Estela Monteiro

University of Lisbon, Lisbon, Lisbon, Portugal

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Publications (51)94.2 Total impact

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    ABSTRACT: In the literature, concepts of “polyneuropathy”, “peripheral neuropathy” and “neuropathy”, are often mistakenly used as synonyms. Polyneuropathy is a specific term that refers to a relatively homogenous process that affects multiple peripheral nerves. Most of these tend to be distal symmetric polyneuropathies that first manifest in the distal portions of the affected nerves. Many of these distal symmetric polyneuropathies are due to toxic-metabolic causes such as alcohol abuse and diabetes mellitus. Other distal symmetric polyneuropathies may result from an overproduction of substances that result in nerve pathology such as is observed in anti-MAG neuropathy and monoclonal gammopathy of undetermined significance. Other “overproduction” disorders are hereditary such as noted in familial amyloid polyneuropathy (FAP). FAP is a manifestation of a group of hereditary amyloidoses; an autosomal dominant and multisystemic disorder wherein the mutant amyloid precursor, transthyretin is produced primarily by the liver. The liver accounts for approximately 98% of all transthyretin production. The diagnosis is confirmed by detecting a transthyretin variant with a methionine for valine substitution at position 30 [TTR (Met30)]. Familial Amyloidotic Polyneuropathy (FAP) – Portuguese type, was first described by a Portuguese neurologist, Corino de Andrade, in 1939 and published in 1951. Most persons with this disorder are descended from Portuguese sailors who sired offspring in various locations but primarily in Sweden, Japan and Mallorca. Their descendants emigrated worldwide such that this disorder has been reported in other countries as well. More than 2000 symptomatic cases have been reported in Portugal. FAP progresses rapidly (about 10 years) with resulting multi-organ involvement and death. Treatments directed at removing this aberrant protein such as plasmapheresis and immunoadsorption proved to be unsuccessful. Liver transplantation has been the only effective solution as evidenced by almost 2000 liver transplants performed worldwide. A new drug “Tafamidis” for FAP was tested and the results of phase III assays are promising. It is well recognized that regular physical activity of moderate intensity has a positive effect on physical fitness as gauged by body composition, aerobic capacity, muscular strength and endurance and flexibility. Physical fitness has been reported to result in the reduction of symptoms and lesser impairment when performing activities of daily living. Exercise has been advocated as part of a comprehensive approach to the treatment of chronic diseases. This chapter discusses the role of exercise training on FAP.
    Contemporary Issues in Peripheral Neuropathy, Edited by Daniel L. Menkes, 01/2014: chapter Familial Amyloid Polyneuropathy (FAP): Clinical Features, Pathophysiology and Treatment: pages 209-224; Nova Science Publishers, Inc., ISBN: 978-1-62948-681-9
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    ABSTRACT: Background. Liver transplantation is nowadays the only effective answer to adjourn the outcome of functional limitations associated with familial amyloidotic polyneuropathy (FAP), a neurodegenerative disease characterized by sensory and motor polyneuropathies. Nevertheless, there is a detrimental impact associated with the after-surgery period on the fragile physical condition of these patients. Exercise training has been proven to be effective on reconditioning patients after transplantation. However, the effects of exercise training in liver transplanted FAP patients have not been scrutinized yet. Methods. The study aimed to evaluate the effects of a 24-week exercise training program (supervised or home-based) on body composition, muscle strength, and walking capacity of liver transplanted FAP patients. To fulfill this goal, a sample corresponding to 33% of all FAP patients who undergone a liver transplantation in the area of Lisbon between January 2006 and December 2008 were followed over time. Three evaluation periods were accomplished: M1 (preexercise training period), M2 (immediate post-exercise training period), and M3 (24 weeks after M2). The former allowed an assessment of the impact of detraining in these patients. Results. The exercise training program improved body composition (lean mass and total body skeletal muscle mass), weight, and walking capacity. The improvements were more pronounced within the patients with supervised exercise training compared with the patients on the home-based program. In general, the benefits of the exercise training perdure even after a 24-week detraining period. Conclusions. Exercise training results in significant improvements on the physical condition of liver transplanted FAP patients.
