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1.
Exp Clin Endocrinol Diabetes ; 119(8): 484-9, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21811961

RESUMEN

BACKGROUND: Although insulin resistance in obesity is established, the link between excess body fat and skeletal muscle insulin resistance is obscure. The aim of this study was to investigate whether cytokines secreted from the subcutaneous adipose tissue are related to the sensitivity of glucose metabolism to insulin in skeletal muscle. METHODS: A meal was given to 14 obese and 10 non-obese women. Plasma samples were taken for 360 min from a forearm vein and from the radial artery for glucose and insulin measurements. Interleukin-6, leptin, TNFα, resistin and adiponectin were measured preprandially from the radial artery and from the superficial epigastric vein. Forearm blood flow was measured with plethysmography. RESULTS: (1) In obese vs non-obese: (a) Glucose uptake by skeletal muscle was decreased (AUC (0-360)369 ± 55 vs. 877 ± 146 µmol/100 g tissue, p=0.001) (b) arterial interleukin-6 (2.5 ± 0.5 vs. 1 ± 0.1 pg/ml, p=0.013) and subcutaneous venous interleukin-6 (5 ± 0.5 vs. 3.4 ± 0.5 pg/ml, p=0.027) were increased (c) arterial leptin (63 ± 7 vs. 5 ± 0.6 ng/ml, p<0.0001) and subcutaneous venous leptin 80 ± 8 vs. 6.5 ± 0.7 ng/ml, p<0.0001) were increased. (2) Arterial interleukin-6 (p=0.002) and subcutaneous venous interleukin-6 (p=0.014) were negatively associated with forearm glucose uptake in obese. (3) No association was found between leptin and forearm glucose uptake, after correcting with fat mass. CONCLUSIONS: In morbid obesity: (1) Subcutaneous adipose tissue releases interleukin-6 which could then mediate insulin resistance in skeletal muscle. (2) Although there is increased secretion of leptin by the subcutaneous adipose tissue, leptin levels are not correlated to the sensitivity of glucose metabolism to insulin in muscle.


Asunto(s)
Resistencia a la Insulina , Interleucina-6/metabolismo , Leptina/metabolismo , Músculo Esquelético/metabolismo , Obesidad Mórbida/metabolismo , Grasa Subcutánea/metabolismo , Adiponectina/sangre , Adulto , Glucemia/análisis , Índice de Masa Corporal , Femenino , Antebrazo/irrigación sanguínea , Glucosa/metabolismo , Humanos , Insulina/sangre , Cinética , Obesidad Mórbida/sangre , Periodo Posprandial , Flujo Sanguíneo Regional , Resistina/sangre , Factor de Necrosis Tumoral alfa/sangre
2.
Horm Metab Res ; 43(8): 537-44, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21626471

RESUMEN

Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.


Asunto(s)
Adiponectina/farmacología , Enfermedad de la Arteria Coronaria/patología , Interleucina-10/biosíntesis , Interleucina-6/biosíntesis , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Depuradores de Clase A/genética , Receptores Depuradores de Clase A/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
3.
J Intern Med ; 268(6): 555-66, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20964741

RESUMEN

Adrenal incidentalomas (AIs) represent adrenal masses that are incidentally discovered whilst investigating symptoms and signs unrelated to adrenal pathology. The onset and natural course of AIs are unknown, and the possible underlying cardiometabolic abnormalities have not been examined in depth. A growing body of clinical and experimental evidence supports the notion that both functioning and, paradoxically, nonfunctioning AIs are associated with a partially expressed or even full-blown metabolic syndrome (MS) phenotype, through yet unclear mechanisms. Subtle, subclinical or even profound adrenal hormone excess and an increased proinflammatory state might explain to some extent the development of MS disturbances. The emerging association between AIs and MS appears to be important in determining the optimal clinical management of these patients and raises speculation about the exact mechanisms of this interesting cause-effect relationship.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Síndrome Metabólico/complicaciones , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Síndrome de Cushing/complicaciones , Humanos , Hidrocortisona/metabolismo , Hallazgos Incidentales
4.
Horm Metab Res ; 39(10): 758-63, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17952840

