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Biomedical subjects

G Parkin

Publications and source records attributed to G Parkin.

At least 19 recordsLinked to original sources

Optimization of anabaenopeptin extraction from cyanobacteria and the effect of methanol on laboratory manipulation.

Anabaenopeptins are commonly occurring bioactive peptides of cyanobacterial origin. Cyanobacteria (blue-green algae) are known to be capable of producing a large number of biologically active peptides, but the widespread occurrence of anabaenopeptins in particular, makes them ideal candidates for investigating the reasons that cyanobacteria produce such a complex spectrum of peptides and the wider implications of their natural function(s). Despite the identification of these peptides in cyanobacterial samples, little is known about the concentrations produced. For this reason, methods for the quantitative extraction of anabaenopeptins from lyophilized cyanobacterial cells were optimized. Higher yields of anabaenopeptins were obtained using aqueous methanol extraction than using water alone. However, repeat extractions using 50, 70 or 90% aqueous methanol did not result in significantly different total yields of the anabaenopeptin variants, ABPN-A and -B. Similarly, little difference was found in the quantification of purified ABPN-A and -B by high performance liquid chromatography with photodiode array detection (HPLC-PDA) when analyzed in methanol solutions of different concentrations. The effects of solvent concentration on the laboratory handling of ABPN-A and -B in glass and plastic containers were also investigated. Significantly lower concentrations of dissolved ABPN-A and -B were found when aqueous solutions came into contact with plastics, but not 50 or 100% methanol.

Anabaena↗

Role of magnetic resonance imaging in the diagnosis and single-stage surgical resection of invasive lobular carcinoma of the breast.

BACKGROUND: Conventional imaging with mammography and ultrasonography has a low sensitivity for diagnosis and a tendency to underestimate the extent of invasive lobular carcinoma (ILC) of the breast. The aim was to determine whether magnetic resonance imaging (MRI) had any advantages for the characterization of ILC. METHODS: Twenty patients with histologically proven ILC underwent preoperative imaging with MRI. MRI was performed to aid detection of malignancy in six patients with a clinically suspicious presentation but normal or indeterminate imaging on mammography and ultrasonography. In 14 patients MRI was performed to determine tumour extent. RESULTS: MRI accurately identified malignancy in five of six patients with normal or indeterminate conventional imaging. In seven of 14 patients in whom MRI was performed to determine tumour extent, it provided significant additional information. These included four patients in whom conventional imaging grossly underestimated tumour size, two patients in whom MRI identified an unsuspected contralateral breast tumour and one patient in whom MRI predicted tumour invasion of the pectoral muscle. The correlation between tumour size on histological examination was better with MRI (r = 0.967) than with mammography (r = 0.663) and ultrasonography (r = 0.673). CONCLUSION: MRI can provide considerable additional information in the detection and characterization of ILC.

Adult↗

Synthesis and structural characterization of PHP[(C(5)Me(4))(2)], a monodentate chiral phosphine derived from intramolecular C-C coupling of tetramethylcyclopentadienyl groups: an evaluation of steric and electronic properties.

The chiral monodentate phosphine PhP[(C(5)Me(4))(2)] is readily obtained by oxidation of the lithium complex Li(2)[PhP(C(5)Me(4))(2)] with I(2), which couples the two cyclopentadienyl groups to form a five-membered heterocyclic ring. The steric and electronic properties of PhP[(C(5)Me(4))(2)] have been evaluated by X-ray diffraction and IR spectroscopic studies on a variety of derivatives, including Ph[(C(5)Me(4))(2)]PE (E = S, Se), Cp*MCl(4)[P[(C(5)Me(4))(2)]Ph] (M = Mo, Ta), Ir[P[(C(5)Me(4))(2)]Ph](2)(CO)Cl, and CpFe(CO)[PhP[(C(5)Me(4))(2)]]Me. For comparison purposes, derivatives of the related phospholane ligand PhP[Me(2)C(4)H(6)] have also been investigated, including Ph[Me(2)C(4)H(6)]PS, Ir[Ph[Me(2)C(4)H(6)]](2)(CO)Cl, Ir[Ph[Me(2)C(4)H(6)]](2)(CO)Me, Ir[PPh[Me(2)C(4)H(6)]](COD)(Cl), and Pd[P[Me(2)C(4)H(6)]Ph][eta(2)-C(6)H(4)C(H)(Me)NMe(2)]Cl. The steric and electronic properties of PhP[(C(5)Me(4))(2)] are determined to be intermediate between those of PPh(2)Me and PPh(3). Thus, the crystallographic cone angles increase in the sequence PPh(2)Me (134.5 degrees) < PhP[(C(5)Me(4))(2)] (140.2 degrees) < PPh(3) (148.2 degrees), while the electron donating abilities decrease in the sequence PPh(2)Me > PhP[(C(5)Me(4))(2)] > PPh(3). Finally, PhP[(C(5)Me(4))(2)] has a smaller cone angle and is less electron donating than the structurally similar phosphine, PhP[Me(2)C(4)H(6)].

