Memory improvement following cardiac transplantation

Seventeen patients with severe cardiomyopathy underwent neuropsychological evaluation prior to and at least 1 year after successful heart transplantation. Study candidates were screened, and individuals with a history of stroke, cardiac arrest, or medical and neurological conditions which might affect brain function were excluded. Pre-transplant testing revealed normal intelligence and normal attentional, language, and executive abilities but impaired recent memory. Following heart transplant, memory functioning improved significantly, reaching normal levels. Other cognitive abilities remained unchanged. Results suggest that cardiomyopathy is associated with mesial temporal dysfunction, possibly attributable to inadequate or reduced cerebral blood flow and related hypometabolism. This cerebral dysfunction is potentially reversible following successful transplantation, which restores cardiac output and cerebrovascular perfusion.     

Situs inversus of donor or recipient in liver transplantation

d-Dicentrine, a naturally occurring aporphine type isoquinoline alkaloid, isolated from the root of Lindera megaphylla Hemsl. (Lauraceae), was evaluated for its potential anti-cancer activity. We found d-dicentrine significantly inhibited the growth of human hepatoma cell line HuH-7 by delaying its doubling time in tissue culture. An in vitro colony forming assay showed that d-dicentrine decreased the colony formation efficiency in both hepatoma cell lines, HuH-7 and MS-G2, used in our study. Biosyntheses of the macromolecules DNA and RNA were also strongly inhibited. An MTT assay in 21 tumor cell lines also revealed that d-dicentrine was most cytotoxic to esophageal carcinoma HCE-6, lymphoma cell lines Molt-4 and CESS, leukemia cell lines HL60 and K562, and hepatoma cell line MS-G2. An in vitro tumor growing assay in the Severe Combined immunodeficiency (SCID) mice showed that intraperitoneal injection of d-dicentrine at the dose of 100 micrograms twice a week for 4 weeks significantly inhibited the tumor incidence of leukemia cell line K562 in SCID mice. All these data indicated that d-dicentrine has potential anti-tumor applications.     

Specification of mouse telencephalic and mid-hindbrain progenitors following heterotopic ultrasound-guided embryonic transplantation

We have demonstrated the utility of ultrasound backscatter microscopy for targeted intraparenchymal injections into embryonic day (E) 13.5 mouse embryos. This system has been used to test the degree of commitment present in neural progenitors from the embryonic ventral telencephalon and mid-hindbrain region. Many E13.5 ventral telencephalic progenitors were observed to integrate and adopt local phenotypes following heterotopic transplantation into telencephalic or mid-hindbrain targets, whereas mid-hindbrain cells of the same stage were unable to integrate and change fate in the telencephalon. In contrast, many mid-hindbrain cells from an earlier developmental stage (E10.5) were capable of integrating and adopting a forebrain phenotype after grafting into the telencephalon, suggesting that mouse mid-hindbrain progenitors become restricted in their developmental potential between E10.5 and E13.5.     

Recurrence of recipient Langerhans'' cell histiocytosis following bilateral lung transplantation

The DNA of the temperate bacteriophage Aaphi23 isolated from the oral bacterium Actinobacillus actinomycetemcomitans was examined structurally both in the phage head and in the prophage. The DNA in phage particles comprises 44 kb linear molecules with a terminal redundancy of 1.6 kb, which represent circular permutations. Thus, DNA is packaged into phage heads by the headful mechanism. The Aaphi23 prophage is integrated into the host chromosome.     

Influence of advanced recipient and donor age on the outcome of corneal transplantation. Australian Corneal Graft Registry

AIMS: The aims of this study were to examine the influence of advanced recipient and donor age on the long term outcome of corneal transplantation. METHODS: Records of 1036 penetrating corneal grafts in recipients aged > or = 80 years at surgery (defined as the elderly subset) and 8092 donor corneas used for transplantation were obtained from the Australian Corneal Graft Register database, Kaplan-Meier graft survival plots were compared using log rank statistics. RESULTS: Elderly recipients constituted 15% of the recipient pool. The major indication for corneal transplantation in the elderly was bullous keratopathy. Graft survival fell with increasing recipient age (p < 0.00001); the major cause of graft failure was rejection (33%). The desired outcome in 51% of cases was to improve vision and in 42% of cases to relieve pain; 23% of elderly recipients achieved a Snellen acuity of 6/18 or better in the grafted eye and 66% recorded improved acuity after transplantation. Elderly recipients suffered more complications and comorbidities in the grafted eye than did younger recipients. Donor age (stratified in 10 year intervals) did not influence corneal graft survival significantly (p = 0.10). CONCLUSIONS: Elderly graft recipients fared less well after corneal transplantation than did younger recipients, but outcomes in terms of long term graft survival and visual rehabilitation were still good. Donor age did not affect graft survival.     