RESUMEN

Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-alpha and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-alpha levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Interleucina-6/genética , Leucocitos Mononucleares/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Interleucina-6/sangre , Interleucina-6/metabolismo , Leucocitos Mononucleares/patología , Persona de Mediana Edad , Nicotinamida Fosforribosiltransferasa/sangre , Nicotinamida Fosforribosiltransferasa/metabolismo , Sobrepeso/sangre , Sobrepeso/complicaciones , Sobrepeso/genética , Sobrepeso/metabolismo , ARN Mensajero/metabolismo , Delgadez/sangre , Delgadez/genética , Delgadez/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
5.
Aliment Pharmacol Ther ; 21(12): 1435-43, 2005 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-15948810

RESUMEN

AIM: To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to beta-blockers for prevention of first bleeding in portal hypertension. METHODS: A sample size of 214 was planned with all sizes of varices. However, the trial was stopped due to increased bleeding in 52 patients in the ligation group. The baseline severity liver disease and endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 +/- 9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 +/- 10.27). RESULTS: The mean follow-up period was 19.5 +/- 13.3 months: five bled in the ligation group (20%), three from varices (two after banding at 11 and 17 days; one during the procedure), and two from gastropathy; two bled in the not-treated group (7%- two both varices) (P = 0.24). There were seven deaths in the ligation group and 11 in the not-treated group (P = 0.39). CONCLUSION: Sixty per cent of the bleeding in the banding group was probably iatrogenic, requiring the study to be stopped. Endoscopic banding ligation was no better than no treatment. This study suggests that ligation may be harmful when used as primary prophylaxis, similar to prophylactic sclerotherapy in the past.


Asunto(s)
Antagonistas Adrenérgicos beta , Endoscopía Gastrointestinal/métodos , Várices Esofágicas y Gástricas/prevención & control , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Causas de Muerte , Contraindicaciones , Várices Esofágicas y Gástricas/cirugía , Femenino , Humanos , Hipertensión Portal/complicaciones , Ligadura/métodos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento
6.
Ann Oncol ; 16(2): 294-9, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15668287

RESUMEN

BACKGROUND: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks. RESULTS: A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm. CONCLUSIONS: The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Taxoides/administración & dosificación , Taxoides/uso terapéutico , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/patología , Docetaxel , Femenino , Humanos , Irinotecán , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Análisis de Supervivencia , Taxoides/efectos adversos , Resultado del Tratamiento
7.
J Clin Immunol ; 24(6): 591-9, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15622443

RESUMEN

Abundant evidence suggests that cytokines involve in the pathogenesis of latent autoimmune diabetes of adults (LADA). This is a slowly progressive form of type 1 diabetes, which is initially diagnosed as type 2 diabetes. In this study, healthy individuals LADA and type 2 diabetic patients were genotyped for IL-6-174G/C, TNF-alpha-308A/G, TGF-beta1-codon10T/C, TGF-beta1-codon25G/C, IL-10-1082A/G, IL-10-819T/C, IL-10-592A/C gene polymorphisms, by sequence-specific-primer polymerase chain reaction methodology. A significant difference in the frequencies of -1082A/G IL-10 alleles was observed, with the -1082*A allele (known to be associated with low IL-10 production), predominating in LADA diabetics than type 2 diabetics (p=0.036). No significant differences of genotypes, phenotypes, or haplotype frequencies in the remaining cytokine polymorphisms were observed. Analysis of allele combinations revealed a significant involvement of the low and high in vitro production IL-10 alleles in the development of LADA and type 2 diabetes, respectively. These results suggest that the G/A mutation at position -1082 of IL-10 promoter gene region might be one of the factors participating to the pathogenesis of LADA diabetes and that identification of cytokine gene polymorphisms might contribute to the characterization of the different types of diabetes mellitus.


Asunto(s)
Citocinas/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético , Adulto , Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/inmunología , Genotipo , Haplotipos , Humanos , Interleucina-10/genética , Interleucina-6/genética , Fenotipo , Reacción en Cadena de la Polimerasa , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta1 , Factor de Necrosis Tumoral alfa/genética
8.
Anticancer Res ; 24(5A): 2967-74, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15517903

