We previously reported that inflammatory arthropathy resembling rheumatoid arthritis (RA) develops among transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR region of human T cell leukemia virus type I (LTR-pX-Tg mice). Because four genes are encoded in this region, we produced transgenic mice that only express the tax gene to examine its role in the development of arthritis. Transgenic mice were produced by constructing DNAs that express the tax gene alone under the control of either its own LTR or CD4 enhancer/promoter and by microinjecting them into C3H/HeN-fertilized ova. We produced seven transgenic mice carrying the LTR-tax gene and nine mice carrying the CD4-tax and found that one of the LTR-tax-Tg mice and five of CD4-tax-Tg mice developed RA-like inflammatory arthropathy similar to LTR-pX-Tg mice, indicating that the tax gene is arthritogenic. On the other hand, the other two LTR-tax-Tg mice had ankylotic changes caused by new bone formation without inflammation. In these ankylotic mice, tax mRNA, inflammatory cytokine mRNA, and autoantibody levels except for TGF-beta1 level were lower than those in LTR-pX- or CD4-tax-Tg mice. These results show that Tax is responsible for the development of inflammatory arthropathy resembling RA and that this protein also causes ankylotic arthropathy. (+info)
(2/85) Total knee arthroplasty in bony ankylosis in gross flexion.
Between June 1993 and December 1994, we performed total knee arthroplasty (TKA) on 27 knees in 24 patients with spontaneous bony ankylosis in severe flexion. The mean age at operation was 43.5 years (30 to 60). No patient had preoperative pain. Three were unable to walk and 21 could manage less than five blocks. The mean duration of the ankylosis was 18.7 years (13 to 25) and its mean position was 105 degree flexion (75 to 135). The preoperative Hospital for Special Surgery Knee Score of 60 points was improved to 87 at the final follow-up three to five years later. All knees were free from pain. The mean range of active flexion in 24 knees was 97 degrees (78 to 115) and the mean arc of movement 91 degrees (78 to 98). The mean fixed flexion deformity was 6 degrees (0 to 25) and the extension lag 8 degrees (0 to 25). Angular deformity was corrected to between 0 degrees and 10 degrees of valgus. Four patients were able to walk one block and 20 five to seven blocks. Thirteen knees (48%) showed some necrosis at the skin edge; one knee required arthrodesis and another resection arthroplasty. One had a recurrence of tuberculous infection requiring arthrodesis. One patient had a rupture of the quadriceps tendon. To date no prosthesis has required revision for loosening. Radiolucency of 1 mm or less about the tibial prosthesis was observed at follow-up in four of the 24 knees. Our results have shown that one-stage TKA and skeletal traction after operation can achieve correction of severe flexion deformity of the knee with marked improvement in the function and quality of life. (+info)
(3/85) Temporomandibular joint ankylosis: the Egyptian experience.
This is a review of 204 patients with temporomandibular joint (TMJ) ankylosis treated according to a definitive protocol in the Cranio-Maxillo-Facial Department of the Alexandria University Hospital during the period 1990-1996 with a follow-up varying from 1.5 to 7 years. A history of trauma was confirmed in 98% of cases. Patients were grouped into: (1) Those with ankylosis not associated with facial deformities. The management involves release of the ankylosed joint(s) and reconstruction of the condyle ramus unit(s) (CRUs) using costochondral graft(s) (CCGs). (2) Those with mandibular ankylosis complicated by facial bone deformities, either asymmetric or bird face. The treatment consists of release of the ankylosis, reconstruction of the CRUs, and correction of jaw deformities--all performed simultaneously. Respiratory embarrassment was an important presenting symptom in the second group, all of whom complained of night snoring, eight of whom had obstructive sleep apnoea (OSA). In this latter group, respiratory obstruction improved dramatically after surgical intervention. The degree of mouth opening, monitored as the interincisal distance (IID) improved from a range of 0-12 mm to over 30 mm in 62% of patients and to 20-30 mm in 29% of patients. However, reankylosis was still around 8% and was attributed to lack of patient compliance in 75% and to iatrogenic factors in 25% of patients. CCGs resorption, whether partial or complete, occurred in 27% of patients, resulting in retarded growth, relapse of deformities and night snoring. (+info)
(4/85) A recessive mutation leading to vertebral ankylosis in zebrafish is associated with amino acid alterations in the homologue of the human membrane-associated guanylate kinase DLG3.
