Development of clinical guidelines for service provision of functional electrical stimulation to support walking: mixed method exploration of stakeholder views.

BACKGROUND: Over the past 20 years Functional Electrical Stimulation (FES) has grown in clinical use to support walking in people with lower limb weakness or paralysis due to upper motor neuron lesions. Despite growing consensus regarding its benefits, provision across the UK and internationally is variable. This study aimed to explore stakeholder views relating to the value of a clinical guideline focusing on service provision of FES to support walking, how people might use it and what should be included. METHODS: A mixed methods exploration sought the views of key stakeholders. A pragmatic online survey (n = 223) focusing on the study aim was developed and distributed to the email distribution list of the UK Association for Chartered Physiotherapists Interested in Neurology (ACPIN). In parallel, a qualitative service evaluation and patient public involvement consultation was conducted. Two group, and seven individual interviews were conducted with: FES-users (n = 6), their family and carers (n = 3), physiotherapists (n = 4), service providers/developers (n = 2), researchers (n = 1) and distributors of FES (n = 1). Descriptive analysis of quantitative data and framework analysis of qualitative data were conducted. RESULTS: Support for clinical guideline development was clear in the qualitative interviews and the survey results. Survey respondents most strongly endorsed possible uses of the clinical guideline as ensuring best practice and supporting people seeking access to a FES service. Data analysis and synthesis provided clear areas for inclusion in the clinical guidelines, including current research evidence and consensus relating to who is most likely to benefit and optimal service provision as well as pathways to access this. Specific areas for further investigation were summarised for inclusion in the first stage of a Delphi consensus study. CONCLUSIONS: Key stakeholders believe in the value of a clinical guideline that focuses on the different stages of service provision for FES to support walking. A Delphi consensus study is being planned based on the findings.

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

BACKGROUND AND PURPOSE: To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. METHODS: During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. RESULTS: The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. CONCLUSIONS: A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena.

Nutrition claims in British women's magazines from 1940 to 1955.

BACKGROUND: The present study examined dietary messages conveyed in articles and advertising in two popular British women's magazines, Woman and Home and Woman's Own, between 1940 and 1954. METHODS: A qualitative analysis of written content was performed, focusing on regularities evident in content, and addressing the construction of the role of women in relation to food provision, as well as assertions for nutritional health. The setting comprised a desk-based study. The study sample encompassed 37 magazines, and yielded a corpus of 569 articles concerned with food or dietary supplements, of which 80.1% were advertisements. RESULTS: Ministry of Food dietary advice featured prominently up to 1945 and advocated food consumption according to a simple nutrient classification. Advertising and article content also used this classification; advocating consumption of food and supplements on the grounds of energy, growth and protection of health was customary. Providing food to meet nutritional needs was depicted as fundamental to women's war effort and their role as dutiful housewives. Advertising in 1950s magazines also focused on nutritional claims, with a particular emphasis on energy provision. CONCLUSIONS: These claims reflected the prevailing food policy and scientific understanding of nutritional health. This analysis of food messages in women's magazines provides lessons for contemporary nutrition policy.

Comparison of droplet spread in standard and laminar flow operating theatres: SPRAY study group.

BACKGROUND: Reducing COVID-19 transmission relies on controlling droplet and aerosol spread. Fluorescein staining reveals microscopic droplets. AIM: To compare the droplet spread in non-laminar and laminar air flow operating theatres. METHODS: A 'cough-generator' was fixed to a theatre trolley at 45°. Fluorescein-stained 'secretions' were projected on to a series of calibrated targets. These were photographed under UV light and 'source detection' software measured droplet splatter size and distance. FINDINGS: The smallest droplet detected was ∼120 µm and the largest ∼24,000 µm. An average of 25,862 spots was detected in the non-laminar theatre, compared with 11,430 in the laminar theatre (56% reduction). The laminar air flow mainly affected the smaller droplets (<1000 µm). The surface area covered with droplets was: 6% at 50 cm, 1% at 2 m, and 0.5% at 3 m in the non-laminar air flow; and 3%, 0.5%, and 0.2% in the laminar air flow, respectively. CONCLUSION: Accurate mapping of droplet spread in clinical environments is possible using fluorescein staining and image analysis. The laminar air flow affected the smaller droplets but had limited effect on larger droplets in our 'aerosol-generating procedure' cough model. Our results indicate that the laminar air flow theatre requires similar post-surgery cleaning to the non-laminar, and staff should consider full personal protective equipment for medium- and high-risk patients.

