Ligament reconstruction in thumb carpometacarpal joint instability: A systematic review.

In thumb carpometacarpal (CMC) instability, laxity of the ligaments surrounding the joint leads to pain and weakness in grip and pinch strength, which predisposes the patient to developing CMC joint arthritis. Recent advancements in joint anatomy and kinematics have led to the development of various surgical reconstructive procedures. This systematic review outlines the available ligament reconstruction techniques and their efficacy in treating nontraumatic and nonarthritic CMC instability. Additionally, we aimed to provide evidence which specific ligament reconstruction technique demonstrates the best results. Four databases (Embase, MEDLINE, Web of Science, and Cochrane Central) were searched for studies that reported on surgical techniques and their clinical outcomes in patients with nontraumatic and nonarthritic CMC instability. Twelve studies were analyzed for qualitative review, including nine different surgical ligament reconstruction techniques involving two hundred and thirty thumbs. All but one of the reported techniques improved postoperative pain scores and showed substantial improvement in pinch and grip strength. Complication rates varied between 0% and 25%. The included studies showed that ligament reconstruction effectively alleviated the patients' complaints regarding pain and instability, resulting in overall high patient satisfaction. Nevertheless, drawing definitive conclusions regarding the superiority of any ligament reconstruction technique remains challenging owing to the limited availability of homogeneous data in the current literature.

Immunological response of sheep to injections of plasmids encoding Toxoplasma gondii SAG1 and ROP1 genes.

Infection with the intracellular protozoan parasite Toxoplasma gondii (T. gondii) causes health problems to both humans and livestock and has a large economic impact worldwide. The immune response in sheep following infection with T. gondii was evaluated using six different combinations of plasmid DNA, recombinant antigen and adjuvant. Sheep were generally vaccinated twice by intramuscular injection with plasmid DNA containing gene sequences for either the surface antigen (SAG1) or the rhoptry protein (ROP1) of T. gondii. Two of the groups injected with plasmid DNA SAG1 were boosted with recombinant protein (SAG1). We investigated the efficacy of including oligodeoxynucleotides (ODN) that contain CG motifs (CpG) and the gene coding for ovine granulocyte-macrophage colony stimulating factor (GM-CSF) as potential adjuvants. Administration of the plasmid encoding the ROP1 gene significantly enhanced both IFN-gamma production from peripheral blood cells when cultured in vitro with Toxoplasma antigen, and ROP1-specific IgG1 and IgG2 antibody levels present in serum. However, injection with SAG1 did not stimulate IFN-gamma production. These results indicate the potential of ROP1, given as plasmid DNA, as a potential vaccine candidate to protect sheep against T. gondii infection.

An 11-Year Overview of the Belgian Donor and Transplant Statistics Based on a Consecutive Yearly Data Follow-up and Comparing Two Periods: 1997 to 2005 Versus 2006 to 2007.

BACKGROUND: The Belgian Transplant Coordinators Section is responsible for the yearly data follow-up concerning donor and transplantation statistics in Belgium and presents herein a 10-year overview. METHODS: The procurement and transplant statistics were compared between 2 periods: Period 1 (P1, 1997-2005) versus Period 2 (P2, 2006-2007). RESULTS: The kidney and liver waiting lists (P1 vs P2) showed an overall decrease for a period of 2 consecutive years in P2; kidney (-170 patients; -18%), and liver (-83 patients; -34%). All other waiting lists (heart, lung, pancreas) remained stable. Mean ED further increased (P1 vs P2); 229 (P1) versus 280 (P2, +22.27%). Non-heart-beating donors were significantly (+288%) more often procured in P2. Mean donor age was 37.9 +/- 17.8 years (P1) versus 46.5 +/- 19.9 years (P2), and mean organ yield per donor was 3.48 +/- 1.7 (P1) versus 3.38 +/- 1.8 (P2). Overall transplant activity per million inhabitants increased 21.1%. CONCLUSION: For 2 consecutive years, the Belgian statistics showed significantly increased donor activity with an impact on waiting list dynamics and transplantation. The mean organ yield per donor was not influenced despite an increased average age and change in reason for death.

