RESUMO
The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; six adults) in a prospective pilot study. All of them followed a GFD for one year. The Yale Global Tics Severity Scale (YGTSS), the Yale-Brown Obsessive-Compulsive Scale—Self Report (Y-BOCS) or the Children’s Yale-Brown Obsessive-Compulsive Scale—Self Report (CY-BOCS), and the Cavanna’s Quality of Life Questionnaire applied to GTS (GTS-QOL) were compared before and after the GFD; 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated obsessive-compulsive disorder (OCD) (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3, (standard deviation (SD) = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved generic quality of life (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.
Assuntos
Dieta Livre de Glúten , Síndrome de Tourette/dietoterapia , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/dietoterapia , Cooperação do Paciente , Projetos Piloto , Gravidez , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Tiques/diagnóstico , Tiques/dietoterapia , Adulto JovemRESUMO
OBJECTIVES: Uveitis is an eye disease that affects humans worldwide. Inflammation of the uveal tract is termed uveitis. Alpha-1-antitrypsin (AAT) deficiency is one of many factors that may be involved in abnormalities such as liver and lung disease, inflammatory joint diseases, and inflammatory eye diseases. In this study, the role of AAT in uveitis is analyzed. DESIGN AND METHODS: AAT phenotyping and serum-trypsin inhibitory capacity (S-TIC) experiments were performed on 103 patients who were referred to the ALZAHRA eye center in Zahedan (southeast of Iran). The same experiments were performed on 167 people who did not suffer from any eye or systemic diseases and served as a control group. RESULTS: The results revealed that the frequency of M1S, M2S, M1Z, and MV phenotypes were significantly higher in uveitis patients (P < 0.001). There was no difference in AAT phenotype frequencies between various types of uveitis (P = 0.1). CONCLUSION: AAT deficiency appears to be a risk factor for uveitis in southeast Iran. More investigation is needed to establish potential benefits of AAT phenotyping tests and AAT therapy in the diagnosis and treatment of uveitis cases with unclear etiology.
Assuntos
Antígeno HLA-B27/genética , Uveíte/genética , alfa 1-Antitripsina/genética , Estudos de Casos e Controles , Etnicidade/genética , Humanos , Irã (Geográfico) , Pan-Uveíte/genética , Fenótipo , Inibidores da Tripsina/sangue , Uveíte Anterior/genética , Uveíte Posterior/genéticaRESUMO
alpha1-Antitrypsin (AAT) circulates in high serum concentrations, and impregnates most body tissues. AAT has a broad anti-inflammatory spectrum, and modulates most inflammatory reactions occurring in human body. Recently, a possible relationship between AAT deficiency (AAT-D) and fibromyalgia (FM) has been raised, with the finding that intravenous infusions of purified human AAT efficiently controlled FM symptoms in two patients with severe hereditary AAT-D. On the other hand, functional magnetic resonance imaging has detected a significant greater activity in pain sensitive areas of the brain in patients with FM, in response to cutaneous stimuli, providing further evidence for a physiological explanation for FM pain. In recent studies abnormal profiles of inflammation markers in serum and biopsies have been found in FM patients. Since most of these inflammation mediators can be inhibited by AAT, these observations would suggest that at least a subset of the FM syndrome could be related to an inflammatory process, possibly due to an imbalance between inflammatory and anti-inflammatory substances, in the soft body tissues. Future directions of research would be: (1) to develop epidemiological studies to determine the gene frequency of AAT deficiency alleles in FM patients; (2) implementation of a double-blind placebo-controlled clinical trial to determine the specific role of AAT augmentation therapy in AAT-D patients with FM; (3) identification of specific laboratory markers for diagnostic and clinical evaluation purposes in FM; (4) application of the newest medical imaging techniques for diagnosis; and (5) identification of genetic, familial, and environmental risk factors suspected to participate in the FM syndrome development.
