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CASE 1: TAI and radiation therapy were performed for a lateral segment and tumor thrombus extended into the left portal branch. Then, we diagnosed a tumor thrombus that extended into the right portal branch and TAI and operation were performed. The patient died about 9 months after the diagnosis of tumor thrombus. CASE 2: An operation was performed for hepatoma involving the right lobe and the tumor thrombus extended into the right portal branch. TAI and TAE were performed for residual tumor. The patient died about 12 months after diagnosis of tumor thrombus. CASE 3: An operation was performed for hepatoma involving an anterior segment and tumor thrombus extended into the right portal branch. Then, TAI, TAE and PMCT were performed for residual tumor. The patient is alive for 33 months with recurrence after the diagnosis of tumor thrombus. CASE 4: An operation was performed for hepatoma involving a posterior segment and tumor thrombus extended into the right portal branch. For recurrent TAI and TAE, radiation therapy was performed. The patient is alive for 20 months without recurrence after the diagnosis of tumor thrombus.

A 63-year-old man visited our hospital complaining of brown urine. A physical examination showed jaundice of the skin and conjunctiva bulbar. Blood tests showed elevated serum levels of bilirubin and hepatobiliary enzymes. A type 2-like mass lesion was found near the papilla of Vater during the endoscopic retrograde cholangiopancreatography and was histologically proven to be a well-differentiated adenocarcinoma. A diagnosis of obstructive jaundice due to primary duodenal cancer arising near the papilla of Vater was made. After the jaundice was decreased by endoscopic biliary stenting, a pancreatoduodenectomy was performed. A histopathological examination of the resected specimen concerning the location and manner of invasion of cancer cells revealed that the cancer arose from the duodenal mucosa near the papilla of Vater.

The purpose of this study was to clarify the etiology of painful bipartite patella in adolescents by histopathological examination of excised specimens. We performed excision of a fragment of painful bipartite or tripartite patella from six patients (six knees). The articular cartilage, interposed tissue, bone, and bone marrow of the excised specimens were histologically examined. The articular cartilage was intact in all but two patellae. The predominant composition of the interposed tissue was fibrous tissue in one patient; fibrous tissue and fibrocartilage in four patients; and fibrous tissue, fibrocartilage, and hyaline cartilage in one patient. In the interposed tissue, diffuse degenerative and necrotic fibrocartilage was observed in four patients and focal necrotic fibrocartilage was seen in two patients. In all patients, the central region of the interposed tissue almost completely lacked blood vessels. Other histological features of the interposed tissue included necrosis of the trabecular bone in three patients, irregularly shaped spicules of immature bone in three patients, and fragments of hyaline cartilage in two patients. In all patients the bone marrow adjacent to the interposed tissue showed numerous small blood vessels, and trabecular bone surfaces and the fibrocartilage surface adjacent to this bone marrow was scalloped and lined with numerous osteoclasts. The striking histopathological features of the interposed tissue were fibrous tissue and necrosis of the fibrocartilage. These abnormalities may ultimately lead to the failure of an accessory ossification center to unite with the main portion of the patella.

The patient was a 44-year-old man, who was investigated for lateral abdominal pain and liver dysfunction, and subsequently referred to our department with a diagnosis of unresectable intrahepatic cholangiocellular carcinoma (CCC). Radiological examinations revealed the huge mass in the right lobe of the liver with intrahepatic metastasis in the left lobe. The main tumor was surgically removed, but the metastases were not removed. A month after the operation, a subcutaneous implant reservoir was indwelled for repeated transcatheter hepatic arterial chemo infusion therapy (5-fluorouracil 500 mg/day continuous infusion, day 1-5, and CDDP 10 mg/day, day 1) from the right femoral artery. After 15 courses of home anti-cancer chemotherapy, abdominal CT revealed that the size of intrahepatic metastasis in the left lobe of the liver had not shown growth, whereas other metastitic sites popped up in the caudate lobe, which were free of chemical agent flow. There was no major complication related to the chemotherapy throughout the post-treatment course. Although he maintained a good level of QOL, he refused further chemotherapy due to depression. He died of liver failure 7 months after the operation. In conclusion, volume reduction surgery followed by transcatheter hepatic arterial chemo infusion might be promising as an effective therapy for non resectable CCC.

A 57-year-old man was found to have elevated levels of HCC markers during an observation of chronic hepatitis C. Diffused hepatoma was involved in the posterior lobe, and tumor thrombus extended into the main portal vein (Vp4). Posterior segmentectomy and tumor thrombectomy were performed. But, CT scan 45 days after the operation showed an enhancement at the residual tumor thrombus in the posterior branch. The patient received a hepatic arterial infusion of 5-FU, followed by hepatic arterial embolization. Then, we chose radiation therapy to the tumor thrombus. The most recent CT showed no enhancement at the reduced tumor thrombus. There have been almost no reports of treatment for residual portal thrombus. Careful observations are necessary in such patients.

Objective: To examine the effects of basic fibroblast growth factor (bFGF) gene-transduced chondrocytes on the repair of articular cartilage defects., Methods: LacZ gene or bFGF gene was transduced into primary isolated rabbit chondrocytes with the use of a recombinant adeno-associated virus (AAV) vector. These gene-transduced chondrocytes were embedded in collagen gel and transplanted into a full-thickness defect in the articular cartilage of the patellar groove of a rabbit. The efficiency of gene transduction was assessed according to the percentage of LacZ-positive cells among the total number of living cells. The concentration of bFGF in the culture supernatant was measured by enzyme-linked immunosorbent assay to confirm the production by bFGF gene-transduced chondrocytes. At 4, 8, and 12 weeks after transplantation, cartilage repair was evaluated histologically and graded semiquantitatively using a histologic scoring system ranging from 0 (complete regeneration) to 14 (no regeneration) points., Results: LacZ gene expression by chondrocytes was maintained until 8 weeks in >85% of the in vitro population. LacZ-positive cells were found at the transplant sites for at least 4 weeks after surgery. The mean concentration of bFGF was significantly increased in bFGF gene-transduced cells compared with control cells (P < 0.01). Semiquantitative histologic scoring indicated that the total score was significantly lower in the bFGF-transduced group than in the control group throughout the observation period., Conclusion: These results demonstrated that gene transfer to chondrocytes by an ex vivo method was established with the AAV vector, and transplantation of bFGF gene-transduced chondrocytes had a clear beneficial effect on the repair of rabbit articular cartilage defects.

Aspirin-intolerant asthma (AIA) is a subtype of bronchial asthma characterized by development of bronchoconstriction evoked by non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit the cyclooxygenase pathway, leading to enhancement of the lipoxygenase pathway. We evaluated allelic association of 370 single nucleotide polymorphisms (SNPs) of 63 candidate genes, mostly from the arachidonic acid metabolic cascade, with AIA. After two rounds of screening with 198 AIA patients, multiple SNPs in the prostaglandin E(2) receptor subtype 2 (EP2) gene were associated with AIA (P<0.05). Among the 77 SNPs identified in the EP2 gene, we selected 17 SNPs on the basis of linkage disequilibrium and allelic frequencies (minor allele frequency >0.1) for further association study. SNPs in the promoter region of the EP2 gene, uS5, uS5b, and uS7, were significantly associated with AIA (permutation P=0.039-0.001). Analysis of haplotypes constructed according to the LD pattern showed a significant association with AIA (permutation P=0.001). The most significantly associated SNP, uS5, located in the regulatory region of the EP2 gene, was in a STATs-binding consensus sequence [AIA 31.1% versus control 22.1% (permutation P=0.0016) or versus aspirin-tolerant asthma 22.2% (permutation P=0.0017)]. Although STAT1 binding was not observed in gel mobility shift assay with HeLa nuclear extract, an unidentified protein was specifically bound to the allelic sequence. In in vitro reporter assay in HCT116 cells, the site containing the uS5 allele showed reduced transcription activity. Taken together, these results suggest that uS5 allele serves as a target of a transcription repressor protein. A functional SNP of the EP2 gene associated with risk of AIA should decrease the transcription level, resulting in reduction of the PGE(2) braking mechanism of inflammation and involvement in the molecular mechanism underlying AIA.

