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Chemokines and their receptors in allergic disease.

Mechanisms of chemoattraction underlie the spatial organization of the cells of the immune system under basal conditions and the localization of these cells to sites of inflammation. The chemokines, a family of around 50 small proteins, play a major role in these processes. Leukocytes are equipped with cell-surface sensors for chemokines. There are 19 such receptors that are differentially expressed on leukocytes: the repertoire of receptor expression depending on the type of leukocyte and its stage in maturation. From observations in animal models, clinical studies, in vitro cell biology, and molecular analysis, a working hypothesis has been established to explain the cellular interactions underlying allergic responses and the chemokines-chemokine receptors involved. Chemokines signal through G protein-coupled receptors that are used typically for sensory functions (eg, detection of olfactory signals in the nose). This type of receptor can be blocked selectively by small-molecule antagonists. This provides the opportunity for the development of therapeutic compounds designed to suppress the recruitment of particular leukocyte types in allergic reactions.

Animals↗

An abnormal clinical course of an ultrasound-guided supraclavicular brachial plexus block using 0.375% bupivacaine.

We report on the case of a reappearance of a supraclavicular nerve block after the apparent initiation of its resolution in a 21-year-old athlete undergoing repair of a valgus impaction syndrome of his right elbow. The patient's anesthetic management consisted of a supraclavicular nerve block and general anesthesia. The patient was discharged home with an apparent resolving nerve block. He returned to the hospital urgently when, at 7 hours after blockade, he lost all motor-sensory function in his arm. His workup ultimately yielded negative results, and the block resolved at 23 hours. In addition to documenting an abnormal course of a supraclavicular block, this case report questions the appropriateness of placing long-acting nerve blocks in outpatients.

Adult↗

Lower median nerve block impairs precision grip.

The purpose of this study was to investigate precision grip impairment caused by a lower median nerve block at the wrist. The median nerve block was achieved by injecting bupivacaine hydrochloride into the carpal tunnel, which acutely simulated a median neuropathy. Seven healthy male subjects were instructed to grip, lift, and hold an instrumented handle within 60s using precision grip. The same tasks were performed before and after the nerve block. Force and torque data were recorded using two miniature 6-component force/torque transducers. The precision grip was quantified by the safety margin (i.e. the difference between the actual grip force and the minimal grip force to keep the object from dropping), the variation of grip force, and the migration area of center of pressure (i.e. the area defined by the center of pressure at a digit-transducer surface while holding the handle). Two subjects were unable to complete the precision grip tasks after the nerve block, and their data were excluded from the analyses. The median nerve block caused significant increases (P<0.05) in the safety margin of the grip force (>50%), the grip force variation (>80%), and the area of center of pressure migration (>250%). Median nerve block at the wrist impairs the fine motor control during precision grip. Our results corroborate the important role played by sensory function in hand fine motor control. Clinically, the measures related to precision grip have the potential to quantify impairment of hand function caused by neuromuscular disorders, to monitor the progress of a hand disorder, and to evaluate the efficacy of a treatment or rehabilitation procedure.

Adult↗

Quantitative sensory findings in patients with bortezomib-induced pain.

UNLABELLED: Bortezomib (PS-341) is a newly developed proteosome inhibitor that shows extremely promising antineoplastic effects against a variety of neoplasias. Neuropathic pain is emerging as a major complication of bortezomib. Although clinical reports have appeared in the literature describing the general symptoms of bortezomib chemoneuropathy, specific quantitative sensory data that detail the sensory deficits that might yield insight to the primary afferent dysfunction contributing to this pain is lacking. In this report, it is shown that patients with bortezomib-induced neuropathic pain have significantly elevated touch detection threshold and slotted peg board time, impaired sharpness detection, and elevated thresholds for the detection of skin warming and heat pain. Patients also had increased reports of cold pain. These data indicate that bortezomib-induced neuropathy is associated with deficits in Abeta, Adelta, and C caliber primary afferent fibers. PERSPECTIVE: This work demonstrates that pain induced by the chemotherapy drug bortezomib is accompanied by dysfunction in all fiber types in sensory nerves. Impaired Abeta and C sensory function also extends into areas of skin that are not perceived as affected by pain.

Aged↗

Arousing properties of the vulvar epithelium.