Change in donor profile influenced the percentage of organs transplanted from multiple organ donors.

We hypothesized that the change in donor profile over the years influenced the percentage of transplantations. We reviewed medical records for all multiple-organ donors (MODs) within our network. The percentage of transplanted organs was compared between 1991-1992 (A) and 2006-2007 (B). In period A, 156 potential MODs were identified compared with 278 in period B. Fifteen potential donors (10%) in period A and 114 (41%) in period B were rejected because they were medically not suitable (40% vs 75%) or there was no family consent (60% vs 25%). Of the remaining effective MODs (141 in period A and 164 in period B), mean (standard deviation = SD) age was 34 (5) years vs 49 (17) years (P < .001). Brain death resulted from craniocerebral trauma in 69% vs 39%, cerebrovascular disease in 24% vs 46%, hypoxia in 4% vs 15%, and brain tumor in 2% vs 0.6% (P < .001). Chest trauma was present in 19% vs 9% (P < .01). The percentage of MODs who received mechanical ventilation for more than 5 days was 8% vs 24% (P < .001). The percentage of organs transplanted in periods A vs B was kidneys, 97% vs 79%; livers, 64% vs 85%; hearts, 60% vs 26%; lungs, 7% vs 35%; and pancreas, 6% vs 13% (P < .001). The number of referred potential MODs increased by 80%, resulting in a small increase in effective MOD organs (17%), mainly because of medical contraindications. The MOD profile changed to older age, fewer traumatic brain deaths, and longer ventilation time. We transplanted more livers, lungs, and pancreases but fewer kidneys and hearts.

Importance of informatics and database management in transplant coordination.

Advanced use of informatics within modern health care has become essential. Transplantation and transplant coordination, a high technically advanced and very specific niche within health care, is strongly depending on time management and exclusion of possible pitfalls within an acute organization at both the donor and the recipient sites. Based on the increased donor and transplant activity, we stratified two goals. The first goal was to improve working methods at the donor site. The second goal was to reduce administrative tasks and increase quality follow-up at the recipient side. For the donor process, we designed a Donor Database, that was created for donor registration and quality data reporting. A 24/24 h accessible website was created and was linked with clinical pathways and reports. For the liver transplant process, we built another database system in FileMaker pro, creating a quality follow-up and reporting methods. Based on a retrospective analysis and review of two executive time periods, we saw a clear improvement in the donor reporting method, and the quality of the procedure. Possible mistakes within the acute organization were easily detected based on clinical pathways provided by the website on one hand, and integrated within the database system on the other hand. We succeeded in bringing high-quality informatics to the floor of donor and transplant procedures and follow-up. Retrospective analysis showed a definite improvement, with a positive impact on data reporting, time management and administrative follow-up.

Evolution in allocation rules for renal, hepatic, pancreatic and intestinal grafts.

Organ transplantation is the victim of his own success. The results of transplantation are excellent and more patients are activated on the waiting list. The need for organs exceeds the supply. Which criteria are used to allocate available grafts to patients on the waiting list ? Organ allocation and finding the "best match" between donor and recipients, is the goal of Eurotransplant, the organ sharing organization for seven European countries (Austria, Croatia, Germany, Luxemburg, Slovenia, The Netherlands and Belgium). Last decade, the allocation system has switched from a "center-driven" (organ allocated to a center) to a "patient-driven" system (organ allocated to a particular patient). For the allocation of abdominal organs some general allocation rules are followed: blood group compatibility, priority for high urgencies. The allocation of kidneys is based on a point score system based on waiting time, HLA and donor location (to reduce the cold ischemia time). In addition to this standard allocation procedure, there are still specific procedures for pediatric recipients and for candidates > or = 65 year old. There is also an "acceptable" mismatch program for recipients at high immunological risk. The liver allocation system recently changed and is now based on the MELD score, a formula that calculates the probability of death within 3 months on the waiting list. For pancreas and intestine, the system is based on blood group, medical urgency, waiting time, donor region and weight (for intestine).

