Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance

BACKGROUND: Recently, we have described a drug (cyclophosphamide [CP] plus busulfan [BU])-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers. Using this method, we have investigated whether or not this regimen can prolong the survival of heart allografts and inhibit the development of posttransplant cardiac allograft vasculopathy (CAV). METHODS: The components of the method are intravenous administration of 1 x 108 allogeneic spleen cells on day 0, intraperitoneal injection of 200 mg/kg of CP and 30 mg/kg of BU on day 2, and intravenous injection of T cell-depleted 1 x 107 allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting was performed on day 28. Chimerism in peripheral blood was followed by flow cytometric analysis, and histological analysis was performed at various times after grafting. RESULTS: In a fully major histocompatability complex (MHC)-mismatched combination of B10.D2 (H-2d, IE+)-->B10 (H-2b, IE-), stable, multilineage-mixed chimerism was observed permanently. B10.D2 heart grafts were accepted permanently in a donor-specific manner, and posttransplant CAV did not develop. CONCLUSIONS: These results demonstrated that the drug-induced tolerance recently established by us can regularly induce a long-lasting heart allograft tolerance without development of CAV.     

Efficacy of perioperative halo-gravity traction for treatment of severe scoliosis (≥100°)

Background

There have been no standardized surgical options for severe scoliotic curvatures ≥100°. Halo-gravity traction is a viable option for surgical treatment of severe scoliosis. The aim of this study was to evaluate the efficacy and safety of perioperative halo-gravity traction for scoliosis curves ≥100° with respect to radiographic outcomes and clinical complications.

Methods

A total of 21 scoliosis patients with ≥100° curves (average 118.7°; range 100°-158°) with a minimum 2-year follow-up (average 41.8 months; range 24.0-97.0 months) who underwent spinal instrumented fusion using perioperative halo-gravity traction were analyzed. Diagnoses were neuromuscular scoliosis (n = 10), idiopathic (n = 9), and congenital (n = 2). In all, 15 patients were treated by the anterior release procedure followed by final posterior fusion and 6 patients by posterior fusion alone. Six patients had only preoperative traction preceding posterior fusion alone, 6 patients only staged traction between anterior release and final posterior fusion, and 9 patients had both preoperative traction preceding anterior release and staged traction preceding final posterior fusion. The average overall traction period in all patients was 67 days (range 10–78 days).

Results

Radiographic outcomes demonstrated 51.3% correction of the major Cobb angle, 40 mm correction of apical vertebral translation, 76 mm increase of T1-S1 length, and 20.7% increase of space available for lungs at the ultimate follow-up (all comparisons P < 0.05). Preoperative traction demonstrated 27.5% correction of the major curve Cobb angle, 51.5 mm increase of T1-S1 length, 14.9% increase of space available for the lungs (all comparisons P < 0.05). Staged traction after anterior release demonstrated 37.2% correction of the major curve Cobb angle, 26.1 mm correction of apical vertebral translation, 56.5 mm increase of T1-S1 length, 14.2% increase of space available for the lungs (all comparisons P < 0.05). There were only two patients with a pin-site problem, and one required débridement. There were no neurological deficits or clinical complications.

Conclusions

Scoliosis patients with ≥100° curves can be managed successfully by corrective fusion surgery concomitant with perioperative halo-gravity traction without significant complications.     

Intra‐articular injection of hyaluronan restores the aberrant expression of matrix metalloproteinase‐13 in osteoarthritic subchondral bone

Subchondral bone is a candidate for treatment of osteoarthritis (OA). We investigated the effects of intra‐articular injection of hyaluronan (IAI‐HA) on subchondral bone in rabbit OA model. OA was induced by anterior cruciate ligament transection, with some rabbits receiving IAI‐HA. OA was graded morphologically, and expression of mRNA was assessed by real‐time RT‐PCR. Tissue sections were stained with hyaluronan‐binding protein, and penetration of fluorescent hyaluronan was assessed. The in vitro inhibitory effect of hyaluronan on MMP‐13 was analyzed in human osteoarthritic subchondral bone osteoblasts (OA Ob) by real‐time RT‐PCR and ELISA. Binding of hyaluronan to OA Ob via CD44 was assessed by immunofluorescence cytochemistry. Expression of MMP‐13 and IL‐6 mRNA in cartilage and subchondral bone, and morphological OA grade, increased over time. IAI‐HA ameliorated the OA grade and selectively suppressed MMP‐13 mRNA in subchondral bone. IAI‐HA enhanced the hyaluronan staining of subchondral bone marrow cells and osteocyte lacunae. Fluorescence was observed in the subchondral bone marrow space. In OA Ob, hyaluronan reduced the expression and production of MMP‐13, and anti‐CD44 antibody blocked hyaluronan binding to OA Ob. These findings indicate that regulation of MMP‐13 in subchondral bone may be a critical mechanism during IAI‐HA. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:354–360, 2011     

