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Microangiopathy should be noted in diabetes with subclinical vascular diseases. Little is known about whether various surrogate markers of systemic arterial trees exacerbate simultaneously in preclinical atherosclerosis. To clarify the association of skin microvascular reactivity with arterial stiffness is essential to elucidating early atherosclerotic changes. The post-occlusive reactive hyperemia of skin microcirculation was evaluated in 27 control and 65 type 2 diabetic subjects, including 31 microalbuminuria (MAU) and 34 normoalbuminuria (NAU) patients. The laser Doppler skin perfusion signals were transformed into three frequency intervals for the investigation of endothelial, neurogenic, and myogenic effects on basal and reactive flow motion changes. The analysis of spectral intensity and distribution provided insight into potential significance of microvascular regulation in subclinical atherosclerotic diseases. Systemic arterial stiffness was studied by the brachial ankle pulse wave velocity (baPWV). Following occlusive ischemia, the percent change of endothelial flow motion was lower in MAU than in NAU and control groups. The MAU group revealed a relative increase in myogenic activity and a decrease in endothelial activity in normalized spectra. The baPWV showed more significant associations with reactive endothelial change (r = - 0.48, P < 0.01) and normalized myogenic value (r = - 0.37, P < 0.05) than diabetes duration and HbA1c. By multivariate regression analysis, only endothelial vasomotor changes independently contributed to the decreased baPWV (OR 3.47, 95% CI 1.63-7.42, P < 0.05). Impaired microcirculatory control is associated with increased arterial stiffness in preclinical atherosclerosis. To identify the early manifestations is necessary for at-risk patients to prevent from further vascular damage.
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Aterosclerosis , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Índice Tobillo Braquial , Microcirculación , Análisis de la Onda del Pulso , Aterosclerosis/diagnóstico por imagen , Rayos LáserRESUMEN
RATIONALE: Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease. PATIENT CONCERNS: A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache. DIAGNOSES: Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2âcm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy. INTERVENTIONS: Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly. OUTCOMES: His symptoms and laboratory data recovered after the operation and medical treatment. LESSONS: This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.
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Adenoma , Insuficiencia Suprarrenal , Eosinofilia , Exantema , Hiponatremia , Hipopituitarismo , Neoplasias Hipofisarias , Accidente Cerebrovascular , Adenoma/complicaciones , Adenoma/diagnóstico , Adenoma/cirugía , Insuficiencia Suprarrenal/complicaciones , Celulitis (Flemón)/complicaciones , Eosinofilia/complicaciones , Exantema/complicaciones , Humanos , Hiponatremia/complicaciones , Hipopituitarismo/complicaciones , Hipopituitarismo/etiología , Imagen por Resonancia Magnética/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/cirugía , Prurito , Accidente Cerebrovascular/complicacionesRESUMEN
Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.
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Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Adulto , Alelos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , China/epidemiología , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , PronósticoRESUMEN
OBJECTIVE: The association between ankle brachial index (ABI) and outcomes in diabetic subjects is controversial. The purpose of this study was to evaluate whether the ABI is more strongly associated with cardiovascular outcomes comparing with non-high-density lipoprotein cholesterol (non-HDL-c). RESEARCH DESIGN AND METHODS: A total of 452 type 2 diabetic subjects followed up for a mean of 5.8 years were grouped by ABI (<0.9 versus ≥0.9) and non-HDL-c (<100mg/dL versus ≥100mg/dL). Primary outcomes were composite events including all-cause mortality, hospitalization for coronary artery disease, stroke, revascularization, amputation and diabetic foot, and the secondary end point was all-cause mortality. RESULTS: Intergroup differences in percentage of men, duration of diabetes, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, triglycerides and estimated glomerular filtration rate were significant. A total of 64 composite events and 17 deaths were recorded. A higher number of composite events occurred in the group with abnormal ABI but optimal non-HDL-c than in those with suboptimal non-HDL-c but normal ABI (29% versus 11%, P < 0.05). A similar trend was observed in all-cause mortality (11% versus 1%, P < 0.05). The ABI was the dominant risk factor for both end points after adjusting other factors (for composite events, hazard ratio = 0.02, 95% CI: 0.00-0.10, P < 0.001 and for all-cause mortality, hazard ratio = 0.01, 95% CI: 0.00-0.28, P = 0.006). CONCLUSIONS: The ABI was more strongly associated with outcomes in diabetes than non-HDL-c. The ABI should be routinely screened in diabetes even without symptom.