Living donor kidney transplantation: analysis of the first 40 cases performed in UZ Leuven.

Living donation kidney transplantation has been popular worldwide to try to increase the donor pool. In Belgium, the rate of living donation kidney transplantation has been traditionally relatively low compared to other countries. This is--in part--due to the relatively higher cadaveric organ offer that is available in Belgium (around 25 donors per million inhabitants), compared to other countries. However, the increasing waiting times on cadaveric waiting list and the superiority of the results of live donation versus cadaveric kidney transplantation have led to a reappraisal of this strategy. In our center a living donation kidney transplant programme was started in 1997. Since then 40 cases of live donation kidney transplantation have been performed and are reported herein.

Abdominal Transplant Surgery and Transplant Coordination University Hospitals Leuven 1997-2007: an overview.

The transplant surgery and transplant coordination department was created in 1997 to meet up with the demand of the growing abdominal transplant surgery and organ procurement activity at the University Hospitals in Leuven. Since then, the procurement activity has increased and is currently distributed within the University Hospital Gasthuisberg and a network of approximately 25 collaborative hospitals. The profile of the donors has changed with older donors and more co-morbidity factors (obesity, hypertension, etc.). This donor activity represents approximately 30% of the national donor pool. Over the last 10 years, more than 1100 kidneys, more than 500 livers, approximately 50 pancreas, and 5 intestines have been transplanted in both adults and children. One year survival equal to- or exceeding 90% has been achieved for all abdominal organs and this compares favorably with international registries. More than 40 multi-visceral transplants {liver in combination with abdominal (kidney, pancreas, intestine) or thoracic (heart, double lung, heart-lung) organs} have been performed with results equivalent to isolated liver transplants and very little immunological graft loss (probably due to the immunoprotective effect of the liver). A live donation program was started for the kidney (40 cases) and for the liver (10 cases) in adults and children and no surgical graft loss has been seen so far. Introduction of new machine perfusion systems (and development of donor protocols) has made it possible to restart a non-heart-beating donor program for kidney transplantation. Experimental demonstration that livers tolerate short periods of warm ischemia has also allowed to start liver transplantation from non-heart-beating donors. In the future, machine perfusion of livers, viability testing, and biological modulation are likely to widen the use of marginal livers for transplantation and improve the results. An immunomodulatory protocol proven in the lab to induce the development of regulatory T cells has been applied clinically to 5 consecutive intestinal transplants. All 5--at the time of writing--have been rejection-free and have achieved nutritional independence. Continuous research and development is warranted to increase the organ donor pool (currently the solely limiting factor of transplantation) and to optimize long-term graft and patient outcome.

Donor categories: heart-beating, non-heart-beating and living donors; evolution within the last 10 years in UZ Leuven and Collaborative Donor Hospitals.

Over the past 10 years, the University Hospitals Leuven and their group of Collaborative Donor Hospitals (approximately 20) have tried to maximize their contribution to the national and Eurotransplant donor pool. In this time period, 1042 potential donors and 703 effective donors were coordinated and their organs allocated through Eurotransplant. This activity represented approximately 30% of the national donor pool and approximately 32% of the national organ pool. For Belgium, the non-heart-beating donor activity represented 11.38% of all donors in 2006. Since 1997, 167 potential live donors have been screened in our center. Of these, 48 transplants (28.74%) (39 kidneys--9 livers) have been performed. A boost of screened candidates was seen over the last 3 years, with a 500% increase of records being evaluated. Although the Belgian live donation activity remains one of the lowest in the world, there has been a clear increase over the last 3 years with about 10% of all kidney transplant activity originating now from live donors.

Overview of the Belgian donor and transplant statistics 2006: results of consecutive yearly data follow-up by the Belgian Section of Transplant Coordinators.

