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I. P. Pavlov and W. B. Cannon: founders of modern physiological thought relative to behavior and the autonomic nervous system.

It was almost a half century ago that I last attended an International Congress in Moscow and Leningrad--the IUPS Congress of 1935. My wife and I traveled far and saw the majesty of this land and its peoples. Here I met the great Pavlov and heard him present his thoughts concerning the conditioning of behavior. Cannon presented his concepts of transmitters and receptors. There were many other famous physiologists present, A. V. Hill and Lord Adrian; Kato of Japan demonstrated single nerve fiber studies. Someone talked of conditioned diuresis; I read a paper on hypothalamic control of the hypophysis. That was the dawn of neuroendocrinology, studies of hypothalamic function, sensory receptors, and the transmitter-receptor era. It was, like now, a time of great scientific endeavor, but there were clouds in the sky--Stalin and Hitler were coming to power, but the U.S.S.R. and America were friends, and in science it is still so. I wonder what some young man here will be able to report 50 years from now.

Autonomic Nervous System↗

Bilateral lower limb hypoesthesia after radical prostatectomy in the hyperlordotic position under general anesthesia.

PURPOSE: To report a case of postoperative bilateral lower limb hypoesthesia occurring after surgery under general anesthesia in the hyperlordotic position for radical prostatectomy. The possible pathophysiologic mechanisms are discussed. CLINICAL FEATURES: This 52-yr-old patient was slightly overweight and was on fenofibrate for hypercholesterolemia. He had no history of cardiovascular disease. Arterial blood pressure was overall well maintained except for a very transient hypotension at surgical incision. Blood loss was moderate and did not require transfusion. Soon after recovery, the patient complained of paresthesia in both legs and neurological examination revealed bilateral lower limb hypoesthesia, compatible with an incomplete medullar syndrome at the level of T12-L1. On postoperative day one, a plain magnetic resonance imaging scan demonstrated a hyperintense signal in the spinal cord from T8 to T9 on T2-weighted images consistent with ischemia of the spinal cord whereas the heterogeneous aspect of the spinal cord was due to an unusually high fat content of the epidural space. Neurological signs improved progressively and one week later the patient had recovered normal sensory functions of both lower limbs. CONCLUSION: Although arterial ischemia is the most common cause of postoperative spinal cord injury, other mechanisms may be invoked. We raise the possibility that a combination of intraoperative risk factors (hypotension, excessive postural changes) with anatomic predispositions (increased epidural venous pressure or fat content, previous bone disease) can produce arterial and/or venous ischemia of the spinal cord.

Humans↗

[Compartment syndrome of the thigh with sciatic nerve paralysis].

UNLABELLED: Acute compartment syndrome of the thigh has been infrequently reported in the literature. Closed femoral fractures and blunt soft tissue trauma are the main causes of this injury. The multiple injured patient in this case report developed a compartment syndrome of the thigh after intramedullary nailing of a comminuted fracture of the femur. Fasciotomy was performed two days after surgery because of extense swelling of the thigh in the ventilated and sedated patient. Sciatic and femoral nerve palsy was recognized after extubation of the patient nine days after the injury. During the following weeks the paresis of the femoral nerve recovered but neither motor nor sensory function of the sciatic nerve could be demonstrated. Therefore an operative revision of the sciatic nerve was performed eighteen weeks after trauma. No direct nerve injury could be detected but there were adhesions around the nerve as a sign of compression neuropathy caused by the compartment syndrome. The tibial component of the sciatic nerve showed a complete recovery within the next months but there was a persisting peroneal nerve palsy. CONCLUSION: Early clinical symptoms of a compartment syndrome like pain, paresthesia and paresis can not be ascertained in a ventilated and sedated patient. Tense swelling of the muscles is often the only detectable sign. Frequent measurements of compartment pressure should be done in these patients. We suggest early decompressive fasciotomy because the morbidity caused by fasciotomy in a borderline compartment syndrome is far outweighed by the morbidity that accompanies an undiagnosed untreated compartment syndrome with possible nerve palsy.

Adult↗

[Differential diagnosis of distal peripheral nerve compression syndrome of the tibial nerve. Case report of primitive neuroectodermal tumor].

Tumors of the tibial nerve are not sufficiently taken into account in the diagnosis of tarsal tunnel syndromes (TTS). They may present with atrophy of the plantar flectors and with disturbances of sensory functions, but far more commonly with pain. Diagnosis is often only achieved after 1-2 years. Taking tumors into account when examining patients presenting with TTS may lead to a more rapid diagnosis and to improvement in patients' prognoses. We present the case of a 37-year-old female in whom a primitive neuroectodermal tumor (PNET) was found to be the cause of long-standing pain in the right foot.

