Asunto(s)
Leiomiosarcoma/secundario , Melanoma/secundario , Neoplasias de la Parótida/secundario , Adenoma Pleomórfico/diagnóstico , Diagnóstico Diferencial , Humanos , Neoplasias Renales/patología , Leiomiosarcoma/diagnóstico , Melanoma/diagnóstico , Neoplasias de la Parótida/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The treatment of cryptorchidism has changed, with surgery now advocated before the age of two years. Delayed treatment affects fertility, malignant potential and psychological stress. AIMS: To assess the pattern of referral of cryptorchid patients to a surgical clinic, management and follow-up. METHODS: A four-year review of 114 cryptorchid patients examined age at presentation, waiting time, timing of surgery and length of follow-up. RESULTS: The mean age at presentation to the surgical clinic was 6.7 years (neonatal to 71). The mean age at orchidopexy was 5.6 years. Seventy per cent had a surgical procedure within eight weeks of presentation to a surgeon. Seven per cent were kept under surveillance until a maximum age of three years before orchidopexy was considered. Only 29% proceeded to surgery before the age of two. Seventeen were referred to a paediatric urology unit for further management. CONCLUSIONS: Orchidopexy seems prudent between one and two years of age. Only one-quarter of patients underwent early orchidopexy. It is vital that it is detected early, by paediatricians at birth or the general practitioners (GPs) at the six-week check up. Prompt referral to a surgeon with a paediatric interest is essential in order to permit surveillance or surgery.
Asunto(s)
Criptorquidismo/cirugía , Testículo/cirugía , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Criptorquidismo/diagnóstico , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Derivación y Consulta , Testículo/patología , Factores de TiempoRESUMEN
We describe the selective non-operative management of 34 patients who had an initial diagnosis of perforated duodenal ulcer made on acute presentation between 1984-1994 in our district surgical unit. Diagnosis of the condition was made on clinical grounds with the aid of an erect chest X-ray which demonstrated pneumoperitoneum in 28 patients (82 per cent). Six patients (18 per cent) who did not respond to non-operative treatment required surgical intervention; 3 patients had an unsealed duodenal ulcer perforation; 2 had a perforated benign gastric ulcer and 1 patient had acute gangrenous cholecystitis. The overall mortality and morbidity rate was 3 per cent and 35 per cent respectively. There were no documented reperforations over a mean follow-up period of 27 months. While these figures are acceptable and comparable with operative intervention for this condition, we do however stress the labour intensive methods and close clinical monitoring that is required to avoid morbid sequelae.
Asunto(s)
Úlcera Duodenal/complicaciones , Úlcera Duodenal/terapia , Úlcera Péptica Perforada/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.
Asunto(s)
Cromosomas Humanos Par 6 , Proteínas del Ojo/genética , Degeneración Macular/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Ligamiento Genético , Marcadores Genéticos , Haplotipos , Humanos , Lactante , Escala de Lod , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaAsunto(s)
Intususcepción/cirugía , Pediatría , Estenosis Pilórica/cirugía , Infección de la Herida Quirúrgica/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Intususcepción/mortalidad , Irlanda , Masculino , Estenosis Pilórica/mortalidad , Derivación y Consulta , Estudios Retrospectivos , Infección de la Herida Quirúrgica/diagnóstico , Tasa de SupervivenciaRESUMEN
Congenital myasthenic syndromes (CMS) define a diverse group of disorders, all of which compromise neuromuscular transmission. Symptoms can be present at birth or appear during childhood, and can range in severity. Both autosomal dominant and recessive forms exist, and a number of clinical subtypes have been described. The cause of many cases of CMS has been traced to mutations in the genes for the acetylcholine receptor (AChR) subunits, previously mapped to chromosomes 2 and 17. Recently, an additional form of CMS known as familial infantile myasthenia (FIM) was linked to chromosome 17p. The gene for FIM has not yet been identified. We examined the DNA from 5 families of Iranian Jewish origin (6 affected individuals) who have been diagnosed with a phenotypically unique form of CMS. Four of the families are consanguinous, and all families originate from the same geographical region, thus it is highly likely that they would carry the same ancestral CMS mutation. We examined these families for linkage to the regions on chromosomes 2 and 17 containing the AChR subunit genes, and to the region on 17p to which FIM was localized. Our data excludes linkage to these regions, suggesting that the clinical differences seen among patients with CMS correlate with locus heterogeneity, and that a defect in a different gene is responsible for the CMS in these patients.
