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Biomedical subjects

A Robertson

Publications and source records attributed to A Robertson.

At least 37 records · Page 2Linked to original sources
PubMed2004

The effect of temperature, humidity and peak inspiratory nasal flow on olfactory thresholds.

Temperature, humidity and nasal peak inspiratory flow rate (PIFR) are potential variables in the quantitative measurement of olfactory thresholds in the clinic. To date, these variables have not been properly evaluated with respect to olfactory perception, and therefore the aim of this study was to determine their effect on the thresholds. These variables were measured on 10 occasions in 10 subjects over a 10-week period. The results obtained were then subjected to statistical analysis using a linear mixed-effect model. This demonstrated that olfactory thresholds are sufficiently independent of room temperature, peak humidity and nasal PIFR in a routine outpatient clinic environment in normal subjects, with no evidence of any statistically significant influence by these variables.

Adult↗
PubMed2004

Effects of leg massage on recovery from high intensity cycling exercise.

BACKGROUND: The effect of massage on recovery from high intensity exercise is debatable. Many studies on massage suffer from methodological flaws such as poor standardisation of previous exercise, lack of dietary control, and inappropriate massage duration. OBJECTIVE: To examine the effects of leg massage compared with passive recovery on lactate clearance, muscular power output, and fatigue characteristics after repeated high intensity cycling exercise, with the conditions before the intervention controlled and standardised. METHODS: Nine male games players participated. They attended the laboratory on two occasions one week apart and at the same time of day. Dietary intake and activity were replicated for the two preceding days on each occasion. After baseline measurement of heart rate and blood lactate concentration, subjects performed a standardised warm up on the cycle ergometer. This was followed by six standardised 30 second high intensity exercise bouts, interspersed with 30 seconds of active recovery. After five minutes of active recovery and either 20 minutes of leg massage or supine passive rest, subjects performed a second standardised warm up and a 30 second Wingate test. Capillary blood samples were drawn at intervals, and heart rate, peak power, mean power, and fatigue index were recorded. RESULTS: There were no significant differences in mean power during the initial high intensity exercise bouts (p = 0.92). No main effect of massage was observed on blood lactate concentration between trials (p = 0.82) or heart rate (p = 0.81). There was no difference in the maximum power (p = 0.75) or mean power (p = 0.66) in the subsequent Wingate test, but a significantly lower fatigue index was observed in the massage trial (p = 0.04; mean (SD) fatigue index 30.2 (4.1)% v 34.2 (3.3)%). CONCLUSIONS: No measurable physiological effects of leg massage compared with passive recovery were observed on recovery from high intensity exercise, but the subsequent effect on fatigue index warrants further investigation.

Adult↗
PubMed2004

Patients awaiting laparoscopic cholecystectomy--can preoperative complications be predicted?

AIMS: To determine the nature and incidence of gallstone-related complications arising in patients awaiting laparoscopic cholecystectomy and to formulate a strategy to detect those most in need of urgent intervention. PATIENTS AND METHODS: A retrospective analysis of the case notes of 337 consecutive patients undergoing laparoscopic cholecystectomy under a single surgeon in a district general hospital between 1995 and 1999. RESULTS: Of patients awaiting laparoscopic cholecystectomy, 65 (19.3%) were documented as suffering significant on-going symptoms, of whom 19 (5.6%) required hospital admission or urgent surgical review at median 8.9 weeks (range 0.1-32.3 weeks) after being placed on the waiting list. Factors predictive of symptom recurrence included: (i) initial acute presentation; (ii) diagnoses of jaundice, pancreatitis, or acute cholecystitis; (iii) elevation of amylase or liver function tests; and (iv) small stones on ultrasonography examination. CONCLUSIONS: A significant proportion of patients awaiting laparoscopic cholecystectomy experience stone-related complications requiring hospital admission. We feel it is possible to reduce this number by selecting those most at risk on the basis of their history and pre-operative investigations for more urgent intervention.

