The frequency of Fabry disease with the E66Q variant in the α-galactosidase A gene in Japanese dialysis patients: a case report and a literature review.

Fabry disease (FD) is an Xlinked disorder resulting in a deficiency in α-galactosidase A (α-Gal) activity. FD is one of the causes of progressive renal dysfunction, but its diagnosis is often delayed or missed completely. We herein report the case of a 70-year-old male who had been receiving hemodialysis (HD) for 23 y who was diagnosed with FD after his participation in a screening program for plasma α-Gal activity for 892 HD patients. He had a low plasma α-Gal activity level and was demonstrated to have an E66Q mutation in exon 2 of the α-Gal gene. One of his daughters had the same mutation. The proband died due to aspiration pneumonia before receiving enzyme replacement therapy. We reviewed previous studies and found E66Q mutation in 36% of Japanese FD patients on HD including the present case. The clinical characteristics of E66Q variant are also discussed.

Surface grafting of biocompatible phospholipid polymer MPC provides wear resistance of tibial polyethylene insert in artificial knee joints.

OBJECTIVE: Aseptic loosening of artificial knee joints induced by wear particles from a tibial polyethylene (PE) insert is a serious problem limiting their longevity. This study investigated the effects of grafting with our original biocompatible phospholipid polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) on the insert surface. METHODS: The hydrophilicity of the PE surface was determined by the contact angle of a water droplet, and the friction torque was measured against a cobalt-chromium alloy component. The wear amount was compared among PE inserts with or without cross-linking and MPC grafting during 5x10(6) cycles of loading in a knee joint simulator. The surfaces of the insert and the wear particles in the lubricant were subjected to electron and laser microscopic analyses. The mechanical properties of the inserts were evaluated by the small punch test. RESULTS: The MPC grafting increased hydrophilicity and decreased friction torque. In the simulator experiment, the wear of the tibial insert was significantly suppressed in the cross-linked PE (CLPE) insert, and even more dramatically decreased in the MPC-grafted CLPE insert, as compared to that in the non-cross-linked PE insert. Surface analyses confirmed the wear resistance by the cross-linking, and further by the MPC grafting. The particle size distribution was not affected by cross-linking or MPC grafting. The mechanical properties of the insert material remained unchanged during the loading regardless of the cross-linking or grafting. CONCLUSION: Surface grafting with MPC polymer furnished the PE insert with wear resistance in an artificial knee joint through increased hydrophilicity and decreased friction torque.

Selection of highly osteogenic and chondrogenic cells from bone marrow stromal cells in biocompatible polymer-coated plates.

To enrich the subpopulation that preserves self-renewal and multipotentiality from conventionally prepared bone marrow stromal cells (MSCs), we attempted to use 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated plates that selected the MSCs with strong adhesion ability and evaluated the proliferation ability or osteogenic/chondrogenic potential of the MPC polymer-selected MSCs. The number of MSCs that were attached to the MPC polymer-coated plates decreased with an increase in the density of MPC unit (0-10%), whereas no significant difference in the proliferation ability was seen among these cells. The surface epitopes of CD29, CD44, CD105, and CD166, and not CD34 or CD45, were detectable in the cells of all MPC polymer-coated plates, implying that they belong to the MSC category. In the osteogenic and chondrogenic induction, the MSCs selected by the 2-5% MPC unit composition showed higher expression levels of osteoblastic and chondrocytic markers (COL1A1/ALP, or COL2A1/COL10A1/Sox9) at passage 2, compared with those of 0-1% or even 10% MPC unit composition, while the enhanced effects continued by passage 5. The selection based on the adequate cell adhesiveness by the MPC polymer-coated plates could improve the osteogenic and chondrogenic potential of MSCs, which would provide cell sources that can be used to treat the more severe and various bone/cartilage diseases.

Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene causes a severe pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a common skeletal dysplasia characterized by disproportionate short stature, early-onset osteoarthrosis, and dysplasia of the spine, epiphysis, and metaphysis. Multiple epiphyseal dysplasia (MED) is a similar but less severe disorder characterized by dysplasia of the epiphysis. Both disorders are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. COMP mutations cluster in a region of the gene that encodes calmodulin-like repeats (CLRs) and correlate closely with disease severity. Typically, mutations in exon 13 that composes the seventh CLR produce severe PSACH phenotypes, whereas mutations found elsewhere in the gene produce mild PSACH or MED phenotypes. We have identified a PSACH patient carrying a novel mutation in exon 18 of COMP that composes the C-terminal globular domain. This mutation produced a severe PSACH phenotype with marked short stature and deformities of the spine and extremities. Our results extend the range of disease-causing mutations within the COMP gene and demonstrate the importance of the additional domain of COMP protein in its in vivo function.

