Intramedullary spinal cord metastasis of ovarian tumor.

STUDY DESIGN: Case report. OBJECTIVES: To report a case of a thoracic intramedullary spinal cord metastasis of ovarian tumor in a 59-year-old woman. SETTING: Shiga, Japan. CASE REPORT: A case of a thoracic intramedullary spinal cord metastasis of ovarian tumor in a 59-year-old woman is reported. She received abdominal ovariectomy for the ovarian adenocarcinoma 4 years before she suffered from back pain and showed neurological symptoms. The thoracic intramedullary lesion was confirmed by preoperative magnetic resonance imaging. She showed complete paralysis before operation. The excision of the tumor was achieved through the posterior approach. Histologically, the diagnosis of metastasis of adenocarcinoma was made. CONCLUSION: Although she did not show any postoperative neurologic recovery, her general condition was good and there was no evidence of recurrence 24 months after surgery.

Antibacterial and antipeptide antibodies in Japanese and Finnish patients with rheumatoid arthritis.

It has been suggested that Proteus infection may be involved in the pathogenesis of rheumatoid arthritis (RA). Bacterial and peptide immune responses in patients with RA and other control subjects were investigated in two geographically different populations. Serum samples from Finnish patients with early ( n=72) and advanced ( n=27) RA and 30 Finnish healthy controls, as well as from Japanese RA patients from two different locations: Tokyo ( n=30) and Otsu ( n=30), 18 patients with systemic lupus erythematosus (SLE) and 23 Japanese healthy controls were all screened for the total, and class-specific (IgG, IgA and IgM) antibodies against Proteus mirabilis, Escherichia coli and Serratia marcescens by indirect immunofluorescence assay. These samples were also tested for the determination of levels of isotypic antibodies against the shared epitope involving 16-mer synthetic peptides containing the EQRRAA or ESSRAL sequences and compared to scrambled control peptide by using an enzyme-labeled immunosorbent assay method. Significantly elevated levels of IgG and IgM antibodies to P. mirabilis and antibodies against both EQRRAA and ESSRAL peptides were detected in sera of Finnish patients with early and advanced RA, and in Japanese patients from Otsu or Tokyo compared to their corresponding control groups. In contrast, no difference either in the total or in any of the isotypic antibodies were observed between these groups when serum samples were screened against each of E. coli and S. marcescens or against the control peptide. Furthermore, there was a significant correlation between the antibody levels against Proteus bacteria only and both EQRRAA and ESRRAL peptides. Our findings support the possibility for specific involvement of P. mirabilis in the etiopathogenesis of RA even in early cases.

Esophageal carcinoma with tracheal stenosis due to tumor invasion and long survival after chemoradiotherapy.

For patients who have esophageal carcinoma with tracheal invasion surgery is usually not indicated because operative complications are considerable and the prognosis is poor. We experienced complete regression of a large esophageal carcinoma with tracheal stenosis due to tumor invasion without tracheo-esophageal fistula. Irradiation of 68 Gy was delivered to a long T field from the neck to the lower thoracic esophagus, and was combined with chemotherapy using cisplatin and 5-fluorouracil. The tumor decreased markedly in size and the tracheal stenosis resolved. The patient has survived for 4 years, although second primary early esophageal carcinoma and hypopharyngeal carcinoma were detected 2 years after his initial chemoradiotherapy. Although the prognosis of advanced esophageal carcinoma with invasion of other organs is usually poor, the effect of chemoradiotherapy can sometimes be dramatic and a good result can be achieved in such patients.

Effects of serotonin 1A agonist on acute spinal cord injury.