A long-term follow-up study was performed on 75 knees of 53 patients after high tibial valgus osteotomy. The earlier results have previously been reported. There were 15 knees in 11 men and 60 knees in 42 women. The follow-up period ranged from 15 to 28 years with a mean of 19 +/- 3 years. The age at osteotomy ranged from 46 to 73 years with a mean of 59.6 +/- 6.7 years. The diagnosis was medial compartmental osteoarthritis (OA) in 68 knees (46 patients) and spontaneous osteonecrosis of the medial femoral condyle in 7 knees (7 patients). Valgus osteotomy was performed above the tibial tuberosity, with removal of a laterally based wedge in all cases, aiming for anatomical valgus angulation of 10 degrees . The American Knee Society Score showed a Knee Score of 37 +/- 20 and a Function Score of 38 +/- 16 preoperatively and 87 +/- 13 and 80 +/- 19 at the final 15 to 28 years' follow-up. The femoro-tibial angle in standing was 186 +/- 6.5 degrees (6 degrees of anatomical varus angulation) before and 171 +/- 7.5 degrees (9 degrees of anatomical valgus angulation) at final follow-up (p < 0.0001), with no apparent loss of limb alignment.

A 65-year-old Japanese man who had been suffering from severe and progressive dyspnea for more than 2 months underwent an extended right hepatectomy for hepatocellular carcinoma (HCC) in August 2001. Radiological examination, performed in August 2003, revealed the mass in the left lobe of the liver extended into the left hepatic vein, the inferior vena cava and the right atrium. Those clinical manifestations were supposedly attributed to HCC tumor thrombus in the right atrium. The decision to carry out the palliative operation for the tumor thrombus was not made because of poor prognosis in light of hemodynamic compromise indicating a reasonable liver function. A sequential course of treatments for the tumor thrombus was performed including transcatheter chemotherapy, transarterial chemoembolization and radiation therapy. Although a radiological response rate was 27% in diameter of the tumor thrombus, the clinical manifestations, such as dyspnea or edema, completely disappeared during the treatment. No surgical standard or interventional regimen for HCC tumor thrombus in the right atrium has been established. However, we here demonstrated the possibility for the treatment of the tumor thrombus with intensive combination therapies.

A 74-year-old male was examined with abdominal CT scan because of general fatigue. Abdominal CT scan indicated enhanced tumors, 9x8 cm in size in subsegment 6/7 and 5 mm in size in subsegment 3. Tumor thrombus was observed in the right portal branch to the main portal vein. We diagnosed the patient with Vp3 hepatocellular carcinoma. A right hepatectomy with extraction of portal venous thrombus was performed. Unresectable tumor was treated with one shot arterial infusion (epi-ADM 40 mg) and TAE 3 times at an interval of three months. The side effect was only a fever and the QOL was good under the treatment. But a tumor in S1 had developed, and the patient died at about 12 months after the operation.

A patient of advanced gall bladder carcinoma with liver metastases and direct invasions to the duodenum and liver underwent a palliative operation, 3 hepatic arterial infusion (HAI) therapies, and radiation therapy at the obstructive common biliary duct. (Palliative operation was a partial resection of duodenum and transverse colon, HAI therapy with 5-FU (1 g/day) was given as a continuous infusion for 6 days, radiation therapy was given 2 Gy/day for 20 times) After the combination therapy, the main tumor of gall bladder and hepatic metastases were decreased and tumor markers were normalized. (CEA 15.1 ng/ml, CA19-9 93 U/ml to CEA 4.4 ng/ml, CA19-9 29 U/ml) Then, an expandable metallic stent (EMS) could be inserted to the stenotic common biliary duct after radiation therapy. Although para-aotic lymph nodes were existent, systemic chemotherapy (UFT 300 mg/day p.o., MMC 2 mg/week div) has been performed as an outpatient with a good quality of life.

In order to investigate the reliability of the transepicondylar line and the condylar line as indicators for lower limb alignment in knee arthroplasty, the femorotibial angle (FTA), and the angle between the transepicondylar line and the tangential line of tibial plateau (angle epsilon) and condylar-plateau angle (CPA) were measured in 107 (78 patients) full-length standing X-ray films of lower limbs. The mean FTA was measured to be 178.0+/-9.3 degrees, the CPA 1.5+/-8.5 degrees and angle epsilon -0.8+/-8.5 degrees. The correlation between FTA and the CPA was analyzed to be significant with a correlation coefficient of 0.63, while another correlation between FTA and angle epsilon was calculated to be significant with a correlation coefficient of 0.81 at the same time. As a result, the correlation of the latter one was highly significant, having a R2 value of 0.648 (P<0.001), while the R2 of the former was only 0.397 (P<0.001). In conclusion, the transepicondylar line could be considered as a more reliable indicator for lower limb alignment, which may play an important role in ligament balancing and improvement of the guiding system in knee arthroplasty.

The incidence and the causes of provoked anterior knee pain in medial osteoarthritis (OA) of the knee were investigated clinically and radiographically. A retrospective study was performed in 179 primary osteoarthritic knees of 129 patients. Provocative tests were conducted on the patellofemoral (PF) joint to induce retropatellar crepitation, grating pain, tenderness around the patella, and pain on deviating the patella. The femorotibial angle (FTA) was measured on standing anteroposterior radiographs as a parameter of limb alignment. The widths of the medial and lateral joint space of the PF joint were measured on skyline views of standing or 30, 60 or 90 degrees knee flexion. The angle of flexion contracture was measured on lateral radiographs of knees with maximum extension. The lateral shift and tilt of the patella were measured on standing skyline views. Retropatellar crepitation was found in 70% of knees, while provoked anterior knee pain was observed in 35-45% of knees with medial OA of the knee. Standing FTA was significantly greater in knees with tenderness around the patella and pain on deviating the patella than in those without these symptoms (P<0.05). The angle of flexion contracture was significantly greater in knees with provoked symptoms in the PF joint than in those without symptoms (P<0.05). The degree of lateral shift was greater in knees with provoked symptoms (P<0.05). Flexion contracture and varus deformity of the knee with lateralization of the patella may be factors aggravating provoked PF symptoms in medial OA of the knee. The radiographic assessment in this series failed to show a significant relationship between the width of the PF joint space and the incidence of provoked PF symptoms.

