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1.
Community Dent Health ; 39(4): 231-239, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36112474

RESUMEN

OBJECTIVES: Explore associations between modifiable maternal pregnancy exposures: pre-pregnancy body mass index (BMI), pregnancy smoking and alcohol consumption with offspring molar-incisor hypomineralisation (MIH) and use negative control analyses to explore for the presence of confounding. METHOD: Using data from a prospective UK birth cohort, Avon Longitudinal Study of Parents and Children, we performed logistic regression to explore confounder adjusted associations between maternal pre-pregnancy BMI and smoking and alcohol consumption during pregnancy with MIH. We compared these with negative control exposure (paternal BMI, smoking and alcohol) and outcome (offspring dental trauma) analyses. RESULTS: 5,536 mother/offspring pairs were included (297 (5.4%) MIH cases). We found a weak, positive association between maternal mean BMI and offspring MIH (Odds Ratio (OR) per 1-kg/m2 difference in BMI: 1.04, 95% confidence interval (CI): 1.00, 1.08). Results of subsequent analyses suggested this effect was non-linear and being driven by women in the highest BMI quintile (OR for women in the highest BMI quintile versus the lowest: 1.61 95%CI: 1.02, 2.60). Negative control analyses showed no evidence of an association between paternal BMI and offspring MIH (OR: 0.94, 95%CI: 0.89,1.00) and maternal BMI and offspring dental trauma (OR: 0.99, 95%CI: 0.96, 1.02). There was no clear evidence of an association for maternal smoking (OR: 0.76, 95%CI: 0.46,1.22) or alcohol consumption (OR: 0.79, 95%CI: 0.56, 1.21) with offspring MIH with results imprecisely estimated. CONCLUSION: We found a possible intrauterine effect for high maternal pre-pregnancy BMI on offspring MIH, but no robust evidence of an intrauterine effect for maternal pregnancy smoking or alcohol consumption. A key limitation includes possible misclassification of MIH. Replication of these results is warranted.


Asunto(s)
Hipoplasia del Esmalte Dental , Incisivo , Diente Molar , Niño , Femenino , Humanos , Embarazo , Índice de Masa Corporal , Estudios Longitudinales , Estudios Prospectivos , Hipomineralización Molar
2.
Community Dent Health ; 39(3): 197-205, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-35852216

RESUMEN

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput 'omics' technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Humanos , Incidencia , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/prevención & control , Pronóstico
4.
Tech Coloproctol ; 22(7): 545-551, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30022331

RESUMEN

BACKGROUND: Botulinum toxin injected into the internal anal sphincter is used in the treatment of chronic anal fissure but there is no standardised technique for its administration. This randomised single centre trial compares bilateral (either side of fissure) to unilateral injection. METHODS: Participants were randomised to receive bilateral (50 + 50 units) or unilateral (100 units) Dysport® injections into the internal anal sphincter in an outpatient setting. Injection-related pain assessed by visual analogue scale was the primary outcome measure. Secondary outcomes were healing rate, fissure pain, incontinence, and global health scores. RESULTS: Between October 2008 and April 2012, 100 patients with chronic anal fissure were randomised to receive bilateral or unilateral injections. Injection-related pain was comparable in both groups. There was no difference in healing rate. Initially, there was greater improvement in fissure pain in the bilateral group but at 1 year the unilateral group showed greater improvement. Cleveland Clinic Incontinence score was lower in the unilateral group in the early post-treatment period and global health assessment (EuroQol EQ-VAS) was higher in the unilateral group at 1 year. CONCLUSIONS: Injection-related pain was similar in bilateral and unilateral injection groups. Unilateral injection was as effective as bilateral injections in healing and improving fissure pain without any deterioration in continence.


