Seeding of hepatocellular carcinoma into the stomach wall following endoscopic ultrasound and fine-needle aspiration biopsy.

Delayed gastrointestinal metastasis is a rare complication of hepatocellular carcinoma (HCC). We present the case of a patient who presented with melaena and microcytic anaemia 6 years after receiving an orthotopic liver transplant for hepatitis B-induced HCC. Oesophagogastroduodenoscopy revealed a fungating gastric mass at the lesser curve and histology from biopsies confirmed metastatic recurrence of HCC in the stomach. The route of metastasis is likely due to iatrogenic seeding of tumour cells during pre-transplant endoscopic ultrasound (EUS) and fine needle aspiration (FNA) biopsy. Subsequent positron emission tomography and magnetic resonance imaging failed to reveal further metastatic disease and the patient was managed with a total gastrectomy. This is the first reported description in the literature of needle-track metastasis in the stomach due to liver EUS-FNA for HCC.

Continuous ambulatory peritoneal dialysis versus automated peritoneal dialysis for end-stage renal disease.

BACKGROUND: Peritoneal dialysis (PD) can be performed either manually as in continuous ambulatory peritoneal dialysis (CAPD) or using mechanical devices as in automated PD (APD). APD has been considered to have several advantages over CAPD such as reduced incidence of peritonitis, mechanical complications and greater psychosocial acceptability. OBJECTIVES: To assess the comparative efficacy of CAPD and APD in patients who are dialysed for end-stage renal disease (ESRD). SEARCH STRATEGY: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Renal Group's specialised register and CINAHL. Authors of included studies were contacted, reference lists of identified RCTs and relevant narrative reviews were screened. Date of most recent search: May 2006 SELECTION CRITERIA: RCTs comparing CAPD with APD in patients with ESRD. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two authors onto a standard form. Relative risk (RR) for dichotomous data and a mean difference (MD) for continuous data were calculated with 95% confidence intervals (CI). MAIN RESULTS: Three trials (139 patients) were included. APD did not differ from CAPD with respect to mortality (RR 1.49, 95% CI 0.51 to 4.37), risk of peritonitis (RR 0.75, 95% CI 0.50 to 1.11), switching from original PD modality to a different dialysis modality (RR 0.50, 95% CI 0.25 to 1.02), hernias (RR 1.26, 95% interval 0.32 to 5.01), PD fluid leaks (RR 1.06, 95% CI 0.11 to 9.83), PD catheter removal (RR 0.64, 95% CI 0.27 to 1.48) or hospital admissions (RR 0.96, 95% CI 0.43 to 2.17). There was no difference between either PD modality with respect to residual renal function (MD -0.17, 95% CI -1.66 to 1.32). One study found that peritonitis rates and hospitalisation were significantly less in patients on APD when results were expressed as episodes/patient-year. Another study found that patients on APD had significantly more time for work, family and social activities. AUTHORS' CONCLUSIONS: APD has not been shown to have significant advantages over CAPD in terms of important clinical outcomes. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. There is a need for a RCT comparing CAPD with APD with sufficiently large patient numbers looking at important clinical outcomes including residual renal function, accompanied by an economic evaluation to clarify the relative clinical and cost-effectiveness of both modalities.

Issues in data monitoring and interim analysis of trials.

