Does F4TCNQ Adsorption on Cu(111) Form a 2D-MOF?

The results of a quantitative experimental structural investigation of the adsorption phases formed by 2,3,5,6-tetrafluoro-7,7',8,8'-tetracyanoquinodimethane (F4TCNQ) on Cu(111) are reported. A particular objective was to establish whether Cu adatoms are incorporated into the molecular overlayer. A combination of normal incidence X-ray standing waves, low-energy electron diffraction, scanning tunneling microscopy, and X-ray photoelectron spectroscopy measurements, complemented by dispersion-inclusive density functional theory calculations, demonstrates that F4TCNQ on Cu(111) does cause Cu adatoms to be incorporated into the overlayer to form a two-dimensional metal-organic framework (2D-MOF). This conclusion is shown to be consistent with the behavior of F4TCNQ adsorption on other coinage metal surfaces, despite an earlier report concluding that the adsorption structure on Cu(111) is consistent with the absence of any substrate reconstruction.

Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in "22-23" week and "24-26" infants.

The hemodynamically significant patent ductus arteriosus (hsPDA) is a controversial topic in neonatology, particularly among neonates at the earliest gestational ages of 22+0-23+6 weeks. There is little, to no data on the natural history or impact of the PDA in extremely preterm babies. In addition, these high-risk patients have typically been excluded from randomized clinical trials of PDA treatment. In this work, we present the impact of early hemodynamic screening (HS) of a cohort of patients born 22+0-23+6 weeks gestation who either were diagnosed with hsPDA or died in the first postnatal week as compared to a historical control (HC) cohort. We also report a comparator population of 24+0-26+6 weeks gestation. All patients in the HS epoch were evaluated between 12-18h postnatal age and treated based on disease physiology whereas the HC patients underwent echocardiography at the discretion of the clinical team. We demonstrate a two-fold reduction in the composite primary outcome of death prior to 36 weeks or severe BPD and report a lower incidence of severe intraventricular hemorrhage (n=5, 7% vs n=27, 27%), necrotizing enterocolitis (n=1, 1% vs n=11, 11%) and first-week vasopressor use (n=7, 11% vs n=40, 39%) in the HS cohort. HS was also associated with an increase in survival free of severe morbidity from the already high rate of 50% to 73% among neonates <24 weeks gestation. We present a biophysiological rationale behind the potential modulator role of hsPDA on these outcomes and review the physiology relevant to neonates born at these extremely preterm gestations. These data highlight the need for further interrogation of the biological impact of hsPDA and impact of early echocardiography directed therapy in infants born less than 24 weeks gestation.

Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy.

BACKGROUND: Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto-motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers. METHODS: Forty-seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age-matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24-hour heart rate variability testing were evaluated. KEY RESULTS: In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = -0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023). CONCLUSIONS AND INFERENCES: The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability.

Regional gastrointestinal contractility parameters using the wireless motility capsule: inter-observer reproducibility and influence of age, gender and study country.

BACKGROUND: The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. AIMS: To describe normative values for motility/contractility parameters across age, gender and testing centres. METHODS: Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators. RESULTS: Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40 years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.4 ± 12 vs 122 ± 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic loge motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times. CONCLUSIONS: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.

Does the addition of virtual reality training to a standard program of inpatient rehabilitation improve sitting balance ability and function after stroke? Protocol for a single-blind randomized controlled trial.

