Electrocardiographic findings in true acute left main coronary total occlusion a subanalisys from ATOLMA registry.

INTRODUCTION: Acute total occlusion of the left main coronary artery (ATOLMA) usually leads to a catastrophic presentation. Prediction of ATOLMA by electrocardiogram (ECG) may contribute to early detection and reperfusion. Limited data have been reported previously. This study aims to identify the admission 12­leads ECG features that can predict the presence of ATOLMA and in-Hospital mortality in these patients. METHODS: The admission ECGs findings in 24 patients from the previously reported ATOLMA multicenter registry were compared to the ECGs findings in 15 patients with an acute subtotal occlusion of the left main (ASOLMA) and to 15 patients with anterior ST-elevation myocardial infarction of the proximal left anterior descending (LADp-STEMI). RESULTS: Some ECG features at presentation can predict an ATOLMA: QRS left axis deviation (-61.17 ± 9 degrees); ST-segment elevation in aVL (1.9 ± 0.65 mm); absence of ST-segment elevation in V1 (0.0 ± 0.6 mm); bifascicular block (58%); fragmented QRS (62.5%); prolongation of QTc interval (465 ± 19 ms) and of QRS interval (136 ± 12 mm). The multivariate analysis found that the independent predictors to distinguish ATOLMA from ASOLMA were aVL ST-segment deviation (OR 5.6(95% CI 1.5-21), p = 0.01) and absence of V1 ST-segment elevation (OR 27(95% CI 1.4-52), p = 0.01); and from LADp-STEMI was QRS width (OR 1.1(95% CI 1.02-1.2), p = 0.02). Fragmented QRS was the only independent predictor of in-hospital mortality in ATOLMA (OR 0.125(95% CI 0.01-0.81), p = 0.03). CONCLUSIONS: aVL ST-segment elevation, the absence of V1 ST-segment elevation, left axis deviation, the presence of bifascicular block, and prolongation of QRS and QTc interval are predictors of ATOLMA. Fragmented QRS predicts in-hospital mortality in ATOLMA.

Major human milk oligosaccharides are absorbed into the systemic circulation after oral administration in rats.

Human milk oligosaccharides (HMO) are involved in many biological functions influencing infant health. Although HMO act locally at the intestine, recent evidence has demonstrated that HMO are partially incorporated into the systemic circulation of breast-fed infants. In the last few years, a large amount of research has been conducted using preclinical models to uncover new biological functions of HMO. The aim of this study was to evaluate the absorption and urine excretion of HMO in rats. We administered a single oral dose of the following HMO: 2'-fucosyllactose (2'-FL), 6'-sialyllactose and lacto-N-neotetraose at different concentrations to adult rats. The time course of absorption of HMO into the bloodstream and their appearance in urine was studied. Our results showed that rats, similar to human infants, are able to effectively absorb a portion of HMO from the intestine into plasma and to excrete them in urine. On the basis of this, we also conducted a specific kinetic absorption study with 2'-FL, the most predominant HMO in human milk, in 9-11-d-old rat pups. Our results confirmed that a significant amount of 2'-FL was absorbed into the systemic circulation and subsequently excreted in urine during lactation in rats in a dose-depended manner. We also found basal levels of these HMO in plasma and urine of adult rats as well as rat pups as a natural result of nursing. Our data suggest that the rat may be a useful preclinical model that provides new insights into the metabolism and functions of HMO.

Quantitative determination of ß-hydroxymethylbutyrate and leucine in culture media and microdialysates from rat brain by UHPLC-tandem mass spectrometry.

