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OBJECTIVES: We compared pancreatogenic (DM3c) and type 2 diabetes mellitus. METHODS: We compared age-, sex-, and diabetes mellitus duration-matched DM3c cases (n = 142) and type 2 diabetes mellitus (n = 142). Pancreatogenic diabetes was considered when it appeared after the diagnosis of pancreatitis or after pancreatic surgery. RESULTS: Pancreatogenic diabetes presented lower body mass index (BMI) [odds ratio (OR), 1.2; 95% confidence interval (CI), 1.13-1.28; P < 0.001], worse glycemic control (OR, 1.196; 95% CI, 1.058-1.35; P = 0.004), required insulin more frequently (OR, 4.21; 95% CI, 2.57-6.93; P = 0.0001), had more hypoglycemic episodes (OR, 3.65; 95% CI, 1.64-8.16; P = 0.001) but lower frequency of dyslipidemia (OR, 0.42; 95% CI, 0.26-0.68; P = 0.001) and arterial hypertension (OR, 0.52; 95% CI, 0.32-0.86; P = 0.01). Pancreatogenic diabetes cases on pancreatic enzyme replacement therapy had lower glycosylated hemoglobin (8.52% vs 9.44%; P = 0.026), serum carotenes (79.1 vs 116.1; P = 0.03), and BMI (23.4 vs 26.1; P = 0.0005) than those not on pancreatic enzyme replacement therapy. Pancreatogenic diabetes onset occurred earlier in necrotizing pancreatitis and after pancreatic surgery. CONCLUSIONS: Pancreatogenic diabetes presents with low BMI and lacks metabolic syndrome components. The type of pancreatic disease or surgery defines its onset time.
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Diabetes Mellitus Tipo 2/diagnóstico , Síndrome Metabólica/fisiopatologia , Adulto , Idoso , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Pâncreas/metabolismoRESUMO
PURPOSE: The aim of this study was to evaluate the prevalence of thyroid dysfunction in a cohort of healthy individuals in Mexico City, as well as to investigate the potential associations of these results with their estimated iodine intake (EII) as reflected by their 24-hour urinary iodine excretion (24-h UIE). METHODS: From the SALMEX cohort, 683 adults provided an appropriate 24-h urine sample. Thyroid function tests and thyroid antibody concentrations were determined in the participants' sera. We analyzed discrepancies between the commonly used urinary parameters to determine the iodine intake status and the performance of thyroglobulin (Tg) as a biomarker of its status in the adult population. RESULTS: The prevalence of dysthyroidism was high, being similar to other studies. Subclinical hypothyroidism was detected in 5.0% of individuals, clinical hypothyroidism in 1.8% of individuals, and sub-clinical hyperthyroidism in 2.8% of individuals. The median EII was 285 µg/d (IQR 215.0-369.0); 94% of individuals had EII >150 µg/d recommended daily allowance (RDA) in adults. The urinary iodine concentration (UIC) and the UIE had relative biases in their averages of 34.4%. The Tg median was 7.21 ng/mL. The prevalence of increased Tg was 6.15%. There was no correlation between Tg and EII (r= 0.019, p= 0.606). CONCLUSIONS: Thyroid dysfunction was highly prevalent in this population. Our cohort revealed a slight discrepancy between dysthyroidism manifestations and iodine intake markers; the latter represent a population with adequate iodine intake. Further studies are necessary to clearly define the prevalence of thyroid dysfunction as well as the iodine nutritional status in Mexico.
