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Towards a better understanding of abdominal bloating and distension in functional gastrointestinal disorders.

Abdominal bloating is an extremely common symptom affecting up to 96% of patients with functional gastrointestinal disorders and even 30% of the general population. To date bloating has often been viewed as being synonymous with an actual increase in abdominal girth, but recent evidence suggests that this is not necessarily the case. This review examines the relationship between the symptom of bloating and the physical sign of abdominal distension, as well as examining the epidemiology, pathophysiology and treatment options available for this debilitating aspect of the functional gastrointestinal disorders. Pathophysiological mechanisms explored include psychological factors, intestinal gas accumulation, fluid retention, food intolerance and malabsorption of sugars, weakness of abdominal musculature, and altered sensorimotor function. Treatment options are currently rather limited but include dietary changes, pharmacological approaches, probiotics and hypnotherapy.

Abdomen↗

Influence of sensory and proprioceptive impairment on the development of phantom limb syndrome during regional anesthesia.

BACKGROUND: The relation between impairment of sensorimotor function and occurrence of phantom limb syndrome (PLS) during regional anesthesia has not been described. This study assessed the temporal relation between PLS and the progression of sensorimotor impairment during placement of a brachial plexus nerve block. METHODS: Fifty-two patients had their arm randomly placed either alongside their body (group A) or in 90 degrees abduction (group B) immediately after brachial plexus nerve block placement. Responses to pin prick, cold, heat, touch, proprioception, and voluntary movement were assessed every 5 min for 60 min. Meanwhile, patients described their perceptions of the size, shape, and position of their anesthetized limb. RESULTS: Phantom limb syndrome occurred 19 +/- 9 min after nerve block placement. Proprioception was impaired and abolished after 22 +/- 9 and 43 +/- 17 min, respectively (P < 0.05 vs. PLS onset). When PLS occurred, responses to pin prick, cold, heat, and proprioception were abolished in 96, 94, 87, and 4% of patients, respectively. Patients were more likely to feel their anesthetized limb in adduction and in abduction in groups A and B (P < 0.05 vs. group A), respectively. After PLS had become motionless, two stereotyped positions were identified: arm adduction, elbow flexion, hand over the abdomen (68% of group A patients) and arm abduction, elbow flexion, hand held close to the homolateral ear (48% of group B patients). CONCLUSIONS: This study provides a better understanding of the determinants of PLS by showing that the final position of PLS is related both to the abolition of proprioception and the initial position of the anesthetized limb.

Adult↗

Current trends in the evaluation and management of female urinary incontinence.

Despite its common occurrence and often seemingly obvious causes, female urinary incontinence requires a thorough and thoughtful evaluation for its proper diagnosis and treatment. With rare exceptions, urinary incontinence is the result of failure of the sphincter mechanism to resist bladder pressures encountered during daily activities. This may be the result of sphincter failure, overactivity of the bladder detrusor muscle or both. In uncomplicated cases, the diagnosis is usually based on an evaluation in the office. Urodynamic and cystoscopic study may be helpful in complex, resistant and recurring cases of urinary incontinence of any cause. Most cases of incontinence may be classified as stress, urge or mixed urinary incontinence. Treatment of stress urinary incontinence focuses on supplementing the urethral continence mechanisms, particularly the urethral supports and periurethral striated muscle function. The current paradigm for the treatment of urge incontinence centres on pharmacologic therapy, primarily by correcting detrusor overactivity with antimuscarinic drugs. Other therapies aimed at altering sensorimotor function may be used in resistant cases. The treatment of mixed urinary incontinence requires consideration of the contribution of each of its components. With proper diagnosis, effective treatment is possible for most patients.

Female↗

Effects of early and late transection of the corpus callosum in children. A study of tactile and tactuomotor transfer and integration.

Five children, aged 6 to 16 years, were tested for unilateral discrimination and interhemispheric transfer of tactile information as well as tactuomotor learning at various intervals before and after therapeutic callosotomy. Comparison of preoperative and postoperative capacities revealed that younger children are considerably less affected by the interruption of callosal transmission than older children. Bilateral organization of speech and participation of the anterior commissure can largely be excluded as possible compensatory mechanisms. The most plausible explanation for the excellent preservation of interhemispheric integration of tactile functions in the younger patients appears to be continued reliance on ipsilateral pathways. The relatively greater deficits observed in the older children, on the other hand, suggest that sensorimotor functions come to depend more extensively on contralateral pathways as the corpus callosum reaches functional maturity.

