Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Rozhl Chir ; 100(1): 21-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33691419

RESUMO

INTRODUCTION: Thyroid surgery in children is a rare operation. The aim of our paper is to point out the specifics of thyroid surgery in children. METHODS: Retrospective analysis of patients hospitalized at the Department of Paediatric Surgery, Faculty of Medicine, Comenius University and National Institute of Childrens Diseases in Bratislava during a 10-year period (20072016) who underwent thyroid surgeries. RESULTS: The retrospective analysis included 81 patients: 66 (81%) girls and 15 (19%) boys. The mean age of the patients was 14 years ±8 months (range 418 years). The most common indications for thyroid surgery were: a nodule in 36 (44.4%) patients, Graves Basedow thyrotoxicosis in 19 (23.5%) patients, and suspected thyroid carcinoma in 11 (13.6%) patients. Cervical lymph node metastases (mts) were diagnosed in 9 (11.1%) patients, and distant pulmonary metastases in 5 (6.17%) patients. Total thyroidectomy (TTE) was performed in 43 (53%) patients, total lobectomy (TL) in 20 (24.7%) patients. Extended surgery on regional lymph nodes was performed in 9 (11.1%) patients. Eight (9.9%) patients underwent reoperation. A total of 12 (14.8%) patients experienced postoperative complications. Unilateral transient recurrent laryngeal nerve (RLN) paralysis occurred in 2 patients, and permanent in one patient. Transient postoperative hypoparathyroidism with hypocalcaemia was reported in 8 (9.9%) patients; no permanent condition of this type was observed. CONCLUSION: Multidisciplinary collaboration ensures that optimal surgical results are achieved in the patients. Experience of the surgeon performing thyroid surgery in children remains crucial.


Assuntos
Neoplasias da Glândula Tireoide , Paralisia das Pregas Vocais , Criança , Feminino , Humanos , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos
2.
Physiol Res ; 69(6): 995-1011, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33129248

RESUMO

Heterozygous inactivating mutations of the glucokinase (GCK) gene are causing GCK-MODY, one of the most common forms of the Maturity Onset Diabetes of the Young (MODY). GCK-MODY is characterized by fasting hyperglycemia without apparent worsening with aging and low risk for chronic vascular complications. Despite the mild clinical course, GCK-MODY could be misdiagnosed as type 1 or type 2 diabetes. In the diagnostic process, the clinical suspicion is often based on the clinical diagnostic criteria for GCK-MODY and should be confirmed by DNA analysis. However, there are several issues in the clinical and also in genetic part that could complicate the diagnostic process. Most of the people with GCK-MODY do not require any pharmacotherapy. The exception are pregnant women with a fetus which did not inherit GCK mutation from the mother. Such a child has accelerated growth, and has increased risk for diabetic foetopathy. In this situation the mother should be treated with substitutional doses of insulin. Therefore, distinguishing GCK-MODY from gestational diabetes in pregnancy is very important. For this purpose, special clinical diagnostic criteria for clinical identification of GCK-MODY in pregnancy are used. This review updates information on GCK-MODY and discusses several currently not solved problems in the clinical diagnostic process, genetics, and treatment of this type of monogenic diabetes.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Glucoquinase/genética , Hiperglicemia/enzimologia , Mutação , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Glucoquinase/metabolismo , Heterozigoto , Humanos , Hiperglicemia/genética , Hiperglicemia/patologia , Gravidez
3.
Physiol Res ; 69(5): 927-932, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-32901502

RESUMO

MEHMO syndrome is a rare X-linked syndrome characterized by Mental retardation, Epilepsy, Hypogenitalism, Microcephaly, and Obesity associated with the defect of protein synthesis caused by the EIF2S3 gene mutations. We hypothesized that the defect in protein synthesis could have an impact on the immune system. We describe immunologic phenotype and possible treatment outcomes in patient with MEHMO syndrome carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. The proband (currently 9-year-old boy) had normal IgG and IgM levels, but had frequent respiratory and urinary tract infections. On subcutaneous immunoglobulin therapy achieving supra-physiological IgG levels the frequency of infections significantly decreased in Poisson regression by 54.5 % (CI 33.2-89.7, p=0.017). The MEHMO patient had had frequent acute infections despite normal IgG and IgM serum levels and responded well to the immunoglobulin treatment.