STUDY DESIGN: We evaluated the effects of serotonin (5-HT) agonists on in vitro models of spinal cord compressive injury. Evoked potentials in injured rat spinal cords (n=24) were recorded during perfusion with 5-HT agonists. OBJECTIVES: To evaluate the therapeutic effects of 5-HT agonists on the recovery of compound action potentials in injured spinal cords. METHODS: Rat dorsal columns were isolated, placed in a chamber, and injured by extradural compression with a clip. Conducting action potentials were activated by supramaximal constant current electrical stimuli and recorded during perfusion with 5-HT agonists and antagonists. RESULTS: After inducing compression injuries, mean action potential amplitudes were reduced to 33.9+/-5.4% of the pre-injury level. After 120 min of perfusion with Ringer's solution, the mean amplitudes recovered to 62.8+/-8.4% of the pre-injury level. At a concentration of 100 micro M, perfusion with tandospirone (a 5-HT1A agonist) resulted in a significantly greater recovery of mean action potential amplitudes at 2 h after the injury (86.2+/-6.9% of pre-injury value) as compared with the control Ringer's solution (62.8+/-8.4% of pre-injury value, P<0.05). In contrast, quipazine (a 5-HT2A agonist) accelerated the decrease of amplitude (54.5+/-11.7% of pre-injury value). 5-HT1A and 5-HT2A agonist did not consistently alter latencies of the action potentials. CONCLUSION: The 5-HT1A receptor agonist was effective for the recovery of spinal action potential amplitudes in a rat spinal cord injury model.

Kyphotic malalignment after anterior cervical fusion is one of the factors promoting the degenerative process in adjacent intervertebral levels.

The aim of this study was to determine whether postoperative malalignment of the cervical spine after anterior interbody fusion surgery promotes degenerative changes in the neighboring intervertebral discs. Forty-two patients who underwent anterior interbody fusion surgery for cervical spondylosis and disc herniation (34 men, 8 women) were followed for an average of 9.8 years. The average age at surgery was 50.2 years. Twenty-three patients underwent a single-level fusion, 17 underwent two-level fusion, and 2 had three levels fused. The Japanese Orthopaedic Association cervical myelopathy score, with a normal score 17 points, was 11.7 before surgery and 14.9 at follow-up. Neurological status was significantly improved postoperatively, and the improvement was preserved thereafter in most cases (paired t-test, P<0.001). Degenerative changes were evident on radiological examination in the levels adjacent to the fused segment in 21 of the 42 (50%) patients. Eight of these 21 patients demonstrated neurological deterioration caused by an adjacent disc lesion. A total of 43% of the patients with adjacent-level degeneration had malalignment of the cervical spine, such as kyphosis or sigmoid curvature. In addition, degenerative change in adjacent intervertebral levels was observed in 77% of kyphoses of the fused segment. These were statistically significant (Fisher exact method, P<0.05, P<0.04, respectively). Our findings suggest that one of the factors promoting degenerative change in adjacent intervertebral levels after anterior cervical fusion for degenerative disorders is postoperative kyphotic change in the cervical spine and the fused segment.

Spondyloarthropathies in Japan: nationwide questionnaire survey performed by the Japan Ankylosing Spondylitis Society.

OBJECTIVE: The Japan Ankylosing Spondylitis Society conducted a nationwide questionnaire survey of spondyloarthropathies (SpA) in 1990 and 1997, (1) to estimate the prevalence and incidence, and (2) to validate the criteria of Amor and the European Spondylarthropathy Study Group (ESSG) in Japan. METHODS: Japan was divided into 9 districts, to each of which a survey supervisor was assigned. According to unified criteria, each supervisor selected all the clinics and hospitals with potential for SpA patients in the district. The study population consisted of all patients with SpA seen at these institutes during a 5 year period (1985-89) for the 1st survey and a 7 year period (1990-96) for the 2nd survey. RESULTS: The 1st survey recruited 426 and the 2nd survey 638 cases, 74 of which were registered in both studies. The total number of patients with SpA identified 1985-96 was 990 (760 men, 227 women). They consisted of patients with ankylosing spondylitis (68.3%), psoriatic arthritis (12.7%), reactive arthritis (4.0%), undifferentiated SpA (5.4%), inflammatory bowel disease (2.2%), pustulosis palmaris et plantaris (4.7%), and others (polyenthesitis, etc.) (0.8%). The maximum onset number per year was 49. With the assumption that at least one-tenth of the Japanese population with SpA was recruited, incidence and prevalence were estimated not to exceed 0.48/100,000 and 9.5/100,000 person-years, respectively. The sensitivity was 84.0% for Amor criteria and 84.6 for ESSG criteria. CONCLUSION: The incidence and prevalence of SpA in Japanese were estimated to be less than 1/10 and 1/200, respectively, of those among Caucasians. The adaptability of the Amor and ESSG criteria was validated for the Japanese population.