OBJECTIVES: To address issues about data monitoring committees (DMCs) for randomised controlled trials (RCTs). DATA SOURCES: Electronic databases. Handsearching of selected books. Personal contacts with experts in the field. REVIEW METHODS: Systematic literature reviews of DMCs and small group processes in decision-making; sample surveys of: reports of RCTs, recently completed and ongoing RCTs and policies of major organisations involved in RCTs; case studies of four DMCs; and interviews with experienced DMC members. All focused on 23 prestated questions. RESULTS: Although still a minority, RCTs increasingly have DMCs. There is wide agreement that nearly all trials need some form of data monitoring. Central to the role of the DMC is monitoring accumulating evidence related to benefit and toxicity; variation in emphasis has been reflected in the plethora of names. DMCs for trials performed for regulatory purposes should be aware of any special requirements and regulatory consequences. Advantages were identified for both larger and smaller DMCs. There is general agreement that a DMC should be independent and multidisciplinary. Consumer and ethicist membership is controversial. The chair is recognised as being particularly influential, and likely to be most effective if he or she is experienced, understands both statistical and clinical issues, and is facilitating in style and impartial. There is no evidence available to judge suggested approaches to training. The review suggested that costs should be covered, but other rewards must be so minimal as to not affect decision-making. It is usual to have a minimum frequency of DMC meetings, with evidence that face-to-face meetings are preferable. It is common to have open sessions and a closed session. A report to a DMC should cover benefits and risks in a balanced way, summarised in an accessible style, avoiding excessive detail, and be as current as possible. Disadvantages of blinded analyses seem to outweigh advantages. Information about comparable studies should be included, although interaction with the DMCs of similar ongoing trials is controversial. A range of formal statistical approaches can be used, although this is only one of a number of considerations. DMCs usually reach decisions by consensus, but other approaches are sometimes used. The general, but not unanimous, view is that DMCs should be advisory rather than executive on the basis that it is the trial organisers who are ultimately responsible for the conduct of the trial. CONCLUSIONS: Some form of data monitoring should be considered for all RCTs, with reasons given where there is no DMC or when any member is not independent. An early DMC meeting is helpful, determining roles and responsibilities; planned operations can be agreed with investigators and sponsors/funders. A template for a DMC charter is suggested. Competing interests should be declared. DMC size (commonly three to eight people) is chosen to optimise performance. Members are usually independent and drawn from appropriate backgrounds, and some, particularly the chair, are experienced. A minimum frequency of meetings is usually agreed, with flexibility for more if needed. The DMC should understand and agree the statistical approach (and guidelines) chosen, with both the DMC statistician and analysis statistician competent to apply the method. A DMC's primary purpose is to ensure that continuing a trial according to its protocol is ethical, taking account of both individual and collective ethics. A broader remit in respect of wider ethical issues is controversial; arguably, these are primarily the responsibility of research ethics committees, trial steering committees and investigators. The DMC should know the range of recommendations or decisions open to it, in advance. A record should be kept describing the key issues discussed and the rationale for decisions taken. Errors are likely to be reduced if a DMC makes a thorough review of the evidence and has a clear understanding of how it should function, there is active participation by all members, differences are resolved through discussion and there is systematic consideration of the various decision options. DMCs should be encouraged to comment on draft final trial reports. These should include information about the data monitoring process and detail the DMC membership. It is recommended that groups responsible for data monitoring be given the standard name 'Data Monitoring Committee' (DMC). Areas for further research include: widening DMC membership beyond clinicians, trialists and statisticians; initiatives to train DMC members; methods of DMC decision-making; 'open' data monitoring; DMCs covering a portfolio of trials rather than single trials; DMC size and membership, incorporating issues of group dynamics; empirical study of the workings of DMCs and their decision-making, and which trials should or should not have a DMC.

Physical measures for treating depression in dialysis patients.

BACKGROUND: Depression is the most common psychological problem in the chronic dialysis population. The diagnosis of depression in patients on chronic dialysis is confounded by the fact that several symptoms of uraemia mimic the somatic components of depression. It affects their physical, psychological and social well-being. Furthermore, the frequent occurrence of cardiovascular problems and the pharmacokinetic consequences of renal impairment may make drug treatment of depression difficult. OBJECTIVES: The aim of this systematic review was to assess the efficacy and safety of physical measures in the treatment of depression in patients who are dialysed for end-stage renal disease. SEARCH STRATEGY: A comprehensive search strategy was employed to identify all Randomised Controlled Trials (RCTs) relevant to the treatment of depression in patients on chronic dialysis. The following database were searched - MEDLINE (1966-March 2004), EMBASE (1980-March 2004), PSYCHINFO (1872-March 2004), The Cochrane Library (Issue 1, 2004). Authors of included studies were contacted, reference lists of identified RCTs and relevant narrative reviews were screened. SELECTION CRITERIA: RCTs comparing drugs with placebo or no treatment, or a comparison of drugs against a combination of electroconvulsive therapy and drugs. DATA COLLECTION AND ANALYSIS: Data were abstracted by two investigators independently onto a standard form and subsequently entered into Review Manager 4.2. Relative risk (RR) for dichotomous data and a (weighted) mean difference (WMD) for continuous data were calculated with 95% confidence intervals (95% CI). MAIN RESULTS: Only one trial, with a total of 12 patients and of eight weeks duration was identified. The trial compared fluoxetine against placebo in depressed patients on chronic dialysis. This study did not show any significant difference in depression scores between the treatment and control groups or safety. AUTHORS' CONCLUSIONS: Firm conclusions on the efficacy of physical methods of treatment cannot be made as we identified only one small RCT that was of short duration. More larger and longer term RCTs are needed in this area. Current screening tools for depression are recognised to have poor specificity in the medically ill due to overlap of somatic symptoms of the medical illness. The development of a valid diagnostic tool would be helpful.