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Índice Tobillo Braquial , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Colesterol/sangre , Diabetes Mellitus Tipo 2/complicaciones , Técnicas de Diagnóstico Cardiovascular/instrumentación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , TaiwánRESUMEN
BACKGROUND/PURPOSE: Iodine deficiency causes a broad spectrum of disorders across all ages. Mandatory salt iodization in Taiwan successfully reduced the goiter rate from 21.6% to 4.3% in schoolchildren surveyed in 1971. The program continued until 2003 when salt iodization was changed from mandatory to voluntary. The purpose of this study was to investigate the iodine status of Taiwanese individuals after the change in the iodine policy. METHODS: Urinary iodine (UI) was measured in samples from adults in the Nutrition and Health Survey in Taiwan 2005-2008. RESULTS: The median UI level was 100 µg/L, and the percentage of populations with UI levels below 100 µg/L and 50 µg/L was 50.1% and 15.1%, respectively, indicating that the iodine status was borderline adequate. Men had a higher UI level than women (102 µg/L vs. 98 µg/L, p = 0.003), and older individuals (age > 60 years) had a lower UI level than younger people, particularly in women. The iodine status of the population < 50 years was sufficient, but it was insufficient in older groups. Mild iodine insufficiency was noted in all areas of Taiwan except the Southern area and Penghu islands, with the lowest UI level of 79 µg/L in the Mountain area. Although the UI level of women of childbearing age (19-44 years) was 103 µg/L, there may be a risk of iodine deficiency during pregnancy. CONCLUSION: The iodine nutrition of the Taiwanese population in 2005-2008 was borderline adequate, with insufficiency in some subgroups. Further monitoring of the iodine status is necessary.
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Bocio/epidemiología , Bocio/prevención & control , Yodo/orina , Cloruro de Sodio Dietético/administración & dosificación , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Embarazo , Distribución por Sexo , Taiwán , Glándula Tiroides/efectos de los fármacos , Adulto JovenRESUMEN
AIMS: Peripheral arterial disease (PAD) could be an additional risk factor for the clinical outcomes in different populations. The purpose of this study was to evaluate the influence of PAD on patients with diabetic kidney disease. METHODS: 362 persons with type 2 diabetes were followed-up for a mean 4.8 years grouped by ankle brachial index (ABI) (<0.9 vs. â§0.9) and albuminuria (with or without). Primary and secondary outcomes were composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation, and diabetic foot) and all-cause mortality. RESULTS: Inter-group differences in duration of diabetes, glycated hemoglobin, creatinine, and estimated glomerular filtration rate were significant. During the follow-up period, 53 composite events were recorded (14.7%) and 13 (3.5%) individuals died. Subjects with albuminuria plus ABI<0.9 had higher risk of composite events than those with albuminuria but normal ABI (p<0.05). The only trend difference between the two groups was in all-cause mortality. Albuminuria plus ABI <0.9 was associated with risk of composite events (hazard ratio [HR] 4.20, 95% confidence interval [CI] 1.77-9.92, p=0.001) and all-cause mortality (HR 17.77, 95% CI 1.93-162.20, p=0.011). CONCLUSIONS: PAD might be an additional risk factor for adverse outcomes in patients with diabetic kidney disease. Further prospective data are required to validate this conclusion.
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Índice Tobillo Braquial , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/diagnóstico , Anciano , Albuminuria/complicaciones , Albuminuria/diagnóstico , Albuminuria/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/complicaciones , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. METHODS: A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (<0.9 vs. ≥0.9) and baPWV (<1,700 cm/s vs. ≥1,700 cm/s). RESULTS: The outcomes were all-cause mortality and composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation and diabetic foot). Inter-group differences in the smoking rate, duration of diabetes, systolic and pulse blood pressure, anti-platelet drugs, estimated glomerular filtration rate, and urine albumin excretion were significant. During the follow-up period, 17 (3.7%) individuals died and composite events were recorded in 64 cases (14.1%). A low ABI plus high baPWV was found be associated with poor outcomes compared with a normal ABI plus low baPWV (p<0.001). Meanwhile, a low ABI plus high baPWV was associated with an increased risk of all-cause mortality [hazard ratio (HR) 17.01, 95% confidence interval (CI) 1.57-183.73, p=0.019] and composite events (HR 8.53, 95% CI 3.31-21.99, p<0.001). CONCLUSION: In this study, the outcomes of patients with a low ABI plus high baPWV were the worst, while the subjects with a low ABI plus low baPWV or normal ABI exhibited similar outcomes. Therefore, the ABI plus baPWV exhibits a better association with the outcomes of T2DM.
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Índice Tobillo Braquial , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/complicaciones , Enfermedad Arterial Periférica/complicaciones , Análisis de la Onda del Pulso , Anciano , Enfermedad de la Arteria Coronaria/epidemiología , Diabetes Mellitus Tipo 2/mortalidad , Angiopatías Diabéticas/fisiopatología , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Enfermedad Arterial Periférica/fisiopatología , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiologíaRESUMEN
Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.
