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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 55 records · Page 3Linked to original sources

Comparison of Roche MONITOR and Organon Teknika NucliSens assays to quantify human immunodeficiency virus type 1 RNA in cerebrospinal fluid.

We compared Roche MONITOR and Organon Teknika NucliSens assays for human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF). Results of 282 assays were highly correlated (r = 0.826), with MONITOR values being 0.29 +/- 0.4 log(10) copies/ml (mean +/- standard deviation) values. Both assays can reliably quantify HIV-1 RNA in CSF.

AIDS-Related Opportunistic Infections↗

Extrinsic muscle activity, foot motion and ankle joint moments during the stance phase of walking.

This study examined stance phase foot kinematics, kinetics and electromyographic (EMG) activity of extrinsic muscles of 18 healthy males. Three-dimensional kinematic and kinetic data were obtained via video analysis of surface markers and a force plate. Ankle joint moments are described about orthogonal axes in a segmental coordinate system. Kinematic data comprise rearfoot and forefoot motion, described about axes of a joint coordinate system, and medial longitudinal arch height. Surface EMG was obtained for tibialis anterior, soleus, gastocnemius medialis and lateralis, peroneus longus and peroneus brevis and extensor digitorum longus. It was concluded that the demands on the controlling muscles are greatest prior to foot flat and after heel rise. Tibialis anterior restrained rearfoot plantarflexion from heel contact to 10% stance, and eversion between 10% stance and footflat. Activity in peroneus longus was consistent with its role in causing eversion after heel contact, then as a stabiliser of the forefoot after heel rise. Activity in peroneus brevis suggested a role in restraining lateral rotation of the leg over the foot, late in stance.

Adolescent↗

An investigation of gender differences in the components influencing the difficulty of spatial ability items.

This study examines the role that gender differences play in the determination of the components influencing the difficulty of spatial ability items. Considerable research has examined the role of gender differences in spatial abilities, with sometimes contradictory findings. In general, the findings show that males tend to outperform females on spatial ability items. Other research has focused on determining the components of items that contribute to their difficulty. This research has usually been based on mixed-gender populations, however. The present study attempts to determine if gender influences the extent to which different components contribute to the difficulty of items. The results indicate that component difficulties show very little variation across gender. This finding supports the notion that any differences in raw scores observed for males and females are not due to differences in the manner in which males and females process spatial information or solve spatial ability items.

Adult↗

Adjuvant activities of immune response modifier R-848: comparison with CpG ODN.

R-848 and imiquimod belong to a class of immune response modifiers that are potent inducers of cytokines, including IFN-alpha, TNF-alpha, IL-12, and IFN-gamma. Many of these cytokines can affect the acquired immune response. This study examines the effects of R-848 on aspects of acquired immunity, including immunoglobulin secretion, in vivo cytokine production, and Ag-specific T cell cytokine production. Results are compared with those of Th1 CpG ODN. R-848 and CpG ODN are effective at skewing immunity in the presence of Alum toward a Th1 Ab response (IgG2a) and away from a Th2 Ab response (IgE). R-848 and CpG ODN are also capable of initiating an immune response in the absence of additional adjuvant by specifically enhancing IgG2a levels. Both R-848 and imiquimod showed activity when given subcutaneously or orally, indicating that the compound mechanism was not through generation of a depot effect. Although CpG ODN behaves similarly to R-848, CpG ODN has a distinct cytokine profile, is more effective than R-848 when given with Alum in the priming dose, and is active only when given by the same route as the Ag. The mechanism of R-848's adjuvant activity is linked to cytokine production, where increases in IgG2a levels are associated with IFN-alpha, TNF-alpha, IL-12, and IFN-gamma induction, and decreases in IgE levels are associated with IFN-alpha and TNF-alpha. Imiquimod also enhances IgG2a production when given with Ag. The above results suggest that the imidazoquinolines R-848 and imiquimod may be attractive compounds for use as vaccine adjuvants and in inhibiting pathological responses mediated by Th2 cytokines.

Adjuvants, Immunologic↗

Selective deuterium exchange during superheated heavy water chromatography-nuclear magnetic resonance spectroscopy-mass spectrometry of sulfonamides.

Superheated deuterium oxide has been investigated as an eluent for reversed-phase HPLC on a polystyrene-divinylbenzene column with UV, 1H NMR and MS detection using a series of sulfonamides as model compounds. In the course of these studies, a selective, specific and efficient deuteration of the methyl groups on a pyrimidine ring was observed during chromatography of certain of the sulfonamides. The potential of this methodology for producing deuterium-labelled compounds from substances bearing suitable substituents is considered. The utility of HPLC-NMR-MS as a means for studying on-column reactions is discussed.