Prevalence of large-joint osteoarthritis in Asian and Caucasian skeletal populations.

OBJECTIVE: To determine ethnic variations of large-joint osteoarthritis (OA) in past populations. METHODS: One thousand two hundred and nine adult skeletons, excavated from archaeological sites in Japan, China and France were assessed for OA as defined by the presence of eburnation. RESULTS: Within Asian skeletal populations, elbow OA and patellofemoral joint OA were more common in hunter-gatherers than in agriculturalists. Compared with Caucasians, the Asian skeletal population had a higher prevalence of tibiofemoral joint OA. CONCLUSION: The relative frequencies of OA within and between ethnic groups at certain joint sites have changed over time from the past to the present.

Did ossification of the posterior longitudinal ligament of the spine evolve in the modern period? A paleopathologic study of ancient human skeletons in Japan.

OBJECTIVE: To investigate the historical origins of ligamentous ossifications of the spine in Japan. METHODS: We studied skeletons of Jomonese of the period 5000-2300 years BP, of Japanese of the 17th-19th century Edo Period, and of Ainu of the 18th-20th century in Japan with special emphasis on spinal ligament ossifications as in the posterior longitudinal ligament. A comparison to our previous study on ancient Chinese skeletons was done. RESULTS: Cervical ossification of the posterior longitudinal ligament (OPLL) was the only ossification that increased significantly in prevalence in people of the near-modern period in comparison to the Neolithic gathering-hunting people. CONCLUSION: Socioeconomic changes from a subsistence gathering-hunting economy to the near-modern livelihood depending on rice-eating and a diet high in vegetable protein are speculated to be responsible for the prevalence increase of cervical OPLL.

Spontaneous atlantoaxial rotatory fixation in old age after cerebral infarction: case report.

STUDY DESIGN: Case report of spontaneous Fielding and Hawkins Type I atlantoaxial rotatory fixation in a 78-year-old man after hemiplegia and homonymous hemianopsia caused by cerebral infarction. OBJECTIVES: To describe a case of spontaneous atlantoaxial rotatory fixation in old age and review previous adult cases of atlantoaxial rotatory fixation without fracture. SUMMARY OF BACKGROUND DATA: Atlantoaxial rotatory fixation in adults is a relatively rare finding and is mainly caused by trauma. To the author's knowledge, there has been no previous report of spontaneous atlantoaxial rotatory fixation in old age. METHODS: The patient's head was fixed in a 40 degrees left-rotated position. Left hemiplegia and homonymous left-side hemianopsia developed due to cerebral infarction. Computed tomography of the cervical spine clearly showed rotatory fixation of the atlas on the axis. RESULTS: Successful reduction was obtained after 1 day of skull traction. CONCLUSIONS: It was hypothesized that repeated left-rotational stress due to homonymous hemianopsia loaded to the atlantoaxial joint caused abnormal laxity of the joint.

Prevalence of hip osteoarthritis and acetabular dysplasia in french and japanese adults.

