RESUMO
AIM: To identify gene mutations in PRSS1 and SPINK1 in individuals with early onset idiopathic chronic or recurrent acute pancreatitis. METHODS: The cationic trypsinogen gene (PRSS1; exons 2 and 3) and the serine protease inhibitor Kazal 1 gene (SPINK1; exon 3) were selectively amplified and sequenced from blood samples of 19 patients admitted to the Pancreas Clinic at our institution with chronic pancreatitis and/or idiopathic recurrent acute pancreatitis that were diagnosed or with onset before age 35. Fifty healthy volunteers served as controls. Whole blood samples were collected and gene specific sequences were amplified by polymerase chain reaction (PCR). All PCR products were subsequently sequenced in order to identify the presence of any mutations. RESULTS: Nineteen patients with pancreatitis (14 males; median age 24 years, range 15-48 years) were included in this study, of which five showed the presence of gene mutations. Direct sequencing results indicated the presence of two previously unidentified mutations in exon 2 of PRSS1 (V39E and N42S) in two patients with recurrent acute pancreatitis. Two cases had the N34S SPINK1 mutation. Analysis of the relatives of one patient homozygous for this mutation showed that five of the six family members carried the N34S SPINK1 mutation. Of these members, three were healthy heterozygous carriers and two were homozygotes (one sibling had diabetes, the other was healthy). Another patient was heterozygous for a novel SPINK1 mutation located on exon 3 (V46D). All members from this patient's family had normal genotypes, indicating that it was a de novo mutation. No mutations in either gene were present in the control subjects. CONCLUSION: Two novel PRSS1 mutations and one novel SPINK1 mutation were identified in Mexican patients with early onset idiopathic recurrent acute pancreatitis.
Assuntos
Proteínas de Transporte/genética , Mutação , Pancreatite Crônica/genética , Pancreatite/genética , Tripsina/genética , Doença Aguda , Adolescente , Adulto , Idade de Início , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/enzimologia , Pancreatite/epidemiologia , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/enzimologia , Pancreatite Crônica/epidemiologia , Fenótipo , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Inibidor da Tripsina Pancreática de Kazal , Adulto JovemRESUMO
Hereditary pancreatitis is an autosomal dominant disorder with 80% penetrance and variable expressivity. The vast majority of cases have been linked to mutations within the cationic trypsinogen gene, also referred to as serine protease 1 (PRSS1). Other than inheritance, PRSS1 pancreatitis has been considered clinically and pathologically indistinguishable from other etiologies of chronic pancreatitis. However, to date, the histologic findings of PRSS1 pancreatitis have not been well described. We, therefore, collected pancreatic specimens from 10 PRSS1 patients of various ages and examined their clinicopathologic features. Patients at the time of resection ranged in age from 9 to 66 years (median, 29 y), with a slight female predominance (60%). All patients reported a history of intermittent abdominal pain, with an age of onset ranging from infancy to 21 years of age. Examination of the gross and microscopic findings suggested a sequential pattern of changes with increasing patient age. In pediatric patients (n=4), although in most cases the pancreas was grossly normal, there was microscopic variation in lobular size and shape. Although the central portions of the pancreas displayed parenchymal loss accompanied by loose perilobular and interlobular fibrosis, the periphery was remarkable for replacement by mature adipose tissue. These changes were more developed in younger adults (n=2), in whom fatty replacement seemed to extend from the periphery to the central portions of the pancreas. With older patients (n=4), the pancreas showed marked atrophy and extensive replacement by mature adipose tissue with scattered islets of Langerhans and rare acinar epithelium concentrated near the main pancreatic duct. In summary, PRSS1 hereditary pancreatitis is characterized by progressive lipomatous atrophy of the pancreas.