The main objective of the present work was to develop a method to determine ß-hydroxymethylbutyrate (HMB) and leucine (Leu) in culture media and brain microdialysates. An accurate, selective, and cost-effective method, based on the use of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), was developed for the identification and quantification of both compounds. The method consisted of sample dilution, direct injection onto the chromatographic equipment, and quantification with a triple quadrupole mass spectrometer using an electrospray ionization interface in positive mode. The procedure and the UHPLC-MS/MS parameters were accurately optimized to achieve the highest recoveries and to enhance the analytical characteristics of the method. For chromatographic separation, an Acquity UPLC BEH Hilic column using acetonitrile-water gradient with formic acid as additive was employed. The total run time was 4 min. The limits of detection (LODs) obtained ranged from 0.01 to 0.04 µg mL(-1), and the limits of quantification (LOQs) ranged from 0.04 to 0.12 µg mL(-1). Precision (expressed as relative standard deviation) was lower than 15 %, and the determination coefficient (R (2)) was higher than 99.0 % with a residual deviation for each calibration point lower than ±25 %. Mean recoveries were between 85 and 115 %. The method was successfully applied to the analysis of both compounds, HMB and Leu, in samples obtained from an experiment of blood-brain barrier (BBB) passage in vitro and to an experiment of brain microdialysis in rats in vivo after an oral challenge with HMB to detect its appearance in the brain.

The athlete gut microbiota: state of the art and practical guidance.

The gut microbiota has been proposed to grant the athlete a metabolic advantage that might be key when optimising performance. While a taxonomic core set of microorganisms characterising the athlete's gut microbiota has not been delineated, some compositional features might be associated with improved metabolic efficiency, which appears to be driven by the production of bacterial metabolites, such as short-chain fatty acids. Not only long-term exercise but also dietary patterns associated with high-level sports practice contribute to this microbial environment, yet isolating the impact of individual dietary components is challenging. The present review synthetises the available evidence on the compositional aspects of the athlete's gut microbiota, discusses mechanisms involved in the bidirectional association between exercise and the gut environment, and evaluates the role of athletes' diet in this interplay. Additionally, a practical approach to indicators commonly reported in metagenomic and metabolomic analyses is provided to explore how these insights can translate to support dietary protocols.

A systematic review of breast milk microbiota composition and the evidence for transfer to and colonisation of the infant gut.

The intestinal microbiota plays a major role in infant health and development. However, the role of the breastmilk microbiota in infant gut colonisation remains unclear. A systematic review was performed to evaluate the composition of the breastmilk microbiota and evidence for transfer to/colonisation of the infant gut. Searches were performed using PUBMED, OVID, LILACS and PROQUEST from inception until 18th March 2020 with a PUBMED update to December 2021. 88 full texts were evaluated before final critique based on study power, sample contamination avoidance, storage, purification process, DNA extraction/analysis, and consideration of maternal health and other potential confounders. Risk of skin contamination was reduced mainly by breast cleaning and rejecting the first milk drops. Sample storage, DNA extraction and bioinformatics varied. Several studies stored samples under conditions that may selectively impact bacterial DNA preservation, others used preculture reducing reliability. Only 15 studies, with acceptable sample size, handling, extraction, and bacterial analysis, considered transfer of bacteria to the infant. Three reported bacterial transfer from infant to breastmilk. Despite consistent evidence for the breastmilk microbiota, and recent studies using improved methods to investigate factors affecting its composition, few studies adequately considered transfer to the infant gut providing very little evidence for effective impact on gut colonisation.

Impact of nutritional status according to GLIM criteria on the risk of incident frailty and mortality in community-dwelling older adults.

