Availability of two forms of dissolved nitrogen to the coral Pocillopora damicornis and its symbiotic zooxanthellae

The relative contribution of dissolved nitrogen (ammonium and dissolved free amino acids DFAAs) to the nitrogen budget of the reef-building coral Pocillopora damicornis was assessed for colonies growing on control and ammonium-enriched reefs at One Tree Island (southern Great Barrier Reef) during the ENCORE (Enrichment of Nutrient on Coral Reef; 1993 to 1996) project. P. damicornis acquired ammonium at rates of between 5.1 and 91.8 nmol N cm(-2) h(-1) which were not affected by nutrient treatment except in the case of one morph. In this case, uptake rates decreased from 80.5 to 42.8 nmol cm(-2) h(-1) (P < 0.05) on exposure to elevated ammonium over 12 mo. The presence or absence of light during measurement did not influence the uptake of ammonium ions. Nitrogen budgets revealed that the uptake of ammonium from concentrations of 0.11 to 0.13 mu M could completely satisfy the demand of growing P. damicornis for new nitrogen. P. damicornis also took up DFAAs at rates ranging from 4.9 to 9.8 nmol N cm(-2) h(-1). These rates were higher in the dark than in the light (9.0 vs 5.1 nmol m(-2) h(-1), P < 0.001). Uptake rates were highest for the amino acids serine, arginine and alanine, and lowest for tyrosine. DFAA concentrations within the ENCORE microatolls that received ammonium were undetectable, whereas they ranged up to 100 nM within the control microatolls. The contribution of DFAAs to the nitrogen budget of P. damicornis constituted only a small fraction of the nitrogen potentially contributed by ammonium under field conditions. Even at the highest field concentrations measured during this study, DFAAs could contribute only similar or equal to 11.3% of the nitrogen demand of P. damicornis. This contribution, however, may be an important source of nitrogen when other sources such as ammonium are scarce or during periods when high concentrations of DFAAs become sporadically available (e.g. cell breakage during fish-grazing).

Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants spastic, spasmodic, and oscillator

Spastic (spa), spasmodic (spd), and oscillator (ot) mice have naturally occurring glycine receptor ( GlyR) mutations, which manifest as motor deficits and an exaggerated startle response. Using whole-cell recording in hypoglossal motoneurons, we compared the physiological mechanisms by which each mutation alters GlyR function. Mean glycinergic miniature IPSC ( mIPSC) amplitude and frequency were dramatically reduced (> 50%) compared with controls for each mutant. mIPSC decay times were unchanged in spa/spa (4.5 +/- 0.3 vs 4.7 +/- 0.2 ms), reduced in spd/spd (2.7 +/- 0.2 vs 4.7 +/- 0.2 ms), and increased in ot/ot (12.3 +/- 1.2 vs 4.8 +/- 0.2 ms). Thus, in spastic, GlyRs are functionally normal but reduced in number, whereas in spasmodic, GlyR kinetics is faster. The oscillator mutation results in complete absence of alpha 1-containing GlyRs; however, some non-alpha 1-containing GlyRs persist at synapses. Fluctuation analysis of membrane current, induced by glycine application to outside-out patches, showed that mean single-channel conductance was increased in spa/spa (64.2 +/- 4.9 vs 36.1 +/- 1.4 pS), but unchanged in spd/spd (32.4 +/- 2.1 vs 35.3 +/- 2.1 pS). GlyR-mediated whole-cell currents in spa/spa exhibited increased picrotoxin sensitivity (27 vs 71% block for 100 mu M), indicating alpha 1 homomeric GlyR expression. The picrotoxin sensitivity of evoked glycinergic IPSCs and conductance of synaptic GlyRs, as determined by nonstationary variance analysis, were identical for spa/spa and controls. Together, these findings show the three mutations disrupt GlyR-mediated inhibition via different physiological mechanisms, and the spastic mutation results in compensatory alpha 1 homomeric GlyRs at extrasynaptic loci.