Wilms' tumor in the Li-Fraumeni cancer family syndrome.

Scrutiny of the family pedigrees of a population-based series of 176 children diagnosed with Wilms' tumor between 1954 and 1990, along with a review of the literature on the Li-Fraumeni cancer family syndrome, indicate that Wilms' tumor may be an uncommon component of the syndrome and that a small proportion of children with Wilms' tumor may be members of Li-Fraumeni syndrome (LFS) families.

Effects of neonatal cholinergic basal forebrain lesions on excitatory amino acid receptors in neocortex.

The role of cholinergic basal forebrain projections in the modulation of cortical plasticity and associated functional changes is currently the subject of renewed attention. Excitatory amino acid receptors have been identified as mediators of cortical topographic efferent and afferent information. In addition some of these receptors, notably the NMDA and metabotropic [mGluR] type, participate in cortical plasticity. Growing evidence suggests that interactions between cholinergic and glutamatergic systems contribute to cognitive cortical functions and their anatomical and physiological substrates. Though cholinergic and glutamatergic mechanisms have both been shown to be involved in cortical morphogenesis, few studies have attempted to study their interactions in development. The present study investigates the effect of neonatal lesions to the cholinergic basal forebrain on NMDA, AMPA and mGluR receptors in BALB/CByJ mice, at two different developmental ages. We demonstrated previously that nBM lesions at birth result in transient cholinergic depletion for the first two postnatal weeks, substantial morphogenetic alterations in neocortex and cognitive deficits by adulthood. We show here that unilateral neonatal lesions result in decreases in NMDA and AMPA receptors but increases in mGluRs during the second postnatal week (PND 14). At 30 days postnatal, lesion mediated changes were attenuated, compared with PND 14, but significant sex differences in control and nBM lesioned mice were apparent. These data support the notion that cholinergic/glutamatergic interactions are important during early cortical morphogenesis. Moreover, our results highlight the fact that cholinergic as well glutamatergic developmental mechanisms are sexually dimorphic.

Statistical assessment of the learning curves of health technologies.

OBJECTIVES: (1) To describe systematically studies that directly assessed the learning curve effect of health technologies. (2) Systematically to identify 'novel' statistical techniques applied to learning curve data in other fields, such as psychology and manufacturing. (3) To test these statistical techniques in data sets from studies of varying designs to assess health technologies in which learning curve effects are known to exist. METHODS - STUDY SELECTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW): For a study to be included, it had to include a formal analysis of the learning curve of a health technology using a graphical, tabular or statistical technique. METHODS - STUDY SELECTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): For a study to be included, it had to include a formal assessment of a learning curve using a statistical technique that had not been identified in the previous search. METHODS - DATA SOURCES: Six clinical and 16 non-clinical biomedical databases were searched. A limited amount of handsearching and scanning of reference lists was also undertaken. METHODS - DATA EXTRACTION (HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW): A number of study characteristics were abstracted from the papers such as study design, study size, number of operators and the statistical method used. METHODS - DATA EXTRACTION (NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH): The new statistical techniques identified were categorised into four subgroups of increasing complexity: exploratory data analysis; simple series data analysis; complex data structure analysis, generic techniques. METHODS - TESTING OF STATISTICAL METHODS: Some of the statistical methods identified in the systematic searches for single (simple) operator series data and for multiple (complex) operator series data were illustrated and explored using three data sets. The first was a case series of 190 consecutive laparoscopic fundoplication procedures performed by a single surgeon; the second was a case series of consecutive laparoscopic cholecystectomy procedures performed by ten surgeons; the third was randomised trial data derived from the laparoscopic procedure arm of a multicentre trial of groin hernia repair, supplemented by data from non-randomised operations performed during the trial. RESULTS - HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW: Of 4571 abstracts identified, 272 (6%) were later included in the study after review of the full paper. Some 51% of studies assessed a surgical minimal access technique and 95% were case series. The statistical method used most often (60%) was splitting the data into consecutive parts (such as halves or thirds), with only 14% attempting a more formal statistical analysis. The reporting of the studies was poor, with 31% giving no details of data collection methods. RESULTS - NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH: Of 9431 abstracts assessed, 115 (1%) were deemed appropriate for further investigation and, of these, 18 were included in the study. All of the methods for complex data sets were identified in the non-clinical literature. These were discriminant analysis, two-stage estimation of learning rates, generalised estimating equations, multilevel models, latent curve models, time series models and stochastic parameter models. In addition, eight new shapes of learning curves were identified. RESULTS - TESTING OF STATISTICAL METHODS: No one particular shape of learning curve performed significantly better than another. The performance of 'operation time' as a proxy for learning differed between the three procedures. Multilevel modelling using the laparoscopic cholecystectomy data demonstrated and measured surgeon-specific and confounding effects. The inclusion of non-randomised cases, despite the possible limitations of the method, enhanced the interpretation of learning effects. CONCLUSIONS - HEALTH TECHNOLOGY ASSESSMENT LITERATURE REVIEW: The statistical methods used for assessing learning effects in health technology assessment have been crude and the reporting of studies poor. CONCLUSIONS - NON-HEALTH TECHNOLOGY ASSESSMENT LITERATURE SEARCH: A number of statistical methods for assessing learning effects were identified that had not hitherto been used in health technology assessment. There was a hierarchy of methods for the identification and measurement of learning, and the more sophisticated methods for both have had little if any use in health technology assessment. This demonstrated the value of considering fields outside clinical research when addressing methodological issues in health technology assessment. CONCLUSIONS - TESTING OF STATISTICAL METHODS: It has been demonstrated that the portfolio of techniques identified can enhance investigations of learning curve effects. (ABSTRACT TRUNCATED)