In 25 patients with rheumatoid arthritis, 36 cases of cemented Kinematic total knee arthroplasty were reviewed clinically and radiographically at 13 to 19 years after surgery. The mean age at the time of surgery was 51.6 +/- 8.9 years. According to the follow-up results evaluated with the Hospital for Special Surgery knee scoring system, 28 knees (77.7%) were classified as good or excellent. The mean flexion angle at follow-up evaluation was 99 degrees +/- 24 degrees (10 degrees -140 degrees ). At the tibial or femoral bone-cement interfaces, a radiolucent line was seen in 10 of 36 knees (27.8%) at follow-up evaluation. The survival rate of prostheses with revision as the endpoint was estimated to be 93.7% at 15 years. Kinematic total knee arthroplasty in rheumatoid arthritis patients provided a good long-term outcome.

The aim of the current study was to document regeneration of the articular cartilage after correction of varus deformity for osteoarthritis of the knee. The repair of articular cartilage after high tibial valgus osteotomy for medial compartmental osteoarthritis was observed in 146 knees of 115 patients. The mean age of the patients at osteotomy was 65+/-7 years (range 47-80). Observations were made through an arthrotomy at the time of removal of the blade plate, an average of 2 years after the initial osteotomy. Regeneration of the degenerated cartilage was classified into three stages. There were no regenerative findings (Stage A) in 13 knees; partial regeneration with fibrocartilaginous tissue (Stage B) in the previous degenerated area (Stage B) in 86 knees; and total coverage by new regenerated fibrocartilage or hyaline-like cartilage (Stage C) in 47 knees. Mature regeneration (Stage C) was observed more frequently in the knees with increased width of the medial joint space after high tibial osteotomy than in those with unchanged width (P<0.01), and in the knees with more than 5 degrees of anatomical valgus angulation after osteotomy than in those with less than 5 degrees (P=0.05). Even the knees with eburnation of subchondral bone in the weight-bearing portion showed Stage C regeneration in 26 out of 80, in contrast with no regeneration in two knees with degenerated cartilage remaining. O'Driscoll's histological and histochemical grading score was higher in the Stage C group (P<0.02). The weight-bearing portion of the medial femoral condyle with exposed bone was concluded to be partially or entirely covered by newly regenerated cartilage after 1 year after adequate correction of varus deformity by high tibial osteotomy without antologous chondrocyte implantation.

Purpose: In this study we radiologically evaluated the effects of extensor carpi radialis longus (ECRL) tendon transfer on the stability and deformity of joints of rheumatoid hands in cases with a postoperative period of more than 5 years., Methods: Synovectomy concomitant with tendon transfer of the ECRL to the extensor carpi ulnaris (Clayton's procedure) was performed in 28 wrists of 23 patients with rheumatoid arthritis. The follow-up period was 8.8 +/- 2.8 years. Pre- and postoperative x-rays were reviewed and measured. Follow-up evaluation included Steinbrocker's classification of the radiocarpal joints, Larsen's grade of the third metacarpophalangeal (MCP) joint, radial angulation of the wrist, ulnar translocation of the carpus, and ulnar drift of the fingers., Results: Nineteen of 28 wrists (68%) were ankylosed (radius-proximal carpal row fusion or radiolunate limited fusion). Radial angulation of the wrist was reduced from 131 degrees +/- 8.8 degrees before surgery to 121 degrees +/- 7.9 degrees after surgery. Dislocation and ulnar translocation of the carpus (UTC) were prevented by surgery (UTC: 1.05 +/- 0.10 before and 1.07 +/- 0.09 after surgery). The mean ulnar drift of the fingers was maintained at the preoperative level (UDF: 14 degrees +/- 5.7 degrees before and 14 degrees +/- 12.9 degrees after surgery). The incidence of alteration (increase and decrease) of UDF of more than 5 degrees between pre- and postoperative evaluation was significantly higher in the group with worsening of Larsen grade of MCP joints than in the group without worsening (with worsening: 7 of 8 MCP joints, without worsening: 8 of 20 MCP joints)., Conclusions: ECRL tendon transfer (Clayton's procedure) provided effective stabilization at more than 5 years (mean, 8.8 y) after surgery. In addition, this method may help to prevent ulnar drift of the fingers if combined with correction of local factors at the MCP joints.

Abstract To study the effect of synthetic lipid A on the expression of the adhesion molecule CD44 in synovium and cartilage, synthetic lipid A (10 μg/ml, 0.5 ml) diluted in 0.025% triethylamine (TEA) was injected into the left knee of male Wistar rats. The equivalent volume of 0.025% TEA was injected simultaneously into the right knee of the same rat as a control. The numbers of infiltrating neutrophils and mononuclear cells in the synovium were counted, and the expression of CD44 was detected immunohistochemically. Infiltration of neutrophils in the synovium of the knee reached a maximum at 12 h after intraarticular injection of lipid A (78.4 ± 5.6 cells/400× field), and had subsided at 7 days after injection (2.1 ± 0.6). CD44 expression in the lining cells of the synovium was detected 24 h after injection (2.5 ± 0.3 cell layers), and it lasted 7 days after injection (2.6 ± 0.4 cell layers). CD44 expression in cartilage started at 24 h (69.0% ± 4.6% positive area of specimen) and lasted 7 days after injection (27.3% ± 3.3%). Intraarticular injection of lipid A was proven to induce acute arthritis and CD44 expression in the synovial lining layers and articular cartilage.

The physiological significance of spectral and fractal components of spontaneous heart rate (HR) variability in the fetus remains unclear. To examine the relationship between circadian rhythms in different measures of HR variability, R-R interval time series obtained by fetal ECGs were recorded continuously over 24 h in five pregnant sheep at 116-125 days gestation. Conventional measures of short-term (STV) and long-term variability (LTV), low-frequency (LF; 0.025-0.15 cycles/beat) and high-frequency (HF; 0.2-0.5 cycles/beat) spectral powers, the LF-to-HF ratio, and fractal dimension values were calculated from 24-h ECG recordings and quantified every 60 min. STV, LTV, and LF and HF spectral powers were minimal during the day but increased significantly to their highest values at night. We found a significant positive correlation between these measures, whereas the cosinor method showed significant similarity between their circadian rhythm patterns. Fetal R-R intervals also exhibited fractal structures. Fetal HR variability had a fractal structure, which was similar between day and night. These results suggested that the circadian rhythms exhibited by STV and LTV during the day were mainly due to changes in frequency components rather than to fractal components of fetal HR fluctuation.

In recent years with ever-increasing numbers of pregnant women wanting to participate in sport activities, the question as to how safe maternal exercise is for mother and fetus has become more important. The effects of pregnancy on maternal cardio-respiratory system include increases in oxygen consumption, cardiac output, heart rate, stroke volume, and plasma volume. The increase in oxygen reserve seen in early pregnancy is reduced later, suggesting that maternal exercise may present a greater physiological stress in the third trimester. The aims of this article are 1) to comment on the evidence relating to the health risks and benefits of physical activity for pregnant women and their unborn fetuses and 2) to realize guidelines for management of maternal exercise. In the absence of either obstetric or medical complications, pregnant women can continue to exercise and derive related benefits. The type, intensity, frequency, and duration of the exercise seem to be important determinants of its beneficial effects. Evidence suggests that weight-bearing exercise produces a greater decrease in oxygen reserve than non weight-bearing exercise. Furthermore, to maintain a heart rate below 150 beats per minute during pregnancy, the intensity of weight-bearing exercise must be reduced. In addition, depending on the individual's needs and the physiologic changes associated with pregnancy, women may have to modify their specific exercise regimens. Although increases in the frequency of uterine contractions have been observed during physical activities, changes are often minimal. In response to moderate exercise, the increase in frequency of uterine contractions is gestation dependent and significant in the third but not in the second trimester. The physiological adaptations to exercise during pregnancy appear to protect the fetus from potential harm and, while an upper level of safe activity has not been established, the benefits of continuing to be active during pregnancy appear to outweigh any potential risks. All decisions about participation in physical activity during pregnancy should however be made by women in consultation with their medical advisers.

