Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal.

Graft function at 6 or 12 mo is positively correlated with renal transplant survival. The 36-mo results of a study that tested whether withdrawing cyclosporine (CsA) from a sirolimus (SRL)-CsA-steroid (ST) regimen would affect renal graft survival are reported. Eligible patients (n = 430) who were receiving SRL-CsA-ST were randomly assigned at 3 mo to remain on SRL-CsA-ST or to have CsA withdrawn (SRL-ST group).

A longitudinal study of antioxidant status in phenylketonuric patients.

Objectives: To investigate the implications of the three main factors of the antioxidant system reported in relation to oxidative damage in phenylketonuric patients: selenium, ubiquinone-10 (Q10) and antioxidant enzymes over 3 years of metabolic follow-up.

Design And Methods: Longitudinal study of 46 phenylketonuric patients (age range: 6 months-34 years). Antioxidants were measured by atomic absorption spectrophotometric, chromatographic and spectrophotometric procedures.

Do adult patients with phenylketonuria improve their quality of life after introduction/resumption of a phenylalanine-restricted diet?

Aim: To evaluate the possible influence of dietary treatment on the quality of life of adult patients with PKU (phenylketonuria) following late introduction or resumption of a Phe-restricted diet.

Methods: Fifteen adult patients with classical PKU (10F, 5M; mean age: 27.5 y, range: 16.

[Factor V Leiden mutation as a cause of venous thrombosis].

Introduction: Venous thrombosis is infrequent in paediatrics. A lot of prothrombotic risk factors have been described. Disturbances of coagulation are present in more than half of children with stroke.

Rapamycin attenuates atherosclerosis induced by dietary cholesterol in apolipoprotein-deficient mice through a p27 Kip1 -independent pathway.

Activation of immune cells and dysregulated growth and motility of vascular smooth muscle cells contribute to neointimal lesion development during the pathogenesis of vascular obstructive disease. Inhibition of these processes by the immunosuppressant rapamycin is associated with reduced neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease (CGVD). In this study, we show that rapamycin elicits a marked reduction of aortic atherosclerosis in apolipoprotein E (apoE)-null mice fed a high-fat diet despite sustained hypercholesterolemia.

Late renal allograft failure between 1990 and 1998 in Spain: a changing scenario.

Background: Our aim was to study time-dependent modifications in the characteristics of renal transplants in Spain during the 1990s and risk factors associated with death-censored graft failure after the first year.

Methods: A total of 3,365 adult patients who underwent transplantation in 1990, 1994, and 1998 with a functioning graft after the first year were included.

Results: Ten-year patient and graft survival rates were 82% and 70%.

Reflex sympathetic dystrophy syndrome in renal transplanted patients under immunosuppression with tacrolimus.

Reflex sympathetic dystrophy syndrome (RSDS), which probably has a multifactorial etiology, may appear after kidney transplantation. Its clinical manifestations include severe periarticular pain with inflammatory signs, especially in knees and ankles, causing functional disability. Symptoms develop during the first 3 months after transplantation and usually disappear 3 to 6 months later without sequelae.

A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.

Renoprotective effects of losartan in renal transplant recipients. Results of a retrospective study.

Background/aims: Chronic allograft nephropathy is the main cause of late graft loss and nonimmunological factors, including hypertension and proteinuria, the principal etiological factors. In this context, blockage of the renin-angiotensin system could be helpful. The aim of the present study was to review the renoprotective efficacy of losartan in a large group of renal transplant patients undergoing long-term follow-up.

Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene.

We describe a novel mutation in the ND6 gene (T14487C) in a patient with Leigh syndrome. Biochemical analyses indicated a low complex I activity in the patient's fibroblasts but normal values in muscle and liver. Cybrid clones showed a specific complex I defect that correlates with the mutant heteroplasmy levels.

Pharmacodynamic approach to immunosuppressive therapies using calcineurin inhibitors and mycophenolate mofetil.

Background: Graft survival depends on adequate immunosuppression. To evaluate the effect on the immune system of immunosuppressive therapies using calcineurin inhibitors (CNIs), several pharmacodynamic indices have been proposed to complement pharmacokinetic data. In this preliminary study we compared some of these parameters during combined immunosuppressant therapies.

