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AIM: The aim of this study was to evaluate the consequences of chronic pouchitis after restorative proctocolectomy for ulcerative colitis. METHOD: Forty-two patients with chronic pouchitis underwent pouch endoscopy with biopsies after a median of 8.3 years of postoperative follow up. The pouchitis disease activity index (PDAI) was calculated. Morphological changes were recorded. Immunohistochemical analyses for cyclooxygenase 2 (COX-2), Ki-67 and p53 were performed, as was DNA flow cytometry. Endoscopy was also carried out in 10 patients without pouchitis and in nine healthy subjects. RESULTS: In patients with chronic pouchitis, the PDAI was 6 (standard error of the mean ± 4). Eighteen (43%) patients used continuous medication. The PDAI correlated positively with villous atrophy (P < 0.05). None of the pouch biopsies showed dysplasia. COX-2 immunostaining was detected in 35 (83.3%) patients with chronic pouchitis, in five (50%) without pouchitis, but in none of the normal controls. COX-2 expression correlated with mucosal atrophy (P < 0.01). In 15 (35.7%) of 42 patients with chronic pouchitis, Ki-67 immunostaining was increased, but no increase was observed in either control group (P < 0.002). No p53 immunopositivity was found, and DNA flow cytometry was normal in all pouches. One of the patients developed adenocarcinoma at the anal anastomosis. CONCLUSION: No dysplastic changes were detected during the first decade after surgery. Routine follow up of patients with chronic pouchitis with a hand-sewn anastomosis may not be necessary, although a small risk of cancer seems to remain at the anal anastomosis. The follow up should be focused on at-risk groups.
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Colitis Ulcerosa/cirugía , Neoplasias Colorrectales/epidemiología , Reservoritis/cirugía , Proctocolectomía Restauradora , Adulto , Anciano , Biopsia , Enfermedad Crónica , Ciclooxigenasa 2/análisis , Femenino , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estadísticas no Paramétricas , Proteína p53 Supresora de Tumor/análisis , Reino Unido/epidemiologíaRESUMEN
Various gastrointestinal infiltrations have been described in patients with chronic lymphocytic leukaemia (CLL). Here, we report a 69-year-old man with CLL and anaemia in whom the macroscopic finding of colonoscopy was normal, but the histological specimens revealed lymphocytic leukemia in ileum and in colon. If a CLL patient has any symptoms suggesting a possible GI manifestation of the haematologic disease or anaemia not explained by bone marrow infiltration or hemolysis, the diagnostic evaluation should include endoscopies with adequate biopsies.
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BACKGROUND: Faecal calprotectin and lactoferrin increasingly serve as surrogate markers of disease activity in IBD. Data on the correlation of these markers with simple endoscopic score for Crohn's disease (SES-CD) and with histological findings are as yet limited. Aim To study the correlation of faecal calprotectin and lactoferrin with SES-CD and histology. METHODS: During 87 consecutive ileocolonoscopies, SES-CD was calculated and biopsy specimens were obtained from the ileum, colon and rectum. Faecal calprotectin and lactoferrin were measured. RESULTS: In ileocolonic or colonic disease, both faecal calprotectin and lactoferrin correlated significantly with colon SES-CD (P < 0.001) and colon histology (P < 0.001). In patients with normal calprotectin or lactoferrin levels, endoscopic and histology scores were significantly lower than in those with elevated concentrations (P < 0.001). In ileal CD, ileal SES-CD correlated with histology (P < 0.001), but not with faecal calprotectin (P = 0.161) or lactoferrin (P = 0.448). CONCLUSION: In ileocolonic and colonic disease, endoscopic score SES-CD and histological findings correlated significantly with faecal calprotectin and lactoferrin. A normal faecal-marker concentration was a reliable surrogate marker for endoscopically and histologically inactive CD. Ileal endoscopic score and histological findings failed, however, to correlate with faecal markers.