PURPOSE: The initiation of genital tactile stimulation is regarded as a precursor to sexual arousal and perhaps in women it is the most easily recognized initiator of central nervous system arousal. Unfortunately little published material details the specific mechanisms preceding arousal, beginning at the epithelial level, which are the sensory precursors to arousal. Little is known about its cutaneous receptors, nerves and the other histochemical properties of this epithelial tissue that contribute to sexual arousal. Sexual sensitivity evaluations target female genital somatosensory pathways for cutaneous sensation by testing evoked potentials of nerves, hot/cold and vibratory sensory discrimination. The anatomical bases of these several sensibilities form a subject for future investigation. We reviewed the known influences and mechanisms responsible for the arousing properties of the epithelium in the female external genitalia as well neural pathways associated with sexual arousal originating from the vulvar epithelium. MATERIALS AND METHODS: A comprehensive review was done of published, relevant clinical and histological material in human and nonhuman vertebrate studies. RESULTS: Tactile stimulation of the vulvar epithelium initiates changes suggesting complex integrative mechanisms. Influences of skin temperature, hormonal environment, mechanical tissue compliance and inflammation as well as the large number of transmitters and neuropeptides involved in peripheral pathways serving female sexual arousal speak of a direct sensory role. CONCLUSIONS: Genital epithelial cells may actively participate in sensory function to initiate sexual arousal by expressing receptors and releasing neurotransmitters in response to stimuli, resulting in epithelial-neuronal interactions.

Animals↗

The effects of spinal cord injury on psychogenic sexual arousal in males.

PURPOSE: We determined if the degree of preservation of sensory function in the T11-L2 dermatomes could be used to determine the potential for psychogenic erectile responses in men with spinal cord injury. MATERIALS AND METHODS: Subjects included 45 men with spinal cord injury and 16 able-bodied control subjects. A 78-minute laboratory based analysis was done of subject subjective arousal, penile circumference, blood pressure, and heart rate responses to audiovisual erotic and audiovisual erotic combined with manual penile stimulation. RESULTS: Able-bodied subjects generally had significantly greater penile circumferences than spinal cord injured subjects during the stimulation periods. The degree of preservation of combined pinprick and light touch sensation in the T11-L2 dermatomes distinguished those who did and did not have a significant increase in penile circumference with audiovisual stimulation. Blood pressure and heart rate readings were generally higher in able-bodied than spinal cord injured subjects throughout the experimental protocol. However, all readings were within normal limits. CONCLUSIONS: Results support the hypothesis that psychogenic erection depends on the sympathetic nervous system. Findings underscore a possible parallel in neurological control of sexual responses between the sexes.

Adult↗

Aortic fenestration for chronic aortic dissection type B complicated by transient ischemic attacks of spinal cord.

Spinal cord injury is a rare complication in patients with aortic dissection. The extrinsic arterial supply to the spinal cord, diminishing caudally, often becomes critically dependent on the great radicular artery (GRA) of Adamkiewicz at the thoracolumbar spine. There are no prior reports of spinal injury or ischemia caused by chronic aortic dissection. We report on a 51-year-old patient with chronic type B dissection of the aorta from below the subclavian takeoff through the iliac arteries, presented with multiple episodes of transient (1 to 5 minutes) spinal ischemic attacks, entailing sudden loss of motor and sensory functions in both legs, with collapse of the patient on the ground. GRA imaging acquired with 64-channel computed tomography angiography enabled aortic fenestration from T11 to L1, performed with supraceliac aortic cross-clamping (T8 to L2) via thoracoabdominal access. We critically appraise the pertinent literature.

Aortic Dissection↗

Compression neuropathy of the radial palmar thumb nerve.

Compression neuropathy of a single digital nerve is a rare entity. We report the case of a patient with numbness in the distribution of the radial digital nerve of the thumb caused by the use of a walking stick. The nerve was compressed between the handle of the stick, the loop and the radial sesamoid bone of the first metacarpophalangeal joint. The site of the lesion was confirmed by electrophysiologic examination. Orthodromic recording of the sensory response from the radial palmar digital nerve of the thumb documented a complete absence of nerve action potential whereas the ulnar digital thumb nerve showed a normal response. Sensory function was restored when a padded ski glove was used to protect the area of the metacarpophalangeal joint whilst using the stick.

Canes↗

Functional MRI localizing in the cerebellum.

Mapping of cerebellar function by functional MRI now enables us not only to re-establish older anatomic findings of somatotopic representations but to gain new insights in the function of the cerebellum and its intimate relations of cerebral regions to serving sensorimotor function, sensory discrimination, and cognitive processing. Consequently, it will change our understanding of neurologic and psychologic failures in patients with inborn errors or neurodegenerative diseases or after neurosurgical procedures.

Brain Mapping↗

Morphometry of otoliths in chicken macula lagena.

