HLA class I antibodies in patients awaiting kidney transplantation and the association with renal graft survival

The presence of alloantibodies against human leukocyte antigens (HLA) in the circulation of a transplant recipient shows a significant negative impact on the outcome of solid-organ transplantations. The aim of this study was to examine the impact on renal graft survival of various patterns of alloantibodies detected among patients awaiting kidney transplantation. Among more than 2000 patients awaiting kidney transplantations between July 1992 and March 2006, were 683 patients who displayed anti-HLA alloantibodies, 318 of whom were enrolled in this study. Each patient was followed for at least 9 months; the presence of HLA alloantibodies was checked every 3 months by an enzyme-linked immunosorbent assay. Among these 318 patients, 55 patients underwent kidney transplantations. Their median follow-up time was 69 (range, 9-129) months, including 267 (84%) who displayed persistent class I HLA alloantibodies. The intermittent presence of class I HLA alloantibodies was seen in 20 (6.3%) patients. Serum class I HLA antibodies which was positive at first then became undetectable in 4 (1.3%) patients. Three (0.9%) patients were unsensitized at first and then developed class I HLA alloantibodies later; & 24 (7.5%) patients had class I HLA alloantibodies only once during the follow-up period. Among these patients, 55 patients received renal transplantations. The median survival time was shortest in the patients with persistent class I HLA alloantibodies (59.9 months) and longest among patients who were positive at first and then became negative thereafter or in whom class I HLA alloantibodies was detected only once (132 months). There was a significant difference in graft survival times between patients who had persistent HLA alloantibodies and those in whom to have class I HLA alloantibodies were detected only once (P < .05). In this study, the persistent presence of class I HLA alloantibodies among pretransplantation patients was associated with poorer renal graft outcomes. Surveys of various patterns of sensitization to class I HLA antigen may help us to perform risk stratification. High-risk patients may need more aggressive approaches to deplete antibody or complement levels.     

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

Summary The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk. Introduction Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1. Methods The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models. Results Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029). Conclusions ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment. Funding Source: This project is supported by CRCG Grant, Bone Health Fund, Matching Grant and Osteoporosis and Endocrine Research Fund of the University of Hong Kong.     

幼龄犬的上颌骨延长

目的 探讨利用牵开成骨技术在幼儿发育期对发育不良的上颌骨进行诱导外科正颌的可能性,牵开成骨是否有碍幼儿上颌骨的继续生长发育。方法 4－6月龄杂种犬13只,行一侧上颌前部根尖下截骨,外置延长器固定,于1周后,按0．5－1mm/d的速度用延长装置牵开,牵开至10－20mm时,固定4－6周,卸下延长器,于术日,牵开前,牵开期间,固定期间定期摄X线片,分批处死动物,行咬合关系变化,三维立体测量及组织学等观察,结果 术侧有确切的延长效果,咬合关系发生变化,延长段经膜内成骨逐渐演谈正常骨组织,术侧的上颌骨除延长段外,生长发育基本与未术侧同步。结论 于颅面生长发育期的幼龄犬行 开成骨,进行诱导外科正颌治疗是有效的,且不致影响其继续生长发育。     

胫骨骨折不同手术固定器材的生物力学研究及其临床意义

目的：确定不同固定器材在胫骨骨折固定中的优缺点。方法：将30具胫骨标本制成中段横行无缺损骨折模型,行单侧外固定支架（UADF）、Crosse-Kempf钉、TCP三种器材固定后,测试各项生物力学性能。结果：抗压刚度GK钉最强,弯曲刚度TCP最强,UADF此二项刚度差,抗扭刚度三者无差异。结论：UADF生物力学性能差,TCP易产生应力遮挡,GK钉固定坚强,术后能早期下地,弹笥模量适中,应力遮挡小,较符合生物力学固定原则。     

Pullout strengths of self-reinforced poly-L-lactide (SR-PLLA) rods versus Kirschner wires in bovine femur