BACKGROUND: Sitting ability and function are commonly impaired after stroke. Balance training has been shown to be helpful, but abundant repetitions are required for optimal recovery and patients must be motivated to perform rehabilitation exercises repeatedly to maximize treatment intensity. Virtual reality training (VRT), which allows patients to interact with a virtual environment using computer software and hardware, is enjoyable and may encourage greater repetition of therapeutic exercises. However, the potential for VRT to promote sitting balance has not yet been explored. The objective of this study is to determine if supplemental VRT-based sitting balance exercises improve sitting balance ability and function in stroke rehabilitation inpatients. METHODS/DESIGN: This is a single-site, single-blind, parallel-group randomized control trial. Seventy six stroke rehabilitation inpatients who cannot stand independently for greater than one minute but can sit for at least 20 minutes (including at least one minute without support) are being recruited from a tertiary-care dedicated stroke rehabilitation unit. Participants are randomly allocated to experimental or control groups. Both participate in 10-12 sessions of 30-45 minutes of VRT performed in sitting administered by a single physiotherapist, in addition to their traditional therapy. The experimental group plays five games which challenge sitting balance while the control group plays five games which minimize trunk lean. Outcome measures of sitting balance ability (Function in Sitting Test, Ottawa Sitting Scale, quantitative measures of postural sway) and function (Reaching Performance Scale, Wolf Motor Function Test, quantitative measures of the limits of stability) are administered prior to, immediately following, and one month following the intervention by a second physiotherapist blind to the participant's group allocation. DISCUSSION: The treatment of sitting balance post-stroke with VRT has not yet been explored. Results from the current study will provide important evidence for the use of low-cost, accessible VRT as an adjunct intervention to increase sitting balance in lower-functioning patients receiving inpatient rehabilitation. The motivating and enjoyable attributes of VRT may increase exercise dosage, leading to improved function and optimal results from rehabilitation. TRIAL REGISTRATION: https://clinicaltrials.gov/; Identifier: NCT02285933. Registered 06 November 2014. Funded by the Heart & Stroke Foundation of Canada and a generous donation from Tony & Elizabeth Graham.

Normal esophageal high-resolution manometry and impedance values in the supine and sitting positions in the population of Northern China.

The aim of this study was to investigate the normal high-resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty-two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P < 0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P < 0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P < 0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application.

Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule: influence of age, gender, study country and testing protocol.

BACKGROUND: The wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AIM: To investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. METHODS: Regional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. RESULTS: For GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17 min, P = 0.0307), and also longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P = 0.0077). Increasing age was associated with shorter small bowel transit time (P = 0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24 h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. CONCLUSIONS: Regional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research.

Audit and review for evidence-based red cell wastage reduction measures.

Stocks of red blood cells (RBC) are held to ideally match supply and demand; hold too great a stock and unnecessary wastage occurs; too low a stock results in delay or lack of blood for the patient. Blood is a precious resource and its supply needs to be managed effectively. The aim was to identify how RBC units are wasted and propose laboratory-based reduction measures that would not compromise the clinical requirements of the patient. Wastage of RBC was investigated using a 'dashboard' query of a laboratory information management system. By employing service improvement tools, proposals were made to reduce unnecessary RBC waste while ensuring an adequate supply to the patient. The efficacy of those proposals was examined using the same dashboard to compare similar periods before and after their introduction. The reduction in RBC wastage for all groups during an eight month period (December to July) was from 6.4% (5.3% non-AB or B RhD-positive) pre-implementation to 4.4% (2.5% non-AB/B RhD-positive) post-implementation. Group O RhD-negative wastage reduced from 10.4% to 4.4% after introduction of waste-saving proposals. However, there was an increase in staff time required to introduce the changes and in associated Group and Screen testing (3.4 to 3.8 per unit issued). RBC wastage was significantly reduced (P<0.0001) by 32.8% (52%, non-AB/B RhD-positive), saving approximately 225 RBC units per annum. Financially, increased associated costs did not negate the savings made by the measures introduced.

Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists.

UNLABELLED: The gastrointestinal hormone motilin has been known about for >40 years, but after identification of its receptor and subsequent development of new tools and methods, a reappraisal of its actions is required. Firstly, it is important to note that motilin and ghrelin receptors are members of the same family (similar genomic organization, gastrointestinal distribution and abilities to stimulate gastrointestinal motility), yet each fails to recognize the ligand of the other; and whereas ghrelin and ghrelin receptors are widespread outside the gastrointestinal tract, motilin and its receptors are largely restricted to the gastrointestinal tract. Secondly, although some studies suggest motilin has activity in rodents, most do not, and receptor pseudogenes exist in rodents. Thirdly, motilin preferentially operates by facilitating enteric cholinergic activity rather than directly contracting the muscle, despite the relatively high expression of receptor immunoreactivity in muscle. This activity is ligand-dependent, with short-lasting actions of motilin contrasting with longer-lasting actions of the non-selective and selective motilin receptor agonists erythromycin and GSK962040. Finally, the use of erythromycin (also an antibiotic drug) to treat patients requiring acceleration of gastric emptying has led to concerns over safety and potential exacerbation of antibiotic resistance. Replacement motilin receptor agonists derived from erythromycin (motilides) have been unsuccessful. New, non-motilide, small molecule receptor agonists, designed to minimize self-desensitization, are now entering clinical trials for treating patients undergoing enteral feeding or with diabetic gastroparesis. Thus, for the translational pharmacologist, the study of motilin illustrates the need to avoid overreliance on artificial systems, on structural information and on animal studies. LINKED ARTICLES: This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.