Health status and quality of life following cardiac transplantation

There is little information regarding the functional status and quality of life of cardiac transplant patients. This investigation is the largest study describing outcome up to 10 years after cardiac transplantation. We conducted a cross-sectional survey of 200 cardiac transplant recipients using the Sickness Impact Profile and a supplementary questionnaire. The response rate was 48%. The median duration post-cardiac transplantation was 2.3 years (range, 0.5 to 9.7 years). The median age was 53 years (range, 27.1 to 68.7). In comparison to previously published studies, our sample of cardiac transplant recipients had worse quality of life than normals, similar scores to cardiac arrest survivors and post-myocardial infarction patients, and better quality of life than patients with low back pain. We found that those not working (44%) reported a lower quality of life. Musculoskeletal-neurologic complaints were highly prevalent, with generalized weakness in 54% responding, fatigue in 42%, and low back pain in 37%. Lower quality of life was found in patients reporting a higher number of musculoskeletal-neurological disorders. We conclude that there are specific areas for rehabilitation intervention in patients post-cardiac transplantation, and suggest areas for future research directed towards enhancing quality of life for cardiac transplant recipients.     

Immunotherapy with donor leukocyte infusions for patients with relapsed acute myeloid leukemia following partially mismatched related donor bone marrow transplantation

Donor leukocyte infusions (DLI) were used to treat 2 patients with AML who relapsed within 4 months of treatment with partially mismatched related donor (PMRD) BMT representing 1-2 HLA-mismatches. No other form of cytoreductive therapy was given to these patients. Both patients developed GVHD (grade II-III) following DLI requiring steroid therapy. One of these patients went into complete remission following development of GVHD and immunophenotypic analysis of peripheral blood showed increased numbers of CD3+/CD8+ T cells, CD56+/CD8+ lymphokine activated killer (LAK) cells and CD16+/CD56+ natural killer (NK) cells expressing intermediate affinity IL-2 receptor P75. Unfortunately, the response was of short duration and the patient relapsed 8 weeks later ultimately resulting in death. The second patient did not show any response to DLI and died of progressive leukemia in conjunction with active GVHD. We conclude that DLI from PMRD carries a high risk for the development of GVHD and may have an anti-leukemia effect for relapsed AML. The anti-leukemic effect from PMRD DLI may be mediated by cytotoxic T lymphocytes, LAK cells and NK cells.     

Evaluation of cardiac status in iron-loaded thalassaemia patients following bone marrow transplantation: improvement in cardiac function during reduction in body iron burden

Iron-induced cardiac disease is the primary cause of death in transfused patients with thalassaemia major. The beneficial effects of deferoxamine mesylate on clinical cardiac disease have been well described but the impact of therapy on subclinical cardiac dysfunction is unknown. To assess the reversibility of subclinical cardiac dysfunction we studied the cardiac status during iron depletion treatment (phlebotomy) in iron overloaded patients, cured of thalassaemia by marrow transplantation, without clinical manifestation of heart failure but with alteration in both left ventricular diastolic function and in contractility property. 32 patients were studied and demonstrated a slight but significant impairment in the morphology and function if compared with matched normal controls. 17 of these patients were submitted to sequential echocardiographic evaluations during the phlebotomy programme. Following completion of the programme, normalization of the indices of contractility and normalization of diastolic function were observed. This study indicates that transplanted thalassaemia patients with subclinical left ventricular diastolic dysfunction and impaired left ventricular contractility may reverse these processes with an effective regimen of iron reduction such as phlebotomy.     

Recipient to donor conduction of atrial tachycardia following orthotopic heart transplantation

Postspinal headache is one of the most common complications of spinal anesthesia and has repeatedly led to controversy concerning needle size and configuration. In an in vitro investigation, we measured cerebrospinal fluid (CSF) leakage with Sprotte, Whitacre, Quincke, and Atraucan needles under physiological conditions in human dura. The puncture characteristics were examined under an electron microscope. The pencil-point needles show 2-3 times less leakage of CSF compared with the cutting Quincke needles of corresponding size. Between the Sprotte and the Whitacre needles, there were no significant differences. The least loss of CSF occurred with the 26-gauge Atraucan needle. Under the electron microscope, a sharply delineated, persistent perforation channel was shown with the Quincke needles, which may explain the high CSF loss. With pencil-point needles, which push the tissue apart bluntly, a large opening on the inside is found, with some tearing of the dura. However, in contrast to the cutting needles, a persistent perforation channel is not manifested. The 26-gauge Atraucan needle, which both cuts and pushes apart conically, shows a relatively discrete opening on the inside, with slight tears in the dura and arachnoidea but without a visible perforation channel. The results of our study show that larger needles (26-gauge Atraucan) that are easier to handle can lead to good and, in some cases even better, puncture results if they have characteristics of both the cutting and the pencil-point needles. IMPLICATIONS: We compared several brands of pencil-point and standard cutting spinal needles of varying sizes. All pencil-point needles had less cerebrospinal fluid leakage, the least loss occurring with 26-gauge Atraucan needles. Electron microscopic examination of the dura after puncture showed characteristic findings with each needle type. We conclude that the combined cutting and pencil-point characteristics seen in the Atraucan needle may have clinical advantages.     