Journal Article↗

Cold climate wetlands: design and performance.

Constructed wetlands are gaining widespread use as a simple, low cost means of wastewater treatment. Introduction of constructed wetlands technology into the northern United States has been limited by the ability of conventional wetland systems to operate without freezing during the winter. A design approach using subsurface-flow constructed wetlands covered with an insulating mulch layer has been demonstrated to prevent freezing. However, introduction of a mulch layer will affect oxygen transfer rates, pollutant removal performance, and plant establishment. These factors must be addressed for successful application of constructed wetlands technology in cold climates.

Biodegradation, Environmental↗

Bis(mercaptoimidazolyl)(pyrazolyl)hydroborato complexes of zinc, cadmium, and cobalt: structural evidence for the enhanced tendency of zinc in biological systems to adopt tetrahedral M[S4] coordination.

The bis(2-mercapto-1-methylimidazolyl)(pyrazolyl)hydroborato derivatives [pzBmMe]2Zn, [pzBmMe]2Co, and [pzBmMe]2Cd have been isolated and structurally characterized by X-ray diffraction. Despite their common [pzBmMe]2M composition, each of these complexes adopts a different structure. Thus, (i) the zinc complex exhibits a tetrahedral Zn[S4] structure in which only the sulfur donors coordinate to zinc, (ii) the cobalt complex exhibits a trigonal-bipyramidal Co[S3NH] structure in which one of the pyrazolyl groups and one of the B-H groups coordinate to cobalt, and (iii) the cadmium complex exhibits a six-coordinate Cd[S4H2] structure in which both B-H groups interact with the cadmium center. These comparisons emphasize that zinc has a greater preference for tetrahedral M[S4] coordination than does either cobalt or cadmium, an observation that is in accord with the prevalent role of zinc in the structural sites of enzymes.

Cadmium↗

Structural studies of the [tris(imidazolyl)phosphine]metal nitrate complexes [[PimPrl,But]M(NO3)]+ (M = Co, Cu, Zn, Cd, Hg): comparison of nitrate-binding modes in synthetic analogues of carbonic anhydrase.

X-ray diffraction studies on a series of cationic divalent metal nitrate complexes supported by the tris(1-isopropyl-4-tert-butylimidazolyl)phosphine ligand, [[PimPri,But]M(NO3)]+ (M = Co, Cu, Zn, Cd, Hg), demonstrate that the nitrate ligand coordination mode is strongly dependent upon the metal. With the exception of that for the HgII derivative, the nitrate ligand coordination modes correlate with the activities of metal-substituted carbonic anhydrases, such that the only MII-carbonic anhydrases which exhibit significant activity, i.e., the Zn and Co species, are those for which the [[PimPri,But]M(NO3)]+ complexes possess strongly asymmetric nitrate ligands. This trend supports the notion that access to a unidentate, rather than a bidentate, bicarbonate intermediate may be a critical requirement for significant carbonic anhydrase activity. Interestingly, the nitrate coordination modes in the series of group 12 complexes, [[PimPri,But]M(NO3)]+ (M = Zn, Cd, Hg), do not exhibit a monotonic periodic trend: the bidenticity is greater for the cadmium complex than for either the zinc or mercury complexes. Since HgII-carbonic anhydrase is inactive, the correlation between nitrate coordination mode and enzyme activity is anomalous for the mercury complex. Therefore, it is suggested that the inactivity of HgII-carbonic anhydrase may be consequence of the reduced tendency of the mercury center in HgII-carbonic anhydrase to bind water.