The influence of heavy water on boron requirements for neutron capture therapy.

Neutron penetration in tissue is a major limitation of thermal NCT, as such much work has centered upon the epithermal neutron beam in an effort to improve this situation. Further gains in neutron flux penetration, and thus therapeutic ratios, are possible if natural water is replaced with heavy water prior to therapy. Applying MCNP to a heterogeneous ellipsoidal skull/brain model, advantage depth and therapeutic depth parameters are studied as a function of heavy water replacement for a range of tumor to blood boron ratios. Both thermal (0.025 eV) and epithermal (2-7 keV) ideal neutron beams are analyzed. Using 10B ratios in the range of documented human uptake, the thermal advantage depth improved by approximately 0.7 cm for 20% D2O replacement, however, the therapeutic depth increased by less than half this value. For the epithermal beam, both the advantage depth and the therapeutic depth increased by over 1 cm. Effects of heavy water replacement on 10B requirements to therapeutically treat the midline of the brain are also evaluated.

Monte Carlo calculations of epithermal boron neutron capture therapy with heavy water.

Much work over the past decade has centred upon the development of epithermal neutron beams for boron neutron capture therapy (BNCT) in an effort to increase thermal-neutron flux penetration and dose homogeneity throughout the brain. While heavy water has been used extensively to improve neutron penetration associated with thermal neutron beams, the effects of heavy water with epithermal neutron beams remain largely unexplored. Applying the Monte Carlo code MCNP to a heterogenous ellipsoidal skull/brain model, the effects of heavy-water replacement are studied for the JRC/ECN Petten HFR epithermal neutron beam. Thermal neutron flux and induced gamma depth dose distributions are calculated for 20% D2O replacement in comparison to standard brain and skull materials. Results are presented for both unilateral and bilateral irradiation. With bilateral irradiation, thermal-neutron flux homogeneity is substantially increased with 20% D2O replacement, thus improving the potential to give lethal doses to boron-10-loaded, disseminated cancer cells whilst avoiding local 'hot spots' to healthy tissue. Additionally, the induced gamma dose is reduced by up to 30%, substantially lowering the background dose to healthy tissue. With bilateral irradiation, 20% D2O replacement increases the therapeutic ratio from 2.25 to 2.75 for over 4 cm depth centred at the midline of the brain. These calculations use documented tumour and blood 10B concentrations for boronophenylalanine (BPA) in humans and recently documented neutron relative biological effectiveness (RBE) values.

Teatment planning figures of merit in thermal and epithermal boron neutron capture therapy of brain tumours.

