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Biomedical subjects

G Scott

Publications and source records attributed to G Scott.

At least 37 records · Page 2Linked to original sources
PubMed2003

The use of tranexamic acid to reduce blood loss during total knee arthroplasty.

HYPOTHESIS: The fall in haemoglobin following unilateral total knee arthroplasty is reduced by tranexamic acid administration. METHODS: 60 patients were studied in total, 30 received tranexamic acid 10 mg/kg on induction and a further dose shortly before the release of the tourniquet. Surgery was performed by the senior author in a standardised fashion using the Freeman Samuelson cemented total knee replacement. Haemoglobin levels were measured 2 weeks pre and 3 days post operatively. Any complications were noted. A control group was matched using the Bone and Joint Research Unit database for age, sex, disease and pre-operative haemoglobin level. This group had been monitored in the same way as the group treated with tranexamic acid. RESULTS: In the group receiving no tranexamic acid the mean fall in haemoglobin was 2.8 g/dl (95% CI of mean 2.5-3.2) and in the group treated with tranexamic acid 1.7 g/dl (95% CI of mean 1.3-2) P<0.01. There were no complications in either group. CONCLUSIONS: The administration of tranexamic acid is an effective method of reducing the haemoglobin fall following knee arthroplasty.

Aged↗
PubMed2003

Effect of lidocaine and NMDA injections into the medial pontobulbar reticular formation on mastication evoked by cortical stimulation in anaesthetized rabbits.

Neurons of the dorsal nucleus reticularis pontis caudalis (nPontc) fire rhythmically during fictive mastication, while neurons of the ventral half tend to fire tonically (Westberg et al., 2001). This paper describes the changes in the pattern of rhythmical mastication elicited by stimulation of the sensorimotor cortex during inhibition or excitation of neurons in this nucleus and adjacent parts of nucleus reticularis gigantocellularis (Rgc) in the anaesthetized rabbit. Masticatory movements and electromyographic (EMG) activity of the masseter and digastric muscles produced by cortical stimulation were recorded before, during and after injections of a local anaesthetic (lidocaine) or excitatory amino acid N-methyl-d-aspartate (NMDA) into nPontc and Rgc through a microsyringe with attached microelectrode to record neuronal activity. Lidocaine inhibited local neurons and modified the motor program, and the effects varied with the site of injection. Most injections into the ventral half of nPontc increased cycle duration, digastric burst duration and burst area. The action of lidocaine in dorsal nPontc was more variable, although burst duration and area were often decreased. The effects on the muscle activity were always bilateral. Lidocaine block of the rostromedial part of Rgc had no effect on movements or on EMGs. Injections of NMDA excited local neurons and when injected into ventral nPontc, it completely blocked mastication. Dorsal injections either had no effect or increased cycle frequency, while decreasing burst duration and area. No increases in EMG burst duration or area were observed with NMDA. Our findings suggest that neurons of ventral nPontc tonically inhibit other parts of the central pattern generator during mastication, while dorsal neurons have mixed effects. We incorporated these findings into a new model of the masticatory central pattern generator.

Anesthesia↗
PubMed2003

Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients.

AIMS: To measure pimecrolimus blood concentrations and to evaluate tolerability and efficacy in children and infants treated topically for atopic dermatitis with pimecrolimus cream 1% for three weeks. METHODS: Three open label, non-controlled, multiple topical dose studies were conducted in children aged 8-14 years (study A, ten patients), and in infants aged 8-30 months (study B, eight patients) and 4-11 months (study C, eight patients). Pimecrolimus blood concentrations were determined on days 4 and 22 of treatment, and at end of study. Efficacy was assessed using the Eczema Area and Severity Index (EASI). RESULTS: Pimecrolimus blood concentrations were consistently low, typically (81%) below 1 ng/ml, with more than half of the measurements below the assay limit of quantitation (0.5 ng/ml) in studies A and B. The highest blood concentration measured throughout the three studies was 2.6 ng/ml. The cream was well tolerated, locally and systemically. The most common adverse event suspected to be related to study medication was a transient mild to moderate stinging sensation at the application site in 5/26 patients. There was no indication of any systemic adverse effect. The patients responded well to therapy with a rapid onset of action, usually within four days. Median reductions of EASI from baseline at day 22 were 55% (study A), 63% (study B), and 83% (study C). CONCLUSION: Three weeks treatment of children and infants with extensive atopic dermatitis, using pimecrolimus cream 1% twice daily, is well tolerated and results in minimal systemic exposure, at which no systemic effect is expected.

Adolescent↗
PubMed2003

Atypical herpes type 2 encephalitis associated with normal MRI imaging.