Voluntary and automatic recruitment of superficial and deep abdominal muscles in adults with and without cystic fibrosis.

UNLABELLED: Recruitment patterns of the superficial and deep abdominal muscles have been well documented in the general population, but not in a group of individuals with a chronic cough, such as individuals with cystic fibrosis (CF), which may alter the recruitment patterns between the abdominal muscles. Therefore the two objectives of this study were (1) to identify whether recruitment of the superficial and deep abdominal muscles during abdominal hollowing (AH) and unilateral leg load (ULL) tasks differed between individuals with CF and a non-CF control group (C); and (2) to compare the muscle activity between the superficial and deep abdominal muscles across these tasks. METHODS: Twenty-eight participants (14 with CF and 14 controls) performed (i) AH in supine at three target pressures of a pressure biofeedback unit (PBU) and (ii) a right-sided ULL. Surface electromyography (EMG) of the abdominal muscles was recorded and the amplitude of the signal was normalized to a maximum value (% max). RESULTS: A 3-way repeated measures ANOVA showed a muscle × task interaction during the AH, but no between group differences. Bonferonni post hoc tests on pooled data showed the deep abdominal muscles to be significantly more active than the superficial muscles. A 2-way repeated measure ANOVA indicated no group differences during the ULL. DISCUSSION: The results of this study demonstrate that adults with stable CF do not recruit their abdominal muscles differently from healthy control subjects during the AH and the ULL tasks. This suggests that coughing is not a risk factor for developing abdominal muscles imbalances in adults with cystic fibrosis.

Individualised assessment of response to clopidogrel in patients presenting with acute coronary syndromes: a role for short thrombelastography?

INTRODUCTION: There is considerable interindividual variation in response to the antiplatelet agent clopidogrel. Hyporesponse predicts negative outcomes in patients presenting with a variety of ischemic cardiac conditions and following intracoronary stent placement. Many tests of clopidogrel activity are time consuming and complex. Short thromboelastography (s-TEG) allows rapid measurement of platelet clopidogrel response. AIMS: We initiated this study to investigate the utility of s-TEG in assessing the response to clopidogrel in patients presenting with acute coronary syndromes (ACS) and to compare these results with established clopidogrel monitoring techniques. METHODS: Patients admitted with unstable angina (UA) or Non ST elevation myocardial infarction (NSTEMI) undergoing coronary angiography were recruited. After routine loading with clopidogrel, all patients were tested with s-TEG and Accumetrics Verify-Now rapid platelet function analyzer (VN-RPFA). We used the modified TEG technique of measuring area under the curve at 15 min (AUC15), which allows a rapid estimation of antiplatelet response. Vasodilator-stimulated phosphoprotein phosphorylation (VASP) was also tested in a subgroup of patients. Clinical follow-up was obtained at 1 year. s-TEG results were correlated with VN-RPFA and VASP findings. RESULTS: A total of 49 patients (33 male, mean age 63) were recruited and tested with s-TEG and VN-RPFA and a total of 39 patients were also assessed with VASP. s-TEG readings correlated well with VN-RPFA (r(2)= 0.54, P < 0.0001) and VASP (r(2)= 0.26, P= 0.001). CONCLUSION: s-TEG provides timely results which compare to current tests of clopidogrel activity. This technique can also be used to measure a variety of other clotting parameters and as such could develop into a valuable near patient test for the interventional cardiologist.

Effective electromagnetic noise cancellation with beamformers and synthetic gradiometry in shielded and partly shielded environments.