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Iodo , Estado Nutricional , Adulto , Estudos Transversais , Humanos , México/epidemiologia , Prevalência , Glândula TireoideRESUMO
BACKGROUND: The 2017 KDIGO guidelines establish a 2B grade recommendation in favor of testing Bone Mineral Density (BMD) by DXA to assess osteoporotic fracture (OPF) risk in patients with CKD G3a-G5D. Still, controversy remains because large studies evaluating it for this particular population are lacking. AIM: To establish the clinical performance of BMD measured by DXA in the evaluation of fracture risk in women with CKD. METHODS: We conducted a 43 year retrospective cohort study with 218 women ≥18â¯years-old with CKD and BMD measurement by DXA of total hip and lumbar spine. Clinical (age, year of CKD onset, comorbidities, BMI, transplant status, treatment), and biochemical (PTH, corrected calcium, phosphate, vitamin D [25 (OH) D3], creatinine, and albumin), parameters were collected from hospital records. All osteoporotic fractures (as defined by the WHO) found in the clinical and radiologic files were registered. RESULTS: 218 women with a median age of 60â¯years (40-73 IQ range) and a CKD evolution time of 12â¯years (7-18 IQ range) were evaluated. Forty-eight (28.23%) presented an OPF. These women were older (57 vs 69â¯years, pâ¯=0.0072) and had a lower BMD. CKD stage did not influence fracture incidence. In the multivariate analysis we found that for each standard deviation decrease in hip and lumbar spine T-Score, the overall fracture risk was 2.7 and 2.04 times higher, respectively. More than 50% of fractures took place within the first ten years of follow-up, especially with GFR <30â¯mL/min/m2 and osteoporosis. Diabetes and hypothyroidism accelerated fracture onset, while renal transplant delayed it. In the ROC analysis, the AUC was largest with the total hip (0.7098, pâ¯= 0.000) and lumbar spine (0.6916, pâ¯= 0.000). CONCLUSIONS: BMD measured by DXA is a useful fracture prediction tool for women with CKD, having a sensibility and specificity similar to that in the general population. It seems to be appropriate for the diagnosis, treatment decisions, and follow-up of patients with renal failure.
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BACKGROUND: Various studies suggest that perioperative concentrations of high-sensitivity troponins are incremental and predictive factors of a major adverse cardiac event (MACE) and all-cause mortality. OBJECTIVE: The objective of the study was to evaluate the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in the development of MACE and all-cause mortality, within 30-days and 1-year follow-up after noncardiac surgery. METHODS: In this prospective cohort study, we included men ≥ 45 years and women ≥ 55 years with ≥ 2 cardiovascular risk factors and undergoing intermediate or high-risk noncardiac surgery. Demographic and clinical information was collected from clinical charts. We measured baseline hs-cTnI 24 h before surgery, and its post-operative concentration 24 h after surgery. RESULTS: In the entire sample, 8 patients (8.6%) developed MACE at 30-days follow-up (4 deaths), 12 (12.9%) within the 1st year (7 deaths), and 17 (18.2%) after complete post-surgical follow-up (10 deaths). We observed higher baseline and post-operative concentrations in patients who presented MACE (12 pg/ml vs. 3.5 pg/ml; p = 0.001 and 18.3 pg/ml vs. 5.45 pg/ml; p = 0.009, respectively). The hazard ratios (HRs) calculated by Cox regression analysis between the hs-cTnI baseline concentration and the post-operative development of MACE at 30-days and 1-year were 5.70 (95% confidence interval [CI], 1.10-29.40) with hs-cTnI > 6.2 pg/ml and 12.86 (95% CI, 1.42-116.34) with hs-cTnI > 3.3 pg/ml, respectively. The estimated post-operative HR death risk at 1-year was 14.43 (95% CI, 1.37-151.61) with hs-cTnI > 4.5 pg/ml. CONCLUSIONS: Pre-operative hs-cTnI was an independent predictive risk factor for MACE at 30-days and 1-year after noncardiac surgery and for all-cause mortality at 1-year after noncardiac surgery.
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BACKGROUND: Various studies suggest that perioperative concentrations of high-sensitivity troponins are incremental and predictive factors of a major adverse cardiac event (MACE) and all-cause mortality. OBJECTIVE: The objective of the study was to evaluate the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in the development of MACE and all-cause mortality, within 30-days and 1-year follow-up after noncardiac surgery. METHODS: In this prospective cohort study, we included men ≥ 45 years and women ≥ 55 years with ≥ 2 cardiovascular risk factors and undergoing intermediate or high-risk noncardiac surgery. Demographic and clinical information was collected from clinical charts. We measured baseline hs-cTnI 24 h before surgery, and its post-operative concentration 24 h after surgery. RESULTS: In the entire sample, 8 patients (8.6%) developed MACE at 30-days follow-up (4 deaths), 12 (12.9%) within the 1st year (7 deaths), and 17 (18.2%) after complete post-surgical follow-up (10 deaths). We observed higher baseline and post-operative concentrations in patients who presented MACE (12 pg/ml vs. 3.5 pg/ml; p = 0.001 and 18.3 pg/ml vs. 5.45 pg/ml; p = 0.009, respectively). The hazard ratios (HRs) calculated by Cox regression analysis between the hs-cTnI baseline concentration and the post-operative development of MACE at 30-days and 1-year were 5.70 (95% confidence interval [CI], 1.10-29.40) with hs-cTnI > 6.2 pg/ml and 12.86 (95% CI, 1.42-116.34) with hs-cTnI > 3.3 pg/ml, respectively. The estimated post-operative HR death risk at 1-year was 14.43 (95% CI, 1.37-151.61) with hs-cTnI > 4.5 pg/ml. CONCLUSIONS: Pre-operative hs-cTnI was an independent predictive risk factor for MACE at 30-days and 1-year after noncardiac surgery and for all-cause mortality at 1-year after noncardiac surgery.