OBJECTIVE: : To determine ethnic variations of acetabular morphology, and to delineate their relationship with hip osteoarthritis (OA). METHODS: : Radiographs of 283 French men, 118 French women, 414 Japanese men and 368 Japanese women, aged 20-79 yr, who underwent intravenous urography were assessed by a single observer for morphometric measurement and hip OA scoring. RESULTS: : The standardized morbidity ratio (SMR) for hip OA was highest in French men and lowest in Japanese men, whereas the SMR for acetabular dysplasia was highest in Japanese women and lowest in French men. French men and women had the highest centre-edge angle, followed by Japanese men then Japanese women. CONCLUSION: : In a large number of subjects assessed by a single observer, this study confirms other previous reports that the relationship between acetabular dysplasia and risk of hip OA is negative.

Purification of a low-molecular-weight phospholipase A(2) associated with soluble high-molecular-weight acidic proteins from rabbit nucleus pulposus and its comparison with a rabbit splenic group IIa phospholipase A(2).

An intervertebral disc is a large peice of avascular cartilage rich in proteoglycans and water consisting of gelatinous nucleus pulposus and fibrous annulus fibrosus. The soluble fraction of rabbit nucleus pulposus exhibited unusually high Ca(2+)-dependent phospholipase A(2) (PLA(2)) activity (about 70% of the total PLA(2) activity). The soluble PLA(2) activity was 6-7-fold higher than those of rabbit annulus fibrosus and spleen. The PLA(2) was bound to an anion-exchange column at pH 7.4, and eluted near the void volume as a broad peak on gel-filtration on a TSKgel SuperSW3000 column developed with a buffer containing 0.1-0.2 M salt. When the gel-filtration column was developed in the presence of 1 M salt, almost all the PLA(2) activity was eluted near the total available volume. The soluble PLA(2) was purified to near homogeneity. A Ca(2+)-dependent PLA(2) was also purified from the fractions extracted with 1 M KBr from nucleus pulposus. For comparison, we purified a Ca(2+)-dependent PLA(2) from the KBr fraction of spleen. The splenic PLA(2) was identical to a group IIa PLA(2), as judged from its N-terminal amino acid sequences and mass spectra. On SDS-polyacrylamide gel electrophoresis the enzymes purified from the soluble and KBr fractions of nucleus pulposus both gave a major 15. 7-kDa band at the same position as splenic group IIa PLA(2). These results suggest that group IIa PLA(2) is associated with soluble high-molecular-weight proteins, most likely proteoglycans, in the extracellular matrix of rabbit nucleus pulposus.

Polymorphic CAG repeats of the androgen receptor gene in Japanese male patients with ankylosing spondylitis.

OBJECTIVE: In view of a possible role of androgens in the pathogenesis of ankylosing spondylitis (AS), we investigated the association between Japanese male patients with AS and CAG microsatellites of the androgen receptor (AR) gene which related to the AR transactivation function. METHODS: Peripheral blood was collected from 39 men with AS and 305 male control subjects. The number of CAG repeats in exon 1 of the AR gene was determined. RESULTS: CAG repeat lengths in AS patients were significantly shorter than those in the controls (median value 22 vs 23; P = 0.03). However, there was no significant difference in CAG repeats between HLA-B27-positive and -negative patients (median value 22 vs 22; P = 0.78). CONCLUSIONS: Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, may play a role in male AS.

Liposarcoma associated with multiple intramuscular lipomas. A case report.

A 71-year-old slender, previously healthy man was admitted to the authors' institution because of a huge painless mass in his left scapular area. Physical examination revealed a second soft tissue mass in his right scapular region and a third soft tissue mass in the anterior side of his right shoulder. Surgical treatment including marginal resection of the second and third small masses followed by wide local resection of the huge tumor was performed. Histologic examination showed that the first mass was a well differentiated lipomalike liposarcoma, whereas the second and third lesions were identified as intramuscular lipomas. A review of the literature showed two cases of retroperitoneal liposarcoma associated with multiple subcutaneous lipomas and two cases of liposarcoma involving an extremity associated with multiple subcutaneous lipomas. There is no previous report in which intramuscular liposarcoma was associated with multiple intramuscular lipomas.