Adolescent↗

Clinical evaluation of the short half-life injectable benzodiazepine midazolam, and of the specific antagonist flumazenil in upper digestive tract endoscopy.

In a first step, midazolam 0.1 mg/kg, midazolam 0.05 mg/kg and diazepam 0.15 mg/kg administered intravenously were blindly evaluated as a sedating preparation in 3 groups of each 30 patients undergoing gastroscopy. Although amnesia is better with midazolam 0.1 mg/kg, the induced sedation is protracted, which is not to be wished in ambulatory patients. On the other side, diazepam 0.15 mg/kg was locally less well tolerated. Taking into consideration the efficacy and the general and local tolerance, the dose of midazolam 0.05 mg/kg seems the best compromise. In a second step, the specific benzodiazepine antagonist flumazenil was blindly evaluated at two intravenous doses, 1 mg and 0.5 mg, against placebo for reversal of midazolam (0.1 mg/kg) induced sedation in gastroscopy patients. 1 mg of flumazenil (and to a lesser degree 0.5 mg) suppresses the sedation and amnesia induced by midazolam and normalizes attention and sensori-motor functions. However a certain degree of resedation can reappear 45-60 min. after the administration of flumazenil. Though this phenomenon did not alter the tests measuring attention and sensorimotor functions and the recovery of memory (contrary to placebo), it incites to be cautious when the drug is given to ambulatory patients.

Amnesia↗

Role of an enriched environment on the restoration of behavioral deficits in Lurcher mutant mice.

Lurcher mutant mice, characterized by massive degeneration of the cerebellar cortex, and normal littermate controls were reared from birth either in standard conditions or in an enriched environment. The effects of this manipulation on motor functions, landmark water maze learning, exploration, and anxiety were evaluated at 3 months of age. Under standard conditions, Lurcher mutants were impaired in comparison to controls on tests of sensorimotor function and had altered exploratory tendencies. The enriched housing improved the motor coordination of Lurcher mutants and decreased the number of trials before reaching criterion in the landmark water maze. In addition to its effects in Lurcher mutants, enriched rearing also increased some behavioral abilities in normal mice. It is hypothesized that enriched housing altered brain morphology or neurochemistry in both normal and cerebellar-damaged animals.

Animals↗

Neuronal plasticity and function.

Neuronal plasticity is a key issue in neuroscience. It is defined as the capability of the neuron to adapt to a changing internal or external environment, to previous experience or to trauma. It appears that during all phases of the individual life span in the nervous system, changes take place that relate to development, degeneration, and regeneration. Growth cones are a focus of neuronal plasticity, and current views emphasize the importance of local intracellular [Ca2+] to the control of their function. Hence, outgrowth of neurites from neurons in culture may be manipulated by drugs that affect intracellular Ca2+ homeostasis. In the adult nervous system, much research deals with synaptic plasticity, especially with the activity-dependent changes seen after long-term potentation of hippocampal synapses. As in the growth cone, such changes involve Ca(2+)-dependent pre- and postsynaptic processes, among which is the activation of protein kinase C. During aging, Ca2+ homeostasis may be slightly disturbed over a long period of time that could result in loss of function seen after a short, toxic high level of intracellular [Ca2+]. In this respect, the beneficial effects of chronic treatment with the L-channel Ca(2+)-blocker nimodipine on sensorimotor function of aged rats is discussed.

Adult↗

The effect of nonspatial water maze pretraining in rats subjected to serotonin depletion and muscarinic receptor antagonism: a detailed behavioural assessment of spatial performance.