The macula lagena located at the apical end of the cochlea in birds is characterized by the presence of numerous otoliths with unclear sensory functions. These otoliths are reported to be similar to those in the vestibular system but their detailed features in morphology are unknown. In the present study, we examined the number, size and shape of otoliths from the macula lagena in Chinese domestic chickens (Gallus Ling Nan) with a scanning electron microscope for morphometry. For chickens aged 10-15 post-hatch days, the otoliths in each macula lagena were counted to be 16,055 +/- 4038 (mean +/- S.D., n = 4). The average length and width were 12.98 +/- 3.70 microm and 5.10 +/- 1.48 microm (n = 526 otoliths), respectively. The ratio of length to width for the otolith was 2.58 +/- 0.39 (n = 526 otoliths) and remained relatively constant despite their variations in physical size. Almost all the otoliths were in regular shape and appeared like isolated cylinders with smooth facets at each end, but a few of them (0.025% of 64,221 otoliths screened) were found to be in odd shapes, such as T-shape and cross-shape. The results suggest that otoliths in the macula lagena and those in the vestibular system of bird's inner ear have similar physical properties and may play a similar role in sensing gravitational and acceleration signals.

Acoustic Maculae↗

Time-frequency analysis of target detection reveals an early interface between bottom-up and top-down processes in the gamma-band.

The early visual gamma-band response is an oscillatory signal evoked approximately 100 ms after stimulation. While some studies have found effects of various cognitive processes on this signal, such effects could not be replicated in other studies. Accordingly, some authors have claimed that evoked gamma-band activity reflects merely sensory functions. To resolve these conflicting positions, we conducted a target detection experiment in which the feature that defined the target could be distributed over a large or a small part of the entire stimulus. Only targets covering a larger area of the entire stimulus evoked stronger gamma-band activity than standards although the over-all stimulus size was identical for all stimuli. This increase in evoked activity resulted from stronger oscillatory power and not exclusively from stronger phase-locking. In contrast, N1 and P3 amplitudes were larger for target stimuli irrespective of the distribution of the relevant stimulus feature. These results are consistent with the notion that early gamma-band activity is generated by feature-selective neural assemblies the activity of which can in fact be modulated by top-down processes. This interaction, however, may be only detectable in scalp-recorded EEG if it affects a sufficient number of neural assemblies.

Adult↗

Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome.

Complex regional pain syndromes (CRPS, type I and type II) are devastating conditions that can occur following soft tissue (CRPS type I) or nerve (CRPS type II) injury. CRPS type I, also known as reflex sympathetic dystrophy, presents in patients lacking a well-defined nerve lesion, and has been questioned as to whether or not it is a true neuropathic condition with an organic basis. As described here, glabrous and hairy skin samples from the amputated upper and lower extremity from two CRPS type I diagnosed patients were processed for double-label immunofluorescence using a battery of antibodies directed against neural-related proteins and mediators of nociceptive sensory function. In CRPS affected skin, several neuropathologic alterations were detected, including: (1) the presence of numerous abnormal thin caliber NF-positive/MBP-negative axons innervating hair follicles; (2) a decrease in epidermal, sweat gland, and vascular innervation; (3) a loss of CGRP expression on remaining innervation to vasculature and sweat glands; (4) an inappropriate expression of NPY on innervation to superficial arterioles and sweat glands; and (5) a loss of vascular endothelial integrity and extraordinary vascular hypertrophy. The results are evidence of widespread cutaneous neuropathologic changes. Importantly, in these CRPS type I patients, the myriad of clinical symptoms observed had detectable neuropathologic correlates.

Adult↗

Novel tools to unravel molecular mechanisms in cilia-related disorders.

Cilia are hair-like organelles extending from the cell surface that execute motile (e.g. respiratory cilia) and/or sensory functions (e.g. renal monocilia). The basic ultrastructure of cilia and flagella has been well established by electron microscopy. Several recent reports have now provided intriguing new insights into the complex molecular composition of cilia and flagella. These data from genome, proteome and transcriptome analyses will facilitate the systematic discovery and understanding of genes responsible for human cilia-related diseases, such as primary ciliary dyskinesia, polycystic kidney disease and male sterility.

Animals↗

Conversion disorder presenting in a patient with an implantable morphine pump and an epidural abscess resulting in paraplegia.

