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Quantitative sensory testing.

Quantitative sensory testing is a reliable way of assessing large and small sensory nerve fiber function. Sensory deficits may be quantified and the data used in parametric statistical analysis in research studies and drug trials. It is an important addition to the neurophysiologic armamentarium, because conventional sensory nerve conduction tests only the large fibers. QST is a psychophysical test and lacks the objectivity of NCS. The results are subject to changes owing to distraction, boredom, mental fatigue, drowsiness, or confusion. When patients are consciously or unconsciously biased toward an abnormal QST result, no psychophysical testing can reliably distinguish these patients from those with organic disease. QST tests the integrity of the entire sensory neuraxis and is of no localizing value. Dysfunction of the peripheral nerves or central nervous system may give rise to abnormalities in QST. As is true for other neurophysiologic tests, QST results should always be interpreted in light of the patient's clinical presentation. Quantitative sensory testing has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. Because longitudinal QST studies of patients in drug trials are usually performed over a period of several months to a few years, reproducibility studies on the placebo-control group should be included. For individual patients, more studies are needed to determine the maximum allowable difference between two QSTs that can be attributed to experimental error. The reproducibility of thermal thresholds may not be as good as that of vibration threshold. Different commercially available QST instruments have different specifications (thermode size, stimulus characteristics), testing protocols, algorithms, and normal values. Only QST instruments and their corresponding methodologies that have been shown to be reproducible should be used for research and patient care. The data in the literature do not allow conclusions regarding the superiority of any QST instruments. The future of QST is promising; however, many factors can affect QST results. As is true for other neurophysiologic tests, QST is susceptible to many extraneous factors and to misuse when not properly interpreted by the clinician.

Carpal Tunnel Syndrome↗

Sensory extinction and sensory reinforcement principles for programming multiple adaptive behavior change.

The role of sensory reinforcement was examined in programming multiple treatment gains in self-stimulation and spontaneous play for developmentally disabled children. Two phases were planned. First, we attempted to identify reinforcers maintaining self-stimulation. Sensory Extinction procedures were implemented in which auditory, proprioceptive, or visual sensory consequences of self-stimulatory behavior were systematically removed and reintroduced in a reversal design. When self-stimulation was decreased or eliminated as a result of removing one of these sensory consequences, the functional sensory consequence was designated as a child's preferred sensory reinforcer. In Phase 2, we assessed whether children would play selectively with toys producing the preferred kind of sensory stimulation. The results showed the following. (1) Self-stimulatory behavior was found to be maintained by sensory reinforcement. When the sensory reinforcer was removed, self-stimulation extinguished. (2) The sensory reinforcers identified for self-stimulatory behavior also served as reinforcers for new, appropriate toy play. (3) The multiple treatment gains observed appeared to be relatively durable in the absence of external reinforcers for play or restraints on self-stimulation. These results illustrate one instance in which multiple behavior change may be programmed in a predictable, lawful fashion by using "natural communities of sensory reinforcement."

Autistic Disorder↗

Role of sensory neurons in restitution and healing of gastric ulcers.

