, and how its recommendations have found their way into policy, also the impact on housing practice. CONCLUSIONS: Public health is closely related to political ideology, whether driven by the State, individual or partnership arrangements. The current political system, the Third Way, seeks to promote a sustainable "social contract" between citizens and the State, public, private and voluntary organizations in delivering community-based change in areas where health inequalities can be most progressively and successfully addressed.
Health Policy↗
Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine.
Netrins are guidance cues that play a fundamental role in organizing the developing brain. The netrin receptor, DCC (deleted in colorectal cancer), is highly expressed by dopaminergic (DA) neurons. DCC may therefore participate in the organization of DA circuitry during development and also influence DA function in the adult. Here we show that adult dcc heterozygous mice exhibit a blunted behavioral response to the indirect DA agonist amphetamine and do not develop sensitization to its effects when treated repeatedly. These behavioral alterations are associated with profound changes in DA function. In the medial prefrontal cortex, dcc heterozygotes exhibit increased tyrosine hydroxylase (TH) protein levels and dramatic increases in basal concentrations of DA and DA metabolites. In contrast, in the nucleus accumbens, dcc heterozygotes show no changes in either TH or DA levels, but exhibit decreased concentrations of DA metabolites, suggesting reduced DA activity. In addition, dcc heterozygous mice exhibit a small, but significant reduction in total number of TH-positive neurons in midbrain DA cell body regions. These results demonstrate for the first time that alterations in dcc expression lead to selective changes in DA function and, in turn, to differences in DA-related behaviors in adulthood. These findings raise the possibility that changes in dcc function early in life are implicated in the development of DA dysregulation observed in certain psychiatric disorders, such as schizophrenia, or following chronic use of drugs of abuse.
Animals↗
Setting and negotiating targets in people with Type 2 diabetes in primary care: a cross sectional survey.
AIMS: To investigate the provision of diabetes care, the frequency of practices setting targets for their diabetic population, the targets set and the frequency of targets being negotiated with people with diabetes. METHODS: Cross-sectional study using a survey of 123 general practices within four Primary Care Trusts in Nottingham UK. RESULTS: Eighty per-cent (99) of practices responded. Of these, 88 and 89%, respectively, had set glycosolated haemoglobin (HbA1c) and blood pressure targets for people with Type 2 diabetes. Twenty-five per-cent (24) of practices reported negotiating targets with almost all people with Type 2 diabetes for HbA1c and 31% (30) for blood pressure. In 46% (45) of practices, the annual diabetic review for some or all of the people with Type 2 diabetes was carried out by the practice nurse alone. In these practices, targets were negotiated with a smaller proportion of people than those where the doctor was involved in the annual review for both blood pressure [43 vs. 64% negotiated blood pressure targets with almost all or many people odds ratio (OR) 0.42 (95% CI 0.19, 0.96), P = 0.04] and HbA1c [39 vs. 60% negotiated HbA1c targets with almost all or many people, OR 0.41 (95% CI 0.18, 0.94), P = 0.03]. CONCLUSIONS: Negotiating targets with people with Type 2 diabetes does not routinely occur in primary care. Targets are negotiated less often in practices where nurses undertake reviews alone and further work is needed to explore the reasons for this.
Blood Glucose↗
Inequalities in glycaemic control in patients with Type 2 diabetes in primary care.
AIMS: To quantify relationships between patient and practice factors and glycaemic control in patients with Type 2 diabetes. METHODS: A cross-sectional study involving 1534 patients with Type 2 diabetes from 42 general practices in Nottingham, UK was undertaken. Patient characteristics were assessed by a clinical interview and case note review and practice characteristics by a questionnaire. The outcome measure was serum HbA(1c) concentration measured at entry to the study. Random effects linear regression was used to model patient and practice factors associated with glycaemic control. RESULTS: In multivariable regression analysis, HbA(1c) increased with increasing body mass index (BMI) [change in HbA(1c) for one unit increase in BMI: 0.03%, 95% confidence interval (CI) 0.01, 0.04], and was higher in those using oral medication (mean difference 0.75%, 95% CI 0.59, 0.92) or insulin compared with diet (mean difference 1.36%, 95% CI 1.10, 1.62). There was a dose-response relationship between HbA(1c) and increasing time since diagnosis. HbA(1c) was negatively associated with age (change per year -0.01%, 95% CI -0.02, -0.004). Patients registered at the most deprived practices had higher HbA(1c) values than those in the least deprived practices (mean difference 0.42%, 95% CI 0.14, 0.71), as did those in practices where annual reviews were carried out by the nurse alone (mean difference 0.24%, 95% CI 0.04, 0.44). CONCLUSIONS: Several patient and practice factors are related to glycaemic control. Poorer glycaemic control was associated with practice level deprivation and nurses undertaking annual reviews alone. Further research is required to explore outcomes of annual reviews undertaken by nurses alone. Greater resources may be needed by primary care teams working in deprived areas to address inequalities in diabetic control.
Administration, Oral↗