Adult↗

Gastric hypersecretion associated to iodoacetamide-induced mild gastritis in mice.

Disturbances of gastric motor, secretory and/or sensory functions are frequently associated with gastritis. The aim of this study was to characterize motor and secretory alterations associated to chemically-induced gastritis in mice. Mild gastritis was induced with 0.1% iodoacetamide administered intragastrically and added to the drinking water for a 6 days period. A significant loss of body weight and a reduction in food and water intake was observed in iodoacetamide-treated animals compared with those receiving vehicle. At the end of the treatment period, no macroscopic alterations were observed in the gastric mucosa of iodoacetamide-treated mice. However, histological sections revealed a mixed inflammatory infiltrate, with a predominance of mast cells in the submucosa; suggesting a mild gastritis. Gastric emptying rate of a nutrient solid meal was not modified in mice with gastritis compared with normal controls. In animals with gastritis, basal gastric acid secretion was increased compared with normal controls. Basal gastric acid secretion was not modified by either indomethacin or compound 48/80. Secretory response to secretagogues (pentagastrin and histamine) was enhanced during gastritis. Hypersecretory responses to both gastrin and histamine in iodoacetamide-treated mice were blocked by the mast cell stabilizer sodium cromoglycate, and enhanced by indomethacin, without affecting the secretory response in normal mice. These results suggest that mild gastritis alters gastric acid secretory responses through a mechanism related, at least partially, to mast cells activation. Moreover, prostaglandins also modulate secretory responses during mild inflammation. This animal model of gastritis might be useful to characterize pathophysiological changes and potential therapeutic targets in secretory-related gastric pathologies.

Animals↗

Weight estimation in a "deafferented" man and in control subjects: are judgements influenced by peripheral or central signals?

It is not yet certain which sources of information are most important in judging the weight of a held object. In order to study this question further, a "deafferented" man and five controls flexed their wrist to lift a container weighing 1,000 g. Direct vision of the arm and weight was denied; the container's vertical position was displayed to the subjects on an oscilloscope at the start of each trial and, then, in most experimental conditions, this display was removed. The weight was then either gradually increased or decreased over 20 s or left unchanged, on a pseudorandom basis. A verbal judgement of its change was required at the end of each trial, lasting 20 or 40 s. Under these conditions, the "deafferented" subject was unable to correctly judge the weight changes (38% accuracy, n.s. chi2, compared with 77% in control subjects), and even the control subjects, when exposed to muscle vibration, made many errors (54% accuracy). However, in many trials, including those in which the weight was unchanged, the vertical height of the container was not held constant by the subjects, but drifted up or down (mean absolute drift: approximately 2 cm). Hence, the change in muscular activation or stiffness could be estimated by the observers in the majority of trials. This allowed the verbal judgements of both the "deafferented" man and of control subjects undergoing muscle vibration to be correlated with the muscle activation produced, independent of the actual weight being tested. Post-hoc predictions of controls' responses during vibration, based on the direction of the change in muscle activity which these drifts in position implied, were 77% and 66% accurate for +/-750 g and +/-375 g tasks and 73% accurate for forearm-vibration trials (P<0.0001, chi2). Predictions of the "deafferented" subject's responses were 64% accurate (P=0.0002, chi2), even though his own responses were at a chance level with respect to the actual weight change. The judgements made by these subjects might have been based upon a peripheral sensory input, as small afferent fibres are still present in the "deafferented" man and vibration only partly blocked sensory function in the control subjects. Care was taken to minimise all other possible cues to the weight changes, e.g. vestibular, thermal, pressure or pain cues. However, peripheral inputs may not be the only signals used in the subjects' perceptual judgements. They might, instead, be based upon a centrally originating, but illusory changing sense of body position or, possibly, a changing sense of effort. In both cases, a perceived discordance between voluntary muscle activation and body image could underlie the subjects' responses. Our data do not yet allow us to distinguish between these alternative peripheral and central hypotheses, but do highlight the need to include perceptions of body position and motion into judgements of force control.

Case-Control Studies↗

Directional sensibility of hairy skin and postural control.