RESUMEN

BACKGROUND: Bladder cancer is a heterogeneous genetic disease and, to date, no specific cytogenetic abnormality has been established. The detection of recurrent genetic changes with common breakpoints is of special interest, facilitating the identification of genes implicated in carcinogenesis. The aim of this study was to investigate recurrent structural chromosomal aberrations with common breakpoints and to correlate them with the histological stage of tumors. MATERIALS AND METHODS: Fifteen patients with transitional cell carcinoma of the bladder were cytogenetically studied by direct culture of primary tumor cells and G-banding technique. RESULTS: Most of the cases studied exhibited very complex karyotypes. Recurrent structural aberrations were observed involving, according to frequency, chromosomal regions 11p15, 3p12, 14q32, 19q13 and 6q23. Isochromosomes i(8q), i(17q) and i(6p) were also observed. CONCLUSION: Conventional cytogenetics continues to be valuable in cancer study, detecting common chromosomal breakpoints. Of interest was the detection of novel recurrent structural chromosomal aberrations including involvement of 11p15, 14q32 and 19q13, while a correlation of recurrent abnormalities observed with tumor stage was also evaluated.


Asunto(s)
Carcinoma de Células Transicionales/genética , Aberraciones Cromosómicas , Neoplasias de la Vejiga Urinaria/genética , Carcinoma de Células Transicionales/patología , Bandeo Cromosómico , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/patología
9.
Horm Metab Res ; 36(8): 559-63, 2004 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15326566

RESUMEN

AIM: To study the effect of two different isoenergetic meals, one rich in carbohydrates and one rich in fat, on plasma active ghrelin levels in lean or obese subjects. METHODS: Eight obese and eight lean women, strictly matched for age, were fed two isoenergetic meals of different composition, one rich in fat and one rich in carbohydrates (CHO), on separate days. Plasma active ghrelin levels were measured just before and at 1, 2 and 3 hours after meal consumption. RESULTS: Overall, plasma active ghrelin levels were significantly lower in the obese compared to the lean women (71.7 +/- 29.7 vs. 222.2 +/- 127.2 pmol/liter respectively, p < 0.0001). Furthermore, ghrelin levels decreased significantly by 30 % from baseline values in the lean subjects in the first hour after the CHO-rich meal (mean difference +/- SD): -66.2 +/- 49.0 pmol/liter (p = 0.03), returning to near-baseline levels by 2 hours, while no significant change was observed in the obese subjects. After the fat-rich meal, active ghrelin levels did not change significantly in either group (p > 0.05). CONCLUSIONS: A fat-rich meal does not suppress plasma active ghrelin levels in either lean or obese women. Moreover, in obese, unlike lean women, a high carbohydrate meal also fails to suppress plasma ghrelin levels, which are already quite low. This suggests that ghrelin-induced satiety mechanisms may be compromised in these subjects.


Asunto(s)
Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Obesidad/sangre , Hormonas Peptídicas/sangre , Delgadez/sangre , Adulto , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Metabolismo Energético , Femenino , Ghrelina , Humanos , Persona de Mediana Edad , Obesidad/metabolismo , Concentración Osmolar , Delgadez/metabolismo
10.
Anticancer Res ; 24(6): 4141-6, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15736465

RESUMEN

BACKGROUND: Multiple myeloma (MM) is charecterized by great clinical heterogeneity. Among known prognostic factors the cytogenetic abnormalities are thought to be of major importance. The aim of this study was to correlate certain chromosomal abnormalities with immunoglobulin isotype and survival in MM patients. PATIENTS AND METHODS: Forty-nine Greek MM patients, homogeneously treated with conventional-dose chemotherapy, were cytogenetically studied by direct culture of bone marrow cells and G-banding technique. RESULTS: Twenty-four patients had a normal karyotype while the remaining 25 patients presented numerical and structural abnormalities. Recurrent structural abnormalities were observed. Translocations involving the 14q32 region were observed in 8 cases, while 6 cases exhibited a del(1)(p12). We confirmed the negative impact of chromosomal abnormalities on the overall survival of MM patients and we also showed that t(11;14) had a worse impact on disease outcome as compared to t(14q32) with an unidentified partner chromosome. The presence of del(1) (p12) significantly worsened the prognosis in MM patients. No correlations existed between the association of immunoglobulin isotype with survival or certain chromosomal changes. CONCLUSION: Further studies are indicated at the molecular level to clarify the exact role and the prognostic value of 1p12 involvement in MM patients.


Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 1/genética , Isotipos de Inmunoglobulinas/genética , Mieloma Múltiple/genética , Mieloma Múltiple/inmunología , Anciano , Anciano de 80 o más Años , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 14/genética , Femenino , Eliminación de Gen , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Pronóstico , Translocación Genética
11.
Clin Endocrinol (Oxf) ; 58(1): 72-7, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12519415

RESUMEN

OBJECTIVE: Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of > 70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS: Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72). CONCLUSIONS: In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.


