Computational modeling of electromechanical propagation in the helical ventricular anatomy of the heart.

The classical interpretation of myocardial activation assumes that the myocardium is homogeneous and that the electrical propagation is radial. However, anatomical studies have described a layered anatomical structure resulting from a continuous anatomical helical disposition of the myocardial fibers. To further investigate the sequence of electromechanical propagation based on the helical architecture of the heart, a simplified computational model was designed. This model was then used to test four activation patterns, which were generated by propagating the action potential along the myocardial band from different activation sites.

Phenotype and genotype heterogeneity in Mediterranean citrullinemia.

We summarize the diagnosis, outcome, and molecular studies of five Mediterranean patients with citrullinemia: four neonatal classical forms and one subacute form, who also suffers from Down syndrome and presented with severe hepatic encephalopathy at age 7. Mutational analysis revealed three alleles with a common mutation and five new mutations: two Moroccan siblings are homozygous for G390R, the subacute form is compound heterozygous for G390R/G117D (new mutation), and the two other neonatal forms are compound heterozygous for four new mutations: V69A/E270Q and T119I(R108L)/?.

Influence of dose and age on the response of the allopurinol test for ornithine carbamoyltransferase deficiency in control infants.

Measurement of urinary orotidine and orotic acid after an oral allopurinol challenge is an important diagnostic test for ornithine carbamoyltransferase deficiency that is sometimes used in infants (< 1 year of age), although there is little information on normal test results in this age group. We found higher orotidine excretion in normal infants than in older children given the test, whereas orotate excretion was similar in both groups. The increased orotidine excretion appears to be due to the use in the infants of higher allopurinol doses per kilogram of body weight than in the children. The normalized-dose dependency of the orotidine response extends even to adult age. Thus, dose-normalized responses should be used in the test and there is no need for careful age-matching of the controls.

[The clinical practice guidelines of the Sociedad Española de Cardiología on cardiomyopathies and myocarditis]. / Guías de práctica clínica de la Sociedad Española de Cardiología en miocardiopatías y miocarditis.

Myocardial diseases are a extraordinarily heterogeneous group of processes that only have in common the fact that they involve heart muscle and that they cause a wide spectrum of myocardial dysfunction. The approach of the management and treatment of the cardiomyopathies is a continuous matter of discussion because the vast majority of alternatives in this field have not been based on the best scientific possible evidence and, since except for the case of heart failure associated with dilated cardiomyopathy. The majority of different options have not been studied by means of large (or even small) randomized trials. Nevertheless, this chapter has tried to provide the reader with different approaches on how to deal with important clinical problems in dilated, hypertrophic and restrictive cardiomyopathies, and in myocarditis as well. For this, we have utilized the most relevant information found coupled with our best clinical judgment, although we admit that many of the clinical recommendations can be controversial.

Optimization of allopurinol challenge: sample purification, protein intake control, and the use of orotidine response as a discriminative variable improve performance of the test for diagnosing ornithine carbamoyltransferase deficiency.

BACKGROUND: The diagnosis of heterozygosity for X-linked ornithine carbamoyltransferase (OCT) deficiency has usually been based on measurement of the increase of orotate and orotidine excretion after an allopurinol load. We examined the choices of analyte, cutoff, and test conditions to obtain maximal test accuracy. METHODS: Urine orotate/orotidine responses to allopurinol load in 37 children (13 OCT-deficient and 24 non-OCT-deficient) and 24 women (7 at risk for carrier status and 17 not related to OCT-deficient children) were analyzed by liquid chromatography after sample purification by anion-exchange chromatography. Diagnostic accuracy was evaluated by nonparametric ROC curves. RESULTS: Sample purification was necessary to prevent interferences. Orotate and orotidine excretion increased with increased protein intake during the test. At a cutoff of 8 mmol orotidine/mol creatinine, sensitivity was 1.0 and specificity was 0. 92 in mild forms of OCT deficiency. Results in monoplex carrier women may differ greatly from those expected because of the genetics of this deficiency. CONCLUSIONS: Standardization of protein intake is required in the allopurinol loading test. A negative response in the face of clinical suspicion should be followed with a repeat test during a protein intake not <2.5 g x kg-1 x day-1. Measurements of orotidine provide better clinical sensitivity than measurements of orotate.

[Advances in biochemistry in the understanding of neurometabolic disorders]. / Avances bioquímicos en el conocimiento de las enfermedades neurometabólicas.

The progress in the knowledge of neurometabolic diseases is due to the conjunction of innovations in several scientific and technological areas. Our review is focused in the biochemical aspects that we consider should be added systematically in the study of these diseases. 1. Analysis of sialotransferrin isoforms; 2. Analysis of specific acylcarnitines, and 3. Study of purine, pyrimidine and neurotransmitter metabolism.