The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of 10B tumour to blood ratios and absolute levels. These relationships were examined using the Monte Carlo neutron photon transport code, MCNP, with an ideal 18.4 cm diameter neutron beam incident laterally upon all ellipsoidal neutron photon brain-equivalent model. Mono-energetic beams of 0.025 eV (thermal) and 35 eV (epithermal) were simulated. Increasing the tumour to blood 10B ratio predictably increases all figures of merit. concentration was also shown to have a strong bearing on the figures of merit when low levels were present in the system. This is the result of a non-10B dependent background dose. At higher levels however, the concentration of 10B has a diminishing influence. For boron sulphydryl (BSH), little advantage is gained by extending the blood 10B level beyond 30 ppm, whilst for D,L,-p-boronophenylalanine (BPA) this limit is 10 ppm. To achieve a therapeutic depth of 6 cm (brain mid-line from brain surface) using the thermal beam, a tumour to blood ratio of 25 with 10 ppm 10B in the blood is required for BPA. Similarly, a tumour to blood ratio of 8.5 with 30 ppm blood 10B is required for the maximum therapeutic depth of BSH to reach the brain mid-line. These requirements are five times above current values for these compounds in humans. Applying the epithermal beam under identical conditions, the therapeutic depth reaches the brain mid-line with a tumour to blood 10B ratio of only 5.7 for BPA. For BSH, the maximum therapeutic depth reaches the brain mid-line with a tumour to blood ratio of only 1.9 with 30 ppm in the blood. Human data for these compounds are very close to these requirements.

Bladder training for urinary incontinence in adults.

BACKGROUND: Urinary incontinence is a common and distressing problem. Bladder training aims to increase the interval between voids and is widely used for the treatment of urinary incontinence. OBJECTIVES: To assess the effects of bladder training for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group trials register (January 2003). The reference lists of relevant articles were searched, and trialists contacted for details of other trials. Date of the most recent search: January 2003. SELECTION CRITERIA: Randomised or quasi-randomised trials of bladder training for the treatment of any type of urinary incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and independently extracted data. Five primary outcomes were prespecified: participant's perception of cure of urinary incontinence; participant's perception of improvement of urinary incontinence; number of incontinent episodes; number of micturitions; and quality of life. Adverse events were also noted. Three hypotheses were tested: bladder training is better than no bladder training; bladder training is better than other treatments; and combining bladder training with another treatment is better than that other treatment alone. MAIN RESULTS: We assessed 73 reports of 36 potentially relevant trials; 28 reports of ten trials were eligible for inclusion with a total of 1366, predominantly female, participants. Not all participants' with overactive bladder, in five trials had urinary incontinence. Data from five trials with 467 participants, all female, are therefore included in the review. The quality of trials was variable. Few data describing long term follow up are available.Is bladder training better than no bladder training? Data were available for 149 women from two trials comparing bladder training with no bladder training. These described only a limited number of prespecified outcomes, which varied across the two trials. Point estimates of effect favoured bladder training however confidence intervals were wide and no statistically significant differences were found for primary outcome variables.Is bladder training better than other treatments? Only two trials including 125 women compared bladder training with drugs: one with oxybutynin and one with imipramine plus flavoxate. In the former trial the only outcomes demonstrating a statistically significant difference were participant's perception of cure at six months (RR 1.69; 95% CI 1.21 to 2.34) and adverse events (RR 0.03; 95% CI 0.00 to 0.44), both favouring bladder training. In the latter trial participant's perception of cure immediately after treatment just achieved statistical significance (RR 1.50; 95% CI 1.02 to 2.21) favouring bladder training, and this difference was maintained at approximately two months post treatment. One comparison of bladder training with pelvic floor muscle training plus biofeedback included 132 women: none of the differences in the primary outcomes achieved statistical significance.Is combining bladder training with another treatment better than that other treatment alone? One trial compared pelvic floor muscle training plus biofeedback supplemented with bladder training versus pelvic floor muscle training plus biofeedback alone and included 125 women. Of the primary outcomes both participants' perception of improvement and quality of life, both immediately after treatment, achieved statistical significance, favouring the bladder training combined with pelvic floor muscle training and biofeedback group (perception of improvement: RR 1.18; 95% CI 1.01 to 1.39; quality of life: MD -47.20; 95% CI -87.03 to -7.37), this was not sustained at three months. REVIEWER'S CONCLUSIONS: The limited evidence available suggests that bladder training may be helpful for the treatment of urinary incontinence, but this conclusion can only be tentative as the trials were of variable quality and of small size with wide confidence intervals around the point estimates of effect. There was also not enough evidence to determine w evidence to determine whether bladder training was useful as a supplement to another therapy. Definitive research has yet to be conducted: more research is required.