Asunto(s)
Inhibidores de la Liberación de Acetilcolina/administración & dosificación , Toxinas Botulínicas Tipo A/administración & dosificación , Fisura Anal/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal , Enfermedad Crónica , Femenino , Humanos , Inyecciones/efectos adversos , Inyecciones/métodos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/etiología , Resultado del Tratamiento , Adulto Joven
5.
Colorectal Dis ; 17(11): 990-5, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25916959

RESUMEN

AIM: Sacral nerve stimulation (SNS) may be offered to patients with constipation who have failed to improve with conservative treatment. The response to SNS is variable, with a significant loss of efficacy in some patients. An increased frequency of stimulation may improve the efficacy of SNS for faecal incontinence. This study aimed to see if alteration of the pulse width or frequency improved the outcome for those with constipation. METHOD: Eleven patients with constipation currently being treated by SNS were recruited from three centres. They were randomized to five different protocols of stimulation each applied for 5 weeks. Group 1 used standard settings (pulse width 210 µs, frequency 14 Hz); in the other four groups (Groups 2-5) the pulse width and/or frequency were halved or doubled. Patients and investigators were blinded to the group allocation. RESULTS: The Cleveland Clinic constipation score varied significantly between the five groups. Group 1 achieved the lowest score mean (± SD) 13.4 (± 4.4) (P = 0.03). The number of digitations per defaecation was the lowest in Group 4, 90 µs and 14 Hz (P < 0.01). No other variable changed significantly. Standard settings were the most preferred by the recruited patients. CONCLUSION: Alteration of pulse width or frequency of stimulation had no significant effect on the outcome of SNS for constipation.


Asunto(s)
Estreñimiento/terapia , Defecación/fisiología , Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro , Calidad de Vida , Adulto , Anciano , Estreñimiento/fisiopatología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
6.
Tech Coloproctol ; 18(8): 731-7, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24952733

RESUMEN

BACKGROUND: Sacral nerve stimulation (SNS) is used as a first-line treatment for faecal incontinence when conservative measures have failed. However, one-third of patients fail to benefit from this treatment. We hypothesised that sacral afferent stimulation can be maximised using pudendal nerve stimulation (PNS) and this may be of benefit in this patient group. The aim of this study was to assess chronic PNS for those who failed to improve with SNS. METHODS: Ten patients who had failed SNS were recruited. All underwent percutaneous insertion of a stimulation lead with four-electrode array adjacent to the pudendal nerve. Continuous bipolar stimulation was administered using an external pulse generator over a 3-week period. Those who experienced a ≥50% reduction in the frequency of incontinent episodes over this period proceeded to chronic stimulation with an implantable pulse generator. RESULTS: Five patients experienced a ≥50% reduction of incontinent episodes during test stimulation and proceeded to chronic stimulation. In these five patients, at a median (range) follow-up of 24 (6-36) months, the median (inter quartile range) frequency of incontinent episodes reduced from 5 (18.25) to 2.5 (3) per week (p = 0.043). Three patients maintained a ≥50% improvement in soiling. There was an improvement in the St Mark's continence Score from 19 (15-24) to 16 (13-19), p = 0.042. There were no significant changes in ability to defer defecation or in quality of life scores. CONCLUSIONS: Pudendal nerve stimulation failed to improve the symptoms in the majority of patient who had failed SNS. Only a third experienced any improvement.


Asunto(s)
Canal Anal/inervación , Defecación/fisiología , Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Adolescente , Adulto , Anciano , Canal Anal/fisiopatología , Incontinencia Fecal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Plexo Lumbosacro , Masculino , Persona de Mediana Edad , Proyectos Piloto , Nervio Pudendo , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto Joven
7.
Br J Surg ; 100(2): 174-81, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23124687

RESUMEN

BACKGROUND: For over 10 years sacral nerve stimulation (SNS) has been used for patients with constipation resistant to conservative treatment. A review of the literature is presented. METHODS: PubMed, MEDLINE and Embase databases were searched for studies demonstrating the use of SNS for the treatment of constipation. RESULTS: Thirteen studies have been published describing the results of SNS for chronic constipation. Of these, three were in children and ten in adults. Test stimulation was successful in 42-100 per cent of patients. In those who proceeded to permanent SNS, up to 87 per cent showed an improvement in symptoms at a median follow-up of 28 months. The success of stimulation varied depending on the outcome measure being used. Symptom improvement correlated with improvement in quality of life and patient satisfaction scores. CONCLUSION: SNS appears to be an effective treatment for constipation, but this needs to be confirmed in larger prospective studies with longer follow-up. Improved outcome measures need to be adopted given the multiple symptoms that constipation may be associated with. Comparison with other established surgical therapies also needs consideration.


