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At least 595 records · Page 33Linked to original sources

PubMed2002

Review article: the complexity of drug development for irritable bowel syndrome.

Drug development for functional gastrointestinal disorders is complex. These conditions involve central and peripheral physiological changes, together with psychological factors. Methodological problems have included a poor appreciation of the physiological and psychological correlates of patients' symptoms, a lack of animal models of proven relevance, and safety issues. Government, patient pressure groups and the Internet can also influence a drug's success. Most recent interest has focused on the serotonin (5-HT) modifying drugs. Cisapride has been withdrawn in some countries because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists, developed to modify visceral sensation, have caused constipation; alosetron, also withdrawn, caused ischaemic colitis. The 5-HT4 agonists induce peristalsis; tegaserod and prucalopride, both delayed in their development due to issues of safety and efficacy, benefit patients with 'constipation-predominant' irritable bowel syndrome or idiopathic constipation. 5-HT1 agonists improve impaired gastric accommodation and symptoms in patients with functional dyspepsia. Antidepressants also affect serotonin metabolism. Previous examples of success in this area involved drugs targeted at peripheral receptors mediating motor function or secretion. Modification of sensory function is a much more challenging objective. The experience with serotonin modifying drugs has been mixed, and some important lessons are there to be learnt.

Antidepressive Agents↗

PubMed1977

Metabolic factors in surgery of peripheral nerves.

Respect for the metabolic changes within the neuron is critical in planning peripheral nerve surgery. Only by understanding the different metabolic responses of the nerve tissue and the supportive tissue can anastomosis be planned where the budding neuron stands its best chance of successfully regenerating across a repair site. Often, a short delay in nerve repair is indicated. With all factors ideal, good motor function can be counted on across one joint from the next group of muscles. Rarely is there good function across two joints. Protective sensory function can be achieved distally even under the most adverse metabolic conditions because of the independent metabolic state of these end organs.

Age Factors↗

PubMed2000

The clinical presentation of uppermost cervical disc protrusion.

OBJECT: The purpose of this study is to clarify the clinical presentation of the C2-C3 cervical herniation disc. SUMMARY OF BACKGROUND DATA: Uppermost cervical disc protrusion is an uncommon condition. The pattern of large central fragments of nucleus impinging on the highest cervical disc region is often poorly localized according to its clinical presentation. METHODS: Eight patients treated with anterior cervical discectomy with fusion for C2-C3 disc herniation participated in a detailed clinical and radiologic review to determine early detection and clarify potential hazards. Each patient's neurologic function was tested and recorded successively by a team of physicians and qualified physiotherapists. RESULTS: Reviewing the symptomatology, most patients presented ascending radicular symptoms secondary to trivial trauma, characterized by suboccipital pain, loss of hand dexterity, and paresthesia over face and unilateral lateral arm. Six (75%) patients had remarkable improvement postoperatively in neurologic function, except for some residual sensory embarrassment in at least 6 months follow-up. CONCLUSIONS: Clinical neurologic examination provides a less precise anatomic basis, to point to a particular upper cervical disc protrusion. Nonspecific neck and shoulder pain, a variety of cervical radiculopathy, and myelopathy may present. However, this rare spondylotic pattern is usually characterized by impairment of motor and sensory function more in the upper extremities than lower extremities and mostly starting following trauma. Radiculopathy generally outweighs the cord sign. Cruciate paralysis associated with vague diffuse and patch regions of hypesthesia over perioral distribution may help to localize this upper cervical lesion. The present study demonstrates that early detection and adequate anterior decompression may provide excellent outcome.

Aged↗

PubMed1995

The effect of age on pharmacokinetics of antiepileptic drugs.

Management of epilepsy in the elderly requires understanding of the unique biochemical and pharmacologic characteristics of this patient population. Accurate assessment of seizures and identification of epilepsy syndromes, thorough neurologic assessment to define etiology, and comprehensive evaluation of the patient's health and living situation are necessary for informed management decisions. Challenges to treatment include concomitant diseases, polypharmacy with accompanying drug interactions, and changes in physiology, such as changes in renal clearance and hepatic function than alter drug absorption, protein binding, metabolism, and elimination. Elderly patients with declining intellectual function, motor impairment, or altered sensory function may be especially susceptible to dose-related CNS side effects of antiepileptic drugs (AEDs). Drugs prescribed for concomitant illnesses such as hypertension, cardiovascular disease, infections, behavioral problems, and gastrointestinal disturbances may alter absorption, distribution, and metabolism of AEDs, with an adverse impact on efficacy and increased occurrence of adverse effects. The AEDs may induce metabolism of other drugs, resulting in decline in target response. Addition of an AED to an elderly patient's medical regimen requires careful review of all prescribed drugs. Optimal care of elderly patients with epilepsy includes use of free drug levels to monitor AED concentrations, careful dose selection, and sensitivity to the social problems that may occur in this population.