We describe a case of chronic atypical herpes simplex type 2 encephalitis in an immunocompromised 68 year old man presenting with headache and cognitive changes without focal neurological or MRI findings. To our knowledge this is the first described case of herpes simplex encephalitis associated with normal MRI brain imaging and non-focal neurological examination. This further expands the range of clinical presentations that may be associated with herpes simplex encephalitis and emphasises the value of PCR for herpes simplex virus in the investigation of encephalitis regardless of imaging findings.

Aged↗
PubMed2003

The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development.

Dentin Matrix Protein 1 (Dmp1) was originally identified from dentin. However, its expression and function in vivo are not clear. To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene. Northern blot analysis shows the expected 5.8-kb Dmp1-lacZ fusion transcript and loss of the wild-type 2.8-kb Dmp1 transcript, confirmed by a lack of immunostaining for the protein. Using heterozygous animals, we demonstrate that Dmp1 is specific for mineralized tissues. Not previously shown, Dmp1 is also expressed in pulp cells. Dmp1-deficient embryos and newborns display no apparent gross abnormal phenotype, although there are a modest expansion of the hypertrophic chondrocyte zone and a modest increase in the long bone diameter. This suggests that DMP1 is not essential for early mouse skeletal or dental development.

Animals↗
PubMed2003

Should the cement mantle around the femoral component be thick or thin?

We have compared the survival and radiological outcome at ten years after total hip replacement using two techniques for preparing the femoral canal. The same prosthesis was used throughout and all operations were performed by the same surgical team. In technique 1 the canal was over-reamed by 2 mm and in technique 2 it was reamed to the same size as the prosthesis. Technique 1 was performed on 92 patients and technique 2 on 97 patients. The survival at ten years was 97.2% (90.6 to 99.2) for technique 1 and 98.8% (92.9 to 99.8) for technique 2. Vertical migration was greater in technique 1 (1.8 mm versus 1.0 mm at five years; p = 0.36). There were significantly more lytic lesions and radiolucent lines at five years (p = 0.0061) with technique 1. We conclude that technique 2 is not worse and may produce better long-term results than current teaching suggests.

Aged↗
PubMed2003

Failure of an uncemented non-porous metal-backed prosthesis with augmentation using impacted allograft for acetabular revision 12- to 17-year results.

We have reviewed 29 patients (30 hips) who had undergone revision total hip arthroplasty using a Freeman metal-backed acetabular component and acetabular impaction allografting. The mean follow-up was for 153 years (12 to 17). Five patients (5 hips) died with the prosthesis in situ and four (4 hips) were lost to follow-up. Twelve hips had failed and in the remaining nine there were minor symptoms. The mean time to failure requiring further surgery was nine years. Excluding patients who were lost to follow-up or had died, 72% of the hips were radiologically loose at the last review. The commonest pattern in those requiring revision was failure of the reinforcement ring in adduction with remodelling of the medial wall. Of the nine patients who had not undergone revision, one with bilateral replacements had no current radiographs and only three of the remaining seven replacements had no radiological signs of loosening. The short-term results for this technique have been reported to be satisfactory, but in the long term they are not. The factors associated with failure include the design of the prosthesis, which has been implicated in disappointing long-term results when used in primary arthroplasty, but not with the frequency of failure found in this series. It seems that the reliance on peripheral screw fixation over a bed of allograft without bridging the graft does not provide sufficient stability to allow incorporation of the graft.

Acetabulum↗
PubMed2003

A femoral component with proximal HA coating. An analysis of survival and fixation at up to ten years.

We describe the survival at ten years of 100 femoral components of the Freeman hip prosthesis. It is proximally hydroxyapatite (HA)-coated and was fixed without cement. Radiological assessment identified radiolucent lines (RLLs) and lytic lesions and was used to measure migration. The criterion of failure was revision or impending revision for aseptic femoral loosening. No femoral components were revised or are awaiting revision for aseptic loosening, giving 100% survival at ten years (95% confidence interval, 95.7 to 100), although 59 were at risk at ten years. Two components were revised for fracture of a ceramic head with damage to the trunnion. Although well fixed in each, for survival analysis we evaluated the hip as if the patient had died. Twelve acetabular components were revised and at each operation the femoral component was found to be well fixed, was not disturbed and remained in the survival analysis. Three patients were lost to follow-up, and 12 died with well-functioning prostheses. Radiologically, all except one of the components appeared to be well fixed with no RLLs and no lytic lesions at the latest follow-up. The mean vertical migration was 0.4 mm at one year, 0.8 mm at two years and 1.4 mm at ten years. One component had migrated 7.6 mm at ten years (2.1 mm in year 1) and developed RLLs in Gruen zones I and II. The symptoms, however, were only minor and revision was not indicated. Our study has shown that proximal HA coating gives effective fixation for a femoral component.

Arthritis, Rheumatoid↗
PubMed2002

Is CPD effective?

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed2002

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria.