This study investigated the stimulatory effect of bone healing on cartilage regeneration. Full-thickness osteochondral defects, 5 mm wide x 3 mm deep, were created in the patellar groove of the right distal end of the femur in 60 mature Japanese white rabbits. The bone defect was made in the medial condyle of the ipsilateral tibia in the experimental group. The control group had only a chondral defect in the patellar groove. At 4, 8, and 12 weeks after surgery, cartilage repair was evaluated macroscopically and histologically using a semiquantitative grading scale. The mean scores of the gross and histological evaluation grade in the experimental group were significantly superior to those in the control group at 8 and 12 weeks ( P << 0.05). These findings suggested that regeneration of articular cartilage defects might be promoted by creation of a periarticular bony defect.

Recirculation following 30 min of ischemia due to transient uterine artery occlusion in pregnant rats at 20 days gestation has previously been found to cause partial recovery and secondary deterioration of the cellular bioenergetic state in the fetal brain, the subsequent damage being ameliorated by a free radical spin trap agent, alpha-phenyl-N-TERT-butylnitrone (PBN). Our objective was to assess whether the secondary deterioration of the cellular bioenergetic state is due to mitochondrial dysfunction and to study whether PBN acts to prevent secondary damage to mitochondria in the fetal rat brain. Fetal neocortical tissues were sampled after 30 min of intrauterine ischemia and after 1, 2 or 4 h of recirculation. PBN or vehicle was given 1 h after recirculation. Homogenates were prepared, and ADP-stimulated, nonstimulated and uncoupled respiratory rates were measured polarographically. Ischemia was associated with a decrease in ADP-stimulated and uncoupled respiratory rates, with a marked fall in the respiratory control ratio, defined as ADP-stimulated divided by nonstimulated respiration (p < 0.01). Recirculation (1 h) brought about partial recovery, but continued reflow (2 and 4 h) was associated with a secondary deterioration of respiratory functions (p < 0.01). The secondary deterioration was prevented by PBN (p < 0.05). The results demonstrate that the secondary deterioration of the cellular bioenergetic state in ischemia-reperfusion is due to secondary mitochondrial dysfunction and that this deterioration may be induced by oxygen-derived free radicals in the immature fetal brain., (Copyright 2003 S. Karger AG, Basel)

Background: The aims of this study were to investigate the results of opening-wedge high tibial valgus osteotomy in patients with medial compartment osteoarthritis of the knee and to examine the usefulness of hydroxyapatite wedges as the supporting material., Methods: Medial opening-wedge osteotomy was performed in twenty-one osteoarthritic knees in eighteen patients who had a mean age of 66.6 years. The mean duration of follow-up was 78.6 months. A medial transverse osteotomy was performed proximal to the tibial tuberosity, with the most lateral 10% of the tibia left intact. The medial side of the osteotomy site was opened to the desired angle of correction. Two hydroxyapatite wedges of the same size (5.0, 7.5, or 10.0 mm) were inserted into the opened osteotomy site along with bone grafts, and the fragments were fixed with two plates. The angle of correction could be adjusted by altering the direction of wedge insertion. The goal was to achieve a final standing alignment of 10 degrees of anatomical valgus angulation., Results: All patients had pain relief and improvement in walking ability after the osteotomy. The mean knee and function scores of the American Knee Society were 60.2 +/- 5.3 and 48.1 +/- 10.4 points, respectively, before the osteotomy and 94.3 +/- 7.3 and 93.1 +/- 9.8 points, respectively, at the time of the final follow-up. Limb alignment, expressed as the standing femorotibial angle, was corrected from 180 degrees +/- 2.9 degrees preoperatively to 169.7 degrees +/- 3.7 degrees (10.3 degrees of anatomical valgus angulation) at the time of the latest follow-up. There were no cases of recurrence of varus deformity or collapse of the hydroxyapatite wedges., Conclusions: After a mean duration of follow-up of 6.6 years, we found that the medial opening-wedge osteotomy of the proximal part of the tibia provided satisfactory clinical results for patients with osteoarthritis of the knee. Use of the porous hydroxyapatite wedges resulted in no collapse or subsidence at the osteotomy site., Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See p. 2 for complete description of levels of evidence.

The levels of fibroblast growth factor 2 (FGF2) in synovial fluid of osteoarthritic knees were measured. The correlation between FGF2 and the severity of cartilage degeneration in varus-deformed knees with medial compartmental osteoarthritis or the articular cartilage regeneration that occurs after high tibial osteotomy (HTO) were investigated. Knees that underwent total knee arthroplasty (TKA) were categorized as either mildly or severely degenerated according to a modified Outerbridge's grading system for degeneration of articular cartilage. Regeneration of articular cartilage was observed in a biopsy specimen from the medial femoral condyle removed with the patient's consent during hardware removal approximately 2 years after HTO. The joint fluid FGF2 level was measured at that time using an enzyme-linked immunosorbent assay. Cartilage regeneration was classified as immature or mature according to the staging for regeneration of articular cartilage. The histological findings were analyzed using Pineda's evaluation method for cartilage regeneration. The mean concentration of FGF2 was 57.4 +/- 17.6 pg/ml in the joint fluid from knees with severely degenerated cartilage. This was higher than the FGF2 concentration found in the mildly degenerated group. Approximately 2 years after HTO the FGF2 level in synovial fluid was lower in knees with mature regenerated cartilage than in those with immature regeneration. Osteoarthritic knees at a more mature regeneration stage had a lower Pineda's histological score. This result suggested that the FGF2 concentration in knees with osteoarthritis was influenced by articular cartilage degeneration and regeneration, and it correlated with the histological evaluation.

Pregnane X receptor (PXR) regulates transcription of drug metabolism genes such as CYP3A4 and MDR1. Several species of PXR transcripts have been reported, including hPAR-2 with an extended amino-terminus. Database search identified a 6-bp deletion at the putative HNF1 binding element on the proximal region flanking to the hPAR-2 transcription start site. Aspirin-induced asthma (AIA) is a typical drug-induced phenotype due to aspirin or nonsteroidal antiinflammatory drugs, and these drugs are metabolized by CYP2C9 and UGT1A6, which are regulated by PXR. We examined a possible association between the 6-bp deletion variant and AIA; 129 AIA patients and 117 controls were genotyped, and no allelic association was observed. Characterization of the hPAR-2 promoter revealed that the proximal region of 1.5-kb from the transcription start site conferred a promoter activity and that the 6-bp deletion diminished the activity. These results suggest that the putative HNF1 binding element is essential for the transcriptional activity of hPAR-2 and also, that substantial numbers of Japanese are in a deficient state. Because of the biological significance of the 6-bp deletion of PXR, the variant might potentially associate with as yet unknown phenotype.