The major challenge of MEG, the inverse problem, is to estimate the very weak primary neuronal currents from the measurements of extracranial magnetic fields. The non-uniqueness of this inverse solution is compounded by the fact that MEG signals contain large environmental and physiological noise that further complicates the problem. In this paper, we evaluate the effectiveness of magnetic noise cancellation by synthetic gradiometers and the beamformer analysis method of synthetic aperture magnetometry (SAM) for source localisation in the presence of large stimulus-generated noise. We demonstrate that activation of primary somatosensory cortex can be accurately identified using SAM despite the presence of significant stimulus-related magnetic interference. This interference was generated by a contact heat evoked potential stimulator (CHEPS), recently developed for thermal pain research, but which to date has not been used in a MEG environment. We also show that in a reduced shielding environment the use of higher order synthetic gradiometry is sufficient to obtain signal-to-noise ratios (SNRs) that allow for accurate localisation of cortical sensory function.

Coronary spasm induced by capecitabine mimicks ST elevation myocardial infarction.

Capecitabine is a chemotherapeutic prodrug that is metabolised to 5-fluorouracil. Supported by the National Institute for Health and Clinical Excellence guidance it is now first-line adjuvant treatment for metastatic colorectal cancer in the UK. Although cardiac chest pain and myocardial ischaemia are well recognised side effects of 5-fluorouracil, their association with capecitabine is not widely appreciated. Two cases are described of coronary spasm secondary to capecitabine in patients referred for emergency invasive treatment of presumed ST elevation myocardial infarction (STEMI). The contemporary treatment of acute coronary syndromes involves aggressive antiplatelet therapy, anticoagulation and cardiac catheterisation. This treatment, although beneficial in most patients, is associated with a small but significant risk of bleeding complications. A wider appreciation of the potential for capecitabine to induce spasm mimicking STEMI is important in order to reduce the risk of the administration of thrombolytics and other potentially dangerous drugs and have a higher threshold for referral for emergency angiography.

Review article: the psychoneuroimmunology of irritable bowel syndrome--an exploration of interactions between psychological, neurological and immunological observations.

BACKGROUND: The pathogenesis of irritable bowel syndrome (IBS) is founded on interactive mechanisms. Disentangling these processes is a prerequisite for the development of effective drug therapy. AIM: To identify the interaction between the various factors implicated in IBS. METHODS: Articles pertaining to IBS pathogenesis focusing on psychoneuroimmunology were identified using following search terms: IBS, animal models, microbiota, probiotics, immunology, visceral hypersensitivity, imaging, psychology and visceral pain. RESULTS: Cerebral imaging using MRI and proton emission tomography scanning has revealed differential regional cerebral activation, whereas stimuli induced activation has been captured by both MRI and cortical evoked potentials. At the peripheral neurological level, the concept of visceral hypersensitivity has been challenged as perhaps representing psychological traits with symptom over-reporting or hyper-vigilance. Gut mucosal immunology is thought to be relevant with immunological changes reflected as peripheral blood cytokine level changes. Molecular technology advances suggest a role for microbiota by activating the gut immunological system. These interactions have been examined in IBS animal models. CONCLUSIONS: Translation of animal model findings to humans is needed to link the various psychological, neurological and immunological changes noted in IBS. This analysis may identify patient sub-groups, which will ultimately be critical for drug testing to be focused accordingly.

Antiplatelet effects of licking an aspirin tablet can be detected by thrombelastography.

Aspirin is a cornerstone of treatment in cardiovascular disease. However, individual responses vary and hyporesponsiveness has been associated with poor outcomes following percutaneous intervention. Point of care assays for detecting the effects of aspirin in individual patients would therefore be useful. Thrombelastography has been shown to correlate with optical aggregation in the assessment of antiplatelet therapies and is suitable for use as a point of care assay. We demonstrate the ability of thrombelastography to detect the profound effects of even the tiny doses of aspirin obtained by licking an aspirin tablet.

Oesophageal afferent pathway sensitivity in non-erosive reflux disease.