    Transplantation 01/2013; 95(2):372-7. · 3.78 Impact Factor
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    ABSTRACT: BACKGROUND: Liver transplantation is nowadays the only effective answer to adjourn the outcome of functional limitations associated with familial amyloidotic polyneuropathy (FAP), a neurodegenerative disease characterized by sensory and motor polyneuropathies. Nevertheless, there is a detrimental impact associated with the after-surgery period on the fragile physical condition of these patients. Exercise training has been proven to be effective on reconditioning patients after transplantation. However, the effects of exercise training in liver transplanted FAP patients have not been scrutinized yet. METHODS: The study aimed to evaluate the effects of a 24-week exercise training program (supervised or home-based) on body composition, muscle strength, and walking capacity of liver transplanted FAP patients. To fulfill this goal, a sample corresponding to 33% of all FAP patients who undergone a liver transplantation in the area of Lisbon between January 2006 and December 2008 were followed over time. Three evaluation periods were accomplished: M1 (pre-exercise training period), M2 (immediate post-exercise training period), and M3 (24 weeks after M2). The former allowed an assessment of the impact of detraining in these patients. RESULTS: The exercise training program improved body composition (lean mass and total body skeletal muscle mass), weight, and walking capacity. The improvements were more pronounced within the patients with supervised exercise training compared with the patients on the home-based program. In general, the benefits of the exercise training perdure even after a 24-week detraining period. CONCLUSIONS: Exercise training results in significant improvements on the physical condition of liver transplanted FAP patients.
    Transplantation 12/2012; · 3.78 Impact Factor
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    Portuguese Journal of Nephrology and Hypertension. 08/2012; 26(3):199-205.
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    ABSTRACT: Familial transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the formation of transthyretin (TTR) amyloid deposits. This crippling and fatal disease is associated with point mutations in TTR, a protein mainly produced in the liver. Hence, liver transplantation is the only treatment capable of halting disease progression. Ideally, liver transplantation should be performed as early as possible in the disease course before significant neurologic disability has been incurred. Early detection of disease before serious pathological lesions occur is crucial for the clinical management of patients and for morbidity delay. Unfortunately, the presence of TTR mutations by itself is not a predictor of disease onset or progression. In the present work, we observed an increased oligomerization of α-synuclein in the saliva of ATTR symptomatic individuals comparatively to asymptomatic carriers of the same TTR mutation and healthy control subjects. Based on this observation, we propose monitoring α-synuclein oligomers in saliva as a biomarker of ATTR progression. Since α-synuclein plays a major role in several neurodegenerative disorders, assessing its oligomerization state in this fluid provides a non-invasive approach to survey these pathologies.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 05/2012; 19(2):74-80. · 2.51 Impact Factor
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    ABSTRACT: Nonadherence has important implications for morbidity and mortality, reduced quality of life, and increased medical costs after transplant. OBJECTIVE; To investigate which psychiatric and psychosocial factors determine adherence after liver transplant. A group of 150 consecutive transplant candidates attending the outpatient clinics of the transplant unit of Hospital de Curry Cabral were studied between January 1,2006, and December 1, 2007. Among these, 84 received a transplant and of those 84, 11 recipients died, 3 received another transplant, and 8 refused to finish the study (62 patients remained). Before transplant, prospective recipients were assessed via the Hospital Anxiety and Depression Scale, the NEO Five-Factor Inventory, and the revised Illness Perception Questionnaire. Both before and after transplant, patients were assessed with the Multidimensional Adherence Questionnaire. Adherence to medication improved significantly from before to after transplant. This kind of adherence after transplant was associated with adherence to medication before transplant and high scores on the personal control dimension of the Illness Perception Questionnaire before transplant. Therefore it might be useful to focus on patients with poor adherence to medication and low scores on the personal control dimension of the Illness Perception Questionnaire before transplant in order to design interventions for them.
