Phenotype of adult Refsum disease due to a defect in peroxin 7.

The biochemical hallmark of adult Refsum disease (ARD) is an isolated deficiency in the breakdown of phytanic acid. This usually results from a PHYH gene defect, although some cases have been found to carry a PEX7 defect. We describe the phenotype of such a patient, indistinguishable from that of classic ARD.

Development of a time-resolved immunofluorometric assay for quantifying platelet-derived microparticles in human plasma.

Platelet-derived microparticles (PMPs) are considered a marker of platelet activation. They vary considerably in size, and flow cytometry, the predominant method used to assay PMPs, is only detecting larger PMPs (>0.1 microm).

Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation.

Background: Atherosclerosis is considered to be a chronic inflammatory disorder. Several large-scale clinical studies demonstrate that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble CD40 ligand, are potent and independent predictors of vascular risk.

Hypothesis: The study was undertaken to investigate the effect of increasing the statin dose from conventional to aggressive treatment on lipids levels, inflammation, and endothelial function in patients with coronary artery disease (CAD).

Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients.

Objectives: This study was initiated to determine whether heart transplant recipients (HTRs) with cardiac allograft vasculopathy (CAV) have increased levels of high-sensitivity C-reactive protein (hsCRP) and to examine whether an increase in hsCRP after heart transplantation predicts the development of CAV. Furthermore, the effect of pravastatin on plasma levels of hsCRP in HTRs was investigated.

Background: The relationship between CAV and hsCRP, as well as the effect of statins on hsCRP in HTRs, has not been well established.

[Cardiac natriuretic peptides as markers for cardiac disease--where do we stand today?].

Background: A common denominator of many cardiac diseases is increased intracardiac pressure and wall stretch. This is accompanied by increased secretion from the heart of cardiac natriuretic peptides ANP and BNP and the N-terminal part of their prohormones (Nt-proANP, Nt-pro-BNP).

Material And Methods: Current evidence for the utility of cardiac natriuretic peptide measurements for diagnosis and follow-up of cardiac disease is reviewed.

[Refsum disease--rare, but world-famous].

Sigvald Bernhard Refsum (1907-91) was an outstanding Norwegian neurologist, highly respected and recognised both nationally and internationally. His main scientific achievement was that he by clinical means singled out a previously unknown disease entity in the multitude of different neurodegenerative features. In his monograph from 1946 he named the disease "heredopathia atactica polyneuritiformis"; however, it was rapidly known as Refsum's disease.

MicroCRP: a highly sensitive CRP method applied in the monitoring of renal allograft recipients.

A new ultrasensitive fluoroimmunometric assay for C-reactive protein (CRP), called MicroCRP assay, has a lower detection limit of 0.05 mg/l, and a CV of 7.6% at concentration 0.

[Measurements of N-terminal proatrial natriuretic factor in children].

Measurement of plasma levels of natriuretic peptides are now in clinical use in adult patients with heart failure. Experiences in adult medicine cannot be extended to paediatric cardiology due to important physiological differences between adults and children. The haemodynamic background of heart failure in children with congenital heart disease is diverse, and there is no relevant functional or echocardiographic grading system.

Elevation of atrial natriuretic peptide prohormone. Hemodynamic background of the elevation of N-terminal natriuretic peptide prohormone in children with congenital heart disease.

We postulated previously that variables related to pulmonary flow are independent predictors of levels of atrial natriuretic peptide in children with congenital heart disease. The aim of this study was to test this hypothesis in relation to other hemodynamic and clinical variables. During catheterization we measured the levels of plasma N-terminal atrial natriuretic peptide prohormone in the plasma of 68 children with congenital heart disease.

Monitored high-dose azathioprine treatment reduces acute rejection episodes after renal transplantation.

Background: Azathioprine (AZA) is widely used in organ transplantation. Common practice is to adjust dose according to body weight only, despite documented pharmacokinetic variability. The purpose of this study was to investigate whether high-dose AZA treatment monitored by 6-thioguanine nucleotides (6-TGN) levels reduces the incidence of rejection episodes in renal transplantation without a corresponding increase in myelotoxicity.

Patterns of azathioprine metabolites in neutrophils, lymphocytes, reticulocytes, and erythrocytes: relevance to toxicity and monitoring in recipients of renal allografts.