Using a model with external ligation of the thigh, the effect of ischemia-reperfusion injury on tumor growth and the activity of lung metastasis was investigated in mice inoculated a spontaneous murine osteosarcoma cell line (POS-1) in vivo. POS-1 cell suspension was inoculated into the right hind footpad of 70 mice. Four weeks after inoculation, the ipsilateral thigh was ligated for 3 h in 15 mice and the contralateral thigh in 15 mice. Another ten mice were inoculated with POS-1 without ligating the thigh. The number of metastatic foci on the lung surface 6 weeks after inoculation was 2.29+/-0.98 (mean+/-SE) foci/lungs in mice with ipsilateral ligation and 6.25+/-2.41 in mice with contralateral ligation, which were significantly lower than control (13.40+/-1.42 in mice no ligation) (P<0.01). The number of metastatic foci on the lung surface in mice with intraperitoneal injection of superoxide dismutase (SOD) and catalase was 3.25+/-0.65 (mean+/-SE) foci/lungs in mice with ligation which was significantly greater than that in mice without SOD and catalase injection 1.29+/-0.97 (P=0.04). Cell viability was 9.12+/-4.07% with 100 microM H(2)O(2) in 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. It revealed that at concentrations of 100 microM H(2)O(2) or higher was cytotoxic to POS-1. In cell invasion assay, the number of invading cells with 10 microM H(2)O(2) was 2.80+/-0.53 cells/field, which was significantly lower than control (5.93+/-0.18) (mean+/-SE), indicating that low-dose H(2)O(2) suppressed invasion of POS-1. These results suggested that reperfusion injury had selective cytotoxicity to POS-1 through producing reactive oxygen species. Activated oxygen was considered to inhibit the regional growth and the ability of lung metastasis of POS-1 cells.

In order to investigate the change in limb alignment in cases of knee flexion deformity, 17 male volunteers aged from 25 to 35 years with no complaints and no knee disorders were selected. The femorotibial angle (FTA), which is the lateral angle at the intersection between the femoral axis and the tibial axis in an anteroposterior radiograph, was employed as an index of limb alignment. FTA in standing on one leg with and without knee flexion was measured. The mean standing FTA was 179.4+/-19 degrees in full extension, which decreased to 176.9+/-2.5 degrees in a mean flexion position of 18+/-3.3 degrees (range 15-25 degrees ) (P<0.002), and in all cases, standing FTA in flexion was smaller (more valgus-angulated) than that in full extension. There was a significant positive relationship with a straight regression line (D=0.101KFA + 0.296, R=0.8505) between the angle of knee flexion (KFA) and the difference (D) in standing FTA between full extension and knee flexion. We conclude that limb alignment became more valgus-angulated with an increase in flexion deformity.

Objective: To assess the windows of therapeutic opportunity for drugs with various chemical actions on fetal growth retardation induced by transient intrauterine ischemia in rats., Methods: At 17 days of gestation, ischemia was induced by 30 min of right uterine artery occlusion. The administration of either alpha-phenyl-N-tert-butyl-nitrone (PBN), FK 506, nifedipine, or MK-801 to pregnant rats was randomly started before occlusion, 1 hour, 3 hours, or 24 hours after recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and were weighed to determine the degree of fetal growth retardation., Results: The vehicle-treated animals exposed to ischemia showed a significant decrease in fetal body weight compared with the normoxic control animals. The growth disturbances were prevented by nifedipine and MK-801 only when given just prior to ischemia. In contrast, PBN and FK 506 had a protective effect even when given 1 hour and 3 hours after the start of recirculation, respectively., Conclusions: The present results indicate that treatment with PBN and FK 506 gives relatively wide windows of therapeutic opportunity in fetal growth retardation induced by transient intrauterine ischemia in rats and suggest the possibility of therapeutic intervention after the start of recirculation.

This study was designed to investigate the influence of maternal aerobic exercise on lipid peroxidation levels and antioxidant enzymatic activities before and after delivery. Predelivery and 1- and 24-hour post partum blood samples were collected from 18 nulliparous healthy pregnant women who exercised regularly throughout the whole period of pregnancy and from 22 matched controls. The plasma concentration of malondialdehyde (MDA) was measured as an indicator of lipid peroxidation. Erythrocyte enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT), were measured as intracellular antioxidant markers. In the control group, MDA increased slightly from predelivery to 1 hour post partum and then increased significantly at 24 hours post partum, with significant increase in SOD and CAT activities. On the other hand, MDA of the exercise group remained unaltered at 1 and 24 hours after delivery. At 1 hour post partum, the SOD and CAT levels of the exercise group increased markedly and then decreased to predelivery levels. The present results indicate that uncontrolled lipid peroxidation occurs during labor and suggest that continuing regular maternal exercise may reduce labor-induced lipid peroxidation by improving the defense capabilities against free radical generation.

Purpose: To compare global cerebral blood supply in healthy pregnant women and nonpregnant women., Materials and Methods: Flow volumes in the common, internal, and external carotid, arteries and the vertebral arteries were determined using color Doppler ultrasonography in 17 nonpregnant women, 55 healthy pregnant women at 10 to 40 weeks gestation, and 24 puerperal women within 1 week after spontaneous delivery. Global cerebral blood flow was defined as the sum of flow volumes in the bilateral internal carotid and vertebral arteries., Results: In the nonpregnant group, mean flow volumes of the common, internal, and external carotid arteries and the vertebral arteries, and mean global cerebral blood flow volume were (mean±SD) 863±108 ml/min, 554 ±94 ml/min, 386±65 ml/min, 115±24 ml/min, and 669±104 ml/min, respectively. During the second trimester, flow volumes of the common and external carotid arteries increased significantly in the healthy pregnant women, to about 130 percent and 140 percent of the nonpregnant level, respectively. Global cerebral blood flow volume remained unchanged during pregnancy., Conclusion: During pregnancy, increase in flow volumes in the common carotid arteries were accompanied by elevated flow volumes of the external carotid arteries but not the internal carotid arteries. This distribution would tend to regulate the volume of global cerebral blood flow throughout the period of pregnancy.

Total knee arthroplasty (cemented) using a ceramic Yokohama Medical Ceramic Knee (YMCK) (Kyocera Corp; Kyoto, Japan) prosthesis was evaluated in 90 knees of 64 patients with severe rheumatoid arthritis, with a mean age of 59 +/- 11 years. The mean follow-up period was 56 +/- 20 months (range, 27 to 97 months). Larsen's grading of rheumatoid arthritis revealed grade 2 in 3, grade 3 in 36, grade 4 in 36, and grade 5 in 15 of 90 knees. Of 64 patients, 9 were judged to have class 1, 30 were judged to have class 2, and 25 were judged to have class 3 functional disability. The American Knee Society knee score and function score improved from 41 +/- 16 and 29 +/- 22 preoperatively to 83 +/- 14 and 50 +/- 29 at the final follow-up (P <.0001) even in patients with multiple joint involvement. Radiographs at the final follow-up showed satisfactory insertion of all prostheses, with no osteolysis. A radiolucent line measuring <1 mm was observed around the tip of the pegs of the patellar dome in 3 knees. Complications consisted of infection (1 case) and femoral fractures (3 cases). There were no cases of ceramic fractures., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Objective: To evaluate both the potential for transferring genes to periosteal cells using an adeno-associated virus (AAV) vector and the potential for gene expression after transplantation of those cells to a cartilage defect in vivo., Methods: Periosteum was obtained from the tibia of 6-week-old rabbits and enzymatically digested. The isolated periosteum derived cells were cultured and the subconfluence cells were infected with a recombinant AAV expressing the LacZ gene (AAV-LacZ). Collagen gel containing the LacZ transferred, periosteum derived cells was transplanted into a full thickness articular cartilage defect in 10 rabbits., Results: Infected cells still growing on the plate continued to express LacZ at least 12 weeks after AAV infection, with the highest percentage of LacZ positive cells reaching 74.4%. The LacZ positive cells were recognized at the transplant sites in 8 out of 10 knees., Conclusion: Gene expression in periosteum derived cells was sustained in vitro for at least 12 weeks using the AAV vector, and for 2 weeks ex vivo after transplantation into a cartilage defect.