[Role of transforming growth factor beta-1 gene polymorphisms in the development of chronic allograft nephropathy in renal transplant recipients].

Background: Chronic allograft nephropathy (CAN) is the main cause of graft loss after the first year of transplantation, and renal biopsies show a predominance of fibrotic lesions. Human transforming growth factor beta-1 (TGF-beta 1) is the principal profibrogenetic cytokine which has been recently implicated in the development of CAN. Seven TGF-beta 1 gene polymorphisms have been recently described and some of them have been related to the development of several diseases.

[West's syndrome. Analysis, aetiological factors and therapeutic options].

West's syndrome (WS), which is also known as infantile myoclonic encephalopathy with hypsarrhythmia, is one of the generalized epileptic syndromes with a cryptogenic or symptomatic origin. It is an age-dependent epileptic syndrome. The latest neuroimaging techniques have enabled us to gain a better understanding of its physiopathology and to identify new aetiological factors responsible for the clinical symptoms.

Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes.

Objective: To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS.

Methods: Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes.

Effect of apolipoprotein polymorphisms in renal transplant recipients.

Cardiovascular disease (CVD) is the main cause of mortality among long-term renal transplant recipients (RTR). On the other hand, allograft chronic nephropathy is the primary cause of graft loss among long-term RTR. Hyperlipidemia is a predisposing factor for both conditions.

Early elimination of cyclosporine in kidney transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions.

Cyclosporine elimination in a regimen including sirolimus has been shown to be a safe and effective approach to improve graft function. Nevertheless, it is still unknown whether the functional benefit of CyA withdrawal coincides with a subsequent reduction in histologic lesions of chronic damage or development of chronic allograft nephropathy. This consideration would forecast a reduction in the rate of long-term graft loss.

Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial.

Background: Proteinuria is a significant independent determinant of the progression of chronic renal diseases. It induces an increased synthesis of angiotensin II, endothelin and profibrogenic growth factors, such as transforming growth factor-beta (TGF-beta), by mesangial and tubular cells. The antiproteinuric effect of angiotensin-converting enzyme inhibitors (ACEIs) in diabetic and non-diabetic nephropathies predicts long-term renoprotection afforded by these drugs.

Plasma thiols and their determinants in phenylketonuria.

Objective: Treatment of phenylketonuria (PKU) patients consists of a phenylalanine-restricted diet supplemented with a tyrosine-, vitamin- and oligoelement-enriched amino-acid mixture. Vitamins and oligoelements may be deficient when compliance with the supplemented special formula is poor. Plasma thiol concentrations (especially homocysteine) depend mainly on B-vitamin intake.

[Botulinum toxin Type A. Indications and results].

Introduction: Since introduction for clinical in the 80s, the botulinum toxin type A is being used with effectiveness in the treatment of different disorders that goes with exaggerated muscular activity. Numerous studies have been demonstrated useful for focal treatment of spasticity.

Patients And Methods: Some indications of the botulinum toxin type A for the treatment of the cerebral palsy are reviewed, emphasizing that it use must be in a global planning.

[Orally administered drugs in the treatment of spasticity].

Spasticity is a common problem in paediatric neurology and its management constitutes a real professional challenge. There are numerous therapeutic options available and their advantages and disadvantages should be carefully weighed up for each individual patient. It is true that we do not have one single final option, but experience and knowledge of the therapeutic possibilities favour the functional improvement of patients suffering from spasticity.

Spectrum of CBS mutations in 16 homocystinuric patients from the Iberian Peninsula: high prevalence of T191M and absence of I278T or G307S.

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency has been extensively studied, but to date, no spectrum of CBS mutations of Spanish homocystinuric patients has been reported. Here we present a mutation analysis of thirteen Spanish and three Portuguese unrelated homocystinuric patients. Ten mutations were found to account for the thirty-two mutant alleles and five of these (C275Y, L338P, S349N, R379Q, and L456P) are reported here for the first time.