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 20 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Alzheimer Disease↗
PubMed2002

Origin and distribution of polycyclic aromatic hydrocarbons in surficial sediments from the savannah river.

Surface sediments collected from the Savannah River, located in the southeastern state of Georgia, USA, in June-July 1994 were analyzed for individual polycyclic aromatic hydrocarbons (PAHs). Three subdivisions of the river were identified for the study: upstream from, adjacent to, and downstream from the city of Savannah. There was high spatial variability in the total PAH (SigmaPAH) concentrations that ranged from 29 to 5,375 ng/g with an average concentration of 1,216 +/- 1,161 (SD). Of the three subdivisions, the highest SigmaPAH concentrations were in the middle segment, which was adjacent to urban and industrial areas. To elucidate sources, molecular indices based on indices among phenanthrene versus anthracene and fluoranthene versus pyrene were used to determine pyrogenic and petrogenic sources, respectively. These indices have been used by other authors to differentiate sources. In most cases, PAHs in sediments nearest the city of Savannah were of high temperature and pyrogenic origin. These pyrogenic PAHs were highly associated with toxicity to benthic organisms. The two-ringed naphthalene and substituted naphthalenes, which are petroleum-related PAHs, were significantly higher in the lower section of the river relative to the subdivisions. This river segment receives inputs primarily from shipping and boating traffic. Perylene, which is indicative of nonanthropogenic terrestrial inputs of carbon, had the highest concentration among the individual PAHs measured. High perylene concentrations were found at stations located upstream and adjacent to forested terrain and where salinity level was low. To discriminate pattern differences and similarities of individual PAHs among samples, principal component analysis (PCA) was performed on the more hydrophobic and persistent nonalkylated PAHs. These differences and similarities were used to infer perylene origin. PCA was performed on 14 nonalkylated PAHs that was normalized to the sum of nonalkylated PAHs, using a correlation matrix. Generally, the PAHs were separated into group patterns according to chemical and physical properties associated with log K(OW), except perylene. Perylene, a five-ringed PAH, was distinctly separated from the other five-ringed PAHs. The sources for perylene are likely from biogenic, terrestrial precursors. The collected data show that pyrogenic PAHs were highly associated with biological effects on benthic organisms, based on bioassay results. Perylene, a nonanthropogenic PAH, was found throughout the river and constituted a large percentage of total PAHs in the upper river.

Animals↗
PubMed2002

Anticonvulsant activity of aqueous extract of Leonotis leonurus.

Water extract of Leonotis leonurus was tested for anticonvulsant activity against seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used and significantly (p < 0.05; Student's t-test) delayed pentylenetetrazole (90 mg/kg)-induced tonic seizures. Similarly, the same doses of L. leonurus extract significantly (p < 0.05; Student's t-test) delayed the onset of tonic seizures produced by picrotoxin (8 mg/kg) and N-methyl-DL-aspartic acid (400 mg/kg). However, all the doses of aqueous extract of L leonurus used did not alter the seizures induced by bicuculline (20 mg/kg) to any significant extent. The data suggest that the extract of L. leonurus has anticonvulsant activity and may probably be acting through non-specific mechanisms, since it affects both gabaergic and glutaminergic systems. High performance liquid chromatography (HPLC) and phytochemical tests carried out respectively show a spectrum profile, characteristic of L. leonurus and the presence of alkaloids, saponins and tannins in the extract.

Animals↗
PubMed2002

Rapid mutation detection by the transgenomic wave analyser DHPLC identifies MYOC mutations in patients with ocular hypertension and/or open angle glaucoma.

AIMS: To rapidly screen Scottish patients with a family history of open angle glaucoma (OAG) or ocular hypertension (OHT) for mutations in the myocilin gene (MYOC) and develop a new rapid screening method for MYOC mutation detection. METHODS: All three exons of the MYOC gene were amplified by PCR from genomic DNA and subjected to direct DNA sequencing. Mutation detection methodology was also developed based on denaturing high performance liquid chromatography (DHPLC). A recurrent mutation was investigated by analysis of microsatellite haplotypes at the MYOC gene locus. RESULTS: Mutations were identified by DNA sequencing in four families. MYOC mutation Q368X was found in three kindreds and the fourth family carried the mutation G367R. The Q368X mutation was found to be associated with the same haplotype for markers closely flanking the MYOC gene. The mutations were identified by direct sequencing and were also readily detected by DHPLC analysis of PCR fragments, demonstrating that this is a robust method for MYOC analysis in future. CONCLUSIONS: Mutations in the MYOC gene were identified in patients presenting with highly variable phenotypes from normal through OHT to severe OAG. Haplotype analysis showed that mutation Q368X is likely to be an ancestral mutation in this population. DHPLC analysis is an accurate, rapid and cost effective method for MYOC mutation analysis in large population samples.

