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Biomedical subjects

S George

Publications and source records attributed to S George.

At least 19 recordsLinked to original sources
PubMed2006

Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis.

OBJECTIVE: C-reactive protein (CRP) has been associated with disease progression in patients with osteoarthritis (OA), but the reasons for this remain unclear. We hypothesized that higher CRP would be related to local inflammatory findings in the joints of patients with OA. METHODS: Plasma and synovial membrane specimens from 54 OA patients undergoing total hip or knee arthroplasty or arthroscopy were obtained. Synovial fluid was obtained from 25 of these patients. Hematoxylin and eosin stained synovial membrane sections were scored for degree of inflammatory cell infiltration. Plasma high-sensitivity CRP (hsCRP) levels, and serum and synovial fluid interleukin (IL)-6 and IL-1beta levels were measured by enzyme-linked immunosorbent assay. RESULTS: Fifty-seven percent of patients with idiopathic OA had inflammatory infiltrates within the synovial membrane. The mean hsCRP level in patients with inflammatory infiltrates was significantly higher than those without inflammation (4.7 +/- 5.0 mg/L vs 1.7 +/- 3.6 mg/L, P = 0.003). There were significant correlations between hsCRP levels and synovial fluid IL-6 (r = 0.64, P = 0.0006), degree of synovial inflammatory infiltration (r = 0.43, P = 0.002), and body mass index (r = 0.31, P = 0.02). Multivariate analysis indicated that only degree of inflammatory infiltrate was significantly associated with hsCRP level (P = 0.026). CONCLUSION: These results suggest that systemic hsCRP levels reflect synovial inflammation in OA patients, perhaps by means of synovial IL-6 production. Future studies are needed to clarify how these infiltrates and their products may contribute to disease pathogenesis.

Adult↗
PubMed2006

The effect of cerebral hypothermia on white and grey matter injury induced by severe hypoxia in preterm fetal sheep.

Prolonged, moderate cerebral hypothermia is consistently neuroprotective after experimental hypoxia-ischaemia; however, it has not been tested in the preterm brain. Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (fetal extradural temperature reduced from 39.4 +/- 0.3 to 29.5 +/- 2.6 degrees C) from 90 min to 70 h after the end of occlusion or sham cooling. Occlusion led to severe acidosis and profound hypotension, which recovered rapidly after release of occlusion. After 3 days recovery the EEG spectral frequency, but not total intensity, was increased in the hypothermia-occlusion group compared with normothermia-occlusion. Hypothermia was associated with a significant overall reduction in loss of immature oligodendrocytes in the periventricular white matter (P < 0.001), and neuronal loss in the hippocampus and basal ganglia (P < 0.001), with suppression of activated caspase-3 and microglia (isolectin-B4 positive). Proliferation was significantly reduced in periventricular white matter after occlusion (P < 0.05), but not improved after hypothermia. In conclusion, delayed, prolonged head cooling after a profound hypoxic insult in the preterm fetus was associated with a significant reduction in loss of neurons and immature oligodendroglia, with evidence of EEG and haemodynamic improvement after 3 days recovery, but also with a persisting reduction in proliferation of cells in the periventricular region. Further studies are required to evaluate the long-term impact of cooling on brain growth and maturation.

Animals↗
PubMed2006

Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists.

To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5-10 identified, who had in turn a similar advantage over those with 0-4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival.

Adenocarcinoma↗
PubMed2006

Induced cerebral hypothermia reduces post-hypoxic loss of phenotypic striatal neurons in preterm fetal sheep.