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Enfermedad de Crohn/diagnóstico , Heces/química , Lactoferrina/análisis , Complejo de Antígeno L1 de Leucocito/análisis , Adulto , Anciano , Biomarcadores , Enfermedad de Crohn/patología , Endoscopía Gastrointestinal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Estadística como Asunto , Adulto JovenRESUMEN
BACKGROUND AND STUDY AIMS: Intestinal metaplasia, especially type III intestinal metaplasia is considered to be a precursor of gastric cancer and because of this it is suggested that these patients should be followed up by gastroscopy. Our aim was to find out the prevalence of intestinal metaplasia and its subtypes, the appearance of intestinal metaplasia in different parts of the stomach, and the correlation of intestinal metaplasia with other histological and endoscopic findings. PATIENTS AND METHODS: A total of 505 consecutive patients, with a mean age+/-S.D. of 54+/-16 years, had two biopsies taken from the antrum, two from the corpus, and, in 272 cases, two from the angulus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney system and the ones with incomplete intestinal metaplasia were further stained for sulphomucin visualisation to divide these into types II and III. RESULTS: The overall prevalence of intestinal metaplasia was 19%. The prevalence of type III intestinal metaplasia was 2.8%, type II intestinal metaplasia was 4.4%, and complete intestinal metaplasia was 11%. Intestinal metaplasia was found most frequently in the antrum and also in the angulus. There was no type III intestinal metaplasia in the corpus. Intestinal metaplasia was found more frequently in patients with atrophic gastritis than in other patients (p < 0.01). The patients with type III intestinal metaplasia were older than the patients without intestinal metaplasia (mean age of 73 versus 51 years). None of the patients with a totally normal appearing stomach in upper gastrointestinal endoscopy had type II or type III intestinal metaplasia. CONCLUSION: The relatively high overall prevalence of intestinal metaplasia was found in patients referred for gastroscopy in a region of low prevalence of Helicobacter pylori infection and low incidence of gastric cancer. Intestinal metaplasia was most often found in the antrum and angulus. Type III intestinal metaplasia was more prevalent in older patients and intestinal metaplasia was more frequently found in patients with atrophic gastritis. Normal appearing endoscopic finding seems to exclude type II and III intestinal metaplasia.
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Neoplasias Intestinales/epidemiología , Intestinos/patología , Neoplasias Gástricas/epidemiología , Estómago/patología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biopsia , Endoscopía Gastrointestinal , Femenino , Finlandia/epidemiología , Humanos , Neoplasias Intestinales/patología , Masculino , Metaplasia/epidemiología , Metaplasia/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND/AIM: To evaluate the safety of budesonide in primary biliary cirrhosis. METHODS: 77 primary biliary cirrhosis patients, with stages I-III at entry, were randomized to use either budesonide 6 mg and ursodeoxycholic acid 15 mg/kg (group A), or ursodeoxycholic acid alone (group B) daily for 3 years. In 22 patients, budesonide pharmacokinetics was determined after 3 years. Bone mass density was measured in 62 patients at baseline and 3 years; in 57 patients also liver biopsies were performed. RESULTS: At 3 years, no significant differences in the pharmacokinetics of budesonide were found between the patients with stages 0-I, II and III primary biliary cirrhosis. In group A, bone mass density in femoral neck and lumbar spine were decreased by 3.6% (P = 0.0002) and 2.8% (P = 0.003) from the baseline. In group B, the corresponding decreases were 1.9% (P = 0.029) and 0.7% (P = 0.25), but the differences between the groups were not statistically significant (P = 0.16 for femoral neck and P = 0.08 for lumbar spine). CONCLUSIONS: The plasma concentrations of budesonide do not significantly differ within stages I-III primary biliary cirrhosis patients. The combination of budesonide and ursodeoxycholic acid may decrease bone mass density in the femoral neck and lumbar spine in some primary biliary cirrhosis patients, and bone mass density is recommended to be monitored during budesonide therapy.