Adult↗
PubMed2003

Torsion of an intra-articular lipoma as a cause of pseudo locking of the knee.

We describe a case of a painful locked knee caused by the torsion of an intra-articular lipoma and review the literature on this unusual condition. There are many cases of locked knee and of intra-articular lipoma but to our knowledge there are no previous documented cases of a torted lipoma being identified as a cause of locking.

Adult↗
PubMed2002

Post-mortem analysis of samples from a human victim of a fatal poisoning caused by the xanthid crab, Zosimus aeneus.

After ingestion of a specimen of the crab Zosimus aeneus (Xanthidae), an East Timorese adult male died within several hours. Xanthid crabs are known to harbour paralytic shellfish toxins (PSTs), tetrodotoxin and palytoxin. A post-mortem examination did not find any obvious pathological abnormalities. This absence of pathologies is more often associated with PSTs and tetrodotoxin intoxication. A second, yet uneaten specimen of Z. aeneus from the same meal, contained a significant amount of PSTs and these same toxins were identified in the gut contents, blood, liver and urine of the victim. Metabolism of the PSTs occurred with the ingested crab harbouring gonyautoxin 2, gonyautoxin 3 and saxitoxin (STX) whereas neoSTX, decarbamoylSTX and STX dominated the PSTs in the victim's urine. The PST composition in the gut contents, in both their identity and proportion, was intermediate between the eaten crab and the urine suggesting that toxin conversion commenced in the victim's gut. The dose consumed by the victim was calculated to be between 1 and 2 microg STX equivalents/kg based upon the concentration in the remains of the cooked crab. The victim's meal did not consist solely of the toxic crab eaten and the possibility of other food items acting in a synergistic manner with the consumed PSTs cannot be discounted.

Adult↗
PubMed2002

Karyotypic aberrations of chromosomes 16 and 17 are related to survival in patients with breast cancer.

BACKGROUND: Breast cancer has a high incidence and associated mortality rate, yet little is known of the sequence of genetic events that underlie the clinical course. METHODS: The study was a comparative genomic hybridization analysis of 40 primary breast cancers with survival data at a mean of 8.4 years. RESULTS: The mean number of aberrations was 9.0, with a mean of 5.5 gains and 3.5 deletions per tumour. The most common aberrations were: gain of 1q (27 of 40), 8q (19 of 40) and 17q (13 of 40), and deletion of 17p (12 of 40) and 8p (11 of 40). These results are consistent with a distinctive pattern of large-scale (karyotypic) genetic change in primary breast cancer. CONCLUSION: The novel findings of this study were that only women who were disease-free had loss of 16q (E-cadherin) in association with a gain of 16p, and 17p13 (p53) loss combined with 17q12 (HER2) amplification was found only in the cancers of women who developed recurrent disease. The karyotypic changes seen in primary breast cancer seem to be associated with outcome and point to the underlying genetic events.

Breast Neoplasms↗
PubMed2002

Interpretation of occupational peak flow records: level of agreement between expert clinicians and Oasys-2.