Adult↗

PubMed2001

Development of the vertebrate inner ear.

The inner ear, also called the membranous labyrinth, contains the cochlea, which is responsible for the sense of hearing, and the vestibular apparatus, which is necessary for the sense of balance and gravity. The inner ear arises in the embryo from placodes, which are epithelial thickenings of the cranial ectoderm symmetrically located on either side of hindbrain rhombomeres 5 and 6. Placode formation in mice is first visible at the 12-somite stage and is controlled by surrounding tissues, the paraxial mesoderm and neural ectoderm. Diffusible molecules such as growth factors play an important role in this process. The activity of several genes confers the identity to the placodal cells. Subsequent cellular proliferation processes under influences from the adjacent hindbrain cause the inner ear epithelium to invaginate and form a vesicle called the otocyst. Combinatorial expression of several genes and diffusible factors secreted from the vesicle epithelium and hindbrain control specification of distinct inner ear compartments. Transplantation studies and inner ear in vitro cultures show that each of these compartments is already committed to develop unique inner ear structures. Later developmental periods are principally characterized by intrinsic differentiation processes. In particular, sensory patches differentiate into fully functional sensory epithelia, and the semicircular canals along with the cochlear duct are elaborated and ossified.

Animals↗

PubMed1992

[Neurologic disorders after injuries of the spine].

The most frequent result of a cervical or dorsal spinal cord injury is a transverse lesion with quadriplegia or paraplegia, total loss of bladder and bowel control, breakdown of sympathetic function, and complete loss of sensory function. Partial cord lesion leading to central/anterior/posterior or Brown-Séquard syndromes are rare. Progressive clinical signs of cord damage are only rarely due to sub- or epidural hematoma or edema; in nearly all cases, they point to a persistent instability of the spine.

Diagnosis, Differential↗

PubMed1987

Rate of aging and dietary restriction: sensory and motor function in the Fischer 344 rat.

Sensory and motor task performance was assessed at 3 to 4 month intervals in chronically underfed and ad libitum-fed control rats from maturity into senescence. Diet-restricted rats weighed less than controls and lived significantly longer. Diminished body mass improved the underfed rats' abilities to hang suspended from a wire, to maintain balance on a narrow beam, and to descend from a wire mesh pole in a coordinated fashion. Underfed rats, however, lost these abilities at the same rate as did control rats. Undernutrition did not affect the startle response to acoustic stimulation, nor did it influence auditory or visual lead stimulus inhibition of the startle response. Both groups of animals showed progressive, age-related losses of sensory-motor function which proceeded at the same rate in each group. Life-prolonging undernutrition did not appear to retard aging of these simple, reflexive behaviors.

Aging↗

PubMed1989

alpha-Difluoromethylornithine (DFMO) disturbed the sensorimotor functional recovery from a sciatic lesion.

The effects of inhibition of polyamine synthesis on the motor and sensory functional neural recovery after a sciatic crush lesion was studied by measuring sensory and motor function of a crushed sciatic nerve after daily exposure to alpha-difluoromethylornithine (DFMO). DFMO increased the time needed for functional motor recovery by 13% in the toe-spread test when the lesion was about 20 mm proximal to the target muscle. DFMO reduced the rate of sensory axonal elongation by 24% in the pinch-test.

Animals↗

PubMed1993

Liquid stool incontinence with severe urgency: anorectal function and effective biofeedback treatment.

The motor and sensory function of the anorectum is well characterised in patients with solid stool incontinence. Fewer data are available in the case of liquid stool incontinence. Anorectal sensorimotor function was studied in 16 patients with liquid stool incontinence and severe urgency (10 with diarrhoea) unresponsive to conventional medical treatment, and in 16 healthy volunteers. The only significant difference found between incontinent patients and controls was a reduction in squeeze duration (p < 0.0001). Fourteen patients were selected to receive biofeedback treatment. Treatment was associated with a substantial improvement in continence in 12 patients and with a significant decrease in urgency (p < 0.05). Bowel frequency was not significantly influenced. Most patients showed a persistent improvement in anal motor function. Functional parameters were not predictive of outcome of treatment; the poor responders showed major psychological problems. In conclusion, an anal motor deficit is often present in disabling liquid stool incontinence. Biofeedback may improve anal continence in 75% of patients.