Patients with non-erosive reflux disease (NERD) report symptoms which commonly fail to improve on conventional antireflux therapies. Oesophageal visceral hyperalgaesia may contribute to symptom generation in NERD and we explore this hypothesis using oesophageal evoked potentials. Fifteen endoscopically confirmed NERD patients (four female, 29-56 years) plus 15 matched healthy volunteers (four female, 23-56 years) were studied. All patients had oesophageal manometry/24-h pH monitoring and all subjects underwent evoked potential and sensory testing, using electrical stimulation of the distal oesophagus. Cumulatively, NERD patients had higher sensory thresholds and increased evoked potential latencies when compared to controls (P = 0.01). In NERD patients, there was a correlation between pain threshold and acid exposure as determined by DeMeester score (r = 0.63, P = 0.02), with increased oesophageal sensitivity being associated with lower DeMeester score. Reflux negative patients had lower pain thresholds when compared to both reflux positive patients and controls. Evoked potentials were normal in reflux negative patients but significantly delayed in the reflux positive group (P = 0.01). We demonstrate that NERD patients form a continuum of oesophageal afferent sensitivity with a correlation between the degree of acid exposure and oesophageal pain thresholds. We provide objective evidence that increased oesophageal pain sensitivity in reflux negative NERD is associated with heightened afferent sensitivity as normal latency evoked potential responses could be elicited with reduced afferent input. Increased oesophageal afferent pain sensitivity may play an important role in a subset of NERD and could offer an alternate therapeutic target.

Exploring the neurophysiological basis of chest wall allodynia induced by experimental oesophageal acidification - evidence of central sensitization.

In somatic models of central sensitisation (CS) allodynia develops following changes to somatic A-beta fibres, allowing these afferents which normally only process innocuous sensations to encode pain. The aim of this study was to determine whether somatic allodynia induced by visceral sensitisation occurs via N-Methyl-D-Aspartate (NMDA) receptor mediated changes to the neurophysiological characteristics of somatic A-beta fibres. Twelve healthy subjects had oesophageal, chest wall and foot pain thresholds (PT) to electrical stimulation measured, and chest wall evoked potentials (CEP) recorded before and 30 minutes after distal oesophageal acidification on 2 separate visits. Intravenous ketamine (an NMDA receptor antagonist) or saline was given 30 minutes post acid with repeated oesophageal and chest wall PT measurements and CEP recordings. Distal oesophageal acidification reduced PT to electrical stimulation on the anterior chest wall (37 +/- 10 mA v 29 +/- 7 mA p = 0.01) and proximal oesophagus (46 +/- 10 mA v 33 +/- 11 mA p = 0.001) but not the foot (37 +/- 25 mA v 39 +/- 23 mA p = 0.12). The induction of chest wall somatic allodynia was accompanied by a reduction in the latency of the P1 (36 +/- 3 ms to 30 +/- 4 ms p = 0.016) and P2 (87 +/- 7 ms to v 76 +/- 7 ms p = 0.049) components of the CEP. NMDA receptor antagonism reversed both visceral and somatic pain hypersensitivity but did not affect CEP latencies. These data provide objective neurophysiological evidence that CS contributes to the development of somatic allodynia following visceral sensitisation.

Neurokinin-1 receptor antagonism in a human model of visceral hypersensitivity.

BACKGROUND: Substance P acting via the neurokinin-1 receptor is involved in the development of hyperalgesia, although studies using neurokinin-1 receptor antagonists (NK-1RA) in human somatic pain have been disappointing. AIM: To evaluate whether Substance P is involved in the development of human visceral pain/hyperalgesia using a selective NK-1RA. METHODS: Using a validated human model of acid-induced oesophageal allodynia, pain thresholds to electrical stimulation (mA) were measured in the proximal oesophagus and the foot (somatic control), pre- and for 4 h postdistal oesophageal acid in 14 healthy subjects, using a double-blind, randomized, two-period, crossover study. Measurements were taken on the third day of dosing with either an oral NK-1RA or matching placebo, with 2 weeks washout between periods. RESULTS: Baseline pain threshold did not differ between treatments (proximal oesophagus 37 +/- 7.4 mA NK-1RA vs. 38 +/- 10.1 placebo P = 0.81, foot 40 +/- 15 mA NK-1RA vs. 38 +/- 14 placebo P = 0.68). NK-1RA did not attenuate the reduction in pain threshold in the proximal oesophagus postacid infusion (AUC-394 +/- 279 NK-1RA vs. -262 +/- 397 placebo P = 0.54). CONCLUSIONS: The lack of effect of NK-1RA on oesophageal pain threshold in our model does not support a role for Substance P in the development of acid-induced oesophageal allodynia.