Chromatography, Liquid↗

Determination of sulphur compounds in beer using headspace solid-phase microextraction and gas chromatographic analysis with pulsed flame photometric detection.

A simple and sensitive method for the analysis of volatile and semi-volatile sulphur compounds in beer at trace levels was developed using headspace solid-phase microextraction (SPME) and gas chromatography with pulsed flame photometric detection. Different SPME fibres were tested and a Carboxen-polydimethylsiloxane coated fibre was found to be the most appropriate. The adsorption and desorption conditions were optimised. The effect of ethanol concentration in the sample on the extraction of analytes was examined. A 60 m non-polar capillary column preceded by a 10 m length of a polar column was found to be capable of separating a wide range of C1-C6 sulphur compounds. The pulsed flame photometric detector enabled increased sensitivity to be obtained over previous methods, such as dynamic headspace followed by conventional flame photometric detection or sulphur chemiluminescent detection, with high sulphur selectivity. Two sulphur compounds, 2-methyl-1-butanethiol and 3-methylthiophene, were identified in beer for the first time.

Beer↗

Exocytotic insertion of calcium channels constrains compensatory endocytosis to sites of exocytosis.

Proteins inserted into the cell surface by exocytosis are thought to be retrieved by compensatory endocytosis, suggesting that retrieval requires granule proteins. In sea urchin eggs, calcium influx through P-type calcium channels is required for retrieval, and the large size of sea urchin secretory granules permits the direct observation of retrieval. Here we demonstrate that retrieval is limited to sites of prior exocytosis. We tested whether channel distribution can account for the localization of retrieval at exocytotic sites. We find that P-channels reside on secretory granules before fertilization, and are translocated to the egg surface by exocytosis. Our study provides strong evidence that the transitory insertion of P-type calcium channels in the surface membrane plays an obligatory role in the mechanism coupling exocytosis and compensatory endocytosis.

Animals↗

Identification of human TGF-beta1 signal (leader) sequence polymorphisms by PCR-RFLP.

Links between disease susceptibility and genetically determined variation in human cytokine expression have recently been described. This has led to a demand for simple methods of identifying cytokine gene polymorphisms of potential clinical relevance. Here, we describe a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for identifying two human transforming growth factor beta1 (TGF-beta1) signal (leader) sequence polymorphisms, T869C (Leu10Pro) and G915C (Arg25Pro). This permits simple and robust identification of TGF-beta1 leader sequence genotypes and demonstrates the physical linkage in cis between T869C (Leu10Pro) and G915C (Arg25Pro). The method does not require previously genotyped standards. The efficacy of enzyme digestion is internally controlled by the presence of conserved restriction sites.

Base Sequence↗

Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis.

OBJECTIVE: To assess the relationship between IL-10 release and anti-inflammatory response following blunt trauma. DESIGN: Prospective longitudinal clinical study. SETTING: Departments of trauma and anaesthetics in a university teaching hospital. PATIENTS: Forty-eight adult patients with a mean injury severity score of 14.5 (range 9-57) were prospectively studied following blunt trauma. MEASUREMENTS AND RESULTS: Venous blood samples were collected on arrival and at 16 and 24 h, and at 3, 5, and 7 days. Peripheral blood mononuclear cell (HLA-DR) expression on CD14 + monocytes was quantified by flow cytometry and serum IL-10 was assayed by ELISA. Anti-inflammatory response was defined as monocyte HLA-DR expression of less than 30% of that seen in healthy controls. Serum IL-10 levels in trauma patients on arrival was significantly elevated, 70.0 [48.0-92.1, 95% confidence interval, (CI)] compared to the control group, 3 (0-5) (P < 0.0001), and monocyte HLA-DR expression was significantly lower, 14.2 (12.1-16.3, 95% CI), in patients versus 25.2 (22.4-28.1) in controls (P < 0.001). Patients with low HLA-DR expression (n = 14) had significantly higher serum IL-10 levels than those whose HLA-DR expression remained above 30% of the control value (n = 34), (P < 0.038). In patients who developed sepsis (n = 11), serum IL-10 levels were greater on admission, [143.7 (80.2-207.2) pg/ml(-1)], and remained elevated during the study period compared with non-complicated patients, [50.16 (33.5-66.8) pg/ml(-1)]. Immediate IL-10 (2 h following trauma) was negatively correlated with simultaneous HLA-DR expression, (r = -0.49, P = 0.0005). CONCLUSION: These findings support the view that IL-10 release regulates monocyte HLA-DR expression and may be related to an anti-inflammatory response and development of sepsis following trauma.