Adult↗

PubMed2001

Electrophysiological recording from neurons controlling sensory and motor functions of the esophagus.

Much work has been done in recent years to understand the functional roles of sensory neurons that regulate reflexes and sensations. Information about the response patterns of spinal dorsal horn and brain stem neurons associated with esophageal functions has become available by using electrophysiological techniques. These techniques allow understanding of response characteristics of neurons to various types of stimuli, neurotransmitters involved in excitation or inhibition of neurons, changes in response characteristics of neurons under pathological conditions, and the shape and size of a particular neuron in the central nervous system, as well as its projection to other areas of the brain. Response properties of primary afferent fibers in the vagus and thoracic sympathetic nerves have been studied in intact animal models by using single-fiber or extracellular microelectrode recording techniques. Recently, the single-fiber recording technique has been used in vitro in isolated esophagus-vagus nerve preparations. Recordings from the brain stem nuclei and thoracic spinal dorsal horn neurons also have examined the response characteristics of second-order neurons receiving afferent input from the esophagus. In the spinal cord, dorsal horn neurons responsive to esophageal distension also receive ipsilateral somatic input (ie, viscero-somatic convergence) from the upper thoracic area. These neurons exhibit sensitization of response after repeated noxious distension of the esophagus or instillation of irritant substances in the esophagus. In the nucleus ambiguus, neurons receiving input from the distal esophagus exhibit excitation to distension of the distal esophagus but undergo inhibition to midthoracic esophageal distension or to swallow. Neurons in the nucleus tractus solitarius receiving input from the distal esophagus exhibit 2 types of responses to proximal and distal esophageal distension. One type of response is a rhythmic firing synchronized with peristaltic contractions of the distal esophagus. This response undergoes inhibition in response to proximal distension. In addition, there is a second, nonrhythmic firing response that occurs both proximal and distal esophageal distension. This observation suggests that swallow-induced inhibition of the distal esophagus is controlled by the preganglionic motor neurons in the brain stem. Electrophysiological studies allow direct understanding of neuronal activities regulating esophageal functions. In vivo recording has an advantage for studying functional roles of the neurons in regulatory reflexes, whereas in vitro recording is useful for more accurate study of receptor pharmacology. Recordings from the central nervous system allow study of the neurotransmitters involved in neuronal function and the circuitry of different reflex mechanisms.

Deglutition↗

PubMed1995

[Detection of subclinical sensory nerve dysfunction in amyotrophic lateral sclerosis--a microneurographic study].

In amyotrophic lateral sclerosis (ALS) sensory function has been considered to be normal on a clinical basis. There are, however, several pathologic reports indicating that peripheral sensory fibers are involved in ALS. To evaluate changes in sensory nerve function quantitatively, we measured compound nerve action potentials (CNAP) of the median nerve by means of intraneural microneurography (MNG) and compared the results between 16 patients with ALS, age-matched 13 patients with Parkinson disease (PD) and 13 healthy controls. A tungsten microelectrode with a tip diameter of 1 micron was inserted percutaneously into the median nerve trunk at the elbow. With supramaximal electric stimulation on the median nerve at the wrist, the largest CNAP was recorded. The configuration of the CNAP was similar among three groups, consisting of a large triphasic wave followed by small multiphaic waves. In ALS patients the peak to peak amplitude (Amp) of the triphasic wave was 189.0 +/- 49.8 microV (mean +/- SD), which was significantly smaller than 273.1 +/- 90.0 microV in PD patients and 325.4 +/- 81.0 microV in normal controls (p < 0.01). The maximal nerve conduction velocity (NCV) in ALS was also reduced when compared with that in PD patients and in normal controls (p < 0.05). The average reduction in Amp in ALS was 58% of that in normal controls, while decrease in NCV was less apparent than Amp and 96% of normal controls. The Amplitude of nerve action potentials is considered to represent the density of large myelinated fibers more than 7 microns around the microelectrode.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed2004

Identification of candidate genes involved in somatosensory functions of cranial sensory ganglia.