Conversion disorders are symptoms or deficits affecting voluntary motor or sensory function that suggest a neurological or medical condition. The psychological symptoms associated with the medical condition must be preceded by conflict or other stressors. We present an individual who developed conversion disorder and paraplegia secondary to a sterile epidural abscess near the tip of her surgically implanted, epidural morphine infusion pump. She manifested at varying times both transient bilateral blindness and pseudoseizures consistent with a diagnosis of conversion disorder. Neurological evaluation for seizure activity and meningitis were negative. The etiology of the sterile epidural abscess remained unknown. The essential features of conversion disorder, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, are discussed. Treatment of patients diagnosed with conversion disorder remains primarily supportive, with the focus on consistency and behavioral management. Extreme caution is suggested in regards to further investigations.

Abscess↗

Tactile directional sensibility: peripheral neural mechanisms in man.

Tactile directional sensibility, i.e. the ability to tell the direction of an object's motion across the skin, is an easily observed sensory function that is highly sensitive to disturbances of the somatosensory system. Based on previous psychophysical experiments on healthy subjects it was concluded that directional sensibility depends on two kinds of information from cutaneous mechanoreceptors; spatio-temporal information and information about friction-induced changes in skin stretch. In the present study responses to similar probe movements as in the psychophysical experiments were recorded from human single mechanoreceptors in the forearm skin. All slowly adapting type 2 (SA2) units were spontaneously active, and with increasing force of friction their discharge rates were modified by probe movements at increasing distances from the Ruffini end-organ, reflecting the high stretch-sensitivity of these units. Slowly adapting type 1 (SA1) and field units responded to the moving probe within well-defined skin areas directly overlying the individual receptor terminals, and compared to the SA2 units their response properties were less dependent on the force of friction. The results suggest that SA1 and field units have the capacity to signal spatio-temporal information, whereas a population of SA2 units have the capacity to signal direction-specific information about changes in lateral skin stretch.

Adult↗

Pituitary adenylate cyclase-activating polypeptide-immunoreactive nerve fibers in rat and human tooth pulps.

The distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) was examined in the tooth pulp. In rat and human tooth pulps, PACAP-immunoreactive (IR) nerve fibers were observed around blood vessels and in the subodontoblastic and odontoblastic layers. The predentine and dentine were devoid of such nerve fibers. The double immunofluorescence method indicated the co-expression of PACAP with calcitonin gene-related peptide (CGRP) or vasoactive intestinal polypeptide (VIP). Virtually all PACAP-IR nerve fibers co-expressed CGRP-immunoreactivity (IR) in the rat tooth pulp suggesting their sensory function. In addition, a retrograde tracing method indicated that PACAP-IR nerve fibers in the rat tooth pulp originated from the trigeminal ganglion. On the other hand, almost all PACAP-IR nerve fibers in the human tooth pulp co-expressed VIP-IR and, thus, thought to be autonomic in nature.

Animals↗

Regeneration of sudomotor and sensory nerve fibres after digital replantation and microneurovascular toe-to-hand transfer.

The end-stage sudomotor and sensory recovery in patients with replanted fingers and patients after microneurovascular toe-to-hand transfer was studied using quantitative electrophysiological investigations (recovery of sensory nerve action potentials and the sympathetic skin response), the ninhydrin test and clinical testing of sensory regeneration (light touch, pain, static and dynamic two-point discrimination). 13 adult patients with 22 replanted digits (11 males, 2 females) aged 21-58 years (mean 42.2 years) and 12 adults and adolescents (8 males, 4 females) aged 13-45 years, (mean 26.8 years) following 14 microneurovascular great and/or second toe-to-hand transfers were studied. The replanted fingers were examined 2-7 years after injury and replantation. The toe-to-hand transfers were examined 2-12 years after injury and transfer. The results show better end-stage recovery of sudomotor and sensory function following finger replantation when compared to microneurovascular toe-to-hand transfer.

Adolescent↗

The fuzzy boundaries of apperceptive agnosia.

Following a trauma that mainly involved the right hemisphere, a 21-year-old girl showed a profound impairment in visual object recognition, without language and intellectual deficit. Her elementary sensory functions were preserved and she performed in the normal range on visual matching tasks, on taks requiring to detect small differences between similar complex shapes and in copying drawings, without any evidence of a line by line approach. Her deficit emerged with tests that, though not implying identification of meaning, demanded to disentangle a form from a confused background and to achieve a highly structured description of the stimulus. In addition to this high-level perceptual processing disorder, there was a deficit in recovering from the visual store the shape of an object, also when the performance did not involve perceptual discrimination, e.g., in drawing from memory or telling the physical difference between two named stimuli. Knowledge of the semantic and contextual attributes of objects was intact. The case is taken as evidence that the borders of apperceptive agnosia may be ampler than usually thought and its distinction from associative agnosia less rigid, with some patients laying in-between the two syndromes.

Adult↗