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Symptoms and physiology in severe chronic constipation.

OBJECTIVE: Symptoms of constipation have been attributed to slow colon transit, irritable bowel syndrome (IBS), or pelvic floor dysfunction (PFD). Our aim was to determine the existence of symptom-based constipation subgroups and whether these correspond to differences in colonic transit and anorectal sensorimotor function. METHODS: Constipated patients (n = 108) completed questionnaires, and underwent colon transit studies, anorectal manometry, and rectal sensory testing. Factor analysis of symptoms was performed. Factor-based symptom scores were correlated with physiological findings. RESULTS: Three symptom factors were identified as compatible with slow colonic transit, IBS, and PFD. There was a significant correlation between the symptoms of slow transit and total and rectosigmoid colon transit. There were also significant correlations between both the IBS symptom score and the number of Manning criteria with measures of rectal hypersensitivity typical of IBS. Neither PFD symptom scores nor symptoms of straining correlated with any electromyographic or manometric measure of anal defecatory function or with rectosigmoid colon transit. Based on physiological testing patients were classified as slow transit, visceral hypersensitivity (typical of IBS), PFD, or no abnormalities found. As expected, slow-transit patients had symptoms of infrequent stools and patients with visceral hypersensitivity had an increased number of Manning criteria for IBS. Patients with PFD physiology and those with no detectable abnormalities had no specific symptoms. CONCLUSIONS: Three symptom-based subgroups for constipation were confirmed: slow transit, IBS, and PFD. Slow transit and IBS symptoms correlated with expected physiology. Conversely, PFD symptoms and physiology did not correlate.

Anal Canal↗

Anorexia nervosa: manifestations and management for the gastroenterologist.

Anorexia nervosa is a complex psychiatric disorder with significant morbidity and mortality. It is important for gastroenterologists to be aware of the physiological effects and potential complications of anorexia nervosa, as they are frequently involved in treating patients with this disorder. We review the classic, GI, and neuroendocrinological features of anorexia nervosa. We also discuss gender differences and treatment options in anorexia nervosa. Further studies of GI physiology and pharmacology are needed to determine whether any disturbances may be amenable to therapeutic intervention. Future treatments directed at improving GI sensorimotor function and neurohormonal abnormalities in patients with anorexia nervosa may impact their nutritional rehabilitation and may have important health economic implications as patients avoid hospitalization and are restored to full activities in society. The current team approach, which incorporates psychiatrists, psychologists, nutritionists, pediatricians, internists, and gastroenterologists in the treatment of patients with anorexia nervosa, will continue to be essential.

Anorexia Nervosa↗

A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS) although evidence of their efficacy is scarce. AIM: Twenty three non-depressed IBS patients were recruited from a tertiary care centre and included in a crossover trial comparing six weeks of treatment with the SSRI citalopram (20 mg for three weeks, 40 mg for three weeks) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug. RESULTS: After three and six weeks of treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life, and overall well being compared with placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double blind parallel arm study confirmed the benefit of citalopram over placebo. CONCLUSIONS: The SSRI citalopram significantly improves IBS symptoms, including abdominal pain, compared with placebo. The therapeutic effect is independent of effects on anxiety, depression, and colonic sensorimotor function.

Abdominal Pain↗

Influence of spinal cord injury on cerebral sensorimotor systems: a PET study.

OBJECTIVES: To assess the effect of a transverse spinal cord lesion on cerebral energy metabolism in view of sensorimotor reorganisation. METHODS: PET and 18F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 11 patients with complete paraplegia or tetraplegia after spinal cord injury and 12 healthy subjects. Regions of interest analysis was performed to determine global glucose metabolism (CMRGlu). Statistical parametric mapping was applied to compare both groups on a pixel by pixel basis (significance level P = 0.001). RESULTS: Global absolute CMRGlu was lower in spinal cord injury (33.6 (6.6) mumol/100 ml/min (mean (SD)) than in controls (45.6 (6.2), Mann-Whitney P = 0.0026). Statistical parametric mapping analysis disclosed relatively increased glucose metabolism particularly in the supplementary motor area, anterior cingulate, and putamen. Relatively reduced glucose metabolism in patients with spinal cord injury was found in the midbrain, cerebellar hemispheres, and temporal cortex. CONCLUSIONS: It is assumed that cerebral deafferentiation due to reduction or loss of sensorimotor function results in the low level of absolute global CMRGlu found in patients with spinal cord injury. Relatively increased glucose metabolism in brain regions involved in attention and initiation of movement may be related to secondary disinhibition of these regions.