BACKGROUND: Oasys-2 is a validated diagnostic aid for occupational asthma that interprets peak expiratory flow (PEF) records as well as generating summary plots. The system removes inconsistency in interpretation, which is important if there is limited agreement between experts. A study was undertaken to assess the level of agreement between expert clinicians interpreting serial PEF measurements in relation to work exposure and to compare the responses given by Oasys-2. METHOD: 35 PEF records from workers under investigation for suspected occupational asthma were available for review. Records included details of nature of work, intercurrent illness, drug therapy, predicted PEF, rest periods, and holidays. Simple plots of PEF and the Oasys-2 generated plots were available. Experts were advised that approximately 1 hour was available to review the records. They were asked to score each work-rest-work (WRW) period and each rest-work-rest (RWR) period for evidence of occupational effect. At the end of each record scores of 0-100% were given for evidence of "asthma" and "occupational effect" for the whole record. Kappa values were calculated for each scored period and for the opinions on the whole record. The scores were converted into four groups (0-25%, 26-50%, 51-75%, 76-100%) and two groups (0-50% and 51-100%) for analysis. This is relevant to scores produced by Oasys-2. Agreement between Oasys-2 scores and each expert was calculated. RESULTS: 24 of 35 records were analysed by seven experts in the allotted time. For whole record occupational effect, median kappa values were 0.83 (range 0.56-0.94) for two groups and 0.62 (0.11-0.83) for four groups. For asthma, median kappa values were 0.58 (0-0.67) and 0.42 (0.15-0.70) for two and four groups respectively. For all WRW and RWR periods kappa values were 0.84 (0.42-0.94) and 0.70 (0.46-0.87) respectively. Agreement between Oasys-2 and individual experts showed a median kappa value of 0.75 (0.50-0.92) for two groups and 0.50 (0.39-0.70) for four groups. Kappa values for the median expert score v Oasys-2 were 0.75 for two groups and 0.67 for four groups. Agreement was poor for records with intermediate probability, as defined by Oasys-2. CONCLUSION: Considerable variation in agreement was seen in expert interpretation of occupational PEF records which may lead to inconsistencies in diagnosis of occupational asthma. There is a need for an objective scoring system which removes human variability, such as that provided by Oasys-2.

Asthma↗
PubMed2001

Laparoscopic cholecystectomy without routine operative cholangiography does not result in significant problems related to retained stones.

BACKGROUND: This study investigated whether failure to identify common bile duct stones at laparoscopic cholecystectomy results in significant postoperative complications related to retained stones. METHODS: We performed a retrospective analysis of the case notes of 377 consecutive patients undergoing laparoscopic cholecystectomy without routine operative cholangiography under a single surgeon in a district general hospital between 1995 and 1999. Highly selective preoperative endoscopic retrograde cholangiopancreatography (ERCP) was employed to identify and manage suspected bile duct stones in pancreatitis, jaundice, persistently elevated liver function tests, or a dilated common bile duct. RESULTS: Eighteen (4.8%) of 377 patients presented postoperatively with symptoms/signs suggesting biliary pathology. Two (0.5%) were confirmed to have retained duct stones/debris (ultrasound/ERCP); both recovered with conservative treatment. Only 1 patient of 274 (0.4%) without preoperative ERCP subsequently presented with a symptomatic retained stone, the other having been stented preoperatively. CONCLUSIONS: Highly selective preoperative ERCP without routine operative cholangiography is not associated with a significant increase in morbidity/mortality related to retained stones following laparoscopic cholecystectomy.

Adolescent↗
PubMed2001

Time course and nerve growth factor dependence of inflammation-induced alterations in electrophysiological membrane properties in nociceptive primary afferent neurons.

Novel findings of changes in nociceptive dorsal root ganglion (DRG) neurons during hindlimb inflammation induced by complete Freund's adjuvant (CFA) injections in the hindpaw and hindleg are reported. These include increased maximum fiber following frequency in nociceptive C- and Adelta-fiber units by 2.7 and 3 times, respectively, and increased incidence of ongoing (spontaneous) activity by 3.3 times (to 54%) and 2.4 times (to 27%), respectively. These changes and the CFA-induced changes in somatic action potential (AP) configuration in nociceptive neurons (Djouhri and Lawson, 1999) were incomplete 24 hr after CFA. The nerve growth factor (NGF) dependence of the inflammation-induced changes was examined by injecting a synthetic NGF sequestering protein [tyrosine receptor kinase A Ig2 (trkA Ig2)] with CFA and subsequently into the CFA injection sites. NGF sequestration prevented some CFA-induced changes in nociceptive neurons including: the increased fiber following frequency (C and Adelta), the increased proportions of units with ongoing activity (C and Adelta), the decreased AP duration (C and Adelta), but not the decreased afterhyperpolarization (AHP) durations (C, Adelta, and Aalpha/beta) (Djouhri and Lawson, 1999). AP variables of nociceptive units with spontaneous activity were examined. The time course of electrophysiological changes in nociceptive units is consistent with processes involving altered protein expression and/or retrograde transport of factors. These results (1) implicate NGF in regulating inflammation-induced decreases in AP duration and in increases in firing rate and spontaneous activity but not in decreases in AHP duration and (2) suggest clinical advantages of reducing NGF in some inflammatory pain states.

