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Background: Physical and psychological distress may occur in patients facing an onco-haematological diagnosis and undergoing complex therapies such as intensive chemotherapy, stem cell transplantation, and immunotherapy. Studies have shown the need for incorporating different therapeutic modalities to respond to patients' physical and psychosocial needs., Aims: The purpose of this study was to evaluate the effectiveness of music therapy treatment on mood, anxiety, depression, and physical discomfort in hospitalized onco-haematological patients., Methods: Forty patients were included in this music therapy study from November 2021 to May 2023. Treatment consisted of individual weekly music therapy sessions. Participants completed the following evaluation instruments before and after the intervention: the Hospital Anxiety and Depression Scale (HADS), Profile of Mood States-Short Form A-Version (POMS-A), and European Organization for Research and Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30). A three-item numerical rating scale (NRS) for anxiety, sadness, and physical discomfort was administered at the beginning and end of each session (pre-/postsession)., Results: Differences (p < 0.05) were shown in NRS scores for anxiety, sadness, and physical discomfort before and after the music therapy sessions. Quality of life (QoL) was affected in almost all items, and patients could be anxious at a nonclinical level, but they were clinically depressed. EORTC QLQ-C30 scores for insomnia and pain related to the hospitalization process got worse after discharge., Conclusions: The interim results of our study showed that music therapy sessions can positively change emotional distress and improve the mood of haematological patients after every session. Despite the difficulties and limitations of this study, this preliminary report contributes to a greater understanding of the potential benefits of music therapy in hospitalized onco-haematological patients., (© 2023. The Author(s).)

Background and Objective: In people with multiple sclerosis (pwMS), concern for potential disease exacerbation or triggering of other autoimmune disorders contributes to vaccine hesitancy. We assessed the humoral and T-cell responses to SARS-CoV-2 after mRNA vaccination, changes in disease activity, and development of antibodies against central or peripheral nervous system antigens., Methods: This was a prospective 1-year longitudinal observational study of pwMS and a control group of patients with other inflammatory neurologic disorders (OIND) who received an mRNA vaccine. Blood samples were obtained before the first dose (T1), 1 month after the first dose (T2), 1 month after the second dose (T3), and 6 (T4), 9 (T5), and 12 (T6) months after the first dose. Patients were assessed for the immune-specific response, annualized relapse rate (ARR), and antibodies to onconeuronal, neural surface, glial, ganglioside, and nodo-paranodal antigens., Results: Among 454 patients studied, 390 had MS (22 adolescents) and 64 OIND; the mean (SD) age was 44 (14) years; 315 (69%) were female; and 392 (87%) were on disease-modifying therapies. Antibodies to the receptor-binding domain were detected in 367 (86%) patients at T3 and 276 (83%) at T4. After a third dose, only 13 (22%) of 60 seronegative patients seroconverted, and 255 (92%) remained seropositive at T6. Cellular responses were present in 381 (93%) patients at T3 and in 235 (91%) patients at T6 including all those receiving anti-CD20 therapies and in 79% of patients receiving fingolimod. At T3 (429 patients) or T6 (395 patients), none of the patients had developed CNS autoantibodies. Seven patients had neural antibodies that were already present before immunization (3 adult patients with MS had MOG-IgG, 2 with MG and 1 with MS had neuronal cell surface antibodies [unknown antigen], and 1 with MS had myelin antibody reactivity [unknown antigen]. Similarly, no antibodies against PNS antigens were identified at T3 (427 patients). ARR was lower in MS and not significantly different in patients with OIND. Although 182 (40%) patients developed SARS-CoV-2 infection, no cases of severe COVID-19 or serious adverse events occurred., Discussion: In this study, mRNA COVID-19 vaccination was safe and did not exacerbate the autoimmune disease nor triggered neural autoantibodies or immune-mediated neurologic disorders. The outcome of patients who developed SARS-CoV-2 infection was favorable., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The atrioventricular node (AV) is considered the electrical connection between the atria and ventricles. There is an electrical pause between activation of the atria and the ventricles (PR segment), but to date the mechanism responsible for this interruption remains unclear. The present communication focuses on the hypothesis that magnetic field dynamics could provide the answer. Proof of this hypothesis is that in Wolff-Parkinson-White syndrome, where there is physical connection between the atria and ventricles (bundle of Kent), there is electrical AV continuity, no PR segment is detected, and catheter ablation of the abnormal bundle restores AV discontinuity. Spontaneous initiation of the heart at the level of the sinus node, the pacemaker of the heart, could also be explained via field dynamics. The known transmembrane pacemaker protein CHN4, present in both sinoatrial and AV nodal cells, could interact with field information to provide specificity in an electronic key-to-lock mechanism interaction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this article, one of the novel mutations, c.208&#95;209+ 8del10, was incorrectly given as c.69&#95;70+8del10. It corresponds to patient 64 in Table 4.