Determination of T1pH relaxation rates in charred and uncharred wood and consequences for NMR quantitation

The performance of three different techniques for determining proton rotating frame relaxation rates (T1pH) in charred and uncharred woods is compared. The variable contact time (VCT) experiment is shown to over-estimate T1pH, particularly for the charred samples, due to the presence of slowly cross-polarizing C-13 nuclei. The variable spin (VSL) or delayed contact experiment is shown to overcome these problems; however, care is needed in the analysis to ensure rapidly relaxing components are not overlooked. T1pH is shown to be non-uniform for both charred and uncharred wood samples; a rapidly relaxing component (T1pH = 0.46-1.07 ms) and a slowly relaxing component (T1pH = 3.58-7.49) is detected in each sample. T1pH for each component generally decreases with heating temperature (degree of charring) and the proportion of rapidly relaxing component increases. Direct T1pH determination (via H-1 detection) shows that all samples contain an even faster relaxing component (0.09-0.24 ms) that is virtually undetectable by the indirect (VCT and VSL) techniques. A new method for correcting for T1pH signal losses in spin counting experiments is developed to deal with the rapidly relaxing component detected in the VSL experiment. Implementation of this correction increased the proportion of potential C-13 CPMAS NMR signal that can be accounted for by up to 50% for the charred samples. An even greater proportion of potential signal can be accounted for if the very rapidly relaxing component detected in the direct T1pH determination is included; however, it must be kept in mind that this experiment also detects H-1 pools which may not be involved in H-1-C-13 cross-polarization. (C) 2002 Elsevier Science (USA).

Psychological characteristics of older versus younger persons with a functional gastrointestinal disorder (FGID)

Functional gastrointestinal disorders commonly affect people of all ages, including the elderly. While population-based studies report significant psychological morbidity in people diagnosed with these disorders it is not clear what effect age has in explaining this relationship. We hypothesised that psychological distress would be higher in older versus younger persons with a FGID from the community. A random sample of 4500 subjects were mailed a questionnaire on gastrointestinal symptoms in the past 12 months (response rate = 72%). Of those fulfilling Rome I criteria for a FGID (n = 988) we then classified subjects into older (>60 years) (n =126) versus younger (18-59 years) (n = 862) categories. Psychological variables included anxiety and depression (Delusions Symptom States Inventory) and neuroticism and extroversion (Eysenck Personality Inventory). Quality of life was assessed using the valid SF-12. Anxiety (4.5 vs. 3.1), depression (3.0 vs. 1.8) and neuroticism (5.7 vs. 4.9) were significantly higher in younger versus older subjects with a FGID. While mental functioning (43.1 vs. 48.3) was significantly more impaired in younger versus older subjects, the reverse was found for physical functioning (48.7 vs. 40.8). Younger people with a FGID experience greater

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p < 0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p < 0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p = 0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p = 0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes. (C) 2004 Elsevier Ltd. All rights reserved.

Ca2+-activated K+ channels in rat otic ganglion cells: Role of Ca2+ entry via Ca2+ channels and nicotinic receptors

1. Intracellular recordings were made from neurones in the rat otic ganglion in vitro in order to investigate their morphological, physiological and synaptic properties. We took advantage of the simple structure of these cells to test for a possible role of calcium influx via nicotinic acetylcholine receptors during synaptic transmission. 2. Cells filled with biocytin comprised a homogeneous population with ovoid somata and sparse dendritic trees. Neurones had resting membrane potentials of -53 +/- 0.7 mV (n = 69), input resistances of 112 + 7 M Omega, and membrane time constants of 14 +/- 0.9 ms (n = 60). Upon depolarization, all cells fired overshooting action potentials which mere followed by an apamin-sensitive after-hyperpolarization (AHP). In response to a prolonged current injection, all neurones fired tonically. 3. The repolarization phase of action potentials had a calcium component which was mediated by N-type calcium channels. Application of omega-conotoxin abolished both the repolarizing hump and the after-hgrperpolarization suggesting that calcium influx via N-type channels activates SK-type calcium-activated potassium channels which underlie the AHP. 4. The majority (70%) of neurones received innervation from a single preganglionic fibre which generated a suprathreshold excitatory postsynaptic potential mediated by nicotinic acetylcholine receptors. The other 30% of neurones also had one or more subthreshold nicotinic inputs. 5. Calcium influx via synaptic nicotinic receptors contributed to the AHP current, indicating that this calcium has access to the calcium-activated potassium channels and therefore plays a role in regulating cell excitability.