Adult↗

Invited review: gender issues related to spaceflight: a NASA perspective.

This minireview provides an overview of known and potential gender differences in physiological responses to spaceflight. The paper covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction. Potential health and functional impacts associated with the various physiological changes during spaceflight are discussed, and areas needing additional research are highlighted. Historically, studies of physiological responses to microgravity have not been aimed at examining gender-specific differences in the astronaut population. Insufficient data exist in most of the discipline areas at this time to draw valid conclusions about gender-specific differences in astronauts, in part due to the small ratio of women to men. The only astronaut health issue for which a large enough data set exists to allow valid conclusions to be drawn about gender differences is orthostatic intolerance following shuttle missions, in which women have a significantly higher incidence of presyncope during stand tests than do men. The most common observation across disciplines is that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders. Individual characteristics usually outweigh gender differences per se.

Exercise↗

Values and limitations of pharyngolaryngoscopy (transnasal, transoral) in patients with dysphagia.

During the last decade, videoendoscopic evaluation of structures and sensorimotor functions of the pharynx and larynx has been established as a valuable tool in the assessment of dysphagia. This method is feasible at a very early stage and in critically ill patients, is not invasive and frequently repeatable. Several authors described the high sensitivity and specificity of this method in detecting the presence of the most important symptoms of swallowing dysfunction: retention, penetration and aspiration. In our study of 39 patients with neurogenic dysphagia, we found high agreement between the results of videoendoscopic and videofluoroscopic examination regarding the registration of the most critical symptom, i.e. aspiration. Moreover, we observed patients who aspirated only their saliva and whose endoscopically verified aspiration problem remained undetected by radiographic examination, probably due to the lower sensory input of saliva as compared to a contrast medium. Since the detection of aspiration of saliva is of high clinical relevance for pulmonary function, the endoscopic examination turned out to be superior, in this particular respect, to the radiographic examination. However, the method fails to provide sufficient information regarding the cause of the observed symptoms or the amount of aspirated material. Six patients in our study exhibited, in addition to the neurological signs, structural changes (diverticula, pouches) or unexpected functional esophageal disturbances (persistent opening of the upper esophageal sphincter, retrograde peristalsis) which could only be detected by radiographic examination. The two methods should therefore be considered complementary.

Adult↗

Postural dependence of reaction time after a VL thalamotomy.

Postural dependence of the EMG-RT of the triceps brachii muscles was measured in 68 parkinsonian patients of which 38 underwent a ventrolateral thalamotomy. A thalamotomy did not affect patients' EMG-RT per se, but it changed the postural dependence of the EMG-RT. After left thalamotomy the position changes of both shoulders did not influence the EMG-RT of the right triceps, and after right thalamotomy the position change of the left shoulder had no influence on the EMG-RT of both triceps. As for the sensorimotor function, it is assumed that the right thalamus has bilateral control on the input system and the left thalamus has bilateral control on the output system.

Adult↗

Phenotypic specification of hindbrain rhombomeres and the origins of rhythmic circuits in vertebrates.

This essay considers the ontogeny and phylogeny of the cranial neural circuitry producing rhythmic behaviors in vertebrates. These behaviors are characterized by predictable temporal patterns established by a neuronal network variously referred to as either a pacemaker, neural oscillator or central pattern generator. Comparative vertebrate studies have demonstrated that the embryonic hindbrain is divided into segmented compartments called rhombomeres, each of which gives rise to a distinct complement of cranial motoneurons and, as yet, unidentified populations of interneurons. We now propose that novel rhythmic circuits were innovations associated with the adoption of cardiac and respiratory pumps during the protochordate-vertebrate transition. We further suggest that the pattern-generating circuits of more recent innovations, such as the vocal, electromotor and extraocular systems, have originated from the same Hox gene-specified compartments of the embryonic hindbrain (rhombomeres 7-8) that gave rise to rhythmically active cardiac and respiratory circuits. Lastly, we propose that the capability for pattern generation by neurons originating from rhombomeres 7 and 8 is due to their electroresponsive properties producing pacemaker oscillations, as best typified by the inferior olive which also has origins from these same hindbrain compartments and has been suggested to establish rhythmic oscillations coupled to sensorimotor function throughout the neuraxis of vertebrates.