BACKGROUND & AIMS: Poor nutritional status leads to multiple adverse outcomes, but few studies have assessed its role as a risk factor for incident frailty and death in community-dwelling older adults. Hence, the aim of this paper is to assess the role of nutritional status using the Global Leadership Initiative on Malnutrition (GLIM) criteria in the risk of frailty and mortality in Spanish community-dwelling older adults. METHODS: We used data from two waves (waves 2 (2011-2013) and 3 (2015-2017)) from the Toledo Study of Healthy Ageing, which is an observational, prospective cohort (average follow-up = 3.18 years) of 1660 older (≥65 years) adults living in the community. Nutritional status categories were defined according to the GLIM criteria, which uses a two-step approach. First, screening for malnutrition risk. Once positive, individuals were classified as malnourished according to some phenotypic (body mass index, grip strength and unintentional weight loss) and etiologic (disease burden/inflammation and reduced food intake or assimilation) criteria. Frailty was assessed using both the Frailty Index (FI) and Frailty Trait Scale (FTS). Mortality data was obtained through the National Death Index. RESULTS: From the 1660 older adults, 248 participants (14.04%) were classified as 'at malnutrition risk' (AMR) and 209 (12.59%) as malnourished (MN). AMR and MN subjects were older and with worse functional status (frailer). Adjusted cross-sectional analysis showed an association between nutritional status and frailty by both FI and FTS. Adjusted longitudinal analyses showed that AMR was associated with higher risk of frailty, using both the FTS (OR: 1.262; 95% CI: 1.078-1.815) and the FI (OR: 1.116; 95% CI: 1.098-1.686), while being malnourished was associated with higher mortality risk (OR: 1.748; 95% CI: 1.073-2.849), but not with incident frailty at follow-up period. CONCLUSIONS: Nutritional status, assessed through GLIM, predicts in a dose-dependent manner the risk of frailty and death. Being at malnutrition risk predicts the risk of becoming frail at follow-up period, whereas being malnourished predicts mortality. These findings highlight the importance of assessing the nutritional status of community-dwelling older adults to identify the ones at risk of developing frailty or death and inform targeted nutrition-focused interventions.

Role of Oral Nutritional Supplements Enriched with ß-Hydroxy-ß-Methylbutyrate in Maintaining Muscle Function and Improving Clinical Outcomes in Various Clinical Settings.

Aging and disease-related malnutrition are well associated with loss of muscle mass and function. Muscle mass loss may lead to increased health complications and associated increase in health care costs, especially in hospitalized individuals. High protein oral nutritional supplements enriched with ß-hydroxy-ß-methylbutyrate (HP-ONS+HMB) have been suggested to provide benefits such as improving body composition, maintaining muscle mass and function and even decreasing mortality rates. The present review aimed to examine current evidence on the effect of HP-ONS+HMB on muscle-related clinical outcomes both in community and peri-hospitalization patients. Overall, current evidence suggests that therapeutic nutrition such as HP-ONS+HMB seems to be a promising tool to mitigate the decline in muscle mass and preserve muscle function, especially during hospital rehabilitation and recovery.

Anatomical Variants in Renal Transplantation, Surgical Management, and Impact on Graft Functionality.

INTRODUCTION: Chronic kidney disease (CKD) is a priority problem due to its high prevalence. According to the modalities of renal replacement therapy, kidney transplantation (TR) offers to be the best alternative. TR presents multiple factors of dependence of success; among them is the management of the anatomical variants of the graft and the surgical decision on the basis of these. Therefore, the objective of this study is to determine the frequency of variants in the graft, its surgical management, and the impact on the functionality of the transplanted kidney. MATERIAL AND METHODS: This was an observational, retrospective study of patients in the renal transplant unit of the Siglo XXI National Medical Center from 2002-2016. The analysis begins in the description of the population doing bivariate analysis to establish relative risks. For variables with a central tendency, the parametric tests analysis of variance, Student t paired, and unpaired will be used. In the case of nominal variables, the proportion's difference will be estimated using the chi-square test, establishing significance when P is ≤ .05. SPSS 21 software was used. RESULTS: There were a total of 773 patients, with 576 transplants from living donors and 197 from deceased donors. In the case of the artery, a greater number of variants is observed-27.8% being alive versus 17.3% of the variants found in deceased donors. For the renal vein, 12.7% of the kidneys were taken from living donor vs 6.1% from deceased donors. This required one more day of hospitalization (6 vs 7 days of single vs multiple vessels); likewise, increases in immediate post-transplant infections were 5% for single vessels vs 8% in the case of multiple variants. CONCLUSIONS: The importance of knowing the anatomical variants prior to the TR allows them to plan the potential surgical maneuvers, decreasing the times aimed at improving the immediate functionality of the renal graft, while also considering the increase in hospital expenses due to the greater number of days of hospitalization.