Action Potentials↗
PubMed2001

Molecular modelling and experimental studies of mutation and cell-adhesion sites in the fibronectin type III and whey acidic protein domains of human anosmin-1.

Anosmin-1, the gene product of the KAL gene, is implicated in the pathogenesis of X-linked Kallmann's syndrome. Anosmin-1 protein expression is restricted to the basement membrane and interstitial matrix of tissues affected in this syndrome during development. The anosmin-1 sequence indicates an N-terminal cysteine-rich domain, a whey acidic protein (WAP) domain, four fibronectin type III (FnIII) domains and a C-terminal histidine-rich region, and shows similarity with cell-adhesion molecules, such as neural cell-adhesion molecule, TAG-1 and L1. We investigated the structural and functional significance of three loss-of-function missense mutations of anosmin-1 using comparative modelling of the four FnIII and the WAP domains based on known NMR and crystal structures. Three missense mutation-encoded amino acid substitutions, N267K, E514K and F517L, were mapped to structurally defined positions on the GFCC' beta-sheet face of the first and third FnIII domains. Electrostatic maps demonstrated large basic surfaces containing clusters of conserved predicted heparan sulphate-binding residues adjacent to these mutation sites. To examine these modelling results anosmin-1 was expressed in insect cells. The incorporation of the three mutations into recombinant anosmin-1 had no effect on its secretion. The removal of two dibasic motifs that may constitute potential physiological cleavage sites for anosmin-1 had no effect on cleavage. Peptides based on the anosmin-1 sequences R254--K285 and P504--K527 were then synthesized in order to assess the effect of the three mutations on cellular adhesion, using cell lines that represented potential functional targets of anosmin-1. Peptides (10 microg/ml) incorporating the N267K and E514K substitutions promoted enhanced adhesion to 13.S.1.24 rat olfactory epithelial cells and canine MDCK1 kidney epithelial cells (P<0.01) compared with the wild-type peptides. This result was attributed to the introduction of a lysine residue adjacent to the large basic surfaces. We predict that two of the three missense mutants increase the binding of anosmin-1 to an extracellular target, possibly by enhancing heparan sulphate binding, and that this critically affects the function of anosmin-1.

Amino Acid Motifs↗
PubMed2001

Structural studies in solution of the recombinant N-terminal pair of short consensus/complement repeat domains of complement receptor type 2 (CR2/CD21) and interactions with its ligand C3dg.