Adult↗
PubMed2002

Evidence for functional partitioning of the rabbit digastric muscle.

The rabbit digastric muscle has a single belly that opens and retracts the mandible. It does not contain connective tissue partitions, and all fibers arise from the same tendon and insert into a single broad site. Historically, it was assumed that the muscle functioned as a single unit. Since we had preliminary evidence that this might not be the case, we carried out five small studies in rabbits. First, we showed that electromyographic (EMG) activity varies between recording sites within the muscle during the masticatory cycle induced by repetitive stimulation of the sensorimotor cortex. We found that EMG activity in the caudal region sometimes began before the anterior EMG during mastication when the jaw swung to the side of the muscle, but the two regions became active at the same time during other patterns. We next showed that separate branches of the mylohyoid nerve enter the anterior, intermediate and caudal regions of the digastric. However, a separate study showed that the motor endplates were distributed across a continuous sheet, consistent with a single anatomical partition. We then stimulated single nerve branches to deplete glycogen. By comparing the optical density of fibers labeled by the periodic acid-Schiff method for glycogen, we were able to show that the three branches innervate separate regions of the muscle. Finally, we applied either FluoroGold or Fast Blue dyes to the central cut ends of the branches to label the cell bodies of the three pools of motoneurons. These were found within the middle and caudal thirds of the trigeminal motor nucleus, but there appeared to be no spatial separation of the three pools or double labeling of cells. We conclude that the digastric muscle contains two and possibly three functional subregions. The fact that the motoneurons are intermingled suggests that the distribution of motor commands to the three pools is not based on their location.

Animals↗
PubMed2002

The natural history and significance of radiolucent lines at a cemented femoral interface.

We studied 185 total hip replacements and related the identification of radiolucent lines (RLLs) at two years to the later development of lytic lesions and loosening. Linear polyethylene wear was also measured. RLLs appeared in 34 hips at a mean of 2.0 years after operation, and lytic lesions in ten hips at 5.7 years. Of 151 THRs without RLLs there was neither rapid migration nor loosening and only one developed a possible lytic lesion. Of 23 hips with non-progressive RLLs there was neither rapid migration nor loosening, but six developed a lytic lesion. By contrast, 11 THRs with progressive RLLs migrated rapidly and seven developed a lytic lesion. Six THRs with progressive RLLs failed. The wear rates were the same in all groups, although limited numbers were available for study. If the surgeon achieves secure initial fixation as shown by slow or no migration and no RLLs during the first two years, it is likely that no lytic lesions will develop by five years or aseptic loosening by ten years. If an imperfect, but adequate, interface is achieved, as shown by slow migration and non-progressive RLLs lytic lesions adjacent to the RLLs may develop by five years, but aseptic loosening will be unlikely at ten. Insecure initial fixation, as shown by more rapid migration and progressive RLLs at two years, is likely to lead to the formation of lytic lesions at five years and loosening at ten. The outcome after THR is therefore determined at the initial operation and may be predicted at two years. The presence of lytic lesions reflects soft tissue at the interface as shown by the RLLs which accompany and promote loosening but, in our study, did not cause it.

Aged↗
PubMed2001

Functional analyses of two alternative isoforms of the transcription factor Pax-5.

The Pax-5 gene plays a central role in B cell development, activation, and differentiation. At least four different isoforms have been identified, of which isoform Pax-5a has been extensively studied, while functions for alternative isoforms were previously unknown. Here, using a transient transfection system, we provide evidence that alternative isoform Pax-5d acts as a dominant-negative regulator by suppressing activity of Pax-5a in a dose-dependent manner. In contrast, co-expression in the presence of alternative isoform Pax-5e causes an increase in Pax-5a activity. Protein studies on Pax-5e using Western blot analysis revealed that this 19-kDa isoform migrates as a 27-kDa species on SDS-polyacrylamide electrophoresis gels, while a mutant Pax-5e form in which a C-terminal cysteine residue has been mutated, runs at the expected 19 kDa. Using both Western blot and immunoprecipitation assays, we further provide evidence that this size discrepancy may be caused by a tight association between Pax-5e and a thioredoxin-like factor. Comparison of various B cell lines as well as resting and lipopolysaccharide-activated mature B lymphocytes shows that increased B cell proliferation correlates with increased levels of Pax-5e/thioredoxin, whereas increased Pax-5d amounts correlate with inhibition of cell growth. Together, our results suggest that during activation and differentiation of B lymphocytes, Pax-5a function is modulated by two alternative spliced isoforms: the dominant negative Pax-5d isoform may mediate inhibition of Pax-5a activity in resting B cells, while alternative isoform Pax-5e associated with thioredoxin may increase Pax-5a activity through an unknown (redox) mechanism.

3T3 Cells↗