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Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios , Troponina I/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de TempoRESUMO
ABSTRACT Background: Various studies suggest that perioperative concentrations of high-sensitivity troponins are incremental and predictive factors of a major adverse cardiac event (MACE) and all-cause mortality. Objective: The objective of the study was to evaluate the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in the development of MACE and all-cause mortality, within 30-days and 1-year follow-up after noncardiac surgery. Methods: In this prospective cohort study, we included men ≥ 45 years and women ≥ 55 years with ≥ 2 cardiovascular risk factors and undergoing intermediate or high-risk noncardiac surgery. Demographic and clinical information was collected from clinical charts. We measured baseline hs-cTnI 24 h before surgery, and its post-operative concentration 24 h after surgery. Results: In the entire sample, 8 patients (8.6%) developed MACE at 30-days follow-up (4 deaths), 12 (12.9%) within the 1st year (7 deaths), and 17 (18.2%) after complete post-surgical follow-up (10 deaths). We observed higher baseline and post-operative concentrations in patients who presented MACE (12 pg/ml vs. 3.5 pg/ml; p = 0.001 and 18.3 pg/ml vs. 5.45 pg/ml; p = 0.009, respectively). The hazard ratios (HRs) calculated by Cox regression analysis between the hs-cTnI baseline concentration and the post-operative development of MACE at 30-days and 1-year were 5.70 (95% confidence interval [CI], 1.10-29.40) with hs-cTnI > 6.2 pg/ml and 12.86 (95% CI, 1.42-116.34) with hs-cTnI > 3.3 pg/ml, respectively. The estimated post-operative HR death risk at 1-year was 14.43 (95% CI, 1.37-151.61) with hs-cTnI > 4.5 pg/ml. Conclusions: Pre-operative hs-cTnI was an independent predictive risk factor for MACE at 30-days and 1-year after noncardiac surgery and for all-cause mortality at 1-year after noncardiac surgery.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Troponina I/sangue , Período Pós-Operatório , Fatores de Tempo , Biomarcadores/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Longitudinais , Sensibilidade e Especificidade , Período Pré-OperatórioRESUMO
INTRODUCTION: Introduction: whether hypovitaminosis D is an overarching cause of increased mortality or a prognostic marker of poor health has not been well elucidated. Objectives: we sought to determine the association of serum 25-hydroxyvitamin D [25-(OH)-D3] levels with the clinical biochemical parameters and mortality risk in chronic diseases. Methods: we reviewed the clinical charts and collected the clinical biochemical parameters of patients diagnosed with chronic conditions who had at least one 25-(OH)-D3 determination, with or without calcium and vitamin D supplementation, and who were selected using a cluster random sampling design (n = 1,705). The analysis was focused on metabolic disorders (type-2 diabetes mellitus [T2DM] and obesity), autoimmune disorders, and mortality. Multivariate logistic regression analyses were performed. Results: low 25-(OH)-D3 levels were reported in 1,433 (84.0%) patients, of which 774 (45.4%) had insufficiency (20-29 ng/mL) and 659 (38.6%) patients had deficiency (< 20 ng/mL). Lower 25-(OH)-D3 levels in T2DM patients were associated with higher glycosylated hemoglobin levels (p < 0.001). Patients with 25-(OH)-D3 levels < 12.5 ng/mL had a higher mortality risk than those with levels ≥ 12.5 ng/mL (HR: 3.339; 95% CI: 1.342-8.308). We observed lower 25-(OH)-D3 levels in patients with grade-III obesity (p = 0.01). We found a higher risk of 25-(OH)-D3 deficiency in rheumatoid arthritis, type-1 diabetes, and systemic lupus erythematosus (p = 0.032, p = 0.002, p = 0.049, respectively). Conclusions: we found a significant relationship between 25-(OH)-D3 levels and glycemic control, body mass index, autoimmune disease, and mortality risk. Nevertheless, whether hypovitaminosis D plays a causal role or is a consequence of chronic disease remains controversial.