It has been shown that capsaicin-sensitive afferent fibers play a crucial role in acute gastroprotection. Release of neurotransmitters such as calcitonin gene-related peptide (CGRP) and the consequent increase in mucosal blood flow have been identified as key factors in the protective effect of the stimulation of these fibers by capsaicin. Conversely the involvement of sensory nerves in the process of tissue repair after acute and chronic gastric mucosal damage has remained largely unexplored. Some studies, however, while demonstrating that the process of rapid repair (restitution) of the gastric mucosa damaged by ethanol is unaffected by capsaicin pretreatment, have shown that the recovery of gastric integrity after mucosal damage induced by sodium taurocholate or monochloramine, a known cytotoxic agent present in H. pylori patients, requires an intact sensory function and the maintenance of an adequate blood supply. In addition, a delayed healing (up to 1 week) of HCl-induced gastric lesions has been reported in capsaicin-deafferented rats, in association with a selective impairment of the hyperemic response to acid. Healing of gastric lesions induced by indomethacin, ischaemia and reperfusion, water restraint stress or concentrated ethanol was delayed in animals with functional ablation of sensory nerves. In a well-validated model, such as chronic gastric ulcers induced in rats by subserosal injection of acetic acid whose lesions last up to 4 weeks, the chemical ablation of sensory neurons negatively interferes with the process of chronic ulcer healing. The delay in ulcer healing was found to be associated with a persistent decrease in tissue levels of gastric CGRP and with a change of inflammatory mediators and growth factors, while gastric secretion and emptying were not concomitantly affected. Taken together, these data suggest that capsaicin-sensitive afferent nerves may play a role in the process of ulcer healing by mediating the hyperemic response through the release of CGRP and facilitating the acid disposal in the mucosa. From a therapeutic perspective, it is obvious that the compound acting on this system could have a role in the healing processes of the stomach damage.

Animals↗

Cerebral vascular accident: some characteristics of occupational therapy evaluation forms.

To determine areas most commonly evaluated by occupational therapists and to ascertain methods in which evaluative information is gathered, 35 evaluation forms currently employed by occupational therapists to assess dysfunction in patients with cerebral vascular accident were collected. Five general areas including motor function, sensory deficit, hadn function, activities of daily living, and visual perception were found to be most frequently listed on the forms. These areas were divided into sub areas to operationally define the information collected. Analysis revealed that the level of measurement most frequently employed by therapists to record evaluate findings was the descriptive level. There was a tendency to collect data at "higher" or more sophisticated levels of measurement in those areas evaluated most frequently. The findings are discussed in relation to professional competency concerns and the need to develop unique occupational therapy evaluative instruments for areas of practice such as cerebral vascular accident.

Cardiac Rehabilitation↗

Case study: high acuity to long-term.

High acuity nursing involves caring for clients who have potentially life-threatening conditions. This care is described as required, due to a disruption in one or more principal organ systems. How high acuity care is differentiated from acute or long term care may be dependent on the client's initial overall condition and/or predicted outcome. The client discussed has sustained a spinal cord injury at the C5 level. This presentation will demonstrate how clients may continually pass through high acuity care circumstances, acute care, to ultimately a long term care situation. Description of this client in a case study format may result in a learning experience for practitioners concerned with the physiological and the psychosocial aspects of their clients who require high acuity, acute and/or long term care. Car or motorcycle accidents account for at least half of all spinal cord injuries. Most are injuries involving cervical segments number 5 and 6. Cord damage can ascend or descend as much as three levels above or below the injury, due to edema or cord compression post trauma (Woll, 1986). Accidents with severe damage to the spinal cord at the C5 level can result in quadriplegia. Injuries of this magnitude can be either complete or incomplete. Complete injuries cause a "... loss of all conscious motor and/or sensory function below the level of injury" while incomplete injury spares some function, motor and/or sensory (Zejdlik, 1992, p.66). The purpose of this article is to present a client case study as a model for practitioners who practice in high acuity, acute, and long term situations. Two nursing theories (self-care deficit and adaptation) will be used as a framework for the case study. An assessment of the client's physical findings, including history, physical examination, and psychosocial status will be described. Nursing diagnoses and nursing interventions for two specific clinical problems will be presented. Recommendations for future research, nursing care and/or referrals will be outlined.

Acute Disease↗

The effects of acute and chronic lipopolysaccharide infusion in rats on the efferent function of sensory nerves in the isolated mesenteric arterial bed.