Animals↗

Physiological factors associated with injurious falls in older people living in the community.

Performance in six tests of sensorimotor function was measured in 50 subjects who were admitted to an acute hospital because of a fall (ICD codes E880-888), but who did not suffer a fracture of the lower limbs as a result. Performances in these tests were compared with 50 subjects of the same age and sex who had not fallen in the previous 12 months. It was found that those admitted to hospital because of a fall had decreased tactile sensation, reduced quadriceps strength and increased body sway on firm and compliant surfaces. The fallers also performed poorly in clinical tests of static and dynamic balance. Psychoactive-drug use was associated with falling and a number of test measures, including body sway, static balance, dynamic balance and quadriceps strength. Twenty-seven percent of fallers had poor outcomes, in that 1 year after testing, they had either suffered three or more additional falls, been readmitted to hospital, been transferred to nursing homes or died.

Accidental Falls↗

Behavioral tests after intracerebral hemorrhage in the rat.

BACKGROUND AND PURPOSE: In humans, intracerebral hemorrhage (ICH) causes marked perihematomal edema formation and neurological deficits. A rat ICH model, involving infusion of autologous blood into the caudate, has been used extensively to study mechanisms of edema formation, but an examination of behavioral outcome would improve its preclinical utility and provide a more rigorous assessment of the pathological cascade of events over time. The purpose of this study was to use a battery of sensorimotor function tests to examine the neurological effects of ICH in the rat and to examine which components of the hematoma are involved in generating those effects. METHODS: The behavioral tests used were forelimb placing, preference for forelimb use for weight shifts during vertical exploration of a cylindrical enclosure, and a corner turn test. Rats were tested from day 1 to day 28 after injection of autologous whole blood; injection of blood plus hirudin (thrombin inhibitor), packed red blood cells, thrombin, or saline; or needle placement only. RESULTS: The battery of tests indicated that there were marked neurological deficits by day 1 after ICH, with progressive recovery of function over 4 weeks. The forelimb placing score paralleled changes in edema. Injection of thrombin caused and injection of hirudin reduced the ICH-induced neurological deficits. Injection of packed red blood cells, which causes delayed edema formation, induced delayed neurological deficits CONCLUSIONS: These tests allow continuous monitoring of neurological deficits after rat ICH and assessment of therapeutic interventions. The time course of the neurological deficit closely matched the time course of cerebral edema for both ICH and injection of blood components. There was marked recovery of function after ICH, which may be amenable to therapeutic manipulation.

Animals↗

Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats.

We produced unilateral photochemical infarcts in the hindlimb sensorimotor neocortex of 186 rats by intravenous injection of the fluorescein derivative rose bengal and focal illumination of the intact skull surface. Infarcted rats showed specific, long-lasting deficits in tactile and proprioceptive placing reactions of the contralateral limbs, mostly the hindlimb. Placing deficits were most prominent during transition to immobility and/or when independent limb movements were required. Administration of flunarizine, a Class IV calcium antagonist, 30 minutes after infarction resulted in marked sparing of sensorimotor function in 30 rats. In contrast to 20 vehicle-treated rats, which remained deficient for at least 21 days, 15 (75%) of the rats treated with 1.25 mg/kg i.v. flunarizine showed normal placing on Day 1 after infarction, whereas the remaining five (25%) recovered within 5 days. Oral treatment of 10 rats with 40 mg/kg flunarizine was also effective. Neocortical infarct volume and thalamic gliosis, assessed 21 days after infarction, did not differ between 30 flunarizine- and 30 vehicle-treated rats. However, when 4-hour-old infarcts were measured in 16 rats, posttreatment with intravenous flunarizine reduced infarct size by 31%. In combination with appropriate behavioral analyses, photochemical thrombosis may constitute a relevant stroke model, in which flunarizine preserved behavioral function during a critical period, corresponding to the spread of ischemic damage.

Animals↗

Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies.

