PubMed Health⌕ Search

Biomedical subjects

W Graf

Publications and source records attributed to W Graf.

At least 19 recordsLinked to original sources
PubMed2002

Outcome of segmental colonic resection for slow-transit constipation.

BACKGROUND: The standard surgical treatment for slow-transit constipation (STC) is subtotal colectomy and ileorectal anastomosis. A segmental resection may serve the same purpose, but with a reduced risk of side-effects such as diarrhoea or incontinence. The aim of this study was to evaluate the functional results following segmental resection in a consecutive series of patients with STC. METHODS: Selection criteria included prolonged segmental transit on oral 111In-labelled diethylene triamine penta-acetic acid scintigraphic transit study, and disabling symptoms resistant to medical therapy and treatment of outlet obstruction. Twenty-eight patients (26 women, median age 52 years) were treated with segmental resection and followed prospectively with a validated questionnaire. RESULTS: After a median of 50 (range 16-78) months, 23 patients were pleased with the outcome. The median (range) stool frequency increased from 1 (0-7) to 7 (0-63) per week (P < 0.001). The number of patients passing hard stools and straining excessively decreased (P = 0.016 and P = 0.041, respectively). The median incontinence score was unchanged. Rectal sensory thresholds were higher in patients in whom the treatment failed (P < 0.001). CONCLUSION: With a symptomatic relief comparable to that after ileorectal anastomosis and less severe side-effects, segmental colectomy may be a better alternative for selected patients with STC. Thorough preoperative evaluation is important and impaired rectal sensation may predict a poor outcome.

Adult↗
PubMed2002

Visual receptive field modulation in the lateral intraparietal area during attentive fixation and free gaze.

The receptive field (RF) of neurons recorded from the lateral intraparietal area (LIP) was quantified using a rapid, computer-driven mapping procedure. For each neuron, the RF was mapped: (1) during attentive fixation and (2) during free visual exploration. RF location, size and internal structure were modulated by the mapping context in over two-thirds of the recorded neurons. The major trend was a proportionally larger amount of neuronal visual resources allocated to central space during fixation, and an attenuated center-to-periphery gradient in the visual field representation during free gaze. A population approach shows that these spatial modulations are accompanied by changes in the signal-to-noise ratio of the information carried in the RF substructure. We related these neurophysiological observations to behavior, by comparing the characteristics of saccades elicited during fixation and free gaze. Together, the results suggest that the dynamics of LIP visual RFs may characterize both the state of engagement of attention and the power of resolution of visual analysis: during fixation, the neural population is locked in a filter state concentrating the processing resources at the fovea, while during free gaze, the population shifts to a detector state spreading the resources more evenly across the visual field.

Animals↗
PubMed2002

Modern concepts of brainstem anatomy: from extraocular motoneurons to proprioceptive pathways.

The extraocular muscles, unlike the skeletal muscles, contain non-twitch muscle fibers. Recent experiments have located the non-twitch motoneurons. They lie around the periphery of the oculomotor, trochlear and abducens nuclei, separate from the more usual twitch motoneurons that cluster within the boundaries of the classical motor nuclei. The premotor inputs to non-twitch neurons were traced by the injection of rabies virus into the distal tip of the lateral rectus muscle. Retrogradely labeled cells were found in areas associated with the neural integrator, vergence and smooth pursuit premotor areas, but not the saccadic premotor burst neurons or the direct vestibulo-ocular pathways. The rabies tracing emphasizes for the first time that the central mesencephalic reticular formation (cMRF) and the supraoculomotor area exert direct premotor control over the non-twitch motoneurons. Because the two sets of motoneurons do not receive the same afferents, they must have different functions; these are not yet clarified. These results are not compatible with the concept of a single final common pathway from motoneurons to eye muscles. Putative sensory receptors, palisade endings, are located at the tips of non-twitch muscle fibers reminiscent of an inverted muscle spindle, which would make the non-twitch motoneurons, gamma-motoneurons. We propose that twitch motoneurons are the major source of tension used for eye movements, whereas non-twitch motoneurons are more important for fine alignment of the eyes. Furthermore, the non-twitch motoneurons could be controlled through sensory feedback networks (including perhaps proprioceptive signals from the palisade endings) that are relayed through the superior colliculus and via cMRF to the non-twitch motoneurons. The clinical repercussions of these hypotheses are discussed.