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Antiinflamatorios/efectos adversos , Densidad Ósea/efectos de los fármacos , Budesonida/efectos adversos , Cirrosis Hepática Biliar/tratamiento farmacológico , Antiinflamatorios/farmacocinética , Budesonida/farmacocinética , Femenino , Humanos , Masculino , Osteoporosis/prevención & control , Resultado del TratamientoRESUMEN
Mutations in genes encoding the two subunits of the beta-cell ATP-sensitive potassium channel (K(ATP)) channel (SUR1 and Kir6.2) are the major cause of congenital hyperinsulinism (CHI). In this study, the K(ATP) channel genes were screened in a population-based study that included all verified Finnish CHI patients (n = 43) in a 27-yr period. Seven different mutations were identified, which accounted for 60% of all cases. The functional consequences of the major missense mutations were studied in vivo by determining acute (1-3 min) plasma insulin and C-peptide responses to calcium (n = 18), glucose (n = 12), and tolbutamide (n = 11) in those CHI patients who were able to take part in these studies. C-peptide and insulin responses to calcium were significantly higher in the patients with SUR1-E1506K mutation, compared with patients without K(ATP) channel mutations. The patients with SUR1-V187D mutation showed a reduced response to tolbutamide but unexpectedly did not show any response to calcium stimulation. A compound heterozygous patient with Kir6.2-(-54)/K67N mutations responded to calcium but also to tolbutamide. In conclusion, our results show that a positive response in the calcium test is indicative of a K(ATP) channel mutation, but all mutations cannot be identified with this method. The insulin response to tolbutamide in patients with SUR1 mutations is impaired to different extents, depending on the genotype. The combination of calcium and tolbutamide tests is a useful tool for the detection of CHI patients with K(ATP) channel dysfunction. Our results, however, also demonstrate the complexity of these responses and the difficulties in their interpretation.
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Hiperinsulinismo/congénito , Hiperinsulinismo/diagnóstico , Insulina , Proteínas de la Membrana , Proteínas de Saccharomyces cerevisiae , Adolescente , Adulto , Péptido C/sangre , Calcio , Niño , Preescolar , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Prueba de Tolerancia a la Glucosa , Glicosiltransferasas , Humanos , Hiperinsulinismo/genética , Insulina/sangre , Islotes Pancreáticos/fisiopatología , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Canales de Potasio de Rectificación Interna/genética , Proteínas Represoras/genética , Análisis de Secuencia de ADN , TolbutamidaRESUMEN
We investigated the significance of the variants of the IRS-2 gene in patients with type 2 diabetes. The entire coding part of the IRS-2 gene was screened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IRS-2 gene with type 2 diabetes was studied in 85 Finnish diabetic patients and 82 Finnish control subjects and in 100 Chinese diabetic patients and 85 Chinese control subjects. The four variants predicting structural changes in the insulin receptor substrate (IRS)-2 protein included an insertion of AAC (Asn) in the Asn repeat sequence centered around codons 29-36 (allele frequencies of 0 vs. 0.6% and 1.5 vs. 0%), the Ala157Thr substitution (0 vs. 0% and 0.5 vs. 0%), the Leu647Val substitution (0.6 vs. 0% and 0 vs. 0%), and the Gly1057Asp polymorphism (31 vs. 31% and 35 vs. 30%) (P = NS for all comparisons). Furthermore, six silent variants were observed (CGC147CGG, CCC155CCG, GCC156GCT, AGT723AGC, TGT816TGC, and CCC829CCT). The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose tolerance (n = 295) or impaired glucose tolerance (n = 38). These data indicate that structural variants of the IRS-2 gene were uncommon in Finnish and Chinese patients with type 2 diabetes. Thus, the variants in the coding part of the IRS-2 gene are unlikely to have a major role in the development of type 2 diabetes in Finnish or Chinese subjects.