Prepulse inhibition (PPI) refers to the reduction in the response amplitude to a startling stimuli (pulse) if it is preceded (i.e. 30-500 ms) by a weak stimulus (prepulse). If the time interval between the prepulse and pulse is more than 500 ms, then an increase in this response amplitude can be seen, termed prepulse facilitation (PPF). PPI is thought to represent an operational index of sensorimotor function whereas PPF is thought to reflect, at least to some degree, sustained attention. Interestingly, PPI is found to be sexually dimorphic, with men exhibiting more PPI than women when subjects are tested without regard to where they are in the menstrual cycle, and to be impaired in several neuropsychiatric disorders known to exhibit sex differences in their clinical presentation. PPF has received relatively less attention in both normal and clinical studies. This study examined sex differences in both PPI and PPF in 62 healthy subjects (34 women, 28 men) using a range of prepulse-to-pulse intervals to elicit PPI (30, 60, 120, 240 and 480 ms) and PPF (1000 and 2000 ms). Men showed higher PPI than women but women showed higher PPF compared to men. These results suggest that reduced PPI in healthy women is not a simple reduction but rather a shift of the inhibition/facilitation curve in the direction of facilitation in women, relative to men. Future studies investigating pharmacological and treatment effects using a prepulse modification paradigm in normal and clinical populations of both sexes would benefit from an examination of sex effects and assessments of both PPI and PPF.

Acoustic Stimulation↗

The cognitive effect profiles of NMDA receptor modulating drugs are resolvable if stimulus complexity is varied in a number discernment task.

Number discernment is at the heart of task accuracy for laboratory animals performing Fixed Consecutive Number (FCN) operant tasks. Narrow-limit FCN tasks, in particular, are useful for measuring working memory in rat subjects because performance efficacy, which is set up to concord with food delivery, depends on a fairly precise quantification of cues generated by the rat's ongoing behavior. Reported here is a behavioral pharmacology study that utilized a group of overtrained and FCN-schedule-compliant rats injected in a randomized series of testing sessions with different types of N-methyl-D-aspartate (NMDA) receptor modulating drugs. Modifications made to the narrow-limit FCN schedule permitted a simultaneous measure of drug-induced compromises in subjects' sensory integrative or motor coordinating capabilities. This highly sensitive model implicated the intrachannel and the glutamate recognition NMDA receptor binding sites as prime mediators of NMDA antagonist associated memory impairments because drugs acting at the mentioned sites lowered counting efficacy without altering sensorimotor function.

Animals↗

Cutaneous electrical stimulation may enhance sensorimotor recovery in chronic stroke.

OBJECTIVE: To investigate whether cutaneous electrical stimulation has a role in the enhancement of sensorimotor function in chronic stroke. SUBJECTS AND SETTING: Fifty-nine patients with chronic stroke received cutaneous stimulation during their three-week-long inpatient rehabilitation. Thirty-two received active treatment in the paretic hand and eight received no-current placebo treatment in the paretic hand. Nineteen patients received active stimulation of the paretic foot. None received stimulation in both upper and lower limbs. INTERVENTION: Cutaneous stimulation was delivered twice daily via a special glove/sock electrode. MAIN OUTCOME MEASURES: Modified Motor Assessment Scale, 10-metre walking test, paretic limb function, limb skin sensation and somatosensory evoked potentials (SEP) were performed before and after the treatment. RESULTS: Modified Motor Assessment Scale (p < 0.001), 10-metre walking test (p < 0.05), paretic hand function (p < 0.01), upper limb skin sensation (p < 0.01) and SEP normality classification of paretic upper limb (p < 0.01) and paretic lower limb (p < 0.5) improved significantly in the treatment group (n = 51) after three weeks of stimulation. When active hand treatment and placebo hand treatment were compared, a significant improvement in the sensory and motor function was observed only in the actively treated group. CONCLUSIONS: Cutaneous stimulation had positive effects in the motor performance, limb sensation and the configuration of SEP of the paretic limb in chronic stroke patients.

Adult↗

Partial neuroprotective effect of pretreatment with tanshinone IIA on neonatal hypoxia-ischemia brain damage.