Assuntos
Epilepsia/genética , Epilepsia/imunologia , Fator de Iniciação 2 em Eucariotos/genética , Genitália/anormalidades , Hipogonadismo/genética , Hipogonadismo/imunologia , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/imunologia , Microcefalia/genética , Microcefalia/imunologia , Mutação , Obesidade/genética , Obesidade/imunologia , Criança , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Genitália/imunologia , Genitália/patologia , Humanos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/patologia , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/tratamento farmacológico , Deficiência Intelectual Ligada ao Cromossomo X/patologia , Microcefalia/tratamento farmacológico , Microcefalia/patologia , Obesidade/tratamento farmacológico , Obesidade/patologia , Fenótipo , Resultado do Tratamento
5.
Bratisl Lek Listy ; 121(2): 129-132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115965

RESUMO

OBJECTIVES: We aimed to study the prevalence of the early onset Type 1 diabetes in Slovakia during the years 1996-2017. BACKGROUND: Prevalence of Type 1 diabetes in young children is increasing worldwide. However, recent data from Slovakia are missing. METHODS: All children with newly diagnosed Type 1 diabetes included in the study were diagnosed in the Children Diabetes Centre in Bratislava during the years 1996-2017. The incidence of T1D in children aged below 3 and below 5 years was calculated and compared to the T1D incidence in older children. Incidence trends were calculated with the Poissed regression. RESULTS: Gender-adjusted incidence of T1D annually increased by 5.4 % (CI: 3.9-6.8; p < 0.001) in children <3 years, and by 3.4 % (95 % CI 2.2-4.6; p<0.001) in children <5 years during the last two decades. Moreover, the proportion of young children <3 years of age among all newly diagnosed children and adolescents increased over time (4.2±2.8 % in years 1996-1998; 12.2±5.8 % in years 2004-2008, and 13.7±7.4 % during the years 2013-2017). CONCLUSION: We found a significant increase in the incidence and proportion of T1D in young children during the last two decades. Similar data were also found in other European countries. This could be explained by changing environmental conditions (Fig. 1, Ref. 32).


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Idoso , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/epidemiologia , Europa (Continente) , Humanos , Incidência , Lactente , Prevalência , Eslováquia/epidemiologia
6.
Physiol Res ; 67(2): 331-337, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29303605

RESUMO

Recently, the genetic cause of several syndromic forms of glycemia dysregulation has been described. One of them, MEHMO syndrome, is a rare X-linked syndrome recently linked to the EIF2S3 gene mutations. MEHMO is characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. Moreover, patients with MEHMO had also diabetes and endocrine phenotype, but detailed information is missing. We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. Both probands had a neonatal hypoglycemia, early onset insulin-dependent diabetes, and hypopituitarism due to dysregulation and gradual decline of peptide hormone secretion. Based on the clinical course in our two probands and also in previously published patients, neonatal hypoglycemia followed by early-onset diabetes and hypopituitarism may be a consistent part of the MEHMO phenotype.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diabetes Mellitus Tipo 1/genética , Epilepsia/genética , Fator de Iniciação 2 em Eucariotos/genética , Genitália/anormalidades , Hipoglicemia/congênito , Hipoglicemia/genética , Hipogonadismo/genética , Hipopituitarismo/congênito , Hipopituitarismo/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Microcefalia/genética , Obesidade/genética , Glândulas Endócrinas/metabolismo , Mutação da Fase de Leitura , Humanos , Recém-Nascido , Masculino , Fenótipo , Fatores de Transcrição
7.
Diabet Med ; 35(3): 386-391, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29278452

RESUMO

BACKGROUND: Therapy with sulfonylurea is preferable to insulin in the majority of individuals with KCNJ11 mutations, but not all of these people achieve target levels of HbA1c in long-term follow-up. We aimed to compare sulfonylurea therapy with insulin treatment in two sulfonylurea-sensitive individuals with a KCNJ11 mutation who had poorly controlled permanent neonatal diabetes mellitus. CASE REPORT: We report on two individuals with a KCNJ11 mutation (p.R201H) who are currently aged 35 (SVK1) and 21 years (SVK2). These individuals were switched from insulin to sulfonylurea in 2005. Data from the first 4 (SVK2) and 8 years (SVK1) of the follow-up showed improved diabetes control and increased quality of life for both individuals. During the following years, however, both individuals failed to retain good diabetes control (HbA1c ≤ 53 mmol/mol; 7.0%). We therefore changed the therapy to a combination of insulin and sulfonylurea in both individuals, or to insulin monotherapy in SVK1, and compared the effects on HbA1c with those of sulfonylurea monotherapy. HbA1c levels in both individuals worsened after adding insulin to sulfonylurea [67 mmol/mol (8.3%) vs 77 mmol/mol (9.2%) in SVK1 and 106 mmol/mol (11.8%) vs 110±19 mmol/mol (12.2±1.7%) in SVK2], and after switching to only insulin therapy in SVK1 [57 mmol/mol (7.4%) vs 62 mmol/mol (7.8%)] when compared with sulfonylurea monotherapy. DISCUSSION: Our data show that sulfonylurea monotherapy might be preferable to insulin in people with permanent neonatal diabetes mellitus sensitive to sulfonylurea even when HbA1c is above target.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Mutação/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adulto , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Adulto Jovem
8.
Physiol Res ; 66(1): 75-84, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-27824480