A case of Fournier's gangrene reconstructed using a rectus abdominis muscle flap

We encountered a case of Fournier's gangrene complicated with vesicorectocutaneous fistula that was treated with a pedicled rectus abdominis muscle flap (pedicled RA m-c flap). A 75-year-old man was admitted with consciousness disorder and swelling of the scrotum. The patient had noticed swelling of the scrotum 4 days before admission, but he had ignored this condition. The scrotum and the penis appeared necrotic. On the basis of clinical and radiological findings, we diagnosed this condition as Fournier's gangrene. Surgical debridement was performed in conjunction with the use of broad-spectrum antibiotics. After the patient's general condition was improved, the broad defect in the perineal tissue was covered with a pedicled rectus abdominis muscle flap. The flap was successful. In Japan, this is the first case of Fournier's gangrene complicated with vesicorectocutaneous fistula that was treated with a pedicled RA m-c flap. In order to determine whether plastic surgery after debridement shortens the duration of hospitalization, we reviewed the cases of 120 patients with Fournier's gangrene in Japan. We conclude that plastic surgery after debridement does not shorten the duration of hospitalization, however, this procedures is very useful to deep and broad defects by Fournier's gangrene.     

Ebstein's anomaly in an adult

A 56-year-old female who had been diagnosed with Ebstein's anomaly was admitted with cyanosis and congestive heart failure. The echocardiogram showed severe tricuspid valve incompetence, displacement of the tricuspid valve and dilatation of the atrialized portion of the right ventricle. Atrial fibrillation was detected in the electrocardiogram. She underwent tricuspid valve replacement and right atrial maze procedure. She is released from congestive heart failure and remains in sinus rhythm 48 months after the operation.     

冠状动脉内多普勒超声研究冠状动脉血流速度

目的:评价冠状动脉内多普勒超声测量冠脉血流速度的应用价值。材料和方法:利用冠状动脉内多普勒血流钢丝(FloWire) 测量21 例冠状动脉狭窄患者和12 例正常冠状动脉的血流速度。结果:左前降支冠脉狭窄远端的平均最大血流速度(APV) 、舒张期最大血流速度(DPV) 和舒张期与收缩期流速比值(DSVR) 均显著低于正常组测值。结论:应用冠脉内多普勒超声技术可评价正常和冠脉狭窄病变患者的冠脉血流速度,这为定量研究冠脉血流动力学提供了新方法。     

Incidence and outcome of osteoporotic fractures in 2004 in Sado City,Niigata Prefecture,Japan

Osteoporotic fracture in elderly populations is increasing worldwide, but there are few data on the incidence and outcome of osteoporotic fractures, including upper extremity and vertebral fracture, during a certain period in a defined geographic area. The purpose of this study was to determine the incidence of osteoporotic fractures in a particular area: Sado City, Niigata Prefecture, Japan. From January to December 2004, osteoporotic fractures of the vertebra, hip, distal radius, and proximal humerus in Sado City were recorded. The incidence, age, gender, type of fracture (for hip fracture), right or left side (for distal radius, proximal humerus, and hip fracture), place of injury, cause of injury, outcome, hospitalization period, and patient status regarding taking of drugs for osteoporosis treatment were checked for each fracture. The incidence was calculated based on the whole population of Sado City. The incidence per 100,000 population was 232.8, 121.4, 108.6, and 37.1 for fractures of the vertebra, hip, distal radius, and proximal humerus, respectively. The total incidence of these four kinds of fracture was 499.9 per 100,000 persons per year. The average age at the time of injury was 81.4, 77.7, 75.7, and 60.2 years old for fractures of the hip, vertebra, proximal humerus, and distal radius, respectively. As the average age increased, the percentage of fractures that occurred indoors also increased; that is, a higher percentage of hip fractures occurred indoors, followed by fractures of the vertebra, proximal humerus, and distal radius. Most patients were not taking anti-osteoporosis drugs before fractures of the hip or vertebra. We determined the incidence of major osteoporotic fractures in 1 year in a defined geographic area. Our data showed that 81% of hip fracture patients also had a vertebral fracture and that the average age at the time of injury was higher for hip fractures than for vertebral fractures. Therefore, these results suggest that vertebral fracture leads to hip fracture, indicating that early fracture prevention and continuous prevention strategies through positive treatment are of importance in osteoporotic elderly people.     