OBJECTIVE: To determine the relative amount of fixation of self-reinforced poly-L-lactide (SR-PLLA) rods and Kirschner wires in bovine cancellous bone by comparing their pullout strength DESIGN: An in vitro laboratory study was performed using bovine femurs. Ten two-millimeter-diameter pins of each type were inserted into cancellous bone and then pulled out, using a material testing machine. The maximum force (pullout strength) was selected over other measurements to compare the amount of fixation of the two types of pins. All of the pins were retrieved for microscopic analysis. A paired t test was performed to analyze the differences between the pullout strength of the two types of pins. SETTING: Orthopaedic Bioengineering Laboratory, University of Louisville School of Medicine, Louisville, Kentucky, U.S.A. SPECIMENS: Two young fresh bovine distal femurs, ten two-millimeter-diameter Kirschner wires, ten two-millimeter-diameter bioabsorbable SR-PLLA rods MAIN OUTCOME MEASUREMENTS: Pullout strength in Newtons, and microscopic pin surface aspect after insertion. RESULTS: Significant differences were noted between the maximum force required to remove the two types of pins (p < 0.01) The K-wire mean pullout force was 37.7 N (SD 13.6), and the SR-PLLA rod mean pullout force was 53.6 N (SD 19.3). Microscopic analysis indicated surface modification only on the SR PLLA rods. DISCUSSION: SR-PLLA composites have shown comparable clinical results to their metallic counterparts. In this study, the pullout strength of SR-PLLA rods was compared with that of conventional K-wires. A significant difference (p < 0.01) favoring bioabsorbable pullout strength was noted. The bioabsorbable pin surface modification during insertion is an interesting finding that warrants further investigation as a potential source of improved fixation. CONCLUSION: SR-PLLA rods retain their hold in bovine cancellous bone better than K-wires. This finding offers to the orthopaedic surgeon more information about new pin fixation methods.     

Use of single saphenous interposition vein graft for primary arterial circuit and secondary recipient site in head and neck reconstruction: a case report

BACKGROUND: Autologous vein grafts are a valuable tool in microsurgical free tissue transfer. Interposition vein grafts offer the surgeon greater freedom when placing the free flap and choosing the recipient vessels, providing valuable options in case recipient vessels are not available for those patients with large wounds. Free flaps transferred to head and neck regions carry a higher risk of failure, which may be expected to increase more with the use of vein grafts. METHODS: We present our case with the double use of a single vein graft for both primary arterial conduit in end-to-end fashion and secondary end-to-side recipient site in the microsurgical reconstruction of a complicated head and neck defect. RESULTS: All these anastomoses and flaps survived perfectly, and the patient was discharged 14 days after the transfer of the second flap. CONCLUSION: Although the anastomosis of 2 flaps to a single vein graft was successful in our case, it represents a higher risk option than different recipient vessels. We provide this alternative procedure in selected patients, as there is no other receipt vessel or recipient blood flow strong enough to supply more than 1 flap.     

Immunosuppressive activity of serum taken from a liver transplant recipient after withdrawal of immunosuppressants

In orthotopic liver transplantation (OLT), tolerance is induced in a certain combination of donors and a recipient in rats and, in some clinical cases, rejection has not occurred in OLT patients after weaning off immunosuppression. However, this mechanism has not yet been elucidated. Among our cases of liver transplantation (LTx), one OLT patient (Patient A) has not required immunosuppressive drugs for the last 5 years, following post-transplant lymphoproliferative disease (PTLD). This patient's serum interleukin-2 levels were undetectable following withdrawal of immunosuppressants. The same serum taken after discontinuing the immunosuppressants inhibited concanavalin A blast cultured cells and up-regulated the IL-4/IFN-gamma gene expression ratio. These results suggested that other proteins were induced following withdrawal of immunosuppressants. Proteomic assay demonstrated 12 differentiated spots exclusive to this patient where immunosuppressants have been discontinued. Haptoglobin, found to have immunosuppressive activity in vitro, may play an important role in the maintenance of drug-free tolerance as a natural immunological suppressor after cessation of immunosuppression. Proteomic analysis will allow us to develop a novel weaning protocol for patients on long-term immunosuppression to avoid major immunosuppressant-related complications.     