Capsaicin-sensitive sensory neurons are stimulated by noxious stimuli, and may be activated in endotoxaemia. The present study investigated the acute and chronic effects of lipopolysaccharide upon the efferent function of these nerves. Conscious rats received infusion (i.v.) of lipopolysaccharide (150 microg kg(-1) h(-1)) or saline for 2 or 24 h. Following infusion, animals were killed and the mesenteric arterial bed isolated and perfused with Krebs' solution. Electrical field stimulation of capsaicin-sensitive sensory nerves was investigated. Postjunctional mechanisms of sensory neurotransmission were examined using calcitonin gene-related peptide, and endothelial and smooth muscle function assessed using acetylcholine and sodium nitroprusside, respectively. All preparations exhibited dose dependency to the agonists, and frequency dependency to electrical field stimulation. No significant differences were observed between the four groups (2-h saline, 24-h saline, 2-h lipopolysaccharide and 24-h lipopolysaccharide) with regard to responses to electrical field stimulation, acetylcholine, sodium nitroprusside or calcitonin gene-related peptide. Thus, the efferent function of capsaicin-sensitive sensory nerves is unaltered in the isolated mesenteric arterial bed prepared ex vivo from rats receiving lipopolysaccharide, either acutely (2 h) or chronically (24 h).

Animals↗

The good side after stroke: ipsilateral sensory-motor function needs careful assessment.

Twenty subjects were examined 4-6 weeks after stroke to establish whether a sensory-motor ipsilateral deficit occurs early after stroke. Each underwent a timed test of repetitive side-to-side movement of both the upper and lower limbs ipsilateral to the cerebral infarct, and an assessment of motor disability using the Motor Assessment Scale. Results were compared with a group studied almost a year after their stroke, and with 41 age-matched healthy volunteers. There was a significantly worse performance (p < 0.005) on the right ipsilateral side, but not the left ipsilateral side, compared with normal volunteers, a finding similar to that of a group previously studied about a year after the stroke. There was no relationship between the severity of the motor deficit and performance of the side, possibly owing to reduction in cerebral activation as a result of a right hemispheric lesion. These observations have importance in rehabilitation and education as well as practical skills, including driving a car and maintaining balance.

Activities of Daily Living↗

The results of nerve grafting in the wrist and hand.

To evaluate the usefulness of nerve grafting we studied 38 patients having 11 median, 7 ulnar, and 33 digital nerve grafts. Group funicular (interfascicular) grafting using magnification was performed in all patients. We followed 12 patients with 8 median and 5 ulnar nerve grafts for at least one year and 18 patients with 27 digital nerve grafts for at least six months. Medical Research Council criteria were used for evaluation of nerve function. Results in our patients and in previously reported patients having nerve grafting or repair were compared. Sensory function following ulnar nerve grafting was significantly better than that following nerve repair. Sensory function following median and digital nerve grafting was as good as that following nerve repair. Motor function following ulnar nerve grafting was as good as that following nerve repair. Previously reported patients having median nerve repairs or grafts had significantly better motor function than our patients.

Adolescent↗

Transient changes of sensory nerve functions in uraemia.

The neurophysiological parameters (conduction velocity, amplitude and rise time of the compound action potential) of two sensory nerves of the lower limb (N. suralis and peronaeus superficialis) were determined bilaterally in five patients. Measurements were carried out at least twice in each subject during a time of great metabolic change. Two patients were recovering from acute renal failure (a single haemodialysis had to be performed on one of them) and three were under chronic maintenance haemodialysis. In the case of the haemodialysis patients, measurements were performed on two successive days, before and after one haemodialysis session. All the neurophysiological parameters showed significant improvement in successive measurements. In one patient the follow-up after acute renal failure revealed a delayed deterioration of the nerve functions, but after one year the values were normal. From the results it seems probable that an acute metabolic disturbance may cause transient inhibition of nerve functions without morphological changes in the nerve fibres.

Action Potentials↗

Analysis of herpes simplex virus ICP0 promoter function in sensory neurons during acute infection, establishment of latency, and reactivation in vivo.