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular matrix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfation-related genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P = 0.043, odds ratio = 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA.

Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.

Osteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population.

Long-term results of rotational acetabular osteotomy in patients with slight narrowing of the joint space on preoperative radiographic findings.

Between 1975 and 1984, we performed rotational acetabular osteotomy in 22 female patients with painful hip dysplasia. At the time of surgery, the patients were in their twenties, and radiographs showed slight narrowing of the joint space. Of these patients, 15 were followed-up for 15 to 22 years (average, 19.8 years) after surgery. The preoperative severity of coxarthrosis in all 15 hips was graded as stage II, according to the classification of coxarthrosis advocated by the Japanese Orthopaedic Association. All 15 patients available for follow-up had had no additional operations on the operated side during the follow-up period. At the time of follow-up, the patients were aged 41 to 48 years (average, 44.3 years). Of the 15 patients, 12 had little or no pain and 14 could walk for more than 30 min without a cane; the severity of coxarthrosis was graded stage I in 3 hips, stage II in 4 hips, stage III in 5 hips, and stage IV in 3 hips. We conclude that rotational acetabular osteotomy is efficacious for patients who have preoperative radiographic findings of slight narrowing of the joint space.

Combined intertrochanteric valgus and rotational acetabular osteotomy.

Results are reported for combined intertrochanteric valgus and rotational acetabular osteotomies in 18 dysplastic hips (17 patients), involving two types of femoral head and neck deformities, after an average followup of 13 years (range, 8.9-22.6 years). The mean age of the patients at the time of surgery was 25 years (range, 11-36 years). Pain was the indication for surgery in all patients. The preoperative deformities were classified into two groups. Hips in Group I had an angular head and a normal or valgus neck. Hips in Group II had an ovoid head, a short neck in varus angulation, and relative overgrowth of the greater trochanter. There were seven hips (seven patients) in Group I, and 11 hips (10 patients) in Group II. The sum of the most recent pain score and gait score of Merle d'Aubigné (a full score of 12 points) was 11 to 12 points for seven of 11 hips of Group II, and 11 to 12 points for only one of the seven hips of Group I. For patients with hip pain in Group II, this operation fairly consistently relieves pain for at least an average of 13 years, but whether the rate of development of osteoarthrosis is retarded is not known.

Long-term results of rotational acetabular osteotomy in young patients with advanced osteoarthrosis of the hip.

Between 1974 and 1987, we performed 38 rotational acetabular osteotomies to treat advanced coxarthrosis caused by acetabular dysplasia in 38 patients who were aged 40 years old or less at the time of surgery. Of these patients, 28 were followed-up for more than 10 years after surgery. The preoperative severity of coxarthrosis was graded as stage III in 21 hips and as stage IV in 7 hips, according to our modification of the classification of coxarthrosis advocated by the Japanese Orthopaedic Association. At the time of follow-up, 27 patients retained their own hip joints on the operated side 10 to 18 years (average, 13 years) after surgery, and the remaining patient had had a secondary total hip replacement 7 years after the surgery. Of the 27 patients who retained their own hip joints on the operated side, 20 had little or no pain and none suffered from severe pain in the operated hip; the severity of coxarthrosis was graded as stage II in 4 hips, as stage III in 9 hips, and as stage IV in 14 hips. We conclude that rotational acetabular osteotomy can be a useful procedure in young patients who have advanced coxarthrosis secondary to acetabular dysplasia.

Rotational acetabular osteotomy for the treatment of dysplastic hips with end-stage osteoarthrosis--a biological alternative to total hip arthroplasty?

We evaluated the results of rotational acetabular osteotomy (RAO) for the treatment of dysplastic hips with end-stage osteoarthrosis. Sixteen patients, aged 15-45 years at the time of surgery, were reviewed at a mean follow-up of 8 years (range 3-17 years). Remodeling of the hip joint occurred in half of the patients, with significant clinical improvement. A subsequent total hip arthroplasty, however, was done within 2 years after RAO in two other patients who had had large bone cysts in the femoral head and acetabulum. We suggest that RAO may be the procedure of choice for selected young patients, especially teenage patients, to postpone total hip arthroplasty.

Colonna capsular arthroplasty: a 33-year follow-up of four patients.

We evaluated the results of Colonna capsular arthroplasty in 4 patients with unilateral congenital dislocation of the hip. All of these patients were female, aged 10-14 years at the time of surgery, and 42-50 years at the time of follow-up. The most striking finding in this study was the good ability to walk. Although radiographs showed considerable joint degeneration, all of these patients had only mild to moderate pain in the hip.

Rotational acetabular osteotomy using biodegradable internal fixation.