INTRODUCCIÓN: Introducción: si la hipovitaminosis D constituye una causa general de mayor mortalidad o un marcador de mal pronóstico para la salud no se ha dilucidado por completo. Objetivos: determinar la asociación de los niveles séricos de 25-hidroxivitamina D [25-(OH)-D3] con los parámetros clínico-bioquímicos y el riesgo de mortalidad en la enfermedad crónica. Métodos: se revisaron los expedientes clínicos y recopilamos los parámetros clínico-bioquímicos de pacientes diagnosticados de enfermedades crónicas que tenían al menos una determinación de 25-(OH)-D3, con o sin suplemento de calcio y vitamina D, y que se seleccionaron mediante muestreo aleatorio por grupos (n = 1705). El análisis se centró en los trastornos metabólicos (diabetes mellitus de tipo 2 [DM2] y obesidad), los trastornos autoinmunes y la mortalidad. Se realizaron análisis multivariados de regresión logística. Resultados: se encontraron niveles bajos de 25-(OH)-D3 en 1433 (84,0%) pacientes, de los cuales 774 (45,4%) tenían insuficiencia (20-29 ng/mL) y 659 (38,6%) tenían deficiencia (< 20 ng/mL) de esta vitamina. Los niveles más bajos de 25-(OH)-D3 en los pacientes con DM2 se asociaron a niveles más altos de hemoglobina glucosilada (p < 0,001). Los pacientes con niveles de 25-(OH)-D3 < 12,5 ng/mL tenían mayor riesgo de mortalidad que aquellos con niveles ≥ 12,5 ng/mL (HR: 3,339; IC del 95%: 1,342-8,308). Apreciamos niveles más bajos de 25-(OH)-D3 en los pacientes con obesidad de grado III (p = 0,01). Se encontró un mayor riesgo de deficiencia de 25-(OH)-D3 en la artritis reumatoide, la diabetes de tipo 1 y el lupus eritematoso sistémico (p = 0,032, p = 0,002, p = 0,049, respectivamente). Conclusiones: apreciamos una relación significativa entre los niveles de 25-(OH)-D3 y el control glucémico, el índice de masa corporal, la enfermedad autoinmune y el riesgo de mortalidad. Sin embargo, sigue siendo controvertido si la hipovitaminosis D desempeña un papel causal o constituye una consecuencia de las enfermedades crónicas.
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Doença Crônica/mortalidade , Vitamina D/análogos & derivados , Adulto , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Masculino , Doenças Metabólicas , Obesidade , Vitamina D/biossíntese , Vitamina D/sangueAssuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobinas Glicadas/metabolismo , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
BACKGROUND: Urine osmolarity (OsmU) is the gold standard for the evaluation of the kidney's urine concentration capacity; nevertheless, urinary density (UD) is often used as a surrogate for its estimation. OBJECTIVE: The objective of this study was to analyze the accuracy of UD in estimating OsmU. MATERIALS AND METHODS: A transversal study including patients with simultaneous determination of UD measured with refractometry and OsmU measured by osmometer (OsmUm). We multiplied the last two digits of the UD by 35, 30, 32, 33.5, and 40 to estimate OsmU; the estimates were considered precise if the value was ± 30 mOsm/kg from the OsmUm. A Bland-Altman analysis was conducted. RESULTS: Among 205 patients, there was no difference between OsmUm and the estimated form when using a factor of 33.5 (p = 0.578). When analyzing by the absence or presence of proteinuria and/or glycosuria, there were no differences when using the factors 35 (p = 0.844) and 32 with adjusted UD (p = 0.898). In the linear correlation analysis, values for Pearson's r = 0.788 and r2 = 0.621 were obtained (p < 0.001). The areas under the curve obtained by the receiver operating characteristics curves to estimate urine osmolarity values < 100 and > 600 mOsm/kg were > 0.90. CONCLUSION: The estimation of the OsmU from UD showed adequate performance. If an osmometer is unavailable, we recommend using the factor 35 for clean samples and 32 with adjusted UD for samples with proteinuria and/or glycosuria.