Objective: The chronology of electrical events that mechanically activate the myocardium has been described as initiating at the level of the septum, spreading to the apex, then to the bodies of both ventricles and eventually to the base of the heart (apex-to base activation). It has recently been suggested that the myocardium is a single muscular band that conforms a double-loop helicoid. Contraction of the myocardium would follow the trajectory of the muscular fibers that originate at the pulmonary artery towards the body of the left ventricle and to the aorta (base-to apex contraction). This would explain the movements of the base of the heart and the twisting motion of the ventricles seen at magnetic resonance studies., Methods: Temporal Fourier analysis of equilibrium radionucleide angiocardiography, by studying the topography of the regional myocardial mechanical displacement corresponding to the wave front of electro-mechanical activation, provides information on the sequence of regional ventricular contraction was used in 29 normal individuals to observe the sequence of myocardial motion., Results: Analysis disclosed that the base of the heart first moves (right then left ventricle) and mechanical movement later descends to involve the apex and the septum. These findings are in concordance with the proposed activation of the helical myocardium and open the way to more complex studies., Conclusions: Although electrical activation of the myocardium (QRS complex) follows a septum-apex-body-base of the left ventricle sequence, mechanical activation follows a base-to-apex sequence. This is likely to be related to anisotropic propagation of the electromechanical stimulus throughout the myocardial band once the electrical stimulus has been delivered at the base of the heart.

Classical homocystinuria is due to cystathionine beta-synthase (CBS) deficiency. More than 130 mutations, which differ in prevalence and severity, have been described at the CBS gene. Mutation p.I278T is very prevalent, has been found in all European countries where it has been looked for with the exception of the Iberian peninsula, and is known to respond to vitamin B6. On the other hand, mutation p.T191M is prevalent in Spain and Portugal and does not respond to B6. We analysed 30 pedigrees from Spain, Portugal, Colombia and Argentina, segregating for homocystinuria. The p.T191M mutation was detected in patients from all four countries and was particularly prevalent in Colombia. The number of p.T191M alleles described in this study, together with those previously published, is 71. The prevalence of p.T191M among CBS mutant alleles in the different countries was: 0.75 in Colombia, 0.52 in Spain, 0.33 in Portugal, 0.25 in Venezuela, 0.20 in Argentina and 0.14 in Brazil. Haplotype analyses suggested a double origin for this mutation. No genotype-phenotype correlation other than the B6-nonresponsiveness could be established for the p.T191M mutation. Additionally, three new mutations, p.M173V, p.I429del and c.69&#95;70+8del10, were found. The p.M173V was associated with a mild, B6-responsive, phenotype.