Asunto(s)
Estreñimiento/terapia , Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro , Adolescente , Adulto , Niño , Enfermedad Crónica , Femenino , Humanos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento
8.
Br J Surg ; 100(3): 330-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23300071

RESUMEN

BACKGROUND: Percutaneous, transcutaneous and sham transcutaneous posterior tibial nerve stimulation was compared in a prospective blinded randomized placebo-controlled trial. METHODS: Patients who had failed conservative treatment for faecal incontinence were randomized to one of three groups: group 1, percutaneous; group 2, transcutaneous; group 3, sham transcutaneous. Patients in groups 1 and 2 received 30-min sessions of posterior tibial nerve stimulation twice weekly for 6 weeks. In group 3, transcutaneous electrodes were placed in position but no stimulation was delivered. Symptoms were measured at baseline and after 6 weeks using a bowel habit diary and St Mark's continence score. Response to treatment was defined as a reduction of at least 50 per cent in weekly episodes of faecal incontinence compared with baseline. RESULTS: Thirty patients (28 women) were enrolled. Nine of 11 patients in group 1, five of 11 in group 2 and one of eight in group 3 had a reduction of at least 50 per cent in weekly episodes of faecal incontinence at the end of the 6-week study phase (P = 0·035). Patients undergoing percutaneous nerve stimulation had a greater reduction in the number of incontinence episodes and were able to defer defaecation for a longer interval than those undergoing transcutaneous and sham stimulation. These improvements were maintained over a 6-month follow-up period. CONCLUSION: Posterior tibial nerve stimulation has short-term benefits in treating faecal incontinence. Percutaneous therapy appears to have superior efficacy to stimulation applied by the transcutaneous route. REGISTRATION NUMBER: NCT00530933 (http://www.clinicaltrials.gov).


Asunto(s)
Incontinencia Fecal/terapia , Nervio Tibial , Estimulación Eléctrica Transcutánea del Nervio/métodos , Canal Anal/fisiología , Análisis de Varianza , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Presión , Estudios Prospectivos , Calidad de Vida , Recto/fisiología , Método Simple Ciego , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Resultado del Tratamiento
9.
Colorectal Dis ; 15(5): 519-26, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23216902

RESUMEN

AIM: This review aimed to assess the published results of posterior tibial nerve stimulation (PTNS) for faecal incontinence. METHOD: A search was performed of PubMed, MEDLINE and Embase to identify studies describing the clinical outcome of PTNS for faecal incontinence. RESULTS: Thirteen studies were identified. These described the outcome of PTNS for faecal incontinence in 273 patients. Four described transcutaneous PTNS, eight percutaneous PTNS and one compared both methods of PTNS with a sham transcutaneous group. One investigated patients with faecal incontinence and spinal cord injury and another with inflammatory bowel disease. There was marked heterogeneity of the treatment regimens and of the end points used. All reported that PTNS improved faecal incontinence. A > 50% improvement was reported in episodes of faecal incontinence in 63-82% of patients. An improvement was seen in urgency (1-5 min). Improvement was also described in the Cleveland Clinic faecal incontinence score in eight studies. Patients with urge and mixed incontinence appear to benefit more than those with passive incontinence. Treatment regimens ranged in duration from 1-3 months. A residual therapeutic effect is seen after completion of treatment. Follow-up ranged from 1-30 months. CONCLUSION: PTNS is effective for faecal incontinence. However, many of the published studies are of poor quality. Comparison between studies is difficult owing to differences in the outcome measures used, technique of PTNS and the timing and duration of treatment.