    Progress in transplantation (Aliso Viejo, Calif.) 03/2012; 22(1):91-4. · 0.81 Impact Factor
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    ABSTRACT: Familial transthyretin amyloidosis (ATTR) is a fatal autosomal dominant disease characterized by the formation of amyloid fibers, mainly composed of transthyretin (TTR). Protein aggregation and amyloid fiber formation are considered concentration dependent processes and since most ATTR patients are heterozygous it is crucial to determine the ratio between mutant and non-mutant TTR forms in human plasma. Using a high resolution mass spectrometry based approach we determined the ratio of TTR forms in ATTR patients, V30M mutation carriers, symptomatic and asymptomatic ones, as well as ATTR patients that received a wild type cadaveric liver transplant. Domino transplanted patients that received a liver from an ATTR patient were also investigated. We found that although wild type TTR is diminished in the plasma of non-transplanted ATTR patients comparatively to healthy subjects, the relationship with the V30M variant does not change with illness progression. Those who received a wild type liver showed no mutant protein while domino transplanted patients presented the same relative amount of V30M as found in asymptomatic and symptomatic individuals. The V30M to wild type TTR ratio in plasma is the same for all ATTR patients studied, showing no variation with disease clinical progression. Our results point to the involvement of additional non-genetic factors on the pathogenesis of this disease.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 12/2011; 18(4):191-9. · 2.51 Impact Factor
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    ABSTRACT: Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease leading to sensory and motor polyneuropathies, and functional limitations. Liver transplantation is the only treatment for FAP, requiring medication that negatively affects bone and muscle metabolism. The aim of this study was to compare body composition, levels of specific strength, level of physical disability risk, and functional capacity of transplanted FAP patients (FAPTx) with a group of healthy individuals (CON). A group of patients with 48 FAPTx (28 men, 20 women) was compared with 24 CON individuals (14 men, 10 women). Body composition was assessed by dual-energy X-ray absorptiometry, and total skeletal muscle mass (TBSMM) and skeletal muscle index (SMI) were calculated. Handgrip strength was measured for both hands as was isometric strength of quadriceps. Muscle quality (MQ) was ascertained by the ratio of strength to muscle mass. Functional capacity was assessed by the six-minute walk test. Patients with FAPTx had significantly lower functional capacity, weight, body mass index, total fat mass, TBSMM, SMI, lean mass, muscle strength, MQ, and bone mineral density. Patients with FAPTx appear to be at particularly high risk of functional disability, suggesting an important role for an early and appropriately designed rehabilitation program.
    Clinical Transplantation 03/2011; 25(4):E406-14. · 1.63 Impact Factor
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    ABSTRACT: Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease that leads to sensory and motor polyneuropathies as well as functional limitations. So far, liver transplantation is the only treatment for FAP because the mutated protein causing the disease is mainly produced in the liver. With the increasing survival of transplant recipients, functional and cardiovascular problems as consequences of immunosuppressant side effects are increasing associated with sedentary lifestyles and/or pretransplantation status. We sought to analyze the impact of exercise training programs on 1 FAP patient's course long-term after liver transplantation. A FAP patient (female; 49 years of age; body mass index = 18.8 kg/m(2)) underwent a liver transplantation 133 months before assessment. She was assessed for body composition, isometric quadriceps muscle strength, functional capacity, fatigue, and levels of physical activity before and after a 6-month period of combined exercise training. After the exercise training program, almost all variables were improved, namely, total body skeletal muscle mass, proximal femoral bone mineral density, quadriceps strength, maximal oxygen consumption on 6 minutes walk test (6mwt) or VO2peak, total ventilation on 6mwt, and fatigue. The improvement in distance on 6mwt (69.2 m) was clinically significant. Preintervention the levels of physical activity were below international recommendations for health; after the program they achieved the recommendations. The results showed an improvement in functional capacity with a decrease in future disability risk associated with a better lifestyle with respect to physical activity levels in 1 patient.