Animals↗
PubMed2001

Space coding in primate posterior parietal cortex.

Neuropsychological studies of patients with lesions of right frontal (premotor) or posterior parietal cortex often show severe impairments of attentive sensorimotor behavior. Such patients frequently manifest symptoms like hemispatial neglect or extinction. Interestingly, these behavioral deficits occur across different sensory modalities and are often organized in head- or body-centered coordinates. These neuropsychological data provide evidence for the existence of a network of polymodal areas in (primate) premotor and inferior parietal cortex representing visual spatial information in a nonretinocentric frame of reference. In the monkey, a highly modular structural and functional specialization has been demonstrated especially within posterior parietal cortex. One such functionally specialized area is the ventral intraparietal area (VIP). This area is located in the fundus of the intraparietal sulcus and contains many neurons that show polymodal directionally selective discharges, i.e., these neurons respond to moving visual, tactile, vestibular, or auditory stimuli. Many of these neurons also encode sensory information from different modalities in a common, probably head-centered, frame of reference. Functional imaging data on humans reveal a network of cortical areas that respond to polymodal stimuli conveying motion information. One of these regions of activation is located in the depth of human intraparietal sulcus. Accordingly, it is suggested that this area constitutes the human equivalent of monkey area VIP. The functional role of area VIP for polymodal spatial perception in normals as well as the functional implications of lesions of area VIP in parietal patients needs to be established in further experiments.

Animals↗
PubMed2001

Representation of the visual field in the lateral intraparietal area of macaque monkeys: a quantitative receptive field analysis.

The representation of the visual field in the primate lateral intraparietal area (LIP) was examined, using a rapid, computer-driven receptive field (RF) mapping procedure. RF characteristics of single LIP neurons could thus be measured repeatedly under different behavioral conditions. Here we report data obtained using a standard ocular fixation task during which the animals were required to monitor small changes in color of the fixated target. In a first step, statistical analyses were conducted in order to establish the experimental limits of the mapping procedure on 171 LIP neurons recorded from three hemispheres of two macaque monkeys. The characteristics of the receptive fields of LIP neurons were analyzed at the single cell and at the population level. Although for many neurons the assumption of a simple two-dimensional gaussian profile with a central area of maximal excitability at the center and progressively decreasing response strength at the periphery can represent relatively accurately the spatial structure of the RF, about 19% of the cells had a markedly asymmetrical shape. At the population level, we observed, in agreement with prior studies, a systematic relation between RF size and eccentricity. However, we also found a more accentuated overrepresentation of the central visual field than had been previously reported and no marked differences between the upper and lower visual representation of space. This observation correlates with an extension of the definition of LIP from the posterior third of the lateral intraparietal sulcus to most of the middle and posterior thirds. Detailed histological analyses of the recorded hemispheres suggest that there exists, in this newly defined unitary functional cortical area, a coarse but systematic topographical organization in area LIP that supports the distinction between its dorsal and ventral regions, LIPd and LIPv, respectively. Paralleling the physiological data, the central visual field is mostly represented in the middle dorsal region and the visual periphery more ventral and posterior. An anteroposterior gradient from the lower to the upper visual field representations can also be identified. In conclusion, this study provides the basis for a reliable mapping method in awake monkeys and a reference for the organization of the properties of the visual space representation in an area LIP extended with respect to the previously described LIP and showing a relative emphasis of central visual field.

Animals↗
PubMed2001

Vestibuloocular reflex of the adult flatfish. III. A species-specific reciprocal pattern of excitation and inhibition.

