Hyperhomocysteinemia and transplant coronary artery disease in cardiac transplant recipients

BACKGROUND: In cardiac transplant recipients, long-term survival may be limited by transplant coronary artery disease (TxCAD). Hyperhomocysteinemia (Hhcy) has been associated with vascular disease and is common in transplant recipients. The objective of this study was to determine the relationship between fasting homocysteine (Hcy) concentrations and TxCAD in a cohort of cardiac transplant recipients. METHODS: Forty-eight patients more than 5 yr after transplant were recruited from a cohort of 72 consecutive patients with in-depth analysis of homocysteine levels from the Cardiac Transplant Clinic. Early morning fasting blood was obtained, and the plasma separated and frozen within 30 min. Hcy concentrations were determined by high-performance liquid chromatography (HPLC) with pulsed integrated amperometry. Coronary angiograms were reviewed in a blinded fashion. TxCAD was diagnosed, using the most recent angiogram, when a >25% lesion was present anywhere in the coronary tree. RESULTS: Forty-eight patients transplanted between 1985 and 1994 were studied. The mean Hcy concentration for the cohort was 23.5+/-5.0 micromol/L, all patients had homocysteine levels above the upper range of normal (5-15 micromol/L). Hcy concentrations were significantly higher in patients with angiographic evidence of TxCAD: 25.0+/-5.9 vs. 21.9+/-3.4 micromol/L, p=0.03. This effect persisted when covariates were taken into account using logistic regression analysis. CONCLUSIONS: Hhcy is associated with TxCAD. Prospective studies are required to confirm this association and to assess the efficacy of Hcy-lowering therapy in this patient population.     

Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas

LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)- associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV- LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non- Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV- associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.     

Elevated plasma 1,25-dihydroxyvitamin D concentrations in infants with hypercalcemia and an elfin facies

We measured plasma concentrations of 1,25-dihydroxyvitamin D (1,25-(OH)2D) in the course of a 6-to-37-month survey of four children with hypercalcemia and an elfin facies (Williams syndrome). Levels of 1,25-(OH)2D were elevated (160 to 470 pg per milliliter) during the hypercalcemic phase of the disease, when the children were five to nine months old, and they decreased thereafter. Plasma 1,25 (OH)2D levels were higher than those found in three children (16 to 60 months old) with the elfin facies syndrome and no hypercalcemia (42 to 71 pg per milliliter) and eight children (1 to 36 months old) with hypercalcemia and no dysmorphy (12 to 140 pg per milliliter), including two children with vitamin D intoxication. Hypercalcemia in the three children with elfin facies was controlled by a low-calcium diet. Serum calcium levels fell to the normal range, and plasma 1,25-(OH)2D levels were normal for age (18 to 105 pg per milliliter) at 14 to 47 months of age, even after appropriate therapy had been discontinued. These observations suggest that hypercalcemia may be the consequence of abnormal synthesis or degradation of 1,25-(OH)2D in children with the elfin facies syndrome.     

Renal Arterial and Venous Endothelin in Hypertensive Patients with or Without Renal Artery Stenosis

Immunoreactive endothelin (ir-ET) levels were measured in the renal veins and aorta of 43 untreated hypertensive patients immediately before renal angiography. None of the patients used antihypertensive medication. Twenty-seven patients had renal artery stenosis, 17 of which were unilateral and 10 bilateral. Seven of the 17 patients with unilateral renal artery stenosis had an elevated renin ratio. Of the 16 patients with essential hypertension 6 had a unilateral small kidney with a normal blood supply. Although there was a trend towards higher levels of ir-ET in patients with renal artery stenosis, no significant differences in endothelin levels (venous or arterial) were found between different groups of patients or groups of kidneys. More than 75% of kidneys extracted endothelin, there being no significant differences between groups of kidneys. In conclusion, our data demonstrate that endothelin levels and renal endothelin extraction are comparable in essential hypertension and in hypertension associated with renal artery stenosis. Whereas renal uptake or endothelin is the rule, some kidneys, however, release this peptide irrespective of the presence or absence of renal artery stenosis.     