Perinatal hypoxic-ischemic injury of the basal ganglia is a significant cause of disability in premature infants. Prolonged, moderate cerebral hypothermia has been shown to be neuroprotective after experimental hypoxia-ischemia; however, it has not been tested in the preterm brain. We therefore examined the effects of severe hypoxia and the potential neuroprotective effects of delayed hypothermia on phenotypic striatal neurons. Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (fetal extradural temperature reduced from 39.4+/-0.3 degrees C to 29.5+/-2.6 degrees C) from 90 min to 70 h after the end of occlusion. Hypothermia was associated with a significant overall reduction in striatal neuronal loss compared with normothermia-occlusion fetuses (mean+/-SEM, 5.5+/-1.2% vs. 38.1+/-6.5%, P<0.01). Immunohistochemical studies showed that occlusion resulted in a significant loss of calbindin-28 kd, glutamic acid decarboxylase isoform 67 and neuronal nitric oxide synthase-immunopositive neurons (n=7, P<0.05), but not choline acetyltransferase-positive neurons, compared with sham controls (n=7). Hypothermia (n=7) significantly reduced the loss of calbindin-28 kd and neuronal nitric oxide synthase, but not glutamic acid decarboxylase-immunopositive neurons. In conclusion, delayed, prolonged moderate head cooling was associated with selective protection of particular phenotypic striatal projection neurons after severe hypoxia in the preterm fetus. These findings suggest that head cooling may help reduce basal ganglia injury in some premature babies.

Animals↗
PubMed2006

Endogenous alpha2-adrenergic receptor-mediated neuroprotection after severe hypoxia in preterm fetal sheep.

Central alpha-adrenergic receptor activity is important for fetal adaptation to hypoxia before birth. It is unclear whether it is also important during recovery. We therefore tested the hypothesis that an infusion of the specific alpha(2)-adrenergic receptor antagonist idazoxan (1 mg/kg/h i.v.) from 15 min to 4 h after profound hypoxia induced by 25 min umbilical cord occlusion in fetal sheep at 70% of gestation (equivalent to the 28-32 weeks in humans) would increase neural injury. After 3 days' recovery, idazoxan infusion was associated with a significant increase in neuronal loss in the hippocampus (P<0.05), expression of cleaved caspase-3 (P<0.05), and numbers of activated microglia (P<0.05). There was no significant effect on other neuronal regions or on loss of O4-positive premyelinating oligodendrocytes in the subcortical white matter. Idazoxan was associated with an increase in evolving epileptiform electroencephalographic (EEG) transient activity after occlusion (difference at peak 2.5+/-1.0 vs. 11.7+/-4.7 counts/min, P<0.05) and significantly reduced average spectral edge frequency, but not EEG intensity, from 54 until 72 h after occlusion (P<0.05). Hippocampal neuronal loss was correlated with total numbers of epileptiform transients during idazoxan infusion (P<0.01; r(2)=0.7). In conclusion, endogenous inhibitory alpha(2)-adrenergic receptor activation after severe hypoxia appears to significantly limit evolving hippocampal damage in the immature brain.

Adrenergic alpha-Antagonists↗
PubMed2006

Electrical transport measurements on self-assembled organic molecular wires.

The electrical properties of supermolecular assemblies of oligo(p-phenylene vinylene) were studied. These materials self-assemble into well-defined cylindrical structures in solution with lengths in the range of 100 nm-10 microm and diameters between 5 and 200 nm. Atomic force microscopy showed that by adjusting the concentration, either individual molecular wires or a dense film could be deposited. The molecular wires showed poor electrical conduction. Several tests were performed that show that it was the molecular wires themselves, not the contacts, that limit the conductivity.

Journal Article↗
PubMed2006

Enterococcus faecalis-mediated biomineralized biofilm formation on root canal dentine in vitro.

Enterococcus faecalis is the most predominant bacteria in teeth with failed root canal therapy and is found to survive harsh conditions prevailing in the root canals of endodontically treated teeth. This study aims to investigate the interaction between E. faecalis and root canal dentine substrate. Towards this end, tooth specimens were prepared and divided into two groups. The tooth specimens in group 1 were incubated with E. faecalis for periods of 2-, 4-, and 6-week intervals and the chemical composition of the biofilm was determined using X-ray diffraction and Fourier transform infrared (FTIR) spectroscopy. The tooth specimens in group 2 were incubated with E. faecalis for a period of 6 weeks and the topography and ultrastructure of the biofilm were examined using scanning electron microscopy (SEM), light microscopy, and laser confocal scanning microscopy. The sediments formed from the bacterial interaction on the dentine (in group 1) were also examined by SEM and FTIR. These experiments highlighted different stages in the interaction of E. faecalis with root canal dentine. Further, a bacterial-induced apatite reprecipitation on mature biofilm was also observed. This ability of E. faecalis to form such calcified biofilm on root canal dentine may be a factor that contributes to their persistence after endodontic treatment.