A detailed behavioural analysis of water maze spatial performance in the rat was utilized to determine the effect of single and combined administration of p-chlorophenylalanine (PCPA; 1000 mg/kg, i.p.), an inhibitor of serotonin biosynthesis, and scopolamine hydrobromide (SCO; 1.0 mg/kg, i.p.), a muscarinic receptor antagonist. In some groups a water maze pretraining regimen known as non-spatial pretraining (NSP) was used to familiarize the animals with the general requirements of the task before spatial training was begun. The results showed that: (a) depletion of serotonin with PCPA had no effect on water maze performance and produced no sensorimotor disturbances; (b) antagonism of muscarinic receptors produced impairments in spatial and sensorimotor function in naive rats but neither effect was observed in rats first given NSP; (c) combined disruption of muscarinic and serotonergic function produced a severe deficit in spatial performance that was only partially alleviated by NSP; and (d) there was an association between poor maze acquisition scores and a high incidence of sensorimotor dysfunction. In addition to the water maze task the rats were also assessed for motoric performance on a beam walking test. The role of cholinergic and serotonergic systems in learning and memory is discussed.

Animals↗

Functional recovery from sciatic nerve crush lesion in the rat correlates with individual differences in responses to chronic intermittent stress.

The aim of the present study was to monitor the influence of chronic stress on functional recovery from a sciatic nerve crush lesion in the rat. Male Wistar rats underwent standard unilateral sciatic nerve crush. Subsequently, chronic stress was induced during the recovery phase using a daily 30 min shock box session where rats received three electric footshocks each session (0.5 sec, 1 mA). Reduced body weight gain, adrenal gland hypertrophy, and thymus involution indicated that the stress rats were chronically stressed. Evaluation of sensorimotor function revealed significant differences in recovery between control and stress groups. Correlational analysis of individual stress rats indicated that recovery of the walking pattern was negatively correlated with adrenal gland and medulla enlargement, thymus involution, and plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone 45 min following the final stress session. In control rats, the index of sciatic nerve function (SF index, expressed as the difference between the injured paw and the intact contralateral paw as a percentage) was significantly correlated with adrenal medulla weight only. The present study reveals that chronic intermittent footshock stress impedes sensorimotor recovery following a sciatic nerve crush lesion and that the consequences of chronic intermittent stress are individually determined. We suggest that the quality of functional locomotor recovery after nerve crush lesion is related to the adaptive capacity or coping style of the individual rat.

Adaptation, Physiological↗

Effects of dibutyryl cyclic AMP on restoration of function of damaged sciatic nerve in rats.

In two experiments, the sciatic nerve of rats was either crushed or hemisected, and N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate or saline was injected intramuscularly near the site of the lesion. In both types of nerve damage, the sensorimotor functions of animals treated with N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate returned earlier than did those of saline-treated control animals.

Animals↗

Pranlukast, a cysteinyl leukotriene receptor-1 antagonist, protects against chronic ischemic brain injury and inhibits the glial scar formation in mice.

We have recently reported the neuroprotective effect of pranlukast (ONO-1078), a cysteinyl leukotriene receptor-1 (CysLT1) antagonist, on cerebral ischemia in rats and mice. In this study, we further determined whether the effect of pranlukast is long lasting and related to the formation of a glial scar in cerebral ischemic mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). After ischemia, pranlukast (0.1 mg/kg) was injected intraperitoneally for 5 consecutive days. Neurological deficits and sensorimotor function were determined during 70 days after ischemia. Brain lesion and glial scar formation were detected at the end of the experiment. Pranlukast did not reduce mortality, but significantly improved neurological deficits and promoted sensorimotor recovery during 70 days. At the end of the experiment, pranlukast significantly reduced lesion volume, and increased neuron densities in the cortex and hippocampal CA1 region in the ischemic hemispheres. Importantly, pranlukast also remarkably reduced the thickness of a scar wall in the ischemic hemispheres. These findings indicate that pranlukast has a long-lasting protective effect on focal cerebral ischemia in mice, and inhibit the ischemia-induced glial scar formation, providing further evidence of the therapeutic potential of pranlukast in the treatment of ischemic stroke.

Analysis of Variance↗

Co-occurrence of developmental delays among preschool children with attention-deficit-hyperactivity disorder.