Xanthone additives for blood storage that maintain its potential for oxygen delivery. I. 2-Hydroxyethoxy- and 2-ethoxy-6-(5-tetrazoyl) xanthones in citrate-phosphate-dextrose-adenine (CPDA-1) blood

Two xanthones, 2-hydroxyethoxy-6-(5-tetrazoyl) (BW A440C) and 2-ethoxy- 6-(5-tetraozyl) (BW A827C), are members of a chemical series tested in vitro as potential additives to citrate-phosphate-dextrose-adenine (CPDA-1) medium for blood storage. P50 was maintained in the presence of these compounds during 42 days' storage by a partial maintenance of 2,3 diphosphoglycerate (2,3 DPG) and by a direct effect on hemoglobin previously reported for BW A827C. Red cell 2,3 DPG levels for BW A440C (n = 5), BW A827C (n = 5), and control (n = 6), respectively, were 3.38 +/− 0.47, 3.44 +/− 0.25, and 1.20 +/− 0.10 mM +/− SEM on day 7; 1.16 +/− 0.13, 1.52 +/− 0.37, and 0.16 +/− 0.02 mM on day 21; and 0.67 +/− 0.09, 0.61 +/− 0.08, and 0.06 +/− 0.006 mM on day 42. Red cell adenine triphosphate levels at the same time intervals were 1.84 +/− 0.09, 1.46 +/− 0.18, and 2.11 +/− 0.04 mM; 2.10 +/− 0.05, 2.07 +/− 0.17, and 2.13 +/− 0.05 mM; and 1.42 +/− 0.13, 1.37 +/− 0.13, and 1.38 +/− 0.06 mM, respectively. The degree of hemolysis was less with the addition of the compounds, and the methemoglobin formation, plasma Na+ and K+, and lactate production were unaffected by the compounds.     

Ceramic Coating in Cemented Primary Total Knee Arthroplasty is Not Associated With Decreased Risk of Revision due to Early Prosthetic Joint Infection

BackgroundProsthetic joint infection (PJI) is one of the most frequent and devastating causes of short-term revision total knee arthroplasty (TKA). In vitro evidence suggests ceramic surfaces demonstrate resistance to biofilm, but the clinical effect of bearing surface modifications on the risk of PJI remains unclear. This premier registry-based study examines the influence of ceramic bearing surface coatings on the outcome in cemented primary TKA.MethodsIn total, 117,660 cemented primary TKAs in patients with primary osteoarthritis recorded in the German arthroplasty registry since 2012 were followed up for a maximum of 3 years. The primary endpoint was risk of revision for PJI on ceramic coated and uncoated cobalt-chromium-molybdenum femoral components. Propensity score matching for age, gender, obesity, diabetes mellitus, depression and Elixhauser comorbidity index, and substratification on common design twins with and without coating was performed.ResultsIn total, 4637 TKAs (85.1% female) with a ceramic-coated femoral component were identified, 42 had been revised for PJI and 122 for other reasons at 3 years. No survival advantage due to the risk of revision for PJI could be determined for ceramic-coated components. Revision for all other reasons demonstrated a significant higher rate for TKAs with ceramic-coated components. However, the results of this were confounded by a strong prevalence (20.7% vs 0.3%) of metal sensitivity in the ceramic-coated group.ConclusionNo evidence of reduced risk for PJI due to ceramic-coated implants in cemented primary TKA was found. Further analysis for revision reasons other than PJI is required.     

Growth Hormone Treatment in Short Children with Chronic Renal Failure and after Renal Transplantation: Combined Data from European Clinical Trials

Growth retardation is common in children with chronic renal failure (CRF). To investigate the efficacy and safety of recombinant human growth hormone treatment in such children and in children after renal transplantation, 43 prepubertal children with CRF, and 30 prepubertal and 25 pubertal patients with a renal transplant were studied. Data are reported for 31, 26 and 17 of these patients, respectively. Median height velocity increased from 4.2 to 9.8 cm/year during the first year of treatment, and to 6.8 cm/year during the second year of treatment in the patients with CRF. In the prepubertal transplant group, median height velocity changed from 3.5 to 8.4 cm/year during the first year and to 5.4 cm/year during the second year. In the pubertal transplant group, median height velocity increased from 3.2 to 6.6 cm/year during the first year and was 4.5 cm/year during the second year. The gain in height SDS for the prepubertal children in both the CRF and transplant groups was approximately 1 SD over 2 years. Treatment was well tolerated, and renal function did not change significantly in any group.