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Biomedical subjects

S Tait

Publications and source records attributed to S Tait.

At least 19 recordsLinked to original sources

Investigating the effect of storm events on the particle size distribution in a combined sewer simulator.

The changes in particle size of sewer sediment particles rapidly eroded from a previously deposited sediment bed are described, using a rotating annular flume as a laboratory scale sewer simulator. This is the first time that particle size distributions of eroded sewer sediments from a previously deposited sediment bed have been monitored in such a controlled experimental environment. Sediments from Loenen, The Netherlands and Dundee, UK were used to form deposits in the base of the annular flume (WL Delft Netherlands) with varying conditions for consolidation in order to investigate the effect of changing consolidation time, temperature and sediment type on the amount and size of particles eroded from a bed under conditions of increasing shear. The median size of the eroded particles did not change significantly with temperature, although the eroded suspended solids concentration was greater for the higher temperature under the same shear stresses, indicating a weaker bed deposit. An increase in consolidation time caused an increase in median size of eroded solids at higher bed shear stresses, and this was accompanied by higher suspended solids concentrations. As the shear stress increased, the solids eroded from the bed developed under a longer consolidation time (56 hours) tended towards a broad unimodal distribution, whilst the size distribution of solids eroded from beds developed under shorter consolidation times (18 or 42 hours) retained a bi- or tri-modal distribution. Using different types of sediment in the flume had a marked effect on the size of particles eroded.

Netherlands↗

Detailed observation and measurement of sewer sediment erosion under aerobic and anaerobic conditions.

A greater understanding of the erosion behaviour of sewer sediments is necessary in order to reliably estimate the amount and nature of the sewer sediments released from deposits in sewers and transported either to waste water treatment plants or discharged into the environment. Research has indicated that microbial activity in sediment can influence the physical release of sediment from in-pipe deposits. This paper reports on a series of erosion tests in which sewer sediments from different sewer networks are kept under different environmental conditions and their resistance to erosion is examined. The erosion tests are carried out under aerobic and anaerobic conditions and two temperatures, one representing ambient sewer temperatures and a lower temperature that significantly suppresses bacterial activity.

Aerobiosis↗

Developments in a methodology for the design of engineered invert traps in combined sewer systems.

Sediments within sewers can have a significant effect on the operation of the sewer system and on the surrounding natural and urban environment. One possible method for the management of sewer sediments is the use of slotted invert traps. Although invert traps can be used to selectively trap only inorganic bedload material, little is known with regard to the design of these structures. This paper presents results from a laboratory investigation comparing the trapping performance of three slot size configurations of a laboratory-scale invert trap. The paper also presents comparative results from a two-dimensional computational model utilising stochastic particle tracking. This investigation shows that particle tracking consistently over-predicts sediment retention efficiencies observed within the laboratory model.

Engineering↗

Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development.

The structurally related cell adhesion molecules L1 and Nr-CAM have overlapping expression patterns in cerebellar granule cells. Here we analyzed their involvement in granule cell development using mutant mice. Nr-CAM-deficient cerebellar granule cells failed to extend neurites in vitro on contactin, a known ligand for Nr-CAM expressed in the cerebellum, confirming that these mice are functionally null for Nr-CAM. In vivo, Nr-CAM-null cerebella did not exhibit obvious histological defects, although a mild size reduction of several lobes was observed, most notably lobes IV and V in the vermis. Mice deficient for both L1 and Nr-CAM exhibited severe cerebellar folial defects and a reduction in the thickness of the inner granule cell layer. Additionally, anti-L1 antibodies specifically disrupted survival and maintenance of Nr-CAM-deficient granule cells in cerebellar cultures treated with antibodies. The combined results indicate that Nr-CAM and L1 play a role in cerebellar granule cell development, and suggest that closely related molecules in the L1 family have overlapping functions.

Animals↗

Quantitative analysis of myocardial perfusion changes with transmyocardial laser revascularization.