We have begun an analysis of the functional architecture of the ICP0 promoter in neurons in vivo with the ultimate goal of determining how this gene is regulated during reactivation in vivo. Promoter/reporter mutants in which the Escherichia coli beta-galactosidase (beta-Gal) gene was driven by various permutations of the ICP0 promoter were employed to permit the analysis of promoter function without the added complications that would arise due to inappropriate regulation of ICP0 protein levels. A whole-ganglion immunohistochemical staining procedure (N. M. Sawtell, J. Virol. 77:4127-4138, 2003) was used for direct comparisons of the expression of the promoter/reporter gene to expression of the native protein in the same cell. In this way, the expression of the putative wild-type promoter could be validated and results for mutant promoters could be compared to expression of the native gene. We found that a DNA fragment from bp -562 through the methionine start codon of the ICP0 gene contained all sequences required for properly regulated ICP0 expression in diverse cell types (including sensory neurons of the trigeminal ganglia [TG]) in vitro and in vivo, as indicated by colocalization of ICP0 and beta-Gal. Truncation of the ICP0 promoter to bp -145 or -129 resulted in the loss of immediate-early (alpha) kinetics. The truncated promoters expressed high levels of the reporter gene with leaky late (gamma1) kinetics in vitro and in some cell types in vivo. Unexpectedly, the truncated promoters did not express in TG neurons. Thus, TAATGARAT or other sequences upstream of bp -145 in the ICP0 promoter are required for basal expression of ICP0 in neurons but are not required for basal expression in other cells in vivo. There was a >95% concordance between reporter and native protein expression detected with the 562-bp promoter in neurons during the acute stage. However, this was not the case during reactivation from latency in vivo, as nearly twice as many neurons contained detectable beta-Gal as contained detectable ICP0. This same 562-bp promoter/reporter cassette, when placed in the context of a latency-associated transcript (LAT) null mutant, resulted in >95% concordance of expression of beta-Gal and ICP0 during reactivation in vivo. These last results strongly suggest that there is a posttranscriptional constraint on the expression of ICP0 protein during reactivation from latency and that this constraint is mediated by LAT.

DNA Replication↗

Org.2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat.

The beneficial effect of short-term (8 days) melanocortin therapy on regenerating peripheral nerves is demonstrated using functional and electrophysiological tests. Following a crush lesion of the rat sciatic nerve, recovery of sensory function is monitored by assessing the responsiveness of the rat to a small electric current applied to the footsole. Recovery of motor function is assessed by means of an analysis of walking patterns. Normalization of the walking pattern reflects reinnervation of different muscle groups. The motor and H-reflex related sensory nerve conduction velocity of the regenerated nerves are longitudinally investigated in the same rats in which the recovery of motor and sensory function had been assessed previously. Functional tests show an enhanced recovery under melanocortin therapy, but in the end both saline- and melanocortin-treated rats show 100% recovery. However, when compared to the contralateral sciatic nerve, in the peptide-treated animals motor nerve conduction in the regenerated nerves has fully recovered after about 90 days following the crush lesion and the sensory conduction after about 120 days, whereas in the saline-treated rats a deficit of 20-40% in both motor and sensory conduction remains. This difference is observed even 214 days following crush.

Adrenocorticotropic Hormone↗

Effects of ageing on sensory nerve function in rat skin.

Human studies have shown an age-related decrease in modulation of skin vascular reactivity by sensory nerves that correlates with a decline in wound repair efficacy. Using a vacuum-induced blister model in the rat hind footpad, we have investigated age-related changes in pre- and post-terminal activity of primary afferents involved in skin neurovascular function. Changes in local skin blood flow were monitored using a laser Doppler flowmeter. Pre-terminal stimulation was achieved by electrical stimulation of the distal end of the sciatic nerve (10 V, 15 Hz and 0.5 ms) in three groups of young, old and neonatally pretreated capsaicin rats (3, 24 and 3 months old, respectively). The effect of post-terminal stimulation, achieved using local perfusion of 1 microM substance P (SP) over the blister base, was examined in young (3 months old), mature (12 months old) and aged (24 months old) rats. In addition to changes in SP responsiveness, other post-terminal changes studied included changes in smooth muscle reactivity to sodium nitroprusside (SNP), which acts directly on smooth muscle and to endothelial cell function using N-nitro-L-arginine (L-NORAG), a selective inhibitor of nitric oxide synthesis and endothelium-dependent relaxation. Electrical stimulation of the sciatic nerve in young rats induced an increase in local blood flow (within 1 min) that was maintained during the stimulation period, while the capsaicin group and the old group showed a significantly increased latency and decreased amplitude of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Analysis of osm-6, a gene that affects sensory cilium structure and sensory neuron function in Caenorhabditis elegans.

