Biomedical subjects

W Graf

Publications and source records attributed to W Graf.

At least 19 recordsLinked to original sources

PubMed2006

Randomized clinical trial of local gentamicin-collagen treatment in advancement flap repair for anal fistula.

BACKGROUND: Endoanal advancement flap repair is widely used in sphincter-preserving surgery for anal fistula, but the high recurrence rate is a major problem. A possible cause of non-healing is local infection of the flap. The aim of this study was to evaluate whether local antibiotic treatment with gentamicin-collagen improves healing after endoanal advancement flap repair for anal fistula. METHODS: Eighty-three patients (52 men and 31 women; mean age 47 (range 17-71) years) who had endoanal advancement flap repair for anal fistula between September 1998 and January 2004 were randomized to surgery with (42 patients) or without (41 patients) application of gentamicin-collagen beneath the flap. Patients were evaluated at 1-3 and 12 months after surgery for healing and/or recurrence. RESULTS: The overall healing rate with no recurrence at 1 year after surgery was 57 per cent (47 of 83). Twenty-six of 42 patients randomized to gentamicin-collagen healed primarily compared with 21 of 41 patients randomized to surgery only. There were no overall differences in healing rate according to sex, previous fistula surgery, complexity of fistula, smoking habit or body mass index. CONCLUSION: Endoanal advancement flap repair for anal fistula has a fairly high primary recurrence rate. Healing was not significantly improved by local application of gentamicin-collagen.

Adolescent↗

PubMed2006

Randomized clinical trial of the effects on anal function of Milligan-Morgan versus Ferguson haemorrhoidectomy.

BACKGROUND: Studies of haemorrhoidectomy usually report postoperative pain, healing and complications, but rarely consider anal function in the longer term. The primary aim of this randomized trial was to compare long-term changes in anal function after open (Milligan-Morgan) and closed (Ferguson) haemorrhoidectomy. METHODS: A total of 225 patients were included in the trial, 115 in the open group and 110 in the closed group. Continence changes were recorded by means of validated questions and an incontinence score. Pain was self-reported using a visual analogue scale. RESULTS: Postoperative pain and complications did not differ between the groups. Time to recovery was 17 days in the Milligan-Morgan group and 15 days in the Ferguson group. After 1 month the wounds were healed in 57.0 per cent of patients in the open group and 70.6 per cent of those in the closed group (P = 0.058). At 1 year, 78.9 per cent of the Milligan-Morgan group and 85.3 per cent of the Ferguson group reported no continence disturbance (P = 0.072). The incontinence score was improved at 1 year in the closed group (P = 0.015), but was unchanged in the open group (P = 0.645). Patients who had the Ferguson procedure were more satisfied with the outcome of surgery (P = 0.047). CONCLUSION: Closed Ferguson haemorrhoidectomy was superior to the open Milligan-Morgan procedure with respect to long-term anal continence and patient satisfaction.

Adult↗

PubMed2004

Oculomotor areas of the primate frontal lobes: a transneuronal transfer of rabies virus and [14C]-2-deoxyglucose functional imaging study.

We used the [14C]-2-deoxyglucose method to study the location and extent of primate frontal lobe areas activated for saccades and fixation and the retrograde transneuronal transfer of rabies virus to determine whether these regions are oligosynaptically connected with extraocular motoneurons. Fixation-related increases of local cerebral glucose utilization (LCGU) values were found around the fundus of the inferior limb of the arcuate sulcus (AS) just ventral to its genu, in the dorsomedial frontal cortex (DMFC), cingulate cortex, and orbitofrontal cortex. Significant increases of LCGU values were found in and around both banks of the AS, DMFC, and caudal principal, cingulate, and orbitofrontal cortices of monkeys executing visually guided saccades. All of these areas are oligosynaptically connected to extraocular motoneurons, as shown by the presence of retrogradely transneuronally labeled cells after injection of rabies virus in the lateral rectus muscle. Our data demonstrate that the arcuate oculomotor cortex occupies a region considerably larger than the classic, electrical stimulation-defined, frontal eye field. Besides a large part of the anterior bank of the AS, it includes the caudal prearcuate convexity and part of the premotor cortex in the posterior bank of the AS. They also demonstrate that the oculomotor DMFC occupies a small area straddling the ridge of the brain medial to the superior ramus of the AS. Our results support the notion that a network of several interconnected frontal lobe regions is activated during rapid, visually guided eye movements and that their output is conveyed in parallel to subcortical structures projecting to extraocular motoneurons.

Animals↗

PubMed2004

Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study.