[Sympathetic reinnervation of the transplanted heart. Study using iodine-123 labeled meta-iodobenzylguanidine]. / Reinervación simpática del corazón trasplantado. Estudio realizado con metayodobenzilguanidina marcada con yodo-123.

INTRODUCTION AND OBJECTIVES: Metaiodobenzylguanidine (MIBG) is an analogue of norepinephrine and its cardiac uptake shows sympathetic innervation. During the heart transplantation the allograft becomes completely denervated. The present study was conducted to assess the evolution of sympathetic re-innervation after transplantation, and to related re-innervation with functional status. PATIENTS AND METHODS: We studied 31 patients from 6 months to 12 years after transplantation by 123I-MIBG studies to evaluate re-innervation and by rest/exercise radionuclide ventriculography to evaluate cardiac function. Myocardial MIBG uptake was quantified by calculating a heart-to-mediastinum ratio (HMR). An HMR > 1.8 was considered normal, moderate between 1.8 and 1.6, mild between 1.6 and 1.3, and absent < 1.3. RESULTS: HMR correlated with time after transplantation (r = 0.607; p < 0.001). HMR of patients studied after 2 years of transplantation was significantly higher (1.62 +/- 0.2 vs 1.34 +/- 0.2; p < 0.05). MIBG uptake was in the anterior region in 3 patients, in the antero-lateral region in 25, and in the antero-lateral and septal regions in 3. From a functional point of view, peak filling rate at exercise was higher in patients studied 2 years after the transplantation (2.7 +/- 0.8 edv/s vs 2.16 +/- 0.5 edv/s; p = 0.02). These patients also showed a higher increase of heart rate with exercise (p < 0.005 vs p < 0.01). CONCLUSIONS: Sympathetic re-innervation increase with time after heart transplantation, and is more frequently seen 2 years after transplantation. Sympathetic re-innervation first appears in the anterior or the antero-lateral regions. A complete re-innervation of the transplanted heart does not occur 12 years after transplantation.

[Evaluation of myocardial viability using perfusion cardiac SPECT. 201-thallium rest/redistribution, 201-thallium rest/reinjection and technetium 99m tetrofosmin rest/postnitrates]. / Valoración de la viabilidad miocárdica mediante SPET cardíaco de perfusión. Talio-201 reposo/redistribución, talio-201 reposo/reinyección y tecnecio-99m tetrofosmina reposo/posnitratos.

INTRODUCTION AND OBJECTIVES: It has been demonstrated that nitrate administration enhances the detection of myocardial viability in thallium-201 and technetium-99m sestamibi myocardial perfusion studies. The aim of this study was to assess the influence of nitrate administration on technetium-99m tetrofosmin myocardial uptake in patients with coronary artery disease and left ventricular dysfunction. PATIENTS AND METHODS: Twenty eight patients with coronary artery disease, previous myocardial infarction and left ventricular ejection fraction < 40% underwent, within 48 hours, rest/postnitroglycerin (0.4 mg sublingually) technetium-99m tetrofosmin single photon emission tomography (SPET), comparing these results with that of thallium-201 rest/redistribution SPET in 13 patients (first group) and with that of thallium-201 rest/reinjection SPET in the other 15 patients (second group). Tomograms based on the 3 spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake > or = 50% of peak activity. RESULTS: The percentage of peak activity at rest or after nitrate administration of technetium-99m tetrofosmin correlated, with that of thallium-201, at rest and after redistribution or reinjection (r = 0.8; p < 0.001). On resting technetium-99m tetrofosmin studies 167 of the 420 segments that were analysed had < 50% of peak activity. 14.5% of these segments showed reversibility after nitrate administration, with an increase in 99mTc-tetrofosmin uptake from 45 +/- 5% to 55 +/- 4% of peak activity (p = 0.001), in the first group, and from 40 +/- 9% to 57 +/- 9% of peak activity (p = 0.003), in the second group. Overall agreement between rest/postnitroglycerin technetium-99m tetrofosmin SPET studies and rest/redistribution or rest/reinjection thallium-201 SPET studies, regarding the presence of myocardial viability, was 87% and 90%, respectively. All except one reversible segments on tetrofosmin studies after nitrates had viability criteria on thallium studies. CONCLUSIONS: Nitrate administration at rest enhances the detection of myocardial viability using technetium-99m tetrofosmin SPET, correlating with viability criteria observed on thallium studies. It represents a simple and useful technique in the assessment of myocardial viability.

National Delphi study to determine competencies for nursing leadership in public health.