The aim of this study was to provide a comprehensive profile of the sensory, motor, language, and intellectual functioning of a non-referred community sample of 49 preschool children with attention-deficit-hyperactivity disorder (ADHD; 39 males, 10 females; mean age 4y 7mo [SD 7mo]; range 3y 10mo-6y) and 48 typically developing children (38 males, 10 females; mean age 4y 8mo [SD 6mo]; range 3y 11mo-6y) matched by age, sex, and maternal education who underwent a broad battery of neurodevelopmental tests. The results showed that the scores of the ADHD group were significantly lower than the comparison group on all measures. In addition, 23 (47%) of the children with ADHD had clinically significant co-occurring deficits in two or more areas. Logistic regression indicated that the only significant predictors of group classification were scores of verbal intelligence and motor and sensory functioning, accounting for 44.1% of the variance. These findings suggest that preschool children with ADHD have multiple developmental deficits over and above the core symptoms of ADHD and emphasize the importance of evaluating the sensorimotor functioning of preschool children with ADHD symptoms.

Attention Deficit Disorder with Hyperactivity↗

Postural motor programming in paraplegic patients during rehabilitation.

One of the basic aims in the rehabilitation of thoracic spinal cord injured (SCI) patients concerns the regaining of sitting posture control. This implies the development of new postural strategies requiring the adjustment of motor programming processes. The aim of this study was to investigate the time course of postural reorganization during active, clinical rehabilitation of thoracic SCI patients with different SCI levels. Thus changes in motor programming in sitting balance control were investigated in two groups of complete low or high thoracic SCI patients. At several stages during the rehabilitation process an experiment was held in which sitting posture was perturbed systematically using submaximal reaching movements over four reaching distances. This bimanual reaching task was presented as a visual precue choice reaction time (RT) task in which reaching distance (i.e. grade of postural perturbation) was precued. Results indicated that in both high and low thoracic SCI patients RTs in movements involving postural perturbation became shorter during the course of the rehabilitation period. However, low thoracic SCI patients were generally slower in the programming of balance perturbing movements than high thoracic SCI patients, a phenomenon that did not change over time. Furthermore, initial differences in RTs as a function of grade of postural perturbation disappeared in both groups in the course of the rehabilitation phase. Precue benefit, equally large for both groups, did not change as a function of rehabilitation time. It is concluded that the observed phenomena signify the gradual development of new central postural control processes in both SCI groups during rehabilitation. Low thoracic SCI patients, having more residual sensorimotor functions, seem to adopt more complex strategies in maintaining and restoring sitting balance that take longer to specify and to programme. High thoracic SCI patients seem to rely on simpler strategies using more passive postural support.

Adolescent↗

Towards a definition of recovery of function.

In this review we consider recovery of function after spinal cord injury, and, in particular, recovery improved following intraspinal cellular transplants. Some recovery occurs spontaneously and this can be especially dramatic in neonates, supporting the notion that developing and adult spinal cord respond differently to injury. Recovery can be improved in both neonates and adults by appropriate cellular transplants into the injury site. We describe several functional tests used in animals with spinal lesions and transplants. We compare the effects of transplants of fetal tissue and genetically modified fibroblasts into neonatal and adult injury sites on recovery of motor and sensorimotor function. Fetal tissue transplants support greater recovery and elicit more regeneration in neonates than in adults. Transplants of fibroblasts modified to produce neurotrophic factors however support both recovery and axonal growth even in adults. The contribution of the transplant to recovery is shown by the loss of function that follows a second lesion just rostral to the original lesion/transplant site. The effect of the re-lesion indicates that the recovery is mediated by the presence of the transplant but the way in which transplants act to promote recovery may include a number of mechanisms, including regeneration and sprouting, neuroprotection, and modifications of organization of spared CNS structures.

Animals↗

Ventrolateral and dorsomedial somatosensory association cortex damage produces distinct somesthetic syndromes in humans.

Five somatosensory cortices have distinctive somatotopic representations, cytoarchitecture, and connectivity: primary somatosensory cortex (SI), ventrolateral association cortices (SII, SIII, and SIV), and dorsomedial association cortex (supplementary sensory area). Patients with focal lesions of ventrolateral (n = 5) and dorsomedial (n = 6) somatosensory association cortices (SACs) and hemiparetic (n = 8) and neurologically normal control patients (n = 14) underwent detailed somesthetic testing that encompassed basic, intermediate, and complex (tactile object recognition) somesthetic functions. Dorsomedial lesions acutely caused severe disruption of somesthetic processing and severe apraxia when the area of damage was extensive and involved anterior and posterior cortices. In contrast, ventrolateral lesions caused tactile agnosia. Chronically, sensorimotor function following dorsomedial damage improved considerably. Tactile agnosia following ventrolateral damage, however, was readily detectable for years following onset. Functional differences between ventrolateral and dorsomedial SACs may reflect parallel processing in dual somatosensory systems.