Feasibility of iterative learning control mediated by functional electrical stimulation for reaching after stroke.

BACKGROUND: An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and functional electrical stimulation (FES) to reduce upper limb impairments, but current systems may not encourage maximal voluntary contribution from the participant because assistance is not responsive to performance. OBJECTIVE: This study aimed to investigate whether iterative learning control (ILC) mediated by FES is a feasible intervention in upper limb stroke rehabilitation. METHODS: Five hemiparetic participants with reduced upper limb function who were at least 6 months poststroke were recruited from the community. No participants withdrew. INTERVENTION: Participants undertook supported tracking tasks using 27 different trajectories augmented by responsive FES to their triceps brachii muscle, with their hand movement constrained in a 2-dimensional plane by a robot. Eighteen 1-hour treatment sessions were used with 2 participants receiving an additional 7 treatment sessions. OUTCOME MEASURES: The primary functional outcome measure was the Action Research Arm Test (ARAT). Impairment measures included the upper limb Fugl-Meyer Assessment (FMA), tests of motor control (tracking accuracy), and isometric force. RESULTS: Compliance was excellent and there were no adverse events. Statistically significant improvements were measured (P

A robotic workstation for stroke rehabilitation of the upper extremity using FES.

An experimental test facility is developed for use by stroke patients in order to improve sensory-motor function of their upper limb. Subjects are seated at the workstation and their task is to repeatedly follow reaching trajectories that are projected onto a target above their arm. To do this they use voluntary control with the addition of electrical stimulation mediated by advanced control schemes applied to muscles in their impaired shoulder and arm. Full details of the design of the workstation and its periphery systems are given, together with a description of its use during the treatment of stroke patients.

Statistical physics of language maps in the USA.

Spatial linguistic surveys often reveal well-defined geographical zones where certain linguistic forms are dominant over their alternatives. It has been suggested that these patterns may be understood by analogy with coarsening in models of two-dimensional physical systems. Here we investigate this connection by comparing data from the Cambridge Online Survey of World Englishes to the behavior of a generalized zero temperature Potts model with long-range interactions. The relative displacements of linguistically similar population centers reveal enhanced east-west affinity. Cluster analysis reveals three distinct linguistic zones. We find that when the interaction kernel is made anisotropic by stretching along the east-west axis, the model can reproduce the three linguistic zones for all interaction parameters tested. The model results are consistent with a view held by some linguists that, in the USA, language use is, or has been, exchanged or transmitted to a greater extent along the east-west axis than the north-south.

Standardized measurement of quality of upper limb movement after stroke: Consensus-based core recommendations from the Second Stroke Recovery and Rehabilitation Roundtable.

The second Stroke Recovery and Rehabilitation Roundtable "metrics" task force developed consensus around the recognized need to add kinematic and kinetic movement quantification to its core recommendations for standardized measurements of sensorimotor recovery in stroke trials. Specifically, we focused on measurement of the quality of upper limb movement. We agreed that the recommended protocols for measurement should be conceptually rigorous, reliable, valid and responsive to change. The recommended measurement protocols include four performance assays (i.e. 2D planar reaching, finger individuation, grip strength, and precision grip at body function level) and one functional task (3D drinking task at activity level) that address body function and activity respectively. This document describes the criteria for assessment and makes recommendations about the type of technology that should be used for reliable and valid movement capture. Standardization of kinematic measurement protocols will allow pooling of participant data across sites, thereby increasing sample size aiding meta-analyses of published trials, more detailed exploration of recovery profiles, the generation of new research questions with testable hypotheses, and development of new treatment approaches focused on impairment. We urge the clinical and research community to consider adopting these recommendations.

Standardized Measurement of Quality of Upper Limb Movement After Stroke: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable.