Adult↗

Compartment syndrome following isolated ankle fracture.

We report two cases of compartment syndrome following isolated ankle fractures. Both required decompression of all the compartments following early clinical diagnosis and measurements of the intra-compartmental pressures.

Adult↗

Simultaneous bilateral femoral fractures: systemic complications in 14 cases.

We have retrospectively reviewed 14 patients with bilateral femoral shaft fractures who attended our institution between January 1993 and March 1999. The mean age of the patients was 38 years (19-75) and the median injury severity score (ISS) was 16 (interquartile range 10-20). Thirteen patients were treated with intramedullary nailing and 1 with plating and nailing within 24 h of admission to hospital. The mean resuscitation requirements were 10.6 (6-16) litres of colloid and crystalloid and 8.6 (4-30) units of blood. The mean intensive care unit/high dependency unit (ICU/HDU) stay was 4 days (1-14) and the mean hospital stay was 36.3 days (3-210). There were 6 cases of adult respiratory distress syndrome (ARDS), 1 compartment syndrome, 1 case of osteomyelitis, 1 above-knee amputation and 2 deaths (14.2%). The mean time to union was 24.5 weeks (12-37). Comparison to patients with unilateral injuries revealed a higher ISS, resuscitation requirements, ARDS, hospital stay and mortality.

Adult↗

Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning.

Delta-opioid receptors are known to participate in the protection found following ischemic preconditioning (IPC), but the role of kappa-receptors in IPC is currently controversial. Langendorff-perfused rat hearts received 35 min regional ischemia and 2 h reperfusion. PC (2 cycles 5 min global ischemia) substantially reduced infarct size. Pharmacological PC with the delta-agonist DADLE (10 nmol/L) had similar protective effects. However, higher dose DADLE (1 micromol/L) had a less beneficial effect, and in conjunction with the delta-antagonist naltrindole unexpectedly increased infarct size (61.5 +/- 2.0%, p<0.05 v 45.9 +/- 2.4% in controls) suggesting a non-delta effect. The universal kappa-opioid agonist bremazocine (30 nmol/L) increased infarct size (61.3 +/- 1.6%, p<0.05 v controls), an effect abrogated by the selective kappa1-antagonist nor-binaltorphimine (BNI). Since opiates are known to have anti-adrenergic effects, which hypothetically may help to mediate IPC, cyclic AMP levels were measured in DADLE and in bremazocine-treated hearts. Decreased levels of cyclic AMP at the start of the regional ischemic period were found in low dose DADLE hearts (0.485 +/- 0/020, n = 8, vs controls, 0.654 +/- 0.025 nmol/g wet weight, p<0.001), but not in high dose DADLE nor in bremazocine treated hearts. Thus, in the isolated rat heart kappa1-opioid receptor activation exacerbates infarct size through an as yet unknown mechanism, suggesting that there could be an "antipreconditioned state". In contrast, delta-activity mediates protection which may be associated with a reduction of tissue cyclic AMP levels.

Animals↗

Complications of tibial shaft soccer fractures.

A retrospective study of AO type 42 tibial diaphyseal fractures that presented to a teaching hospital over a 54 month period was made to identify the proportion sustained whilst playing soccer, determine their characteristics and report treatment and outcome. Sport accounts for 73/329 (22.1%) of these fractures and soccer 58/73 (79. 5%) of these. All patients were male with mean age of 24.3 years (range 8-48). Fifty-four fractures were closed and 93.1% (54/58) were situated in the middle third or at the junction of the middle and distal thirds of the diaphysis. Fifty-six (96.6%) had simple or wedge patterns and 45 (77.6%) were right sided. Forty-four (76.2%) were treated non-operatively in plaster, 12 (20.3%) by intramedullary nails and two (3.4%) with external fixators. Two patients were lost to follow-up and the remaining 56 fractures united at a mean of 6.5 months. There were 21 complications in 19/56 (33.9%) patients which included 8/56 (14.3%) delayed/non-unions requiring surgery. There was a significantly higher complication rate for operated fractures (p<0.005) but no significant link to AO fracture type. Thus we cannot assume that treatment of these common fractures is without risk, especially if they are treated operatively.

Adolescent↗