Asunto(s)
Heterogeneidad Genética , Enfermedades Neuromusculares/genética , Femenino , Ligamiento Genético , Haplotipos , Humanos , Masculino , Enfermedades Neuromusculares/congénito , Linaje , Fenotipo , Reacción en Cadena de la PolimerasaAsunto(s)
Cromosomas Humanos Par 16 , Distrofias Hereditarias de la Córnea/genética , Mapeo Cromosómico , Cromosomas Artificiales de Levadura , Bases de Datos Factuales , Familia , Genes Recesivos , Marcadores Genéticos , Haplotipos , Humanos , Islandia , Escala de Lod , Repeticiones de MicrosatéliteRESUMEN
BACKGROUND: Macular corneal dystrophy (MCD) is an inherited autosomal recessive disorder that has been subdivided into two primary immunophenotypes, MCD types I and II. The MCD type I gene has been localised previously to chromosome 16q22 and suggestive evidence provided that MCD type II gene is also linked to this region. Here an unusual family is reported where both MCD types I and II are found in a single sibship. METHODS: Immunoreactivity to an anti-keratan sulphate monoclonal antibody (5-D-4) was evaluated in patients' serum and in corneal tissue obtained at keratoplasty. Chromosomal haplotypes were constructed using microsatellite repeat markers spanning the region of the MCD type I locus. RESULTS: Immunological studies demonstrated that two of the affected siblings have MCD type II while one has MCD type I. Haplotype analysis suggests that all three affected sibs inherited one identical parental haplotype. However, the two MCD types differ in their alternative chromosome with both MCD type II children sharing an identical haplotype, different from their MCD type I sibling. CONCLUSION: The findings in this study support the hypothesis that the genes for MCD types I and II co-localise to the same region of chromosome 16 and are likely to be due to allelic manifestations of the same abnormal gene.
Asunto(s)
Distrofias Hereditarias de la Córnea/genética , Haplotipos , Repeticiones de Microsatélite , Anciano , Anciano de 80 o más Años , Distrofias Hereditarias de la Córnea/clasificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Marcadores Genéticos , Humanos , Inmunofenotipificación , Sulfato de Queratano/sangre , Masculino , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, autosomal dominant disorder characterized by progressive ptosis, dysphagia, and extremity weakness. Linkage of OPMD to 14q11.2-q13 has been reported in a series of French-Canadian families. Tightly linked markers have been defined and haplotype analysis in these data show a single segregating disease chromosome throughout the OPMD French-Canadian families. We have ascertained and sampled five multigenerational outbred American OPMD families. Four of the five families have known French-Canadian ancestry while the fifth is of English/Scottish origin. Linkage analysis was performed using standard likelihood methods. A peak multipoint lod score of 6.30 was obtained for the marker MYH7.1 in the OPMD families. The English/ Scottish family exhibited a different chromosomal haplotype for the OPMD alleles than the families of French-Canadian origin. These data suggest this family may represent a second, possibly independent mutation in this disorder. Linkage was confirmed to chromosome 14q11.2-q13 with no evidence of genetic heterogeneity.
Asunto(s)
Cromosomas Humanos Par 14 , Ligamiento Genético , Distrofias Musculares/genética , Músculos Oculomotores , Músculos Faríngeos , Adulto , Edad de Inicio , Salud de la Familia , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linaje , Estados UnidosRESUMEN
PURPOSE: Age-related macular degeneration (AMD) is a genetically complex disorder. Tissue inhibitor of metalloproteinases-3 (TIMP3) on chromosome 22 has been identified as a gene that is mutated in Sosby's fundus dystrophy, an autosomal-dominant macular dystrophy that phenotypically resembles AMD. The purpose of this study was to determine whether TIMP3 is a major susceptibility gene for the AMD phenotype. METHODS: Thirty-eight multiplex families with AMD were identified in Massachusetts and North Carolina. The macular findings were graded according to a modification of the grading system used in the Age-Related Eye Disease Study, and persons with extensive intermediate drusen, any large drusen, geographic atrophy, or evidence of exudative maculopathy were coded as affected for the purpose of the analysis. Linkage analysis was performed using both model-dependent (lod score) and model-independent (sibpair) methods. For the lod score analysis, both autosomal-dominant as well as recessive low penetrance "affecteds only" analyses were examined. Three markers, D22S280, D22S529, and D225268, linked tightly and flanking the TIMP3 locus, were chosen for the analysis. Association studies were performed by examining one randomly chosen affected person per family and comparing the patients with AMD with a series of age, gender, and ethnically matched control subjects with no known history of AMD. RESULTS: Lod score analysis excluded linkage in these data for an approximately 10-cm interval surrounding the TIMP3 gene for all models tested. In addition, no significant findings were observed with either the sibpair or the association study. CONCLUSIONS: No evidence of linkage or association or both was found between AMD and TIMP3 in these 38 families. These data suggest that although clinically similar, the genetic defect in Sorsby's fundus dystrophy is of a different cause than the majority of the genetic causes of AMD.