The second Stroke Recovery and Rehabilitation Roundtable "metrics" task force developed consensus around the recognized need to add kinematic and kinetic movement quantification to its core recommendations for standardized measurements of sensorimotor recovery in stroke trials. Specifically, we focused on measurement of the quality of upper limb movement. We agreed that the recommended protocols for measurement should be conceptually rigorous, reliable, valid and responsive to change. The recommended measurement protocols include four performance assays (i.e. 2D planar reaching, finger individuation, grip strength, and precision grip at body function level) and one functional task (3D drinking task at activity level) that address body function and activity respectively. This document describes the criteria for assessment and makes recommendations about the type of technology that should be used for reliable and valid movement capture. Standardization of kinematic measurement protocols will allow pooling of participant data across sites, thereby increasing sample size aiding meta-analyses of published trials, more detailed exploration of recovery profiles, the generation of new research questions with testable hypotheses, and development of new treatment approaches focused on impairment. We urge the clinical and research community to consider adopting these recommendations.

The clinical effectiveness of static resting splints in early rheumatoid arthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of static resting splints in early RA. METHODS: A multicentre, randomized, trial was conducted. Patients (n = 120) received either static resting splints [positioned with the wrist in neutral, MCP joint (MCPJ) and IP joint (IPJ) in a maximum of 60 degrees and 30 degrees of flexion, respectively] plus standardized occupational therapy or standardized occupational therapy alone. Change in grip strength (Ns), structural impairment (MCPJ ulnar deviation), applied dexterity (Button Board), self-report hand ability [Michigan Hand Outcomes Questionnaire (MHQ)], hand pain and morning hand stiffness were assessed at 0 and 12 months. RESULTS: Data for 56 (97%) splinted and 60 (97%) control group patients were analysed. Splint wear adherence was moderate; 24.5% 'never wore' the splints. The adjusted mean difference between groups for handgrip was -14.2 Ns (P = 0.342; 95% CI -43.7, 5.4); MCPJ ulnar deviation -1.1 degrees (P = 0.657; 95% CI = -6.2, 3.9); dexterity 0.1 s (P = 0.975; 95% CI = -6.6, 6.8) and self-report ability -3.0 on the MHQ score (P = 0.426; 95% CI -10.5, 4.5). Pain scores were unchanged in either group (P = 0.15). The occurrence of morning hand stiffness was reduced in a small group of splinted patients (P = 0.021), but the duration shortened in control patients (P = 0.010). CONCLUSIONS: There was no significant difference between the two interventions on grip strength, deformity, hand function and pain. The data favoured the control group and this study suggests that resting splints should not be used as a routine treatment of patients with early RA.

A qualitative study exploring views and experiences of people with stroke undergoing transcranial direct current stimulation and upper limb robot therapy.

Background Neurorehabilitation technologies used mainly in research such as robot therapy (RT) and transcranial direct current stimulation (tDCS) can promote upper limb motor recovery after stroke. Understanding the feasibility and efficacy of stroke rehabilitation technologies for upper limb impairments is crucial for effective implementation in practice. Small studies have explored views of RT by people with stroke; however experiences of people receiving tDCS in combination with RT have never been explored. Objective To explore views and experiences of people with sub-acute and chronic stroke that had previously taken part in a randomised controlled trial involving tDCS and RT for their impaired upper limb. Methods An interview study includes open and closed questions. Face-to-face interviews were audio recorded. Open-ended question responses were transcribed and analyzed using thematic analysis; closed questions were analyzed using descriptive analysis. Results Participants felt that RT was enjoyable (90%) and beneficial for their affected arm (100%). From the open question data, it was found that the intervention was effective for the impaired arm especially in the sub-acute stage. Main reported concerns were that tDCS caused painful, itching and burning sensations and RT was sometimes tiring and difficult. Participants recommended that future research should focus on designing a more comfortable method of tDCS and develop a robot that promotes hand movements. Conclusions This study provides new knowledge about the benefits and barriers associated with these technologies which are crucial to the future effective implementation of these tools in practice.

Analysis of the quality of wrist movement during a simple tracking task.

Objective assessment of stroke-patients' ability to control arm movements is vital for evidence-based therapy and progress monitoring. This study compares three different indices to quantify the quality of wrist movement during a task involving tracking a target on a screen. Each method is assessed in terms of agreement between assessors (Bland and Altman limits of agreement); repeatability of readings by the same assessor (reliability coefficient); and external validity on data collected from a sample of people with impaired upper limb function and an age matched unimpaired control group. The three indices were the root mean square difference between the wrist movement and the target signal, the cross correlation between these two signals, and an estimate of the signal-to-noise ratio in the wrist movement. External validity was investigated by calculating the correlation between each measure for wrist movement, and upper limb function assessed by the action research arm test. The results of the Bland and Altman limits of agreement show that all indices were similar in performance. The cross correlation had the highest reliability coefficient for the impaired group. In terms of external validity, the cross correlation and signal-to-noise indices showed the strongest association with functional performance and may thus be the more relevant for future clinical investigations.