We describe the characterization of the zebrafish homologue of the human gene DLG3. The zebrafish dlg3 gene encodes a membrane-associated guanylate kinase containing a single PDZ domain. This gene was cloned using a gene-trap construct inserted in the gene's first intron. The insertion co-segregates with a viable mutation called humpback (hmp), which leads to formation of ankylotic vertebrae in adult fishes. Insertion and mutation have both been mapped to chromosome 12, in a segment which is syntenic with region p12 to q12 of human chromosome 17. The hmp mutant phenotype, however, appears to be due to two point mutations in the guanylate kinase domain rather than to the transgene insertion itself. The results of this study are discussed in the light of the possible function of the guanylate kinase domain. (+info)
(5/85) Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?
The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised. (+info)
(6/85) Persistence of deciduous molars in subjects with agenesis of the second premolars.
The purpose of the present study was to investigate persistent primary second molars in a group of young people in their late twenties with agenesis of one or two second premolars. In 1982-83 it was decided, in connection with the orthodontic evaluation of 25 patients, to allow 35 primary molars (one or two in each patient) to remain in situ. All patients had mixed dentitions and agenesis of one or two premolars. The primary teeth were generally in good condition, although root resorption and infra-occlusion (compensated by occlusal composite onlays) occurred. In 1997, 18 of the 25 patients with a total of 26 retained primary molars were reexamined, comprising a clinical examination for exfoliation, extraction, loosening, and ankylosis, and a radiographic examination for root resorption, tooth morphology (crown and root), and alveolar bone contour. The examination showed that the degree of root resorption was unaltered in 20 of the 26 primary molars. In the permanent dentitions, where these primary molars persisted, there were no morphological deviations. Three of the six remaining primary molars had been extracted and three showed extensive resorption. In three of the 26 primary molars the infra-occlusion had worsened. The present study shows that persistence of primary second molars in subjects with agenesis of one or two premolars, and normal morphology of the permanent dentition can be an acceptable, semi-permanent solution for the patient. Whether this could also be an acceptable long-term solution will be shown by follow-up studies. (+info)
(7/85) Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.
Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. This constellation of clinical signs is unique, but some overlap can be recognized with other ectodermal dysplasia syndromes, for example ectrodactyly--ectodermal dysplasia--cleft lip/palate (EEC; OMIM 604292), limb--mammary syndrome (LMS; OMIM 603543), acro-dermato-ungual-lacrimal-tooth syndrome (ADULT; OMIM 103285) and recessive cleft lip/palate--ectodermal dysplasia (CLPED1; OMIM 225060). We have recently demonstrated that heterozygous mutations in the p63 gene are the major cause of EEC syndrome. Linkage studies suggest that the related LMS and ADULT syndromes are also caused by mutations in the p63 gene. Thus, it appears that p63 gene mutations have highly pleiotropic effects. We have analysed p63 in AEC syndrome patients and identified missense mutations in eight families. All mutations give rise to amino acid substitutions in the sterile alpha motif (SAM) domain, and are predicted to affect protein--protein interactions. In contrast, the vast majority of the mutations found in EEC syndrome are amino acid substitutions in the DNA-binding domain. Thus, a clear genotype--phenotype correlation can be recognized for EEC and AEC syndromes. (+info)
(8/85) The management of local complications of total hip replacement by the McKee-Farrar technique.
One thousand and forty-two McKee-Farrar prostheses of the present design inserted in Norwich from January 1965 to December 1972 have been reviewed retrospectively to determine the incidence of complications needing revision. Of prostheses implanted for more than two years, 6-6 per cent needed revision for loosening (cup 3-5 per cent; stem 2-2 per cent; both components 0-9 per cent). Of the total number, 2-3 per cent became infected and 1-9 per cent dislocated. Most dislocations needed only a single closed reduction but 0-8 per cent were revised. The outcome of revision operations was also assessed. Of revisions for loosening, 40 per cent needed no further operation but 23 per cent required excision; pelvic fracture or bone destruction around the components made success unlikely. Revisions for dislocation were disappointing. Of all revisions 17 per cent became infected. Excision arthroplasty is better than a series of failed revisions in an elderly patient. (+info)