Pediatric brain stem tumor presenting as a pure motor hemiparesis.

The clinical syndrome of pure motor hemiparesis occurs with lacunar lesions in the internal capsule or in the basis pontis in hypertensive adults. It has been described in three patients with brain stem tumors of which two were children. A 3 1/2 years old boy with a brain stem tumor which presented as pure motor hemiparesis is described.

EMG area scaling and velocity modulations in a spatiotemporally constrained movement.

Research examining the electromyographic (EMG) burst structure of rapid discrete limb movements has led to discordant findings concerning agonist burst duration. Some research has shown that duration varies as a function of movement speed while other research has shown burst constancy. Unfortunately, much of this research may be confounded by not carefully controlling movement termination accuracy and movement time (MT). Due to these potential problems, the present study was conducted to determine the effects of strict spatiotemporal constraints on EMG characteristics of a rapid elbow flexion-extension response under two movement extent conditions across five different MTs. Results revealed that a decreased MT was accompanied by a decreased agonist (biceps) burst duration and increased agonist burst amplitude. The burst duration and amplitude both increased as the movement extent increased with MT held constant. None of three current theoretical perspectives of rapid movement control (the impulse-timing model, the speed-control system hypothesis, or the speed-sensitive strategy) could fully account for these results. Instead, a control strategy was exhibited in which moving faster was accomplished by relative scaling of burst area via concomitant expansion of burst amplitude and compression of burst duration.

Localized muscular fatigue duration, EMG parameters and accuracy of rapid limb movements.

While much is known about the physiological basis of local muscular fatigue, little is known about the kinematic and electromyographic (EMG) consequences of brief fatiguing isometric contractions. Five male subjects performed a horizontal elbow flexion-extension reversal movement over 90° in 250 ms to reversal before and after one of five single maximal isometric elbow flexions ranging in duration from 15-120 s. Surface EMG signals were recorded from the biceps brachii, the long head of the triceps, the clavicular portion of the pectoralis major, and the posterior deltoid. Spatial and temporal errors were computed from potentiometer output. During the fatiguing bouts, maximum voluntary force dropped linearly an average of 4% in the 15 s condition and 58% in the 120 s condition relative to maximum force. The associated biceps rectified-integrated EMG signal increased from the onset of each fatigue bout for 15-30 s, then decreased over the remainder of the longer bouts. Following the fatigue bout, subjects undershot the target distance on the first movement trial in all conditions. Following short fatigue durations (i.e. 15-30 s), the peak biceps EMG amplitude was disrupted and movement velocity decreased, but both measures recovered within seconds. As fatigue duration increased, progressive decreases in peak velocity occurred with increased time to reversal, reduced EMG amplitude, and longer recovery times. However, the relative timing of the EMG pattern was maintained suggesting the temporal structure was not altered by fatigue. The findings suggest that even short single isometric contractions can disrupt certain elements of the motor control system.

An impulse-timing theory for reciprocal control of muscular activity in rapid, discrete movements.

Much remains to be learned about how agonist and antagonist muscles are controlled during the production of rapid, voluntary movements. In an effort to summarize a wide body of existing knowledge and stimulate future research on this subject, an impulse-timing theory is presented which attempts to predict the activity of reciprocal muscles based on certain characteristics of a movement. The basic tenet of the theory is that variables of movement time, movement distance and inertial load have fairly predictable effects on the underlying muscular activity of the agonist and antagonist muscles during the production of rapid and discrete, voluntary movements. The theory is derived from the kinematic work of Schmidt, Zelaznik, Hawkins, Frank and Quinn (1979) and supporting evidence from studies which have used electromyographic (EMG) recordings of agonist and antagonist muscles during rapid movements. Issues related to synergistic muscle control, central and peripheral control of reciprocal muscle activity, muscle control, and neurological disorder and the relationship between impulse-timing and mass-spring control are discussed in the final section.

The coding of location.

