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Gallbladder motor function in gallstone patients: sonographic and in vitro studies on the role of gallstones, smooth muscle function and gallbladder wall inflammation.

Gallbladder motility was studied by ultrasound in 100 healthy adult volunteers and 150 gallstone patients, in a subgroup of whom gallstone burden, type and number, gallbladder histology and tensiometric responses of gallbladder strips to cholecystokinin octapeptide were evaluated. Patients were divided into contractors (n = 108) and hypocontractors (n = 42), according to their gallbladder motility pattern in vivo. Contractors showed slower gallbladder emptying and increased fasting and postprandial residual volumes, although the ejected amount of bile was greater than that of controls (20.2 +/- SEM 1.1 vs 16.0 +/- 0.7 ml; p < 0.001). In contrast, hypocontractors exhibited slower and less complete gallbladder emptying than controls with a reduction in the absolute amount of ejected bile. Although gallbladder wall inflammation was mild and comparable in specimens from both groups of patients, the thickness of the muscular layer was greater in hypocontractors than in contractors (1073 +/- 76 vs 745 +/- 75 microns, p < 0.01) and related inversely to postprandial ejected volume (r = -0.42; p < 0.03; n = 32) but positively to gallstone volume (r = 0.40; p < 0.03; n = 32). Compared to contractors, gall-bladder muscle strips of hypocontractors exhibited a decrease in frequency and amplitude of spontaneous contraction and in maximal stress and receptor sensitivity to cholecystokinin octapeptide (0.1 nM-1 microM). Postprandial gallbladder evaculation was unaffected by stone number, and by the presence or absence of stone calcification. Gallstone volume was larger in hypocontractors (19.4 +/- 3.0 ml vs 9.6 +/- 0.9 ml, p < 0.001) than contractors. The comparison of in vitro contractility patterns between cholesterol, mixed and pigment stone patients showed a more severe defect in patients with cholesterol and mixed stones than in those with pigment calculi. In conclusion, in gallstone patients: (i) gallbladder motor dysfunction manifests mainly with increased fasting and postprandial residual volumes in contractors and with markedly increased postprandial residual volumes and decreased gallbladder emptying in hypocontractors; (ii) gallbladder kinetics seem to be influenced by stone volume and cholesterol content of calculi but not stone number, calcification or mild chronic cholecystitis; (iii) a form of hypertrophic leiomyopathy is observed in gallstone patients with the most impaired gallbladder motor function.

Adult↗

Study on motor functions of antrum after highly selective vagotomy (HSV) plus mucosal antrectomy.

To elucidate the effects of highly selective vagotomy plus mucosal antrectomy (HSV-MA) antral functions, eighteen dogs were randomly divided into control, HSV and HSV-MA group for determining gastric emptying, antral myoelectric activity and antral pressure. The tests were performed 4 months after operation in the HSV-MA and HSV group. By roentgenoscopy, the gastric and duodenal shape were normal, and gastric peristalsis was clearly seen in all the dogs in the three groups. The beginning and ending time of gastric emptying in the HSV-MA group were 5.0 +/- 0.06 minutes and 4.0 +/- 0.4 hours respectively, which were similar to those in the control and HSV group (P > 0.05). The frequency of antral myoelectric action potential in the HSV-MA group (3.11 +/- 0.65 cycles/minutes) was significantly lower than those in the control and HSV group (P < 0.05). Intramuscular injection of pentagastrin significantly increased the frequency of antral myoelectric action potential (P < 0.01) in all groups, and eliminated the difference among them before the injection. The antral pressure wave occurred immediately following the antral myoelectric action potential waves. The antral pressure values in the control and HSV-MA group were similar (P > 0.05), and were significantly lower than that in the HSV group (P < 0.05). Intramuscular injection of pentagastrin significantly increased the antral pressure (P < 0.001) in all groups and eliminated the difference among them before the injection. These evidences suggest that the motor function of the reconstructed antrum following HSV-MA nearly reached normal level despite a lower antral myoelectric frequency. Combined with other reports, HSV-MA has a good clinical prospect as an operation for the treatment of chronic duodenal ulcer.

