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Differential efficacy of serotonergic drugs FG5974, FG5893, and amperozide in reducing alcohol drinking in P rats.

Amperozide (FG5606), a 5-HT2 receptor antagonist, is well known to suppress alcohol consumption in different rat models of drinking. The present study compared the efficacy of three drugs, FG5974, FG5893, and amperozide, which have differential affinities for 5-HT1A and 5-HT2A receptors, on alcohol drinking in the genetic alcohol-preferring (P) rat. After preference for alcohol vs. water was determined over 10 days when concentrations of alcohol were increased from 3% to 30%, the maximal concentration of alcohol preferred by each animal was selected for drug testing. A 4-day predrug preference test was followed by SC injection of the saline control vehicle or doses of 1.0 and 2.5 mg/kg FG5974, FG5893, or amperozide given at 1600 and 2200 h for 4 days. Alcohol preference testing concluded with a final 4-day interval. A total daily dose of 5.0 mg/kg FG5974 reduced absolute g/kg intake of alcohol and proportional intakes of the P rats significantly; the lower dose of FG5974 also reduced alcohol drinking significantly following treatment. The mixed 5-HT1A agonist/5-HT2A antagonist, FG5893, which suppresses drinking in cyanamide-treated rats, was without effect on alcohol ingested by the P rats. However, amperozide caused a dose-dependent decline in both absolute intakes and proportion of alcohol that was more intense than that of FG5974. The control vehicle failed to alter alcohol drinking and, like the FG compounds, did not affect food intake or body weight. Although the inhibition of alcohol drinking by amperozide corresponds precisely with previous findings, the effect of FG5974 contrasts to results obtained with a structurally analogous drug FG5893. Thus, the genetic strain of rat as well as the nature of the chemical characteristics of a 5-HT agonist/antagonist will determine the differential efficacy of a drug in influencing the volitional drinking of alcohol.

Alcohol Drinking↗

Oculomotor apraxia: the presenting sign of Gaucher disease.

Oculomotor apraxia may be idiopathic or a symptom of a variety of diseases. In Gaucher disease, oculomotor deficit is characterized by a failure of volitional horizontal gaze with preservation of vertical movements. We present 2 sisters, 6 1/2 and 5 1/2 years of age, in whom the presenting sign was oculomotor apraxia. Oculomotor apraxia has not been previously reported as the presenting manifestation of Gaucher disease.

Apraxias↗

The effects of cadmium on the self-administration of ethanol and an isocaloric/isohedonic equivalent.

During a period of baseline fluid intake recording, adult male rats were presented with a three-bottle, two-fluid choice test that offered either a 10% ethanol solution (v/v) and tap water as alternatives, or a sucrose/quinine solution and tap water as alternatives. The sucrose/quinine solution was equivalent to the ethanol solution both in terms of calories and palatability. After intakes stabilized, half of the animals from each test condition were placed on a diet containing 100 ppm cadmium and the remaining half of the animals were placed on a standard laboratory diet. After 60 days of exposure to their respective diets, all animals were presented their earlier test solutions, both in a nonchoice and choice format. The results from the choice test indicated that although cadmium treatment did not produce a clear preference for ethanol over water, cadmium exposure was associated with a significant increase in ethanol consumption. Moreover, the self-administration of the isocaloric/isohedonic equivalent (sucrose/quinine solution) was unaffected by cadmium contamination. These data are discussed in terms of their implications for both nutritional and sensory-impairment accounts of metal-related changes in the volitional intake of ethanol.

Alcohol Drinking↗

Motor assessment of cocaine/polydrug exposed infants at age 4 months.