Biocompatible Materials↗
PubMed2006

Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group.

BACKGROUND: Photoallergic contact dermatitis can be difficult to diagnose if not appropriately investigated. Currently, the most common U.K. photoallergens appear to be sunscreen chemicals. The investigation of choice is photopatch testing (PPT), which is probably underused. In part, this is due to differences in methodology and results interpretation. OBJECTIVES: To conduct PPT using a group of sunscreen chemicals, defined indications and a standardized methodology including interpretation and relevance of reactions in patients attending for investigation at 17 centres across the U.K., Ireland and the Netherlands. METHODS: Patients (n = 1155) who fulfilled the inclusion criteria were investigated with PPT using sunscreen chemicals in addition to suspected topical products. Readings were taken at 24, 48 and 72 h following standardized ultraviolet A irradiation (5 J cm(-2)). The clinical relevance of any reaction was recorded. RESULTS: Of the 1155, 130 had allergic reactions (11.3%). Of these, 51 had photoallergy (PA) (4.4%), 64 had contact allergy (CA) (5.5%), and 15 patients had combined PA and CA (1.3%). Multiple PA was seen in some. The most common photoallergen was benzophenone-3 (27 reactions; 21%). Most reactions (60%) were clinically relevant. The most common indication for testing in patients found to have PA was a history of reacting to a sunscreen (41%). The other 59% had an exposed-site dermatitis/skin problem or a photodermatosis. Some centres (n = 8) performed readings after the standard 48-h reading, and an extra 32 PA and 22 CA reactions were detected, which were not evident at 48 h. A new photoallergen (octyl triazone) was detected in two patients. CONCLUSIONS: Sunscreen PA and CA are probably equally uncommon. Most reactions, of both reaction types, were relevant clinically. A large proportion of patients (59%) found to have PA was unaware of reacting to a sunscreen chemical, suggesting that PA should be considered as an explanation in any exposed-site dermatitis. Although this study focused on reactions at 48 h postirradiation, readings performed up to 96 h, while inconvenient, add value by detecting additional relevant responses. A previously unknown photoallergen was found, highlighting the need for awareness of novel photoallergens in the marketplace. A standardized PPT method not only encourages more use of this investigation, but also facilitates comparison of results between centres and so will improve our understanding of PA.

Adolescent↗
PubMed2006

Measuring autonomy in disabled people: Validation of a new scale in a UK population.

OBJECTIVE: To evaluate the validity and reliability of an English version of the Impact on Participation and Autonomy Questionnaire (IPA). The original Dutch IPA has been shown to load onto five factors. DESIGN: A validation study. SETTING: Outpatients clinics and people's homes. SUBJECTS: Two hundred and thirteen people with multiple sclerosis, rheumatoid arthritis, spinal cord injury, and general practice attendees, stratified by level of disability (median age 54, 42% male, 58% female). INCLUSION CRITERIA: English as first language, aged 18-75, Mental Status Questionnaire score >6. INTERVENTIONS: Self- and interviewer-administered outcome measures. MAIN MEASURES: IPA, including one new item (66 participants completed the IPA on a second occasion). OTHER MEASURES: Short Form-36 Health Survey (SF-36), London Handicap Scale, three domains of the Functional Limitations Profile (FLP): household management, social integration, emotion. RESULTS: Confirmatory factor analysis confirmed the construct validity of the IPA (Normal Fit Index = 0.98, Comparative Fit Index = 0.99), indicating a good fit to the model. Convergent and discriminant validity were confirmed by the predicted associations, or lack of, with the exception of a poor association between the 'social life/relationships' IPA subscale and FLP-emotion. Internal reliability of the IPA was confirmed (Cronbach alphas >0.8; item-total correlations for all subscales >0.5). Test-retest reliability was confirmed for all items (weighted kappas >0.6) and subscales (intraclass correlation coefficients >0.90). CONCLUSIONS: The English IPA is a valid, reliable and acceptable measure of participation and autonomy in people with a range of conditions and can make a unique and fundamental contribution to outcome assessment. Further research is required to examine the responsiveness of the IPA to change over time, its clinical utility and suitability for use with people from ethnic minorities and with older people.