PURPOSE: To identify competencies needed by nurse leaders in public health programs. DESIGN: Five-round national Delphi. SAMPLE: Convenience sample of members of major public health nursing associations and nurse and non-nurse public health leaders in the USA. METHODS: Mailed survey in 1994-1995 using a modified snowball technique based on a modification of the Pew Foundation health professions' competencies for Round 1. Four additional rounds produced consensus. FINDINGS: Initially, 62 competencies were identified. Factor analysis resulted in four factors: political competencies, business acumen, program leadership, and management capabilities; 57 competencies were clustered in the four groupings and accounted for 91.4% of the variance. CONCLUSIONS: Graduate schools in nursing and public health must prepare students with broad-based competencies from a variety of disciplines. Findings of this national survey provide a database for curriculum development and evaluation of programs to prepare nurse leaders for roles in public health-based delivery systems.

Plasma free fatty acids in mitochondrial fatty acid oxidation defects.

Plasma free fatty acid profiles from patients suffering from various mitochondrial beta-oxidation deficiencies were analyzed by gas chromatography-mass spectrometry. cis-4-Decenoic acid (10:1n-6) in medium-chain acyl-CoA dehydrogenase deficiency and cis-5-tetradecenoic acid (14:1n-9) in very-long-chain and 3-hydroxy-long chain acyl-CoA dehydrogenase deficiencies are characteristic of these diseases. In addition, patients with 3-hydroxy-long chain acyl-CoA dehydrogenase deficiency showed a specific increase of 3-hydroxy-long chain fatty acids. The study of plasma free fatty acids is an easy and useful methodology for the diagnostic approach of some mitochondrial beta-oxidation deficiencies, allowing us to establish a quick differentiation between medium- and long-chain defects.

Missense mutations in codon 225 of ornithine transcarbamylase (OTC) result in decreased amounts of OTC protein: a hypothesis on the molecular mechanism of the OTC deficiency.

Mutations P225L and P225R were identified in codon 225 of the gene for ornithine transcarbamylase (OTC) in two patients with the neonatal form of OTC deficiency. The mutations occur at a CpG dinucleotide and eliminate a unique MspI restriction site in exon 7 of the OTC gene. They do not alter existing splice sites or create new sites, as judged from the nucleotide sequence. Both mutations are associated with undetectable levels of OTC antigen in liver homogenates, and with either complete lack of OTC activity (P225R mutation) or very small residual activity (0.15% of normal in the P225L mutation). The residual activity observed with P225L exhibits normal pH dependence, little or no increases in the Km values for ornithine and carbamoyl phosphate and normal stability at either 37 degrees C or, in the presence of 0.66 mol/L urea, at 0 degree C. The latter conditions were used to examine whether the P225L mutation favours dissociation of the active OTC trimer. Given the normal stability and lack of tendency to dissociation of the mutant enzyme, it appears likely that the dramatic reduction in the level of OTC protein is due to inefficient conversion of the mutant OTC precursor polypeptide (pOTC) into the correctly localized, appropriately folded, mature enzyme trimer, suggesting degradation of pOTC in transit to the mitochondria.

[4 proposals for ventricular remodelling in the surgical treatment of dilated myocardiopathy]. / Cuatro propuestas para la remodelación ventricular en el tratamiento quirúrgico de la miocardiopatía dilatada.

Four surgical procedures are proposed to achieve an efficient remodelling of the ventricles with a low injury to heart muscle, for the treatment of the dilated cardiomyopathy. Those procedures are based the partial ventriculectomy technique of Batista an on the new conception of the macroscopical myocardium structure of the ventricles evidenced in the second half of the present century.

[Atypical coarctation. Repair with Dacron graft and aortic sarcoma]. / Coartación atípica. Corrección con injerto de Dacron y sarcoma de aorta.

A patient with a localized severe stenosis of his lower thoracic aorta is described. He presented a coarctation like syndrome with hypertension, pulseless legs and left ventricular failure. At surgery a biopsy of the lesion and bypass graft were performed. Pathology diagnosed intimal hyperplasia. Twenty eight months later he developed a sarcoma.

Methylmalonic aciduria with homocystinuria: biochemical studies, treatment, and clinical course of a Cbl-C patient.

A patient with infantile onset methylmalonic aciduria and homocystinuria (Cbl-C mutant) is described. Therapy with hydroxycobalamin, folate and vitamin B6 improved his condition. As hypomethioninaemia and homocystinaemia persisted, he was treated with intramuscular methylcobalamin, but without success. Treatment with betaine started at 25 months of age, normalized plasma methionine and elicited disappearance of homocystinaemia. Results of biochemical studies in cultured fibroblasts paralleled those described for other Cbl-C patients except that methylmalonyl-coenzyme A mutase activity in disrupted fibroblasts was in the normal range.