Fifty nondrug-exposed infants and 74 cocaine/polydrug-exposed infants were evaluated on the Movement Assessment of Infants (MAI). The test provides an assessment of risk for motor dysfunction at age 4 months. There was a significant difference in total risk scores between the two groups of infants with cocaine-exposed infants having higher total risk scores (p less than .0001). Categorical risk scores revealed significant differences between the infants in muscle tone, primitive reflexes, and volitional movement with cocaine-exposed infants scoring more poorly in each category (p less than .0001). The groups scored differently on 11 of the 49 MAI items in those categories. Placement of infants within previously established ranges of risk scores (0-7 = no risk; 8-13 questionable risk; greater than 13 = high risk) revealed a significant difference in distribution between the two groups (p less than .0001). Earlier studies of the effects of intrauterine drug exposure have not revealed significant differences in motor development. The MAI demonstrated differential assessments of risk for motor dysfunction between cocaine-exposed and nondrug-exposed infants.

Analysis of Variance↗

Suppression of alcohol preference in high alcohol drinking rats: efficacy of amperozide versus naltrexone.

The selectively bred high alcohol drinking (HAD) line of rat is considered as a potential model of one type of alcoholism. The purpose of the present experiments was to compare the efficacy of two drugs on the volitional drinking of the HAD rats: the 5-HT2A receptor antagonist, amperozide, and a nonselective antagonist of opiate receptors, naltrexone. To determine the pattern of alcohol drinking of the HAD rats, a standard preference test was used in which water was offered with alcohol increased in concentrations from 3% to 30% over 11 days. The maximally preferred concentration of alcohol of each rat was offered for 4 days and ranged from 7% to 20% with a mean intake of 6.9 g/kg per day. Initially, 1.0 mg/kg amperozide, 2.5 mg/kg naltrexone, or the saline vehicle were injected twice daily for 4 days at 1600 and 2200 hours. Secondly, 2.0 mg/kg amperozide, 5.0 mg/kg naltrexone, or the saline vehicle were administered also for 4 days. After the drug sequences, alcohol preference tests continued for another 4 days. Whereas the saline vehicle was without effect on drinking, the administration of either drug caused a significant dose-dependent reduction in the daily intake of alcohol by the HAD rats in terms of absolute g/kg and proportion of alcohol to water consumed. A comparison of the drinking response to the higher doses of the two drugs showed that amperozide was more efficacious in suppressing alcohol intake than naltrexone. Niether amperozide nor naltrexone exerted any significant effects on food and water intakes or on body weight. These results support the concept of a functional link in the brain between the serotonergic and opioidergic systems postulated to underlie, in part, the aberrant drinking of alcohol. A marked dissociation between the temporal patterns of drinking after naltrexone and amperozide treatment suggests that the opiate receptors mediate the immediate reinforcing effects of alcohol, whereas the more vegetative phenomena underlying addictive properties of alcohol are regulated by 5-HT2A receptors postsynaptic to serotonergic neurons. Finally, the inhibitory actions of both drugs imply that multiple receptor mechanisms within the mesolimbic and other systems in the brain underpin the addictive liability to alcohol.

Alcohol Deterrents↗

Characteristics and variability of lower limb motoneuron responses to transcranial magnetic stimulation.

The characteristics and variability of the short latency responses to transcranial magnetic stimulation (TMS) were examined in 188 single lower limb motor units. Information about the cortically evoked postsynaptic potentials was derived from peristimulus time histograms generated from the discharge times of single, rhythmically active, motor units. Tibialis anterior (TA) motoneurons were almost exclusively facilitated and response magnitudes were consistent within a motoneuron pool as indicated by low coefficients of variation (CV). The net cortical effect on soleus (SOL) and medial gastrocnemius (MG) motoneurons was significantly weaker than in TA (P < 0.001) and the responses were non-homogeneous within a motoneuron pool, both in terms of response amplitude and direction. The occurrence of strong facilitatory and inhibitory responses or an absence of a response within a given MG motoneuron pool was associated with CVs about 13 times that of TA and 4 times that of SOL. The large CVs may be indicative of the existence of subgroups of motoneurons differentiated by their response to TMS. Examination of only excitatory responses resulted in comparable CVs across the muscles tested. It is suggested that the degree of non-homogeneity within a motoneuron pool reflects the ability of the cortex to modulate other inputs. Selective cortical activation of specific groups (or subgroups) of motoneurons may set up appropriate conditions suited to a particular volitional task.