Clinometric properties of a clinical spasticity measurement tool.

PURPOSE: To investigate clinometric properties of an Anglo-Dutch spasticity measurement tool (ADSMT), an objective tool providing information about both neurophysiological and biomechanical aspects of spasticity about the wrist joint in the clinical setting. METHOD: ADSMT measurements were performed with 12 healthy and 11 participants with post-stroke spasticity, and consisted of assessing the maximum range of passive wrist movement (pROM) and passive wrist extension at different cycle rates. Outcome measures were wrist angle, flexor and extensor activation, and resistance to movement. Intra-class Correlation Coefficients (ICCs) were calculated for inter-rater and test-retest reliability. Validity was investigated by calculating Spearman's rho between ADSMT outcome measures and the Modified Ashworth Scale (n=12), the Action Research Arm Test (n=6), and a validated wrist rig (n=6). RESULTS: Impaired participants had higher flexor activity and higher resistance to movement during passive wrist extension compared to unimpaired participants. For all outcome measures inter-rater and test-retest reliability were satisfactory to good and concurrent validity was sufficient. CONCLUSIONS: Outcome measures related to wrist flexor activity and resistance to movement during extension are promising for spasticity assessment using the ADSMT. Further knowledge on reference values and practicality is necessary for this tool to become incorporated in the clinical setting.

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis.

OBJECTIVE: To systematically review the methodology in particular treatment options and outcomes and the effect of multiple sessions of transcranial direct current stimulation (tDCS) with rehabilitation programmes for upper extremity recovery post stroke. METHODS: A search was conducted for randomised controlled trials involving tDCS and rehabilitation for the upper extremity in stroke. Quality of included studies was analysed using the Modified Downs and Black form. The extent of, and effect of variation in treatment parameters such as anodal, cathodal and bi-hemispheric tDCS on upper extremity outcome measures of impairment and activity were analysed using meta-analysis. RESULTS: Nine studies (371 participants with acute, sub-acute and chronic stroke) were included. Different methodologies of tDCS and upper extremity intervention, outcome measures and timing of assessments were identified. Real tDCS combined with rehabilitation had a small non-significant effect of +0.11 (p=0.44) and +0.24 (p=0.11) on upper extremity impairments and activities at post-intervention respectively. CONCLUSION: Various tDCS methods have been used in stroke rehabilitation. The evidence so far is not statistically significant, but is suggestive of, at best, a small beneficial effect on upper extremity impairment. SIGNIFICANCE: Future research should focus on which patients and rehabilitation programmes are likely to respond to different tDCS regimes.

Biomechanical approaches applied to the lower and upper limb for the measurement of spasticity: a systematic review of the literature.

PURPOSE: To review and characterise biomechanical approaches for the measurement of spasticity as one component of the upper motor neurone syndrome. METHOD: Systematic literature searches based on defined constructs and a four-step review process of approaches used or described to measure spasticity, its association with function or associated phenomena. Most approaches were limited to individual joints and therefore, to reflect this trend, references were grouped according to which body joint(s) were investigated or whether it addressed a functional activity. For each joint, references were further sub-divided into the types of measurement method described. RESULTS: A database of 335 references was established for the review process. The knee, ankle and elbow joints were the most popular, perhaps reflecting the assumption that they are mono-planar in movement and therefore simpler to assess. Seven measurement methods were identified: five involving passive movement (manual, controlled displacement, controlled torque, gravitational and tendon tap) and two involving active movement (voluntary and functional). Generally, the equipment described was in an experimental stage and there was a lack of information on system properties, such as accuracy or reliability. Patient testing was either by cohort or case studies. The review also conveyed the myriad of interpretations of the concept of spasticity. CONCLUSIONS: Though biomechanical approaches provide quantitative data, the review highlighted several limitations that have prevented them being established as an appropriate method for clinical application to measure spasticity.