Background: The cysteinyl leukotrienes (CysLTs) mediate their biological actions through two receptors: CysLT(1) receptor and CysLT(2) receptor., Objective: This study was undertaken to examine the direct effects of CysLTs on eosinophils, such as chemotaxis and degranulation, focusing on CysLT(1)., Methods: Eosinophils were isolated from venous blood from normal volunteers who had no history of allergy (purity >99%). They were subjected to reverse transcription-PCR analysis and flow-cytometric analysis for CysLT(1). Binding assays were performed with [(3)H]LTD(4). Purified eosinophils loaded with Fura-2 acetoxymethyl ester were stimulated with CysLTs, and Ca(2+) influx was measured. Eosinophil migration in response to CysLTs was measured using a 96-well multiwell Boyden chamber. Eosinophils were treated with LTD(4) at 10(-6) M for 60 min followed by incubation for 4 h at 37 degrees C in the presence or absence of IL-5 and eosinophil-derived neurotoxin (EDN) release was evaluated., Results: The expression of the mRNA and protein of CysLT(1) on eosinophils and [(3)H]LTD(4)-specific binding to eosinophils were observed. Neither Th1 cytokine (IFN-gamma) nor Th2 cytokines (IL-4 or IL-5) affected CysLT(1) expression in eosinophils. CysLTs induced an increase in intracellular free Ca(2+) in eosinophils via CysLT(1), as suggested by the efficient inhibition by a CysLT(1) antagonist, pranlukast, in addition to the rank order of potency being LTD(4), LTC(4) and LTE(4). LTD(4) stimulated eosinophils to migrate at 10(-6) M via CysLT(1). LTE(4) also induced significant eosinophil migration at 10(-6) M. LTD(4) enhanced EDN release induced by IL-5 via CysLT(1)., Conclusion: CysLTs induce migration and enhance degranulation in eosinophils via CysLT(1). Accordingly, interaction of CysLTs and CysLT(1) on eosinophils has the potential to play a prominent role in the pathophysiology of asthma., (Copyright 2002 S. Karger AG, Basel)

Objective: Recently, microsomal prostaglandin (PG) E synthase (mPGES) was cloned as a terminal enzyme catalyzing PGH2 to PGE2. We investigated mPGES as well as cyclooxygenase (COX)-2, catalyzing arachidonic acid to PGH2, in synovial cells from patients with rheumatoid arthritis (RA). The effect of dexamethasone on mPGES expression was also studied., Methods: Synovial cells were treated with interleukin 1beta (IL-1beta) and dexamethasone under various conditions, and expression of mPGES mRNA and protein was analyzed by Northern blot and Western blot, respectively. Conversions of arachidonic acid or PGH2 to PGE2 were measured by ELISA. Subcellular localization of mPGES and COX-2 was determined by immunofluorescent microscopic analysis., Results: mPGES mRNA and protein expression were significantly upregulated by IL-1beta in synovial cells. COX-2 mRNA and protein were also upregulated by IL-1beta, but with a different time course from that of mPGES. Conversion of PGH2 to PGE2 increased by IL-1beta and was correlated with mPGES expression. Increased conversion of arachidonic acid to PGE2 was maintained when mPGES and COX-2 were coexpressed. Subcellular localization of mPGES and COX-2 overlapped in the perinuclear region in IL-1beta stimulated synovial cells. Dexamethasone inhibited mRNA and protein expression for mPGES and increased conversion of arachidonic acid to PGE2, but inhibition of mPGES was weaker compared with that of COX-2 in IL-1beta stimulated cells., Conclusion: The results suggest that abundant PGE2 production at inflammation sites such as rheumatoid synovia is caused by the coordinated upregulation of mPGES and COX-2. Thus mPGES might be a potential new target for therapeutic strategies to control PGE2 synthesis specifically in patients with RA and other inflammatory diseases.

Objective: To investigate the roles of NF-kappa B and I-kappa B in chondrocytes in the cartilage destruction of mouse collagen-induced arthritis., Methods: DBA/1 mice were immunized with bovine type II collagen (C II) emulsified with Freund's incomplete adjuvant. Histological abnormalities in the mouse knees were evaluated in sections stained with hematoxylin and eosin, or toluidine blue. Immunostaining using anti-NF-kappa B and anti-I-kappa B antibodies was performed to observe the expression and nuclear shift of NF-kappa B and I-kappa B in articular chondrocytes., Results: Loss of metachromasia of perichondrial cartilage was found in 8 out of 10 knees of the mice at 5 weeks, and in all 10 knees at 7 weeks after C II-immunization. The mean percentage of NF-kappa B-positive chondrocytes at 3, 5 and 7 weeks and in the control was 33.6 +/- 7.6, 54.9 +/- 2.7, 75.9 +/- 1.0 and 27.9 +/- 3.8%, respectively. The mean percentage of NF-kappa B-positive nuclei was 9.1 +/- 0.7, 19.5 +/- 3.7, 47.5 +/- 3.0 and 8.6 +/- 0.1%, respectively. NF-kappa B-positive chondrocytes significantly increased from 3 to 7 weeks in a time-dependent manner (p < 0.0001). The percentage of I-kappa B-positive chondrocytes at 3, 5 and 7 weeks and in the control was 15.5 +/- 1.7, 41.1 +/- 2.5, 51.2 +/- 5.7 and 12.1 +/- 2.1%, respectively. I-kappa B-positive chondrocytes significantly increased from 3 to 5 weeks (p < 0.005)., Conclusion: These findings suggest that nuclear shift of NF-kappa B localization causes cartilage destruction in the early stage of arthritis in DBA/1 mice immunized with C II.

In order to obtain better range of motion in knees with osteoarthritis, medial and lateral parapatellar retinaculo-capsular release operations were performed at the time of high tibial osteotomy, with fixation using dual plating on medial compartmental knee osteoarthritis (29 knees) or spontaneous osteonecrosis of the medial femoral condyle (15 knees). At removal of the blade plate, 1 to 2 years after the initial osteotomy, the same release procedures were performed together with resection of adhesive soft tissue and resection of osteophytes, which were obstacles to full flexion. A grading system (Grade 0-3) was proposed to evaluate the duration (min) of formal floor sitting. After these procedures, the patients were able to sit on the floor with 155-165 degrees of flexion for more than 30 min (Grade 3) in 20 knees, for 10-29 min (Grade 2) in seven, for less than 10 min (Grade 1) in nine and were unable to sit on the floor (Grade 0) in eight knees. Maximum knee flexion and total range of motion were 142+/-8.4 degrees and 137+/-11 degrees before and 152+/-6.6 degrees and 151+/-7.4 degrees after surgery, respectively. The American Knee Society Knee Score and Function Score were 61+/-17 and 46+/-16 before, and 97+/-5 (P<0.0001) and 91+/-13 (P<0.0001) after surgery at the final follow-up, respectively. The femoro-tibial angle in standing with one leg was 183+/-6 degrees (3 degrees of anatomical varus angulation) before and 170+/-3 degrees (P<0.0001) (10 degrees of anatomical valgus angulation) after surgery., (Copyright 2002 Elsevier Science B.V.)