Thrombelastography: current clinical applications and its potential role in interventional cardiology.

Thrombelastography is a bedside blood test used to assess patients' haemostatic status. It has a well-established role in hepatobiliary and cardiac surgery and is also used in obstetrics and trauma medicine to assess coagulation and identify the causes of post-operative bleeding. It is not routinely used in the diagnosis or treatment of thrombosis although recently it has been shown to predict thrombotic events post-operatively and after percutaneous intervention (PCI). In cardiovascular medicine the importance of the platelet in the pathophysiology of vascular events is increasingly apparent. As a result antiplatelet therapy is a cornerstone of the treatment for coronary disease, particularly in the setting of acute coronary syndromes. The increasing utilization of stents, particularly drug-eluting devices, in PCI has also necessitated widespread use of antiplatelet agents to minimize the risk of stent thrombosis. A quick, accurate and reliable test to measure the effect of platelet inhibition by antiplatelet agents on clotting in an individual patient would be of profound clinical value. The results from such a test could provide prognostic information, allow treatment with antiplatelet agents to be tailored to the individual and identify resistance to one or more of these agents. Optimization and tailoring of anti-platelet therapy in patients with cardiovascular disease, particularly those undergoing PCI, using such a test may reduce morbidity and mortality from thrombotic and haemorrhagic complications. Current methods of assessing platelet activity measure platelet count and function in isolation. Optical aggregation is the most widely used method for assessing platelet function but it is relatively time consuming, measures platelet function in isolation rather than in the context of clot formation and is not a bedside test. By contrast the modified thrombelastograph platelet mapping kit marketed by Haemoscope can be used to assess the effects of antiplatelet agents on ex vivo blood clotting, thus giving a measurement more relevant to in vivo responses. This represents a potentially powerful tool to assess response of individual patients to antiplatelet therapy, particularly in the context of PCI.

Assessing the temporal reproducibility of human esophageal motor-evoked potentials to transcranial magnetic stimulation.

BACKGROUND: Although the electrophysiological properties and reproducibility of somatic limb motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) are well characterized, little is known about the reproducibility of MEPs for viscerosomatic structures such as the esophagus. AIM: To determine the temporal reproducibility of esophageal MEPs to TMS. METHODS: MEPs to TMS were recorded from the proximal esophagus, using a swallowed catheter housing a pair of electrodes, in eight healthy subjects at five stimulus intensities (SI) (motor threshold [MT] to 20% above MT). For each SI, 20 consecutive TMS stimuli at 5-second intervals were delivered over a single scalp site (dominant hemisphere at site exhibiting MT at lowest SI) and repeated 40 and 80 minutes thereafter. MEP amplitudes and latencies were measured, and means were sequentially calculated for each SI and then log-transformed. The repeatability coefficients (RC) for the three time points were calculated across each set of 20 stimuli and presented as an exponential ratio. RESULTS: Best RC (amplitude/latency) were achieved at 120% SI relative to MT, being 1.8/1.2 (optimal = 1.0). For lower intensities of 115%, 110%, 105%, and 100% SI, the RC were 2.1/1.2, 2.1/1.1, 2.4/1.2, and 2.6/1.4, respectively. For all SI, the greatest reductions in RC occurred over the first 10 stimuli, with little additional gain beyond this number. CONCLUSIONS: Latencies of esophageal MEP to TMS across intensities are highly reproducible, whereas amplitudes are more stimulus intensity-dependent, being most reliable and reproducible at the highest stimulus strengths. SIGNIFICANCE: Using careful parameters, TMS can be used reliably in future studies of viscerosomatic structures, although the size of the response variability needs to be taken into account when assessing changes in cortico-fugal activity.