Theoretical and methodological considerations in the measurement of spasticity.

PURPOSE: To discuss the measurement of spasticity in the clinical and research environments, make recommendations based on the SPASM reviews of biomechanical, neurophysiological and clinical methods of measuring spasticity and indicate future developments of measurement tools. METHOD: Using the results of the systematic reviews of the biomechanical, neurophysiological and clinical approaches, methods were evaluated across three dimensions: (1) validity, reliability and sensitivity to change; (2) practical quality such as ease of use and (3) qualities specific to the measurement of spasticity, for example ability to be applied to different muscle groups. Methods were considered in terms of applicability to research and clinical applications. RESULTS: A hierarchy of measurement approaches was identified from highly controlled and more objective (but unrelated to function) to ecologically valid, but less objective and subject to contamination from other variables. The lack of a precise definition of spasticity may account for the problem of developing a valid, reliable and sensitive method of measurement. The reviews have identified that some tests measure spasticity per se, some phenomena associated with spasticity or consequential to it and others the effect of spasticity on activity and participation and independence. CONCLUSIONS: Methods appropriate for use in research, particularly into the mechanism of spasticity did not satisfy the needs of the clinician and the need for an objective but clinically applicable tool was identified. A clinical assessment may need to generate more than one 'value' and should include evaluation of other components of the upper motor neurone syndrome. There is therefore a need for standardized protocols for 'best practice' in application of spasticity measurement tools and scales.

Physical rehabilitation for critical illness myopathy and neuropathy: an abridged version of Cochrane Systematic Review.

Intensive care unit (ICU) acquired or generalised weakness due to critical illness myopathy (CIM) and polyneuropathy (CIP) are major causes of chronically impaired motor function that can affect activities of daily living and quality of life. Physical rehabilitation of those affected might help to improve activities of daily living. Our primary objective was to assess the effects of physical rehabilitation therapies and interventions for people with CIP and CIM in improving activities of daily living such as walking, bathing, dressing and eating. Secondary objectives were to assess effects on muscle strength and quality of life, and to assess adverse effects of physical rehabilitation. On 16 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register and on 14 July 2014 we searched CENTRAL, MEDLINE, EMBASE and CINAHL Plus. In July 2014, we searched the Physiotherapy Evidence Database (PEDro) and three trials registries for ongoing trials and further data about included studies with no language restrictions. We also handsearched relevant conference proceedings and screened reference lists to identify further trials. We planned to include randomised controlled trials (RCTs), quasi-RCTs and randomised controlled cross-over trials of any rehabilitation intervention in people with acquired weakness syndrome due to CIP/CIM. We would have extracted data, assessed the risk of bias and classified the quality of evidence for outcomes in duplicate, according to the standard procedures of The Cochrane Collaboration. Outcome data collection would have been for activities of daily living (for example, mobility, walking, transfers and self care). Secondary outcomes included muscle strength, quality of life and adverse events. The search strategy retrieved 3587 references. After examination of titles and abstracts, we retrieved the full text of 24 potentially relevant studies. None of these studies met the inclusion criteria of our review. No data were suitable to be included in a meta-analysis. There are no published RCTs or quasi-RCTs that examine whether physical rehabilitation interventions improve activities of daily living for people with CIP and CIM. Large RCTs, which are feasible, need to be conducted to explore the role of physical rehabilitation interventions for people with CIP and CIM. This paper is based on a Cochrane Review published in in the Cochrane Database of Systematic Reviews (CDSR) 2015, Issue 3, DOI: 10.1002/14651858.CD010942.pub2. (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the CDSR should be consulted for the most recent version of the review.

A double-blinded randomised controlled trial exploring the effect of anodal transcranial direct current stimulation and uni-lateral robot therapy for the impaired upper limb in sub-acute and chronic stroke.