Tanshinone IIA is a compound purified from the Chinese herb Danshen (Radix Salviae Miltiorrhiza Bge). The neuroprotective effect of tanshinone IIA was investigated in a neonatal rat model of hypoxia-ischemia brain damage. Hypoxia-ischemia encephalopathy was induced in rats at day 7 of postnatal age by ligation of the right common carotid artery, followed by 2 h of hypoxia. Tanshinone IIA (10 mg/kg, i.p.) was injected daily from day 2 before surgery for 9 or 16 d. Our results demonstrated significant and sustained brain damage in the hypoxia-ischemia- and vehicle-treated groups at 1 and 3 wk after surgery. Treatment with tanshinone IIA significantly reduced the severity of brain injury, as indicated by the increase in ipsilateral brain weight and neuron density, compared with those of sham-operated animals. The recovery of sensorimotor function and histology was observed in animals that received tanshinone IIA. The plasma of tanshinone IIA-treated rats exhibited higher antioxidant activities, as reflected by the oxygen radical absorbance capacity assay, compared with the vehicle-treated rats. In the neural progenitor cell line C17.2 that was subjected to 2,2'-azobis (2-amidino propane hydrochloride)-induced oxidative stress, tanshinone IIA increased cell viability and protected against mitochondrial damage (JC-1 assay). Our results suggest that tanshinone IIA has antioxidative activities and that treatment that is started before a hypoxic-ischemic insult is partially neuroprotective. Further studies are required to elucidate whether rescue treatment with tanshinone IIA is effective and to determine whether its protective effect is also associated with secondary cooling of the brain.

Abietanes↗

Introduction to the Special Issue on Normal Neuropsychological Development in the School-Age Years.

In neuropsychological research on normal development relatively little interest has been devoted to age-related changes in school age. This is surprising in light of the significance of the changes that take place in this period of life, the availability of normative data, and the ongoing research on neural development. The studies included in this issue take a closer look at normative data from school-age children of various ages in performances of attention, language, sensorimotor functions, perceptual functions, memory and learning, and functional asymmetries. A finding evident in many of the studies is that age effects seem to be more accentuated below 9 to 10 years than after that age. It is hoped that this special issue will draw attention to the scarcity of data in this realm and to the possibilities of utilizing existing databases for study on normal development in school age.

Child↗

Neglect induced by thalamotomy in humans: a quantitative appraisal of the sensory and motor deficits.

Stereotactic lesions for the treatment of tremor and rigidity in patients with Parkinson's disease are occasionally followed by neglect of the use of contralateral extremities for spontaneous movement when there are no specific sensory or motor deficits. A group of patients with neglected extremities was compared with a group of patients in which thalamotomy did not produce neglect. Neglect was shown by changes in motor performance, somatosensory evoked potentials (SEP) and electroencephalographic frequency induced by the lesion, as well as radiological evidence of brain atrophy and place and extension of lesions. Reaction time to both auditory and somatosensory stimuli was significantly increased only in the extremities contralateral to the lesion of patients with neglect; tremor decreased equally in both groups, and other motor abilities remained unchanged. P-200 component of SEP decreased in amplitude and increased in latency only in cases with neglect, particularly ipsilateral to the lesion; early components and mean electroencephalographic frequency remained unchanged. Brain atrophy was significant in patients with neglect, particularly for the posterior portion of the 3rd ventricle. No differences in size and location of the lesions were found between the groups. Results indicate that this type of neglect is not secondary to lesions in specific sensory of motor pathways, but to lesions of structures coupling sensorimotor functions and the process of attention and that midline thalamic nuclei atrophy precipitates the neglect, perhaps by critically decreasing the amount of reticulothalamocortical projections engaged in selective attention.

Adult↗

Temporal window of vulnerability to repetitive experimental concussive brain injury.

OBJECTIVE: Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease. METHODS: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury. RESULTS: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P < 0.05) or mice receiving a single concussion (P < 0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P < 0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 hours and 1 week after injury in all animals sustaining a single concussion, the occurrence of a second concussion 3 days later resulted in significantly greater traumatic axonal injury (P < 0.05) than that resulting from a single CBI. CONCLUSION: These data suggest that a single concussion is associated with behavioral dysfunction and subcellular alterations that may contribute to a transiently vulnerable state during which a second concussion within 3 to 5 days can lead to exacerbated and more prolonged axonal damage and greater behavioral dysfunction.

Animals↗