    Transplantation Proceedings 01/2011; 43(1):257-8. · 0.95 Impact Factor
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    ABSTRACT: Purpose: To evaluate the effects of a six months exercise training program on walking capacity, fatigue and health related quality of life (HRQL). Relevance: Familial amyloidotic polyneuropathy disease (FAP) is an autossomic neurodegenerative disease, related with systemic deposition of amyloidal fibre mainly on peripheral nervous system and mainly produced in the liver. FAP often results in severe functional limitations. Liver transplantation is used as the only therapy so far, that stop the progression of some aspects of this disease. Transplantation requires aggressive medication which impairs muscle metabolism and associated to surgery process and previous possible functional impairments, could lead to serious deconditioning. Reports of fatigue are common feature in transplanted patients. The effect of supervised or home-based exercise training programs in FAP patients after a liver transplant (FAPTX) is currently unknown. Participants: Thirty nine FAPTX subjects between 2 and 12 months post liver transplant were randomly assigned into three groups: a control group (CG) of 14 patients (11 males and 3 females, 34±10years, BMI 22.1±3.1kg/m2) without any exercise intervention; a supervised exercise training group (EG) of 8 patients (5 males and 3 females, 34±7years, BMI 20.4±4.5kg/m2) and an home-based exercise training group (HB) of 15 patients who exercised at home with a twice-monthly feed-back (4 males and 11 females, 35±5years, BMI 22.3±4.3kg/m2). Methods: EG and HB groups exercised during 6 months, 3 times a week, 1 hour of aerobic and resistance exercise at moderate intensity. Walking capacity (WCp) was assessed by 6 minutes walk test (6mwt). Fatigue levels and HRQL were assessed by Multidimensional Assessment of Fatigue questionnaire (MAF) and Medical Outcome Study-36 item (SF-36) questionnaire respectively. Analysis: In order to analyse changes resulting of intervention program, a variable was created resulting from difference between post-intervention values and pre-intervention values. To analyse differences between groups, One-way Anova (or kruskall-Wallis in case of skewed data) was performed with correspondent's post-hoc tests. Statistical significance was set at p<0.05. Results: WCp expressed by body weight × walking distance was better (p<0.05) for EG but not for HB or CG. Neither groups have reported significant changes in fatigue or HRQL as result of exercise training program. Conclusions: Supervised exercise has proved to be significantly more effective than home-based exercise in improving WCp in liver transplanted FAP patients. Although not significant, HB group has presented higher values for difference in WCp than CG. This increase in WCp reflects a better functional exercise level for daily physical activities. So, it seems that clearly these patients benefit from an exercise training program. However, this exercise program has not changed fatigue levels and HRQL. Implications: The knowledge of results of home-based versus supervised exercise programs is of major importance for physical therapist intervention. In fact, a supervised program seems to be more effective in positively change walking capacity. However, since our program was not suitable to change fatigue and HRQL in FAPTx patients, other kind of prescription should be studied to objectively change these results. This knowledge will be of major importance for effective interventions of physiotherapists in transplantation and physical condition field
    Physiotherapy 01/2011; 97(S1):eS1241-eS1242. · 1.57 Impact Factor
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    ABSTRACT: Recognizing the potential impact of psychiatric and psychosocial factors on liver transplant patient outcomes is essential to apply special follow-up for more vulnerable patients. The aim of this article was to investigate the psychiatric and psychosocial factors predicted medical outcomes of liver transplanted patients. We studied 150 consecutive transplant candidates, attending our outpatient transplantation clinic, including 84 who had been grafted 11 of whom died and 3 retransplanted. We observed that active coping was an important predictor of length of stay after liver transplantation. Neuroticism and social support were important predictors of mortality after liver transplantation. It may be useful to identify patients with low scores for active coping and for social support and high scores for neuroticism to design special modes of follow-up to improve their medical outcomes.
    Transplantation Proceedings 01/2011; 43(1):155-7. · 0.95 Impact Factor
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    ABSTRACT: Alcoholic liver disease (ALD) is one of the most important indications for liver transplantation. Discordant conclusions have been found concerning quality of life and mental health after transplantation in this particular group. The aim of this work was to investigate improvements in mental health and quality of life among transplanted patients for ALD. We studied 45 consecutive transplant candidates with ALD, attending the outpatient clinics. Among these patients we transplanted 24 with the control candidates remaining in wait for transplantation. There was a significant improvement in all mental health and quality of life dimensions among the transplanted ALD group. We also observed a favorable evolution of coping mechanisms (CM) in this group. There is a favorable adjustment of ALD patients after transplantation as shown in CM evolution, which might explain the improved mental health and quality-of-life dimensions.
    Transplantation Proceedings 01/2011; 43(1):184-6. · 0.95 Impact Factor
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    ABSTRACT: Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease.
    PLoS ONE 01/2011; 6(10):e24850. · 3.53 Impact Factor
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    ABSTRACT: No abstract available.