Effect of sivelestat sodium on acute lung injury after acute aortic dissection

Acute lung injury is a frequent and serious complication in patients with acute aortic dissection (AAD). Elevated neutrophil elastase has been reported to be one of the major determinants occurring in AAD. On admission, we administered sivelestat sodium hydrate, a neutrophil elastase inhibitor, to 11 patients with AAD who were medically treated to prevent lung injury. We compared their clinical course with that of 12 patients of control group in which sivelestat was not used prophylacticaly. Although there were 5 patients (42%) who suffered from respiratory failure and needed mechanical ventilation in the control group, no one needed intubation in the sivelestat group. Our study suggested that sivelestat sodium hydrate could be effective in preventing intubation due to respiratory failure. Further prospective study is necessary to evaluate prophylactic administration of sivelestat sodium hydrate in AAD.     

The role of graft and host accommodation in a hamster-to-rat cardiac transplantation model

BACKGROUND: We evaluated the importance and mechanism of graft and host accommodation in hamster-to-rat cardiac xenotransplantation models. METHODS: To evaluate graft accommodation, accommodated hamster grafts (Group 2) were transplanted to na?ve host rats treated with FK506, and compared with na?ve hamster grafts (Group 1). To evaluate host accommodation, three groups were evaluated: naive hamster hearts were transplanted to na?ve hosts treated with FK506 (Group 3: 0.5 mg/kg, Group 4: 1.0 mg/kg) and splenectomy, and compared with accommodating hosts (Group 5) with FK506 0.5 mg/kg and splenectomy. We examined graft survival, histopathology, antihamster antibodies and B-1 cells in blood. RESULTS: Graft survival in Group 2 (3.4+/-0.9 days) was not significantly different from that in Group 1 (2.8+/-0.4 days). Graft survival in Groups 4 and 5 (>30 days) was significantly prolonged compared with that in Group 3 (6.0+/-0.7 days). Histopathology of Groups 1-3 showed humoral rejection, whereas Groups 4 and 5 showed normal histology and expression of protective genes. In Groups 1-3, antihamster immunoglobulin (Ig) M and B-1 cells increased significantly compared to Groups 4 and 5, where IgM and B-1 cells remained low or were reduced. CONCLUSIONS: Host accommodation was more important than graft accommodation. Accommodating grafts expressing protective genes were rejected with an elevation of both IgM and B-1 cells. In accommodated hosts, both IgM and B-1 cells decreased, suggesting that B-1 cells may be responsible for the production of antihamster antibodies. These results suggest that sufficient suppression of B-1 cells, resulting in decreased titers of antihamster antibodies, may play an important role in host accommodation.     

Primary carcinoid of the testis associated with carcinoid syndrome

Testicular carcinoid is a rare disease accounting for less than 1% of all testicular neoplasms. It rarely manifests symptoms of carcinoid syndrome. Recent reports have noted that only 1.1-3.1% of testicular carcinoid tumors are complicated by carcinoid syndrome. In general, large tumor size and the presence of carcinoid syndrome are features associated with a malignant course. In the present case, pathological findings revealed pure carcinoid of the testis without metastasis. Moreover, watery diarrhea due to carcinoid syndrome disappeared and the serum serotonin level normalized following orchiectomy. The patient was followed up for 12 months with whole body computed tomography scan and assessment of serotonin levels. To date, there is no evidence of tumor recurrence. These findings suggest that monitoring serum serotonin levels may be useful as a marker during follow up of this type of tumor.