Biomedical subjects

C Hunter

Publications and source records attributed to C Hunter.

At least 19 recordsLinked to original sources

PubMed2006

Clinico-immunologic aspects of botulinum toxin type B treatment of cervical dystonia.

In this multicenter study of 100 patients with cervical dystonia, we examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity of BTX-B limits its long-term efficacy.

Botulinum Toxins↗

PubMed2006

Effects of 17beta-estradiol on blood-brain barrier disruption during focal cerebral ischemia in younger and older rats.

This study was performed to compare the effects of 17beta-estradiol on blood-brain barrier disruption in focal cerebral ischemia between younger and older rats. Younger (three-month-old) and older (24-month-old) ovariectomized female Fischer 344 rats were studied. In one half of each age group, a 500 microg 17beta-estradiol 21-day release pellet and in another half, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion, the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to examine the degree of blood-brain barrier disruption. In all four groups, the Ki in the ischemic cortex was higher than in the corresponding contralateral cortex. There was no significant difference in the Ki in both cortices among the groups. The volume of dextran distribution of the ischemic cortex was only greater than in the corresponding contralateral cortex in the older 17beta-estradiol-treated group, and the volume of that group was greater than the younger 17beta-estradiol-treated group (4.00 +/- 1.29 VS. 2.13 +/- 0.88 ml/100 g). After analyzing the difference in Ki between the ischemic cortex and the contralateral cortex in each animal, the difference was significantly greater in the older 17beta-estradiol-treated rats than the older vehicle-treated rats (3.40 +/- 2.10 VS. 1.26 +/- 1.44 microl/g/min). In the younger rats, however, 17beta-estradiol did not significantly affect the difference. Our data showed that 17beta-estradiol treatment failed to attenuate the BBB disruption in the cerebral ischemic cortex in the older or younger Fischer 344 rats. However, our data also suggest the possibility that 17beta-estradiol could aggravate the BBB disruption in older rats.

Aging↗

PubMed2005

Effects of 17beta-estradiol on blood-brain barrier disruption in focal ischemia during GABA(A) receptor inhibition.

We performed this study to determine whether gamma-aminobutyric acid (GABA(A)) receptor inhibition could reverse the effect of 17beta-estradiol on blood-brain barrier (BBB) disruption in focal cerebral ischemia. Young ovariectomized rats were implanted with a 500 microg 17beta-estradiol 21-day release pellet or with a vehicle pellet 21 days before the experiments. Forty-five minutes after middle cerebral artery (MCA) occlusion, half of each group was infused with bicuculline (a GABA(A) receptor antagonist) 1 mg/kg/min for 2 min followed by 0.1 mg/kg/min up to the end of experiments. The other half was infused with the same volume of normal saline. The transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution (70,000 Daltons) were determined to measure the degree of BBB disruption one hour after MCA occlusion. In the control vehicle-treated animals, the Ki in the ischemic cortex (7.2 +/- 2.6 microl/g/min) was higher than in the contralateral cortex (2.5 +/- 1.4 microl/g/min). After bicuculline infusion, the Ki in the ischemic cortex increased (10.6 +/- 5.4 microl/g/min) although the increase was not statistically significant. In the 17beta-estradiol treated animals, the Ki in the ischemic cortex (3.8 +/- 1.6 microl/g/min) was lower than control vehicle-treated rats. With bicuculline infusion, the Ki in the ischemic cortex (14.5 +/- 6.8 microl/g/min) was markedly increased. In the non-ischemic cortex, there was no significant difference in Ki among the experimental groups. The volume of dextran distribution was not significantly different between the experimental groups in the ischemic or non-ischemic cortex. Our data suggests that part of the reason for the decreased BBB disruption in the focal ischemic area after 17beta-estradiol treatment could be due to the interaction between GABA(A) receptors and 17beta-estradiol.

Algorithms↗

PubMed2005

Chaos in orbits due to disk crossings.

We study orbits of halo stars in simple models of galaxies with disks and halos to see if the cumulative effects of the sudden changes in acceleration that occur at disk crossings can induce chaos. We find that they can, although not in all orbits and not in all potentials. Most of the orbits that become chaotic stay relatively close to the disk and range widely in the radial direction. Heavier disks and increased halo flattening both enhance the extent of the chaos. A limited range of experiments with a three-component model of the Milky Way with an added central bulge finds that many chaotic disk-crossing orbits can be expected in the central regions, and that prolateness of the halo is much more effective than oblateness in generating chaos.

Journal Article↗

PubMed2004

Do benefits and barriers differ by stage of adoption for colorectal cancer screening?

