Kidney transplant monitoring by anti donor specific antibodies

Donor-specific anti-HLA antibodies were studied by cytotoxicity crossmatching (CTXM) and flow cytometry crossmatching (FCXM) in 117 kidney transplant candidates; the same study was carried out in 33 cadaver-donor kidney recipients, during the first 3 post-transplant months, for which donor cells were available. Pre-transport evaluation showed that 82.9 % of subjects were CTXM negative/FCXM negative, 6.8 % of patients were positive in both tests, and 10.3 % were CTXM negative/FCCM positive. Post-transplant monitoring for donor-specific antibodies (Abs-DS) showed that nine recipients (27.3 %) were FCXM positive; six of them were IgG + and three IgM +. In comparing these results with the clinical course, a significant association between FCXM IgG + and rejection episodes was observed (P < 0.01).     

How four and twelve weeks of implantation affect the strength and stiffness of a tendon graft securely fixed in a bone tunnel: a study of Evolgate fixation in an extra-articular model ovine model

Healing of a tendon graft to a bone tunnel is slower than the healing of a bone plug. Therefore, the device chosen for hamstring fixation may need to maintain its strength and stiffness longer than the device chosen for bone-tendon-bone fixation. We evaluated, in an extraarticular ovine model, how 4 and 12 weeks of implantation affect the strength of a tendon graft fixed to bone with the Evolgate. The long digital extensor tendon was transplanted and fixed with the Evolgate into a 30-mm long, 8 mm diameter bone tunnel drilled in the tibial metaphysis of both posterior limbs of 15 skeletally mature Suffolk sheep. Immediately after implantation, and 4 and 12 weeks later, biomechanical cyclic load tests in 50 N increments were performed until failure to evaluate the ultimate failure load (UFL). Histological analysis was also performed at 4 and 12 weeks. Biomechanical tests revealed a UFL of 339±120 N at time 0, and increases to 635±19 N (4 weeks) and to 867±80 N (12 weeks). The differences between all 3 groups were significant (p<0.001, paired t test). The histological evaluation showed a layer of cellular, fibrous tissue between the tendon and the bone, along the length of the bone tunnel; this layer progressively matured and reorganized during the healing process. The collagen fibers that attached the tendon to the bone resembled Sharpey’s fibers. The strength of the interface significantly and progressively increased between weeks 4 and 12 after transplantation, and was associated with a degree of bone ingrowth noted histologically. The use of the Evolgate seems not to interfere with the bone ingrowth after implantation, allowing an improvement in strength of the bonetendon- device complex.     

Cell mediated immunity (CMI) and post transplant viral infections — Role of a functional immune assay to titrate immunosuppression

Cell mediated immunity (CMI) was assessed by the ImmuKnow assay in 12 patients after kidney transplantation, who presented with viral infection. Treatment included lowering of immunosuppression in all cases and antiviral treatment if indicated. The assay was repeated during the follow up. The ImmuKnow assay at time of presentation of viral infections was 56.8 ± 58.2 (range 3–178; median 22) ATP ng/ml. With the clearance of viral infection and lowering of immunosuppression, the assay showed an increase in the level of CMI at 194.5 ± 118.9 (range 53–409; median 150) ATP ng/ml. There was viral clearance or stabilization in all cases and there was no incidence of allograft rejection. The ImmuKnow assay of CMI can be used to titrate initial immunosuppression reduction and its subsequent increase, in patients with viral infection after transplantation.     

Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease.

OBJECTIVES: We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001). Moreover, 1,607 (29%) patients underwent coronary revascularization and were censored. Ischemia at SE, resting wall motion score index, and age were independent predictors of death and hard events in both diabetic and nondiabetic patients. Compared with a normal test, ischemia and scar test patterns were associated to significantly lower age-corrected five-year hard event-free survival in diabetic as well as nondiabetic patients. However, a normal test was associated with a greater than two-fold annual event rate in diabetic patients as compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5% vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.     

Low molecular weight advanced glycation end products predict mortality in asymptomatic patients receiving chronic haemodialysis.