Asunto(s)
Neoplasias de la Corteza Suprarrenal/fisiopatología , Hiperfunción de las Glándulas Suprarrenales/fisiopatología , Densidad Ósea , Neoplasias de la Corteza Suprarrenal/complicaciones , Hiperfunción de las Glándulas Suprarrenales/complicaciones , Anciano , Antropometría , Femenino , Cuello Femoral/fisiopatología , Humanos , Hallazgos Incidentales , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Posmenopausia
12.
J Clin Endocrinol Metab ; 87(4): 1646-53, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11932296

RESUMEN

The role of desmopressin, alone or in combination with CRH, in the differential diagnosis between Cushing's disease (CD) and ectopic ACTH secretion (EAS) still remains uncertain. Based on existing data, the desmopressin test is regarded as an alternative to the CRH stimulation test and, when given in combination with CRH, it has been suggested to completely discriminate between patients with CD and EAS. However, assessment of these tests has been limited in only a small number of patients with EAS. Desmopressin is a relatively specific V2 vasopressin receptor (V2R) agonist. Although expression of V3 vasopressin receptor (V3R) is common in tumors with EAS, the expression of V2R has not been extensively investigated. In the present study, we report our findings of the desmopressin and the combined CRH-desmopressin test in a series of patients with CD and EAS; also, the expression of V2R and V3R was investigated in tumors with EAS by a RT-PCR method. We assessed a cohort of 31 patients with ACTH-dependent Cushing's syndrome, including 26 patients with CD and five cases with histologically confirmed EAS. To avoid bias of predetermined criteria, univariate curves of the receiver operating characteristics (ROC) were constructed by plotting the sensitivity against 1-specificity at each level of the percent cortisol (F) and ACTH responses to these tests. Following desmopressin administration there was an overlap of the percent F and ACTH responses among patients with CD and EAS, and the area under the ROC curve for both these responses was not significantly different than that occurring by chance. This was also true for the percent F response following the combined CRH-desmopressin test. However, the area under the ROC curve for the percent ACTH rise following the combined test was significantly different; the point of the ROC curve closest to 1 corresponded to a percent ACTH rise of 218% (88% sensitivity and 80% specificity). Expression of V2R and V3R mRNA was investigated in four of the five excised tumors with EAS and revealed the presence of the V2R in all, whereas the V3R mRNA was expressed in three of these cases. In conclusion, in this series the desmopressin test produced a significant overlap of responses between CD and patients with EAS and, therefore, is of limited value in the differential diagnosis of the ACTH-dependent Cushing's syndrome. This is most probably due to the expression of the V2R in tumors with EAS. Moreover, following the combined CRH-desmopressin test only the ACTH but not the F responses were diagnostically useful, but still far from completely discriminating patients with CD and EAS.


Asunto(s)
Síndrome de ACTH Ectópico/diagnóstico , Hormona Adrenocorticotrópica/fisiología , Hormona Liberadora de Corticotropina , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Desamino Arginina Vasopresina , Síndrome de ACTH Ectópico/metabolismo , Adulto , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/metabolismo , ARN Mensajero/metabolismo , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Vasopresinas/genética , Receptores de Vasopresinas/metabolismo
13.
Aliment Pharmacol Ther ; 16(3): 569-75, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11876712

RESUMEN

BACKGROUND: There are no guidelines on second-line therapies for Helicobacter pylori eradication failures of omeprazole-clarithromycin-amoxicillin triple therapy. AIM: To compare the efficacy of two second-line therapies for persistent H. pylori infection. METHODS: Over a 6-year period, patients with persistent H. pylori infection following omeprazole-clarithromycin-amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology. RESULTS: Of the 95 randomized patients, 88 (93%) completed the study. Age, sex, smoking, ulcer/non-ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention-to-treat analysis, eradication was achieved in 41 of the 49 patients (84%; 95% confidence interval, 70.4-92.7%) and 27 of the 46 patients (59%; 95% confidence interval, 43.3-73.0%) of the tetracycline- and clarithromycin-containing groups, respectively (P=0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P=0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P=0.036). CONCLUSIONS: Tetracycline-containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole-amoxicillin-clarithromycin regimen.