BACKGROUND: The Belgian Section of Transplant Coordinators, created in 1997 under the auspices of the Belgian Transplant Society, is in charge of the collection of the national data about donor/procurement activities. METHODS: Data are collected in all Belgian transplant centers. An annual report is finalized by combining these data with data from the Eurotransplant database. RESULTS: An increase of both potential donors (n = 501, +14.4%) and effective donors (n = 273, +16.7%) was observed in 2006 versus 2005. Among effective donors, 28 were non-heart-beating donors (10.25%). Overall donor ratio was 26.26 donors per million inhabitants. Within potential donors, absence of organ harvesting was due to medical contraindications (28%), family refusal (13%), or legal refusal (2%). Donor mean age was 46.4 years and mean organs/donor was 3.21 +/- 1.7. An overall reduction of Belgian waiting lists was observed in 2006 as compared with 2005 (-5.7% for kidney, -25.7% for liver, -9.4% for heart, -6.7% for lung, and -11.7% for pancreas), while waiting list mortality was 18% for liver, 11% for heart, and 7% for lung. As compared with 2005, transplant activities increased for kidney (n = 485, +24.3%), heart +/- lungs (n = 73, +7.3%), and lungs (n = 83, +39.4%) but decreased for liver (n = 236, -2.1%). Living donation represented 8.45% for kidney (+28.1% vs 2005) and 8% for liver transplantation (-29.6%). CONCLUSION: Globally, a marked increase of procurement and transplant activities was observed in 2006, allowing to limit waiting list and waiting list mortality. Further increase of living donor activity and non-heart-beating donation remains necessary to extend the donor pool.

Liver transplantation using non-heart-beating donors: Belgian experience.

UNLABELLED: Mortality on liver transplantation (OLT) waiting lists has increased dramatically. Until recently, non-heart-beating donors (NHBD) were not considered suitable for OLT, because of a higher risk of primary graft nonfunction (PNF) and biliary strictures. However, recent experimental/clinical evidence has indicated that NHBD-OLT is feasible when the period of warm ischemia is short. PURPOSE: To characterize the results of NHBD-OLT in Belgium, a survey was sent to all Belgian OLT centers. RESULTS: Between January 2003 and November 2005, 16 livers originating from NHBD were procured and transplanted. The mean donor age was 48.8 years, including 9 males and 7 females with mean time of stop-therapy to cardiac arrest being 18 minutes and from cardiac arrest to liver cold perfusion, 10.5 minutes. Mean recipient age was 52.2 years including 12 males and 4 females. Mean cold ischemia time was 7 hours 15 minutes. No PNF requiring re-OLT was observed. Mean post-OLT peak transaminase was 2209 IU/L, which was higher among imported versus locally procured grafts. Biliary complications occurred in 6 patients requiring re-OLT (n = 2), endoscopic treatment (n = 2), surgical treatment (n = 1), or left untreated (n = 1). These tended to be more frequent after prolonged warm ischemia. Graft and patient survivals were 62.5% and 81.3%, respectively, with a follow-up of 3 to 36 months. CONCLUSION: This survey showed acceptable graft/patient survivals after NHBD-LT. The NHBD-liver grafts suffered a high rate of ischemic injury and biliary complications and therefore should be used carefully, namely with no additional donor risk factors, lower risk recipients, and short cold/warm ischemia.

Purification, partial characterization, and clinical evaluation of an adenocarcinoma-associated antigen.

The current investigation describes the purification and partial characterization of a new adenocarcinoma-associated antigen (ACAA). ACAA is a large molecular weight glycoprotein (Mr 790,000 by size chromatography on Sepharose CL-6B) that migrates in the alpha 1 region upon electrophoresis and is eluted from a DEAE-cellulose column at a 0.1 M NaCl concentration. ACAA is immunochemically and biochemically different from carcinoembryonic antigen, alpha-fetoprotein, pancreatic oncofetal antigen, human pancreatic tissue antigen, CA 19-9, ferritin, and acute-phase proteins. Assays for ACAA were carried out using a solid-phase sandwich enzyme immunoassay. The results indicate that ACAA is present in sera of all individuals. Patients with cancer have higher serum levels of ACAA than normal individuals. The greatest frequency of elevated serum values of ACAA was seen in patients with lung and pancreatic cancers followed by colorectal, breast, and prostate cancer. The measurement of ACAA levels may be valuable in the diagnosis and clinical management of patients with certain cancers.