BACKGROUND: Neurorehabilitation technologies such as robot therapy (RT) and transcranial Direct Current Stimulation (tDCS) can promote upper limb (UL) motor recovery after stroke. OBJECTIVE: To explore the effect of anodal tDCS with uni-lateral and three-dimensional RT for the impaired UL in people with sub-acute and chronic stroke. METHODS: A pilot randomised controlled trial was conducted. Stroke participants had 18 one-hour sessions of RT (ArmeoSpring) over eight weeks during which they received 20 minutes of either real tDCS or sham tDCS during each session. The primary outcome measure was the Fugl-Meyer assessment (FMA) for UL impairments and secondary were: UL function, activities and stroke impact collected at baseline, post-intervention and three-month follow-up. RESULTS: 22 participants (12 sub-acute and 10 chronic) completed the trial. No significant difference was found in FMA between the real and sham tDCS groups at post-intervention and follow-up (p = 0.123). A significant 'time' x 'stage of stroke' was found for FMA (p = 0.016). A higher percentage improvement was noted in UL function, activities and stroke impact in people with sub-acute compared to chronic stroke. CONCLUSIONS: Adding tDCS did not result in an additional effect on UL impairment in stroke. RT may be of more benefit in the sub-acute than chronic phase.

Computer graphics in drug design: molecular modeling of thyroid hormone-prealbumin interactions.

Computer graphics modeling of the thyroxine-prealbumin complex provides a detailed picture of the interactions between thyroxine and prealbumin. A wide variety of thyroid hormone analogue-prealbumin complexes were modeled by calculating the molecular surfaces of the analogues and the prealbumin hormone-binding site. Analogues with high binding affinity were observed to fill more of the hormone-binding site than low-affinity analogues. These surface models described many aspects of the hormone-protein interaction which were not obvious using simple wire models and led us to develop a model which accounts for thyroid hormone-prealbumin structure-activity relationships and ultimately to predict and measure the relative binding affinities of four previously untested thyroid hormone analogues to prealbumin.

The pharmacological characterization of 5-HT3 receptors in three isolated preparations derived from guinea-pig tissues.

1. The pharmacological characterization of the 5-HT3 receptors in guinea-pig isolated tissues is described. The tissues used were ileum (longitudinal muscle-myenteric plexus), colon and vagus nerve. The guinea-pig isolated colon is a novel preparation. 2. In the guinea-pig isolated ileum, 5-hydroxytryptamine (5-HT, 1 x 10(-8)-3 x 10(-5) M) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (3 x 10(-7)-1 x 10(-4) M) caused concentration-related contractions. The 5-HT concentration-response curve was biphasic whilst the 2-methyl-5-HT curve was monophasic. The EC50 value for the low potency portion of the 5-HT curve was 4.1 x 10(-6) M. The EC50 for 2-methyl-5-HT was 1.23 x 10(-5) M. Selective 5-HT3 receptor antagonists caused rightward shifts of the 2-methyl-5-HT curve and the lower potency portion of the 5-HT curve. Neither ketanserin (1 x 10(-6) M) nor methysergide (1 x 10(-5) M) antagonized the responses to 5-HT or 2-methyl-5-HT. 3. In the guinea-pig isolated colon, 5-HT (3 x 10(-7)-3 x 10(-5) M; EC50 2.4 x 10(-6) M) caused contractions which were mimicked by 2-methyl-5-HT (1 x 10(-6)-1 x 10(-4) M; EC50 7.2 x 10(-6) M). Selective 5-HT3 receptor antagonists caused rightward displacements of the 5-HT concentration-response curves. Neither ketanserin (1 x 10-6 M) nor methysergide (1 x 10- 5M) had any effect on responses to 5-HT or 2-methyl- 5-HT. 4. In the guinea-pig isolated vagus nerve, 5-HT (1 x 10-6-3 x 1O-4M) and 2-methyl-5-HT (1 x i0-S- 1 X 10-3m; EC50 7.6 x 10- M) caused depolarizations; at higher concentrations there were afterhyperpolarizations. The maximum response to 2-methyl-5-HT was less than half that to 5-HT. Selective 5-HT3 receptor antagonists caused rightward displacements of the 5-HT concentration-response curves. Antagonists at other 5-HT receptors (ketanserin, 1 x 10- M and methysergide, 1 x 10-6 M) had no effect. 5. The estimated affinity values of 5-HT3 receptor antagonists correlated well between the three models. Phenylbiguanide was inactive as an agonist or antagonist (up to 1 x 1O-4M) in each preparation. 6. Comparisons with antagonist affinity values obtained in the rat isolated vagus nerve revealed marked differences. Antagonists were generally more potent on the rat isolated vagus nerve, although the differences varied considerably between antagonists. 7. The results are discussed in terms of species-related receptor differences.