Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model

BACKGROUND: Recently, tissue-engineered chondrocyte transplantation has been tried to treat full-thickness cartilage defects. We developed an injectable type II collagen gel scaffold by chemically reacting type II collagen with polyethylene glycol crosslinker. This type II collagen was prepared from the nasal septa of cattle. In the present study, chondrocytes embedded in type II collagen gel were injected into rabbit full-thickness cartilage defects without a periosteal graft, and the feasibility for clinical application of the gel was evaluated. METHODS: Chondrocytes were isolated from 1-kg New Zealand white rabbits. A full-thickness articular cartilage defect (5 mm diameter, 4 mm depth) was created on the patellar groove of the femur of 16 male 3-kg New Zealand white rabbits. A type II collagen solution of mixed chondrocytes at a density of 1 x 10(7) cells/ml was injected and transplanted into the defect in the right knee. The controls were the defect only in the left knee. At 4, 8, 12, and 24 weeks after operation, four cases from each group were evaluated macroscopically and histologically. RESULTS: After injection into the cartilage defect, the gel bonded to the adjacent cartilage and bone within several minutes. Macroscopic examination revealed that the surface of the transplanted area was smooth and exhibited similar coloration and good integration with the surrounding cartilage at 12 and 24 weeks after transplantation. Histological examination at 8 weeks revealed favorable hyaline cartilage regeneration with good chondrocyte morphology. At 12 and 24 weeks, reparative cartilage remained rich in type II collagen. According to O'Driscoll histological scores, significant differences between the transplanted and control groups were apparent at 12 and 24 weeks. Immunohistochemical staining indicated sufficient type II collagen synthesis in regenerated cartilage 8 weeks after transplantation, and it was maintained until 24 weeks. CONCLUSIONS: These results indicate that type II collagen gel is suitable for injection into cartilage defects without any covering of a graft and offers a useful scaffold during chondrocyte transplantation.     

Behçet’s disease complicated by IgA nephropathy with nephrotic syndrome

A 65-year-old woman with a 48-year history of Behçet’s disease associated with nephrotic syndrome is described. Immunofluorescence study revealed IgA nephropathy. Following treatment with an angiotensin II type-I receptor-blocker, an anti-platelet drug, and an HMG-CoA reductase inhibitor, accompanied by dietary restrictions of protein and sodium, proteinuria was markedly decreased. This report describes our experience with a rare entity of Behçet’s disease complicated by nephrotic syndrome due to IgA nephropathy. Routine urine examination and renal biopsy are needed for the detection and diagnosis of renal problems with Behçet’s disease.     

Combined Major Hepatectomy and Pancreaticoduodenectomy for Locally Advanced Biliary Carcinoma: Long-Term Results

BACKGROUND: This study aimed to define the role of combined major hepatectomy and pancreaticoduodenectomy in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure. METHODS: A retrospective analysis was conducted on 28 patients who underwent a combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma (n = 17) or gallbladder carcinoma (n = 11). Major hepatectomy was defined as hemihepatectomy or more extensive hepatectomy. Altogether, 11 patients underwent a Whipple procedure, and 17 had a pylorus-preserving pancreaticoduodenectomy. The median follow-up time was 169 months. RESULTS: Morbidity and in-hospital mortality were 82% and 21%, respectively. Overall cumulative survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9 months). The median survival time was 6 months with a 2-year survival rate of 0% in 11 patients with residual tumor, whereas the median survival time was 26 months with a 5-year survival rate of 18% in 17 patients with no residual tumor (P = 0.0012). Residual tumor status was the only independent prognostic factor of significance (relative risk 4.65; P = 0.003). There were three 5-year survivors (two with diffuse cholangiocarcinoma and one with gallbladder carcinoma with no bile duct involvement) among the patients with no residual tumor. CONCLUSIONS: Combined major hepatectomy and pancreaticoduodenectomy provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse cholangiocarcinoma and gallbladder carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.     