Persons with Disabilities↗
PubMed2005

Determination of free and protein-bound methadone and its major metabolite EDDP: enantiomeric separation and quantitation by LC/MS/MS.

OBJECTIVE: To measure free and protein-bound R- and S-enantiomers of methadone and its major metabolite, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in serum. METHODS: To determine free fraction, samples were filtered using ultrafiltration membranes with a molecular weight cut-off of 10,000 Da and extracted using liquid-liquid extraction. The solvent extract was evaporated and reconstituted in mobile phase for analysis by LC/MS/MS. Total analyte was determined by extracting unfiltered samples. Enantiomeric separation was by chiral chromatography. RESULTS: LC conditions resulted in baseline separation of R- and S-EDDP, and 85% resolution of methadone enantiomers. Precision of spiked specimens for both R- and S-methadone and R- and S-EDDP was less than 10% at 100 nM, and did not exceed 20% at 10 nM. CONCLUSIONS: Using minimal sample clean-up and a total instrument run-time of 10 min, a rapid, sensitive and highly specific method was developed for quantitation of free and total R- and S-enantiomers of methadone and EDDP.

Chromatography, Liquid↗
PubMed2005

Free and bound enantiomers of methadone and its metabolite, EDDP in methadone maintenance treatment: relationship to dosage?

OBJECTIVES: To determine the effects of metabolism and protein binding on the relationship between administered dose, blood levels of R methadone and biological response by measuring the free and protein-bound forms of the R and S enantiomers of methadone and EDDP, its metabolite. DESIGN AND METHODS: To measure free and total drug, trough levels were collected from 45 methadone clients. To measure free methadone, samples were filtered using ultrafiltration with a MW weight cut-off of 10,000 and extracted using liquid-liquid extraction. The solvent was evaporated and samples reconstituted in mobile phase for analysis by LC/MS/MS. Total analyte was determined by extracting unfiltered samples. Enantiomeric separation of methadone and EDDP was by chiral chromatography. RESULTS: The presence of unmetabolized methadone suggested that none of the patients were very fast metabolizers. R and S forms were metabolized at the same rate at all administered doses. Free R methadone levels correlated both with methadone dose and with the total amount of R methadone. The free fraction of R methadone (%free R) was higher at lower doses than at high doses, varied from 5 to 25% and was inversely proportional to the total dose of administered drug in a relationship that was logarithmic and non-linear. CONCLUSIONS: By measuring the free, biologically active form of the drug, we were unable to account for the large variations in dose required between different patients to prevent the onset of withdrawal symptoms. The reason for the large range in dosage may be multifactorial.

Blood Proteins↗
PubMed2005

The acute effect of alcohol on decision making in social drinkers.

RATIONALE: Many studies have reported the long-term adverse effects of alcohol on executive cognitive function in chronic alcohol abusers, yet little research has investigated the acute effects of alcohol in social drinkers. Studies on acute effects report alcohol-induced deficits on tasks that require executive cognitive processes, with alcohol acting to increase preservative errors and reduce planning. AIM: The present investigation examines the acute effects of a moderate dose of alcohol on a decision-making task that involves participants making a forced choice between two simultaneously presented binary-outcome gambles. METHODS: Alcohol (0.6 g/kg) or placebo was administered to 32 social drinkers. Participants completed the task, making a total of 80 decisions about gambles that varied in the magnitude of expected gains, losses and the probability with which these outcomes were delivered. Participants also chose between gambles probing identified non-normative biases in human decision making, namely, risk aversion for choosing between gains and risk seeking for choosing between losses. RESULTS: All participants picked the experimental gamble more frequently when the probability of winning was high vs low, when the gains were large vs small and when the losses were small vs large; the alcohol group had an impaired ability to factor in the magnitude of gains and the likelihood of winning when the losses were large. Deliberation time did not differ between the groups. CONCLUSION: These data suggest that alcohol given acutely impairs risky decision making. In particular, alcohol impairs one's ability to alter responding in light of changing prospective rewards in order to make favourable decisions.

Adult↗