Asunto(s)
Envejecimiento/fisiología , Mapeo Cromosómico , Degeneración Macular/genética , Proteínas/genética , Anciano , Ligamiento Genético , Haplotipos , Humanos , Escala de Lod , Linaje , Inhibidor Tisular de Metaloproteinasa-3RESUMEN
Familial spastic paraparesis (SPG) is a clinically and genetically heterogeneous group of disorders. At least three loci have been implicated in autosomal dominant pure SPG and mutations in either of two loci may cause the X-linked form. Although the penetrance is high for all forms by age 60, there is wide variation in clinical characteristics, including age of onset. Two-point and multi-point linkage analyses in nine families provided supportive evidence that the most common form of SPG is linked to chromosome 2 (SPG4). Haplotype analysis localized the critical region to a 6 cM interval between D2S392 and D2S367. By haplotype analysis, the disease in at least one family does not appear to be linked to any of the presently known SPG loci, suggesting that there is at least one additional SPG gene. Evaluation at ages of onset in 11 families gave suggestive evidence for anticipation with mean age of onset in parents (41.3 years) being older than mean age of onset in children (26.9 years; P < 0.005).
Asunto(s)
Cromosomas Humanos Par 2/genética , Paraplejía Espástica Hereditaria/genética , Edad de Inicio , Mapeo Cromosómico , Femenino , Ligamiento Genético , Marcadores Genéticos/genética , Haplotipos/genética , Humanos , Masculino , Linaje , Recombinación GenéticaRESUMEN
The Charcot-Marie-Tooth (CMT) neuropathies are a group of disorders exhibiting neurophysical, pathological and genetic heterogeneity. CMT2 is a diagnostic subtype of this group of disorders characterized by variable expression and age-of-onset and normal or slightly diminished nerve conduction velocities. Previously, linkage and heterogeneity had been reported in CMT2 with linked families localizing to chromosome 1p (CMT2A). Recently a second CMT2 locus has been described on chromosome 7 in a single large CMT2 family (CMT2D). We have performed pedigree linkage analysis on 15 CMT2 families (N = 371 individuals, 106 affected family members) and have confirmed linkage to chromosome 7. Furthermore, using both admixture and multipoint linkage analysis we show conclusive evidence for additional heterogeneity within this clinical subtype with evidence of families that exclude linkage to both the CMT2D and CMT2A regions. In addition, unlike the previous report we found no obvious consistent clinical differences between the linked family types.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Cromosomas Humanos Par 7/genética , Mapeo Cromosómico , ADN/genética , Salud de la Familia , Femenino , Heterogeneidad Genética , Ligamiento Genético , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite , LinajeRESUMEN
We examined 11 Caucasian pedigrees with autosomal dominant 'uncomplicated' familial spastic paraplegia (SPG) for linkage to the previously identified loci on chromosomes 2p, 14q and 15q. Chromosome 15q was excluded for all families. Five families showed evidence for linkage to chromosome 2p, one to chromosome 14q, and five families remained indeterminate. Homogeneity analysis of combined chromosome 2p and 14q data gave no evidence for a fourth as yet unidentified SPG locus. Recombination events reduced the chromosome 2p minimum candidate region (MCR) to a 3 cM interval between D2S352 and D2S367 and supported the previously reported 7 cM MCR for chromosome 14q. Age of onset (AO) was highly variable, indicating that subtypes of SPG are more appropriately defined on a genetic basis than by AO. Comparison of AO in parent-child pairs was suggestive of anticipation, with a median difference of 9.0 years (p<0.0001).
Asunto(s)
Cromosomas Humanos Par 2/genética , Genes Dominantes , Paraplejía/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , Mapeo Cromosómico , Cromosomas Humanos Par 14/genética , ADN/genética , Salud de la Familia , Femenino , Heterogeneidad Genética , Ligamiento Genético , Genotipo , Humanos , Lactante , Escala de Lod , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , LinajeRESUMEN
Autosomal dominant hypophosphatemic rickets (ADHR) is an inherited disorder of isolated renal phosphate wasting, the pathogenesis of which is unknown. We performed a genome-wide linkage study in a large kindred to determine the chromosome location of the ADHR gene. Two-point LOD scores indicate that the gene is linked to the markers D12S314 [Z(theta) = 3.15 at theta = 0.0], vWf [Z(theta) = 5.32 at theta = 0.0], and CD4 [Z(theta) = 3.53 at theta = 0.0]. Moreover, multilocus analysis indicates that the ADHR gene locus is located on chromosome 12p13 in the 18-cM interval between the flanking markers D12S100 and D12S397. These data are the first to establish a chromosomal location for the ADHR locus and to provide a framework map to further localize the gene. Such studies will permit ultimate identification of the ADHR gene and provide further insight into phosphate homeostasis.