Adult↗

Distributed motor processing in cerebral cortex.

Responding to a visual cue requires processing throughout many areas in the brain. The anatomical pathways connecting these diffuse areas are numerous. One way to study the cognitive processing associated with volitional movement is to identify common physiological properties in each area. Recently, the discovery that neuronal activity is broadly tuned in many of these cortical areas has led to new insights into the physiological structure of the process underlying cognition in this distributed system.

Animals↗

Double dynamic graciloplasty and coloperineal pull-through after abdominoperineal resection.

In patients with a very low rectal carcinoma, an abdominoperineal resection with the creation of a permanent colostomy is the surgical treatment of choice. Creation of a colostomy can be avoided without compromise to oncological safety. The distal colon is pulled through to the perineum and both gracilis muscles are used to create a new sphincter and pelvic floor. These muscles are electrically stimulated by an implanted neurostimulator. Contraction is then no longer dependent upon volition and, due to fibre transformation, the muscle will become fatigue-resistant. The outcome in 11 patients was assessed. After a mean follow-up of 1.3 years, continence was achieved in 7 patients, and 2 patients are awaiting completion of the therapy. In 2 patients, necrosis of the distal colon led to failure of the technique. There was no local recurrence, but 2 patients had distant metastasis. Double dynamic graciloplasty after abdominoperineal resection proves to be an oncologically safe procedure with a reasonable chance of continence and a life without a stoma in the majority of patients.

Adenocarcinoma↗

Gaze-evoked amaurosis from vitreopapillary traction.

PURPOSE: We report four patients with gaze-evoked amaurosis attributable to incomplete posterior vitreous detachment and ensuing vitreopapillary traction. We present these cases to illustrate and extend the spectrum of vitreopapillary syndromes and to draw attention to vitreopapillary traction and its expected manifestations in both optic disk appearance and optic nerve and retinal function. DESIGN: This is a retrospective observational case series culled from tertiary neuro-ophthalmology practice. METHODS: Patients were evaluated with direct and indirect ophthalmoscopy, Hruby (precorneal) lens, three-mirror Goldmann contact lens, macular contact lens, formal perimetry, fundus photography, fluorescein angiography, and orbital ultrasound. RESULTS: Four patients with gaze-evoked amaurosis had disk edema associated with a partial posterior vitreous separation. These patients were young and had atypical posterior vitreous detachments characterized by persisting vitreopapillary attachments. CONCLUSIONS: Gaze-evoked amaurosis is a rare visual obscuration precipitated by changes in volitional gaze, usually associated with an underlying orbital mass. We extend its etiologies to implicate the vitreous through traction expressed at the optic disk. In our cases, vitreopapillary traction elevated the nerve head and eye movements precipitated transient visual phosphenes followed by gaze-evoked amaurosis caused by traction transmitted from the vitreous to superficial nerve fibers of the retina and disk.

Adult↗

Can women without visible pubococcygeal muscle in MR images still increase urethral closure pressures?

OBJECTIVE: The purpose of this study was to determine if the ability to increase maximum urethral closure pressure (MUCP) with a pelvic muscle contraction is impaired in women without pubococcygeal muscle (PCM). STUDY DESIGN: This was a cross-sectional study of continent women comparing those with (n=28) and those without (n=17) PCM as identified by MR scans. A pelvic muscle contraction was performed simultaneously with recordings of urethral and bladder pressures. RESULTS: Eighty-six percent of the women with PCM compared with 41% of the women without could volitionally increase (>5 cm H(2)O) their MUCP. Those with PCM generated a mean intraurethral pressure rise of 14.0 (10.8) cm H(2)O, compared with 6.2 (8.7) cm H(2)O in those without (P=.015). Among women who could produce a visible pressure rise, there was not a statistically significant difference between groups (with PCM=17.2 [7.8] cm H(2)O; without PCM=14.7 [7.5] cm H(2)O; P=.457). CONCLUSION: Selective women without visible PCM can increase MUCP.