Development of a fully quantitative approach to the interpretation of stress echocardiography using radial and longitudinal myocardial velocities

Background: Tissue Doppler may be used to quantify regional left ventricular function but is limited by segmental variation of longitudinal velocity from base to apex and free to septal walls. We sought to overcome this by developing a composite of longitudinal and radial velocities. Methods and Results. We examined 82 unselected patients undergoing a standard dobutamine echocardiogram. Longitudinal velocity was obtained in the basal and mid segments of each wall using tissue Doppler in the apical views. Radial velocities were derived in the same segments using an automated border detection system and centerline method with regional chords grouped according to segment location and temporally averaged. In 25 patients at low probability of coronary disease, the pattern of regional variation in longitudinal velocity (higher in the septum) was the opposite of radial velocity (higher in the free wall) and the combination was homogenous. In 57 patients undergoing angiography, velocity in abnormal segments was less than normal segments using longitudinal (6.0 +/- 3.6 vs 9.0 +/- 2.2 cm/s, P = .01) and radial velocity (6.0 +/- 4.0 vs 8.0 +/- 3.9 cm/s, P = .02). However, the composite velocity permitted better separation of abnormal and normal segments (13.3 +/- 5.6 vs 17.5 +/- 4.2 cm/s, P = .001). There was no significant difference between the accuracy of this quantitative approach and expert visual wall motion analysis (81% vs 84%, P = .56). Conclusion: Regional variation of uni-dimensional myocardial velocities necessitates site-specific normal ranges, probably because of different fiber directions. Combined analysis of longitudinal and radial velocities allows the derivation of a composite velocity, which is homogenous in all segments and may allow better separation of normal and abnormal myocardium.

Mass transfer correlations for rotating drum bioreactors

Evaporative cooling is extremely important for large-scale operation of rotating drum bioreactors (RDBs). Outlet water vapour concentrations were measured for a RDB containing wet wheat bran with the aim of determining the mass transfer coefficient for evaporation from the bran bed to the headspace. Mass transfer was expressed as the mass transfer coefficient times the area for transfer per unit volume of void space in the drum. Values of ka' were determined under combinations of aeration superficial velocities ranging from 0.006 to 0.017 ms(-1) and rotation rates ranging from 0 to 9 rpm. Mass transfer coefficients were evaluated using a variety of residence time distributions (RTDs) for flow in the gas phase including plug flow and well-mixed and a Central Jet RTD based on RTD studies. If plug flow is assumed, the degree of holdup at low effective Peclet (Pe(eff)) numbers gives an apparent under-estimate of ka' compared with empirical correlations. Values of ka' calculated using the Central Jet RTD agree well with values of ka' from literature correlations. There was a linear relationship between ka' and effective Peclet number: ka' = 2.32 x 10(-3) Pe(eff). (C) 2002 Elsevier Science B.V. All rights reserved.

Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy

To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. Methods. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. Results. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (116.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1 %, P < 0.01). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (11975 vs: 1128 mg, P < 0.01). The incidence of FM with VPA doses greater than or equal to 1100 mg was 30.2% vs. 3.2% with doses < 1100 mg (P < 0.01). Conclusions. There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy. (C) 2004 Elsevier Ltd. All rights reserved.

Isolation and characterization at cholinergic nicotinic receptors of a neurotoxin from the venom of the Acanthophis sp Seram death adder

The present study describes the isolation of the first neurotoxin (acantoxin IVa) from Acanthophis sp. Seram death adder venom and an examination of its activity at nicotinic acetylcholine receptor (naChR) subtypes. Acantoxin IVa (MW 6815; 0.1-1.0 muM) caused concentration-dependent inhibition of indirect twitches (0.1 Hz, 0.2 ms, supramaximal V) and inhibited contractile responses to exogenous nicotinic agonists in the chick biventer cervicis nerve-muscle, confirming that this toxin is a postsynaptic neurotoxin. Acantoxin IVa (1-10 nM) caused pseudo-irreversible antagonism at skeletal muscle nAChR with an estimated pA(2) Of 8.36 +/- 0.17. Acantoxin IVa was approximately two-fold less potent than the long-chain (Type 11) neurotoxin, alpha-bungarotoxin. With a pK(i) value of 4.48, acantoxin IVa was approximately 25,000 times less potent than a-bungarotoxin at alpha7-type neuronal nAChR. However, in contrast to alpha-bungarotoxin, acantoxin IVa completely inhibited specific [H-3]-methyllycaconitine (MLA) binding in rat hippocampus homogenate. Acantoxin IVa had no activity at ganglionic nAChR, alpha4beta2 subtype neuronal nAChR or cytisine-resistant [H-3]-epibatidine binding sites. While long-chain neurotoxin resistant [H-3]-MLA binding in hippocampus homogenate requires further investigation, we have shown that a short-chain (Type 1) neurotoxin is capable of fully inhibiting specific [H-3]-MLA binding. (C) 2004 Elsevier Inc. All rights reserved.