Assuntos
Fibromialgia/fisiopatologia , alfa 1-Antitripsina/fisiologia , Fibromialgia/tratamento farmacológico , Fibromialgia/epidemiologia , Humanos , alfa 1-Antitripsina/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVE: Alpha-1-antitrypsin deficiency (AATD) is an hereditary disorder with increased risk of pulmonary emphysema and chronic liver diseases in children and adults. Since it is possible currently in Spain to apply alpha-1-antitrypsin replacement therapy to AATD patients, the objective of this study was to calculate the total number of subjects affected by PIS and PIZ AATD, and its phenotypic distribution. SUBJECTS, MATERIAL AND METHOD: Selection of published studies on allelic frequencies PIS and PIZ according to the following criteria: a) alpha-1-antitrypsin phenotyping performed by isoelectrofocusing; b) rejection of "screening studies"; c) statistic precision factor score of 5, and d) samples representative of the Spanish general population. RESULTS: Four out 34 cohorts were selected. Mean gene frequencies (per 1,000) were: 104 (95% confidence interval [CI], 96-113) for PI*S and 17 (95% CI, 14-21) for PI*Z. These data indicated that it would exist in Spain 9,173,181 AATD subjects (95% CI, 9,167,966-9,178,398), with the following phenotypic distribution: 7,358,263 (95% CI, 6,696,222-8, 072,328) for PIMS; 1,222,041 (95% CI, 972,767-1,539,805) for PIMZ; 436,023 (95% CI, 369,057-514,244) for PISS; 144,827 (95% CI, 107,227-195,038) for PISZ; and 12,026 (95% CI, 7,788-18,493) for PIZZ. The global prevalence was 1 out of 4.4 individuals, with the following distribution: PIMS 1/5; PIMZ 1/33; PISS 1/92; PISZ 1/278; and PIZZ 1/3,344. CONCLUSIONS: AATD is a frequent but underdiagnosed disease in Spain.
Assuntos
Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Adulto , Criança , Estudos Epidemiológicos , Frequência do Gene , Genótipo , Humanos , Fenótipo , Prevalência , Espanha/epidemiologiaRESUMO
UNLABELLED: . BACKGROUND: Currently, there is a remarkable lack of genetic epidemiological studies on alpha 1-antitrypsin (AAT) deficiency in about half of the 193 countries of the World. This fact impedes the establishment of a true prevalence pattern of this deleterious hereditary disorder in extensive regions of human population. 2. OBJECTIVES: The aim of the present study was to generate detailed maps of the frequency distribution of the two most frequent AAT deficiency alleles (i.e., PI*S and PI*Z) in all areas of the World. 3. MATERIALS AND METHODS: Available data provided by epidemiological studies performed in 94 of 193 countries worldwide was used to develop detailed maps of these two alleles, We employed an informatics mathematical approach, namely: the ArcMap [a component of ESRI's ArcGIS Geographical Information System (GIS), for Microsoft Windows], based on the inverse distance weighting (IDW) multivariate interpolation method, which creates new numerical points from known data, using a simple logarithm based in the distance existing between them 4. RESULTS: In this method, PI*S and PI*Z frequencies were represented by colored scales, where qualitative colors were converted into quantitative data, providing information on their distribution in all parts of the world. This approach not only confirmed our previous data, but also provided digital images of the remaining regions of all continents. 5. CONCLUSIONS: By using this approach, striking differences were found among regions, and unsuspected significant values of the PI*S and PI*Z alleles frequencies were obtained for several geographic regions where have not been studied yet. In fact, some of these regions might be considered as priority targets for further screening studies on AAT deficiency, in order to identify, and properly manage, individuals at risk for the diverse adverse health effects associated with AAT deficiency.