Mechanical stress induces the expression of high molecular mass heat shock protein in human chondrocytic cell line CS-OKB.

OBJECTIVE: Mechanical stress is an important regulator of chondrocyte function, but it is unknown how chondrocytes respond to mechanical stress. This study was performed to clarify the underlying mechanisms in human chondrocytes. DESIGN: Using a Flexercell strain unit (25% maximal elongation, 0.05 Hz-cyclic manner, and 48 h), mechanical stimulation was applied to confluent CS-OKB cells, human chondrocytic cells. To analyze transcriptional changes in response to mechanical stress, differential display reverse transcription-polymerase chain reaction (DDRT-PCR) and Northern blot analysis were performed. RESULTS: Among several differentially displayed fragments, one fragment (927 bp) tentatively named as SIC (Stress-Induced Chondrocytic) 1 was isolated from the human chondrocytic cell line and identified as one of the high molecular mass heat shock proteins. CONCLUSION: Mechanical stress induces the expression of a high molecular mass heat shock protein corresponding to SIC 1 in human chondrocytic cells. SIC 1 may play an important role in the mechanical stress-responded metabolism of human chondrocytes.

Vitamin D receptor gene polymorphisms and osteoarthritis of the hand, hip, and knee: acase-control study in Japan.

OBJECTIVE: To investigate the association between vitamin D receptor (VDR) gene polymorphisms andJapanese female patients with osteoarthritis (OA) of the hand, hip, and knee. METHODS: BsmI,ApaI, andTaqI restriction fragment length polymorphisms (RFLPs) of the VDR gene were analysed in 270Japanese female patients with radiographic OA of the hand, hip, tibiofemoral (TF) joint, andpatellofemoral (PF) joint, as well as in female controls. RESULTS: There was no significant association between the VDR gene RFLPs and OA of the hand, hip, TFjoint, PF joint, or polyarticular involvement. The previously detected preventive genotype of the VDRgene was uncommon in our test population. CONCLUSION: The relative importance of VDR gene polymorphism in the development of OA may vary betweenethnic groups.

Altered postnatal expression of insulin-like growth factor-I (IGF-I) and type X collagen preceding the Perthes' disease-like lesion of a rat model.

The spontaneously hypertensive rat (SHR) is a widely used animal model for the study of hypertension. It also exhibits an osteonecrosis of the femoral epiphysis that resembles the clinical features of Perthes' disease in humans. In this rat model, occlusion of the epiphyseal vessels occurs as a result of a breakdown of the mechanically vulnerable epiphysis. The postnatal development of the epiphysis recapitulates the serial events of the endochondral ossification (i.e., cartilage formation), chondrocyte hypertrophy, cartilage mineralization, vascularization, and introduction of osteoblasts that form the secondary ossification center within the epiphysis. In the present study, a detailed radiographic and histological analysis demonstrates that the osteonecrosis is preceded by a disturbance of the cartilage mineralization and a disturbance of the ossification, despite a normal hypertrophy of the epiphyseal cartilage. These observations suggest that abnormal development of the femoral epiphysis occurs much earlier than manifestation of the osteonecrosis. They lead us to a hypothesis that yet-unclarified transitional events between the cartilage hypertrophy and the cartilage mineralization may be affected in SHRs. Type X collagen is a developmentally regulated matrix molecule that is implicated in the mineralization of the hypertrophied chondrocytes. We show that the expression of type X collagen during epiphyseal ossification is delayed in SHRs (vs. normal controls), suggesting disturbed growth and/or differentiation of the epiphyseal chondrocytes. Postnatal growth and differentiation of the chondrocytes at least partly depend on insulin-like growth factor-I (IGF-I), which is produced by the chondrocytes in response to the pituitary growth hormone and stimulates cartilage growth in situ. The present study demonstrates an altered IGF-I expression during early postnatal life in SHRs and suggests that the altered IGF-I expression as well as the following delay in upregulation of type X collagen may cause the mechanical vulnerability of the femoral epiphysis in SHRs.