Binding Sites↗

Validation of a physically based catchment model for application in post-closure radiological safety assessments of deep geological repositories for solid radioactive wastes.

The physically based river catchment modelling system SHETRAN incorporates components representing water flow, sediment transport and radionuclide transport both in solution and bound to sediments. The system has been applied to simulate hypothetical future catchments in the context of post-closure radiological safety assessments of a potential site for a deep geological disposal facility for intermediate and certain low-level radioactive wastes at Sellafield, west Cumbria. In order to have confidence in the application of SHETRAN for this purpose, various blind validation studies have been undertaken. In earlier studies, the validation was undertaken against uncertainty bounds in model output predictions set by the modelling team on the basis of how well they expected the model to perform. However, validation can also be carried out with bounds set on the basis of how well the model is required to perform in order to constitute a useful assessment tool. Herein, such an assessment-based validation exercise is reported. This exercise related to a field plot experiment conducted at Calder Hollow, west Cumbria, in which the migration of strontium and lanthanum in subsurface Quaternary deposits was studied on a length scale of a few metres. Blind predictions of tracer migration were compared with experimental results using bounds set by a small group of assessment experts independent of the modelling team. Overall, the SHETRAN system performed well, failing only two out of seven of the imposed tests. Furthermore, of the five tests that were not failed, three were positively passed even when a pessimistic view was taken as to how measurement errors should be taken into account. It is concluded that the SHETRAN system, which is still being developed further, is a powerful tool for application in post-closure radiological safety assessments.

Fresh Water↗

A physically based approach to modelling radionuclide transport in the biosphere.

Calculations of radiological risk are required to assess the safety of any potential future UK deep underground repository for intermediate-level and certain low-level solid radioactive wastes. In support of such calculations, contaminant movement and dilution in the terrestrial biosphere is investigated using the physically based modelling system SHETRAN. Two case studies are presented involving modelling of contaminants representing long-lived poorly sorbed radionuclides in the near-surface aquifers and surface waters of hypothetical catchments. The contaminants arise from diffuse sources at the base of the modelled aquifers. The catchments are characterised in terms of detailed spatial data for topography, the river network, soils and vegetation. Simulations are run for temperate and boreal climates representing possible future conditions at a repository site. Results are presented in terms of the concentration of contaminants in the aquifer, in soils and in surface waters; these are used to support the simpler models used in risk calculations.

Climate↗

A prospective comparative study of moderate versus high protein intake for critically ill patients with acute renal failure.

Critically ill patients with acute renal failure are traditionally treated with low-protein diets to help control uremia. This dietary approach may be deleterious to the patient's nutritional status and unnecessary, especially if continuous renal placement therapies (CRRT) are used. However, the optimal amount of protein supplementation during CRRT is unknown. In patients receiving CRRT, a high protein intake may result in a positive nitrogen balance in the absence of uncontrolled uremia. Accordingly, we studied nitrogen metabolism in two consecutive cohorts of acute renal failure patients receiving equal amounts of calories but variable amounts of nitrogen. One group received protein according to the preferences of the attending clinician, the other a high and fixed amount of protein (2.5 g/kg/day). Patients treated according to attending clinician preferences received significantly less dietary protein (1.2 g/kg/day vs. 2.5 g/kg/day; p < 0.0001) and had a negative mean nitrogen balance of -5.5 g/day. Patients receiving a high and fixed amount of protein had a less negative mean nitrogen balance (-1.92 g/day). Such patients were more likely to experience a positive nitrogen balance during any 24-h period (53.6% vs. 36.7%; p < 0.05). They also required more aggressive hemofiltration to maintain control of uremia (mean ultradiafiltrate volume: 2145 mL/h vs. 1658 mL/h; p < 0.0001) and had a significantly higher but still acceptable mean plasma urea level (26.6 mmol/L vs. 18 mmol/L; p < 0.0001). Survival was not significantly different in the two groups (37.5% vs. 31.3%). We conclude that a high-protein diet can be safely administered to critically ill patients with acute renal failure receiving continuous renal replacement therapy. Such a high protein intake improves nitrogen balance when compared to moderate protein intake. A low protein intake is unnecessary in patients treated with CRRT.