In 2003, over 148,300 people were expected to be diagnosed and 56,000 to die from colorectal cancer (CRC). First-degree relatives (FDRs) of people with colon cancer have a two- to eight-fold increased risk for CRC. Despite evidence that screening is effective, adherence with screening recommendations in this at-risk population is low. This study's purposes were to (1) identify perceived benefits and barriers of fecal occult blood testing (FOBT), sigmoidoscopy and colonoscopy, and (2) compare demographic characteristics and perceived benefits and barriers by stage of adoption for CRC screening. Participating FDRs (n = 257) completed a 40-min structured telephone interview. Despite high rates of agreement with the benefits of screening, most FDRs were not contemplating being screened. Of those 50 and older, most were in precontemplation for FOBT, sigmoidoscopy and colonoscopy. Older age was related to stage for FOBT and sigmoidoscopy, but not colonoscopy. Lack of provider recommendation also was related to stage. Consistent with theoretical predictions, precontemplators had (1) higher rates of endorsement of specific barriers to screening and (2) lower rates of endorsement of benefits than contemplators or actors. For morbidity and mortality reduction, participation in routine, periodic screening is imperative. These findings can guide development of screening-promoting interventions.

Age Factors↗

PubMed2003

Spatial and temporal bacterial quality of a lowland agricultural stream in northeast Scotland.

Stream water concentrations of the faecal coliform group of sanitary indicator bacteria were monitored in the Newmills Burn, a small agriculturally intensive tributary of the River Don in Aberdeenshire. The results indicated that during its passage through the catchment, stream water became significantly contaminated with faecal coliform bacteria from the main agricultural land use inputs of livestock grazing and organic waste applications. Point sources of faecal coliform bacteria in terms of farmyard runoff, however, also appeared to be important in contributing to the spatial pattern of contamination. Significant temporal variation was observed in response to the hydrological behaviour of the catchment. Higher flows and more frequent washout of stored bacteria in winter and spring months led to lower faecal coliform concentrations than were detected during the summer. Maximum faecal coliform concentrations were measured during rainfall events and the varying responses associated with these helped to identify the importance of different sources of bacteria in the catchment and the mechanisms transferring them. The overall impact on the water quality of the Newmills Burn was considered as having a potentially serious threat to the health of downstream recreational users of the River Don, as well as to the large proportion of the local population who rely on private water supplies.

Agriculture↗

PubMed2002

Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease.

OBJECTIVE: To determine whether the Nurr1 gene, which is critical for the development and maintenance of nigral dopaminergic neurons, is a risk factor associated with PD. BACKGROUND: The Nurrl gene is highly expressed in the dopaminergic neurons in the midbrain. Knockout of the gene results in agenesis of nigral dopaminergic neurons and heterozygous knockout mice increases 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. METHODS: This study included 105 patients with familial PD (fPD) and 120 patients with sporadic PD (sPD) and 221 age-matched healthy control subjects. The polymorphisms and mutations of the Nurr1 gene in patients with PD were initially examined by heteroduplex analysis and sequencing analysis from PCR-amplified Nurr1 gene fragments. A polymorphism in the BseRI restriction site was identified, and a relatively large-scale analysis then was conducted by three independent investigators who were blinded to the clinical status of the subjects. RESULTS: A homozygous 7048G7049 polymorphism was found in intron 6 of the Nurr1 gene, which was significantly higher in fPD (10/105; 9.5%) and in sPD (5/120; 4.2%) compared with healthy control subjects (2/221; 0.9%). The mean age and the SD at onset of these homozygote patients with PD was 52 +/- 15 years for fPD and 46 +/- 7 years for sPD. The clinical features of these homozygote patients with PD did not differ from those of typical PD. CONCLUSIONS: The homozygote polymorphism of 7048G7049 in intron 6 of the Nurr1 gene is associated with typical PD.

Adult↗

PubMed2002

A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson's disease.