In juvenile flatfish the vestibuloocular reflex (VOR) circuitry that underlies compensatory eye movements adapts to a 90 degrees relative displacement of vestibular and oculomotor reference frames during metamorphosis. VOR pathways are rearranged to allow horizontal canal-activated second-order vestibular neurons in adult flatfish to control extraocular motoneurons innervating vertical eye muscles. This study describes the anatomy and physiology of identified flatfish-specific excitatory and inhibitory vestibular pathways. In antidromically identified oculomotor and trochlear motoneurons, excitatory postsynaptic potentials (EPSPs) were elicited after electrical stimulation of the horizontal canal nerve expected to provide excitatory input. Electrotonic depolarizations (0.8-0.9 ms) preceded small amplitude (<0.5 mV) chemical EPSPs at 1.2-1.6 ms with much larger EPSPs (>1 mV) recorded around 2.5 ms. Stimulation of the opposite horizontal canal nerve produced inhibitory postsynaptic potentials (IPSPs) at a disynaptic latency of 1.6-1.8 ms that were depolarizing at membrane resting potentials around -60 mV. Injection of chloride ions increased IPSP amplitude, and current-clamp analysis showed the IPSP equilibrium potential to be near the membrane resting potential. Repeated electrical stimulation of either the excitatory or inhibitory horizontal canal vestibular nerve greatly increased the amplitude of the respective synaptic responses. These observations suggest that the large terminal arborizations of each VOR neuron imposes an electrotonic load requiring multiple action potentials to maximize synaptic efficacy. GABA antibodies labeled axons in the medial longitudinal fasciculus (MLF) some of which were hypothesized to originate from horizontal canal-activated inhibitory vestibular neurons. GABAergic terminal arborizations were distributed largely on the somata and proximal dendrites of oculomotor and trochlear motoneurons. These findings suggest that the species-specific horizontal canal inhibitory pathway exhibits similar electrophysiological and synaptic transmitter profiles as the anterior and posterior canal inhibitory projections to oculomotor and trochlear motoneurons. Electron microscopy showed axosomatic and axodendritic synaptic endings containing spheroidal synaptic vesicles to establish chemical excitatory synaptic contacts characterized by asymmetrical pre/postsynaptic membrane specializations as well as gap junctional contacts consistent with electrotonic coupling. Another type of axosomatic synaptic ending contained pleiomorphic synaptic vesicles forming chemical, presumed inhibitory, synaptic contacts on motoneurons that never included gap junctions. Altogether these data provide electrophysiological, immunohistochemical, and ultrastructural evidence for reciprocal excitatory/inhibitory organization of the novel vestibulooculomotor projections in adult flatfish. The appearance of unique second-order vestibular neurons linking the horizontal canal to vertical oculomotor neurons suggests that reciprocal excitation and inhibition are a fundamental, developmentally linked trait of compensatory eye movement circuits in vertebrates.

Abducens Nerve↗
PubMed2001

Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder.

We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5-generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition.

Adolescent↗
PubMed2000

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↗
PubMed2000

Sacculo-ocular reflex connectivity in cats.

The otolith system contributes to the vestibulo-ocular reflexes (VOR) when the head moves linearly in the horizontal plane or tilts relative to gravity. The saccules are thought to detect predominantly accelerations along the gravity vector. Otolith-induced vertical eye movements following vertical linear accelerations are attributed to the saccules. However, information on the neural circuits of the sacculo-ocular system is limited, and the effects of saccular inputs on extraocular motoneurons remain unclear. In the present study, synaptic responses to saccular-nerve stimulation were recorded intracellularly from identified motoneurons of all twelve extraocular muscles. Experiments were successfully performed in eleven cats. Individual motoneurons of the twelve extraocular muscles--the bilateral superior recti (SR), inferior recti (IR), superior obliques (SO), inferior obliques (IO), lateral recti (LR), and medial recti (MR) were identified antidromically following bipolar stimulation of their respective nerves. The saccular nerve was selectively stimulated by a pair of tungsten electrodes after removing the utricular nerve and the ampullary nerves of the semicircular canals. Stimulus intensities were determined from the stimulus-response curves of vestibular N1 field potentials in order to avoid current spread. Intracellular recordings were performed from 129 extraocular motoneurons. The majority of the neurons showed no response to saccular-nerve stimulation. In 17 (30%) of 56 extraocular motoneurons related to vertical eye movements (bilateral SR and IR), depolarizing and/or hyperpolarizing postsynaptic potentials (PSPs) were observed in response to saccular-nerve stimulation. The latencies of PSPs ranged from 2.3 to 8.9 ms, indicating that the extraocular motoneurons received neither monosynaptic nor disynaptic inputs from saccular afferents. The majority of the latencies of the depolarization, including depolarization-hyperpolarization, were in the range of 2.3-3.3 ms. Latencies of hyperpolarizations were typically longer than those of depolarizations. Only one contralateral SO motoneuron of 43 recorded oblique extraocular motoneurons (bilateral SO and IO) showed a depolarization-hyperpolarization in response to saccular-nerve stimulation at a latency of 2.5 ms. None of 30 recorded horizontal extraocular motoneurons (bilateral LR and MR) responded to stimulation of the saccular nerve. The neural linkage in the sacculo-ocular system is relatively weak in comparison to the utriculo-ocular and sacculo-collic systems, suggesting that the role of the sacculo-ocular system in stabilizing eye position may be reduced when compared with utriculo-ocular and semi-circular canal-ocular reflexes.