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Diabetes Mellitus Tipo 2/genética , Variación Genética , Fosfoproteínas/genética , Edad de Inicio , Sustitución de Aminoácidos , Pueblo Asiatico , Secuencia de Bases , Glucemia/metabolismo , China/etnología , Exones , Finlandia , Intolerancia a la Glucosa/genética , Prueba de Tolerancia a la Glucosa , Humanos , Proteínas Sustrato del Receptor de Insulina , Resistencia a la Insulina , Péptidos y Proteínas de Señalización Intracelular , Fosfoproteínas/química , Mutación Puntual , Polimorfismo Genético , Receptor de Insulina/fisiología , Valores de Referencia , Población BlancaRESUMEN
To study the induction of nitric oxide synthase (NOS) in different forms of pouchitis, we divided patients in five groups: 1) ulcerative colitis, no pouch; 2) no-pouchitis; 3) chronic asymptomatic pouchitis; 4) chronic active pouchitis; and 5) acute pouchitis. Ileal biopsies were scored for NOS-2 (inducible) and NOS-3 (endothelial) immunoreactivity and acute inflammation. In group 1, most specimens lacked NOS-2 immunoreactivity. In group 2, some specimens showed NOS-2 immunoreactive epithelium. In group 3, areas of NOS-2-immunoreactive epithelium were consistently observed in most specimens. In groups 4 and 5, most specimens showed moderate-to-extensive epithelial NOS-2 staining. NOS-2 immunoreactivity scores of groups 1-5 were 0.25 +/- 0.16, 0.67 +/- 0.19, 1.19 +/- 0.40, 2.0 +/- 0.23, and 2.18 +/- 0.12, respectively. Corresponding acute inflammation scores were 0, 0.53 + 0.17, 1.00 +/- 0.33, 1.80 +/- 0.20, and 1.64 +/- 0.15. NOS-2 score correlated with acute inflammation score (p < 0.0001), indicating that NOS-2 induction correlates with both the clinical degree of pouchitis and the severity of acute inflammation. NOS-3 immunoreactivity increased in all pouchitis groups.
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Colitis Ulcerosa/enzimología , Óxido Nítrico Sintasa/metabolismo , Reservoritis/enzimología , Humanos , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo IIIRESUMEN
The aim of this study was to develop an endorectal MRI strategy for prostatic cancer. We evaluated the MR images from 44 consecutive prostatic cancer patients treated by radical prostatectomy. Each sequence from every examination was assessed separately with a specific tumor map drawn. Tumor localization, capsular penetration, and seminal vesicle invasion were marked on maps on the basis of T2 and DESS (dual-echo steady-state) sequences. Thirty patients also had T1-weighted images, and these were assessed with regard to possible tumor outgrowth. The maps were compared with histopathological findings from radical prostatectomy specimens. According to our study, DESS equaled T2 in every respect. No statistically significant differences between the sequences were found with respect to detecting either tumor localization, outgrowth, or seminal vesicle invasion. DESS is a potential new sequence in prostatic MRI as it has been proven to parallel the routinely used T2-weighted imaging.
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Colonoscopía , Imagen Eco-Planar/métodos , Procesamiento de Imagen Asistido por Computador , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Anciano , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Variaciones Dependientes del Observador , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/cirugía , Recto , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: Although Helicobacter pylori is sensitive to complement lysis in vitro, chronic infection persists for years. We tested whether H. pylori acquires complement resistance by binding glycolipid-tailed inhibitors from the host. METHODS: Gastric biopsy specimens from H. pylori-infected patients (n = 10) and noninfected controls (n = 6) were analyzed for complement deposition and expression of the complement regulators protectin (CD59) and DAF. Protectin binding and complement sensitivity analyses were performed with the NCTC strain 11637 (CagA(+)) and 2 clinical isolates 9:0 (CagA(+)) and 67:20 (CagA(-)). RESULTS: In the noninfected mucosa, protectin was strongly expressed on the membranes of epithelial cells, but in the infected epithelia the expression was granular and more focused to the mucus. H. pylori bacteria in the gastric pits were often positive for protectin but negative for C5b-9. An opposite pattern was seen on the surface mucosa. In vitro analyses using (125)I-CD59 and bacteriolysis assays showed that protectin bound to H. pylori and protected CagA(+) strains against complement killing. In an enzyme-linked immunosorbent assay, the binding of CD59 correlated inversely with the appearance of the C5b-9 neoantigen. CONCLUSIONS: Binding of protectin inhibits membrane attack complex assembly on H. pylori and may thereby contribute to their survival on the gastric mucosa.