Transmyocardial laser revascularization (TLR) is a technique of creating left ventricular transmural channels in patients with refractory angina. We aimed to measure perfusion changes quantitatively using technetium-99m methoxyisobutyl isonitrile. Perfusion scans were performed on 94 TLRs and in 94 control patients at rest and during exercise at assessment, and 3-, 6-, and 12-month follow-up. A serial set of scans allowed direct comparison of each patient over all visits. Bull's-eyes were divided into 5 anatomic regions and a 20-region model. Severity values were calculated for rest, stress, and each cardiac region using a threshold of 1 for analysis. Higher scores indicated greater severity of ischemia and lower perfusion. At 3-month follow-up, the severity was significantly worse during TLR than in control patients both during stress (0.172 +/- 0.003 and 0.161 +/- 0.003, respectively, p = 0.007) and at rest (0.170 +/- 0.003 and 0.158 +/- 0.003, respectively, p = 0.002). At 6 months, severity during stress was 0.176 +/- 0.003 with TLR and 0.162 +/- 0.003 in controls (p = 0.001), with no significant difference at rest. At 12 months, there was no significant difference between TLR and control groups at stress and rest. Regional severity deteriorates during TLR compared with control patients anteriorly (p = 0.001, p = 0.0016, p = 0.005 at 3, 6, and 12 months), apically (p = 0.005, p = 0.0046, p = 0.032, respectively), and laterally (p <0.0001, p = 0.001, p = 0.002, respectively). An apparent improvement is observed in the inferoseptal region at 6- and 12-month follow-up-an area not lasered. Thus, TLR appears to produce deterioration in resting myocardial perfusion in lasered regions, and improvement in nonlasered regions, with no difference in exercise-induced myocardial ischemia compared with that in control patients.

Angina Pectoris↗

A UK trial-based cost--utility analysis of transmyocardial laser revascularization compared to continued medical therapy for treatment of refractory angina pectoris.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) is used to treat patients with refractory angina considered unsuitable for conventional forms of revascularization. Using patient specific data from a single centre UK randomised-controlled trial, we aimed to determine whether, from a UK National Health Service (NHS) perspective, TMLR plus standard medical management is cost-effective when compared with standard medical management alone. METHODS: One hundred and eighty-eight patients assessed as having refractory angina, and not suitable for conventional forms of revascularization were randomized to receive TMLR and medical management (94) or medical management alone (94). Costs to the UK NHS of TMLR (where appropriate), and all secondary sector health care contacts and cardiac-related medication in the 12 months following randomization, were collected. Patient utility as measured using the EuroQol EQ-5D questionnaire was combined with 12-month survival data to generate quality adjusted life years (QALYs). RESULTS: The mean cost per patient over the year from hospitalization for TMLR was 11,470 pounds sterling and for medical management alone was 2586 pounds sterling, giving a cost difference of 8901 pounds sterling (95% confidence interval (CI) 7502 pounds sterling--10,008 pounds sterling: P < 0.0001). The mean QALY difference, in favour of TMLR was 0.039 (95% CI -0.033 to 0.113: P = 0.268). This gives an incremental cost per QALY of over 228,000 pounds sterling. Analysis of stochastic uncertainty and of sensitivity to gross changes in key parameters consistently produces very high costs per QALY. CONCLUSIONS: The policy implications are clear: for such patients TMLR is an inefficient use of UK health service resources. This conclusion would not be changed by considerable improvements in effectiveness or reductions in cost.

Aged↗

An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction.

Two major isoforms of the cell adhesion molecule neurofascin NF186 and NF155 are expressed in the central nervous system (CNS). We have investigated their roles in the assembly of the node of Ranvier and show that they are targeted to distinct domains at the node. At the onset of myelination, NF186 is restricted to neurons, whereas NF155 localizes to oligodendrocytes, the myelin-forming glia of the CNS. Coincident with axon ensheathment, NF155 clusters at the paranodal regions of the myelin sheath where it localizes in apposition to the axonal adhesion molecule paranodin/contactin-associated protein (Caspr1), which is a constituent of the septate junction-like axo-glial adhesion zone. Immunoelectron microscopy confirmed that neurofascin is a glial component of the paranodal axo-glial junction. Concentration of NF155 with Caspr1 at the paranodal junctions of peripheral nerves is also a feature of Schwann cells. In Shiverer mutant mice, which assemble neither compact CNS myelin nor normal paranodes, NF155 (though largely retained at the cell body) is also distributed at ectopic sites along axons, where it colocalizes with Caspr1. Hence, NF155 is the first glial cell adhesion molecule to be identified in the paranodal axo-glial junction, where it likely interacts with axonal proteins in close association with Caspr1.