Comparison of specificity of quantitative myocardial contrast echocardiography for diagnosis of coronary artery disease in patients with versus without diabetes mellitus

Impaired coronary flow reserve is widely reported in diabetes mellitus (DM) but its effect on myocardial contrast echocardiography (MCE) is unclear. We sought to identify whether DM influences the accuracy of qualitative and quantitative assessment of coronary artery disease (CAD) using MCE in 83 patients who underwent coronary angiography (60 men, 27 with DM; 56 +/- 11 years;). Destruction replenishment imaging was performed at rest and after combined dipyridamole-exercise stress testing. Ischemia was identified by the development of new wall motion abnormalities, qualitative MCE (new perfusion defects apparent 1 second after flash during hyperemia), and quantitative MCE (myocardial blood flow reserve < 2.0 in the anterior circulation). Qualitative and quantitative assessment of perfusion was feasible in 100% and 92% of patients, respectively. Significant left anterior descending coronary stenosis (> 50% by quantitative angiography) was present in 28 patients (including 8 with DM); 55 patients had no CAD (including 19 with DM). The myocardial blood flow reserve was reduced in patients with coronary stenosis compared with those with no CAD (1.6 +/- 1.1 vs 3.8 +/- 2.5, p < 0.001). Among patients with no CAD, those with DM had an impaired flow reserve compared with control patients without DM (2.4 +/- 1.0 vs 4.5 +/- 2.8, p = 0.003). In conclusion, DM significantly influenced the quantitative, but not the qualitative, assessment of MCE, with a marked reduction in specificity in patients with DM. (c) 2005 Elsevier Inc. All rights reserved.

Myocardial and vascular dysfunction and exercise capacity in the metabolic syndrome

The metabolic syndrome (MS) is associated with cardiovascular risk exceeding that expected from atherosclerotic risk factors, but the mechanism of this association is unclear. We sought to determine the effects of the MS on myocardial and vascular function and cardiorespiratory fitness in 393 subjects with significant risk factors but no cardiovascular disease and negative stress echocardiographic findings. Myocardial function was assessed by global strain rate, strain, and regional systolic velocity (s(m)) and diastolic velocity (e(m)) using tissue Doppler imaging. Arterial compliance was assessed using the pulse pressure method, involving simultaneous radial applanation tonometry and echocardiographic measurement of stroke volume. Exercise capacity was measured by expired gas analysis. Significant and incremental variations in left ventricular systolic (s(m), global strain, and strain rate) and diastolic (e(m)) function were found according to the number of components of MS (p <0.001). MS contributed to reduced systolic and diastolic function even in those without left ventricular hypertrophy (p <0.01). A similar dose-response association was present between the number of components of the MS and exercise capacity (p <0.001) and arterial compliance. The global strain rate and em were independent predictors of exercise capacity. In conclusion, subclinical left ventricular dysfunction corresponded to the degree of metabolic burden, and these myocardial changes were associated with reduced cardiorespiratory fitness.' Subjects with MS who also have subclinical myocardial abnormalities and reduced cardiorespiratory fitness may have a higher risk of cardiovascular disease events and heart failure. (C) 2005 Elsevier Inc. All rights reserved.

Pharmacological treatment and perceived health status during 1-year follow up in patients diagnosed with coronary artery disease, but ineligible for revascularization. Results from the Euro Heart Survey on Coronary Revascularization

Background It has been recognized that a clinically significant portion of patients with coronary artery disease (CAD) continue to experience anginal and other related symptoms that are refractory to the combination of medical therapy and revascularization. The Euro Heart Survey on Revascularization (EHSCR) provided an opportunity to assess pharmacological treatment and outcome in patients with proven CAD who were ineligible for revascularization. Methods We performed a secondary analysis of EHS-CR data. After excluding patients with ST-elevation myocardial infarction and those in whom revascularization was not indicated, 4409 patients remained in the analyses. We selected two groups: (1) patients in whom revascularization was the preferred treatment option (n = 3777, 86%), and (2) patients who were considered ineligible for revascularization (n = 632, 14%). Results Patient ineligible for revascularization had a worse risk profile, more often had a total occlusion (59% vs. 37%, p < 0.001), were treated more often with ACE-inhibitors (65% vs. 55%, p < 0.001) but less likely with aspirin (83% vs. 88%, p < 0.001). Overall, they had higher case-fatality at 1-year (7.0% vs. 3.7%, p < 0.001). Regarding self-perceived health status, measured via the EuroQol 5D (EQ-5D) questionnaire, these same patients reported more problems on all dimensions of the EQ-5D. Furthermore, in the revascularization group we observed an increase between discharge and 1-year follow up (utility score from 0.85 to 1.00) whereas patients ineligible for revascularization did not improve over time (utility score remained 0.80) Conclusion In this large cohort of European patients with CAD, those considered ineligible for revascularization had more co-morbidities and risk factors, and scored worse on self-perceived health status as compared to revascularized patients in the revascularization group. With the exception of ACE-inhibitors and aspirin, there were no major differences regarding drug treatment between the two groups. Given these clinically significant observations, there appears to be a role for nurse-led, multidisciplinary, rehabilitation teams that target clinically vulnerable patients whose symptoms remain refractory to standard medical care.