Asunto(s)
Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/fisiología , Tetraciclina/uso terapéutico , Adolescente , Adulto , Anciano , Antiácidos/efectos adversos , Antiácidos/uso terapéutico , Antibacterianos/efectos adversos , Bismuto/efectos adversos , Bismuto/uso terapéutico , Claritromicina/efectos adversos , Interacciones Farmacológicas , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Dispepsia/complicaciones , Dispepsia/microbiología , Femenino , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Metronidazol/efectos adversos , Metronidazol/uso terapéutico , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Análisis Multivariante , Omeprazol/efectos adversos , Omeprazol/uso terapéutico , Tetraciclina/efectos adversos , Insuficiencia del Tratamiento
14.
Dig Dis Sci ; 46(7): 1567-72, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11478511

RESUMEN

There is evidence that Helicobacter pylori eradication might predispose to gastroesophageal reflux disease (GERD). The aim of this prospective study was to examine the effectiveness of antisecretory treatment, after successful H. pylori eradication, in preventing GERD, since no data exist so far. Eighty initially H. pylori(+) patients, without GERD at the time of H. pylori eradication [50 peptic ulcer (PU) and 30 nonulcer (NU), 55 men, 25 women, median age 38 years, range 19-57], after successful H. pylori eradication were randomized to recieve either omeprazole 20 mg daily (group A) or no treatment (group B) for one year. All patients underwent upper gastrointestinal endoscopy at 0, 6, and 12 months or when GERD symptoms occurred. There were 40 patients in each group, and there were no statistically significant differences between the two groups in terms of sex, age, body weight, ulcer/no ulcer ratio, and other demographic data. Seven patients from group A and five patients from group B were lost to follow-up, and therefore there were 33 and 35 patients in groups A and B, respectively, who completed the study. One of 33 patients in group A (3%) and 10/35 (28.5%) in group B developed GERD symptoms during follow-up (P = 0.0022). The respective values for esophagitis were 0/33 (0%) and 6/35 (17.1%) (P = 0.0083). In conclusion, antisecretory treatment in H. pylori(+) patients, after successful eradication, is effective in preventing GERD.


Asunto(s)
Antiulcerosos/uso terapéutico , Ácido Gástrico/metabolismo , Reflujo Gastroesofágico/prevención & control , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Omeprazol/uso terapéutico , Adulto , Endoscopía Gastrointestinal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
15.
Int J Obes Relat Metab Disord ; 25(7): 1018-26, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11443501

RESUMEN

BACKGROUND: Tumor necrosis factor alpha (TNFalpha), a cytokine produced at inflammatory sites and in adipose tissue, is known primarily for its detrimental effects on insulin action. There is evidence to suggest that TNFalpha may also influence beta-cell function. Leptin is another adipose tissue-derived hormone that might also act on beta-cells. OBJECTIVE: We explored the independent and combined effects of TNFalpha and leptin upon basal and glucose-stimulated insulin transcription and secretion in the HIT-T15 pancreatic beta cell line. METHODS: Cells were cultured for 40 h in the presence of near-normal basal (7 mM) or high (16.7 mM) glucose and treated with either TNFalpha (1, 10 and 50 ng/ml) or leptin (10, 50 and 100 ng/ml) or both together. Insulin concentrations were measured by radioimmunoassay. Insulin mRNA levels were evaluated by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method, after normalization with beta-actin mRNA. RESULTS: TNFalpha significantly suppressed basal and glucose-stimulated insulin secretion and proinsulin mRNA transcription in a dose-dependent manner, an effect that was more powerful in the presence of high glucose. Leptin also inhibited dose-dependent insulin mRNA and protein at both glucose concentrations, but did not appear to further potentiate the suppressive effects of TNFalpha. CONCLUSION: TNFalpha suppresses both basal and glucose-stimulated insulin transcription and secretion in HIT-T15 cells, an effect that is enhanced significantly by high glucose. Leptin also independently inhibits basal and glucose-stimulated insulin secretion and transcription but does not modify TNFalpha effects. These effects might contribute to the abnormalities of glucose metabolism that characterize conditions of increased TNFalpha and/or leptin production.