Dunn osteosarcoma cell growth was observed in C3H/Hej mouse subcutaneous air pouch. Inoculation with Dunn osteosarcoma cell suspension was performed by injection into air pouches of 70 mice on Day 7 after the initial injection of air. The developmental pattern of the tumor cell colonies was classified histologically into five stages. In Stage 0 (stage of no tumor cells), there were no tumor cells. In Stage 1 (focal stage), the colonies were limited to the lining-cell layers. In Stage 2, (segmental stage) the colonies protruded into the cavity of the pouch. In Stage 3 (annular stage), the total surface of the inner wall of the pouch was occupied by tumor cells. In Stage 4 (occlusive stage), the cavity of the pouch was fully occupied by tumor cells. The tumor was observed to develop to stage 1 in all mice 7 days after inoculation. The colonies were all found to be settled initially in the deeper layer of lining cells. Thus, the mouse air-pouch model is useful for direct observation of osteosarcoma cell growth.

Objective: Endometrial perfusions were measured by Doppler ultrasound to evaluate the influence of spontaneous menstrual cycles and to study the effect of clomiphene citrate., Methods: Flow waveforms in right and left uterine arteries were obtained by using transvaginal color Doppler ultrasonography in infertile women with 60 spontaneous menstrual cycles and 37 clomiphene citrate stimulated cycles from the follicular to the luteal phase., Results: In the spontaneous menstrual cycles, the uterine arterial blood flow increased significantly from the follicular phase to the day of ovulation and then increased markedly to about 200 approximately 230% of the follicular phase after the 6th day of ovulation. In the clomiphene citrate stimulated cycles, the uterine arterial blood flow did not change during the periovulatory period and then increased significantly to about 180 approximately 220% of the follicular phase after the 6th day of ovulation., Conclusions: In the present study, the clomiphene citrate stimulated cycles showed lower endometrial perfusion during the periovulatory period compared with those in the spontaneous menstrual cycles. The results suggest that the assessment of endometrial perfusion with Doppler ultrasound can be used to reveal unexplained infertility problems in induced ovarian cycles.

The aim of this study was to explore whether nifedipine influences the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats. Intrauterine ischemia was induced by a 30-min occlusion of the right uterine artery at 20 days of gestation in Wistar rats. Nifedipine (1 mg kg(-1)) or vehicle was injected subcutaneously before the onset of ischemia or 1 h after the start of recirculation. Fetuses were delivered by cesarean section at the end of ischemia (n=6 with vehicle; n=6 with nifedipine pretreatment) or at 4 h of recirculation (n=6 with vehicle; n=6 with nifedipine pretreatment; n=6 with nifedipine posttreatment), and the cerebral mitochondrial respiration was measured polarographically. Tissue oxygen tension was evaluated in placental and fetal cerebral tissues (n=5 with vehicle; n=5 with nifedipine pretreatment). The vehicle treated animals showed a significant decrease in mitochondrial activities at the end of ischemia and 4 h of recirculation. Nifedipine attenuates the secondary deterioration at 4 h of recirculation when given just prior to ischemia, but had no neuroprotective activity when given 1 h after the start of recirculation. Nifedipine pretreatment had no influence on oxygen delivery in placenta and fetal cerebrum during and after ischemia. Despite the short therapeutic window, the treatment of nifedipine attenuates the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats when given just prior to ischemia.

Recirculation after transient intrauterine ischemia has previously been found to be accompanied by secondary mitochondrial dysfunction in the immature rat brain. This study was performed to assess the efficacy of combined treatment with ascorbic acid and alpha-tocopherol in improving secondary brain damage. On the 17th day of gestation, transient intrauterine ischemia was induced by 30 minutes of uterine artery occlusion. Either vehicle, ascorbic acid, alpha-tocopherol, or combination of ascorbic acid and alpha-tocopherol was randomly administered to pregnant rats before and after occlusion. The pups were delivered by cesarean section at 21 days of gestation, and cerebral neocortical tissue was sampled. The mitochondrial respiration was measured polarographically in homogenates. In the ischemia uterine horn, mitochondrial activity of the vehicle treatment decreased significantly to 56% of nonischemic controls. Treatment with ascorbic acid or alpha-tocopherol alone demonstrated a moderate improvement of the secondary mitochondrial dysfunction to 64% and 62% of nonischemic controls, respectively. The combined treatment caused a normalization of mitochondrial activity to 91% of nonischemic controls. These results indicate that combined treatment with ascorbic acid and alpha-tocopherol has a more protective effect against secondary mitochondrial dysfunction after transient intrauterine ischemia compared with the administration of ascorbic acid or alpha-tocopherol alone.

Hydroxyapatite (HAP) cement was implanted in the femur of rats with experimentally induced osteoporosis, and the osteogenic response was studied histomorphologically. Osteoporosis was induced with ovariectomy with either a normal diet or a low-calcium diet. The rats fed a low-calcium diet after ovariectomy showed a decrease in both cumulative photodensity and the cortical thickness index. There was significant bone conduction in the femur of these rats, but the development of new bone was late, and the affinity index was small. The change in the affinity index with time was similar between the ovariectomy group and the ovariectomy/low calcium-group, suggesting the possibility that estrogen plays a major role in bone conduction.

Objectives: To evaluate the outcome of a minimally invasive treatment of unstable two-part proximal humeral fractures using a J-nail., Design: Retrospective case series., Patients: Forty-one unstable two-part proximal humeral fractures (thirty women and eleven men) with a mean age of sixty-five years (range 18 to 95 years) were studied., Intervention: Closed reduction and internal fixation with J-nails., Main Outcome Measures: All fractures were classified using Neer's classification and were displaced and unstable. Forty of the two-part fractures were at the surgical neck and one at the anatomic neck. All patients had a closed reduction and intramedullary fixation using three J-nails. The mean follow-up period was twenty-nine months (range 2 to 4 years). Clinical assessment was performed by doctors who did not participate in the primary surgery and was graded according to Neer's scoring system., Results: All patients experienced immediate pain relief. At the two-year follow-up, the mean angles of active forward elevation, abduction, and extension were 138 degrees (range 80 to 180 degrees), 132 degrees (range 80 to 170 degrees), and 65 degrees (range 40 to 85 degrees), respectively. According to Neer's criteria, the outcome was excellent in twenty-five patients, satisfactory in twelve, unsatisfactory in three, and a failure in one. The final Neer's score showed a significant negative correlation with age (p < 0.01)., Conclusion: J-nail fixation has the advantage of being an almost closed method without the disadvantage of muscle transfixation associated with other methods. The procedure is simple and involves minimal invasion of the soft tissue. Shoulder and elbow function is not impeded because the nails are inserted just below the distal part of the deltoid muscle insertion. This surgical technique may be one of the more reliable and effective treatments for proximal humeral fractures.