Assuntos
Mutação , Pâncreas/patologia , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Tripsina/genética , Adolescente , Adulto , Idoso , Atrofia , Criança , Progressão da Doença , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Lipomatose/enzimologia , Lipomatose/genética , Lipomatose/patologia , Masculino , Pessoa de Meia-Idade , Pâncreas/enzimologia , Pâncreas/cirurgia , Pancreatectomia , Pancreatite Crônica/complicações , Pancreatite Crônica/enzimologia , Pancreatite Crônica/cirurgia , Fenótipo , Resultado do TratamentoRESUMO
BACKGROUND: Alcoholic or biliary acute pancreatitis may need different therapeutic approaches. AIM: Assessing the validity of lipase/amylase ratio in differentiating biliary from alcoholic acute pancreatitis/acutized chronic pancreatitis. METHODS: Nine male patients (mean age and standard deviation: 39.8 +/- 7.0 years) with alcoholic acute pancreatitis/acutized chronic pancreatitis (group I) and 29 patients, 8 male and 21 female (mean age: 43.6 +/-19.9 years), with biliary acute pancreatitis (group II) were evaluated. Serum lipase and amylase levels were measured in patients with symptoms for no more than 48 hours. The lipase/amylase ratio was calculated based on serum lipase and amylase levels and expressed as multiples of their respective superior reference values. RESULTS: Mean levels of serum lipase (4,814 +/- 3,670 U/L) and amylase (1,282 +/- 777 U/L) in patients of group I were comparable to group II (2,697 +/- 2,391 and 1,878 +/- 1,319 U/L, respectively), but the mean lipase/amylase ratio was significantly higher in group I (4.4 +/- 3.6) than in group II (2.2 +/- 2.2). Lipase/amylase ratio >3 occurred at significantly higher proportions in patients of group I (66.7%) than of group II (24.1%), differentiating the two groups with sensitivity of 67% and specificity of 76%. CONCLUSIONS: 1) Amylase and lipase serum levels did not differ in the two groups evaluated; 2) the lipase/amylase ratio >3 was more often seen in alcoholic acute pancreatitis/acutized chronic pancreatitis than biliary acute pancreatitis, and it may be useful in differentiating these two causes of pancreatitis.
Assuntos
Amilases/sangue , Doenças Biliares/complicações , Lipase/sangue , Pancreatite/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Enzimáticos Clínicos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Pancreatite Alcoólica/diagnóstico , Pancreatite Alcoólica/enzimologia , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/enzimologia , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
RACIONAL: Pancreatites agudas de causas alcoólica ou biliar podem necessitar de abordagens terapêuticas diferentes. OBJETIVO: Verificar a validade da relação lipase/amilase em diferenciar as causas alcoólica ou biliar na pancreatite aguda/pancreatite crônica agudizada. MÉTODOS: Foram avaliados nove pacientes com pancreatite aguda/pancreatite crônica agudizada alcoólica, todos homens, com idade média (desvio padrão) de 39,8 ± 7,0 anos (grupo I) e 29 com pancreatite aguda biliar, sendo 8 homens e 21 mulheres, com idade média de 43,6 ± 19,9 anos (grupo II). As amilasemias e lipasemias foram determinadas em pacientes com sintomatologia há, no máximo, 48 horas. A relação lipase/amilase foi calculada utilizando-se valores de amilasemia e lipasemia expressas como múltiplos de seus respectivos valores superiores de referência. RESULTADOS: As médias das lipasemias (4.814 ± 3.670 U/L) e amilasemias (1.282 ± 777 U/L) no grupo I foram semelhantes às do grupo II (2.697 ± 2.391 e 1.878 ± 1.319 U/L, respectivamente), mas a média das relações lipase/amilase foi significantemente maior no grupo I (4,4 ± 3,6) do que no grupo II (2,2 ± 2,2). Relação lipase/amilase >3 foi significantemente mais freqüente no grupo I (66,7 por cento) do que no grupo II (24,1 por cento) e diferenciou os dois grupos com sensibilidade de 67 por cento e especificidade de 76 por cento. CONCLUSÕES: 1) as amilasemias e lipasemias não diferenciaram os dois grupos avaliados; 2) relação lipase/amilase >3 é mais freqüente na pancreatite aguda/pancreatite crônica agudizada alcoólica do que na pancreatite aguda biliar, e pode ser útil na diferenciação destas duas causas de pancreatite.