People can feel and report the direction of very small movements which cause changes in the tension of the forearm's hairy skin. This subjective sensory function may perhaps reflect more fundamental sensorimotor tasks. The hypothesis was investigated by measuring body sway and movement of six female and male volunteers who were performing the tandem-stance Romberg test with open and closed eyes. The increase in sway and movement after eye closure was reduced significantly when the subjects were allowed to use one forearm to touch a spatially fixed object from below. Three objects were used, a solid Perspex rod, an easily rotating steel ball, and a pointed metal peg whose tip was attached to the skin with a droplet of contact glue. Possible mechanical support could be excluded on basis of the objects' technical properties and the magnitudes of forearm movements. Movement of the forearm relative to an object could provide spatial information about changes of the forearm's position in space. Likewise, changes of skin tension that were caused by such movements could be useful. The Perspex rod and the steel ball might provide both types of information. However, the glued peg only caused changes of skin tension, but reduced sway and movement equally effectively. Therefore, information from tension receptors of the forearm's hairy skin underlying the accurate subjective directional sensibility also appears to participate in basic motor control.

Adult↗

Regional bone loss after orthotopic liver transplantation in inbred rats: the role of hepatic denervation.

Bone loss and long-term persistence of osteoporosis with increased fracture risk are common after liver transplantation. It is unknown whether transplantation-induced disruption of hepatic nerves, serving numerous regulatory metabolic and sensory functions, is herein involved. To test this possibility, we measured bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and studied dynamic histomorphometry, radiocalcium kinetics, and biochemical parameters in 7 liver-transplanted and 7 sham-operated inbred rats. Although liver function was normal in TX rats, trabecular BMD of the first lumbar vertebra and total BMD of the femoral diaphysis were decreased by 13% and 6%, respectively, 9 months postsurgery. The breaking force of the femur was significantly lower by 21%. However, bone mass in the femoral and tibial metaphysis was preserved as evidenced by pQCT measurements and histomorphometry. Trabecular width and wall thickness were significantly decreased in vertebral cancellous bone, whereas indices of bone formation and resorption were normal or slightly reduced. Serum minerals, mineral balance, fractional and net absorption of Ca and Mg, serum calciotropic hormones, IGF-I, leptin, specific activity of 45Ca in bone, 45Ca excretion, and biochemical indices of bone formation and bone resorption remained unchanged. We conclude that liver transplantation-related denervation causes cancellous and cortical bone loss in well-innervated bone sites such as the lumbar spine and the long bone diaphysis. Cancellous bone loss in TX rats is due to an impairment of osteoblast team performance and subsequent trabecular thinning. The mechanism uncovered by our study may contribute to long-term bone loss after liver transplantation.

Animals↗

Percutaneous hydrodynamic thrombectomy for femoral arterial thrombosis after arterial catheterization.

We report on a 3-year-old boy in whom a complete occlusive thrombus in the right femoral artery was removed rapidly and successfully using a hydrodynamic thrombectomy catheter. There was no bleeding complication, reocclusion, vascular injury, or loss of motor or sensory function. Hydrodynamic thrombectomy can be an important part of the treatment of thrombosis in children.

Angiography↗

Spinal epidural hemangioma related to pregnancy.

We report the case of a 39-year-old woman with adolescent idiopathic scoliosis presenting with myelopathy secondary to a spinal epidural hemangioma. MRI showed an epidural soft tissue mass within the spinal canal between T5 and T9 with severe spinal cord compression. Symptoms had a temporal relationship to her pregnancy. Surgical removal of the epidural hemangioma rapidly relieved her symptoms and neurologic deficits. Follow-up examination 2 years later demonstrated normal motor and sensory function, without any neurologic sequelae or progression of deformity.

Adult↗

Short-term effects of sacral nerve stimulation for idiopathic slow transit constipation.

This study assessed the short-term clinical and physiological effect of continuous sacral nerve stimulation in patients with slow transit constipation. Some patients with idiopathic slow transit constipation are unresponsive to conservative treatments, while colectomy has a variable and poorly predictable outcome. Sacral nerve stimulation is a less invasive and reversible procedure that enables direct neuromodulation of the pelvic floor and hindgut. It has been used successfully in the treatment of urologic disorders and fecal incontinence, and some of these patients with concurrent constipation have also noted improved stool frequency and rectal evacuation. Eight women (median age 47 years, median symptom duration 31 years, median stool frequency once per 6 days) were implanted with a temporary percutaneous stimulating S3 electrode for 3 weeks, attached to an external stimulator (Medtronic, Minneapolis,USA). A bowel symptom diary card, anorectal physiological studies, and a radiopaque marker transit study were completed before and during stimulation. Two patients had cessation or marked diminution of symptoms, including normalization of bowel frequency. Colonic transit did not return to normal in any patient. Rectal sensory threshold to distension was decreased during stimulation. Percutaneous temporary sacral nerve stimulation symptomatically improved a minority of patients with resistant idiopathic slow transit constipation. Sensory function was altered by stimulation. Further studies are required to identify patients who may benefit and to assess a range of stimulation parameters.