    Psychotherapy and Psychosomatics 11/2010; 80(1):60-1. · 9.38 Impact Factor
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    ABSTRACT: PURPOSE: To identify, characterize and perform a relative quantification of human transthyretin (TTR) variants in human saliva. EXPERIMENTAL DESIGN: Serum and saliva samples were collected from healthy and familial amyloidotic polyneuropathy (FAP) patients, proteins separated by SDS-PAGE, TTR bands excised, in-gel digested and analyzed by MALDI-FTICR. RESULTS: We identified and performed a relative quantification of mutated and native TTR forms in human saliva, based on FTICR-MS. The results are quantitatively identical to the ones obtained with human serum. In FAP patients subjected to cadaveric liver transplant, the TTR mutant form is no longer detected in saliva, while in patients receiving a domino liver from a FAP donor the mutant form of TTR becomes detectable in saliva, thus demonstrating the serum origin of TTR in saliva. CONCLUSIONS AND CLINICAL RELEVANCE: Saliva TTR originates in serum and the ratio of mutant to native TTR is preserved. The method provides a non-invasive detection of mutated TTR and a relative quantification of TTR forms. Diagnostic and disease prognosis of FAP is crucial at early stages of the disease and after liver transplantation, the only curative therapy. A suitable non-invasive method was developed for monitoring the most important FAP biomarker in human saliva.
    PROTEOMICS - CLINICAL APPLICATIONS 07/2010; 4(6-7):674-8. · 1.81 Impact Factor
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    Medicine and science in sports and exercise 05/2010; 42(5):S235. · 4.48 Impact Factor
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    ABSTRACT: Introduction: Familial amiloidotic polineuropathy (FAP) is an autossomical and dominant neurodegenerative disease related with systemic deposition of amyloid fibre mainly on peripheral nervous system. Clinically, is translated by an autonomous sensitive-motor polyneuropathy with beginning nearly always in foot, involving subsequently the hands. Until now, the unique available treatment for FAP disease is liver transplantation requiring medication that negatively affect muscle metabolism and force production mechanism. To our knowledge there are no quantitative characterizations of peak force in FAP patients or any comparison with healthy people. This knowledge will be extremely important to verify clinical and functional evolution of this disease and eventually prescribe an effective rehabilitation program. Purpose: The purpose of this study was to analyse and compare levels of hand grip strength (peak force and endurance) in FAP patients with (FAPTx) or without (FAPNTx) a liver transplant with a group of healthy people (GC). Material and methods: The total sample of individuals where two hundred and six, assigned in 3 groups: 59 patients PAFNTx (23 males, 36 female; age 35 ± 8 years); 90 patients PAFTx (53 males, 37 females; age 34 ± 8years) e 62 healthy persons (GC) (30 males, 32 females; age 33 ± 9 years). Grip strength was assessed by a portable grip dynamometer E-link (Biometrics Ltd, UK). All measurements were taken on standardized positions with standardized orders. The value noted to peak force was classified according to American College of Sports Medicine norms for grip strength. Results: The 3 groups are differents (p < 0,05) for weigth, body mass index (BMI) and grip strength in both hands and endurance for left hand. Negative correlations between age and grip strength were found for PAFNTx and PAFTx but not for GC. Conclusions: According to our results FAP patients have lower values for grip strength in both hands than healthy subjects and consequently a worse classification in ACSM norms. Most patients present grip strength values lower than medium values or even precarious. These results could present predictable negative functional implications, showing also the necessity of a rehabilitation program with specificity at hand motor level.
    Acta Médica Portuguesa. 01/2010; 23(5):803-810.
  • ERA EDTA 2010; 01/2010
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    ABSTRACT: Transthyretin (TTR) is a homotetrameric protein involved in thyroid hormone transport in blood and in retinol binding in the central nervous system. More than 80 point mutations in this protein are known to be associated with the formation of amyloid deposits and systemic amyloidotic pathologies. Age at onset varies according to the mutation but considerable variations also occur for subjects carrying the same mutation. Moreover, wild-type TTR forms amyloid deposits in systemic senile amyloidosis, a geriatric disorder. An accurate diagnostic and the choice of therapeutic options depend on the identification of the specific mutation. Previous characterization of TTR variants by mass spectrometry required the use of antibodies for sample enrichment. We developed a novel assay based on ultra high-resolution mass spectrometry to identify human TTR variants. The method, requiring a very low sample amount, is based on SDS-PAGE fractionation of human serum, followed by peptide mass fingerprinting by MALDI-FTICR-MS (matrix assisted laser desorption ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry). Moreover, it is possible to perform a relative quantification of wild type and mutant TTR forms by mass spectrometry. The method was tested and validated with the V30M mutant, involved in familial amyloidotic neuropathy of Portuguese type.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 12/2009; 16(4):201-7. · 2.51 Impact Factor
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    Portuguese Journal of Nephrology and Hypertension. 10/2009; 24(1):45-50.