BACKGROUND: To the extent that excitotoxicity may play a role in the pathogenesis of certain neurodegenerative disorders, antagonists of glutamate, an excitatory neurotransmitter, should exert neuroprotective effects in these disorders, including Parkinson's disease (PD). METHODS: Patients in early stages of PD, not previously treated with levodopa, were randomized to receive riluzole 50mg capsules orally, taken twice daily or a matching placebo. All subjects were evaluated at baseline (pre-treatment), at 1, 3 and 6 months (post-treatment), and following a 6-week washout. After the washout, all subjects were offered an enrollment in an open label, 1-year, extension study. The principal investigator (JJ), however, remained blinded to the original assignment during the entire study. The patients were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hoehn & Yahr (HY) stage, and Schwab and England (SE) ADL scale. The quantitative assessments included Movement Time (MT) and Reaction Time (RT). Additionally, the time to initiate dopaminergic therapy was assessed. Safety was determined at each visit by clinical history and examination, a panel of blood safety laboratory tests including complete blood count, chemistry profile, and liver function studies. RESULTS: Twenty patients with a mean age of 62+/-9.02 (range: 46-73) years and mean duration of symptoms of 18+/-9.53 (range: 6-36) months were enrolled. One patient withdrew from the study because he needed more aggressive treatment of his symptoms. Analysis of the efficacy variables showed no meaningful symptomatic effect of riluzole on UPDRS score. Likewise, there was no significant change in the median HY stage, SE ADL rating, or the MT/RT. Seventeen patients (mean age 62+/-9.26) elected to continue in the open label extension study. Although the observed deterioration in UPDRS scores seemed to be more pronounced in the placebo group than in the riluzole group, the difference did not reach statistical significance. There was no statistically significant difference in the latency between enrollment and start of symptomatic therapy when patients initially treated with riluzole were compared to those initially treated with placebo (8.3 vs 9 months). CONCLUSIONS: This pilot and extension study showed that riluzole, 100mg/day, was well tolerated in patients with early PD. No evidence of symptomatic effect of riluzole was observed. Because of the exploratory nature of the design and small size of the study, it was not possible to determine whether riluzole affected the natural history of PD. The encouraging results from our study, however, suggest that larger, longitudinal studies are warranted.

Aged↗

PubMed2002

A sharp debridement procedure devised by specialist nurses.

In the clinical governance era, self-education is not adequate training for nurses to carry out sharp debridement, which is a risky process. Specialist nurses in south-east London drew up a workable procedure for training and practice.

Debridement↗

PubMed2001

IL-12 suppression during experimental endotoxin tolerance: dendritic cell loss and macrophage hyporesponsiveness.

Endotoxin tolerance, the transient, secondary down-regulation of a subset of endotoxin-driven responses after exposure to bacterial products, is thought to be an adaptive response providing protection from pathological hyperactivation of the innate immune system during bacterial infection. However, although protecting from the development of sepsis, endotoxin tolerance also can lead to fatal blunting of immunological responses to subsequent infections in survivors of septic shock. Despite considerable experimental effort aimed at characterizing the molecular mechanisms responsible for a variety of endotoxin tolerance-related phenomena, no consensus has been achieved yet. IL-12 is a macrophage- and dendritic cell (DC)-derived cytokine that plays a key role in pathological responses to endotoxin as well as in the induction of protective responses to pathogens. It recently has been shown that IL-12 production is suppressed in endotoxin tolerance, providing a likely partial mechanism for the increased risk of secondary infections in sepsis survivors. We examined the development of IL-12 suppression during endotoxin tolerance in mice. Decreased IL-12 production in vivo is clearly multifactorial, involving both loss of CD11c(high) DCs as well as alterations in the responsiveness of macrophages and remaining splenic DCs. We find no demonstrable mechanistic role for B or T lymphocytes, the soluble mediators IL-10, TNF-alpha, IFN-alphabeta, or nitric oxide, or the NF-kappaB family members p50, p52, or RelB.

Animals↗

PubMed2001

Practice unwinds and disengagements.

Many employed physicians are being forced to consider entering the private practice arena as physicians networks and groups are contemplating total or partial divestitures. Still other physicians are evaluating the possibility of leaving their current practice or hospital based network and opening their own practice. This article is designed to better prepare a physician for this situation ad proactively plan for their future.

Community Networks↗

PubMed2000

NMR kinetic studies on the decomposition of beta-amidozinc reagents: optimization of palladium-catalyzed cross-coupling with acid chlorides.

The decomposition of beta-amidozinc reagent 4 by beta-elimination has been shown to be a unimolecular process in both THF and DMF as solvent, with relative rates of 4:1 at room temperature, and activation parameters have been determined. These results indicate the beta-elimination is a syn-process. NMR experiments reveal that as little as 2 equiv of DMF can have a significant stabilizing influence on reagent 4. Use of a mixture of DMA and toluene as the bulk solvent, in place of DMF, has allowed successful palladium-catalyzed cross-coupling reactions of both 4 and the homologous reagent 5 with acid chlorides to yield unsymmetrical ketones (nine examples).

Amides↗

PubMed2000

The pharmacokinetic and clinical effects of tolcapone on a single dose of sublingual apomorphine in Parkinson's disease.