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Antígenos CD59/metabolismo , Proteínas del Sistema Complemento/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/metabolismo , Radioisótopos de Yodo , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Antígenos CD59/inmunología , Activación de Complemento/inmunología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Gastritis/inmunología , Gastritis/microbiología , Gastritis/patología , Glicosilfosfatidilinositoles/inmunología , Glicosilfosfatidilinositoles/metabolismo , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Humanos , Inmunidad Innata/inmunología , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Unión Proteica/inmunología , Estómago/inmunología , Estómago/microbiología , Estómago/patología , Virulencia/inmunologíaRESUMEN
We evaluated the effect of intrauterine device (IUD), patient age and hormone replacement therapy (HRT) on cytology outcome in Pap smears together with the important IQC procedures: 1) manual double-screening by cytotechnologists, and 2) retrospective senior pathologist review during 1996-1999. The results from primary double-screening (119 of 87,409 Pap smears) showed an excellent inter-observer correlation. The estimation of hormonal effects showed higher incidence of disagreements (p=0.013) in patients <47 yr. Some individual trends were found in the assessments of both cellular atypia (p=0.012) and Papanicolaou classification (p=0.018). The IUD had no influence on the accuracy when the degree of inflammatory reaction was evaluated (p>0.050), but showed an adverse effect on the estimation of cellular atypia (p=0.001). HRT distinctly equalized the entire sample material, since fewer disagreements were found in the age groups <47 yr and >47 yr when estimating the hormonal effects (p=0.013), inflammatory reaction (p=0.044) or cellular atypia (p=0.006) compared to those without HRT. The continuous cytopathologist supervision had a positive impact on the accuracy of hormonal effect estimation during the 4 years. The senior cytopathologists' reviews (354 of 87,409 Pap smears) showed mutually good interobserver correlation, and diagnostic conclusions of the same specimens differed only slightly between the cytopathologists. We found these state-of-the-art cytopathological IQC procedures to be effective and fit-for-purpose when evaluating hormonal effects, inflammatory reaction and cellular atypia.
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Prueba de Papanicolaou , Frotis Vaginal , Adulto , Factores de Edad , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Persona de Mediana Edad , Control de Calidad , Estándares de Referencia , Frotis Vaginal/normasRESUMEN
The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.
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Apolipoproteínas E/genética , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Edad de Inicio , Anciano , Alelos , Enfermedad Coronaria/etiología , Femenino , Finlandia/epidemiología , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the role of the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in the etiology of late-onset type 2 diabetes in Finnish and Chinese subjects. RESEARCH DESIGN AND METHODS: The whole coding regions of the genes encoding for HNF-1alpha and HNF-4alpha, including approximately 800 bp of the HNF-1alpha promoter, were investigated in 40 Finnish subjects (fasting C-peptide 50-570 pmol/l) and 47 Chinese subjects with type 2 diabetes by single-strand conformation polymorphism (SSCP) analysis. Frequencies of the variants of these genes were analyzed by restriction fragment-length polymorphism analysis in additional samples of 100 Finnish diabetic patients and 82 Finnish control subjects and in 58 Chinese diabetic patients and 51 Chinese control subjects. RESULTS: No previously reported gene defects were detected, but one novel functionally silent GCC-->GCG variant (nucleotide 73, exon 10) was observed in the HNF-4alpha gene in a Chinese diabetic patient. Interestingly, the Ala98Val substitution of the HNF-1alpha gene occurred at a significantly higher frequency in 140 Finnish diabetic patients compared with 82 control subjects (P = 0.014). The Ala98Val variant was not, however, associated with abnormalities in insulin secretion evaluated by oral and intravenous glucose tolerance tests in subjects with normal (n = 295) or impaired (n = 38) glucose tolerance. CONCLUSIONS: Variants in the HNF-1alpha and HNF-4alpha genes are unlikely to play a major role in the pathogenesis of late-onset type 2 diabetes in Finnish and Chinese subjects. However, the association of the Ala98Val variant of the HNF-1alpha gene with type 2 diabetes in Finnish subjects may indicate a diabetogenic locus close to the HNF-1alpha gene.