Female↗

[Replacement enterocystoplasty in man (except Hautmann): principles and technical considerations].

Orthotopic urinary reservoir using a bowel segment has become the most favoured form of diversion after radical cystectomy. Ideal neobladder has to (i) store the urine with a low pressure bladder substitute, (ii) protect the upper urinary tract and (iii) provide a better quality of life enabling volitional voiding. A lot of techniques have bee described to construct a reservoir, however, all of them are based on the principle of intestinal loop detubulation. Many intestinal segments have been used, but ileum seems to be preferred in Europe. The upper urinary tract is mainly protected by a low neobladder pressure, rather than an additional antireflux flap-valve-type implantation technique which may increase the risk of uretero-enteric stricture. No significant difference in functional outcome can be observed among the several techniques. In selected cases, orthotopic bladder replacement is well tolerated and feasible and appears to be the gold standard after cystectomy.

Cystectomy↗

Effect of a splint on measures of sustained grip exertion under different forearm and wrist postures.

Despite the facts that gripping tasks have been found to be highly correlated with CTS and that splints are gaining popularity as personal protective equipment, the influence of splints on grip performance has not been determined adequately. The present study intends to investigate the influence of splints without the volar parts as well as of forearm and wrist postures on grip performances including maximal volitional contraction (MVC), maximum acceptable sustained time (MAST), cumulated exertion output (CEO), and normalized exertion level (NEL). Twenty college-student volunteers, 10 males and 10 females, were recruited. The factors of interest were gender, forearm position, wrist deviation, and splint (with and without). The forearm positions were set at 30 degrees internal shoulder rotation, 0 degrees internal shoulder rotation, and 30 degrees external shoulder rotation, the angles being measured between the sagittal plane and the long axis of dominant forearm. The wrist deviations were extension 30 degrees , neutral, and flexion 30 degrees , the angles being measured between the sagittal plane and the long axis of the grip gauge. The results indicate that the gender effect is the most dominantly significant on all evaluated response variables. Males have more MVC (220 vs. 337N), longer MAST (20.2 vs. 10.5s), and greater CEO (4306 vs. 1638Ns), but less NEL (66.6 vs. 73.9%MVC). The forearm posture is shown to be significant only on MVC. In addition, the effect of wrist posture cannot shift all responses, nor can the effect of splints. In general, a splint without volar part seems to be recommended while performing infrequent and forceful gripping tasks under the consideration of prevention, but there should be more information about the application of a splint without volar part while performing a repetitively gripping task.

Adolescent↗

The effects of glove thickness and work load on female hand performance and fatigue during a infrequent high-intensity gripping task.

In various workplaces, gloves are commonly employed to protect the hands with the design rationale of 'the thicker the gloves, the better the protection'. Therefore, the present paper investigated the effects of glove thickness on hand performance and fatigue during two infrequent high-intensity gripping tasks, such as 5-s and sustained tasks. The hand performance was evaluated by maximum volitional contraction (MVC) and its associated time needed to reach the MVC (TMVC), and the total force generation (TFG) during the sustained task. The hand fatigue was assessed by MVC degeneration (DeltaMVC), the shift in time needed to reach the MVC (DeltaTMVC), and the maximal endurance time (MET) associated with the sustained task. Ten female subjects took part in the experiment voluntarily. The four-gloved conditions included bare hand, wearing one layer (Cotton-1), wearing two layers of cotton gloves (Cotton-2), and covering the handle with two layers of cotton glove and exerting with the bare hand (Covered-2). The results indicates that wearing gloves decreased the grip MVC, and the thicker the gloves, the less the grip MVC, but the wearing style did not change the MVC (Cotton-2 MVC was indifferent from Covered-2 MVC). As to muscular fatigue, on the other hand, wearing gloves did not affect DeltaMVC, MET, TMVC, or DeltaTMVC. Due to the greater bare-hand MVC and indifferent MET, bare-hand TFG was better than those conditions with gloves. Finally, the load specified here did not alter TMVC or DeltaTMVC, but the greater the load, the more strength degeneration (DeltaMVC) was induced.