BACKGROUND: Alcoholic or biliary acute pancreatitis may need different therapeutic approaches. AIM: Assessing the validity of lipase/amylase ratio in differentiating biliary from alcoholic acute pancreatitis/acutized chronic pancreatitis. METHODS: Nine male patients (mean age and standard deviation: 39.8 ± 7.0 years) with alcoholic acute pancreatitis/acutized chronic pancreatitis (group I) and 29 patients, 8 male and 21 female (mean age: 43.6 ± 19.9 years), with biliary acute pancreatitis (group II) were evaluated. Serum lipase and amylase levels were measured in patients with symptoms for no more than 48 hours. The lipase/amylase ratio was calculated based on serum lipase and amylase levels and expressed as multiples of their respective superior reference values. RESULTS: Mean levels of serum lipase (4,814 ± 3,670 U/L) and amylase (1,282 ± 777 U/L) in patients of group I were comparable to group II (2,697 ± 2,391 and 1,878 ± 1,319 U/L, respectively), but the mean lipase/amylase ratio was significantly higher in group I (4.4 ± 3.6) than in group II (2.2 ± 2.2). Lipase/amylase ratio >3 occurred at significantly higher proportions in patients of group I (66.7 percent) than of group II (24.1 percent), differentiating the two groups with sensitivity of 67 percent and specificity of 76 percent. CONCLUSIONS: 1) Amylase and lipase serum levels did not differ in the two groups evaluated; 2) the lipase/amylase ratio >3 was more often seen in alcoholic acute pancreatitis/acutized chronic pancreatitis than biliary acute pancreatitis, and it may be useful in differentiating these two causes of pancreatitis.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amilases/sangue , Doenças Biliares/complicações , Lipase/sangue , Pancreatite/diagnóstico , Doença Aguda , Ensaios Enzimáticos Clínicos , Diagnóstico Diferencial , Valor Preditivo dos Testes , Pancreatite Alcoólica/diagnóstico , Pancreatite Alcoólica/enzimologia , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/enzimologia , Pancreatite/etiologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: One of the complications of diabetes mellitus is the development of pancreatic exocrine insufficiency. AIM: To study pancreatic exocrine function in diabetics patients. MATERIAL AND METHODS: Seventy two diabetic patients were included in the protocol, but two were withdrawn because an abdominal CAT scan showed a chronic calcified pancreatitis, previously undiagnosed. Fecal elastase was measured by ELISA and the presence of fat in feces was assessed using the steatocrit. RESULTS: Mean age was 60+/-12 years and 67 (96%) patients had a type 2 diabetes. Fecal elastase was normal (elastase >200 microg/g) in 47 (67%) patients, mildly decreased (100-200 microg/g) in 10 (14%) and severely decreased in 13 (19%). There was a significant association between elastase levels and time of evolution of diabetes (p=0.049) and between lower elastase levels and the presence of a positive steatocrit (p=0.042). No significant association was found between elastase levels and other chronic complications of diabetes such as retinopathy, nephropathy, neuropathy, microangiopathy or with insulin requirement. CONCLUSIONS: One third of this group of diabetic patients had decreased levels of fecal elastase, that was associated with the time of evolution of diabetes. Patients with lower levels of elastase have significantly more steatorrhea. Among diabetics it is possible to find a group of patients with non diagnosed chronic pancreatitis.
Assuntos
Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Insuficiência Pancreática Exócrina/enzimologia , Fezes/enzimologia , Elastase Pancreática/análise , Idoso , Biomarcadores/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Insuficiência Pancreática Exócrina/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Pancreática , Pancreatite Crônica/enzimologia , Pancreatite Crônica/fisiopatologia , Fatores de TempoRESUMO
Background: One of the complications of diabetes mellitus is the development of pancreatic exocrine insufficiency. Aim: To study pancreatic exocrine function in diabetics patients. Material and methods: Seventy two diabetic patients were included in the protocol, but two were withdrawn because an abdominal CAT scan showed a chronic calcified pancreatitis, previously undiagnosed. Fecal elastase was measured by ELISA and the presence of fat in feces was assessed using the steatocrit. Results: Mean age was 60±12 years and 67 (96%) patients had a type 2 diabetes. Fecal elastase was normal (elastase >200 µg/g) in 47 (67%) patients, mildly decreased (100-200 µg/g) in 10 (14%) and severely decreased in 13 (19%). There was a significant association between elastase levels and time of evolution of diabetes (p=0.049) and between lower elastase levels and the presence of a positive steatocrit (p=0.042). No significant association was found between elastase levels and other chronic complications of diabetes such as retinopathy, nephropathy, neuropathy, microangiopathy or with insulin requirement. Conclusions: One third of this group of diabetic patients had decreased levels of fecal elastase, that was associated with the time of evolution of diabetes. Patients with lower levels of elastase have significantly more steatorrhea. Among diabetics it is possible to find a group of patients with non diagnosed chronic pancreatitis.