RESUMO

Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p.Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Genetic etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation.


Assuntos
Inquéritos Epidemiológicos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Receptores de LDL/genética , Adulto , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Eslováquia/epidemiologia , Estatística como Assunto/métodos , Adulto Jovem
9.
Endocr Regul ; 49(3): 137-40, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26238496

RESUMO

OBJECTIVES: The mutations in gene for the melanocortin-4 receptor (MC4R) are the most common etiology factors of monogenic obesity development. Recently, it has been shown that current life style has a significant impact on the phenotype of MC4R mutation carriers - increases the penetrance of the mutations. We aimed to study the impact of the current age on the time of obesity onset among MC4R mutation carriers. METHODS: DNA analysis of the MC4R gene was performed in 268 unrelated Slovak and Moravian obese children and adolescents 18 years and 28 blood relatives >18 years of the probands with a mutation. RESULTS: Three different previously described heterozygous loss of function MC4R mutations (p.Ser19Alafs*34, p.Ser127Leu, and p.Gly181Asp) were found in 3 <18 years probands, 3 adult probands, and 6 adult obese/overweight family relatives. The age of obesity onset in mutation carriers was 1 year in all probands in the children group and 1-35 years (median 11 years) in adults. The age of the obesity onset significantly correlated (R=0.809, p=0.028) with the current age in all of the MC4R mutation carriers. CONCLUSIONS: The age of obesity onset in the present child generation of MC4R mutation carriers is decreasing compared to the age of onset in their parents' generation. This is in agreement with similarly increasing penetrance of obesity in MC4R mutation carriers and it points out to escalation of obesogenic potential of environment.


Assuntos
Mutação , Obesidade Infantil/genética , Receptor Tipo 4 de Melanocortina/genética , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , República Tcheca/epidemiologia , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Lactente , Masculino , Obesidade Infantil/diagnóstico , Obesidade Infantil/epidemiologia , Fenótipo , Fatores de Risco , Eslováquia/epidemiologia , Adulto Jovem
10.
Endocr Regul ; 49(3): 164-81, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26238499

RESUMO

Familial hypercholesterolemia (FH) is the world's most abundant and the most common heritable disorder of lipid metabolism. The prevalence of the disease in general population is 1:500. Therefore the approximate number of FH patients all over the world is 14 million. From the genetic point of view the disease originates as a result of mutations in genes affecting the processing of LDL particles from circulation, resulting in an increase in LDL cholesterol and hence total cholesterol. These are mutations in genes encoding LDL receptor, apolipoprotein B, proprotein convertase subtilisin/kexin 9 and LDL receptor adaptor protein 1. Cholesterol depositing in tissues and blood vessels of individuals creates tendon xanthoma, xanthelesma and arcus lipoides cornae. Due to the increased deposition of cholesterol in blood vessels, atherosclerosis process is accelerated, what leads to a significantly higher risk of premature cardiovascular diseases. Therefore, early clinical diagnosis confirmed by the DNA analysis, and effective treatment are crucial to reduce the mortality and high risk of premature atherosclerotic complications.


Assuntos
Apolipoproteína B-100/genética , Hiperlipoproteinemia Tipo I/genética , Mutação , Pró-Proteína Convertases/genética , Receptores de LDL/genética , Serina Endopeptidases/genética , Anticolesterolemiantes/uso terapêutico , Apolipoproteína B-100/sangue , Biomarcadores/sangue , Colesterol/sangue , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Hiperlipoproteinemia Tipo I/epidemiologia , Fenótipo , Valor Preditivo dos Testes , Prevalência , Prognóstico , Pró-Proteína Convertase 9 , Pró-Proteína Convertases/sangue , Receptores de LDL/sangue , Fatores de Risco , Serina Endopeptidases/sangue
11.
Physiol Res ; 64(6): 883-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26047380

RESUMO

The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97(th) percentile for age and sex and obesity onset up to 11 years (mean 4.3+/-2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.