Adult↗

Fine motor control in adults with and without chronic hemiparesis: baseline comparison to nondisabled adults and effects of bilateral arm training.

OBJECTIVES: To characterize fine motor control through finger tapping in both arms of 10 patients with chronic stroke, to make baseline comparisons with matched controls, and to examine the responsiveness of deficits seen in stroke patients after 6 weeks of bilateral arm-based training. DESIGN: Nonrandomized controlled, cohort before-after trial. SETTING: Research institution. PARTICIPANTS: Ten people from the community with chronic unilateral ischemic stroke and 10 age- and sex-matched healthy controls. Participants with hemiparesis had completed all conventional care and were more than 6 month poststroke. Inclusion criteria were at least 6 months since a unilateral stroke, ability to follow simple instructions and 2-step commands, volitional control of the nonparetic arm, and at least minimal antigravity movement in the shoulder of the paretic arm. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measurements included rate and timing consistency of unilateral tapping at a preferred and a maximal rate and the accuracy and stability of interlimb coordination in bilateral simultaneous (inphase) and alternating (antiphase) tapping at a preferred rate. RESULTS: Nonparetic finger control was similar to that of the nondisabled participants except under bilateral conditions, where it was less consistent. A subgroup with residual paretic finger function, had slower and less consistent paretic finger tapping, as well as less accurate and more variable interlimb coordination; however, basic bilateral coupling relationships were preserved. Bilateral arm-based training improved bilateral nonparetic consistency but slowed unilateral preferred tapping. Training also improved paretic fine motor control in 2 of 4 participants with mild stroke severity. The 2 responders, with dominant hemisphere lesions, indicated a possible recovery advantage with bilateral training for such lesions. CONCLUSIONS: In general, nonparetic finger control for tapping was preserved but paretic finger control was compromised. Disruption of nonparetic control of tapping, particularly consistency of tapping, occurred during bilateral tapping tasks but was responsive to 6 weeks of bilateral arm-based training. Despite the apparent lack of training specificity, the generalizable effects of bilateral arm training to fine motor interlimb coordination may reflect central motor control mechanisms for upper-extremity coordination, which may be accessed and may influence the recovery of arm function after stroke.

Chronic Disease↗

Neuromuscular electric stimulation effect on lower-extremity motor recovery and gait kinematics of patients with stroke: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of neuromuscular electric stimulation (NMES) of the tibialis anterior muscle on motor recovery and gait kinematics of patients with stroke. DESIGN: Randomized, controlled, assessor-blinded trial. SETTING: Rehabilitation ward and gait laboratory of a university hospital. PARTICIPANTS: A total of 25 consecutive inpatients with stroke (mean age, 55y), all within 6 months poststroke and without volitional ankle dorsiflexion. INTERVENTION: Both the NMES group (n=12) and the control group (n=13) participated in a conventional stroke rehabilitation program, 5 days a week for 4 weeks. The NMES group also received 10 minutes of NMES to the tibialis anterior muscle of the paretic limb. MAIN OUTCOME MEASURES: Brunnstrom stages of motor recovery and kinematic characteristics of gait. RESULTS: Brunnstrom stages improved significantly in both groups (P<.05). In total, 58% of the NMES group and 61% of the control group gained voluntary ankle dorsiflexion. Between-group difference of percentage change was not significant (P>.05). Gait kinematics was improved in both groups, but the difference between groups was not significant. CONCLUSIONS: NMES of the tibialis anterior muscle combined with a conventional stroke rehabilitation program was not superior to a conventional stroke rehabilitation program alone, in terms of lower-extremity motor recovery and gait kinematics.