RESUMO
BACKGROUND: Our earlier publications have demonstrated that alpha-1 antitrypsin (AAT) deficiency is not a rare disorder in the United States with at least 33,728 PI*ZZ homozygote individuals at risk. METHOD: Using data on the prevalences of the two most common deficiency alleles PI*S and PI*Z in the five major individual ethnic subgroups in the United States, the numbers of heterozygotes for PI*MS and PI*MZ, and compound heterozygotes/homozygotes for PI*SS, PI*SZ and PI*ZZ have been determined for each ethnic subgroup. RESULTS: When the data for the prevalence of AAT deficiency in individual cohorts are displayed as a function of ethnic subgroup, striking differences are found in the numbers in each of the five phenotypic classes of PI*S and PI*Z. This type of analysis has demonstrated striking differences in the risk for AAT deficiency in each of these five ethnic subgroups. This analysis as a function of ethnic subgroup also has demonstrated that there are higher numbers of each of the five PI*S and PI*Z deficiency classes, namely PI*MS, PI*SS, PI*MZ, PI*SZ and PI*ZZ. CONCLUSIONS: This analysis has demonstrated that the highest risk for AAT deficiency is found in Whites, followed by Hispanics and Blacks with the lowest prevalence among Mexican Americans and no risk among Asians. The numbers for those at risk for AAT deficiency in the United States are well documented and in the present analysis there are, for example, a total of 48,904 PI*ZZ homozygotes at risk. The critical question for our healthcare professionals is 'When will the medical community acknowledge that AAT deficiency is a prevalent and well-documented human genetic disorder and develop appropriate mechanisms for early diagnosis, medical follow-up and treatment both in the United States and worldwide?'
Assuntos
Grupos Raciais/estatística & dados numéricos , Deficiência de alfa 1-Antitripsina/epidemiologia , alfa 1-Antitripsina/genética , Alelos , Bases de Dados Factuais , Humanos , Fenótipo , Prevalência , Estados Unidos/epidemiologia , Deficiência de alfa 1-Antitripsina/etnologia , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
Formalin-fixed, paraffin-embedded skin tissue sections were collected from a matched cohort of 63 fibromyalgia syndrome (FMS) patients and 49 volunteers from the general population with both alpha1-antitrypsin (AAT) normal and deficiency variants. These tissues were examined for the expression of the broad-spectrum inhibitor AAT, the serine proteinases elastase and tryptase, the proinflammatory cytokines MCP-1 and TNFα, the endothelium biomarker VEGF, and the inflammation/nociception-related receptor PAR(2). The most relevant finding of the study was a significantly increased number of mast cells (MCs) in the papillary dermis of all FMS patients (greater than or equal to five to 14 per microscopic high power field) compared to zero to one in controls (p < 0.001). MCs strongly stained with tryptase, AAT and PAR(2) antibodies, exhibited a spindle-like shape and were uniformly distributed around blood vessels and appendages. MCP-1 and VEGF expressed weak/moderate positivity in most samples, with a higher expression in controls than in FMS patients (p < 0.001 and 0.051, respectively). No differences in elastase and TNFα were found between both groups. Moreover, no histological differences were found between samples from AAT deficiency and normal AAT phenotypes. Our results indicate that FMS is a MC-associated condition. MCs are present in skin and mucosal surfaces throughout the human body, and are easily stimulated by a number of physical, psychological, and chemical triggers to degranulate, releasing several proinflammatory products which are able to generate nervous peripheral stimuli causing CNS hypersensitivity, local, and systemic symptoms. Our findings open new avenues of research on FMS mechanisms and will benefit the diagnosis of patients and the development of therapeutics.