Effects of estrogen on interleukin-6 production in rheumatoid fibroblast-like synoviocytes.

OBJECTIVE: In view of the importance of estrogen and IL-6 in the pathogenesis of rheumatoid arthritis (RA), the effects of 17 beta-estradiol (E2) on interleukin (IL)-6 production in cultured rheumatoid fibroblast-like synoviocytes were investigated. METHODS: Cultured fibroblast-like synoviocytes obtained from RA joints were treated with the vehicle (control), as well as 10(-8) and 10(-6) M of E2, with or without IL-1 beta stimulation. After 72 hours of culture, the levels of IL-6 in supernatants were measured by ELISA. RESULTS: Treatment with 10(-8) and 10(-6) M of E2 had no effect on the constitutive production of IL-6 in cultured fibroblast-like synoviocytes. However, E2 increased IL-1 beta-induced IL-6 production in a dose-dependent manner, with a mean 12.5% increase with 10(-8) M of E2 (p = 0.048) and 33.4% with 10(-6) M (p < 0.0001) versus the control. CONCLUSION: Estrogen up-regulates IL-1 beta-induced IL-6 production in cultured fibroblast-like synoviocytes, possibly contributing to the enhancement of rheumatoid inflammation in synovial tissues.

Possible association of CYP17 gene polymorphisms with the onset of rheumatoid arthritis.

OBJECTIVE: The etiologic role of sex hormones in rheumatoid arthritis (RA) has been discussed. Cytochrome P450c 17 alpha (CYP17) regulates steroidogenesis and the restriction fragment length polymorphisms (RFLPs) of the CYP17 gene are related to serum sex hormone production. In this study, the relationship between CYP17 gene RFLPs and RA was investigated. METHODS: Genomic DNA was extracted from the peripheral blood of 91 male and 285 female patients with RA, as well as from 380 male and 579 female controls, and the RFLPs of the CYP17 gene (denoted as the A1 and A2 alleles) were determined. Clinical variables were recorded for the RA patients. RESULTS: There were no significant differences in CYP17 genotype distribution between the male RA patients and male controls, nor between the female RA patients and female controls. RA patients with the A2 allele tended to develop the disease at a younger age than those without (in men 50.1 vs 54.7 yrs, p = 0.15; in women 43.9 vs 47.4 yrs, p = 0.038). In women, having the A2 allele was a weak protective factor against developing RA at an older age (odds ratio: 0.63, 95% confidence interval: 0.41-0.95, p = 0.026). CONCLUSION: The RFLPs of the CYP17 gene may constitute a disease modifying factor through sex hormone production.

Expression of genes for estrogen receptors alpha and beta in human articular chondrocytes.

OBJECTIVE: To investigate the gene expression of estrogen receptor (ER) alpha and ERbeta in human articular chondrocytes. METHODS: 16 articular cartilage specimens were obtained from 15 patients during surgery. Three of the specimens were from men and 13 from women; three from hip joints and 13 from knee joints; four were normal and 12 showed osteoarthritic cartilage. Total RNA was extracted from the articular chondrocytes and the expression of both ERalpha and ERbeta genes was investigated by the reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Gene expressions of ERalpha were detected in all specimens and those of ERbeta were found in 15 specimens by the RT-PCR method. There was a significant correlation between the amounts of ERalpha and ERbeta. Expression levels of both genes were significantly higher in men than in women. There were no significant differences in the expression levels of both ER genes between the hip and knee joint sites, nor between normal and osteoarthritic tissues. CONCLUSION: This study is to our knowledge the first to demonstrate the gene expression of both ERalpha and ERbeta in human articular chondrocytes. Since there are some functional differences between the two receptors, the effects of estrogen on cartilage metabolism should be elucidated by two different receptor mechanisms.