We have shown that the characteristics of tissue trees obtained by the hierarchical cluster analysis of DNA microarray data suggest the cellular expression patterns of genes in the gene clusters [J. Neurosci. Res. 74 (2003) 818]. We here identified three gene clusters containing 11 genes as a potential pool of candidate genes related to somatosensation in cranial structures such as the face, oral cavity and pharynx. To obtain the cellular expression profiles, eight genes other than three genes analyzed previously were subjected to in situ hybridization analysis. The results show that all of the 11 profiles are roughly similar and suggest that the positive cells are probably somatosensory neurons in two cranial sensory ganglia, the trigeminal and petrosal ganglia. The expression profiles and probable physiological functions of the 6 genes such as trkA, NaN and galanin suggest their direct involvement in specific somatosensory functions such as nociception. The function of another gene, calretinin, is putatively related to mechanosensation and proprioception. The roles of the remaining four genes, including aquaporin 1 and two EST clones, in sensory neurons are unknown, and may provide clues to understand the sensory function in TG and PG.

Animals↗

PubMed1997

Effect of steroid therapy on parameters of peripheral autonomic dysfunction in leprosy patients with acute neuritis.

Recent electrophysiological studies on peripheral autonomic dysfunction in leprosy patients show a high prevalence of autonomic dysfunction as measured by abnormal vasomotor reflexes (VMR) and absent sympathetic skin response (SSR). Nothing is known about the reversibility of these autonomic parameters with treatment. Since there is evidence that small fiber function may be the most reversible component in neuropathies, we measured the effect of steroid treatment on autonomic parameters together with motor and sensory functions in leprosy patients with acute neuritis. Control subjects were investigated for repeatability testing of autonomic function. Due to a relatively high variability on repeat VMR testing in the controls, we defined a change in VMR testing as a change of > 30%. With this definition, the VMR of 14.8% of the patients improved, 75% remained unchanged, and 10.2% worsened. Absent SSR became positive in 16.6% and remained unchanged in 83.4%. Improvement in sensory motor functions was seen in 21.2% and 1.3% of the patients, respectively.

Acute Disease↗

PubMed2006

Evaluation of allodynia and pain associated with postherpetic neuralgia using current perception threshold testing.

OBJECTIVES: Postherpetic neuralgia has various clinical features, and the implicated pathophysiologic mechanisms are controversial. This study was carried out to clarify the roles of peripheral sensory nerves in the production of allodynia and ongoing pain. Current perception threshold (CPT) testing was used to evaluate the sensory function. METHODS: The intensities of ongoing pain and dynamic allodynia were assessed using a numeric rating scale (0-10). Assessment of sensory nerve function was performed by a series of 2,000-, 250-, and 5-Hz stimuli using CPT testing. These measurements were made in ipsilateral and contralateral area. RESULTS: CPTs at all frequencies in the ipsilateral area were significantly higher than those in the contralateral area. There were significant and inverse correlations between the intensity of allodynia and CPTs at all frequencies. No correlation was found between the intensity of ongoing pain and CPTs at any frequency. There was no correlation between the intensity of ongoing pain and the intensity of dynamic allodynia. CONCLUSIONS: The intensity of dynamic allodynia in postherpetic neuralgia correlates with the preserved functions of Abeta, Adelta, and C fibers. In contrast, the intensity of ongoing pain does not correlate with either the preserved function of C fibers or the intensity of dynamic allodynia. Therefore, it is suggested that postherpetic neuralgia might be a pain syndrome including both peripheral and central mechanisms.

Aged↗

PubMed2004

Functional dyspepsia: motor abnormalities, sensory dysfunction, and therapeutic options.

Functional dyspepsia is a common condition, but as yet, the underlying etiology is unclear. In this article, upper gastrointestinal motor and sensory physiology are reviewed and the current evidence for motor and/or sensory functional abnormalities causing dyspeptic symptoms is presented. The complex interrelationship between abnormal motor activity and sensation is explored, as well as the potential roles for autonomic dysfunction and psychological state in modulating gastrointestinal sensation and motor function. Finally, based on clinical trial evidence, a treatment pathway for functional dyspepsia is suggested.

Dyspepsia↗

PubMed1995

Inter-observer variability in the assessment of nerve function in leprosy patients in Ethiopia.