Monitoring of azathioprine (AZA) therapy by the measurement of 6-thioguanine nucleotides (6-TGN) concentrations in red blood cells (RBC) may improve safety and ensure optimal immunosuppressive effects of AZA in organ transplantation. The authors explored the rationale for such monitoring by measuring thiopurine metabolites in peripheral blood cell types that are more relevant to the effects and kinetics of AZA and its active metabolites. Neutrophil granulocytes were isolated by density gradient centrifugation, and CD4+ lymphocytes and reticulocytes by using specific immunomagnetic beads.

Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene.

Refsum disease is an autosomal-recessively inherited disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells in the CSF. All patients exhibit accumulation of an unusual branched-chain fatty acid, phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), in blood and tissues. Biochemically, the disease is caused by the deficiency of phytanoyl-CoA hydroxylase (PhyH), a peroxisomal protein catalyzing the first step in the alpha-oxidation of phytanic acid.

Possibilities for therapeutic drug monitoring of azathioprine: 6-thioguanine nucleotide concentrations and thiopurine methyltransferase activity in red blood cells.

The objectives of this study were to establish monitoring of azathioprine (AZA) treatment in renal allograft recipients by red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) measurements and to characterize the variability of RBC thiopurine methyltransferase (TPMT) activity and the effects on 6-TGN levels and the incidence of rejection episodes. In 82 renal allograft recipients, the effect of standard AZA dosage (3 mg/kg tapered to 1 mg/kg) was compared with higher dosages (3 mg/kg for several days) under 6-TGN monitoring. The authors measured TPMT in these patients and in a group not receiving AZA.

Serum N-terminal proatrial natriuretic factor in children with congenital heart disease.

An objective and simple method of establishing and grading heart failure in children is needed. The N-terminal of the atrial natriuretic factor prohormone, called proANF, is stable in vitro, relatively easy to measure and has been demonstrated as a clinically useful marker of heart failure in adults. We measured proANF in 62 children with congenital heart disease and in 62 age-matched controls, in order to examine the relationship of proANF to different clinical and haemodynamic parameters.

Evaluation of an enzymatic immunoassay for free thyroxine determination in canine serum.

Free thyroxine (FT4) and cholesterol were measured in 400 dogs with either suspected hypothyroidism or dermatological signs such that hypothyroidism needed to be ruled out. Hypothyroidism was diagnosed in 68 dogs from the history, physical examination and stated lower reference limit (< 7 pmol/L) for FT4 in euthryoid dogs. Dogs with FT4 concentrations in the range 6-9 pmol/L were finally categorized as hypo- or euthyroid either on the basis of retesting after 2 months or on their clinical response to thyroid replacement therapy over at least 2 months.

Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and cataract in two siblings--a new recessive syndrome?

Two siblings with atypical methylmalonic aciduria and progressive encephalopathy are reported. Initial symptoms were failure to thrive and growth retardation from the first year of life, progressing to severe mental retardation, microcephaly, dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in the urine was substantially lower than in classical methylmalonic acidemia and was not reduced by vitamin B12 therapy.

Monitoring of azathioprine treatment by determination of 6-thioguanine nucleotide concentrations in erythrocytes.

Thioguanine nucleotides (6-TGN) are intracellular metabolites that may contribute to the antiproliferative effects of AZA. The objectives of our study were to describe the variability of 6-TGN concentrations during AZA therapy and to investigate possible correlations between 6-TGN levels and subsequent myelosuppression. We measured 6-TGN concentrations in RBC of 65 renal transplant recipients from day 0 until 11-64 days after transplantation.

Muscle contraction increases the in vivo structural strength to the same degree in osteopenic and normal rat tibiae.

The increase in structural capacity due to muscle contraction in the lower leg was investigated in osteopenic and normal rats. Osteopenia was induced by ovariectomy combined with a low-calcium diet (0.01%).

Kinetics of mercaptopurine and thioguanine nucleotides in renal transplant recipients during azathioprine treatment.

The purpose of this study was to examine the pharmacokinetics of mercaptopurine (6-MP) and thioguanine nucleotides (6-TGN) during azathioprine treatment. Plasma profiles and urinary excretion of 6-MP and 6-TGN concentrations in red blood cells (RBCs) were measured repeatedly during the first 3 weeks following transplantation in 10 adults, who had received kidney grafts from living related donors. Mean maximal 6-MP plasma concentration (Cmax) was 340 nmol/L (SD = 290), mean time to Cmax (Tmax) was 2 h (SD = 1.