Animals↗

Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice.

The Prx gene in Schwann cells encodes L- and S-periaxin, two abundant PDZ domain proteins thought to have a role in the stabilization of myelin in the peripheral nervous system (PNS). Mice lacking a functional Prx gene assemble compact PNS myelin. However, the sheath is unstable, leading to demyelination and reflex behaviors that are associated with the painful conditions caused by peripheral nerve damage. Older Prx-/- animals display extensive peripheral demyelination and a severe clinical phenotype with mechanical allodynia and thermal hyperalgesia, which can be reversed by intrathecal administration of a selective NMDA receptor antagonist We conclude that the periaxins play an essential role in stabilizing the Schwann cell-axon unit and that the periaxin-deficient mouse will be an important model for studying neuropathic pain in late onset demyelinating disease.

Animals↗

Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial.

BACKGROUND: Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management. METHODS: 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk. FINDINGS: Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical-management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001). INTERPRETATION: Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients.

Angina Pectoris↗

A novel rat tetraspan protein in cells of the oligodendrocyte lineage.

The tetraspanin/transmembrane 4 superfamily gene superfamily encodes proteins that span the plasma membrane four times. Tetraspan proteins are implicated in proliferation, motility, and differentiation in various cell types, and in some cells they may link plasma membrane proteins into signalling complexes. Using a subtractive cDNA library prepared from oligodendrocytes and their progenitor cells, we have identified Tspan-2 as a member of this superfamily. In situ hybridization analysis revealed robust expression in cells of the oligodendrocyte lineage in comparison with the Plp gene, a well-characterized marker for myelin-forming glia in the CNS. Rat Tspan-2 mRNA is restricted to the nervous system and is detectable by northern blot shortly after birth in the CNS. Subsequently the gene is up-regulated strongly between postnatal day 3 and 10, and expression levels continue to rise up to postnatal day 22. These data indicate that Tspan-2 is likely to play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath.

Amino Acid Sequence↗

The transmyocardial laser revascularization international registry report.

AIMS: This report aimed to provide an analysis of the data submitted from Europe and Asia on transmyocardial laser revascularization. METHODS AND RESULTS: Prospective data was recorded on 967 patients with intractable angina not amenable to conventional revascularization in 21 European and Asian centres performing transmyocardial laser revascularization using the PLC Medical Systems CO2 laser. Patient characteristics, operative details and early complications following transmyocardial laser revascularization were recorded. The in-hospital death rate was 9.7% (95% confidence interval 7.8% to 11.6%). Other early complications were consistent with similar cardiothoracic surgical procedures. There was a decrease of two or more Canadian Cardiovascular Score angina classes in 47.3%, 45.4% and 34.0% of survivors at 3, 6 and 12 months follow-up, respectively (P=0.001 for each). Treadmill exercise time increased by 42 s at 3 months (P=0.008), 1 min 43 s at 6 months (P<0.001) and 1 min 50 s at 12 months (P<0.001) against pre-operative times of 6 min. CONCLUSION: Uncontrolled registry data suggest that transmyocardial laser revascularization may lead to a decrease in angina and improved exercise tolerance. It does, however, have a risk of peri-operative morbidity and mortality. Definitive results from randomized controlled trials are awaited.

Adult↗

Trimethoprim resistant dihydrofolate reductases in normal faecal flora isolated in India.

A high incidence of resistance to trimethoprim has been shown in the normal faecal flora in a population in south India. The dihydrofolate reductase (dhfr) genes mediating transferable resistance to trimethoprim have been identified. Unusually, in this study, the dhfrV was shown to be the predominant resistance gene (dhfrV 50% of transconjugants, dhfrIa 30%), the dhfrIb was also detected being distinguished from the dhfrV by an oligo-probe. However, when non-transferable resistance was considered, the dhfrIa was the most prevalent of the dhfrs identified. All those plasmids harbouring the dhfrIa were shown to possess Tn7. All the plasmids that probed positive for the dhfrV and the dhfrIb were shown to be associated with the integrase of the Tn21-like transposons, but 8 of the dhfrV genes were not associated with the Tn21 resolvase. The dhfrIV was shown to be present in all seven plasmids that produced low level trimethoprim-resistance. The dhfrV, first characterized in Sri Lanka, would seem to have a local distribution in this region of Asia but is distinguishable from the dhfrIb only by the use of an oligo-probe.