One of the major problems in leprosy is to detect any change in nerve function early enough so as to increase the chances of recovery and prevent disability. Several tests have been developed to assess nerve function and are used in leprosy control programs worldwide, but they are frequently performed by different workers on different occasions and under variable conditions. In this study we investigated the variability between different groups of observers in the assessment of nerve function in leprosy patients in Ethiopia. Sensory function was assessed by using a set of nylon monofilaments (NF) and a ball-point pen (BP), and motor function was assessed by using voluntary motor testing (VMT). We also studied the variability between observers in the assessment of the clinical signs of neuritis. Duplicate measurements were performed in random order on 50 leprosy patients by two physio-technicians and on 50 other patients by two health assistants. The percent agreement between observers was calculated for each single nerve, and weighted kappa statistics were used to assess whether agreement was better than expected due to chance alone. Systematic differences between observers were evaluated using the Wilcoxon signed rank test. On sensory testing, inter-observer variability was found to be related to the training and experience of the observer, to the nerve tested, and to the neurological status of the patient. When tests were performed by physio-technicians, we observed 32% to 58% agreement with the NF test and 71% to 84% agreement with the BP test, measured on different scales. After weighting for the scale difference, the agreement seemed comparable with these methods but the differences in measurements with the BP test were found to be dependent upon the neurological status of the patient. The variability between observers differed according to the nerve tested, and there was some evidence of systematic differences between observers with both methods. When performed by the health assistants, agreement was between 34% and 46% with the NF and between 66% and 82% with the BP tests. After weighting for the scale difference, the agreement seemed comparable but the BP was not liable to the systematic differences seen in the NF results. These differences could be attributed to the differences in the experience of the workers with these tests. With the VMT, small variability between observers was found for all nerves tested, except the facial nerve, when performed by both the physio-technicians and by the health assistants (72% to 98% agreement).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2004

The effect of brain-derived neurotrophic factor on sensory and autonomic function after lingual nerve repair.

Brain-derived neurotrophic factor (BDNF) is important in the response to peripheral nerve injury and may enhance regeneration. We have assessed its role in the functional recovery of sensory afferents and autonomic efferents after repair of the chorda tympani and lingual nerves in the cat. Six months after entubulation repair, with or without the incorporation of BDNF at the repair site, the recovery of secretomotor and vasomotor efferents was determined by recording salivary flow from the submandibular gland and temperature changes on the tongue surface, each evoked by stimulation of the repaired nerve. Electrophysiological recordings from the lingual and chorda tympani nerves proximal to the repair were undertaken to characterise mechanosensitive, thermosensitive, and gustatory afferents. When compared with data from uninjured control animals, both repair groups showed changes in receptor sensitivity and spontaneous discharge, and persistent reductions in conduction velocity, proportion of gustatory and thermosensitive units, rate of salivary secretion, and vasomotor responses. Comparisons between the outcome of repair with or without BDNF revealed few differences. In the BDNF group, fewer units in the chorda tympani responded to gustatory or thermal stimuli and the sensitivity of the gustatory units was lower. The conduction velocity of afferents in the lingual nerve was also lower, but the mechanoreceptive field size was higher. Thus, despite its known trophic role in the gustatory system, BDNF had not enhanced recovery of these or other fibre populations. We conclude that the application of BDNF to a site of lingual nerve repair has a negative effect on the long-term outcome.

Animals↗

PubMed2004

Long-term effects of transient chemically induced colitis on the visceromotor response to mechanical colorectal distension.

Acute gastrointestinal infections with transient mucosal inflammation frequently precede the onset of functional GI disorders with altered visceral sensory function. We hypothesized that an acute inflammation of the mucosa is linked to long-lasting alterations of afferent visceral pathways. Utilizing abdominal wall electromyography, we tested the visceromotor response to tonic rectal distension (60 mm Hg/3 min) in fasted, conscious, male Lewis rats (n = 40) with a barostat device before and 2, 4, 15, and 17 weeks after rectal instillation of saline or trinitrobenzenesulfonic acid plus ethanol. Tissue samples from paired controls were obtained to assess histologic tissue alterations. Inflammatory changes were present up to 2 weeks after acid/ethanol instillation but not after saline instillation. Compared to baseline measurements, the visceromotor response to colorectal distension increased significantly and reached a maximum 17 weeks (P < 0.001) after induction of colitis, while it decreased in control experiments (P < 0.05). In conclusion, these data suggest that an acute inflammation has long-term effects on somatosensory functioning.

Animals↗