Restoration of the cAMP second messenger pathway enhances cardiac preservation for transplantation in a heterotopic rat model

Current organ preservation strategies subject graft vasculature to severe hypoxia (PO2 approximately 20 Torr), potentially compromising vascular function and limiting successful transplantation. Previous work has shown that cAMP modulates endothelial cell (EC) antithrombogenicity, barrier function, and leukocyte/EC interactions, and that hypoxia suppresses EC cAMP levels. To explore the possible benefits of cAMP analogs/agonists in organ preservation, we used a rat heterotopic cardiac transplant model; dibutyryl cAMP added to preservation solutions was associated with a time- and dose-dependent increase in the duration of cold storage associated with successful graft function. Preservation was also enhanced by 8-bromo-cAMP, the Sp isomer of adenosine 3',5'monophosphorothioate, and types III (indolidan) and IV (rolipram) phosphodiesterase inhibitors. Neither butyrate alone nor 8-bromoadenosine were effective, and the cAMP-dependent protein kinase antagonist Rp isomer of adenosine 3',5'monophosphorothioate prevented preservation enhancement induced by 8-bromo-cAMP. Grafts stored with dibutyryl cAMP demonstrated a 5.5-fold increase in blood flow and a 3.2-fold decreased neutrophil infiltration after transplantation. To explore the role of cAMP in another cell type critical for vascular homeostasis, vascular smooth muscle cells were subjected to hypoxia, causing a time-dependent decline in cAMP levels. Although adenylate cyclase activity was unchanged, diminished oxygen tensions were associated with enhanced phosphodiesterase activity (59 and 30% increase in soluble types III and IV activity, respectively). These data suggest that hypoxia or graft ischemia disrupt vascular homeostasis, at least in part, by perturbing the cAMP second messenger pathway. Supplementation of this pathway provides a new approach for enhancing cardiac preservation, promoting myocardial function, and maintaining vascular homeostatic properties.     

Postoperative heterotopic ossification in patients with ankylosing hyperostosis on the spine (Forestier's disease)

Heterotopic ossification following hip surgery occurred in three patients with ankylosing hyperostosis of the spine. No technical difficulty during surgery was encountered in these individuals. The occurrence of this postoperative complication, coupled with the appearance of bony outgrowths at sites of ligament attachment throughout the axial and extra-axial skeleton in patients with ankylosing hyperostosis of the spine, suggests the presence of an underlying ossifying diathesis, diffuse idiopathic skeletal hyperostosis (DISH). A significant number of patients with DISH possess the second segregant series antigen, HLA-B27, a feature they share with individuals with other arthropathies characterized by abundant ossification; this gene may be closely related to one which influences bone formation. The possible association of postoperative heterotopic ossification and ankylosing hyperostosis of the spine indicates that a radiographic examination of the vertebral column in patients undergoing hip surgery may be a useful screening procedure.     

Effect of family environment and donor source on patient equality of life following renal transplantation.

The authors examined the degree to which the supportiveness of a patient's family environment predicts change in quality of life following renal transplantation. The sample consisted of 95 patients receiving renal grafts from either a living donor or a cadaveric donor. Patients were initially assessed prior to transplantation with follow-up assessment occurring an average of 5.5 months after transplantation. Among patients receiving a living-donor kidney, those reporting a more supportive family environment exhibited reduced depression, improved mobility, and improved social functioning. However, those living-donor recipients reporting less family support exhibited increased depression and diminished mobility and social functioning after transplantation. Patients receiving a kidney from a cadaveric donor showed modest improvements in quality of life regardless of the degree of family support. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of donor and recipient antigen-presenting cells in priming and maintaining T cells with indirect allospecificity

BACKGROUND: It has been suggested that the sensitization of recipient T lymphocytes against peptides derived from allogeneic major histocompatibility complex (MHC) antigens in the context of self-MHC molecules may contribute to the pathogenesis of chronic allograft rejection. The purpose of this study was to quantitate and characterize the indirect alloresponse in renal transplantation. METHODS: An HLA-A2-negative patient whose A2-positive kidney transplant failed as a result of chronic rejection was selected for this study. T-cell clones were raised using a cocktail of peptides corresponding to polymorphic regions of the A2 sequence and studied by measuring their proliferation using [3H]thymidine incorporation. The presence in vivo of HLA-A2-specific T cells was assessed using limiting dilution analysis. RESULTS: T-cell clones were specific for a single peptide of HLA-A2, residues 92-120, and restricted by HLA-DRB1*1502. The frequency of interleukin-2-secreting T cells specific for this A2 peptide was 1:86,000, only 2-fold lower than that measured against the recall antigen tetanus toxoid. Capitalizing on the similarity of the donor and recipient DR15 alleles (DRB1*1501 and 1502), the question was addressed as to how these T cells had been primed in vivo. Although the large majority of clones responded to A2 synthetic peptide presented by both DR15 alleles, only 3 of 10 clones responded to cells co-expressing DRB1*1501 and A2. CONCLUSION: These data suggest that antigen presentation by recipient APCs is responsible for maintaining T cells with indirect allospecificity in vivo and that, in the context of partial DR matching, indirect presentation by the parenchymal cells of the graft may serve to induce tolerance in T cells with indirect allospecificity.