Apomorphine (APO) is a potent dopamine agonist that is partially metabolized by catachol-O-methyl transferase (COMT). Tolcapone was the first COMT inhibitor available for use as adjunctive therapy to levodopa in Parkinson's disease (PD). In order to determine whether this compound might increase the serum area under the curve (AUC) of APO and whether this results in any clinical benefit, we administered 200mg doses of tolcapone to five fluctuating PD patients taking an investigational sublingual APO preparation. Serial tapping speed and gait speed were assessed at 15min intervals over four hours, in conjunction with APO serum levels, following a single dose of APO, both before and five days after starting tolcapone (600mg/day). Serum APO levels tended to be higher (12.6%), and clinical measures suggested improvement during the APO "on" period after the addition of tolcapone (22.5% improvement in gait speed, and 7.6% improvement in tapping speed), but neither reached statistical significance. Further trials, involving larger samples are needed to clearly establish the pharmacokinetic and clinical effect of tolcapone in PD patients taking APO.

Journal Article↗

PubMed2000

Regulated expression of nullo is required for the formation of distinct apical and basal adherens junctions in the Drosophila blastoderm.

During cellularization, the Drosophila embryo undergoes a large-scale cytokinetic event that packages thousands of syncytial nuclei into individual cells, resulting in the de novo formation of an epithelial monolayer in the cortex of the embryo. The formation of adherens junctions is one of the many aspects of epithelial polarity that is established during cellularization: at the onset of cellularization, the Drosophila beta-catenin homologue Armadillo (Arm) accumulates at the leading edge of the cleavage furrow, and later to the apicolateral region where the zonula adherens precursors are formed. In this paper, we show that the basal accumulation of Arm colocalizes with DE-cadherin and Dalpha-catenin, and corresponds to a region of tight membrane association, which we refer to as the basal junction. Although the two junctions are similar in components and function, they differ in their response to the novel cellularization protein Nullo. Nullo is present in the basal junction and is required for its formation at the onset of cellularization. In contrast, Nullo is degraded before apical junction formation, and prolonged expression of Nullo blocks the apical clustering of junctional components, leading to morphological defects in the developing embryo. These observations reveal differences in the formation of the apical and basal junctions, and offer insight into the role of Nullo in basal junction formation.

Animals↗

PubMed2000

Gabapentin for essential tremor: a multiple-dose, double-blind, placebo-controlled trial.

Essential tremor (ET) is a common movement disorder that often becomes refractory to conventional pharmacologic management. Open-label studies suggest that gabapentin is efficacious for ET, but the results of controlled trials have been mixed. To determine the efficacy and tolerability of gabapentin in ET, we conducted a double-blind, placebo-controlled, cross-over trial evaluating two doses (1800 mg per day and 3600 mg per day; N = 25). Patients on other ET medications were maintained on their concurrent medications for 3 months prior to study initiation and throughout the study. Twenty patients (mean age, 69.9 +/- 6.1 yrs) completed the study. Overall, patient global assessments (p <0.05), observed tremor scores (p <0.005), water pouring scores (p <0.05), and activities of daily living scores (p <0.005) significantly improved. Accelerometry scores, spirographs, and investigator global impression scores did not improve. The results were similar for high and low doses. Statistical regression models did not demonstrate any significant predictors for response. Gabapentin may be effective in some cases of ET.

Acetates↗

PubMed2000

Mechanical ventilation and high-efficiency vacuum cleaning: A combined strategy of mite and mite allergen reduction in the control of mite-sensitive asthma.

BACKGROUND: The relationship between exposure to house dust mite (HDM) allergens and prevalence of sensitization to these allergens in patients with asthma has been confirmed in many studies. Mite population growth is regulated by humidity. Reducing humidity and removing allergen by efficient vacuuming should control mite allergen and reduce symptoms. OBJECTIVE: We sought to investigate the effect of mechanical ventilation and high-efficiency vacuuming on HDM numbers and Der p 1 concentrations in the homes of mite-sensitive asthmatic subjects and to evaluate the effect of any reductions on symptoms. METHODS: The homes of 40 HDM-sensitive asthmatic subjects were randomized to receive (1) mechanical ventilation and a high-efficiency vacuum cleaner (HEVC); (2) mechanical ventilation alone; (3) an HEVC alone; and (4) no intervention. Homes and patients were monitored for 12 months. Change in absolute humidity, mite numbers, Der p 1 concentrations, lung function, bronchial hyperresponsiveness, and symptom scores were analyzed. RESULTS: Homes with mechanical ventilation achieved significantly lower humidity levels than those without (P <.001), with an associated reduction of mite numbers (P <.05) and Der p 1 concentrations (P <.001 ¿in nanograms per gram, P =.006 ¿in milligrams per square meter) in bedroom carpets and some other mite sources in the ventilated areas of the homes. The addition of a vacuum cleaner enhanced this effect. There was a trend for an improvement in histamine PC(20) (P =.085) in the patients whose homes were ventilated. CONCLUSION: The use of a mechanical ventilation system in suitable homes resulted in some reduction in numbers of HDM and Der p 1 concentrations. The addition of an HEVC slightly enhanced the effect but not sufficiently to see an improvement in symptoms.