Asunto(s)
Insulina/genética , Insulina/metabolismo , Leptina/farmacología , ARN Mensajero/análisis , Factor de Necrosis Tumoral alfa/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Glucosa , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Radioinmunoensayo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transcripción Genética
16.
Am J Med ; 110(9): 703-7, 2001 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-11403754

RESUMEN

BACKGROUND: Strains of Helicobacter pylori with the cytotoxine-associated gene A (cagA) are linked to severe forms of gastroduodenal disease. Although eradication of H. pylori may predispose to the development of reflux esophagitis, the effects of CagA status on risk of esophagitis after successful H. pylori treatment are not known. METHODS: We studied 50 consecutive patients without esophagitis in whom H. pylori was eradicated successfully. CagA status was determined by immunoblotting sera from patients against H. pylori antigens. Patients underwent upper gastrointestinal endoscopy before eradication and 6, 12, 18, and 24 months after eradication or when reflux symptoms occurred. Biopsy specimens of the antrum and corpus were evaluated for gastritis before H. pylori eradication and at the end of the study. The sum of the scores for acute and chronic inflammation (both measured on a 0 [absent] to 3 [severe] scale) comprised the total gastritis severity score. RESULTS: In a multivariate proportional hazards regression analysis, positive CagA serology (hazard ratio [HR] = 10, 95% confidence interval [CI]: 1.3 to 81) and moderate-to-severe corpus gastritis (total severity score > or =4) before eradication (HR = 2.3, 95% CI: 1.2 to 6.1) were independent risk factors for the development of esophagitis after H. pylori eradication. CONCLUSION: Patients infected with strains of H. pylori that are cagA-positive are at increased risk of developing esophagitis after eradication of H. pylori.


Asunto(s)
Proteínas Bacterianas/inmunología , Esofagitis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Adulto , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/patología , Helicobacter pylori/inmunología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
17.
Eur J Haematol ; 64(3): 145-50, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10997879

RESUMEN

Splenectomy in patients with non-Hodgkin's lymphoma (NHL) is performed for either diagnostic or therapeutic reasons. We report on a series of 29 patients with NHL and splenomegaly who underwent splenectomy during the years 1979-1998 in our hospital. According to the indication for splenectomy our patients were categorized in three groups. Group A: In 20 patients splenectomy was performed for diagnostic reasons. Group B: Three patients were splenectomized for autoimmune haemolytic anaemia (AIHA). Group C: Six patients underwent splenectomy because of hypersplenism. A definitive histopathological diagnosis of NHL was obtained in all patients of group A. Hypersplenism and AIHA were resolved in all patients after splenectomy. One (3.5%) patient died postoperatively because of septicemia complicated by disseminated intravascular coagulation. Six postoperative complications were observed in 4 (14%) patients. Splenectomy, with an acceptable surgical risk, has the potential to establish the diagnosis of NHL in patients with splenomegaly without lymphadenopathy and negative bone marrow findings. Moreover, splenectomy has the capacity to modify the disease course in patients with NHL complicated by AIHA or hypersplenism.


Asunto(s)
Linfoma no Hodgkin/cirugía , Esplenectomía , Adulto , Anciano , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/cirugía , Biopsia , Médula Ósea/patología , Femenino , Humanos , Hiperesplenismo/cirugía , Hígado/patología , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Bazo/patología
18.
Eur J Gastroenterol Hepatol ; 12(7): 727-31, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10929897

RESUMEN

OBJECTIVES: Rapid, reliable in-office tests are needed for applying the adopted screen-and-treat strategy in Helicobacter pylori-positive young dyspeptic patients. DESIGN: We have evaluated the performance characteristics of a whole-blood antibody (WBA) test for the detection of H. pylori infection under in-office conditions. METHODS: In a prospective double-blind study, 183 untreated patients referred to a tertiary centre for endoscopy because of dyspepsia were studied. Patients were defined as H. pylori-positive if two out of three tests (histology, rapid urease test, Gram staining of biopsy smears) were positive, and H. pylori-negative if all three tests were negative. An in-office test detecting IgG antibodies to H. pylori (FlexPack HP, Abbott Diagnostics) was used with capillary blood and compared with an ELISA detecting IgG (quantitative) and IgA (qualitative) H. pylori serum antibodies. RESULTS: Of the 183 patients, 139 were defined as H. pylori-positive. The in-office test had 79% sensitivity, 95% specificity, 98% positive and 59% negative predictive value. The respective values for IgG serum antibodies were 94, 70, 91 and 79% and those for IgA antibodies were 86, 82, 94 and 64%. About 50% of the false-negative in-office tests had a serum IgG antibody titre > 100 units. Co-evaluation of our data with published reports suggested that both the median sensitivity and negative predictive value of the kit are significantly inferior when performed with whole-blood (five studies) compared with serum (nine studies) (82 versus 92% and 82 versus 93% respectively, P < 0.035). CONCLUSIONS: Improvement of the performance characteristics of FlexPack HP in-office test is needed. However, the test may be a useful tool for identifying H. pylori-positive patients in younger age groups who could be managed without upper gastrointestinal endoscopy.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Adolescente , Adulto , Anciano , Biopsia con Aguja , Método Doble Ciego , Dispepsia/etiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Probabilidad , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Estadísticas no Paramétricas
19.
Gastrointest Endosc ; 51(6): 652-8, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10840295