Ribonucleotides: conditionally essential nutrients shown to enhance immune function and reduce diarrheal disease in infants.

It remains a goal of pediatric nutrition to provide optimal nourishment for infants who are not fed human milk. Investigators have attempted to emulate the composition and functionality of human milk, the gold standard for infant nutrition. These efforts began with the analysis of milk components and continued with assessments of biological effects that culminated in clinical studies in infants. This chapter summarizes the path that researchers followed to study ribonucleotides and their role in infant nutrition. Based on analytical methods for the quantification of ribonucleotides in human milk, investigators assessed their potential impact on the immune systems of infants and looked for concomitant mechanistic explanations. These inquiries evolved into clinical trials in which ribonucleotide-supplemented formula performance was compared with that of non-supplemented formulas and with human milk. This chapter intends to summarize an area of pediatric nutrition that has yielded both enlightening evidence and seemingly contradictory data.

Intestinal toxicity induced by 5-fluorouracil in pigs: a new preclinical model.

BACKGROUND: The goal of this study was to develop an animal model of intestinal injury induced by 5-fluorouracil (5-FU) in pigs. METHODS: Six domestic pigs were used as control (healthy group) and another 6 malnourished pigs orally received 5-FU (treated group). After 4 weeks of treatment, pigs were sacrificed and jejunum, ileum and colon were isolated for histological, immunological and biochemical analyses. RESULTS: 5-FU caused a decrease in the intestinal mass. Disaccharidase, and phosphate alkaline activities, and glutathione redox cycle were disrupted by 5-FU. Histopathological alterations in the crypts and villous were greater in the small intestine than in the colon. 5-FU decreased the number of peripheral and intestinal leukocytes, promoting an increase in T-cytotoxic cells and a decrease in T-helper and B cells. CONCLUSION: This pig model of intestinal dysfunction closely mimics the common side effects of cancer chemotherapy in humans, and provides a useful tool for evaluating novel antimucotoxic agents.

Invasive assessment of coronary flow reserve impairment in severe aortic stenosis and ecochadiographic correlations.

OBJECTIVES AND BACKGROUND: Patients with aortic stenosis (AS) may have impaired coronary flow reserve (CFR) despite angiographically normal coronary arteries. This is the first report of invasive thermodilution-derived CFR and IMR in patients with AS and their associations with echocardiographic parameters for AS assessment. METHODS: Thirty-six consecutive severe AS patients and ten patients without AS underwent prospectively cardiac catheterization and coronary physiological parameters were determined in the left anterior descending (LAD). Mean transit time (Tmn), a surrogate of absolute coronary flow, was obtained from the coronary thermodilution curve. RESULTS: In AS patients we found a high LAD flow at rest (Tmn rest 0.55±0.3 vs 0.99±0.4, p=0.01) and a low flow at hyperemia (Tmnhyp 0.44±0.2 vs 27.7±0.1, p=0.02) and consequently a severe CFR impairment (1.4±0.4 vs 3.8±1.4, p<0.001) compared with controls. An elevated index of microvascular resistance (IMR) (32.7±16 vs 17.8±6.5, p=0.01) and a low baseline microvascular coronary resistance (48.1±29 vs 84±34, p=0.02) were also found. In AS patients there were significant correlations between CFR and left ventricular mass index (r=-0.32; p=0.02), and the ratio of acceleration time to ejection time (AT/ET) (r=-0.4; p=0.01) a non-flow dependent echocardiographic parameter for AS assessment. Multiple linear stepwise regression analysis showed that AT/ET (ß=-0.441, p=0.019) was the only independently variable associated with CFR CONCLUSIONS: In severe AS, invasive CFR shows a progressive decrease with AS severity and a good correlation with echocardiographic parameters of AS, especially with flow-independent ones.