We used biodegradable poly-L-lactide screws in rotational acetabular osteotomy in 41 hips of 41 patients, and studied the complications after an average follow-up of 4.9 years (range 1.0-7.7 years). There were 39 females and 2 males, their average age at the time of the operation was 32 years (range 12-55 years). A small subcutaneous abscess appeared around the non-absorbable sutures in 2 patients after surgery. There was 1 case of thrombophlebitis and 1 of local dermatitis. The small subcutaneous abscess resolved after the removal of the suture material in the 2 cases, and the thrombophlebitis resolved with aspirin. The local dermatitis persisted but was cured by local steroid therapy over 5.8 years. The incidence of local dermatitis after the use of biodegradable implants should be further investigated.

Long-term outcome of rotational acetabular osteotomy: 145 hips followed for 10-23 years.

We report the long-term outcome of rotational acetabular osteotomy in 145 dysplastic hips of 131 patients after an average follow-up of 13 (10-23) years. The mean age at operation was 28 (11-52) years. The radiographic severity of osteoarthrosis before operation, according to the criteria of the Japanese Orthopaedic Association, was stage I (no degenerative change) in 63 hips, stage II (early degenerative stage) in 49, stage III (progressive stage) in 21 and stage IV (end stage) in 12. The clinical outcome based on the Merle d'Aubigné and Postel score was excellent or good for 90 (80%) of the 112 hips which had stage I or II osteoarthrosis preoperatively, and was excellent or good for only 9 of the 33 hips which had stage III or IV osteoarthrosis (p < 0.001, chi-square test). The radiographic severity of osteoarthrosis at the most recent review was stage I or II for 79 (70%) of the 112 hips which had stage I or II osteoarthrosis preoperatively. The long-term outcome of rotational acetabular osteotomy was satisfactory for a dysplastic hip with little, if any, osteoarthrosis, but was unsatisfactory for a hip with more advanced osteoarthrosis.

Complete endoscopic carpal tunnel release in long-term haemodialysis patients.

The roof of the carpal tunnel (or canal) consists of the distal portion of the flexor retinaculum, the flexor retinaculum (or the transverse carpal ligament) and the proximal portion of the flexor retinaculum. We tried to determine which anatomical structures were relevant to complete endoscopic carpal tunnel decompression in long-term haemodialysis patients with carpal tunnel syndrome. Carpal tunnel pressure was measured using the continuous infusion technique before and after endoscopic release of the flexor retinaculum, distal portion of the flexor retinaculum and the proximal portion of the flexor retinaculum respectively in 257 hands. We concluded that release of the distal portion of the flexor retinaculum, in addition to the flexor retinaculum, is essential for complete carpal tunnel decompression in long-term haemodialysis patients.

Complete endoscopic carpal canal decompression.

We made a model of the endoscopic decompression of the carpal canal in clinical cases. The model entailed the release of the transverse carpal ligament, ie, the flexor retinaculum, first; then the transverse fibers: deep layer of the midpalmar fascia or distal portion of the flexor retinaculum; and, finally, release of the forearm fascia. Carpal canal pressure was measured using the continuous infusion technique, and the carpal canal was observed endoscopically at each step. Carpal canal pressure data were analyzed by using the Wilcoxon matched pairs signed-rank test. When the transverse carpal ligament and the transverse fibers were divided, carpal canal pressure was significantly statistically lower than that with release of the transverse carpal ligament alone. We conclude that release of both the transverse carpal ligament and the transverse fibers are essential for complete decompression of the carpal canal in endoscopic surgery.

Long-term follow-up results of rotational acetabular osteotomy in painful dysplastic hips: efficacy in delaying the onset of osteoarthritis.

We evaluated the results of rotational acetabular osteotomies in 13 severely dysplastic hips (11 patients) with subluxation. All of the patients were women, aged 20 to 35 years at the time of surgery, and 40 years or more at the time of follow-up. At a minimum follow-up period of 10 years, the patients had minimal or no pain. Of the 13 hips, 12 showed no significant findings of osteoarthritis. Comparing the outcome of these patients with the natural evolution of severely dysplastic hips, we concluded that rotational acetabular osteotomy may prevent the onset of osteoarthritis.

Evaluation of carpal canal pressure in carpal tunnel syndrome.

Preoperative electrophysiologic testing and intraoperative carpal canal pressure measurements were performed on 957 hands in 647 patients with clinical signs of carpal tunnel syndrome. Fifty-five symptomatic hands in 48 patients were normal in both distal sensory latency and distal motor latency preoperatively. Carpal canal pressure was, however, significantly elevated compared to control data in all 55 hands. After complete subcutaneous release of the carpal canal using the Universal Subcutaneous Endoscope system, carpal canal pressure was reduced to within the normal control range. Clinical symptoms of carpal tunnel syndrome improved in all 55 hands. Postoperative electrophysiologic data remained within normal range in patients who agreed to receive electrophysiologic examinations.