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Pueblo Asiatico/genética , Diabetes Mellitus Tipo 2/genética , Variación Genética , Proteínas Nucleares , Fosfoproteínas/genética , Factores de Transcripción/genética , Población Blanca/genética , Adulto , Edad de Inicio , Anciano , Alanina , Sustitución de Aminoácidos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Péptido C/sangre , China , Proteínas de Unión al ADN/genética , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Exones , Femenino , Finlandia , Prueba de Tolerancia a la Glucosa , Factor Nuclear 1 del Hepatocito , Factor Nuclear 1-alfa del Hepatocito , Factor Nuclear 1-beta del Hepatocito , Factor Nuclear 4 del Hepatocito , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ValinaRESUMEN
Phosphatidylinositol (PI) 3-kinase is a key signaling molecule in insulin-stimulated glucose transport. Therefore, we investigated the catalytic subunit p110beta, of human PI 3-kinase as a candidate gene for type 2 diabetes. Human p110beta gene was cloned from the placental genomic library. All 22 exons, intronic regions flanking the exons and 1.5 kb of the proximal/5' region of the p110beta gene, were screened for variants by single-strand conformation polymorphism analysis in 79 Finnish patients with type 2 diabetes . Allele frequencies of the variants were also determined in 77 nondiabetic control subjects. No variants were found in exons in diabetic patients. However, we identified two nucleotide polymorphisms in the proximal/5' region of the p110beta gene and a variation in the number of 2-bp repeat sequence (TA)n in intron 4. The allele frequencies did not differ between diabetic and control subjects. Our results may indicate that the catalytic subunit p110beta of PI 3-kinase plays such a fundamental role in the insulin-signaling pathway that structural variants are not likely to exist in that gene. The importance of the polymorphisms in the proximal/5' region of the p110beta gene for insulin signaling remains to be determined.
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Clonación Molecular , ADN/química , Diabetes Mellitus Tipo 2/enzimología , Variación Genética , Fosfatidilinositol 3-Quinasas/genética , Alelos , Catálisis , Exones , Frecuencia de los Genes , Biblioteca de Genes , Humanos , Intrones , Fosfatidilinositol 3-Quinasas/química , Fosfatidilinositol 3-Quinasas/metabolismo , Placenta/enzimología , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To investigate the possible association of the variants in the nucleotide binding fold regions of the sulfonylurea receptor 1 (SUR1) gene with gestational diabetes mellitus (GDM), type 2 diabetes, and altered insulin secretion in Finnish subjects. RESEARCH DESIGN AND METHODS: The nucleotide binding fold regions of the SUR1 gene were amplified with polymerase chain reaction and screened by the single-strand conformational polymorphism analysis in 42 subjects with GDM and 40 subjects with type 2 diabetes. Detected variants were further investigated in 377 normoglycemic subjects by restriction fragment-length polymorphism analysis. The effect of the variants of the SUR1 gene on first-phase insulin secretion was studied in 295 normoglycemic subjects. RESULTS: In subjects with GDM or type 2 diabetes, one amino acid change (S1369A), four silent substitutions (R1273R, L829L, T759T, and K649K), and three intron variants were identified in the nucleotide binding fold regions of the SUR1 gene. A tagGCC allele of exon 16 splice acceptor site was more frequent in subjects with GDM (0.55 allele frequency, n = 42) and type 2 diabetes (0.60, n = 40) than in normoglycemic subjects (0.43, n = 377) (P1 = 0.024 and P2 = 0.009, respectively). Similarly, an AGG allele of the R1273R polymorphism was more common in subjects with GDM (0.87) and type 2 diabetes (0.87) than in normoglycemic subjects (0.74) (P1 = 0.009 and P2 = 0.001, respectively). However, the S1369A, R1273R, and cagGCC-->tagGCC variants of the SUR1 gene were not associated with altered first-phase insulin secretion in 295 normoglycemic subjects. CONCLUSIONS: These results suggest that a functional variant that contributes to the risk of GDM and type 2 diabetes may locate close to the SUR1 gene.