Assuntos
Obesidade Infantil/genética , Receptor Tipo 4 de Melanocortina/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Fenótipo , Eslováquia
12.
Endocr Regul ; 46(3): 167-86, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22808909

RESUMO

Hearing loss is one of the most widespread sensory disorders. The incidence of deafness in general population is 1:1000 newborns. About one half of the cases of the congenital sensorineural hearing loss (SNHL) is inherited. Recessive mutations in the gap junction beta 2 (GJB2) gene are the most common genetic causes of the nonsyndromic SNHL. The GJB2 encodes a protein connexin 26 which forms a subunit of gap junction essential for the correct function of the inner ear. The syndromic SNHL is associated with a wide range of other symptoms, which encompass also dysfunctions of endocrine organs. The Pendred syndrome associated with the hearing impairment is characterized by a prelingual, bilateral sever to profound SNHL, goiter, and iodine organification defect. It is an autosomal recessive disorder, which develops due to mutations in pendrin, an anion channel encoded by SLC26A4 gene. Another important type of syndromic hearing loss is the Maternally Inherited Diabetes and Deafness syndrome, which is caused by several mitochondrial DNA mutations. These mutations are clinically manifested by a hearing impairment with development of the diabetes in the adult age. Hearing impairment occurs during puberty when sensation of high frequency tones is affected following with further progress to profound bilateral sensorineural hearing impairment in the whole frequency range. This review deals with the molecular mechanisms of common genetic causes of the hereditary SNHL along with the selected endocrinopathies emphasizing that the DNA analyses along with the functional studies significantly contribute to the early SNHL diagnosis followed by personalized therapy and genetic counseling.


Assuntos
Conexinas/genética , DNA Mitocondrial , Doenças do Sistema Endócrino/genética , Perda Auditiva Neurossensorial/genética , Mutação , Animais , Conexina 26 , Surdez/genética , Diabetes Mellitus Tipo 2/genética , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/fisiopatologia , Predisposição Genética para Doença , Bócio Nodular/genética , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Hereditariedade , Humanos , Doenças Mitocondriais , Fenótipo
13.
Endocr Regul ; 46(2): 99-105, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22540858

RESUMO

OBJECTIVES: Glucokinase (GCK) diabetes is a mild form of the monogenic diabetes characterized by the fasting hyperglycemia without signs of metabolic syndrome and very low risk for chronic complications of diabetes. For the Type 2 diabetes (T2D), signs of the metabolic syndrome with high risk for chronic micro- and macro-vascular complications are typical. The prevalence of the GCK-diabetes is estimated from 0.5 to 1% in the diabetic patients. The T2D is the most prevalent type of the diabetes (it encompasses more than 85% of all the diabetic patients). According to the epidemiology, the coincidence of these two diabetes subtypes may occur; nevertheless no case reports on the above mentioned two diabetes subtypes have been published. The aim of the study was: 1) to perform the DNA analysis in three brothers, two of them with the fasting hyperglycemia and one with normal glucose tolerance, and their father with T2D metabolic syndrome and 2) to study the coincidence of the GCK-diabetes with T2D and its effect on the diabetic phenotype. PATIENTS AND METHODS: We report about a Roma (Gypsy) family consisting of three brothers: 17 years old probant and two older brothers (21 and 25 years), and their father. The probant is suffering from fasting hyperglycemia. His 25 years old diabetic brother and their father suffer from obesity, hypertension, dyslipidemia, and hyperglycemia. The glucokinase gene was analyzed by direct sequencing in each of the brothers and their father, and appropriate phenotype characteristics were also carried out on each of the family members. RESULTS: In the proband and his diabetic brother with the fasting hyperglycemia, a heterozygous mutation of the glucokinase gene p.Arg36Trp was found. The proband's phenotype was consistent with the GCK-diabetes, while the diabetic brother displayed already features of the metabolic syndrome. Although, the latter one suffered from the overweight, hypertension, and elevated triglycerides, his fasting hyperglycemia (8.3 mmol/l) was still consistent with the GCK-diabetes. Their father is also a heterozygous mutation carrier of the same mutation displaying all the features of the metabolic syndrome. In his case, the fasting hyperinsulinemia (43.5 µU/ml) and fasting plasma glucose (10.4 mmol/l) are more typical for the T2D than GCK-diabetes. CONCLUSIONS: We found coincidence between the GCK-diabetes and T2D in the members of a single Roma (Gypsy) family. Since the chronic complications are rare in the GCK-diabetes, the major risk factor for the further morbidity may be in the development of the T2D. The overlapping of the GCK-diabetes with other types of diabetes, particularly the T2D, makes the diagnostics difficult and therefore, it might be one of the reasons why the estimated prevalence of the GCK-diabetes seems to be higher than the real one as it has been reported in several studies.