The effect of weight loss after bariatric surgery on albuminuria

BACKGROUND: Bariatric surgery achieves long-term weight loss in obese adults with improvement of diabetes and hypertension. Little is known about the effect of this weight loss on renal parameters. METHODS: We performed a retrospective study of 94 obese adults who had Roux-en-Y gastric bypass surgery with a mean 12-month follow-up. Baseline (preoperative) mean age was 49 years, 76% were female, 37 had blood pressure (BP) >or= 140/90 mmHg and 32 had Type 2 diabetes. 73 patients had normoalbuminuria (urine albumin creatinine ratio (ACR) <30 mg/g) while 21 had microalbuminuria (ACR 30<300 mg/g). RESULTS: At follow-up (postoperative), we observed a decrease in mean body weight (133.6 to 97.9 kg, p<0.0001), mean hemoglobin A1c (6.3 to 5.6%, p<0.0001) and mean systolic blood pressure (132.7 to 114.0 mmHg, p<0.0001). There was a significant reduction in ACR (median with interquartile range) from 9.5 (5-28) to 5.5 (3-10) mg/g, p < 0.0001. Fewer patients had microalbuminuria (22.2 to 6.2%, p=0.004) after surgery. Subgroup analysis revealed that significant decrease in ACR was present in the 32 patients with diabetes (16.5 (5-67) to 6.0 (4-11) mg/g, p=0.001) and in the 37 patients with metabolic syndrome (8.0 (5-16) to 6.0 (3-13) mg/g, p=0.012), while 25 patients with obesity alone had a lower ACR (6.5 (4-13) to 4.5 (3-8) mg/g, p=0.270). Multiple linear regression analysis showed change in hemoglobin A1c (p=0.011) and baseline level of ACR (p<0.0001) to be significantly associated with change in ACR. CONCLUSION: We conclude that obese adults have a reduction in albuminuria after surgical weight loss, most importantly in patients with diabetes or metabolic syndrome.     

Apatite cement containing cis-diamminedichloroplatinum implanted in rabbit femur for sustained release of the anticancer drug and bone formation

To treat malignant bone tumors, anticancer drugs are administered systemically, simultaneously with surgical therapy. However, drugs administered systemically have considerable invasive action on bone and other organs, and are also associated with various side effects. A bone-cementing material that can maintain high concentrations of anticancer drug at local sites and which can improve local structural weakness after tumor resection would constitute an ideal therapeutic means of treating malignant bone tumors. We therefore applied the concept of a drug delivery system and developed an implant containing calcium phosphate cement and the anticancer drug, cis-diamminedichloroplatinum (CDDP). The results of a sustained release test showed that the in-vitro cumulative release ratio of an implant containing 20% CDDP was over 60%, and a release rate of 0.1 mg/day was maintained. Experiments in vivo, using adult rabbits implanted with 10% CDDP, showed that the platinum (Pt) concentration in local bone marrow was an average 3200 μg/tissue·g 6 weeks after implantation. The concentration of Pt in the systemically administered group was 0.2 μg/tissue·g at 6 weeks. The Pt concentrations in other organs of the implanted group were: 3 μg/tissue·g or less in the kidney, and 2 μg/tissue·g or less in liver. These values were lower than those in the systemically administered group (3.5 and 2.1 μg/tissue·g, respectively). Local bone formation was observed by 12 weeks after implantation. Our implant maintained high Pt concentrations at local sites and the bone that formed reinforced the implant. Received: February 7, 2001 / Accepted: July 23, 2001     

Viability of liver grafts from fasted donor rats: relationship to sinusoidal endothelial cell apoptosis

Previous studies have shown that livers from fasted donors appear to tolerate long-term preservation better than livers from fed donors, but the mechanism is not clear. Some studies have shown that the apoptosis of sinusoidal endothelial cells (SEC) appeared to be a pivotal mechanism of ischemia/reperfusion injury in liver transplantation. The purpose of the present investigation was to evaluate the relation of SEC apoptosis to liver viability in rats after liver transplantation, comparing findings for fasted and fed donors. Wistar rats were used as donors and recipients. The fed group had access to solid feed and water ad libitum. The fasted group was allowed access only to water for 4 days prior to liver harvest. All rat livers were preserved with University of Wisconsin (UW) solution at 2 °C for 24 h. After preservation, the livers were orthotopically transplanted, and survival time was measured. Apoptosis was determined by in-situ staining for apoptotic cells, using a TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay and electron microscope (EM) examination separately. The 14-day survival rates after 24-h preservation were 0% (0/11) for recipients of livers from fed donors and 91% (10/11) for recipients of livers from fasted donors. There was no significant difference in the numbers of TUNEL-positive SEC after 24-h preservation between the two groups. However, at 6 h after transplantation, the number of TUNEL-positive SEC was significantly higher in the fed group than in the fasted group. These results suggest that donor fasting decreases SEC apoptosis after reperfusion alone, and that this may be related to the protection of the liver graft from reperfusion injury. Received: December 22, 2000 / Accepted: February 15, 2001     

Increased levels of serum matrix metalloproteinase-3 in haemodialysis patients with dialysis-related amyloidosis