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Transportadoras de Casetes de Unión a ATP , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Variación Genética , Insulina/metabolismo , Polimorfismo Conformacional Retorcido-Simple , Canales de Potasio de Rectificación Interna , Canales de Potasio/genética , Receptores de Droga/genética , Adulto , Anciano , Sustitución de Aminoácidos , Exones , Familia , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Secreción de Insulina , Intrones , Masculino , Mutación Puntual , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Embarazo , Receptores de SulfonilureasRESUMEN
BACKGROUND: Both Gleason score and prostate-specific antigen (PSA) concentration are prognostic factors for prostate cancer. We assessed our ability to localize cancer lesions based on Gleason scores and PSA values by endorectal coil magnetic resonance imaging (MRI). We also evaluated whether the size of the prostate affects tumor detectability. METHODS: We compared the findings of MRI and histopathological results of radical prostatectomy specimens from 63 patients; they were divided into four groups, based on Gleason score and also on serum PSA concentration. Furthermore, the possible effect of prostatectomy specimen weight on MRI interpretation was examined. RESULTS: A highly significant difference appeared in detection of cancer lesions based on their differentiation grade. No statistically significant difference existed between PSA groups in detection of tumors, but the large size of the prostate seemed to render image interpretation more difficult. CONCLUSIONS: Endorectal MRI detects poorly differentiated prostate cancer lesions more accurately than clinically insignificant tumors.
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Imagen por Resonancia Magnética , Neoplasias de la Próstata/diagnóstico , Anciano , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Dietary components may be both causal and protective in cases of pancreatic carcinoma, but the preventive potential of single constituents has not been evaluated. The authors report the effects of alpha-tocopherol and beta-carotene supplementations on the rates of incidence of and mortality from pancreatic carcinoma in a randomized, controlled trial. METHODS: The 29,133 participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study were male smokers who were ages 50-69 years at the time they were randomized into 1 of the following 4 intervention groups: dl-alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both AT and BC, and placebo. The daily supplementation lasted for 5-8 years. Incident cancers were identified through the national Finnish Cancer Registry and death certificates of the Statistics Finland. Results were analyzed by supplementation with Cox regression models. RESULTS: Effects of both supplementations were statistically nonsignificant. The rate of incidence of pancreatic carcinoma was 25% lower for the men who received beta-carotene supplements (n = 38) compared with the rate for those who did not receive beta-carotene (n = 51) (95% CI, -51% to 14%). Supplementation with alpha-tocopherol (n = 51) increased the rate of incidence by 34% (95% CI, -12% to 105%) compared with the rate for those who did not receive alpha-tocopherol. Mortality from pancreatic carcinoma during the follow-up, adjusted for stage and anatomic location of the tumor, was 19% (95% CI, -47% to 26%) lower among those who received beta-carotene and 11% (95% CI, -28% to 72%) higher among those who received alpha-tocopherol as compared with those who did not receive supplementation. CONCLUSIONS: Supplementation with beta-carotene or alpha-tocopherol does not have a statistically significant effect on the rate of incidence of pancreatic carcinoma or the rate of mortality caused by this disease.
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Antioxidantes/uso terapéutico , Carcinoma/prevención & control , Neoplasias Pancreáticas/prevención & control , Sistema de Registros , Vitamina E/uso terapéutico , beta Caroteno/uso terapéutico , Anciano , Antioxidantes/administración & dosificación , Carcinoma/mortalidad , Quimioprevención , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Fumar , Vitamina E/administración & dosificación , beta Caroteno/administración & dosificaciónRESUMEN
BACKGROUND: We have observed increased serum tumor markers, especially carbohydrate antigen 19-9 (CA 19-9) levels, in patients with acute liver failure (ALF) being evaluated for liver transplantation, raising the question of potential malignancy. In chronic liver disease increased serum alpha-fetoprotein (AFP) may be a sign of liver regeneration, but little is known of these markers in ALF. The aim of this study was to evaluate the causes of overexpression of tumor markers in patients with non-malignant ALF. METHODS: The serum AFP, carcinoembryonic antigen (CEA), and CA 19-9 levels were compared with the liver function tests in 33 patients with acute liver failure and in 78 patients with chronic non-malignant liver disease being evaluated for liver transplantation. Immunohistochemical stainings of the tumor markers were performed on explanted liver specimens. RESULTS: The AFP (1-218 U/ml) and CA 19-9 (10-6520 U/ml) levels were significantly higher in the patients with ALF than in the patients with chronic liver disease (P < 0.01). The AFP and CA 19-9 values also correlated with the total serum bilirubin level. In the patients with ALF the immunohistochemical staining for CA 19-9 was highly positive in periportal transformed ductular hepatocytes and correlated positively with the serum CA 19-9 values (P < 0.001). The stainings for AFP or CEA showed no or only slight positivity in the patients with increased serum values of the tumor markers. CONCLUSIONS: In patients with ALF increased serum levels of CA 19-9 reflect the amount of transformed ductular hepatocytes without any evidence of malignancy. Increased CA 19-9 values should not be the cause of delay when an ALF patient needs an urgent liver transplantation.
Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Fallo Hepático Agudo/sangre , alfa-Fetoproteínas/análisis , Femenino , Humanos , Inmunohistoquímica , Hígado/química , Hígado/patología , Fallo Hepático Agudo/diagnóstico , Pruebas de Función Hepática , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/diagnóstico , Trasplante de Hígado , Masculino , Persona de Mediana EdadRESUMEN
Three cases of intrahepatic biliary cystadenoma with mesenchymal stroma and one case of biliary cystadenocarcinoma are presented. Their immunohistochemical features and the surgical treatment are discussed together with a brief review of the literature. The benign cystadenomas stained positive for cytokeratin and CA 19-9 in the epithelium of the cyst wall. Mesenchymal stromal cells were strongly positive for a-SMA and moderately positive for desmin. The epithelium of the cystadenocarcinoma, however, was positive only for cytokeratin and the stroma only for a-SMA. Our findings indicate that biliary cystadenomas seem to be of primitive hepatobiliary origin. Furthermore, the malignant variant cystadenocarcinoma may loose its immunoreactivity for CA 19-9 and desmin.
Asunto(s)
Adenoma de los Conductos Biliares , Neoplasias de los Conductos Biliares , Conductos Biliares Intrahepáticos , Colangiocarcinoma , Cistadenocarcinoma , Cistoadenoma , Adenoma de los Conductos Biliares/química , Adenoma de los Conductos Biliares/patología , Adenoma de los Conductos Biliares/cirugía , Adulto , Neoplasias de los Conductos Biliares/química , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/química , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Cistadenocarcinoma/química , Cistadenocarcinoma/patología , Cistadenocarcinoma/cirugía , Cistoadenoma/química , Cistoadenoma/patología , Cistoadenoma/cirugía , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana EdadRESUMEN
PURPOSE: We assess the accuracy of endorectal coil magnetic resonance imaging (MRI) for detecting tumor localization, capsular penetration and seminal vesicle invasion in clinically organ confined prostate cancer. We also evaluate intra-observer and interobserver agreement in interpreting MRI studies. MATERIALS AND METHODS: MRI studies of 51 consecutive patients a mean of 61 years old with biopsy proved prostate cancer were retrospectively read twice by 2 radiologists in random order. Both radiologists marked tumor localization, capsular penetration and seminal vesicle invasion on standard tumor maps. These findings were compared with the histopathological results of radical prostatectomy specimens. RESULTS: The overall accuracy of detecting cancer localization was 61%. The detection rate for cancer foci less than 5 mm. was only 5% but for lesions greater than 10 mm. it was 89%. There was 91 and 80% accuracy for detecting capsular penetration and seminal vesicle invasion, respectively. Sensitivity and specificity were 60 and 63, 13 and 97, and 59 and 84% for localization, capsular penetration and seminal vesicle invasion, respectively. Intra-observer and interobserver agreement ranged from fair to good (kappa coefficient 0.240 to 0.647). CONCLUSIONS: Endorectal MRI seems to be better than previously reported for detecting seminal vesicle invasion and tumor foci in the anterior half of the prostate. Sensitivity in detecting minor capsular penetration of the tumor was low, which can probably be improved by methodological development. MRI may be useful for locating cancer foci in patients with high prostate specific antigen values but repeatedly negative biopsy findings.