Patients with peritoneal or local metastases from colorectal cancer have a poor prognosis. However, aggressive treatments by debulking surgery and infusional intraperitoneal (i.p.) chemotherapy have been tried and appear to benefit selected patients. We assayed the effects of debulking surgery and i.p. chemotherapy with respect to survival and compared the results with matched control patients treated by intravenous (i.v.) chemotherapy. In all, 18 patients with peritoneal and/or local metastases from colorectal adenocarcinoma underwent debulking surgery followed by 5-fluorouracil (5-FU) 550 mg m(-2) day(-1) i.p. and leucovorin (LV) 60 mg m(-2) day(-1) i.v. The chemotherapy was started the day after surgery and was given daily for 6 days and repeated monthly for totally eight courses. The control patients, matched for age, gender, performance status and metastatic site, were randomly selected from controlled clinical chemotherapy trials and treated with i.v. 5-FU+LV or i.v. methotrexate+5-FU+LV. There was no treatment-related mortality. The median survival among i.p. patients was 32 months compared to 14 months in the control group. In all, 11 patients who underwent macroscopically radical surgery had a longer survival than those who were not radically operated (P=0.02). These results indicate that patients with peritoneal metastases and/or locally advanced cancers but without distant metastases may benefit from cytoreductive surgery combined with i.p. chemotherapy.

Adenocarcinoma↗

PubMed2004

Randomized clinical trial comparing conservative and surgical treatment of neurogenic faecal incontinence.

BACKGROUND: The treatment of choice in idiopathic (neurogenic) faecal incontinence is controversial. In a randomized study levatorplasty was compared with anal plug electrostimulation of the pelvic floor with respect to functional outcome and physiological variables. METHODS: Thirty-one patients underwent levatorplasty and 28 anal plug electrostimulation of the pelvic floor over 3 years. The results were evaluated at 3, 12 and 24 months after completion of treatment by means of a validated questionnaire and anorectal manometry and manovolumetry. RESULTS: Incontinence scores were significantly reduced during the entire observation period in both groups (P < 0.001) as was the use of pads (P = 0.003 to P < 0.001). The proportion of patients reporting improvement in physical and social handicap was greater in the levatorplasty group after 3, 12 and 24 months (P = 0.036 to P < 0.001). No significant changes in physiological variables were observed in either group. CONCLUSION: Better results were obtained with levatorplasty than with anal plug electrostimulation of the pelvic floor in patients with idiopathic (neurogenic) faecal incontinence. Levatorplasty should be therefore be considered the treatment of choice for this condition.

Adult↗

PubMed2004

Uptake of 5-fluorouracil (5-FU) in peritoneal metastases in relation to the route of drug administration and tumour debulking surgery. an autoradiographic study in the rat.

Patients with peritoneal metastases from colorectal cancer have a poor prognosis. Aggressive treatment by debulking surgery and intraperitoneal (i.p.) chemotherapy has been suggested as an alternative therapy. However, the drug penetrance into the tumour in relation to the administration route and surgical reduction of the tumour is not well known. We compared locoregional administration with intravenous (i.v.) injection. Thirty-four in-bred rats with peritoneal metastases were randomly allocated into eight groups and injected with 14C-labelled 5-fluorouracil (5-FU) either through the i.v. or i.p. route, with or without a preceding tumour debulking, and were sacrificed after 2 or 8 h. Tumour radioactivity was visualised by autoradiography and quantified by a computer-based image analysis. After 8 h, 19 debulked and i.p.-injected tumours had a higher drug uptake, 63.2+/-28 (mean+/-standard deviation (SD)) kBq/g than 62 native i.p.-injected tumours (32.8+/-14) or 22 debulked and i.v.-injected tumours (18.5+/-18, P=0.002). After 8 h, 9 small tumours ( /=median 571 pixels), 16 debulked and i.p.-injected tumours had a higher radioactivity (drug uptake) (150.7+/-63) at 2 h than 49 i.p.-injected native tumours (48.5+/-59) or 11 reduced and i.v.-injected tumours (19.9+/-13, P=0.03). At 8 h, 10 debulked and i.p.-injected tumours had a higher drug uptake (50.3+/-24) than 33 native and i.p.-injected (30.8+/-10) or 14 debulked and i.v.-injected tumours (16.0+/-19, P=0.001). These results indicate that a debulking procedure and locoregional treatment of peritoneal metastases is associated with an increased level of 5-FU in the tumours.

Adenocarcinoma↗

PubMed2004

Transanal endoscopic microsurgery: clinical and functional results.

OBJECTIVE: Transanal endoscopic microsurgery (TEM) has become increasingly common in the management of rectal adenomas and also in selected cases of rectal carcinomas. The aim of this study was to assess the results in a consecutive series of patients after introducing the TEM technique. PATIENTS AND METHODS: All 58 patients operated with TEM from January 1996 to January 1999 were evaluated in a retrospective review. Forty-eight patients answered a clinically validated questionnaire a median of 22 months after TEM. Eighty patients who had undergone transanal excision and 12 who had undergone York Mason's procedure served as a reference group with respect to recurrence rates. RESULTS: The complication rate was 5% (immediate) and 14% (long-term). The overall 30-day mortality rate was zero. An impairment of continence was seen in 18 (37%) patients. Of these, all 18 experienced varying degree of incontinence to liquid stool, 14 also to flatus and 5 of them even to solid stool. The recurrence rate was 11% in adenomas and 14% in cancers; T1, 1 (10%) recurrence and T2, 1 (50%) recurrence. There was a correlation between operating time and impairment of continence as well as recurrence rate. CONCLUSION: TEM is a safe procedure, having a low recurrence rate and an acceptable functional outcome.