Background: It is recognized that matrix metalloproteinase‐3 (MMP‐3) is abundantly expressed in active rheumatoid synovium, and that serum level of MMP‐3 is a useful marker for diagnosis of rheumatoid arthritis and for evaluation of prognosis in joint destruction. Little is known about serum MMP‐3 levels in haemodialysis (HD) patients, and thus, the association between serum MMP‐3 and dialysis‐related amyloidosis (DRA) has yet to be elucidated. Methods: Serum levels of MMP‐3 were measured by enzyme immunoassay in 150 HD patients, 90 without DRA and 60 with DRA, before HD. Simple regression analysis was performed to investigate the relationship between serum level of MMP‐3 and clinical parameters, including age, HD duration, C‐reactive protein and β2 microglobulin (BMG). Results: Serum levels of MMP‐3 were significantly higher in HD patients with DRA than in HD patients without DRA (258.2 ± 118.1 vs 201.5 ± 98.4 pg/mL, P = 0.0017), and both levels were significantly higher than those of healthy subjects (45.6 ± 13.4 pg/mL, P < 0.0001). Serum MMP‐3 levels significantly correlated with serum levels of BMG (r = 0.197, P = 0.0164) and HD duration (r = 0.168, P = 0.0427). Moreover, serum MMP‐3 levels significantly correlated with serum BMG levels in HD patients without DRA (r = 0.341, P = 0.0012), but not in HD patients with DRA. Conclusion: Our results suggest that matrix metalloproteinase activity increases in HD patients, which may be associated with BMG and DRA.     

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

OBJECTIVE: Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. METHODS: The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). RESULTS: Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). CONCLUSIONS: The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.     

Acute cardiac tamponade due to a bleeding pericardial cyst in a 3-year-old child

We report a case of a pericardial cyst complicated with acute cardiac tamponade in a 3-year-old child with no previous cardiac history who was transferred to our university hospital because of hemodynamic shock. A chest roentgenogram revealed marked cardiac enlargement, and transthoracic echocardiography showed massive pericardial effusion with a moving cystic structure. Percutaneous needle aspiration yielded bloody pericardial fluid. Emergency drainage of the pericardial effusion and resection of the cyst were performed through a median sternotomy. We found a blood-containing cyst that was attached to the right atrium near the sinus node and to the inferior wall of the pericardial cavity.     

Implications of MYCN amplification in patients with stage 4 neuroblastoma who undergo intensive chemotherapy

Background/Purpose

This study aims to clarify the implications of MYCN amplification in patients with high-risk neuroblastomas treated with 2 different regimens of induction chemotherapy established by the Japan Study Group for Advanced Neuroblastoma.

Methods

Between 1985 and 2003 in Japan, 392 patients with stage 4 neuroblastomas who were older than 12 months were treated with 2 regimens of induction chemotherapy (the combination of cyclophosphamide [CTX], cisplatin [CDDP], pirarubicin, and vincristine or etoposide). Regimen 91A3 or 98A3 (A3) (CTX 2400 mg/m², CDDP 125 mg/m²) was a higher dose combination of CTX and CDDP than regimen 85A1 or 91A1 (A1) (CTX 1200 mg/m², CDDP 90 mg/m²). The 392 cases were classified into 3 groups (A, 1 copy; B, 2-9 copies; C, more than 10 copies) based on the MYCN amplification status by a Southern blot analysis.

Results

The 5-year overall survival rate (5-YS) was 41.1% for all 392 cases. Regarding the MYCN amplification status, the 5-YS was 46.6% for A group (n = 227), 22.7% for B group (n = 26), and 36.0% for C group (n = 139). A flouresence in situ hybridization analysis showed the presence of the cells with more than 10 copies in cases with 2 to 9 copies based on the Southern blot findings. Of the 227 patients in a group, the 5-YS was 46.7% for the 70 cases treated by A3 and 47.0% for 154 cases treated by A1 (nonsignificant). The 5-YS of the 210 patients with stem cell transplantation (SCT) (51.%) was significantly better than that of the 127 patients without SCT (41.1%) (P < .05).

Conclusions

Regarding the MYCN amplification status, the tumor aggressiveness might thus be different between 2 and 9 copies and a single copy of MYCN. In neuroblastomas with 2 and 9 copies of MYCN based on a Southern blot analysis, the MYCN amplification status should be analyzed using the flouresence in situ hybridization method. Induction chemotherapy followed by SCT according to the Japan Study Group for Advanced Neuroblastoma protocol improved the outcome of neuroblastomas with MYCN amplification; however, obtaining a further improvement in the long-term survival of stage 4 neuroblastomas may therefore require the development of an even more effective treatment modality.