Action Potentials↗

Motor function following developmental exposure to PCBS and/or MEHG.

Recent studies raise concern for combined exposure to polychlorinated biphenyls (PCBs) and methylmercury (MeHg), two environmental contaminants that are found in fish and seafood. Past accidental poisonings in humans show that exposure to high levels of either contaminant is associated with motor impairments, including alterations in cerebellar functions such as balance and coordination. Epidemiological studies of lower level exposures suggest some neuromotor impairment in exposed children, but the majority of these studies have focused on cognitive endpoints rather than examining a full-range of motor function. In particular, the cerebellum could be a sensitive target for combined PCB and MeHg toxicity. MeHg exposure during development damages the cerebellum along with cortical areas, and PCBs may also cause cerebellar damage via thyroid hormone disruption during development. In addition, in vitro studies report interactive effects of PCBs and MeHg on ryanodine-sensitive calcium signaling. Ryanodine receptors are found especially within the cerebellum, and alterations in calcium signaling within the cerebellum could impair long-term depression and subsequent motor learning. This article reviews the motor impairments reported in humans and laboratory animals following exposure to PCBs and/or MeHg during development. There is need for a better understanding of the interactive effects of PCBs and MeHg, especially in regard to motor function.

Animals↗

Physiological methods to measure motor function in humans and animals with spinal cord injury.

This article compares some physiological methods commonly used to measure the functional capability of the motor system in humans and animals after spinal cord injury. Some of the differences between animal and human experimentation are considered first. Then we discuss how to measure the effectiveness of conduction through the motor system. We describe ways to assess the integration of different inputs at the spinal cord and to measure the responsiveness of the neuromuscular system. We conclude that comparisons across species are invaluable to understand the control of movement, both before and after injury.

Animals↗

Impairment of motor function after frontal lobe resection with preservation of the primary motor cortex.

We investigated the clinical course and characteristics of the motor deficits in patients who underwent surgical resection of the frontal lobe for tumorous lesions. Only patients who met the following criteria were included in the present study: 1) postoperative MRI revealed that resection of the frontal lobe involved the area closely adjacent to the primary motor cortex, but 2) the D wave of the corticospinal MEP did not decrease in amplitude below 50% of the original level during surgery. The extent of resection was classified into 4 groups. In Group A (6 cases), resection was limited within the area above the superior frontal sulcus and posterior to a line vertical to the line connecting the anterior and posterior commissures at the anterior commissure (AC vertical line). Resection was extended anterior to the AC vertical line in Group B (4 cases) or below the superior frontal sulcus in Group C (5 cases). In Group D (3 cases), resection was extended to both of these two boundaries. Severe motor paresis and/or apraxia of the upper and lower extremities were noted in all patients of Group D immediately after surgery. A complete recovery in the lower extremity was observed in these patients, while disturbance in the fine movements of the upper extremity remained for more than 1 year after the surgery. Disturbance in the fine movements and/or apraxia of the upper extremity were observed immediately after surgery in 2 of the Group A patients (33%), 2 of the Group B patients (50%) and 3 of the Group C patients (60%). However, a rapid recovery occurred in these patients, and only a subtle or mild disturbance remained for more than 1 year after the surgery in one of the Group B and one of the Group C patients. Permanent and severe motor deficit is rarely induced when resection of the frontal lobe is limited to only the SMA proper (corresponding roughly to Group A), the SMA proper and pre-SMA (corresponding roughly to Group B), or the SMA proper and premotor cortex (corresponding roughly to Group C), insofar as the primary motor cortex is preserved. Disturbance in fine movements of the upper extremity is frequently induced for the long term when wide areas of the SMA proper, pre-SMA as well as premotor cortex are resected altogether (corresponding roughly to Group D).

Adult↗

Perceptual-motor functioning in children with phenylketonuria.