Adenocarcinoma↗

PubMed2004

Anorectal physiology in relation to clinical subgroups of patients with severe constipation.

OBJECTIVE: The aim of this study was to evaluate anorectal physiology in relation to clinically defined subgroups of patients with idiopathic constipation and to analyse relationships between anorectal physiology and rectal evacuation. SUBJECTS AND METHODS: One hundred consecutive patients with idiopathic constipation were clinically categorized as slow transit (n=19), outlet obstruction (n=52) and a group with mixed symptoms (n=29). They were examined by recording anal pressures and also rectal volumes in response to stepwise increases in rectal pressure (5-60 cm H2O). The manovolumetric results were compared with 28 sex and aged matched controls. Rectal evacuation was measured by computer-based image analysis of rectal emptying rate in defaecography. RESULTS: The rectal pressure thresholds for filling, urge and pain did not differ between the groups but there were proportionally more patients in the slow transit and mixed group with thresholds for filling exceeding 25 cm H2O (P=0.04). In total, 18% of patients had impaired sensitivity which was associated with long duration of symptoms (P < 0.05). Patients with grossly impaired rectal sensitivity (filling threshold > 40 cm H2O) had impaired rectal evacuation (P < 0.05). The rectal compliance was increased in the slow transit and mixed group (P < 0.01-0.05) in the pressure interval 5-15 cm H2O. Anal resting and squeeze pressures did not differ between the groups although 7/19 in the slow transit group had values around the lower limit of controls. Slow wave frequency was lower in all patient groups (P < 0.001 vs. controls). Rectal evacuation was not related to sphincter function or to rectal compliance. CONCLUSIONS: Clinical categorization of constipated patients defines groups where altered anorectal physiology is not uncommon. Constipation with symptoms of infrequent defaecation may be associated with impaired rectal sensitivity and increased rectal compliance whereas outlet obstruction symptoms are not clearly related to changes in anorectal physiology.

Adult↗

PubMed2004

Scintigraphic assessment of slow transit constipation with special reference to right- or left-sided colonic delay.

OBJECTIVE: Subtotal colectomy and ileorectal anastomosis for slow transit constipation has several side-effects. The motor abnormality in some patients may be segmental which could motivate a limited resection of the colon. Therefore a diagnostic tool to identify a segmental colonic motor dysfunction is needed. The aim of this study was to evaluate a scintigraphic method to assess colonic transit with special reference to right- or left-sided delay. METHODS: Twenty-three constipated patients (19 women, mean age 50 years) with slow colonic transit on radio-opaque marker studies and 13 healthy individuals (11 women, mean age 46 years) were studied. All subjects were examined with oral (111)Indium-DTPA scintigraphy. The scintigraphic results for patients and controls were presented as geometric centre of radioactivity and percent activity over time in the right, the left and the recto-sigmoid colon. The inter-observer variation in the interpretation of the scans was also evaluated. RESULTS: There was no difference in transit time between the groups of patients and controls in the right colon whereas the patients had a significant delay in the left colon (P < 0.05). Two patients had a marked delay in the right colon followed by relatively rapid transit in the left colon. The inter-observer correlation was good comparing the right, the left and the recto-sigmoid colon (r = 0.58-0.98, P < 0.01-0.001). CONCLUSION: The results indicate that colonic scintigraphy with oral (111)Indium-DTPA may help to select patients for a left or, in a few cases, a right hemicolectomy for slow transit constipation.

Adult↗

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

Endoanal ultrasound or magnetic resonance imaging for preoperative assessment of anal fistula: a comparative study.

OBJECTIVE: To compare endoanal ultrasound (EUS) with a 10-MHz probe vs. bodycoil magnetic resonance imaging (MRI) in the preoperative evaluation of anal fistula. SUBJECTS AND METHODS: 23 patients with fistula in the anal region underwent preoperative 0.5 T bodycoil MRI and 10 MHz EUS which included probing in 6 patients. The results of the EUS and MRI were compared against the surgical findings as a reference method. RESULTS: In classification of the primary tract there was agreement between EUS and surgical findings in 14 (61%) and between MRI and surgery in 11 (48%). Concerning the presence of an internal opening the corresponding figures were 17 (74%) and 10 (43%) and in judging the presence of an extension or an abscess 15 (65%) vs. 11 (48%), respectively. In three out of eight patients with nonhealing or recurrence after surgery preoperative imaging had shown an extension and/or an abscess that was not identified by the surgeon. CONCLUSION: EUS, sometimes complemented with probing, is well comparable to bodycoil MRI in classifying and describing the topography of an anal fistula.

Journal Article↗

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↗