Asunto(s)
Cromosomas Humanos Par 12 , Hipofosfatemia Familiar/genética , Femenino , Genes Dominantes , Ligamiento Genético , Humanos , Masculino , Repeticiones de Microsatélite , LinajeAsunto(s)
Fibromatosis Abdominal/complicaciones , Síndrome de Gardner/complicaciones , Enfermedades Peritoneales/complicaciones , Adulto , Fibromatosis Abdominal/cirugía , Síndrome de Gardner/cirugía , Humanos , Masculino , Mesenterio/patología , Mesenterio/cirugía , Enfermedades Peritoneales/cirugíaRESUMEN
One hundred and forty nine patients underwent thyroid and parathyroid surgery over a nine year period. The most common indications for surgery were the presence of a solitary thyroid nodule (56%) or the onset of pressure symptoms (30%). Carcinoma was found in 7.4% of cases. Wound complications occurred in 5%. The permanent nerve injury rate was 0.67%. The incidence of permanent hypothyroidism after surgery was 4%. No patients developed permanent hypoparathyroidism.
Asunto(s)
Evaluación de Resultado en la Atención de Salud , Enfermedades de la Tiroides/cirugía , Glándula Tiroides/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Nódulo Tiroideo/cirugía , TiroidectomíaRESUMEN
Oculopharyngeal muscular dystrophy is a late-onset, autosomally dominant disorder characterized by progressive ptosis, dysphagia, and extremity weakness. Linkage of oculopharyngeal muscular dystrophy to 14q11.2-q13 has been reported in a series of French Canadian families. Haplotype analysis in these data shows a single segregating disease chromosome, suggesting a founder effect in this population. We ascertained and sampled for linkage studies 5 multigenerational American families with oculopharyngeal muscular dystrophy. Four of the 5 families have known French Canadian ancestry while the fifth is of English/Scottish origin. A peak multipoint lod score of 6.30 was obtained for the marker MYH7.1 in the families, confirming linkage to 14q11.2-q13. The English/Scottish family exhibited a different chromosomal haplotype for the oculopharyngeal muscular dystrophy alleles than did the families of French Canadian origin. These data suggest that this family may represent a second, possibly independent mutation in this disorder.
Asunto(s)
Cromosomas Humanos Par 14 , Distrofias Musculares/genética , Edad de Inicio , Alelos , Canadá , Mapeo Cromosómico , Intervalos de Confianza , Inglaterra/etnología , Francia/etnología , Ligamiento Genético , Marcadores Genéticos , Haplotipos , Humanos , Escala de Lod , Distrofias Musculares/clasificación , Distrofias Musculares/fisiopatología , Músculos Oculomotores , Músculos Faríngeos , Escocia/etnologíaAsunto(s)
Enfermedad de Charcot-Marie-Tooth/clasificación , Enfermedad de Charcot-Marie-Tooth/genética , Neuropatías Hereditarias Sensoriales y Autónomas/clasificación , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Cromosomas Humanos Par 3/genética , Femenino , Ligamiento Genético , Neuropatías Hereditarias Sensoriales y Autónomas/diagnóstico , Humanos , Escala de Lod , MasculinoRESUMEN
Despite changes in management and the advances in therapeutics, surgeons are still required to treat the complications of peptic ulceration. A retrospective review of all open surgical interventions for complications of peptic ulcer disease between January 1983 and December 1993 was carried out. There were no exclusion criteria. Open gastric surgery accounted for 3% of all inpatient surgical procedures and 13% of all the major operations. There were 341 adult and 132 paediatric procedures performed in the 11 year period. Acute gastric procedures accounted for 34% of major gastric surgery in this district unit. 76 perforated ulcers and 39 bleeding ulcers required surgery. 38% of the patients were over 70 years. The perioperative mortality was 13.9% (4% for those under 70 years). The overall morbidity rate was 71% and procedure-related morbidity rate was 17%. Acute gastric surgery has a very high inpatient morbidity and is associated with a significant mortality particularly in elderly patients.