Adult↗

Assessments of anal canal sensitivity in patients with soiling 5 years or more after colectomy, mucosal proctectomy, and ileal J pouch-anal anastomosis for ulcerative colitis.

INTRODUCTION: To clarify the significance of anal canal sensitivity contribution to soiling in patients after ileal J pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), we studied the sensory function of the anal canal. METHODS: Forty patients with UC who had undergone IPAA with ileostomy closure at least 60 to 132 months (mean 103.6 months) previously, and who had no preoperative or postoperative complications were recruited. They were divided into two groups: group A [n = 26; patients without soiling (16 males, 10 females; ages 15-49 years, mean 36.6 years)] and group B [n = 14; patients with soiling (10 men, 4 women; ages 24-56 years, mean 40.9 years)] compared with group C [n = 28; control subjects (18 men, 10 women; aged 19-49 years, mean 38.5 years)]. Patients with soiling were also divided into three groups (B1, rare soiling; B2, occasional soiling; B3, frequent soiling). The anal canal sensitivity threshold was measured using an anal canal electrosensitivity test (ACEST). The measurement point of anal canal was divided into three parts: lower part [1 cm below the dentate line (DL), middle part (just on the DL), and upper part (1 cm above the DL]. A small electric current from a constant-current generator was passed between the electrodes until the patient felt a sensation often described as tingling or pulsing. The threshold of sensitivity was assessed in the upper, middle, and lower parts of the anal canal. RESULTS: In patients of group C, recording at the middle part of the anal canal showed the best results. The anal canal sensitivity threshold of group B was significantly higher than those of groups A and C at the upper and middle parts (P < 0.0001, respectively). There were no significant differences at the lower part among groups. The anal canal sensitivity threshold of subgroup B3 was significantly higher than those of groups B1 or B2 at both the upper part (P = 0.0002, P = 0.0038, respectively) and middle part (P = 0.0001, P = 0.0480, respectively). There were no significant differences at the lower part among groups. CONCLUSIONS: The ACEST shows significantly lower sensitivity in the proximal and middle anal canal in IPAA patients with soiling.

Adolescent↗

Molecular characterization and mapping of ATOH7, a human atonal homolog with a predicted role in retinal ganglion cell development.

The human ATOH7 gene encodes a basic helix-loop-helix (bHLH) transcription factor that is highly similar to Drosophila Atonal within the conserved bHLH domain. The ATOH7 coding region is contained within a single exon. We mapped ATOH7 to Chromosome (Chr) 10q21.3-22.1, a region syntenic to the segment of mouse Chr 10 where Atoh7 (formerly Math5) is located. The evolutionary relationship between ATOH7 and other atonal homologs was investigated using parsimony analysis. A direct comparison of ATH5/7 and ATH1 protein subgroups to Atonal also revealed a nonrandom distribution of amino acid changes across the bHLH domain, which may be related to their separate visual and proprioceptive sensory functions. Among bHLH genes, ATOH7 is most closely related to Atoh7. This sequence conservation extends significantly beyond the coding region. We define blocks of strong homology in flanking human and mouse genomic DNA, which are likely to include cis regulatory elements. Because targeted deletion of Atoh7 causes optic nerve agenesis in mice, we propose ATOH7 as a candidate for human optic nerve aplasia and related clinical syndromes.

Amino Acid Sequence↗

[Flicker provocation with LED full-field stimulation in normals and glaucoma patients].

BACKGROUND: Flicker light is an easy method to test sensory function after stress. The aim of this study was to determine the influence of flicker stress on temporal contrast sensitivity in healthy controls and patients with glaucomatous alteration of the optic disk. METHODS: A commercially available full-field stimulator (Retiport, Roland Consult) equipped with white LEDs was modified to perform psychophysical tests. The patients underwent measurements of the recovery time interval from cessation of flicker stress until recognition of a pregiven flicker contrast after photo stress. In addition, we studied contrast sensitivity with a continuous flickering target and with a flicker burst protocol avoiding adaptation to prevailing flicker. All tests were performed at a constant retinal illumination and at a frequency of 37 Hz for provocation as well as for contrast sensitivity tests. SUBJECTS: Normal healthy controls (40), "preperimetric" (62), and "perimetric" (52) open-angle glaucoma patients were studied. Exclusion criteria were age lower than 31 years, visual acuity under 0.6, and perimetric mean defect more than 9.5 dB. RESULTS: Recovery time after flicker stress was significantly longer in patients than in normals and longer in perimetric than in preperimetric patients. Analysis in perimetric patients revealed a larger area under ROC for the provocation test (0.95) than in contrast sensitivity tests (continuous flicker method: 0.90, flicker burst mode: 0.84). CONCLUSION: High-power LEDs which are installed in modern full-field devices can be used as a helpful tool to study psychophysical properties. In the present study it could be shown that threshold, adaptation, and recovery of temporal transfer characteristics are impaired in many patients with glaucoma.