Mutation in the Caenorhabditis elegans gene osm-6 was previously shown to result in defects in the ultrastructure of sensory cilia and defects in chemosensory and mechanosensory behaviors. We have cloned osm-6 by transposon tagging and transformation rescue and have identified molecular lesions associated with five osm-6 mutations. The osm-6 gene encodes a protein that is 40% identical in amino acid sequence to a predicted mammalian protein of unknown function. We fused osm-6 with the gene for green fluorescent protein (GFP); the fusion gene rescued the osm-6 mutant phenotype and showed accumulation of GFP in ciliated sensory neurons exclusively. The OSM-6::GFP protein was localized to cytoplasm, including processes and dendritic endings where sensory cilia are situated. Mutations in other genes known to cause ciliary defects led to changes in the appearance of OSM-6::GFP in dendritic endings or, in the case of daf-19, reduced OSM-6::GFP accumulation. We conclude from an analysis of genetic mosaics that osm-6 acts cell autonomously in affecting cilium structure.

Alleles↗

Dynein-dynactin function and sensory axon growth during Drosophila metamorphosis: A role for retrograde motors.

Mutations in the genes for components of the dynein-dynactin complex disrupt axon path finding and synaptogenesis during metamorphosis in the Drosophila central nervous system. In order to better understand the functions of this retrograde motor in nervous system assembly, we analyzed the path finding and arborization of sensory axons during metamorphosis in wild-type and mutant backgrounds. In wild-type specimens the sensory axons first reach the CNS 6-12 h after puparium formation and elaborate their terminal arborizations over the next 48 h. In Glued1 and Cytoplasmic dynein light chain mutants, proprioceptive and tactile axons arrive at the CNS on time but exhibit defects in terminal arborizations that increase in severity up to 48 h after puparium formation. The results show that axon growth occurs on schedule in these mutants but the final process of terminal branching, synaptogenesis, and stabilization of these sensory axons requires the dynein-dynactin complex. Since this complex functions as a retrograde motor, we suggest that a retrograde signal needs to be transported to the nucleus for the proper termination of some sensory neurons.

Animals↗

Auditory and visual dysfunction following lead exposure.

The effects of lead exposure on cognitive function have been intensively studied during the past decade, but relatively little effort has been made to understand the impact on sensory function. Subtle impairments of visual and/or auditory processing, however, could have profound effects on learning. The objectives of this paper are to review what is known about the effects of lead exposure on visual and auditory function and to identify related research needs. In particular, the effects of lead exposure on sensory function in children, which have not been studied adequately, will be discussed. Evidence from human and animal studies reveal that lead exposure impairs auditory function. The cochlear nerve and more central structures appear to be preferentially sensitive in both developing and mature humans and experimental animals. Elevations in hearing thresholds and increased latencies of brainstem auditory evoked potential have been reported at low-moderate levels of lead exposure. Higher doses of lead increase the threshold of the auditory nerve action potential, produce segmental demyelination and axonal degeneration of the cochlear nerve, but appear to have no effect on cochlear microphonics or structure. Lead exposure affects both the retina and visual cortex of the developing and mature visual system. Low to moderate level developmental lead exposure produces selective rod deficits which can be detected with electrophysiological and behavioral techniques. At slightly higher levels of lead exposure the visual cortex is affected. A wide range of functional and neurochemical effects on retinal function occurring at blood lead levels below 20 micrograms/dl, the current level of concern, have been observed in rats. Structural, biophysical and photochemical similarities of rods in rats, monkeys and humans argue the relevance of this data for pediatric lead screening. To date, however, rod-mediated visual functions have not been examined in lead-exposed children. Undetected sensory deficits of these kinds may have profound impact on the motor and mental development of children as well as on the quality of life of affected adults. There is clearly a need for more extensive sensory testing in children and workers to screen for lead-induced health effects and in animal models to clarify the mechanisms of lead neurotoxicity.