BACKGROUND: Advanced glycation end products (AGEs) have biological properties that may contribute to the premature cardiovascular mortality of haemodialysis patients. This study examines the hypothesis that low molecular weight forms of fluorescent AGEs (LMW fluorescence) predict mortality in haemodialysis patients. METHODS: The LMW fluorescence was measured in 85 patients treated with chronic haemodialysis and prospectively followed for 4 years. The primary outcome of all-cause mortality was assessed using Cox proportional hazards regression model. RESULTS: At the end of the follow-up period 37 (44%) patients died. The median LMW fluorescence level was 24.2 arbitrary units (range: 10.6-148.1 AU) and the receiver operator characteristic (ROC) curve cut-off for mortality was 37.0 AU. The LMW fluorescence predicted death both as a binary variable at the ROC cut-off, and as a continuous log-transformed variable when adjusted for age, albumin and C-reactive protein (CRP). Adjusted for age, albumin and CRP, the hazard ratio for mortality was 3.05 (1.41-6.60, P = 0.005) for LMW fluorescence as a binary variable and 2.71 per log unit (1.37-5.38, P = 0.004) as a continuous log-transformed variable. CONCLUSION: The low molecular weight forms of AGEs predict mortality in patients receiving chronic haemodialysis, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients.     

Knee-ankle-foot orthosis in children with duchenne muscular dystrophy: user views and adjustment.

BACKGROUND: The use of knee ankle foot orthoses (KAFOs) to prolong independent mobility is a widely used rehabilitation strategy for children with Duchenne muscular dystrophy (DMD). AIMS: To explore views and adjustment of families with a child with Duchenne muscular dystrophy to the use of KAFOs. METHODS: interviews with families of children aged 8-18 years with DMD; questionnaires on psychiatric adjustment (SDQ for children; GHQ for parents). RESULTS: In total, 17 parents and 9 children took part. Families experienced the introduction of KAFOs as a signal for illness deterioration and a re-awakening of the feelings experienced at diagnosis. Nevertheless, the majority expressed a positive attitude and over two-thirds satisfaction with KAFOs use. High psychiatric risk was found in 2/17 children (12%; expected 10%) and 7/17 main carers (41%; expected 20-30%). CONCLUSION: Most families were satisfied with KAFOs use, and its implementation was well tolerated especially by the children. However, mental distress was high in main carers who emphasized the importance of full preparation and support in this rehabilitation technique.     

Characterization of a YAC containing part or all of the Norrie disease locus

It has been shown from pulsed-field gel electrophoresis (PFGE)that the monoamine oxidase genes A and B (MAOA & MAOB) andDXS7 loci are physically very close. We have therefore extendedstudies on their relationship through the characterisation ofa 650 kb YAC isolated using L1.28 (recognising the DXS7 locus)as a probe. Restriction mapping of the YAC indicates that itcontains both MAOA and MAOB genes in addition to the DXS7 locus.The map derived from the YL1.28-YAC is compatible both withthe map from an independently derived YAC carrying MAOA andB genes and with the long range genomic map for the region.A series of subclones prepared from a 'phage library (lambdaDASH II) of the YAC have been characterised and have been employedto determine the end point of the deletion of a Norrie disease(NDP) patient who has been shown to lack both DXS7 and MAO codingsequences. The pattern of retention of subclones in the deletionpatient place the end point of the deletion within 30–130kb of the proximal end of the YAC. By combining the data withestablished recombination analysis, we provide evidence thatall or part of the NDP lies in the interval of approximately250kb within the YAC.     

Systemic fungemia and hepatic localizations of Fusarium solani in a liver transplanted patient: an emerging fungal agent.

The incidence of invasive fungal infection is increasing especially in the field of transplantation, affecting as many as 50% of bone marrow transplant (BMT) patients with neutropenia and 5-20% of solid-organ transplant (SOT) recipients. Fusarium species are soil saprophytes and plant pathogens. They may cause superficial mycoses or important opportunistic infections in patients with bone marrow suppression and neutropenia, they have been rarely described in solid organ recipients, and up to now there have been no reports of such infection in isolated liver transplanted patients. We describe a case of disseminated Fusarium solani infection with hepatic localization in a liver transplanted patient that resolved with the administration of amphotericin B. Our observation confirms that Fusarium spp. are emerging pathogens that may most frequently affect not only BMT patients and patients with hematological malignancies, but also SOT patients. They may cause both localized and disseminated infection. In conclusion, Fusarium spp. etiology should be considered in the context of infectious diseases following liver transplantation.