Children with treated phenylketonuria (PKU) have been described as being at high risk for perceptual-motor dysfunction. In this study, the Wechsler Intelligence Scale for Children (WISC) and the Bender Gestalt test were administered to 19 school age children with treated PKU and of average intelligence who have been off diet from five months to six years four months. Perceptual-motor performance was evaluated, and school functioning was rated by classroom teachers. Substantial impairment of perceptual-motor functioning as measured by the Bender Gestalt test and lower WISC performance IQs than verbal IQs were observed in children of average intelligence. Quality of dietary control was found to be associated with performance on the Bender Gestalt test. These findings suggest the possibility of a specific deficit that could seriously interfere with academic progress, but which is not signalled by obvious impairment of overall intellectual functioning.

Achievement↗

Survival motor neuron function in motor axons is independent of functions required for small nuclear ribonucleoprotein biogenesis.

Spinal muscular atrophy (SMA) is a motor neuron degenerative disease caused by low levels of the survival motor neuron (SMN) protein and is linked to mutations or loss of SMN1 and retention of SMN2. How low levels of SMN cause SMA is unclear. SMN functions in small nuclear ribonucleoprotein (snRNP) biogenesis, but recent studies indicate that SMN may also function in axons. We showed previously that decreasing Smn levels in zebrafish using morpholinos (MO) results in motor axon defects. To determine how Smn functions in motor axon outgrowth, we coinjected smn MO with various human SMN RNAs and assayed the effect on motor axons. Wild-type SMN rescues motor axon defects caused by Smn reduction in zebrafish. Consistent with these defects playing a role in SMA, SMN lacking exon 7, the predominant form from the SMN2 gene, and human SMA mutations do not rescue defective motor axons. Moreover, the severity of the motor axon defects correlates with decreased longevity. We also show that a conserved region in SMN exon 7, QNQKE, is critical for motor axon outgrowth. To address the function of SMN important for motor axon outgrowth, we determined the ability of different SMN forms to oligomerization and bind Sm protein, functions required for snRNP biogenesis. We identified mutations that failed to rescue motor axon defects but retained snRNP function. Thus, we have dissociated the snRNP function of SMN from its function in motor axons. These data indicate that SMN has a novel function in motor axons that is relevant to SMA and is independent of snRNP biosynthesis.

Amino Acid Sequence↗

Effect of sodium valproate on motor function regulated by the activation of GABA receptors.

Sodium valproate is an anticonvulsant which elevates GABA levels in the brain. GABA interacts with dopamine functionally in certain areas of the brain involved in motor behavior such as the nucleus accumbens and the substantia nigra. In order to determine whether GABA can play a functional role in the pharmacological effects of valproate, both valproate and GABA were injected directly into these two brain areas and the effects of these compounds on motor function were studied. Both GABA and sodium valproate inhibited in a dose dependent manner the hyperactivity induced by the bilateral injection of dopamine into the nucleus accumbens. Picrotoxin, a GABA antagonist, blocked the inhibitory effect of valproate. When injected into the pars reticulata of the substantia nigra, both sodium valproate and GABA enhanced apomorphine-induced circling in rats with a unilateral lesion of lateral hypothalamus caused by 6-hydroxydopamine. This effect was blocked by the systemic administration of picrotoxin. These observations suggest that sodium valproate can produce effects that result from the activation of GABA receptor sites in the brain.

Animals↗

Experimentally induced ulcers and gastric sensory-motor function in rats.