Adolescent↗

PubMed2000

The relationship between body mass index and waist circumference: implications for estimates of the population prevalence of overweight.

OBJECTIVE: Body mass index (BMI) based on self-reported height and weight is a systematically biased, but acceptable measure of adiposity and is commonly used in population surveys. Recent studies indicate that abdominal obesity is more strongly associated with obesity-related health problems than is adiposity measured by BMI. The purpose of this study was to determine the relationships of both measured and self-reported BMI with measured waist circumference in a randomly selected sample of Australian adults. DESIGN: Cross-sectional survey with self-reported and laboratory-based measures of adiposity. SUBJECTS: 1140 randomly-selected Australian adults aged 18-78 y resident in the city of Adelaide, South Australia. MEASUREMENTS: Data on self-reported and measured height and weight as well as measured waist circumference were drawn from the Pilot Survey of the Fitness of Australians database. The proportion of men and women with acceptable BMI (BMI</=25 kg/m2) and with excess abdominal adiposity (>/=94 cm for men and >/=80 cm for women) was determined. Differences in the prevalence of overweight based on BMI alone or BMI and waist circumference were also determined. RESULTS: Compared with the prevalence based on self-reported BMI alone, the prevalence of overweight among men based on self-reported BMI and waist circumference combined was 2.4%, 5.3%, 19.1% and 7.5% greater for men aged 18-39 y, 40-59 y, 60-78 y and for all men, respectively. Among women, compared with the prevalence based on self-reported BMI alone, the prevalence of overweight based on the combined measures was 9.9%, 24.0%, 33.3% and 20.6% greater for women aged 18-39 y, 40-59 y, 60-78 y and for all women, respectively. CONCLUSIONS: If waist circumference is used as the criterion, then the prevalence of overweight among Australian adults, and probably other Caucasian populations, may be significantly greater than indicated by surveys relying on self-reported height and weight. The development of valid self-reported measures of waist circumference for use in population surveys may allow more accurate epidemiological monitoring of overweight and obesity.

Abdomen↗

PubMed2000

Accuracy of administrative data in trauma: splenic injuries as an example.

BACKGROUND: Accurate data are needed to evaluate clinical outcomes, therapeutic modalities, and quality of care in trauma. Administrative data, usually used for billing, have been used to evaluate performance and assess therapy in other medical specialties. This study was performed to determine whether administrative databases are accurate in the recording of information about trauma patients with splenic injuries. METHODS: Patients who had blunt splenic injuries were identified using a state trauma registry. The medical records of those patients were reviewed. The data collected by chart review were compared with data in the statewide administrative database of patients who had splenic injuries at the same four Level I and II trauma centers in the same 5-year period. Age, sex, admission date, and hospital were matched to assure comparison of the identical cohort. chi2 analysis was used to compare dichotomous data and Student's t test continuous data. RESULTS: The administrative database identified 641 and the trauma registry identified 529 patients with a diagnosis of splenic injury. A total of 401 patients were found in both databases. Of these, 120 (22.7%) patients were not recorded in the administrative database. Injury Severity Score was underreported by the administrative database (25.74 +/- 14.7 vs. 19.52 +/- 11, p < 0.0001). The administrative database underreported orthopedic, chest, and head injuries (317 vs. 215, 325 vs. 228, and 234 vs. 155, respectively; all p < 0.0001). Use of abdominal computed tomographic scan and diagnostic peritoneal lavage were also underreported (260 vs. 56 and 104 vs.17, both p < 0.0001). The number of operations on the spleen and number of orthopedic procedures were underreported (259 vs. 225, p < 0.014 and 147 vs. 94, p < 0.0001). Complications were markedly underreported by the administrative database (200 vs. 47, p < 0.0001) CONCLUSION: This study shows that administrative data lack accuracy in the recording of associated injuries, injury severity, diagnostics, procedures, and outcomes data in patients with splenic injuries. Whether these data should be used to evaluate treatment modalities or quality of care in trauma is questionable.

Adult↗