Maternal Body Weight and Gestational Diabetes Differentially Influence Placental and Pregnancy Outcomes.

CONTEXT: Maternal obesity and gestational diabetes mellitus (GDM) can both contribute to adverse neonatal outcomes. The extent to which this may be mediated by differences in placental metabolism and nutrient transport remains to be determined. OBJECTIVE: Our objective was to examine whether raised maternal body mass index (BMI) and/or GDM contributed to a resetting of the expression of genes within the placenta that are involved in energy sensing, oxidative stress, inflammation, and metabolic pathways. METHODS: Pregnant women from Spain were recruited as part of the "Study of Maternal Nutrition and Genetics on the Foetal Adiposity Programming" survey at the first antenatal visit (12-20 weeks of gestation) and stratified according to prepregnancy BMI and the incidence of GDM. At delivery, placenta and cord blood were sampled and newborn anthropometry measured. RESULTS: Obese women with GDM had higher estimated fetal weight at 34 gestational weeks and a greater risk of preterm deliveries and cesarean section. Birth weight was unaffected by BMI or GDM; however, women who were obese with normal glucose tolerance had increased placental weight and higher plasma glucose and leptin at term. Gene expression for markers of placental energy sensing and oxidative stress, were primarily affected by maternal obesity as mTOR was reduced, whereas SIRT-1 and UCP2 were both upregulated. In placenta from obese women with GDM, gene expression for AMPK was also reduced, whereas the downstream regulator of mTOR, p70S6KB1 was raised. CONCLUSIONS: Placental gene expression is sensitive to both maternal obesity and GDM which both impact on energy sensing and could modulate the effect of either raised maternal BMI or GDM on birth weight.

Analysis of 17 neurotransmitters, metabolites and precursors in zebrafish through the life cycle using ultrahigh performance liquid chromatography-tandem mass spectrometry.

An ultrahigh performance liquid chromatography-tandem mass spectrometry method for the identification and quantification of neurotransmitters, metabolites and precursors at different stages in zebrafish life was developed. Betaine, glutamine, glutamic acid, γ-aminobutyric acid, phosphocholine, glycerophosphocholine, cytidine 5'-diphosphocholine, choline, acetylcholine, dopamine, norepinephrine, serotonin, tyrosine, epinephrine, tryptophan, 5-hydroxyindolacetic acid and agmatine were selected as analytes. The method consisted of a simple deproteinization of samples using methanol and formic acid, subsequent injection onto the chromatographic equipment and quantification with a triple quadrupole mass spectrometer detector using an electrospray ionization interface in positive mode. Limits of detection ranged from 0.02 to 11ngmL(-1) and limits of quantification from 0.1 to 38ngmL(-1), depending on the analyte. The method was validated according to US Food and Drugs Administration (FDA) guideline for bioanalytical assays. Precision, expressed as relative standard deviation (%RSD), was lower than 15% in all cases, and the determination coefficient (R(2)) was equal or higher than 99.0% with a residual deviation for each calibration point lower than ±25%. Mean recoveries were between 85% and 115%. The method was applied to determine of these compounds in zebrafish from early stages of development to adulthood and showed the time-course of neurotransmitters and others neurocompounds through the life cycle. The possibility of measuring up to 17 compounds related with the main neurotransmitter systems in a simple analytical method will complement and reinforce the use of zebrafish in multiple applications in the field of neurosciences. The proposed method will facilitate future studies related with brain development.