Objective: To assess the value of joint fluid analysis for determining cartilage degradation and prognosis in spontaneous osteonecrosis (ON) of the knee., Methods: Synovial fluid was obtained from 30 knees with spontaneous ON (26 medial femoral condyles, 4 medial tibial plateaus) as well as from 50 knees with medial compartmental osteoarthritis (OA) as a control. Levels of chondroitin 6-sulfate (C6S), C4S, and hyaluronic acid were measured with high-performance liquid chromatography. The lesion size, appearance of the articular cartilage, and results of magnetic resonance imaging (MRI) were compared with the results of joint fluid analysis., Results: The mean +/- SD level of C6S was 82.2 +/- 36.6 nmoles/ml in joint fluid from ON knees, which was significantly higher than the levels in knees with grade 2 (47.2 +/- 20.0 nmoles/ml) and grade 3 (55.8 +/- 29.2 nmoles/ml) OA. The C6S:C4S ratio was highest in lesions with mild articular changes and reflected the macroscopic alteration of cartilage overlying the ON lesion. The concentration of C6S in the 9 knees with lesions that covered > or = 40% of the condyle (99.0 +/- 32.9 nmoles/ml) was higher than that in the 17 knees with lesions that covered <40% of the condyle (67.2 +/- 31.7 nmoles/ml). Knees with bone marrow edema on MRI had a higher level of C6S than did knees with a fibrous-like appearance., Conclusion: While radiologic staging was useful for indicating the size of the ON lesion, it was less valuable for determining articular cartilage damage. Joint fluid analysis may provide more precise information about articular cartilage degradation in ON, and the findings may also be of prognostic significance.

High tibial osteotomy was performed in 73 knees of 50 patients with medial and patellofemoral compartmental osteoarthritis of the knee, which was combined with anterior advancement of the distal fragment. At the operation, parapatellar release of the retinaculum and subperiosteal elevation of contracted medial soft tissue were also adjoined. The average age of the patients at the time of surgery was 64 years. The follow-up period was an average of 58 months. On overall clinical results assessed with the Knee Society score, the average total knee score was improved from preoperative 50 points to postoperative 94, and the preoperative average functional score of 47 points increased to 92 postoperatively. At follow-up, pain from a grinding patella was not found in 68 of 73 knees and pain from grinding and deviating of the patella was relieved in more than 96% of all cases. The mean femorotibial angle was reduced from preoperative 185 degrees to postoperative 167 degrees. On skyline view, the width of the lateral facet joint space was widely opened postoperatively, particularly on the flexion angle of 90 degrees. This operative procedure successfully relieved patellofemoral symptoms of the patients with medial and patellofemoral compartmental osteoarthritis of the knee.

Background: In aortic root remodeling operation, it is difficult to perform graft sizing and tailor a graft appropriately. Thus the aim of this study was to create guidelines for sizing and tailoring that would help to standardize the operation., Methods: We studied the anatomy of the aortic root and assessed the reliability of three equations reported to assist in graft sizing with aortic root casts obtained from 127 cadavers., Results: Yacoub's equation and ours accurately predicted the diameter at the sinotubular junction. Three cusps of the aortic valve were not equal in size. Sinus height of the aortic root was unpredictable., Conclusions: Based on these results, we recommend that aortic root remodeling operation should be performed as follows: (1) graft sizing should be performed using Yacoub's way or our way; (2) the tube graft should be cut into three parts in proportion to the size of each cusp; and (3) the position of the commissures in the tube graft should be secured with sutures first, and the depth of the sinuses should be determined later.

Objective: The objective of the present study was to explore whether prenatal dexamethasone treatment influences mitochondrial maturation in the fetal rat brain., Study Design: Mitochondrial respiration was measured polarographically with homogenates of fetal cerebral cortical tissues on day 16 (with saline solution, n = 8; with dexamethasone, n = 8), day 18 (with saline solution, n = 8; with dexamethasone, n = 8), and day 20 (with saline solution, n = 8; with dexamethasone,n = 8) of gestation. Four doses of dexamethasone (0.1 mg small middle dot kg) or vehicle (saline solution) were given, with an interval of 12 hours, until 12 hours before each measurement., Results: In the vehicle-treated animals, mitochondrial respiratory activity was increased significantly after day 18 of gestation. Dexamethasone-treated animals showed a significant increase in mitochondrial activity at day 16 of gestation compared with vehicle-treated animals., Conclusion: The results indicate that prenatal dexamethasone treatment contributes to the precocious maturation of mitochondrial activity in the fetal rat brain. Because acceleration in cerebral mitochondrial activities is required immediately after birth to maintain high-energy phosphate levels, the precocious maturation may be crucial for the successful outcome of the preterm infant.

Objective and Methods: One of the reasons of the wide variation in the management of RA in Japan might be due to the different behaviors between internists and orthopedists. To investigate this possibility, a survey was done at the 44th annual meeting of Japan Rheumatism Association in 2000., Results: Four hundred and ninety clinicians responded to our survey, including 212 internists and 252 orthopedists, respectively. In the management of RA, there was a wide difference between two groups. In particular, although both agreed that an appropriate communication between internists and orthopedists is necessary, half of the orthopedists answered that they don't refer their patients to internists. There was a wide variation in their ways of evaluations and prescribing behaviors. In particular, the use of DMARDs, both as monotherapy and combination, was significantly different between two groups., Conclusions: There was a great difference in the management of RA by internists and orthopedists. These results might be associated with the outcome of RA patients in Japan. Dissemination of information concerning the management of RA, such as guidelines, as well as the establishment of a better health care system is necessary.

Objective and Methods: To gain insight into the current management of RA in Japan, a survey was done at the 44th annual meeting of Japan Rheumatism Association in 2000., Results: Four hundred and ninety clinicians responded to our survey, including 212 internists and 252 orthopedists, respectively. In the management of RA, there was a wide difference between their present behaviors and the ideal way they believe. In particular, an appropriate communication between internists and orthopedists was lacking. There was a wide variation in their evaluations and prescribing behaviors. The treatment of RA in Japan turned out to be unique compared with those in the US and Europe. Prescriptions with little evidence were not unusual., Conclusions: There was a great variation among Japanese clinicians in the management of RA. These results might be associated with poor outcomes of RA patients in Japan. Dissemination of information concerning the management of RA, such as guidelines, as well as the establishment of a better health care system is necessary.

We histologically analyzed tissue biopsy specimens obtained from 4 cases of revised cementless ceramic knee prostheses. Particles were isolated from the specimens, and their size and composition were determined. Implants were removed for aseptic loosening at an average of 64 months. Histologically, polyethylene particles were seen in all cases. The concentration of the particles showed wide variation among cases. The concentration of the particles also showed a wide variation among different biopsy locations, suggesting that the particles were not distributed uniformly around the knee prostheses. Although we analyzed only 4 cases, our results show good correlation between radiographic evidence of geographic osteolysis and the concentration of wear particles. Multiple biopsy specimens may be necessary to characterize adequately particle migration around knee prostheses.

Neural elements are widely distributed in synovium of osteoarthritic knees. In medial compartmental osteoarthritic knees, medial synovium is exposed to mechanical stimuli due to osteophytes and lateral thrust, which may accumulate neuropeptides, especially substance P, in free nerve endings. Free nerve endings containing a large amount of substance P may provoke pain sensation in synovium, and release substance P to the surrounding tissue in subsynovial tissue, which induces synovitis. Neural system may modulate synovitis as well as pain pathway in osteoarthritis of the knee.