Muscle metabolism during constant- and alternating-intensity exercise around critical power

Few studies have focused on the metabolic responses to alternating high- and low-intensity exercise and, specifically, compared these responses to those seen during constant-load exercise performed at the same average power output. This study compared muscle metabolic responses between two patterns of exercise during which the intensity was either constant and just below critical power (CP) or that oscillated above and below CP. Six trained males (mean +/- SD age 23.6 +/- 2.6 y) completed two 30-minute bouts of cycling (alternating and constant) at an average intensity equal to 90% of CR The intensity during alternating exercise varied between 158% CP and 73% CP. Biopsy samples from the vastus lateralis muscle were taken before (PRE), at the midpoint and end (POST) of exercise and analysed for glycogen, lactate, PCr and pH. Although these metabolic variables in muscle changed significantly during both patterns of exercise, there were no significant differences (p > 0.05) between constant and alternating exercise for glycogen (PRE: 418.8 +/- 85 vs. 444.3 +/- 70; POST: 220.5 +/- 59 vs. 259.5 +/- 126mmol.kg(-1) dw), lactate (PRE: 8.5 +/- 7.7 vs. 8.5 +/- 8.3; POST: 49.9 +/- 19.0 vs. 42.6 +/- 26.6 mmol.kg(-1)dw), phosphocreatine (PRE: 77.9 +/- 11.6 vs. 75.7 +/- 16.9; POST: 65.8 +/- 12.1 vs. 61.2 +/- 12.7mmol.kg(-1)dw) or pH (PRE: 6.99 +/- 0.12 vs. 6.99 +/- 0.08; POST: 6.86 +/- 0.13 vs. 6.85 +/- 0.06), respectively. There were also no significant differences in blood lactate responses to the two patterns of exercise. These data suggest that, when the average power output is similar, large variations in exercise intensity exert no significant effect on muscle metabolism.

Vitamin A is associated with the inflammatory marker CRP in cystic fibrosis

We have observed that vitamin A levels, deficient in patients with severe disease, returned to normal post lungtransplant independent of oral supplementation or pancreatic sufficiency. We hypothesised that vitamin A is associated with disease severity and the inflammatory marker C-related peptide (CRP). Data from RCH paediatric and TPCH adult CF clinic subjects (ns138 CF, 138 control, aged 5–56 yr), who had participated in a study of bone mineral density (BMD) in which vitamins A, E, D, and CRP, height, weight and lung function had been measured was used. Groups were compared using t- or Wilcoxon-tests, and predictors of vitamin A examined usingmultiple regression. Vitamin A was lower in CF subjects (1.23"0.5 vs. 1.80"0.6 mmolyl, P-0.0001), increasingwith age in paediatric subjects but to a lesser extent in the CF group (Ps0.0007). CRP was correlated with age (rs0.6, P-0.0001). FEV1% predicted (FEV) (57.93"23.0 vs. 70.63"21.8, Ps0.0014), weight z-score (WTZ) (y0.76"0.9 vs. y0.12"1.0, Ps0.0002), lumbar spine BMD z-score (y1.08"1.3 vs. y0.50"1.2, Ps0.009) were lower, and CRP higher (median 7.0, IQR 2–4 vs. median 1.0, IQR 1–3 mgy l, P-0.0001) in vitamin A insufficient CF subjects (61 insufficient vs. 71 sufficient). In all subjects, control status (P-0.0001), WTZ (Ps0.02), vitamin E (Ps 0.0003), CRP (Ps0.001), 1,25 dihydroxy vitamin D (1,25 vit. D) (Ps0.0007), and child, adolescent or adult grouping (all P-0.0001) were predictive of vitamin A. In the CF group, CRP (Ps0.01), Vitamin E (P-0.0001) and 1.25 vit. D (Ps 0.006), but not FEV, were predictive. The normal increase in vitamin A with age was not observed in CF subjects, who had lower levels at any age. This failure of normal increase in vitamin A had a consistent association with increasingCRP , supportingthe hypothesis that increased inflammation may result in increased vitamin A consumption.