Auditory Perceptual Disorders↗

Surgical results in Brown syndrome.

Surgical treatment for Brown superior oblique tendon sheath syndrome, now called Brown syndrome, has been advocated for patients with abnormal head posture or manifest hypotropia in primary gaze. Several surgical procedures with variable results and complications have been reported without consensus. Techniques and results of treatment for Brown syndrome at two institutions were reviewed. Charts of all patients who had undergone surgical treatment at Texas Children's Hospital, Houston, Tex, and Riley Hospital for Children, Indianapolis, Ind, between 1965 and 1989 were reviewed. The review yielded 38 patients. Superior oblique tenectomy was the most efficacious initial procedure. Surgery was successful in the treatment of anomalous head posture associated with Brown syndrome. There was no loss of sensory function as a result of surgery, but surgery did not inevitably lead to improved sensory function. We do not advocate superior oblique weakening combined with simultaneous surgery for iatrogenic superior oblique palsy as an initial procedure for Brown syndrome, since nearly one-half of our patients did not develop superior oblique palsy when followed for more than 1 year.

Adolescent↗

Long-term results of free radial forearm flap used for oral reconstruction: functional and histological evaluation.

PURPOSE: The aim of this study was to evaluate the radial forearm flap with regard to recovery of sensory function, general performance status, cutaneous blood flow and histological observations. PATIENTS AND METHODS: Thirty patients (23 male and 7 female) with oral carcinoma underwent immediate reconstruction with radial forearm flap after ablative surgery and returned for evaluation. Interviews were conducted to assess the degree of articulation and mastication. RESULTS: Sensory function tests suggested the restoration of cutaneous sensibility of the forearm flap. Histological findings indicated mucosa-like changes of flaps about 10 months after reconstruction. The clarity of conversation recovered favorably in most patients. However, the degree of recovery was generally related to the time after surgery. CONCLUSION: The radial forearm flap is a unique flap with specific characters that allowed for best available functional reconstruction of the oral cavity in terms of restoration of sensation, performance, and histological changes to adapt to the new oral environment.

Adult↗

Pharmacological treatment of irritable bowel syndrome--from concept to sales.

Functional gastrointestinal disorders are characterised by central and peripheral physiological changes, associated with psychological factors. Successful drug development has been hindered by lack of adequate characterisation of the nature of symptoms and their physiological and psychological correlates. Animal models of chronic stress are lacking. High levels of drug safety are now demanded for treating non-life threatening conditions. Once close to market, patient pressure groups, health care providers and insurers, government, and the internet can all influence a drug's success. Serotonin-modifying drugs have been the main recent focus of development, with mixed results. Cisapride has been withdrawn because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists have been developed on the questionable assumption that they modify visceral sensation in patients. Problems have arisen with alosetron being associated with ischaemic colitis and a high incidence of constipation. The 5-HT4 agonists have their major effect on inducing peristalsis, and may modify gut secretion and sensory function. Tegaserod and prucalopride show promise in patients with constipation and related symptoms. 5-HT1 agonists may play a role in treating functional dyspepsia, partly by improving impaired gastric accommodation to a meal. Antidepressants, often found to be clinically beneficial in these disorders, also affect serotonin metabolism. Past successes, such as loperamide or the somatostatin analogue octreotide, involved targeting end organ receptors influencing motor function or secretion. Modifying sensory function is much more challenging. Future research with novel compounds need to keep these recent lessons in mind.

Antidepressive Agents↗