Prior studies have demonstrated that inflammation can sensitize visceral afferent neurons, contributing to the development of hyperalgesia. We hypothesized that both afferent and efferent pathways are affected, resulting in changes in motor and sensory function. Kissing ulcers (KU) were induced in the distal stomach by injecting 60% acetic acid for 45 s into a clamped area of the stomach. In controls, saline was injected into the stomach. A balloon catheter was surgically placed into the stomach, and electromyographic responses to gastric distension were recorded from the acromiotrapezius muscle at various times after ulcer induction. The accommodation reflex was assessed by slowly infusing saline into the distally occluded stomach. Gastric pressure changes in response to vagal stimulation were measured in anesthetized rats. Contractile function of circular muscle strips was examined in vitro using force-displacement transducers. KU caused gastric hypersensitivity that persisted for at least 14 days. Fluid distension of the stomach led to a rapid pressure increase in KU but not in control animals, consistent with an impaired accommodation reflex. Gastric ulcers enhanced the contractile response to vagal stimulation, whereas the effect of cholinergic stimulation on smooth muscle in vitro was not changed. These data suggest that inflammation directly alters gastric sensory and motor function. Increased activation of afferents will trigger vagovagal reflexes, thereby further changing motility and indirectly activating sensory neurons. Thus afferent and efferent pathways both contribute to the development of dyspeptic symptoms.

Acetic Acid↗

Acute and chronic effects of intrathecal galanin on behavioural and biochemical markers of spinal motor function in adult rats.

The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N'-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 analogue, RX 77368 (pGlu-His-3,3'-dimethyl-ProNH2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 micrograms) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 micrograms) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 microgram, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord region.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Objective changes in motor function during placebo treatment in PD.

OBJECTIVE: To examine the frequency, temporal development, and stability of objectively derived motor changes during placebo treatment in PD and to define the clinical domains and demographic groups most affected. BACKGROUND: Placebo effects are documented in neurology, but the timing and specific disabilities most susceptible to changes during placebo treatment in PD have not been examined. METHODS: The authors examined the placebo-treated group from a randomized, multicenter, placebo-controlled clinical trial of monotherapy ropinerole in PD patients without motor fluctuations. In 105 patients, they evaluated placebo-associated effects on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), dividing the motor examination into four categories: tremor, bradykinesia, rigidity, and gait/balance/midline functions. The motor UPDRS and its subscales were compared over time (at baseline and at 4, 12, and 24 weeks) using Wilcoxon's signed rank test. They applied a rigorous definition of placebo-associated improvement as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by > or =2 points. RESULTS: During the 6-month study, 16% of subjects improved on placebo treatment. The prevalence of response was steady (8 to 9%) at any one visit without a predominance of an early effect. No patient showed a placebo-associated improvement on all visits. All domains of parkinsonian disability were subject to placebo-associated improvement, with a trend toward more response in bradykinesia and rigidity than in tremor or gait/balance/midline function. Gender, age, disease duration, and baseline disability score did not influence the likelihood of improvement in association with placebo treatment. CONCLUSION: Based on a rigorous definition of placebo-associated improvement, prominent improvements in objective measures of PD disability occur during clinical trials. Because placebo-associated improvements occur throughout a 6-month trial, placebo-controlled studies in PD should be at least 6 months to capture early as well as late improvements.

Aged↗

Examination of motor function in lesions of the spinal cord by stimulation of the motor cortex.

Electrical stimulation of the motor cortex was performed in 3 patients with cervical cord trauma and in 3 with cervical myelopathy caused by cervical spondylosis. Abnormal conduction in central motor tracts was demonstrated in 5 of the 6 patients; yet in 4 of these, cortical somatosensory evoked potentials from the same limb were of normal latency. In the remaining patient who had normal motor latencies, the somatosensory evoked potentials were delayed on one side. Electrophysiological examination of the motor pathways by cortical stimulation may therefore be of considerable value in the assessment and management of patients with traumatic and compressive disease of the spinal cord.

Adult↗

Effect of pallidotomy on postural control and motor function in Parkinson disease.