Assuntos
Citocinas/metabolismo , Fibromialgia/enzimologia , Mastócitos/patologia , Pele/enzimologia , alfa 1-Antitripsina/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Quimiocina CCL2/metabolismo , Feminino , Fibromialgia/etiologia , Fibromialgia/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Elastase Pancreática/metabolismo , Receptor PAR-2/metabolismo , Pele/patologia , Triptases/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Deficiência de alfa 1-Antitripsina/complicaçõesRESUMO
Abnormalities in blood inflammatory markers have been associated with clinical manifestations and the pathogenesis of the fibromyalgia syndrome (FMS); a relationship between inherited alpha1-antitrypsin deficiency (AATD) and FMS has also been recently raised. In this study, plasma levels of inflammatory markers in FMS patients with and without AATD have been investigated. Blood samples from 138 age-matched females (79 FMS) and 59 general population (GP), with normal MM [n = 82 (59.4%)] and with MS, MZ, SZ, and ZZ AATD genotypes [n = 56 (40.6%)], were analyzed by ELISA for monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFalpha), soluble TNFalpha receptors I and II, interleukin-8, and vascular endothelial growth factor (VEGF). Plasma levels of MCP-1, VEGF, and TNFalpha were significantly lower in FMS and GP subjects with AATD compared with those with normal MM-AAT genotypes. Moreover, plasma levels of MCP-1, VEGF, and TNFalpha were lower in AATD subjects with FMS than in those without FMS (P = 0.000, 0.000, and 0.046, respectively). No statistical differences were found for the other substances measured. Furthermore, a logistic regression model based on plasma MCP-1 cutoff value of Assuntos
Quimiocina CCL2/sangue
, Fibromialgia/sangue
, Fator de Necrose Tumoral alfa/sangue
, Fator A de Crescimento do Endotélio Vascular/sangue
, Deficiência de alfa 1-Antitripsina/sangue
, Feminino
, Fibromialgia/complicações
, Fibromialgia/genética
, Genótipo
, Humanos
, Pessoa de Meia-Idade
, Curva ROC
, Análise de Regressão
, Estatísticas não Paramétricas
, Deficiência de alfa 1-Antitripsina/complicações
, Deficiência de alfa 1-Antitripsina/genética
RESUMO
BACKGROUND: Alpha1-antitrypsin (AAT) deficiency is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The objective of the present screening was to estimate the AAT gene frequency and prevalence and to identify AAT deficiency cases in a large cohort of Lithuanian patients with COPD. METHODS: A nationwide program of AAT deficiency was conducted in 1167 COPD patients, defined according to the GOLD criteria. Patients were collected from outpatient clinics in five different Lithuanian regions (Kaunas, Vilnius, Siauliai, Klaipeda and Alytus). AAT serum concentrations were measured by nephelometry; PI-phenotypes characterized by isoelectric-focusing. RESULTS: Mean age and FEV(1) were 62.0 (10.3) and 54.7% (10.9), respectively. Ninety-one AAT deficiency genotypes (40 MZ, 39 MS, 1 SS, 3 SZ and 8 ZZ) were identified. Calculated PI(*)S and PI(*)Z frequencies, expressed in per 1000, were 18.8 (95% CI: 13.9-25) and 25.3 (95% CI: 19.4-32.7), respectively. The calculated AAT gene prevalence (Hardy-Weinberg principle) was: 1/1.09 for MM, 1/28 for MS, 1/2814 for SS, 1/20 for MZ, 1/1049 for SZ and 1/1565 for ZZ. Calculated Odds ratio (OR) for PI(*)Z in COPD vs. Lithuanian healthy people was of 1.87 (P=0.004). CONCLUSION: The OR for each genotypic class demonstrated a significant increase of MZ, SZ and ZZ genotypes in COPD patients. The results of the present study, with a significant number of ZZ individuals detected, support the general concept of targeted screening for AAT deficiency in countries like Lithuania, with a large population of COPD patients and low awareness among care-givers about this genetic condition.