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list.

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.

A heterophile system in human renal transplantation. X. HTA sensitivity includes sensitivity to human B lymphocytes.

Antibodies that react with heterophile transplantation antigen (HTA) have been shown previously not to react with HLA-A, B, or C antigens. This paper presents evidence that anti-HTA does react with a subpopulation of human lymphocytes which is comprised primarily of B cells. Anti-HTA reactivity was removed from sera by absorption with each of three different human B lymphocyte cell lines, but it was unaffected by absorption with platelets or thymocytes. Selected high titer anti-HTA sera absorbed with human platelets, human blood group type AB erythrocytes, and sheep erythrocytes caused lysis of a lymphocyte subpopulation principally composed of B lymphocytes. Absorption of these sera with rat erythrocytes removed both lymphocytic activity and anti-HTA activity. Antibody recovered by affinity purification with rat erythrocyte membrane preparations contained both lymphocytic and anti-HTA reactivity. These data, considered with previous studies, seem to establish that B cell sensitization may be acquired by a substantial segment of the population by natural immunization from enteric flora and/or by infections with enteric bacteria.

A heterophile system in human renal transplantation. IX. Comparison of heterophile transplantation antibodies to antivascular endothelial cell antibodies.

Antibodies to heterophile transplant antigen (HTA) were tested for reactivity with antigens on human umbilical cord antigenic specificities on isolated endothelial cells. Furthermore, there are antigens on endothelial cells that are distinct from HLA-A,B, C, and from HTA. It is concluded that the HTA and the VEC antigens are different.

A heterophile system in human renal transplantation. VIII. The morphological distribution of the antigen in rat tissues.

The morphological distribution of heterophile transplant antigen (HTA) was determined in rat tissues using an indirect immunofluorescence technique. Human anti-HTA sera were used to localize HTA in rat kidney, liver, heart, skeletal muscle, spleen, and stomach. HTA was found in basement membrane and supporting stromal elements of all tissues studied. In the kidney, HTA was demonstrated in tubular basement membrane but not glomerular basement membrane. No evidence for cell surface antigen distribution could be ascertained except for erythrocyte membranes. HTA was not found on endothelium of rat blood vessels. We know of no antigens previously implicated in histocompatibility that are stromal in location.

Soluble HLA antigens and ELISA--a new technology for crossmatch testing.

A soluble HLA ELISA for the detection of donor specific anti-HLA class I IgG antibodies was developed and compared with microlymphocytotoxicity. Donor sHLA was prepared from donor blood or purified blood lymphocytes and captured onto monoclonal antibody coated ELISA plates. After incubation of captured HLA with test serum, bound IgG antibodies were detected using a peroxidase-conjugated anti-human IgG antibody. Serum samples from patients on waiting lists to receive kidney transplants were tested by lymphocytotoxicity (AHG protocol) and/or sHLA ELISA in four different laboratories using HLA preparations from eight organ donors. Concordant crossmatch results were obtained for 854 (99%) of 864 ELISA crossmatches. In contrast, concordant results were obtained for 234 (91%) of 256 lymphocytotoxicity crossmatches. Interlaboratory reproducibility of ELISA results was 99%. In contrast, interlaboratory reproducibility of lymphocytotoxicity assay results was 78%. Endpoint titrations of serum specimens containing anti-HLA antibodies demonstrated equivalent sensitivity of ELISA and AHG lymphocytotoxicity crossmatch and similar sensitivity of ELISA and flow cytometry crossmatch. Specimens tested positive by lymphocytotoxicity without DTT treatment but negative with DTT treatment were tested negative by ELISA. Comparison of lymphocytotoxicity and ELISA crossmatch results showed an agreement of 94%. This demonstrates that detection of anti-donor HLA class I antibodies by ELISA is a reliable alternative to microlymphocytotoxicity testing.

