Risk markers for later cardiovascular diseases in liver-transplanted children and adolescents.

BACKGROUND: Increased risk of cardiovascular diseases is well described after adult liver transplantation, whereas the risk in the pediatric population still is discussed. The aim of this study was to investigate the prevalence of metabolic syndrome in pediatric liver transplant recipients and whether measurements of carotid intima media thickness and pulse wave velocity were increased compared to healthy controls. METHODS: We included 42 pediatric liver transplantation recipients and examined them for markers of metabolic syndrome, liver fibrosis measured by shear wave velocity, body fat measured by DXA scans and carotid intima-media thickness, and pulse wave velocity (n = 41 for the carotid scans). The ultrasound measurements of carotid intima-media thickness and pulse wave velocity were also conducted on 82 healthy children and adolescents matched on height and age, respectively. RESULTS: Participants had a median age of 13.03 years, and median time since transplantation was 8.54 years. Compared to healthy controls, liver-transplanted patients had significantly increased intima-media thickness measurements in both control groups whereas there was no significant difference with regard to pulse wave velocity. Two patients (6.25%) were diagnosed with metabolic syndrome. Within the group of liver-transplanted pediatric patients, only elevated body mass index was associated with elevated carotid intima-media thickness measurement. Elevated pulse wave velocity was only associated with abdominal obesity. Factors not significantly correlated with either were age, sex, metabolic syndrome, hyperglycemia, triglycerides, years since transplantation, fibrosis of the liver, body fat content, smoking habits, HDL cholesterol levels, hypertension, and mono-drug versus multi-drug therapies. CONCLUSION: Pediatric liver transplant recipients do have an increased risk of increased carotid intima-media thickness.

Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy.

OBJECTIVE: Patients with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy lack neuronal nitric oxide synthase (nNOS). nNOS mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects by a phosphodiesterase 5 (PDE5) inhibitor (sildenafil) improves skeletal and cardiac muscle performance. Sildenafil also improves blood flow in patients with BMD. We therefore hypothesized that sildenafil would improve blood flow, maximal work capacity, and heart function in patients with BMD. METHODS: A randomized, double-blind, placebo-controlled crossover design with two 4-week periods of treatment, separated by 2-week washout was used. We assessed brachial artery blood flow during maximal handgrip exercise, 6-minute walk test, maximal oxidative capacity, and life quality; cardiac function was evaluated by magnetic resonance imaging (MRI) at rest and during maximal handgrip exercise. Muscle nNOS and PDE5 were tested with Western blotting in 5 patients. RESULTS: Sixteen patients completed all skeletal muscle evaluations, and 13 completed the cardiac MRI investigations. Sildenafil had no effect on any of the outcome parameters. No serious adverse effects were recorded. PDE5 and nNOS were deficient in 5 of 5 biopsies. INTERPRETATION: Despite positive evidence from animal models of dystrophinopathy and physiological findings in patients with BMD, this double-blind, placebo-controlled clinical study showed no effect of sildenafil on blood flow, maximal work capacity, and heart function in adults with BMD. This discrepancy may be explained by a significant downregulation of PDE5 in muscle.

Interobserver and intraobserver variation of two-dimensional and three-dimensional anal endosonography in the evaluation of recurrent anal cancer.

PURPOSE: This study was designed to evaluate the interobserver and intraobserver agreement of two-dimensional (2-D) and three-dimensional (3-D) anal endosonography for the detection of local recurrence anal carcinoma. METHODS: Thirty-six patients were treated for anal carcinoma, and seven had recurrent disease. They were investigated by using 3-D endosonography at Rigshospitalet from July 2001 to January 2005 because of suspected local recurrence. The 3-D endosonographic examinations were reviewed from the hard disc by two observers who twice reviewed all 2-D examinations (the axial projection) as well as all 3-D examinations (the axial, as well as the reconstructed coronal and sagittal projections). The observers scored each examination according to the following scale regarding presence of local recurrence: 1 = no finding/benign findings; 2 = properly benign findings; 3 = suspicious findings/malignant findings. Kappa statistic-statistic was used to evaluate interobserver and intraobserver variation. RESULTS: Three-dimensional endosonography achieved better interobserver agreement than 2-D endosonography: kappa 3-D 0.34-047 vs. kappa 2-D 0.15-0.28 and better intraobserver agreement: kappa 3-D 0.34-0.62 vs. kappa 2-D 0.22-0.28. These differences showed P < 0.05. CONCLUSIONS: Three-dimensional endosonography proved to have significantly better interobserver and intraobserver agreement than 2-D endosonography concerning detection of recurrent anal cancer. Three-dimensional endosonography seems to be less dependent of the individual examiner than 2-D endosonography.

Dilatation of aortic grafts over time: what to expect and when to be concerned.

Dilatation of aortic prosthetic grafts is commonly reported, but most reports are anecdotal, with little objective data in the literature. We performed a prospective trial of 303 patients who underwent prosthetic graft repair for aortic aneurysm or occlusive disease, randomizing patients between insertion of a woven polyester or expanded polytetrafluoroethylene (ePTFE) graft. Patients were followed with computed tomography and ultrasonography for up to 5 years in order to assess the frequency and magnitude of postoperative dilatation. Graft dilatation was documented in patients with polyester grafts at 12 months. Thereafter and up to 60 months, polyester grafts did not dilate further. After 5 years, polyester prostheses had dilated by 25% and ePTFE by 12.5%, as determined by computed tomography imaging. These observations suggest that dilatation of prosthetic grafts is more frequent with knitted polyester grafts compared with ePTFE. Dilatation occurs within the first year after implantation and can be, in part, explained by a discrepancy between the initial nominal graft diameter and its diameter after clamp release, probably due to an in vivo adaptation of the textile structure. Interestingly, graft dilatation did not appear to be associated with an increased frequency of graft-related complications.