Insuficiencia suprarenal secundaria al uso de corticoides inhalados: reporte de caso / Adrenal insufficiency secondary to use of inhaled corticosteroids: case report

La insuficiencia suprarrenal es un síndrome que se produce por la disminución de niveles séricos de glucocorticoides, la cual se clasifica en primaria o secundaria, según la etiología. El uso prolongado de corticoides exógenos a altas dosis puede producir una inhibición en el eje hipotálamo-hipofisiario-adrenal, y la supresión aguda de éstos produce insuficiencia suprarrenal secundaria. Los glucocorticoides inhalados, usados ampliamente como tratamiento del asma bronquial, pudiesen tener un impacto a nivel del eje adrenal, principalmente en la población pediátrica. Por el momento, si bien hay reportes de casos que evidencian insuficiencia suprarrenal secundaria al uso de corticoides tanto tópicos como inhalatorios, aún es materia de discusión esta interacción a nivel sistémico, con artículos que se contraponen en sus resultados. Se presenta un caso clínico de una paciente usuaria de glucocorticoides inhalatorios por el antecedente de asma bronquial, que desarrolla una clínica de insuficiencia suprarrenal en el periodo de lactancia.

Adrenal insufficiency is a syndrome that is produced by the decrease in serum glucocorticoid levels, which is classified as primary or secondary, according to the etiology. Prolonged use of exogenous corticosteroids at high doses may cause inhibition in the hypothalamic-pituitary-adrenal axis, and acute suppression of these results in secondary adrenal insufficiency. Inhaled glucocorticoids, widely used as a treatment for bronchial asthma, could have an impact at the level of the adrenal axis, mainly in the pediatric population. At the moment, although there are reports of cases that show adrenal insufficiency secondary to the use of both topical and inhalation corticosteroids, this interaction at systemic level is still a matter of discussion, with articles that contrast in their results. We present a clinical case of a patient using inhaled glucocorticoids due to a history of bronchial asthma, which develops a clinical of adrenal insufficiency in the period of breastfeeding.

Páncreas ectópico, diagnóstico diferencial de lesión gástrica subepitelial: reporte de caso y enfrentamiento inicial / Ectopic pancreas, differential diagnosis of subepithelial gastric lesion: case report and initial confrontation

Subepithelial lesions are generally an incidental diagnosis with an prevalence of 0.4%. These tumors represent a great diagnostic challenge, mainly when ruling out potentially malignant lesions, such as gastrointestinal stromal tumor (GIST), lymphomas and carcinomas. Among the many differential diagnosis, the ectopic pancreas arises with an prevalence of 1-2% in general population. The first diagnostic approach is performed using upper digestive endoscopy, computed tomography and endosonography. This last one has a diagnostic performance of less than 50%, which increases to 90% when it is associated with a histopathological examination. There is no current consensus regarding the management and monitoring of these lesions. Based on the imaging and histological characteristics, the possibilities range from observation to endoscopic or surgical resection. In this context, we will present a clinical case of ectopic pancreas as an incidental finding, and afterwards the diagnostic and therapeutic breakdown of subepithelial lesions.

Las lesiones subepiteliales son pesquisadas generalmente de manera incidental, con una prevalencia de 0,4%. Estos tumores suponen un gran desafío diagnóstico, principalmente al momento de descartar lesiones potencialmente malignas, como el tumor estromal gastrointestinal (GIST), linfomas y carcinomas. Dentro de los posibles diagnósticos, surge el páncreas ectópico, con una prevalencia de hasta 1-2% en la población general. La primera aproximación diagnóstica se realiza mediante endoscopia digestiva alta, tomografía computarizada y la endosonografía, ésta última con un rendimiento diagnóstico menor del 50%, que aumenta hasta el 90% al asociar el examen histopatológico. No existe consenso actual respecto al manejo y seguimiento de estas lesiones, que según sus características imagenológicas e histológicas, va desde la observación hasta la resección endoscópica o quirúrgica. En este contexto, se presenta un caso clínico de páncreas ectópico como hallazgo incidental y el desglose diagnóstico y terapéutico de las lesiones subepiteliales.