Skeletal changes after modified intraoral vertical ramus osteotomy for correction of mandibular prognathism.

BACKGROUND: Orthognathic surgery is widely used to correct congenital and acquired dentofacial discrepancies. Various surgical procedures have been advocated for correction of mandibular prognathism. In this study, a modified intraoral vertical ramus osteotomy has been developed for surgical correction of mandibular prognathism. The aim of this study is to identify contributing factors to skeletal change by analysing cephalometric changes after modified intraoral vertical ramus osteotomy. METHODS: Forty-one patients, treated for absolute mandibular prognathism by bilateral modified intraoral vertical ramus osteotomy, were evaluated cephalometrically with reference to the menton point. A set of four standardised lateral cephalograms were obtained from each subject preoperatively (T1) and immediately postoperatively (T2), prior to removal of maxillomandibular fixation (T3), and at 1-year postoperatively (T4). The mean setback of the menton was 12.4 mm in the horizontal direction. Relapse was defined as forward movement of the menton during the 1-year follow-up. RESULTS: The highly significant backward movements in a horizontal direction were observed during the maxillomandibular fixation period (T3-T2). Moreover, highly significant forward movement was observed following the maxillomandibular fixation period (T4-T3). After 1-year follow-up (T4-T2), the mean changes of the menton were 0.1 mm backward in the horizontal direction. CONCLUSIONS: In this series, the mean skeletal change compared with the amount of setback was less than 1% (0.1/12.4 mm) in backward movement. The results suggest that the modified intraoral vertical ramus osteotomy technique is useful and the more stable approach for correction of severe mandibular prognathism.     

Ventricular peritoneal shunt malfunction after operative correction of scoliosis: report of three cases

Background contextTwo of the most common disease processes associated with hydrocephalus in children are spina bifida and intraventricular hemorrhage of prematurity, both of which are known to be also associated with spinal deformity in later childhood. The occurrence of shunt malfunction after mechanical injury or stress to the hardware has been well documented. Newer techniques in the treatment of neuromuscular scoliosis, including anterior release with segmental fixation, have resulted in more powerful corrections of these large spinal deformities. A new potential cause of shunt malfunction is the aggressive correction of scoliosis.PurposeTo report patients with neuromuscular curves averaging 100° who were subsequently recognized to have perioperative shunt malfunction.Study designThree case studies from a university hospital setting were included.Patient sampleAll three children were young adolescents and had-long term shunts. Two of the children had spina bifida and a third had cerebral palsy. All children underwent anterior release of their scoliosis with posterior segmental instrumentation, with unit rods and sublaminar wires. All had significant correction of their scoliosis.Outcome measuresMalfunctioning of the ventriculoperitoneal shunts were recorded.MethodsChart reviews of three cases were analyzed.ResultsTwo children had shunt malfunctions within a month of their surgery, and one child had intraoperative recognition and externalization of the shunt.ConclusionsOlder children undergoing repair of neuromuscular scoliosis are often preadolescents or adolescents who have the same indwelling shunt systems originally implanted in early infancy. The shunt may be brittle and calcified, and the peritoneal catheter may be short. The correction of scoliosis often results in an almost instantaneous growth of a few inches. Because of the potential difficulty in recognizing shunt malfunction in the perioperative period, consideration should be given for elective revision of the peritoneal catheter in children at risk.     

DNA Methylation Profiling Identifies EYA4 Gene as a Prognostic Molecular Marker in Hepatocellular Carcinoma

Background

DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values.

Materials and Methods

DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene.

Results

Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050).

Conclusions

EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.