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Concentração Osmolar , Osmometria/métodos , Urinálise/métodos , Urina/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Glicosúria/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria/epidemiologia , Refratometria/métodos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Worldwide, the cases of type 2 Diabetes Mellitus (DM2) has doubled in the last two decades. In the same period, obesity rates have triplicated, mainly because of the increase in the caloric intake and physical inactivity. According to the World Health Organization (WHO), more than 6 billion people consume cow´s milk and dairy products. By far, this amount exceeds the number o patients suffering from DM2. The increased consumption of highly caloric beverages including whole cow´s milk has incited several countries to publish recommendations on and encourage the intake of low fat milk and non-fat or reduced fat dairy products intake. Because of the multifactorial basis of DM2 and the controversial evidence regarding the relationship between cow's milk consumption and DM2 development, it is difficult to establish an optimal amount of milk per day for a good health, with no side effects. It is necessary to inform the general population on the nutritional value and health benefits of cow's milk.
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Diabetes Mellitus Tipo 2/etiologia , Ingestão de Energia , Leite/efeitos adversos , Obesidade/etiologia , Animais , Bovinos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Obesidade/epidemiologia , Obesidade/prevenção & controleRESUMO
Thyroid hormone resistance is a syndrome characterized by a reduced response to thyroid hormone with different degrees of resistance at target tissues. We present the clinical features, physical findings, and study protocol in a woman with thyroid hormone resistance. An arginine to tryptophan mutation on the ß isoform of the thyroid hormone receptor gene was demonstrated. Thyroid hormone resistance is an uncommon cause of thyroid dysfunction. It is necessary to perform an adequate study and confirmation to avoid an inadequate and ineffective treatment of this condition.
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Receptores beta dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/fisiopatologia , Adulto , Feminino , Humanos , Mutação , Síndrome da Resistência aos Hormônios Tireóideos/genéticaRESUMO
We report on a rare case of an adult with severe hypercalcemia secondary to the ectopic secretion of parathyroid-related peptide (PTH-rP) from a penile squamous cell cancer (PC). A patient of 47 years old was admitted with warty lesions and areas of ulceration covered by purulent material in a large area of the groin, scrotum and penis. Laboratory tests revealed severe hypercalcemia and elevation of PTH-rP; the biopsy reported PC. Hypercalcemia was successfully treated with zoledronic acid, however, the tumor displayed aggressive behavior, which resulted in a poor prognosis for the patient.
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Carcinoma de Células Escamosas/metabolismo , Hipercalcemia/etiologia , Hormônio Paratireóideo/metabolismo , Neoplasias Penianas/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Hipercalcemia/tratamento farmacológico , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pelve/diagnóstico por imagem , Doenças Raras/etiologia , Doenças Raras/metabolismo , Tomografia Computadorizada por Raios X , Ácido ZoledrônicoRESUMO
We report on a rare case of an adult with severe hypercalcemia secondary to the ectopic secretion of parathyroid-related peptide (PTH-rP) from a penile squamous cell cancer (PC). A patient of 47 years old was admitted with warty lesions and areas of ulceration covered by purulent material in a large area of the groin, scrotum and penis. Laboratory tests revealed severe hypercalcemia and elevation of PTH-rP; the biopsy reported PC. Hypercalcemia was successfully treated with zoledronic acid, however, the tumor displayed aggressive behavior, which resulted in a poor prognosis for the patient.