Asunto(s)
Terapia por Estimulación Eléctrica , Incontinencia Fecal/terapia , Nervio Tibial , Terapia por Estimulación Eléctrica/métodos , Humanos
10.
Colorectal Dis ; 15(12): 1504-9, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24118972

RESUMEN

AIM: Posterior tibial nerve stimulation (PTNS) has been shown to improve faecal incontinence in the short term. The optimal treatment regimen is unclear with wide variations in protocol reported in the literature. The study aimed to assess two different regimens of transcutaneous PTNS and to establish whether increasing the frequency of stimulation increases the effectiveness. METHOD: Thirty patients were randomized to receive once daily or twice weekly PTNS for a 6-week period. The treatment was carried out by the patient at home after instruction. The primary investigator was blinded to the patient allocation until the study had ended, at which point the symptoms were assessed. No further stimulation was given after 6 weeks and the patients were followed until their symptoms returned to the pre-stimulation state (baseline). The primary outcome measure was a change in the frequency of incontinent episodes. RESULTS: Three patients in the daily group and none in the twice weekly group achieved complete continence. Only patients from the daily group showed a significant reduction in median (interquartile range) incontinent episodes per week from 5 (11.13) to 3.5 (4.31) (P = 0.025). There was no significant change in the frequency of defaecation nor in the ability to defer defaecation. Patients in the daily group experienced a significant improvement in the domains of lifestyle [2.2 (1.7) to 2.6 (1.65), P = 0.04] and embarrassment [1.7 (0.85) to 2.15 (0.4), P = 0.04] on the Rockwood Fecal Incontinence Quality of Life assessment. No adverse events were reported. CONCLUSION: Transcutaneous PTNS can safely be used by the patient at home. Daily treatment may be more effective than twice weekly treatment. Larger studies are needed to investigate this further.


Asunto(s)
Incontinencia Fecal/terapia , Nervio Tibial , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , Resultado del Tratamiento , Adulto Joven
11.
Colorectal Dis ; 15(9): 1140-4, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23692279

RESUMEN

AIM: Chronic idiopathic anal pain is a common condition of unknown aetiology. Patients may have co-existing psychiatric disorders and existing treatments are often ineffective. A small number of published case reports suggest that sacral nerve stimulation (SNS) could treat this condition. This pilot study aimed to investigate the efficacy of SNS for the treatment of chronic anal pain. METHOD: Ten patients with chronic idiopathic anal pain were recruited. All had failed to respond to conservative treatments. Clinical and psychological evaluation was performed in all patients prior to SNS. Temporary stimulation of the S3 foramina was performed for 3 weeks and outcome assessed by comparison of a pain score diary and visual analogue score obtained during stimulation and at baseline. Primary outcome was defined as a > 50% reduction in pain score. RESULTS: Of the 10 patients recruited, five were found to have clinical depression. Four patients withdrew from the study prior to testing and six underwent peripheral nerve evaluation (PNE). Three patients had > 50% reduction in pain score and progressed to permanent SNS. Of these, only one had good pain control at latest follow-up of 5 years; the remaining two patients obtained no benefit and had their devices removed or deactivated. These two patients both had depression that was also not improved by SNS. CONCLUSION: This study would suggest that SNS is not an effective treatment for chronic anal pain in the majority of patients. PNE is not an effective means of identifying which of these patients are likely to respond to permanent SNS.


Asunto(s)
Canal Anal/inervación , Enfermedades del Ano/terapia , Dolor Crónico/terapia , Terapia por Estimulación Eléctrica/métodos , Plexo Lumbosacro , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor , Proyectos Piloto , Resultado del Tratamiento
12.
Br J Surg ; 99(10): 1445-52, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22961528

RESUMEN

BACKGROUND: Sacral nerve stimulation is an established treatment for faecal incontinence. Nearly half of all patients experience loss of efficacy at some point. Standard reprogramming restores efficacy for some, but not all, patients. This study aimed to determine whether alternative stimulator settings would increase treatment efficacy. METHODS: Patients with sustained loss of efficacy were recruited from two international specialist centres. A number of alternative stimulation parameters were tested using a double-blind randomized crossover study design. Stimulation settings tested were pulse frequencies of 6.9 and 31 Hz, and pulse widths of 90 and 330 µs, compared with one standard setting of 14 Hz/210 µs. Treatment efficacy was evaluated using a disease-specific quality-of-life score (Fecal Incontinence Quality of Life Scale, FIQLS) and a bowel habit diary completed before randomization, during the study period and after 3 months of follow-up with one preferred setting. RESULTS: Fifteen patients were analysed. With one preferred setting, three of four subdomains in the FIQLS improved significantly. The mean(s.d.) total number of incontinence episodes dropped from 11.7(10.8) to 4.8(4.5) per 3 weeks (P = 0.011) and improvements were maintained after 3 months of follow-up. Optimal pacemaker settings were individual, but a trend towards highest patient satisfaction and improved treatment outcome was evident for high-frequency stimulation (31 Hz/210 µs), which was preferred by eight of the 15 patients. CONCLUSION: Patients experiencing loss of efficacy can experience improvement if alternative pacemaker settings are tested. High-frequency stimulation (31 Hz/210 µs) was preferred by more than half of the patients, and improved treatment outcome was sustained at 3 months.


Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Estudios Cruzados , Método Doble Ciego , Incontinencia Fecal/fisiopatología , Incontinencia Fecal/psicología , Estudios de Seguimiento , Humanos , Registros Médicos , Persona de Mediana Edad , Prioridad del Paciente , Presión , Calidad de Vida , Resultado del Tratamiento
13.
Colorectal Dis ; 14(1): 98-103, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21054744

RESUMEN

AIM: Pudendal nerve stimulation (PNS), which is an alternative to sacral nerve stimulation, requires neurophysiological confirmation of correct siting of the electrode. We describe a modification of the existing technique where placement is assisted by guidance to the ischial spine by a finger introduced per anum. METHOD: Cadaveric dissection was carried out to confirm the accuracy of this new approach. The surface marking of the ischial spine is marked. A stimulating needle electrode inserted through a skin incision at this point, is advanced towards the ischial spine using a finger introduced per anum as a guide. Once effective stimulation of the pudendal nerve is confirmed by observed and palpated contraction of the anal musculature, a permanent stimulating electrode is inserted and the position confirmed by radiological screening. RESULTS: Using cadaveric studies, the correct surface markings for needle placement were confirmed. This technique was then applied successfully for in vivo insertion of the needle electrode in 20 patients with bowel dysfunction, with only one lead displacement occurring over a mean follow-up period of 12 months. CONCLUSION: Finger-guided assistance of PNS electrode insertion is simple and reproducible without requiring neurophysiological confirmation of nerve stimulation to ensure correct lead location.


Asunto(s)
Estreñimiento/terapia , Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Nervio Pudendo/fisiología , Cadáver , Estreñimiento/fisiopatología , Electrodos Implantados , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nervio Pudendo/anatomía & histología , Resultado del Tratamiento
14.
J Dent Res ; 101(12): 1526-1536, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35771046

RESUMEN

Dental care-related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah's Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment-specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.


Asunto(s)
Ansiedad al Tratamiento Odontológico , Calidad de Vida , Ansiedad al Tratamiento Odontológico/genética , Ansiedad al Tratamiento Odontológico/psicología , Estudio de Asociación del Genoma Completo , Estudios Longitudinales , Neurotensina , Humanos , Adolescente , Adulto
15.
Clin Genet ; 79(6): 554-60, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20636395

RESUMEN

Familial gastrointestinal stromal tumours (GISTs) are rare but otherwise well-characterized tumour syndromes, most commonly occurring on a background of germline-activating mutations in the tyrosine kinase receptor c-KIT. The associated clinical spectrum reflects the constitutive activation of this gene product across a number of cell lines, generating gain-of-function phenotypes in interstitial cells of Cajal (GIST and dysphagia), mast cells (mastocytosis) and melanocytes (hyperpigmentation). We report a three-generation kindred harbouring a c-KIT germline-activating mutation resulting in multifocal GISTs, dysphagia and a complex melanocyte hyperpigmentation and hypopigmentation disorder, the latter with features typical of those observed in Waardenburg type 2 syndrome (WS2F). Sequencing of genes known to be causative for WS [microphthalmia transcription factor (MITF), Pax3, Sox10, SNAI2 ] failed to show any candidate mutations to explain this complex cutaneous depigmentation phenotype. Our case report conclusively expands the clinical spectrum of familial GISTs and shows a hitherto unrecognized link to WS. Possible mechanisms responsible for this novel cause of WS2F will be discussed.