Detection of complex gangliosides in human amniotic fluid.

Gangliosides are possibly very potent immunosuppressive molecules. Here we show that human amniotic fluid contains high concentrations of a number of previously unnoted, structurally complex and highly polar gangliosides. These unusual molecules are present early in pregnancy (first trimester), increase in concentration with gestational age, and reach maximum levels (0.8 microM) at term. Since similar gangliosides have been detected in human placenta, trophoblast, and amnion, we suggest that these molecules are shed into the amniotic fluid bathing these tissues.

Decreased levels of circulating CD4+ T lymphocytes during normal human pregnancy.

Peripheral blood mononuclear cell (PBMC) populations during human pregnancy have been investigated by many authors, although the different results obtained, principally in relation to T cells, are very discrepant. In this study we aimed to exclude all the possible causes of these discrepancies: small sample size; diurnal rhythm of CD4+ T cells; smoking habits; haemodilution which occurs during pregnancy and inappropriate statistical analysis; in order to determine whether gestation has a definite effect on PBMC populations. We found that the percentage of CD4+ T lymphocytes decreases in the first and second trimesters, returns to the non-pregnant level in the third trimester and remains there in the postpartum period. The percentages of CD3+ T lymphocytes run parallel to those of CD4+ while CD8+ T lymphocytes do not vary. The proportion of CD16+ cells, which include mature NK cells, diminishes in the second trimester and this reduction is maintained in the third trimester and the puerperium. No variation was found in the other PBMC studied (CD20+ lymphocytes, CD14+ monocytes and D/DR+ cells). When parity was considered no difference was seen between primiparous and multiparous women in any of the cell populations tested.

New strategies for old problems: tardive dyskinesia (TD). Review and report on severe TD cases treated with clozapine, with 12, 8 and 5 years of video follow-up.

Tardive dyskinesia (TD) is the most feared and troublesome extrapyramidal side-effect of prolonged neuroleptic (NL) treatment. We present a review of TD. Its pathophysiology remains elusive, although extrapyramidal symptoms (EPS) increase the liability for TD. Nowadays, therefore, avoidance of all EPS remains the best preventive strategy, as it is not possible to predict which liable patients will develop TD, or of what type or severity. TD frequently includes dystonic features, and is more disabling when these dystonias are present. Clozapine (CLZ) has been reported to be effective in suppressing nearly 60% of TD syndromes, specially those with dystonic features. Based on the few reports in the literature on CLZ and TD by the early 1980s, we started to videotape the first severe TD patient treated with CLZ in 1984. We present the first three case reports of severe TD, with prominent disabling dystonic features, treated with CLZ and videotaped since pretreatment and then periodically for 12, 8 and 5 years of follow-up, respectively. The patients' current diagnosis, gender and age are: Case 1, DSM-IV Schizophrenia Residual Type, male, 39 years; Case 2, DSM-IV Polysubstance Related Disorder, Borderline Personality Disorder, female, 28 years; Case 3, DSM-IV Schizoaffective Disorder, male, 40 years. Two of them presented with a recurrence of TD because of CLZ interruption within the first 2 months of treatment, with no further breakthrough to date. The first two cases have complete remission of TD; the third case is still improving after 5 years of CLZ treatment, with only minor dystonic features persisting that constitute no impairment for work or daily routines at present. All patients, independent of their psychiatric primary diagnosis, have shown significant and progressive improvement in both motor and psychosocial aspects. None of them has been rehospitalized. Long-term treatment and follow-up is required to avoid TD recurrence and to assure full assessment of treatment effectiveness. Ideally, periodic video recording with standardized examination is advisable for long-term follow-up and outcome assessment. At present, CLZ could be regarded as the drug of choice for patients with TD, specially for those with disabling and or dystonic features and who require ongoing NL therapy. The use of novel antipsychotic agents for TD treatment and prevention, with their low EPS liability, is promising, but has yet to be tested.