Assuntos
Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Roma (Grupo Étnico)/genética , Roma (Grupo Étnico)/estatística & dados numéricos , Adulto , Saúde da Família , Feminino , Genótipo , Humanos , Masculino , Linhagem , Fenótipo , Prevalência , Fatores de Risco , Eslováquia , Adulto Jovem
14.
Vnitr Lek ; 57(11): 937-45, 2011 Nov.
Artigo em Eslovaco | MEDLINE | ID: mdl-22165700

RESUMO

Monogenic diabetes mellitus is a type of diabetes, where genetics without any other factors is strong enough to cause the disease. According to the clinical features monogenic diabetes can be divided to the mild familial early onset diabetes, familial fasting hyperglycemia, diabetes with extrapancreatic features and neonatal diabetes mellitus. During the last several years the number of genes causing monogenic diabetes has continuously increased. The clinical picture of the monogenic diabetes is very heterogeneous, thus DNA analysis is required for identification of the diabetes etiology, which influences also the choice of treatment. This article is an overview of current knowledge on monogenic diabetes, focusing at the clinically and epidemiologically most important forms.


Assuntos
Diabetes Mellitus/genética , Complicações do Diabetes/genética , Humanos , Mutação
15.
Diabetologia ; 54(11): 2801-10, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21814873

RESUMO

AIMS/HYPOTHESIS: An accurate molecular diagnosis of diabetes subtype confers clinical benefits; however, many individuals with monogenic diabetes remain undiagnosed. Biomarkers could help to prioritise patients for genetic investigation. We recently demonstrated that high-sensitivity C-reactive protein (hsCRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype-phenotype relationship and compare different hsCRP assays. METHODS: High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121 participants (8.1%) with hsCRP values >10 mg/l. The discriminative power of hsCRP with respect to diabetes aetiology was assessed by receiver operating characteristic curve-derived C-statistic. RESULTS: In all centres and irrespective of the assay method, meta-analysis confirmed significantly lower hsCRP levels in those with HNF1A-MODY than in those with other aetiologies (z score -21.8, p < 5 × 10(-105)). HNF1A-MODY cases with missense mutations had lower hsCRP levels than those with truncating mutations (0.03 vs 0.08 mg/l, p < 5 × 10(-5)). High-sensitivity CRP values between assays were strongly correlated (r (2) ≥ 0.91, p ≤ 1 × 10(-5)). Across the seven centres, the C-statistic for distinguishing HNF1A-MODY from young adult-onset type 2 diabetes ranged from 0.79 to 0.97, indicating high discriminative accuracy. CONCLUSIONS/INTERPRETATION: In the largest study to date, we have established that hsCRP is a clinically valid biomarker for HNF1A-MODY in European populations. Given the modest costs and wide availability, hsCRP could translate rapidly into clinical practice, considerably improving diagnosis rates in monogenic diabetes.


Assuntos
Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Técnicas de Diagnóstico Molecular , Adulto , Idade de Início , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Europa (Continente) , Glucoquinase/química , Glucoquinase/genética , Fator 1-alfa Nuclear de Hepatócito/química , Fator 4 Nuclear de Hepatócito/química , Fator 4 Nuclear de Hepatócito/genética , Heterozigoto , Humanos , Metanálise como Assunto , Pessoa de Meia-Idade , Mutação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
Vnitr Lek ; 56(10): 1043-9, 2010 Oct.
Artigo em Eslovaco | MEDLINE | ID: mdl-21105449

RESUMO

High prevalence of obesity in all of age categories is currently one of the biggest problem in medicine. Identification of etiology of obesity can individualise an approach to the patient and it is essential for choosing a target management and therapy. Beside the largest group with polygenic inheritance are clinically important also patients with "syndromic obesity", where obesity is only one of the signs and monogenic obesity, where obesity is the major clinical phenotype (patients with mutations in gene for leptin, leptine receptor, prohormone convertase 1, melanocortine receptor 4, brain-derived neurotropic factor and tyrosin kinase receptor B). The monogenic obesity includes 3-4% of all patients with obesity. This review article brings newest insight on genetics, clinical manifestation, diagnostics and therapy of these diseases.