Asunto(s)
Tumores del Estroma Gastrointestinal/genética , Síndromes Neoplásicos Hereditarios/genética , Síndrome de Waardenburg/genética , Alelos , Trastornos de Deglución/genética , Trastornos de Deglución/patología , Tumores del Estroma Gastrointestinal/patología , Mutación de Línea Germinal , Humanos , Hiperplasia , Células Intersticiales de Cajal/patología , Masculino , Persona de Mediana Edad , Mutación Missense , Plexo Mientérico/patología , Síndromes Neoplásicos Hereditarios/patología , Linaje , Fenotipo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Análisis de Secuencia de ADN , Síndrome de Waardenburg/patología
16.
Colorectal Dis ; 13 Suppl 2: 23-8, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21284799

RESUMEN

AIM: The aim of this article was to determine the effect of sacral nerve stimulation (SNS) on the treatment of faecal incontinence, constipation, irritable bowel syndrome, mixed urinary and bowel disorders, spinal injury and neurodegenerative disease, pain syndromes, and sexual dysfunction. METHOD: A Medline search was performed including the keywords and/or MeSH headings of 'sacral nerve stimulation', 'neuromodulation', 'artificial pacemaker', 'faecal incontinence', 'constipation' and 'anal pain'. Further studies were identified by cross-referencing from relevant articles and by appraisal of recent peer-reviewed conference abstracts and proceedings. RESULTS: SNS has been used for the treatment of urinary, bowel and sexual dysfunction, as well as pain resulting from such disorders, and dysfunction arising from nerve injury and degenerative disease. There is a paucity of high quality evidence to support the use of SNS for the majority of novel indications at present. CONCLUSION: Good quality prospective, cross-over studies are required to determine the true benefits of SNS. Further research into patient selection, operative technique and stimulation parameters for existing indications will ensure a place for SNS in the future treatment algorithm of functional pelvic floor disorders.


Asunto(s)
Estreñimiento/terapia , Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Plexo Lumbosacro , Incontinencia Urinaria/terapia , Humanos , Pronóstico , Resultado del Tratamiento
17.
Colorectal Dis ; 13(9): 1030-4, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20718837

RESUMEN

AIM: Sacral nerve stimulation (SNS) is considered a first-line surgical treatment option for faecal incontinence. There is little information on long-term results. The results of SNS for faecal incontinence performed at a single centre over a 10-year period are reported. METHOD: A cohort analysis of consecutive patients treated with SNS for faecal incontinence over a 10-year period was carried out. Data were collected prospectively using bowel habit diaries and St Mark's and Cleveland Clinic incontinence scores. Treatment success was defined as a >50% reduction in episodes of faecal incontinence compared with baseline. RESULTS: Temporary SNS was performed in 118 patients, and 91 (77%) were considered suitable for chronic stimulation. The median period of follow up was 22 (1-138) months. Seventy patients were followed for 1 year with success in 63 (90%). Of 18 patients followed for 5 years, 15 (83%) reported continued success, 11 (61%) maintained full efficacy, 4 (22%) reported some loss, and 3 (17%) reported complete loss. Three patients with a 10-year follow up had no loss in efficacy. Overall, complete loss of efficacy was observed in 14 (16%) patients at a median of 11.5 months following implantation. A further 5 (6%) patients showed deterioration with time. In 9 (47%), no reason for the deterioration in symptoms could be identified. CONCLUSIONS: SNS can be effective for up to 10 years. Some patients experience deterioration in symptoms over time. The reasons for this are often not evident.


Asunto(s)
Canal Anal/inervación , Terapia por Estimulación Eléctrica , Incontinencia Fecal/terapia , Canal Anal/fisiopatología , Estudios de Cohortes , Incontinencia Fecal/fisiopatología , Estudios de Seguimiento , Humanos , Plexo Lumbosacro , Factores de Tiempo , Resultado del Tratamiento
18.
Colorectal Dis ; 13(8): e196-202, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21689329