Relatamos um caso raro em um adulto com hipercalcemia grave secundária à secreção ectópica de peptídeo relacionado ao paratormônio (PTH-rP) de um carcinoma de células escamosas do pênis (CP). Um paciente de 47 anos foi admitido com lesões verrucosas e áreas de ulceração cobertas por material purulento em uma grande área da virilha, escroto e pênis. Os testes laboratoriais revelaram hipercalcemia grave e elevação do PTH-rP; a biópsia mostrou um CP. A hipercalcemia foi tratada de forma bem-sucedida com ácido zoledrônico. Entretanto, o tumor apresentava um comportamento agressivo, resultando em um prognóstico ruim para o paciente.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas , Hipercalcemia/etiologia , Hormônio Paratireóideo , Neoplasias Penianas , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Hipercalcemia/tratamento farmacológico , Imidazóis/uso terapêutico , Pelve , Doenças Raras/etiologia , Doenças Raras/metabolismo , Tomografia Computadorizada por Raios XRESUMO
We report a rare case of an adult with advanced liver failure in the setting of an untreated congenital panhypopituitarism. A 32-years-old man presented with a newly onset seizure episode secondary to hypoglycemia. In the initial exploration, we found eunuchoid habitus, absence of secondary sexual characteristics, ascites, and hepatic encephalopathy. Hormonal evaluation confirmed the absence of anterior hypophyseal hormones and the liver function tests showed derangement of liver function. Magnetic Resonance Imaging (MRI) showed hypoplastic adenohypophysis and ectopic posterior pituitary gland. In the approach to liver disease, no cause was identified, besides the untreated panhypopituitarism.
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OBJECTIVES: To assess the presence of a local angiotensin-generating systems (LAGS) and its participation in tumor growth in the human pancreatic cancer derived cell line Capan-1. METHODS: Capan-1 cells were cultured in Dulbecco modified Eagle medium, and angiotensin I was assayed by radioimmunoassay and angiotensin II and vascular endothelial growth factor were assayed by enzyme-linked immunosorbent assay in the supernatant. Immunohistochemistry and reverse transcription-polymerase chain reaction were performed for the expression of AT1 and AT2 receptors. Angiotensin II binding assays and blockade were studied. RESULTS: High levels of both angiotensins I and II were found in Capan-1 cells, although neither angiotensin I nor angiotensin II was detected in the cell culture supernatant. Reverse transcription-polymerase chain reaction and immunocytochemistry revealed that Capan-1 cells do not express AT1 and AT2 receptors; however, specific binding to the cell membrane was identified for angiotensin II. Neither exogenous angiotensin II nor Dup753 (specific AT1 receptor blocker) affected Capan-1 cells' proliferation or vascular endothelial growth factor secretion. CONCLUSIONS: Detection of both angiotensin I and angiotensin II along with specific binding of angiotensin II in Capan-1 cells provides evidence of the existence of a LAGS that operates in an intracrine manner. Intracellular angiotensin II may play a role in the aggressiveness of pancreatic cancer and is a possible target for therapeutic agents.
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Angiotensina II/biossíntese , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Sítios de Ligação , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Espaço Intracelular/metabolismo , Losartan/farmacologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Association studies provide a powerful approach to link DNA variants and genetic predisposition to complex diseases. In this study, we determined the genotype and allelic frequencies of genes encoding enzymes involved in alcohol metabolism in alcoholic and nonalcoholic subjects of related ethnicity. A total of 118 individuals of Otomi Mexican Indian ancestry were included. Fifty-nine were chronic alcoholics according to WHO criteria and alcohol dependents according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria. They were compared to 59 teetotalers or alcohol consumers of <10 g per day. The restriction fragment length polymorphisms analyzed were ADH1B/MaeIII, ALDH2/MboII, CYP2E1/DraI, CYP2E1/RsaI, and CYP2E1/TaqI. Of the studied polymorphisms, a significant difference between alcoholic and nonalcoholic Otomies was observed only in the CYP2E1/TaqI. The common genotype in alcoholics was A1/A2 (54%), and in nonalcoholics the homozygous A2/A2 (63%) (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.13-0.60; P=.002). The frequency of the mutant allele A1 was significantly higher in alcoholics than in nonalcoholics (41 vs. 21%; OR: 2.4; 95% CI: 1.3-4.3; P=.003). This documents the presence of a polymorphism of CYP2E1 that is overexpressed in alcoholic Otomies, in which the variant allele (A1 of CYP2E1/TaqI) is associated with increased susceptibility to alcoholism. The appreciation that this finding may be an additional factor contributing to the high frequency of liver cirrhosis in Otomies requires further investigation.