Animals↗
PubMed2000

Differential activity of topotecan, irinotecan and SN-38 in fresh human tumour cells but not in cell lines.

The topoisomerase I inhibitors topotecan irinotecan (CPT-11) and its metabolite SN-38 were studied in a panel of cell lines and in primary tumour cells from patients, using a non-clonogenic cytotoxicity assay. All three substances showed similar activity patterns in the panel of cell lines established to classify the drugs mechanistically. In the patient tumour cells the drugs had different effects. In haematological and ovarian cancer samples, SN-38 was much more potent than topotecan, followed by irinotecan, while in colorectal cancer samples only irinotecan showed substantial activity. This in vitro activity pattern seems to agree with clinical experiences to date. The inactivity of SN-38 in colorectal cancer suggests irinotecan may also have some other role in addition to being a prodrug to SN-38. This study raises questions as to the role and relevance of early preclinical model systems in anticancer drug development, and suggests that important information can be obtained from studies using primary cultures of human tumour cells.

Antineoplastic Agents↗
PubMed2000

Factors influencing the functional outcome of restorative proctocolectomy in ulcerative colitis.

BACKGROUND: Restorative proctocolectomy is considered to be the procedure of choice in the operative treatment of ulcerative colitis. The aim of this study was to evaluate the functional outcome following operation and to identify possible predictive factors. METHODS: Some 168 patients (median age 32 years, 102 men) with ulcerative colitis underwent restorative proctocolectomy. The functional outcome was evaluated by a symptom index created from a questionnaire at a median of 29 (13-123) months of follow-up. The records of these patients were reviewed, and preoperative, peroperative and postoperative variables were registered and related to outcome. RESULTS: The response rate to the questionnaire was 155 (92 per cent) of 168. The symptom index was related to patients' overall assessment of outcome. In spite of a perceived good result many patients experienced a number of symptoms. Age over 50 years (P < 0.01), presence of extraintestinal manifestations (P < 0.05) and late complications, such as anastomotic stricture (P < 0.05), pouchitis (P < 0.01) and anal pain (P < 0.05), were related to a less favourable outcome. CONCLUSION: While preoperative data may help in selecting patients suitable for restorative proctocolectomy, prevention of late complications seems most important in improving the functional outcome.

Adolescent↗
PubMed2000

Results of surgical treatment for faecal incontinence.

BACKGROUND: This prospective study was designed to evaluate the results of anterior levatorplasty and sphincteroplasty for faecal incontinence with respect to symptomatic and physiological outcome. METHODS: Thirty-one patients with idiopathic (neurogenic) faecal incontinence underwent anterior levatorplasty and 20 patients with traumatic anal sphincter injury underwent anal sphincteroplasty. The outcome of repair was evaluated at 3 and 12 months using a validated questionnaire and anorectal manometry/manovolumetry. RESULTS: Eighteen of 31 patients in the levatorplasty group reported continence to solid and liquid stools 1 year after operation compared with two patients before surgery (P < 0.01). The corresponding figures in the sphincteroplasty group were ten and two of 20 respectively (P < 0.05). The incontinence score was improved in both groups after 1 year, from a median score of 14 to 3 in the levatorplasty group (P < 0.001) and from 8.5 to 3.5 in the sphincteroplasty group (P < 0.01). Improvements in the degree of social and physical handicap were also observed in both groups. No changes were seen in anal canal pressures or rectal sensation in either group. CONCLUSION: Despite different aetiologies and surgical approaches, anterior levatorplasty and sphincteroplasty yielded similarly successful results in patients with faecal incontinence. Although a marked symptomatic improvement was seen in both groups, no associated physiological alterations could be detected. The reason for the improvement is thus unclear, but it may result from a stenosing effect in the anal canal.

Adult↗
PubMed1999

Eye position encoding in the macaque ventral intraparietal area (VIP).

Many neurons in area VIP encode the location of visual stimuli in a non-retinocentric frame of reference. In this context the question needed to be addressed whether the underlying coordinate transformation of the incoming visual signals could be generated within area VIP or whether this information would have to arrive from other areas. We tested 74 neurons in area VIP of two awake monkeys for an influence of eye position while animals performed a fixation task. More than half of the neurons (40/74) revealed an eye position effect. At the population level, however, this effect was balanced out. We suggest that local connections within area VIP could be used to generate an encoding of visual information in a non-retinocentric frame of reference.