Cystinuria is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids that results in urolithiasis of cystine. Cystinuria is caused by defects in the amino acid transport system b0,+ (i.e. the rBAT/b0,+AT heteromeric complex). Mutations in SLC3A1, encoding rBAT, cause cystinuria type A, characterized by a silent phenotype in heterozygotes (phenotype I). Mutations in SLC7A9, encoding b0,+AT, cause cystinuria type B, in which heterozygotes in most cases hyperexcrete cystine and dibasic amino acids (phenotype non-I). To facilitate in vivo investigation of b0,+AT in cystinuria, Slc7a9 knockout mice have been generated. Expression of b0,+AT protein is completely abolished in the kidney of Slc7a9-/- mice ('Stones'). In contrast, Stones expressed significant amounts of rBAT protein, which is covalently linked to unidentified light subunit(s). Stones mice present a dramatic hyperexcretion of cystine and dibasic amino acids, while Slc7a9+/- mice show moderate but significant hyperexcretion of these amino acids (phenotype non-I). Forty-two per cent of Stones mice develop cystine calculi in the urinary system. Calculi develop during the first month of life and grow throughout the life span of the animals. Histopathology in kidney reveals typical changes for urolithiasis (tubular and pelvic dilatation, tubular necrosis, tubular hyaline droplets and chronic interstitial nephritis). The fact that some Stones mice, generated in a mixed genetic background, develop cystine calculi from an early age, while others do not develop them in their first year of life, suggests the involvement of modifier genes in the lithiasis phenotype. Thus, Stones provide a valid model of cystinuria which can be used in the study of genetic, pharmacological and environmental factors involved in cystine urolithiasis.

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. All five novel mutations were found to affect evolutionarily conserved residues suggesting that they may impair enzyme function. Interestingly, neither of the two common CBS mutations, I278T and G307S, was detected in this series, and no patient was found to respond to pyrodoxine. Enzyme activities in cultured fibroblasts from 10 of the patients were assayed, and they ranged from 0 to 13 % of controls analyzed in parallel. The T191M mutation (which has only ever been reported once before in a Spanish patient) accounted for 50% of the mutant alleles. Comparison of the clinical data of seven patients homozygous for T191M indicated that this genotype is a poor predictor of the phenotype. A common haplotype was identified in all the T191M chromosomes of Spanish origin, while a different one was present in the four T191M chromosomes from Portuguese patients., (Copyright 2003 Wiley-Liss, Inc.)

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease., (Copyright 2003 Wiley-Liss, Inc.)

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.

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.

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.

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.

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.

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.

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.

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.

The indium-111 labeled Fab fragment of antimyosin monoclonal antibody was used to study cardiac rejection and the time course of myocyte damage after transplantation. Fifty-three studies were performed in 21 patients, 17 men and 4 women, aged 19 to 54 years (mean 37 +/- 8), from 7 to 40 months after transplantation. Repeat studies were available in 8, and 10 were studied after the first year of transplantation. A heart-to-lung ratio was used for quantitation of uptake (normal 1.46 +/- 0.04). Differences between absent (1.69 +/- 0.29) and moderate (1.90 +/- 0.36) rejection were significant (p less than 0.03). Antimyosin ratio at 1 to 3 months (1.89 +/- 0.35) differed from that at greater than 12 months (1.65 +/- 0.2) (p less than 0.01). Repeat studies revealed a decrease in antimyosin ratio in 5 patients with uneventful clinical course; 2 had persistent activity after transplantation and suffered heart failure from rejection. After 1 year of transplantation uptake was within normal limits in 7 of 10 patients, and high uptake was associated with vascular rejection in 1. Because they can define evolving patterns of myocardial lesion activity, antimyosin studies could be useful both in patient management and in concentrating resources for those patients who most require them. The heart-to-lung ratio is suggested to monitor sequentially the degree of myocyte damage after transplantation.

The development of the central nervous system has been verified using biochemical techniques in two premature infants with intrauterine growth retardation. In both cases a retard of brain growth and maturity was detected. In the case less affected alterations consisted in a decrease in size of forebrain and cerebellum and a diminution of the DNA in cerebrum. In the other case sizes of cerebrum, cerebellum and brain stem were markedly reduced. The values of DNA and RNA were also lower than in controls being cerebellum and brain stem the more altered regions. The lipid composition of cerebrum, cerebellum and brain stem is also reported for both cases.