Aged↗

Comparison of electrolytic and ibotenic acid lesions in the lateral hypothalamus.

Electrolytic lesions in the lateral hypothalamus (LH) seriously affect ingestive behavior and sensorimotor functions in the rat. We here report that bilateral infusions of the neurotoxin, ibotenic acid (IBO) in the LH yield a decrease in body weight, but not to the same extent as electrolytic lesions. The sensorimotor impairments were most severe after electrolytic lesions. When tested in a residential maze on days 5-7 and 18-20 after surgery, both lesioned groups showed no lack of motivation to seek food and water. Histological examination of the LH following IBO exposure revealed extensive degeneration of neuronal cell bodies with little evidence of non-specific damage. Biochemical analysis of the rostral forebrain content of norepinephrine (NE) and serotonin (5-HT) revealed that the fibers passing through the LH remained largely intact in the IBO treated rats. The results suggest that the observed aphagia and adipsia is not due to a lack of motivation, but rather reflects changes in the process which operate to initiate eating and drinking. Furthermore, selective neuronal degeneration induced the same behavioral changes as the electrolytic ones, though not to the same extent.

Animals↗

Haloperidol decreases hyperkinetic paw treading induced by globus pallidus lesions in the rat.

Systemic haloperidol injections decrease the severity of several hyperkinetic syndromes caused by damage to the basal ganglia in humans. A model of hyperkinesia in the rat, exaggerated paw treading triggered by oral sensory stimulation, has been reported previously to result from lesions of the globus pallidus or ventral pallidum/substantia innominata. This hyperkinesia appears as forepaw and forelimb extension and retraction, which can be emitted vigorously and repeatedly for up to minutes at a time. The present study aimed to discover whether this experimental hyperkinesia is pharmacologically similar to human hyperkinetic syndromes: can it be suppressed by neuroleptic administration? Systemic injections of haloperidol (2 mg/kg), diazepam (5 mg/kg, as a sedative comparison), or vehicle were given to rats that expressed the paw treading syndrome after pallidal lesions. Effects on hyperkinetic treading and on tests of sensorimotor function were compared. Results indicated that haloperidol was effective in ameliorating the hyperkinesia in rats with bilateral globus pallidus lesions but not in rats with ventral pallidum/substantia innominata lesions. By contrast, diazepam, which produced sedation and sensorimotor impairment, did not decrease the hyperkinesia induced by either lesion. Although only haloperidol decreased hyperkinetic treading after globus pallidus lesions, haloperidol produced less of a sensorimotor impairment than diazepam on climbing, hanging, and righting reflex tests. These results implicate a specific role for dopamine neurotransmission in the expression of triggered hyperkinetic treading induced by globus pallidus lesions.

Animals↗

The effects of subdural haematoma on spatial learning in the rat.

Although memory deficits are one of the most persistent consequences of human subdural haematoma, cognitive functioning has hardly been investigated in the rat subdural haematoma model. In the present study, the effects on spatial learning of right- and left-sided unilateral subdural haematoma and of bilateral subdural haematoma induced above the sensorimotor cortical areas were evaluated. Spatial learning was assessed by standard acquisition in the Morris water escape task (five sessions). Additional issues addressed were sensorimotor functioning (footprint analysis), recovery of cognitive functioning (tested by an overtraining and a reversal training) and replicability of induced cognitive deficits. Following unilateral subdural haematoma surgery, hardly any impairments in the Morris water escape task were observed: rats with a unilateral right-sided subdural haematoma showed very mild, transient deficits, whereas rats with left-sided subdural haematoma were indistinguishable from controls. Bilateral subdural haematoma surgery led to a clear, although transient, performance deficit. We conclude that animals with bilateral subdural haematoma may provide a promising cognitive deficit model for investigating recovery of function.

Animals↗