Human complement receptor type 2 (CR2, CD21) is a cell surface receptor that binds three distinct ligands (complement C3d, Epstein-Barr virus gp350/220, and the low-affinity IgE receptor CD23) via the N-terminal two of fifteen or sixteen short consensus/complement repeat (SCR) domains. Here, we report biophysical studies of the CR2 SCR 1-2 domain binding to its ligand C3dg. Two recombinant forms of CR2 containing the SCR 1-2 and SCR 1-15 domains were expressed in high yield in Pichia pastoris and baculovirus, respectively. Circular dichroism spectroscopy showed that CR2 SCR 1-2 receptor possessed a beta-sheet secondary structure with a melting temperature of 59 degrees C. Using surface plasmon resonance, kinetic parameters for the binding of either CR2 SCR 1-2 or the full-length SCR 1-15 form of CR2 showed that the affinity of binding to immobilized C3d is comparable for the SCR 1-15 compared to the SCR 1-2 form of CR2. Unexpectedly, both the association and dissociation rates for the SCR 1-15 form were slower than for the SCR 1-2 form. These data show that the SCR 1-2 domains account for the primary C3dg binding site of CR2 and that the additional SCR domains of full-length CR2 influence the ability of CR2 SCR 1-2 to interact with its ligand. Studies of the pH and ionic strength dependence of the interaction between SCR 1-2 and C3d by surface plasmon resonance showed that this is influenced by charged interactions, possibly involving the sole His residue in CR2 SCR 1-2. Sedimentation equilibrium studies of CR2 SCR 1-2 gave molecular weights of 17 000, in good agreement with its sequence-derived molecular weight to show that this was monomeric. Its sedimentation coefficient was determined to be 1.36 S. The complex with C3d gave molecular weights in 50 mM and 200 mM NaCl buffer that agreed closely with its sequence-derived molecular weight of 50 600 and showed that a 1:1 complex had been formed. Molecular graphics views of homology models for the separate CR2 SCR 1 and SCR 2 domains showed that both SCR domains exhibited a distribution of charged groups throughout its surface. The single His residue is located near a long eight-residue linker between the two SCR domains and may influence the linker conformation and the association of C3d and CR2 SCR 1-2 into their complex. Sedimentation modeling showed that the arrangement of the two SCR domains in CR2 SCR 1-2 is highly extended in solution.

Amino Acid Sequence↗
PubMed2001

Tomato Ve disease resistance genes encode cell surface-like receptors.

In tomato, Ve is implicated in race-specific resistance to infection by Verticillium species causing crop disease. Characterization of the Ve locus involved positional cloning and isolation of two closely linked inverted genes. Expression of individual Ve genes in susceptible potato plants conferred resistance to an aggressive race 1 isolate of Verticillium albo-atrum. The deduced primary structure of Ve1 and Ve2 included a hydrophobic N-terminal signal peptide, leucine-rich repeats containing 28 or 35 potential glycosylation sites, a hydrophobic membrane-spanning domain, and a C-terminal domain with the mammalian E/DXXXLphi or YXXphi endocytosis signals (phi is an amino acid with a hydrophobic side chain). A leucine zipper-like sequence occurs in the hydrophobic N-terminal signal peptide of Ve1 and a Pro-Glu-Ser-Thr (PEST)-like sequence resides in the C-terminal domain of Ve2. These structures suggest that the Ve genes encode a class of cell-surface glycoproteins with receptor-mediated endocytosis-like signals and leucine zipper or PEST sequences.

Amino Acid Sequence↗
PubMed2001

Induced myelination and demyelination in a conditional mouse model of Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A, a hereditary demyelinating neuropathy, is usually caused by overexpression of peripheral myelin protein 22 (PMP22) due to a genomic duplication. We have generated a transgenic mouse model in which mouse pmp22 overexpression can be regulated. In this mouse model, overexpression of pmp22 occurs specifically in Schwann cells of the peripheral nerve and is switched off when the mice are fed tetracycline. Overexpression of pmp22 throughout life (in the absence of tetracycline) causes demyelination. In contrast, myelination is nearly normal when pmp22 overexpression is switched off throughout life by feeding the mice tetracycline. When overexpression of pmp22 is switched off in adult mice, correction begins within 1 week and myelination is well advanced by 3 months (although the myelin sheaths are still thinner than normal), indicating that the Schwann cells are poised to start myelination. Upregulation of the gene in adult mice (which had previously had normal pmp22 expression) is followed by active demyelination within 1 week, which had plateaued by 8 weeks. This indicates that Schwann cells with mature myelin are sensitive to increased amounts of pmp22 such that they rapidly demyelinate. Thus, demyelination can largely be corrected within a few months, but the correction will be sensitive to subsequent upregulation of pmp22.

Animals↗