Contrast Sensitivity↗

Global processing of spectrally complex sounds in macaques (Macaca mullata) and humans.

How nonhuman species perceive the world is a biological question of fundamental importance, and has major significance for establishing the validity and possible limitations of animal models of human sensory function and perception. Studies in comparative hearing have revealed that almost all animals, including monkeys, are worse than humans at discriminating tone frequencies. Less is known, however, about comparative differences in discriminating more spectrally complex sounds. We compared the capacity of macaques and humans to discriminate complex sound patterns by measuring spectral-contrast sensitivity using stimuli having sine-modulated power spectra, analogous to sine-wave gratings used in visual studies. We found that the auditory system of the macaque is far less sensitive than the human system over the sine-profile frequency range tested (0.5-2.0 cycles/octave). These results indicate that rhesus macaques hear at least some spectrally complex sounds with less fidelity than do humans, and demonstrate large differences in primate species' abilities to process low-resolution spectral patterns. These results cannot be accounted for by traditional, narrowband peripheral filter models of spectral analysis, but instead, imply the involvement of a central, frequency integration process that may differ significantly across species.

Animals↗

Brachial plexus gunshot injury in an infant.

We present the case of an infant with a gunshot lesion in the brachial plexus. Intraoperative nerve action potential recordings suggested posterior cord neurolysis and medial and lateral cord grafting. After 3 years' follow-up complete recovery of motor and sensory function was seen as a result of immense nerve regeneration capability and brain plasticity. According to our knowledge this is the first reported case of such a mechanism of injury in an infant.

Brachial Plexus↗

Epidermal innervation density after partial sciatic nerve lesion and pain-related behavior in the rat.

The epidermis is innervated by fine nerve endings that are thought to have important sensory functions including nociception. Their role in neuropathic pain is as yet unclear. We used rats with a chronic constriction injury (CCI) of the sciatic nerve, a model of painful partial nerve injury, to examine the temporal course of the epidermal innervation density in correlation with corresponding nerve fiber numbers in the sciatic nerve and with pain-related behavior of the rats. A significant reduction of protein gene product 9.5 (PGP 9.5)-immunoreactive (ir) fibers and a nearly complete loss of calcitonin gene-related peptide (CGRP)-ir fibers was found after CCI in the epidermis as well as in the sciatic nerve. Reappearance of epidermal fibers was delayed compared to the regeneration of nerve fibers in the sciatic nerve. The maximum of pain-related behavior occurred at the time of maximal reduction of epidermal nerve fiber density. Possible explanations for this apparent discrepancy could be the presence of abnormal electrophysiological properties in the few remaining epidermal fibers, the lack of inhibition by intact fibers, or the generation of hyperalgesia in deeper layers of the skin. The number of PGP 9.5-ir Langerhans cells was increased after CCI, and this increase also temporally correlated with the presence of thermal hyperalgesia and mechanical allodynia, supporting a role of Langerhans cells in the generation of pain.

Animals↗

A novel population of neuronal cells expressing the olfactory marker protein (OMP) in the anterior/dorsal region of the nasal cavity.

The olfactory marker protein (OMP) is expressed in mature chemosensory neurons in the nasal neuroepithelium. Here, we report the identification of a novel population of OMP-expressing neurons located bilaterally in the anterior/dorsal region of each nasal cavity at the septum. These cells are clearly separated from the regio olfactoria, harboring the olfactory sensory neurons. During mouse development, the arrangement of the anterior OMP-cells undergoes considerable change. They appear at about stage E13 and are localized in the nasal epithelium during early stages; by epithelial budding, ganglion-shaped clusters are formed in the mesenchyme during the perinatal phase, and a filiform layer directly underneath the nasal epithelium is established in adults. The anterior OMP-cells extend long axonal processes which form bundles and project towards the brain. The data suggest that the newly discovered group of OMP-cells in the anterior region of the nasal cavity may serve a distinct sensory function.

Animals↗