Soluble HLA class II concentrations in normal individuals and transplant recipients. Comparison with soluble HLA class I concentrations.

We developed an ELISA to quantify soluble HLA class II (S-HLA-II) in 702 sera obtained from normal subjects, patients with end-stage renal disease, and recipients of renal, hepatic, and cardiac transplants. Concentrations of S-HLA-II were detectable in 124 of 126 normal individuals. The distribution of normal values described a monophasic curve with a skewed distribution. In transplant recipients, there were no differences between preoperative and posttransplant values, but values in liver patients were significantly higher than in kidney patients, and values for heart patients were lowest of all groups. There were periodic variations in concentrations in individual patients, but these were unrelated to rejection, infection, or any other apparent clinical event. S-HLA-II was consistently present in the urine. All of these observations contrast with previous observations concerning soluble HLA class I (S-HLA-I) molecules, which were almost the precise reverse. It seems likely that these clear differences in S-HLA-II and S-HLA-I concentrations relate to different physiologic processes in either production, function, or elimination.

Serologic allogeneic chimerism.

BACKGROUND: At least some transplanted livers secrete soluble human leukocyte antigens (sHLA) of donor phenotype into the body fluids of recipients. The individuals in whom this phenomenon occurs are by definition serologic allogeneic chimeras. Because an allogeneic transplanted liver may induce tolerance to itself and other organs in animals of the donor strain, and because maintenance of a soluble antigen in the circulation of any animal in sufficient quantity for a sufficient period generally leads to tolerance, this phenomenon may be biologically important. This study was performed to determine how common this phenomenon is and whether it occurs after transplantation of organs other than the liver. METHODS: We studied 445 serum samples obtained from transplant recipients (liver, n=12; kidney, n=18; and heart, n=8) before and at various intervals after transplantation. All patients studied had allografts that had functioned for more than 1 year. We used an enzyme-linked immunosorbent assay to quantitate sHLA-A2 and sHLA-A1/A3/A11 (as a cross-reacting group). Donor and recipient combinations were selected in which measurable allotypes in donors were not present in recipients. In some instances, an additional allotype was present in a recipient but not in a donor. RESULTS: All liver transplant recipients had detectable donor sHLA in their serum samples after transplantation. In 72% of kidney and 50% of heart transplant recipients, donor sHLA was found persistently in serum samples obtained after transplantation. Interestingly, all heart transplant recipients of HLA-A3, but none of HLA-A2, had detectable donor sHLA in their serum samples, a finding that may be due to technical reasons. High and stable serum concentrations of donor sHLA characterize long-term stable allograft function. CONCLUSIONS: Donor sHLA is produced by all transplanted livers, most transplanted kidneys, and at least half of (but probably more) transplanted hearts. The hypothesis that donor sHLA may be tolerogenic to liver transplants can be expanded to include kidney and heart transplants.

HLA in human serum--quantitation of class I by enzyme immunoassay.

A solid-phase, enzyme-linked immunoassay was used to quantitate the soluble fraction of HLA-class I. The sera of 318 individuals were studied, as well as the urine of six individuals with normal renal function. The stability of blood concentrations of the soluble HLA was also evaluated. The data justify the following six conclusions. (1) All normal people have circulating HLA (mean = 357 ng/ml). (2) The population can be divided into one group of low secretors (mean = 162.4 +/- 65.2 ng/ml) and another group of high secretors (mean = 540.7 +/- 185.9 ng/ml) (P less than 0.01). (3) Blood levels in each individual are reasonably consistent over short (days) and long (years) periods of time. (4) The mean concentration of soluble HLA-class I in all renal failure patients was 590 ng/ml, significantly higher than normal (P = less than 0.05); it was highest in patients on peritoneal dialysis (mean = 683 ng/ml) in spite of substantial chronic loss in peritoneal dialysate. (5) Renal allograft recipients with stable allograft function also had mean values greater than normal at 554 ng/ml (P less than 0.05). (6) Soluble HLA-class I was not detected in the urine of individuals with normal renal function.