Assuntos
Obesidade/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Humanos , Mutação , Pró-Opiomelanocortina/genética , Pró-Proteína Convertases/genética , Receptores para Leptina/genética
17.
Diabet Med ; 27(6): 631-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20546279

RESUMO

AIMS: Mutations in HNF4A cause a form of monogenic beta-cell diabetes. We aimed to identify mutations in the pancreas-specific P2 promoter of HNF4A in families with suspected HNF4A diabetes and to show that they impaired the function of the promoter in vitro. METHODS: We screened families with a clinical suspicion of HNF4A monogenic beta-cell diabetes for mutations in the HNF4A P2 promoter. We investigated the function of the previously reported HNF4A P2 promoter mutation -192C>G linked to late-onset diabetes in several families, along with two new segregating mutations, in vitro using a modified luciferase reporter assay system with enhanced sensitivity. RESULTS: We identified two novel HNF4A P2 promoter mutations that co-segregate with diabetes in two families, -136A>G and -169C>T. Both families displayed phenotypes typical of HNF4A monogenic beta-cell diabetes, including at least two affected generations, good response to sulphonylurea treatment and increased birthweight and/or neonatal hypoglycaemia. We show that both of these novel mutations and -192C>G impair the function of the promoter in transient transfection assays. CONCLUSIONS: Two novel mutations identified here and the previously identified late-onset diabetes mutation, -192C>G, impair the function of the HNF4A P2 promoter in vitro.


Assuntos
Diabetes Mellitus/genética , Fator 4 Nuclear de Hepatócito/genética , Regiões Promotoras Genéticas/genética , Idade de Início , Feminino , Humanos , Masculino , Mutação , Linhagem , Transfecção , População Branca/genética
18.
Anesth Analg ; 80(2): 368-72, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7818126

RESUMO

To evaluate the use of oxygen therapy in the immediate postoperative period, 293 postsurgical patients who had not had thoracic, upper abdominal, or neurologic surgery were randomly assigned upon admission to the postanesthesia care unit (PACU) to receive: 1) 4 L unhumidified O2 via nasal cannula, 2) 40% oxygen by face tent, 3) nurse-coached lung hyperinflations, or 4) no oxygen enhancing regimen. Oxygen saturation was measured on all patients at the time of arrival in the PACU, after 15 min, and after 30 min in the PACU. Only 11 patients in all groups (4%) had their O2 saturation decrease to less than 90% during this time. Ten of these had an initial O2 saturation of 92% or less. Significant differences in O2 saturation were found at 15 min and 30 min between Groups 1 and 2 which received O2 compared to Groups 3 and 4 which did not receive supplemental oxygen. The clinical significance of these differences is open to question. Complaints of dryness were most common in those receiving unhumidified oxygen by nasal cannula. Fourteen percent of patients receiving oxygen by face tent found it uncomfortable and complained of nausea. Supplemental oxygen is not essential in maintaining adequate oxygen saturation in these PACU patients when oxygen saturation levels are more than 92% upon admission to the PACU.


Assuntos
Oxigênio/sangue , Oxigênio/uso terapêutico , Cuidados Pós-Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
AACN Clin Issues Crit Care Nurs ; 2(4): 741-7, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1683246

RESUMO

Patient-controlled analgesia (PCA), a system by which patients self-administer intravenous doses of narcotics using specially programmed infusion pumps, has been used for pain management in acute care settings for nearly two decades. The safety and effectiveness of PCA has been documented in many acutely ill patient populations. Its introduction into critical care practice in the last five years has provided an important adjunct to traditional methods of pain management. However, intravenous narcotics of any type can provoke hemodynamic or respiratory complications in these compromised patients. Nursing expertise is a key factor in the successful implementation of PCA in critically ill patients.


Assuntos
Analgesia Controlada pelo Paciente , Cuidados Críticos , Analgesia Controlada pelo Paciente/enfermagem , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Contraindicações , Humanos , Fatores de Risco
20.
Crit Care Nurse ; 10(1): 43-7, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2357874

RESUMO

Surgery and the critical illness of a loved one can be a situational life crisis for family members. Establishing a meaningful nurse-family relationship is critical to the success of all other interventions. Close contact with families, and an awareness of the impact of the family on patient outcomes make nurses the ideal professionals to provide care to families during this crisis.


Assuntos
Família/psicologia , Unidades de Terapia Intensiva , Cuidados de Enfermagem , Procedimentos Cirúrgicos Operatórios/psicologia , Humanos , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Relações Profissional-Família
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA