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Noun-verb differences? a question of semantics: a response to shapiro and caramazza.

We presented a new model using the sensory/functional theory of semantic category deficits to explain noun/verb deficits in aphasia. The predictions arising from this model were tested on a small number of patients exhibiting grammatical and/or semantic category specific deficits in picture naming. The results lent support for the theory presented. Shapiro and Caramazza (this issue) raised several objections to this theory (which they call the "extended sensory functional theory," or ESFT). In this article we address their concerns about the validity of the ESFT and conclude that it is indeed a useful model that provides a parsimonious explanation for many diverse patterns of deficits.

Aphasia↗

TRPP2 channel regulation.

Polycystin-2, or TRPP2 according to the TRP nomenclature, is encoded by PKD2, a gene mutated in patients with autosomal-dominant polycystic kidney disease. Its precise subcellular location and its intracellular trafficking are a matter of intense debate, although consensus has emerged that it is located in primary cilia, a long-neglected organelle possibly involved in sensory functions. Polycystin-2 has a calculated molecular mass of 110 kDa, and according to structural predictions it contains six membrane-spanning domains and a pore-forming region between the 5th and 6th membrane-spanning domain. This section irst introduces the reader to the field of cystic kidney diseases and to the PKD2 gene, before the ion channel properties of polycystin-2 are discussed in great detail.

Animals↗

Kinocilia in the developing stria vascularis of the rat pup.

The mammalian stria vascularis undergoes certain developmental changes in the postnatal rat. The present study was designed to examine the ultrastructure of the stria vascularis in rat pups from immediately after birth to 20 days postpartum. The cochlea were removed with the animals under xylazine (Rompun) anesthesia and were prepared for transmission electron microscopy. Each of the three cell types in the stria were found to contain kinocilia up until 12-17 days of age. The presence of kinocilia in the intermediate and basal cells has not been previously described. Findings suggest that these organelles may serve a motile and/or sensory function to assist in the maturation of cell functions, particularly ion transport, during early stages of development.

Aging↗

Three-dimensional structure of the gustatory cell in the mouse fungiform taste buds: a computer-assisted reconstruction from serial ultrathin sections.

Taste buds in fungiform papillae of the mouse were examined with transmission electron microscopy and computer-assisted, three-dimensional reconstruction from serial ultrathin sections. In accord with observation by Murray (1971), four distinct cell types, type I, II, III and basal cells, were identified. Of these, only the type III cell made synaptic contacts with nerve terminals and contained both small, clear vesicles and dense-cored granules. The former vesicles were synaptic-type and accumulated in the cytoplasm just below the synaptic in membrane thickenings. This finding clearly indicates a sensory function for the type III cell. One to three type III cells were identified within a taste bud. The type III cell had at most eight synapses with nerve terminals. One nerve fiber making two synapses with the type III cell was occasionally observed in its terminal region.

Animals↗

Heterotopic neurons in human spinal nerve roots: what is their clinical significance?

The significance of heterotopic nerve cells in human spinal nerve roots was studied. Heterotopia was a consistent finding in 230 routine necropsy series (neuropathologically normal) and 16 spinal cord malformation cases, the incidence ranging between 2.1% and 10.9%. It was more frequently found in the cervical posterior roots than in the anterior roots or in other segmental levels. The heterotopia was not increased in dysraphic anomalies. Aberrant sensory nerve cells in the posterior roots and aberrant motor cells in the anterior roots were morphologically ascertained. The clinical significance of the sensory function of the heterotopia in the anterior roots is discussed and compared with previous experimental data.

Adult↗

Comparison of melatonin-binding sites in the brain of two amphibians: an autoradiographic study.

Neuroanatomic comparison of the binding capability of 2-[125I] iodomelatonin in the crested newt Triturus carnifex Laur. and the green frog Rana esculenta, using quantitative autoradiographic techniques, revealed a heterogeneous distribution pattern. The highest and relatively high binding activities were shown to occur in the optic tracts and in the suprachiasmatic area of the hypothalamus and the optic tectum, respectively, of both species. Low or no 2-[125I] iodomelatonin binding values were obtained in the preoptic nucleus, the tuberal hypothalamus, the medulla oblongata, the septum and the dorsal pallium. A differential binding pattern was observed in the amygdaloid nucleus pars lateralis, the striatum and the hindbrain of these amphibians. Indeed, notably high binding levels were shown to occur in the former two brain areas of the crested newt, whereas high levels were displayed in the latter brain region of the green frog. On the basis of elevated quantities of melatonin receptors in mesencephalic, hypothalamic and telencephalic sites, it seems plausible to ascribe some important sensory functions to this receptor system in both species. The remarkably different binding activities in the brain of the two amphibians could be correlated with the simpler cytoarchitectonic brain structure of urodeles and with species-specific variations.

Animals↗

Ilio-psoas hematoma--its detection, and treatment with special reference to hemophilia.

Pain around the hip joint and femoral neuropathy in a patient with a bleeding coagulopathy should alert the physician to the possibility of an iliopsoas haematoma. Unfortunately this diagnosis is often missed. Clinically, reduced hip motion, a mass in the iliac fossa and alteration in the motor and sensory function of the femoral nerve may be noted. If the pain is on the right side, appendicitis must be excluded. Ultrasound is the diagnostic aid of choice, being more sensitive than computerized tomography or radioisotope investigations. Treatment should be gradual, gentle and protracted to avoid recurrent bleeding episodes.

Hematoma↗

Influence of isaxonine on the target phenomenon, muscle fibre size and neuromuscular junction in the tenotomized and denervated gastrocnemius muscle of the rat.

Isaxonine is reported to accelerate the rate of peripheral nerve regeneration, stimulate axonal sprouting and promote motor and sensory function recovery. The target phenomenon in muscle fibers is the morphological expression of increased stretch activity in a diseased muscle. It can be produced in the gastrocnemius muscle of the rat by tenotomy and is inhibited by simultaneous denervation. The influence of isaxonine on this experimental model was studied. Twenty Wistar rats were submitted to bilateral section of the Achilles tendon and section of the left sciatic nerve. In ten rats, treated with isaxonine, the qualitative and quantitative changes in the gastrocnemius muscle were compared with the control group over a period of 3 weeks. No statistical differences were observed in the occurrence and inhibition of the target phenomenon, the muscle fibre size and the neuromuscular junction. Isaxonine has no direct effect on a diseased muscle with an intact nerve supply, nor in the early stages after complete denervation.

Achilles Tendon↗

Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations and prognosis in 398 patients with spinal cord compression.

We reviewed all medical records concerning patients suffering from spinal cord or cauda equina compression (SCC) secondary to cancer, in the eastern part of Denmark, from 1979 through 1985. During the period the incidence of SCC in cancer patients went up from 4.4% to 6%. However, this increase was not significant. The series comprised 398 cases, with carcinoma of the prostate (19%), lung (18%), breast (14%) and kidney (10%) accounting for 61%. The symptoms were evaluated in accordance with the patients rating of pain, motor deficits, sphincter control and paraesthesia, whereas the clinical manifestations were classified on the basis of motor deficit and bladder dysfunction. During the period preceding the diagnosis of SCC, 83% of the patients suffered from back pain, 67% from deteriorating gait and 48% had retention of the urine. In 35% of the patients there was no sphincter disturbance and 10% had normal sensory function. The outcome of treatment was estimated by changes in motor deficits and sphincter function, and depended primarily on the patients condition at the time of the diagnosis. Of the patients who were able to walk before treatment, 79% remained ambulatory, whereas only 18% of the non-ambulatory patients regained walking ability. Patients treated by decompressive laminectomy followed by radiotherapy apparently had a better response than patients treated with surgery or irradiation alone, but when the patients pre-treatment motor function was taken into account, no significant difference was observed. The study may call for a properly randomized trial with careful stratification of tumour biology, performance status and neurological deficits.

Adolescent↗

Frontotemporal epidural approach to trigeminal neurinomas.

From 1980 through 1993 a series of 44 patients with trigeminal neurinomas was treated. Five of them were operated on for the remainder of the tumour as they had undergone previous surgery elsewhere, 35 were operated on for the first time, and 4 were not operated on for various reasons. An epidural approach to the neurinomas originating in the branches of the Vth nerve peripherally to the Gasserian ganglion (GG) was used. In the neurinomas originating in the GG or in the root of the Vth nerve, either an epidural-transdural approach or an epidural-transdural-transpetrous approach was used. All tumours operated on using the approach described in this article were completely removed. In 10 patients, the Vth nerve sensory deficits increased in comparison with preoperative deficits; in 9 their state remained unaltered; and in 11 the sensory function of the Vth nerve improved. In those patients who had experienced pre-operative atypical trigeminal pain, the pain disappeared after surgery. There was no additional treatment: radiosurgery, irradiation or chemotherapy. Histopathological examination did not reveal any malignant changes in the tumours in any of the patients. Based on our own experience and on the published data it is believed that the best treatment for trigeminal neurinomas is complete microsurgical removal of the lesion.

Adolescent↗

Nerve suture without tension, a method for repairing transected peripheral nerves.

An analysis of primary epineural end to end sutures of transsected peripheral nerves, operated upon before 1970, showed good motor and sensory function in only 60%. With the new perineural suturing technique without tension and if necessary by using autologous nerves for bridging large nerve defects the good results raised to 87%.

Humans↗

Autonomic influences on colorectal motility and pelvic surgery.

The nervous control of the motility of the human distal bowel was investigated by two physiological studies of electrical stimulation of sacral parasympathetic outflow in patients with high spinal injuries and in patients with intractable constipation following pelvic surgery. Identical and reproducible motility responses of the left colon, rectum, and anal sphincters were obtained by sequential electrical stimulation of anterior sacral roots S2, S3, and S4 in patients with spinal injury. S2 stimulation provoked isolated low-pressure colorectal contractions. S3 stimulation initiated frequency-dependent high-pressure colorectal motor activity which appeared peristaltic and was enhanced with repetitive stimuli. S4 stimulation increased colonic and rectal tone. Quantitative responses were maximal at the splenic flexure and rectum. Pelvic floor activity was stimulated in increasing magnitude from S2 to S4. These results of distal bowel motility were achieved by an implanted Brindley stimulator. A newer generation of externally active stimulators are envisaged for the control of lower bowel in fecal incontinence. Women with intractable constipation following hysterectomy had significantly increased rectal volume and compliance together with deficits of rectal sensory function. Following stimulation with Prostigmine (neostigmine) a colorectal motility gradient was paradoxically reversed in the patients following hysterectomy, thus constituting a functional obstruction. Denervation supersensitivity was demonstrable in 2 patients tested with carbachol provocation. These findings suggest dysfunction in the autonomic innervation of the hindgut in some patients following hysterectomy.

Adult↗

Automated nerve fiber counting using an array processor in a multi-minicomputer system.

It has been suggested that recovery of motor and sensory function in the site distal to a peripheral nerve lesion should be improved if the nerve bundles (fasciculi) are matched and individually sutured. Three parameters are proposed to provide quantitative data: the count of the nerve fibers that regenerate, the number of functional regenerated nerve fibers, and a measurement of end organ reinnervation. A thin cross section of a transected and repaired sciatic nerve of a mongrel cat is fixed, stained, photographed, and digitized through a microscope 6 months following nerve repair. The data arrays are then subjected to four basic processing routines: edge enhancing, thresholding, template matching, and peak detection. Finally, the peaks are counted and provide an estimate of the number of nerve fibers in the nerve under study. Comparing counts of nerve fibers proximal and distal to the transection site of the nerve provide data on the proportion of regeneration present at various times. The content of this paper is, to a large extent, describing the implementation of the needed image-processing algorithms for automated counting on the Multi-MiniComputer System (MMCS). Optimal use of the AP-120B array processor and the pipeline processing provided by using the Eclipse 200s and the Nova 3 make a marked improvement in overall throughput.

Animals↗

Rectal cancer in anorectal malformation with rectovestibular fistula: sphincter-restoring surgery by anterior resection and dynamic vaginoanograciloplasty.

PURPOSE: The aim of this study was to describe and discuss the anosphincter-restoring procedure adopted in an adult patient with rectal cancer, affected by anorectal atresia and rectovestibular fistula not previously treated. METHODS: After anterior resection and transverse dissection of the rectovaginal septum, a straight double-staple low colorectal anastomosis was performed. A subcutaneous tunnel was extended from the inter-rectovaginal space, surrounding the pseudoanal orifice. The tunnel housed a left gracilis muscle arranged counter-clockwise and connected to an implanted stimulator. The vaginal and anorectal flaps were sutured longitudinally, thereby spacing out the two orifices and creating an anorectal angle. A temporary loop right colostomy was performed. RESULTS: The postoperative course was uneventful. After continuous electrostimulation training and colostomy takedown, the patient had improved continence (stimulator on) and normal defecation (stimulator off). CONCLUSIONS: The solution described seemed a suitable alternative to a pull-through procedure, which would have involved a colocutaneous anastomosis and the loss of the anorectal sensory function. Any previous anal transposition or pull-through procedures would have prevented the saving of the pre-existing "anus," because of the interruption of the residual mesenteric vascular supply to the anorectal remnant secondary to mesorectal excision.

Aged↗

Results of neurophysiologic evaluation in fecal incontinence.

PURPOSE: Several methods of neurophysiologic assessment exist in the investigation of patients with fecal incontinence. However, the clinical significance of the information gained is uncertain. The aim of this prospective study was to evaluate the results of pudendal nerve terminal motor latency and fiber density in relation to clinical variables and manometric measurements. METHODS: Seventy-two patients with fecal incontinence (63 women; mean age, 62; range, 24-81 years) responded to a bowel questionnaire and underwent anorectal manovolumetry, anal ultrasonography, defecography, and electromyography, including pudendal nerve terminal motor latency and fiber density. RESULTS: Pudendal neuropathy (pudendal nerve terminal motor latency > 2.5 ms) was found in 46 percent and increased fiber density (> 1.7) in 82 percent. Pudendal neuropathy and increased fiber density were most common in patients with rectal prolapse or intra-anal intussusception. No difference was seen concerning anal resting and incremental pressures, rectal compliance, rectal sensibility or severity of incontinence in patients with unilateral, bilateral, or marked (> 4 ms) pudendal neuropathy vs. patients with normal pudendal nerve terminal motor latency. In contrast, patients with increased fiber density had lower incremental pressures (P < 0.05) and stated decreased rectal sensibility (P < 0.05) compared with those with normal fiber density. These differences were most pronounced in patients with neurogenic or idiopathic incontinence. CONCLUSIONS: Pudendal neuropathy and increased fiber density are common in patients with fecal incontinence. Fiber density but not pudendal nerve terminal motor latency was correlated with clinical and manometric variables. The severity of nerve injury correlated with anal motor and sensory function in patients with neurogenic or idiopathic incontinence. The routine use of pudendal nerve terminal motor latency in the assessment of patients with fecal incontinence can be questioned.

Adult↗

Increased globotriaosylceramide in familial dysautonomia.

Familial Dysautonomia (FD) is an autosomal recessive disease of unknown etiology, occurring primarily in Ashkenazi Jews. Patients are neurologically impaired, with deficits primarily in autonomic and sensory functions. The biochemical and genetic defects have remained elusive, precluding carrier detection and prenatal diagnosis. High-performance liquid chromatography data indicated up to a threefold increase in the neutral glycosphingolipid globotriaosylceramide in Dysautonomic fibroblasts and lymphoblasts. Total ganglioside values, measured by colorimetric, fluorometric or specific sodium borohydride incorporation, were decreased. Affected fibroblasts exhibited a range of pleomorphic phenotypes, such that the usual swirl-like confluent growth pattern of normal fibroblasts was distorted to varying degrees, suggesting abnormalities in the FD plasma membrane, possibly affecting cell-cell contacts. The glycosphingolipid increase could not be accounted for on the basis of markedly decreased alpha-galactosidase activity, as in Fabry's disease, where patients also display decreased autonomic function.

Cell Line↗

Decreased incorporation of D-glucosamine into glycosphingolipids of intact Familial Dysautonomia lymphoblasts.

Familial Dysautonomia (FD) is an autosomal recessive Ashkenazi Jewish genetic disease, of unknown etiology, involving deficits in both autonomic and sensory functions. Previously, we found statistically significant increases in globotriaosylceramide (Gb3) in FD fibroblasts and lymphoblasts, and a decrease in ganglioside levels. FD fibroblasts exhibited pleiomorphic changes at the light microscopy level, suggestive of changes in the plasma membrane. We described an increase in Gb3 on the surface of synchronized cells at the G1/S boundary of the cell cycle, based on Gb3-verotoxin (derived from E. coli) interactions. Using D-glucosamine-1-14C as an in vitro precursor, we herein report a marked decrease in the rate of incorporation of D-glucosamine into the sialic acid and the N-acetylgalacto/glucosamine moieties of gangliosides and neutral glycosphingolipids in intact FD compared to control lymphoblasts. The total ganglioside content of FD cells (primarily GM3, measured as incorporation of 3H from NaB3H4) was also decreased. These data indicate differences in the turnover of sialic acid and N-acetylated sugar constituents in FD vs normal cells.

Carbohydrate Conformation↗