Enterobacteriaceae↗

Dissemination of the TEM-I beta-lactamase gene into disparate plasmids in faecal strains of Escherichia coli isolated in Vellore, south India.

The genetic basis for ampicillin resistance in commensal strains of Escherichia coli isolated in Vellore, south India has been examined. Of the 58 strains tested, 41% could transfer ampicillin resistance to a standard E. coli host strain. With the exception of one isolate, transferable ampicillin resistance was shown to result from the presence of the TEM-I beta-lactamase which was found on a wide variety of plasmid types.

Ampicillin Resistance↗

The incidence of antibiotic resistance in aerobic faecal flora in south India.

During a field study in South India in 1989, faecal specimens were collected from residents in villages and the town of Vellore in South India. Examination of the faecal specimens revealed that virtually the whole population carried commensal bacteria resistant to trimethoprim, ampicillin and chloramphenicol. Most specimens contained more than one type of bacterium resistant to each antibiotic. There was less resistance to nalidixic acid, with a higher proportion in the town (33%) than in the villages (13%). Although there was little cross-resistance of the ampicillin-resistant strains to later generation cephalosporins, 50% were resistant to the combination of amoxycillin and clavulanic acid. There was no significant cross-resistance of the nalidixic acid-resistant strains to fluorinated 4-quinolones, despite the free availability of ciprofloxacin and norfloxacin in the area. The probable reason for the high incidence of resistance to first generation antimicrobials is the extensive use of these agents, coupled with continuous exposure to large numbers of faecal micro-organisms.

Bacteria, Aerobic↗

Antibacterial activity of lomefloxacin.

Lomefloxacin has marked activity against Gram-negative bacilli including Enterobacteriaceae, non-fermenting strains and Haemophilus influenzae with 98% of all isolates tested having MICs of 0.25 mg/l or less. Sixty-eight per cent of Pseudomonas aeruginosa strains were sensitive to 1 mg/l with a few strains resistant to 8 or 16 mg/l. Gram-positive cocci were more resistant, particularly streptococci, where the MICs vary between 1 and 8 mg/l. Bactericidal activity was similar to inhibitory activity and the effect of increasing serum concentrations and bacterial inocula was minimal. The MIC and MBC were increased in the presence of urine, particularly at an acid pH 5. Comparative MICs showed that lomefloxacin was more active than ofloxacin and pefloxacin, similar to norfloxacin but less active than ciprofloxacin for Gram-negative bacteria but not for Gram-positive cocci. Comparative studies with sensitivity disc concentrations showed that a 5 micrograms disc was more satisfactory than the 10 micrograms disc as the zone sizes were more suitable for routine testing. Solutions of lomefloxacin showed instability in bright sunlight when 52% of activity was lost in 1 h. Similar instability was shown in impregnated discs which lost up to 40% activity in 6 h exposure. Lomefloxacin showed a wide range of activity against Gram-negative bacteria including multiresistant strains and Pseudomonas spp. Gram-positive bacteria were less susceptible, with streptococci more resistant than staphylococci. Lomefloxacin is well absorbed after oral administration giving high blood and urine concentrations and its prolonged half-life means once daily dosing in the treatment of many types of bacterial infection may be possible.

4-Quinolones↗

Pharmacokinetic study of lomefloxacin and its effect on the faecal flora of volunteers.

In a volunteer pharmacokinetic study mean peak serum concentrations of lomefloxacin of 7.19 mg/l were obtained 1.5 h after an oral dose of 400 mg. Women had higher concentrations than men. Urinary excretion was 34% in 6 h and 63% in 24 h and the mean peak concentration was 699 mg/l. Saliva concentrations were 37% of those in serum. Lomefloxacin was detectable in the faeces up to seven days after the last dose. The major effect of lomefloxacin on the faecal flora of volunteers following a four day course of 400 mg once daily was the elimination of strains of Enterobacteriaceae and an increase in the numbers of Gram-positive cocci, mainly streptococci. There was no effect on anaerobic bacteria or yeasts. Lomefloxacin was well tolerated and no side effects were recorded. No bacterial resistance was detected after treatment.

4-Quinolones↗