RESUMEN

BACKGROUND: Analysis of primary prevention studies of the use of beta-blockers has shown clear reductions in variceal bleeding in cirrhotic patients with varices. In contrast, the usefulness of prophylactic endoscopic sclerotherapy, alone or in combination with propranolol, in the management of these patients is still under investigation. The present study compared the efficacy of combined sclerotherapy and propranolol versus propranolol alone in the primary prevention of hemorrhage in cirrhotic patients with varices and high (greater than 18 mm Hg) intraesophageal variceal pressure. METHODS: Patients were randomly assigned to propranolol (42 patients) or to propranolol plus sclerotherapy (44 patients). The mean duration of follow-up was 26.8 +/- 7.7 and 24.6 +/- 9.8 months, respectively. RESULTS: During this period 23% of the patients in the combination group experienced at least 1 episode of bleeding due to varices or congestive gastropathy as compared with 14% in the propranolol group (not significant). Twenty-three patients (52%) in the combination group developed complications as compared with 8 (19%) in the propranolol group (p = 0.002). The mortality rate was similar in both groups (14% and 18%, respectively). The only independent factor predictive of survival was the level of serum albumin. CONCLUSIONS: Endoscopic sclerotherapy should not be used for the primary prevention of hemorrhage in cirrhotic patients at high risk of variceal bleeding who are undergoing treatment with propranolol.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Várices Esofágicas y Gástricas/complicaciones , Esofagoscopía , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Propranolol/uso terapéutico , Escleroterapia/métodos , Femenino , Estudios de Seguimiento , Hemorragia Gastrointestinal/mortalidad , Humanos , Masculino , Manometría , Persona de Mediana Edad , Cooperación del Paciente , Estudios Prospectivos , Tasa de Supervivencia
20.
Dig Dis Sci ; 45(1): 63-7, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10695615

RESUMEN

Factors affecting Helicobacter pylori eradication rate with omeprazole (OME), clarithromycin (CL), and amoxicillin (AMO) have not been extensively studied. We have investigated the effect of age, sex, smoking, ulcer disease, compliance with therapy, H. pylori colonization density, degree and activity of antral gastritis, the coexistence of corpus gastritis, and the presence of lymphoid follicles on H. pylori eradication rate. We studied 80 consecutive H. pylori-positive patients, with duodenal ulcer (N = 35) or nonulcer dyspepsia (N = 45) treated with OME 20 mg, CL 500 mg, and AMO 1 g, each given twice daily for 10 days. H. pylori was eradicated in 71/80 (88.8%, 95% CI 82-96%) patients. The regimen failed to eradicate the only strain (1.8%, 95% CI 0-5.2%) that was clarithromycin resistant. Multivariate discriminant analysis showed that two histological variables (Wilks lambda = 0.74, chi2 = 23.41, df = 2, P< 0.001), absence of lymphoid follicles in routine gastric biopsies (F = 13.63, P<0.001) and coexistence of antral and body gastritis (F = 13.68, P<0.001), significantly increased H. pylori eradication rate. No other factor examined predicted H. pylori eradication with this regimen. Our data suggest that body gastritis is a positive and presence of lymphoid follicles in routine gastric biopsies is a negative predictive factor of treatment outcome with the omeprazole, clarithromycin, and amoxicillin regime.


Asunto(s)
Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Claritromicina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Omeprazol/uso terapéutico , Penicilinas/uso terapéutico , Quimioterapia Combinada , Femenino , Gastritis/microbiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento
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