Biomechanical Phenomena↗

Aberrant reflexes and function of the pelvic organs following spinal cord injury in man.

Spinal cord injuries can be devastating on quality of life and lost opportunities due to their impact on bladder, bowel and sexual functions. Supra-sacral spinal lesions can cause incontinence by interrupting those pathways, which normally coordinate the bladder, bowel and sphincters. From a scientific perspective, neural control of the pelvic organs is one of the most intriguing in the body, involving both somatic and autonomic pathways participating in an exquisitely fine integration of lumbo-sacral reflexes. This review details the interactions of somatic and autonomic lumbo-sacral pathways responsible for coordinating the bladder and sphincters, the nature of their aberration post-injury and those aspects of neural control of the pelvic organs that are amenable to neurophysiological examination in man. It will focus in greater detail on how measurement of pelvic floor and sphincter reflexes can be used to assess the modulatory effects of sacral autonomic pathways on sacral somatic reflexes and vice versa including the so called "guarding reflex" and vesical inhibitory reflexes. The effects of volitional modulation of these reflexes will be discussed in relation to people with both complete and incomplete lesions. Finally the possible utility of such neurophysiological measures for complementing the established neurological classification and the assessment of somatic sensory-motor impairment in spinal cord injury will be discussed.

Animals↗

Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study.

BACKGROUND: Successful control of affect partly depends on the capacity to modulate negative emotional responses through the use of cognitive strategies. Although the capacity to regulate emotions is critical to mental well-being, its neural substrates remain unclear. METHODS: We used functional magnetic resonance imaging to ascertain brain regions involved in the voluntary regulation of emotion and whether dynamic changes in negative emotional experience can modulate their activation. Fourteen healthy subjects were scanned while they either maintained the negative affect evoked by highly arousing and aversive pictures (e.g., experience naturally) or suppressed their affect using cognitive reappraisal. In addition to a condition-based analysis, online subjective ratings of intensity of negative affect were used as covariates of brain activity. RESULTS: Inhibition of negative affect was associated with activation of dorsal anterior cingulate, dorsal medial prefrontal, and lateral prefrontal cortices, and attenuation of brain activity within limbic regions (e.g., nucleus accumbens/extended amygdala). Furthermore, activity within dorsal anterior cingulate was inversely related to intensity of negative affect, whereas activation of the amygdala was positively covaried with increasing negative affect. CONCLUSIONS: These findings highlight a functional dissociation of corticolimbic brain responses, involving enhanced activation of prefrontal cortex and attenuation of limbic areas, during volitional suppression of negative emotion.

Adult↗

Hypoglossal nerve transfer in obstetric brachial plexus palsy.

A cost-benefit analysis was performed of hypoglossal nerve transfer in six patients with obstetric brachial palsy taking into account the factors donor site morbidity and extent of recovery. Hypoglossal nerve transfer was employed in four children for elbow flexion only; in two patients for elbow flexion as well as for elbow extension. The transfer was part of an extended brachial plexus reconstruction for treatment of obstetric brachial plexus palsy. After a mean post-operative interval of 52 months (SD+/-8.1), two professional speech therapists investigated late donor site morbidity by analyzing elementary and communicative functions. The functional result for the arm was assessed using the Mallet scale and by performing a physical examination. Following hypoglossal nerve transfer, early donor site morbidity was significant causing great anxiety in the parents. Late donor site morbidity consisted of serious oral problems in a number of the children. They also showed clear associated movements in the arm during mouth/tongue activity. Recovery of powerful volitional elbow flexion was achieved in four cases only. We do not believe that the sacrifice of such an important function as exerted by the hypoglossal nerve is balanced by the gain demonstrated in our series.

Brachial Plexus↗