RESUMEN

AIM: A knowledge of the principles of neurostimulation is essential to achieve optimal efficacy and minimize adverse effects. The aim of this article was to review the current evidence regarding device programming in the management of patients having sacral nerve stimulation (SNS) for faecal incontinence. METHOD: A Medline search was performed including the keywords and/or MeSH headings of sacral nerve stimulation, neuromodulation, artificial pacemaker, faecal incontinence, programming, adverse effects and complications. Further studies were identified by cross-referencing from relevant articles and by appraisal of recent peer-reviewed conference abstracts and proceedings. RESULTS: Neurostimulator programming is an important component of SNS. Efficacy can be improved or restored with reprogramming. Adverse stimulation is often reversible, and nonstimulation-related complications are correctable. A total loss of efficacy can be explained in over one-half of patients. CONCLUSION: An improved outcome of SNS can be achieved by selecting the best possible stimulation parameters individualized to each patient. Further research into the optimal settings is needed.


Asunto(s)
Canal Anal/inervación , Terapia por Estimulación Eléctrica/efectos adversos , Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados , Humanos , Plexo Lumbosacro , Reoperación
19.
Colorectal Dis ; 13(8): e187-95, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21689330

RESUMEN

AIM: Faecal incontinence is estimated to affect between 2 and 3% of Western adult populations. In recent years sacral nerve stimulation has become an important treatment modality, often as the first-line surgical therapy. The aim of this article was to review the current evidence regarding patient selection and surgical technique and to evaluate the logistics of providing a neurostimulation service. METHOD: A Medline search was performed including the keywords and/or MeSH headings of sacral nerve stimulation, neuromodulation, artificial pacemaker, faecal incontinence, patient selection, predictive factors and anal canal. Further studies were identified by cross-referencing from relevant articles and by appraisal of recent peer-reviewed conference abstracts and proceedings. RESULTS: Despite the success of sacral nerve stimulation for several pathophysiological causes of incontinence, case selection is of paramount importance. Sacral nerve stimulation should not be offered outside a multidisciplinary pelvic floor unit. Temporary evaluation using diary cards can lead to false positive and negative results. Adherence to a meticulous surgical technique, using low amplitude stimulation to guide lead placement, provides optimal clinical outcome. CONCLUSION: The short-term outcome of sacral nerve stimulation is dependent on patient factors and operative technique. Despite this, specific preoperative predictive factors of treatment success have yet to be identified.


Asunto(s)
Canal Anal/inervación , Terapia por Estimulación Eléctrica/métodos , Incontinencia Fecal/terapia , Cuidados Preoperatorios , Terapia por Estimulación Eléctrica/economía , Electrodos Implantados , Humanos , Plexo Lumbosacro , Selección de Paciente
20.
Colorectal Dis ; 12(2): 141-3, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19508525

RESUMEN

OBJECTIVE: In patients undergoing sacral nerve stimulation (SNS), a temporary percutaneous stimulation wire is often used to assess the clinical response to therapy prior to chronic stimulation. The aim of this study was to evaluate the incidence of bacterial colonization of screening wires and risk of clinical infection in patients undergoing prolonged temporary SNS screening. METHOD: Data were collected prospectively on a consecutive series of patients undergoing temporary SNS for bowel dysfunction. Procedures were performed using a standardized percutaneous technique with a single shot of either co-amoxyclav 1.2 g or cefuroxime 1.5 g given intravenously on induction. Adherent polyurethane dressings were applied to secure the wire. At the end of the screening period the wire and dressings were removed, the skin entry site was cleaned using an alcohol wipe and the wire removed via an aseptic technique. The distal tip of the wire was then cut and sent for culture. RESULTS: Thirteen wires were removed at a median of 21 (range 16-29) days following insertion. There were no signs of local or systemic infection. Seven of the thirteen wires (54%) were found to have deep bacterial colonization. The commonest organisms isolated were staphylococcus species. There was no correlation between the length of time the lead had been implanted and the incidence of bacterial colonization. CONCLUSION: Bacterial colonization of the temporary stimulation wire is common but appears to be associated with a low risk of clinical infection. A single peri-operative dose of antibiotics does not appear to prevent colonization.


Asunto(s)
Terapia por Estimulación Eléctrica/efectos adversos , Electrodos Implantados/microbiología , Contaminación de Equipos , Infecciones Estafilocócicas/diagnóstico , Canal Anal/inervación , Incontinencia Fecal/terapia , Humanos , Estudios Prospectivos
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