Acute Kidney Injury↗

Indirect learning of event sequences: the effects of divided attention and stimulus continuity.

In a serial reaction time (SRT) task, the learning curve is sleeper when the stimuli are presented in a repeating sequential manner rather than in random order (Nissen & Bullemer, 1987). This is true even when subjects report being unaware of the presence of the repeating sequence. The present study examines the nature of this learning under conditions designed to reduce attentional resources and to disrupt the continuity of stimuli. In the first three experiments, subjects were trained in the SRT task, with or without the addition of a secondary tone counting task, and with repeating or non-repeating sequences. The results suggest that some sequence learning occurred despite the presence of a secondary task. Experiment 4 examined the extent of sequence learning when the inter-stimulus interval was varied between trials. The overall results suggest that despite reduced attentional allocation and discontinuous stimulus presentation, some sequence learning occurs. This result supports other work suggesting a dissociation between learning when measured explicitly, and when assessed through performance indicators.

Adult↗

Treatment of sepsis-associated severe acute renal failure with continuous hemodiafiltration: clinical experience and comparison with conventional dialysis.

The syndrome of sepsis-associated severe acute renal failure is a frequent component of sepsis-induced multiorgan failure. Continuous hemofiltration techniques are often used in its dialytic management but little is known about their impact. The aim of this study is to define the biochemical and clinical impact of continuous hemodiafiltration (CHD) in the management of this syndrome and to retrospectively compare it to that of conventional dialysis. A prospective, cohort study and retrospective comparison with historical controls was conducted at an intensive care unit (ICU) of a tertiary institution. Eighty-seven consecutive septic patients with acute renal failure were treated by continuous hemodiafiltration and 40 consecutive similar patients by conventional dialysis. All new cases of severe acute renal failure with sepsis were treated by means of continuous hemodiafiltration. Historical controls were treated by means of conventional dialysis. Illness and sepsis severity were assessed on admission and prior to initiation of treatment. Biochemical variables were assessed daily. Outcome was measured as discharge from the ICU, duration of oliguria and discharge from hospital. Of the 87 patients treated by hemodiafiltration, 86 had multiorgan failure, 71 (81.6%) septic shock and 52 (59.8%) bacteremia/fungemia. Their APACHE II score on admission was 29.9 and their mean organ failure score prior to treatment was 4.3. Hemodiafiltration resulted in a significant fall in mean urea and creatinine levels within 24 h and in the correction of acidosis. The mean alveolar-arterial gradient fell from 276 to 211 mm Hg (p < 0.02) within 24 h of therapy. Complications were few and mostly related to vascular access.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Severe acute renal failure: a comparison of acute continuous hemodiafiltration and conventional dialytic therapy.

It is unknown whether continuous renal replacement techniques result in diminished morbidity and mortality when compared to conventional dialytic techniques. To investigate this issue a previously described, retrospectively studied group of critically ill patients with severe acute renal failure treated by conventional dialysis (CD) was compared to a prospectively studied group of similar patients treated by acute continuous hemodiafiltration (ACHD). A combined retrospective and prospective clinical and laboratory investigation was carried out for 234 consecutive critically ill patients with severe acute renal failure in the intensive care unit of a tertiary institution. Biochemical, clinical and outcome data in all patients treated by conventional dialytic techniques (intermittent hemodialysis and/or peritoneal dialysis) during a 5-year period were retrospectively analyzed, and a prospective analysis of the same biochemical, clinical and outcome data in all patients treated by acute continuous hemodiafiltration was done over a similar time span, with statistical comparison of findings. One hundred and fifty patients were treated by ACHD and 84 by CD. ACHD patients were more severely ill (mean APACHE II score: 28.2 vs. 25.8; p < 0.01) and older (mean age: 59.9 vs. 55.5 years; p < 0.01). There were no significant differences in the incidence of sepsis, bacteremia and need for mechanical ventilation. ACHD resulted in better control of uremia (mean steady-state plasma urea level: 20.1 vs. 31.7 mmol/l; p < 0.001) and hyperphosphatemia (mean serum phosphate: 1.26 vs. 1.95 mmol/l) after 24 h of initiation of therapy. It also allowed the administration of full nutritional support in a significantly greater percentage of patients (91.3 vs. 64.8%; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