Assuntos
Doença Pulmonar Obstrutiva Crônica/complicações , Deficiência de alfa 1-Antitripsina/diagnóstico , Idoso , Estudos de Coortes , Feminino , Frequência do Gene , Humanos , Lituânia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/genética , Índice de Gravidade de Doença , Fatores Sexuais , Espirometria/métodos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
Alpha-1 antitrypsin deficiency is known as a significant genetic risk factor for COPD for carriers of phenotype PIMZ, and for phenotypes PIZZ and PISZ. Genetic epidemiological studies for alpha-1 antitrypsin deficiency conducted by others on both COPD patients and concurrent non-COPD controls were used to estimate the risk factors for all six phenotypic classes (namely, the normal phenotype PIMM, and the 5 deficiency allele phenotypes: PIMS, PIMZ, PISS, PISZ, and PIZZ). Studies on alpha-1 antitrypsin deficiency in white (Caucasian) COPD and non-COPD populations in 6 countries were combined to obtain estimates of the prevalence of the PIS and PIZ deficiency alleles in the combined COPD and non-COPD cohorts. The odds ratios for each of the six phenotypic classes of alpha-1 antitrypsin deficiency were calculated for a hypothetical population of 19.3 million white COPD patients in the United States of America. This approach demonstrated that 1,829,673 alpha-1 antitrypsin deficiency patients would be detected by testing 19.3 million white COPD patients and 536,033 in white non-COPD concurrent controls. The odds ratios for each of the phenotypic classes among white COPD patients demonstrate highly significant decreases in the normal phenotype PIMM, no significant change in the PIMS and PISS deficiency phenotypes, but highly significant increases in the prevalences of the PIMZ, PISZ, and PIZZ deficiency phenotypes. The result of the present study supports the concept of targeted screening for alpha-1 antitrypsin deficiency in countries with large populations of white (Caucasian) COPD patients.
Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Deficiência de alfa 1-Antitripsina/epidemiologia , Comorbidade , Frequência do Gene , Humanos , Programas de Rastreamento , Razão de Chances , Fenótipo , Doença Pulmonar Obstrutiva Crônica/genética , Fatores de Risco , Fumar/epidemiologia , Deficiência de alfa 1-Antitripsina/diagnósticoRESUMO
PURPOSE: To determine the frequencies of the protease inhibitor (PI) deficiency alleles of alpha1-antitrypsin deficiency (AAT Deficiency) in indigenous populations in 12 countries in Sub-Sahara Africa because of their potential impact on the health in these populations with regard to the high risk for development of liver and lung disease. In addition, to discuss the unique susceptibility of these populations and emigrants to Europe and the New World to the adverse health effects associated with exposure to environmental microbes, chemicals, and particulates. METHODS: Detailed statistical analysis of the 24 control cohort databases from genetic epidemiological studies by others were used to estimate the allele frequencies and prevalence for the two most common deficiency alleles PIS and PIZ and to estimate the numbers at risk in each of the local Sub-Sahara populations as well as those who have emigrated from these countries to Europe and the New World. RESULTS: The present study has provided evidence for the presence of both PIS and PIZ in the general populations of Nigeria, Republic of South Africa, and Somalia, the PIS allele in Angola, Botswana, Cameroon, Mozambique, Namibia, and the Republic of Congo, and only the PIZ allele in Mali. CONCLUSION: AAT Deficiency is found in both the Black and "Colored" populations in many of the Sub-Sahara countries in Africa, providing evidence for the presence of AAT Deficiency in such populations in Europe and in the New World. Such populations should be screened for AAT Deficiency and made aware of their unique susceptibility to exposure to chemical and particulate agents in the environment.
Assuntos
Emigração e Imigração , Grupos Raciais , Deficiência de alfa 1-Antitripsina/epidemiologia , África do Norte/epidemiologia , Alelos , Estudos de Coortes , Bases de Dados como Assunto , Europa (Continente)/epidemiologia , Genótipo , Humanos , Prevalência , Saúde Pública , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
Two Spanish sisters with alpha1-antitrypsin (AAT) deficiency and fibromyalgia (FM) started AAT replacement therapy with commercial alpha1-antitrypsin infusions in 1992. They both experienced a rapid, progressive, and constant control of their FM symptoms during the next 6 years (1992-98). However, in 1998, treatment of both patients was affected by the worldwide commercial shortage of AAT replacement therapy; replacement therapy infusions were halted for about 4-6 consecutive months every year for 5 years. As a result, we observed a striking recurrence of FM symptoms. Equally striking was the total disappearance of these symptoms when AAT replacement therapy infusions were resumed.