Fabrication and Repair of Cartilage Defects with a Novel Acellular Cartilage Matrix Scaffold

The objectives of this study were to develop a three-dimensional acellular cartilage matrix (ACM) and investigate its possibility for use as a scaffold in cartilage tissue engineering. Bovine articular cartilage was decellularized sequentially with trypsin, nuclease solution, hypotonic buffer, and Triton x 100 solution; molded with freeze-drying process; and cross-linked by ultraviolet irradiation. Histological and biochemical analysis showed that the ACM was devoid of cells and still maintained the collagen and glycosaminoglycan components of cartilage. Scanning electronic microscopy and mercury intrusion porosimetry showed that the ACM had a sponge-like structure of high porosity. The ACM scaffold had good biocompatibility with cultured rabbit bone marrow mesenchymal stem cells with no indication of cytotoxicity both in contact and in extraction assays. The cartilage defects repair in rabbit knees with the mesenchymal stem cell-ACM constructs had a significant improvement of histological scores when compared to the control groups at 6 and 12 weeks. In summary, the ACM possessed the characteristics that afford it as a potential scaffold for cartilage tissue engineering.

Coxiella buvnetii infection of an aortic graft with multiple vertebral body erosion

Q fever is caused by Coxiella burnetii and often has an insidious clinical presentation. We describe a rare case of Q fever infection of an aortic graft presenting with pyrexia and constant severe midlumbar pain due to erosion of multiple vertebral bodies. After successful treatment with graft resection and extra-anatomic vascular reconstruction, the patient continues on lifelong antibiotic therapy. We also present regional Q fever epidemiologic data together with a review of all previously documented cases of Q fever infections of vascular prostheses.

Does angiotensin blockade influence graft outcome in renal transplant recipients with IgA nephropathy?

IgA nephropathy (IgAN) is a frequent cause of end-stage renal disease (ESRD) and recurrent disease causes deterioration and graft loss in transplant recipients. No definitive management is known to reduce the risk or severity of recurrent IgAN, and the evidence to support the use of renin-angiotensin system blockade in such patients is limited.

Long-term graft survival in patients with flexible open-loop anterior chamber intraocular lenses

Purpose. To evaluate the long-term graft survival in patients with flexible open-loop anterior chamber intraocular lenses (AC IOL). Methods. We retrospectively reviewed the records of patients with aphakic/pseudophakic bullous keratopathy who underwent penetrating keratoplasty and flexible open-loop AC IOL implantation in our institution from 1983 to 1988. Results. 79 eyes from 77 patients were included in the study. Mean follow-up was 50 months (range 1 to 123 months). At last follow-up 61 eyes (77.2%) had clear grafts. Among them, the visual acuity was = 20/40 in 14 eyes (23.0%), 20/50-20/100 in 22 eyes (36.1%), 20/200-20/400 in 9 eyes (14.8%) and = CF in 16 (26.2%). Increment of glaucoma medications and/or glaucoma surgery was the most frequent complication (37 eyes, 46,8%). Cystoid macular edema was newly diagnosed in 10 eyes (12.7%). Conclusions. Flexible, open-loop anterior chamber lens are a viable option in the treatment of patients with aphakic or pseudophakic bullous keratopathy undergoing penetrating keratoplasty.

Long-term graft survival in patients with flexible open-loop anterior- chamber intraocular lenses

Purpose. To evaluate the long-term graft survival and complications of flexible, open-loop anterior-chamber intraocular lenses in patients with penetrating keratoplasty for pseudophakic or aphakic bullous keratopathy. Methods. We reviewed charts of all consecutive patients who underwent penetrating keratoplasty for pseudophakic or aphakic bullous keratopathy combined with implantation of a flexible, open-loop, anterior-chamber intraocular lens at our institution between 1983 and 1988. One-hundred one eyes of 99 patients were evaluated. Graft-survival rates were calculated by using the Kaplan-Meier actuarial method. Results. Mean follow-up was 49.8 months (range. 1-144). The probability of graft survival at 1, 2, 4, 6, and 8 years was 93, 87, 78, 65, and 65%, respectively. A total of 25 (24.8%) grafts failed. Progressive corneal edema without signs of rejection was the most common finding in patients with failed grafts (10 eyes, 40%). The most frequent complication observed was newly diagnosed or worsening of preexisting glaucoma (46 eyes, 45.5%). Conclusions. Our long-term results support flexible, open-loop anterior-chamber intraocular lenses as a reasonable option, at the time of penetrating keratoplasty, in patients with pseudophakic and aphakic bullous keratopathy.

Autologous scleral patch graft in tube shunt surgery

Purpose . To investigate alternative surgical method to cover subconjunctival portion of the tube in tube shunt surgery in glaucoma Methods. In thirteen eyes of twelve patients who underwent tube shunt surgery at WEH between July 1991 to November 1996 a "rotating" autologous scleral lamellar graft was created to cover the subconjuctival course of the tube. These patients were followed for clinical signs of conjuctival breakdown, graft melt, tube erosion, anterior staphylomas, graft related inflammation, infections or graft related complications. Results. The patients were followed up for a mean of 16 5 months( range 1-60 months). All eyes tolerated the autologous graft well without any clinical evidence of tube erosions, graft melting , graft related or intraocular inflammation Conclusions The use of autologous sciera, to cover the tube in a tube shunt procedure appears to be effective and without inappropriate short term risk. It offers the advantages of availability , lower cost, and eliminates the potential risk of transmission of infectious disease( i.e. slow-virus, HIV etc.).