OBJECTIVE: To investigate the effects of pallidotomy on postural reactions and other motor parkinsonian deficits. DESIGN: Comparison of performance by patients before and after pallidotomy on tests of balance and function. SETTING: A Parkinson disease Center of Excellence and Center for Human Performance Testing at a university hospital and research center. PARTICIPANTS: Twenty-nine patients with Parkinson disease undergoing pallidotomy. MAIN OUTCOME MEASURES: Performance results on the United Parkinson's Disease Rating Scale (UPDRS), activities of daily living and motor subscales (parts II and III). and posturography (sensory organization test), which were collected before and 3 and 6 months after surgery with patients in the practically defined off state (medication withheld for at least 12 hours). RESULTS: Data were analyzed with a paired Wilcoxon and Spearman correlation. There was a significant improvement in mean +/- SD UPDRS motor subscale score after pallidotomy (before surgery, 52.43+/-13.46; after surgery, 43.93+/-15.15; z= 3.63; P=.003). There were no significant changes in the UPDRS activities of daily living subscale or average stability scores when the group was examined as a whole. However, examination of individual data revealed that 9 (56%) of 16 patients who could stand independently before surgery showed improvement in either the number of falls or the average stability score. No patient who was unable to stand independently before surgery was able to stand independently after it. CONCLUSION: Pallidotomy helped improve overall motor function in patients with parkinsonism and, for some patients, also improved postural stability.

Aged↗

The role of surface loops (residues 204-216 and 627-646) in the motor function of the myosin head.

A characteristic feature of all myosins is the presence of two sequences which despite considerable variations in length and composition can be aligned with loops 1 (residues 204-216) and 2 (residues 627-646) in the chicken myosin-head heavy chain sequence. Recently, an intriguing hypothesis has been put forth suggesting that diverse performances of myosin motors are achieved through variations in the sequences of loops 1 and 2 [Spudich, J. (1994) Nature (London) 372, 515-518]. Here, we report on the study of the effects of tryptic digestion of these loops on the motor and enzymatic functions of myosin. Tryptic digestions of myosin, which produced heavy meromyosin (HMM) with different percentages of molecules cleaved at both loop 1 and loop 2, resulted in the consistent decrease in the sliding velocity of actin filaments over HMM in the in vitro motility assays, did not affect the Vmax, and increased the Km values for actin-activated ATPase of HMM. Selective cleavage of loop 2 on HMM decreased its affinity for actin but did not change the sliding velocity of actin in the in vitro motility assays. The cleavage of loop 1 and HMM decreased the mean sliding velocity of actin in such assays by almost 50% but did not alter its affinity for HMM. To test for a possible kinetic determinant of the change in motility, 1-N6-ethenoadenosine diphosphate (epsilon-ADP) release from cleaved and uncleaved myosin subfragment 1 (S1) was examined. Tryptic digestion of loop 1 slightly accelerated the release of epsilon-ADP from S1 but did not affect the rate of epsilon-ADP release from acto-S1 complex. Overall, the results of this work support the hypothesis that loop 1 can modulate the motor function of myosin and suggest that such modulation involves a mechanism other than regulation of ADP release from myosin.

Actins↗

A comparison of oral structure and oral-motor function in young males with fragile X syndrome and Down syndrome.

This study compared the oral structure and oral-motor skills of 59 boys with fragile X syndrome (FXS), 34 boys with Down syndrome (DS), and 36 developmentally similar typically developing (TD) boys. An adaptation of the J. Robbins and T. Klee (1987) Oral Speech Motor Protocol was administered to participants and their scores on measures of oral structure and accuracy on speech motor and oral-motor tasks were analyzed. Boys with FXS scored lower than TD boys on oral structure, most oral function tasks, and all speech function tasks. Boys with DS scored lower than boys with FXS and TD boys on oral structure, and lower than TD boys on 1 oral function task and all speech function tasks. Boys with FXS and TD boys scored higher on speech function than oral function tasks, while boys with DS scored higher on oral function than speech function tasks. Boys with FXS and boys with DS repeated single syllable words with greater accuracy than multiple syllable words, while the TD boys produced both types of words with equal accuracy. These results suggest that boys with FXS and boys with DS exhibit atypical oral structure and motor function, yet differ in specific oral-motor patterns.

Adolescent↗