Animals↗
PubMed1999

Is electrostimulation of the pelvic floor an effective treatment for neurogenic faecal incontinence?

BACKGROUND: This study was designed to evaluate the results of electrostimulation of the pelvic floor for faecal incontinence. METHODS: Twenty-four patients with neurogenic (n = 20) or idiopathic (n = 4) incontinence were treated on 12 occasions. Twenty were women, and the mean age was 63 years (range, 26-85 years). The result was evaluated at 3 and 12 months with a validated questionnaire and anorectal manometry. RESULTS: Eleven patients (46%) reported improvement after 3 months, and the Miller's incontinence score was reduced (P < 0.01). Resting pressures, rectal compliance, and the length of the high-pressure zone were unchanged, but squeeze pressures tended to decrease. A lower threshold was seen for the rectoanal inhibitory reflex (RAIR) (P < 0.01), and the saline infusion test tended to show improved retention (P = 0.07). Nine of 13 patients followed up for 1 year claimed improvement. The most pronounced subjective improvement was seen in patients with moderate incontinence. CONCLUSIONS: Electrostimulation was successful in a substantial proportion of the patients. The threshold for RAIR was lowered, and the saline infusion test tended to improve, but variables reflecting sphincter competence did not improve. Moderate incontinence was prognostically favourable, and electrostimulation might therefore be an alternative to surgery in this group.

Anal Canal↗
PubMed1999

The longitudinal high-pressure zone profile in patients with fecal incontinence.

OBJECTIVE: The aim of this study was to evaluate differences in the longitudinal high-pressure zone (HPZ) profile between incontinent patients and healthy controls. METHODS: One hundred and fifty-six patients with fecal incontinence (mean age 63 yr; 139 women, 17 men) and 25 healthy controls (mean age 54 yr; 20 women, five men) underwent anorectal manometry with a perfused catheter using a station pull-through technique. RESULTS: Maximum resting pressure (MRP) and maximum squeeze pressure (MSP) were lower in patients (p < 0.001) and the HPZ was shorter in patients (p < 0.05). The ratio MRP/sum of resting pressures within HPZ did not differ between the groups. The severity of incontinence measured as an incontinence score was correlated to MSP (p < 0.05) and sum of squeeze pressure within HPZ (p < 0.05), but not to any other variable. The relative pressure amount during rest in the distal half of HPZ was higher in controls (63% vs 56%, p < 0.05), but this was not seen during squeeze. CONCLUSIONS: These results suggest that the main difference between incontinent patients and healthy controls is a greater magnitude of the pressure profile in the latter group. Furthermore, the relative pressure accumulation during rest tended to be more distally located within the HPZ.

Adult↗
PubMed1999

Defecographic study of rectal evacuation in constipated patients and control subjects.

PURPOSE: To validate a computer-based area calculation method of quantification of rectal evacuation by using defecography videotapes and to use that method to compare evacuation in constipated patients with that in control subjects. MATERIALS AND METHODS: For validation of the method, simultaneous defecography and weight measurements were compared in 36 patients with constipation or incontinence. Evacuation was calculated as the rate of change of the contrast medium-covered rectal area (percentage per second) or of the evacuated amount of contrast medium (percentage per second [relative] and grams per second [absolute]). After method validation, from a series of 215 consecutive constipated patients, individuals with an isolated radiologic diagnosis of intussusception greater than 0.6 cm (n = 27), rectocele greater than 2 cm (n = 19), enterocele (n = 12), or paradoxic puborectal muscle contraction (n = 12) were selected. Rectal evacuation in these groups was compared with that in 30 control subjects. RESULTS: Rectal evacuation rates measured at defecography correlated well with weighed amounts of evacuated contrast medium during the initial and total evacuation periods in 21 patients without contrast medium leak (r = 0.92, P < .001). Constipation overall, a rectocele greater than 2 cm, or paradoxic puborectal muscle contraction were associated with impaired evacuation (P < .001). CONCLUSION: Area calculations of rectal evacuation reflect rectal emptying. A rectocele greater than 2 cm or a paradoxic puborectal muscle contraction may be associated with obstructed defecation.

Adult↗