One prediction of the recent target hypothesis for movement control (MacNeilage, 1970; Russell, 1976) holds that location reproduction is not solely dependent upon stored kinesthetic information. Three experiments were performed to test this prediction by requiring the subject to reproduce the location with the limb opposite to the one used for criterion production. This switched-limb procedure was assumed to force the subject to rely upon more abstract information rather than the kinesthetic cues of the criterion movement. With movement direction invariant, switched-limb reproduction was equal to same-limb reproduction. The alteration of movement direction hampered switched-limb reproduction but same-limb reproduction was not greatly affected. These findings gave some support to the target hypothesis but suggested that the context of the movement may affect the potency of the location code. Implications of the switched-limb technique for future research were briefly discussed.

Temporal constraints in the control of prehensile movement.

Three experiments were conducted to investigate the control of the manipulation (i.e., finger-thumb aperture) and transportation (i.e., wrist velocity) components in prehensile movement (Jeannerod, 1981, 1984). In all experiments, subjects were seated and instructed to grasp a dowel mounted on a joystick following a discrete movement over a set distance. Thus, the amount of dowel movement following the grasp could be determined. In Experiment 1, the tolerance (i.e., the amount of allowable dowel movement) was manipulated using a computer-generated boundary around the dowel. The results indicated that the transportation component changed dependent on the tolerance condition, and there were trends that maximum aperture was also affected. Experiment 2 manipulated both tolerance and dowel size (i.e., diameter) factorially in a within-subject design. Dowel size affected only the manipulation component, supporting Jeannerod's (1981) earlier work, but tolerance clearly influenced both components. Experiment 3 investigated Wing, Turton, and Fraser's (1986) proposition that speed of movement influences aperture size. Distance and movement time were combined factorially to produce conditions with different average velocities. Maximum aperture was dependent on the movement time rather than the speed of movement. The relation between the control of the components was examined by using a new method of calculating within-trial correlations between aperture size and wrist velocity in Experiments 2 and 3. The correlations were related to the temporal aspects of the movement with higher correlations in the rapid movement time conditions. Also, the temporal occurrence of maximum aperture remained invariant across the different movement conditions. In general, the results suggest a strong functional linkage between the two components, which may be dependent on the temporal characteristics of the movement.

The independence of recall and recognition in motor learning.

A basic tenet of both current closed-loop theories of motor learning (Adams, 1971; Schmidt, 1975) is that the generation of response specifications during learning is required for the development of recall memory. Two experiments were performed to test this tenet by attempting to demonstrate the development of recall memory in the absence of response specification production. The task in both experiments required blindfolded subjects to learn to produce a rapid, novel criterion movement on a linear positioning device. Control subjects in both experiments actively produced movements during learning with knowledge of results (KR) while experimental subjects in Experiment 1 experienced only the endpoint locations and in Experiment 2 were passively moved to the endpoint locations. Following initial KR trials, both experimental and control groups attempted to actively produce the criterion movement in the absence of KR. The results of both experiments support closed-loop theory that active practice is required to develop recall memory. There was some suggestion, however, that passive experience with sensory feedback may also aid recall memory development, contrary to the two closed-loop theories.

Distance and movement time effects on the timing of agonist and antagonist muscles: a test of the impulse-timing theory.

The experiment examined the effects of movement time (MT) and distance on the timing at electromyographic (EMG) activity from an agonist and antagonist muscle during rapid, discrete elbow movements in the horizontal plane. According to impulse-timing theory (Wallace, 1981) MT, not distance moved, should have a pronounced effect on the timing of EMG activity (duration of initial agonist and antagonist burst and time to onset of initial antagonist burst). The levels of MT were 100 and 160 msec and the levels of distance were 27 degrees and 45 degrees of elbow flexion. In general support of impulse-timing theory, the results of the three EMG timing measures showed that MT had a more pronounced effect on these measures than distance. In addition, the timing of EMG activity in relation to total MT remained fairly consistent across the four MT-distance conditions.

An empirical note on attaining a spatial target after distorting the initial conditions of movement via muscle vibration.

Can one's limb be accurately positioned to a spatial location without a veridical estimate of the initial conditions of movement? The experiment reported here examined this question by distorting perception of a limb's starting position via muscle vibration. Subjects executed rapid flexion movements under no-vibration, contralateral arm vibration, and ipsilateral arm vibration conditions. Vibration was applied to the biceps for 10 sec prior to the start of a reproduction movement. The results showed that vibration on the ipsilateral arm caused a significant increase in reproduction error, relative to the no-vibration and contralateral-vibration conditions. This finding provides additional evidence that accurate knowledge about the initial conditions of movement is a necessary component in positioning a limb.