Search

Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real-time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA forms mut (n = 19), cblA (n = 9) and cblB (n = 4). All the mut (0) and some of the cblB patients had the most severe clinical and biochemical manifestations, displaying non-inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl) in vitro and high plasma odd-numbered long-chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast, mut (-) and cblA patients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in the MUT gene, including mut (0) and mut (-) changes, affected mRNA stability. A new sequence variation (c.562G>C) in the MMAA gene was identified. Most of the cblA patients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense-mediated decay (NMD).

Aims: New interventional techniques to diagnose coronary artery stenosis, such as calculation of myocardial fractional flow reserve (FFR) with a guidewire and pressure transducer, provide a functional assessment of coronary lesions. The present study was designed to investigate the occurrence of cardiac events in patients with coronary syndromes and negative FFR findings in moderately severe coronary stenosis in order to determine the usefulness of this technique in predicting coronary events during follow-up for problems commonly encountered in clinical practice. A further objective was to evaluate the safety of deferring angioplasty in patients with a negative FFR result., Methods: We studied 43 patients with 44 moderately severe coronary artery stenoses on angiography and FFR > or = 0.75. Mean age of the patients was 58 +/- 11.4 years. The indications for coronary angiography included recent unstable angina in 24 (55.8%) patients, recent acute myocardial infarction in 10 (23.2%) patients, 5 (11.6%) patients with a coronary stent who had symptoms of uncertain cause, and stable angina in 4 (9.3%) patients., Results: During a mean follow-up period of 10.7 +/- 5.9 months, clinical events (unstable angina) occurred in five patients. In three patients, the initially investigated artery was involved, and in the two patients who required coronary revascularization, unstable angina was related with an artery different from the one studied initially., Conclusions: Patients with recent coronary syndromes and negative FFR findings in moderately severe coronary stenosis were unlikely to have cardiac events during a 10-month follow-up period. Our findings suggest that FFR is a potentially useful indicator of the likelihood of cardiac events and thus represents a useful aid in clinical decision-making in the hemodynamics laboratory. This diagnostic technique also is potentially useful in identifying patients for whom angioplasty can be safely deferred.

Background: New techniques to evaluate coronary artery disease, such as calculation of myocardial fractional flow reserve (FFR) with a guidewire and pressure transducer, provide a functional assessment of coronary lesions. The present study was designed to determine the correlation between FFR and dobutamine stress echocardiography in patients with moderately severe coronary stenosis in order to judge the usefulness of FFR for commonly encountered clinical problems., Methods and Results: We studied 21 patients with 23 moderately severe coronary artery stenoses on angiography. The FFR was calculated and dobutamine stress echocardiography was performed to detect ischemia. Of the 16 stenoses with a negative FFR (> or = 0.75), dobutamine echocardiography also was negative. In the seven stenoses with a positive FFR (< 0.75), dobutamine echocardiography was positive in three. The efficacy of FFR in detecting ischemia that was confirmed with stress echocardiography was sensitivity 100%, specificity 80%, positive and negative predictive value 42.8%, and 100%, respectively, with a global predictive value 82.6%. A moderate degree of correlation was found between the two diagnostic tests (kappa [kappa] = 0.51)., Conclusions: FFR correlates moderately well with dobutamine stress echocardiography in the assessment of moderately severe lesions in patients for whom coronary arteriography is usually indicated. However, its high negative predictive value makes FFR a useful aid in reaching clinical decisions promptly in the hemodynamics laboratory.

A linear correlation was established between aspartic acid racemization ratio from cave bear dentine collagen and absolute dating. The high correlation coefficient obtained allowed age calculation through amino acid racemization. Aspartic acid and glutamic acid racemization kinetics have also been explored in dentine from a North American black bear (Ursus americanus Pallas). Three sample sets were prepared for kinetic heating experiments in nitrogen atmosphere: one water soaked, one with a water-saturated nitrogen atmosphere, and one without any moisture. It was possible to show that the presence of water is a factor controlling amino acid racemization rate. The aspartic acid in a heating experiment at 105 degrees C shows an "apparent kinetics reversal" which can be explained by a progressive hydrolysis of amino acid chains (proteins and polypeptides). Because of the low potential of collagen preservation over long periods of time, the apparent kinetics reversal phenomenon will not affect the dating of old material where no traces of collagen remain. An apparent kinetics reversal was not observed in glutamic acid, which racemizates more slowly., (Copyright 2001 Wiley-Liss, Inc.)

The case of a patient with neonatal propionic acidaemia is reported. Despite an initially favourable response to the administration of an artificial formula, the patient finally died when 9.5 months old. Protein tolerance never exceeded 1.3 g kg-1 day-1. During the remission periods, when ingesting the formula, 3-hydroxypropionic acid was excreted alone or together with tiglylglycine and/or methylcitrate. In a period of ketoacidosis, in addition to these three metabolites and those of ketoacidosis, elevations of 2-methyl-3-oxovaleric acid, propionylglycine and 2-methyl-3-hydroxybutyric acid were found. A severe deficiency of propionyl-CoA carboxylase in cultured fibroblasts was detected; biotin, when added to the fibroblasts culture media, did not stimulate this enzyme activity. The effectiveness of the administered formula is discussed.