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

Ninety-one patients were studied serially for chimeric status following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA) or Fanconi Anaemia (FA). Short tandem repeat polymerase chain reaction (STR-PCR) was used to stratify patients into five groups: (A) complete donor chimeras (n = 39), (B) transient mixed chimeras (n = 15) (C) stable mixed chimeras (n = 18), (D) progressive mixed chimeras (n = 14) (E) recipient chimeras with early graft rejection (n = 5). As serial sampling was not possible in Group E, serial chimerism results for 86 patients were available for analysis. The following factors were analysed for association with chimeric status: age, sex match, donor type, aetiology of aplasia, source of stem cells, number of cells engrafted, conditioning regimen, graft-versus-host disease (GvHD) prophylaxis, occurrence of acute and chronic GvHD and survival. Progressive mixed chimeras (PMCs) were at high risk of late graft rejection (n = 10, P <0.0001). Seven of these patients lost their graft during withdrawal of immunosuppressive therapy. STR-PCR indicated an inverse correlation between detection of recipient cells post-SCT and occurrence of acute GvHD (P = 0.008). PMC was a bad prognostic indicator of survival (P = 0.003). Monitoring of chimeric status during cyclosporin withdrawal may facilitate therapeutic intervention to prevent late graft rejection in patients transplanted for SAA.

The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells

The role of hydrogen sulfide (H2 S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2 S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1-0.5 mM) decreased LPS-induced production of nitrite (NO2 (-) ), PGE2 , TNF-a and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-?B activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-a converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activity and decreased TNF-a, IL-1ß, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.

The effect of socioeconomic deprivation on corneal graft survival in the United Kingdom

Objective: To investigate the effect of socioeconomic deprivation on cornea graft survival in the United Kingdom.

Design: Retrospective cohort study.

Participants: All the recipients (n = 13?644) undergoing their first penetrating keratoplasty (PK) registered on the United Kingdom Transplant Registry between April 1999 and March 2011 were included.

Methods: Data of patients' demographic details, indications, graft size, corneal vascularization, surgical complication, rejection episodes, and postoperative medication were collected at the time of surgery and 1, 2, and 5 years postoperatively. Patients with endophthalmitis were excluded from the study. Patients' home postcodes were used to determine the socioeconomic status using a well-validated deprivation index in the United Kingdom: A Classification of Residential Neighborhoods (ACORN). Kaplan–Meier survival and Cox proportional hazards regression were used to evaluate the influence of ACORN categories on 5-year graft survival, and the Bonferroni method was used to adjust for multiple comparisons.

Main Outcome Measures: Patients' socioeconomic deprivation status and corneal graft failure.

Results: A total of 13?644 patients received their first PK during the study periods. A total of 1685 patients (13.36%) were lost to follow-up, leaving 11?821 patients (86.64%) for analysis. A total of 138 of the 11?821 patients (1.17%) developed endophthalmitis. The risk of graft failure within 5 years for the patients classified as hard-pressed was 1.3 times that of the least deprived (hazard ratio, 1.3; 95% confidence interval, 1.1–1.5; P = 0.003) after adjusting for confounding factors and indications. There were no statistically significant differences between the causes of graft failure and the level of deprivation (P = 0.14).

Conclusions: Patients classified as hard-pressed had an increased risk of graft failure within 5 years compared with the least deprived patients.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article

Traumatic Graft Dehiscence after Penetrating Keratoplasty

Objective: To determine the incidence and to explore the risk factors for traumatic graft dehiscence after penetrating keratoplasty. Design: Retrospective case note review. Participants: Five hundred seventy-two consecutive cases were included. Intervention: All subjects who underwent penetrating keratoplasty in 1 regional center between 1992 and 2004 inclusive. Main Outcome Measures: Cases that experienced postoperative traumatic graft dehiscence were identified. Results from 12 other similar studies were pooled for comparison. Results: Fifteen eyes (2.6%) were treated for traumatic wound dehiscence after penetrating keratoplasty. The most striking feature of this series was the bimodal relationship of age and cause of graft dehiscence, with older patients involved in falls and younger patients in accidental or deliberate trauma. Factors that may influence the risk of traumatic graft dehiscence are discussed, in the light of the present findings and pooled data from previous series. Conclusions: This case series indicates that there is long-term risk of traumatic wound dehiscence after penetrating keratoplasty. Younger patients, especially males, should be made aware that their eye, after keratoplasty, will always be vulnerable to injury. High-risk situations should be avoided if possible. Older patients at particular risk should have adequate risk reduction strategies, social support, and supervision, in particular to minimize the risk of falls. © 2008 American Academy of Ophthalmology.

Favorable effect on acute and chronic graft-versus-host disease with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow transplantation from HLA-identical sibling donors for acquired aplastic anemia

Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.