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Pregnenodionas/farmacocinética , Administración Oral , Área Bajo la Curva , Pueblo Asiatico , Femenino , Voluntarios Sanos , Humanos , Masculino , ComprimidosRESUMEN
Taiwan was an iodine deficiency area and endemic goiter was common in 1940's. Mandatory salt iodization started in 1967, and a 1971 survey indicated that goiter rates in children decreased from 21.6% to 4.3%. To understand iodine status before the change of national salt iodization program in 2003, from mandatory to voluntary salt iodization, we retrospectively measured urinary iodine concentrations of samples collected from children in the Nutrition and Health Survey in Taiwan 2001-2002. The median UI level for children aged 6-12 years was 123 µg/L (no differences between males and females). Females aged 10-12 years had the lowest urinary iodine levels. The percentages of this population with urinary iodine levels below 100, 50, and 20 µg/L were 35.2% ± 1.0%, 4.4% ± 0.4%, and 0.2% ± 0.1%, respectively. Older children were more likely to have low urinary iodine levels. People living in different areas of Taiwan had a median urinary iodine levels ranged from 113 µg/L to 164 µg/L (males: 113-153 µg/L; females: 105-174 µg/L), with the highest level in Penghu islands, and the lowest level in the eastern and southern (Southern area 2) areas. According to international criteria, iodine status in 2001-2002 was adequate, comparable to the surveyed goiter rates (4.3%, classified as iodine sufficiency) in 1971, inferring that iodine nutrition remained adequate and stable during this period. The present study is of great importance in documenting the iodine status of Taiwan before the change from mandatory to voluntary salt iodization to serve as a baseline data for future trend analysis in iodine nutrition.
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Encuestas Epidemiológicas/métodos , Yodo/orina , Política Nutricional , Estado Nutricional/fisiología , Cloruro de Sodio Dietético/administración & dosificación , Distribución por Edad , Niño , Femenino , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Yodo/administración & dosificación , Masculino , Estudios Retrospectivos , Distribución por Sexo , TaiwánRESUMEN
BACKGROUND: Although thyroid diseases exist in patients with renal failure, thyroid function tests are not routine tests in patients on chronic hemodialysis (HD). Therefore, the impact of thyroid diseases on erythropoietin (EPO) dosage in HD patients is not well defined. This study evaluated the relationship between the dose of EPO and the presence or absence of thyroid dysfunction in HD patients. METHODS: This study included 1013 adult patients on HD who did not have a malignancy, liver cirrhosis, thalassemia, iron deficiency, gastrointestinal bleeding, or a major operation within 6 months. Patients were characterized as being euthyroid, or having the sick euthyroid syndrome, primary hypothyroidism, subclinical hypothyroidism, hyperthyroidism, or subclinical hyperthyroidism based on thyroid function tests. Routine biochemistry profiles including an index of the efficiency of HD, along with clinical data over the previous 6-month period, were collected and analyzed. Multiple regression models were employed to assess the relationship between the dose of EPO and the presence or absence of thyroid status. RESULTS: The mean monthly EPO dosages were 77.7±37.0, 70.2±40.6, 90.8±68.4, 78.5±46.7, and 82.3±41.2 µg, respectively, in the sick euthyroid syndrome, euthyroid patients, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism groups (p<0.05). After adjustment of all other variables in multiple regression, the mean monthly EPO dosage was 19.00±8.59 µg more in hypothyroid patients compared with euthyroid patients (p=0.027). Further, considering an interaction with the presence of diabetes, the mean monthly EPO dosage in patients with either hypothyroidism or subclinical hypothyroidism and diabetes was 54.66±17.12 µg (p=0.001) and 31.51±10.38 µg more than that of euthyroid patients, respectively (p=0.002). CONCLUSIONS: In HD patients, the EPO dosage required to maintain the target hemoglobin level is significantly higher in patients having both hypothyroidism or subclinical hypothyroidism and diabetes than in euthyroid patients.
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Nefropatías Diabéticas/complicaciones , Eritropoyetina/administración & dosificación , Hematínicos/administración & dosificación , Fallo Renal Crónico/complicaciones , Diálisis Renal/efectos adversos , Enfermedades de la Tiroides/complicaciones , Glándula Tiroides/fisiopatología , Anciano , Anemia Hemolítica/etiología , Anemia Hemolítica/prevención & control , Estudios Transversales , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/terapia , Monitoreo de Drogas , Eritropoyetina/uso terapéutico , Síndromes del Eutiroideo Enfermo/complicaciones , Síndromes del Eutiroideo Enfermo/epidemiología , Síndromes del Eutiroideo Enfermo/fisiopatología , Femenino , Hematínicos/uso terapéutico , Humanos , Hipertiroidismo/complicaciones , Hipertiroidismo/epidemiología , Hipertiroidismo/fisiopatología , Hipotiroidismo/complicaciones , Hipotiroidismo/epidemiología , Hipotiroidismo/fisiopatología , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la Enfermedad , Taiwán/epidemiología , Enfermedades de la Tiroides/epidemiología , Enfermedades de la Tiroides/fisiopatologíaRESUMEN
Systemic microvascular complications are related to the presence of diabetic neuropathy. This study investigated the associations of blood flow oscillations with peripheral neuropathy in 25 controls and 3 diabetic groups including clinical (24), subclinical (27) and without neuropathy (26). Laser Doppler skin perfusion was transformed into three low-frequency subintervals corresponding to endothelial, neurogenic and myogenic vasomotor controls. The average vasomotion was significantly reduced in clinical neuropathy group and characterized by endothelial and neural but not smooth muscle-related changes. The normalized spectrums revealed a relative increase of myogenic and decrease of neurogenic activity in subclinical neuropathy group. The myogenic component showed a statistically inverse correlation with postural fall in systolic blood pressure (r = -0.32, p < 0.01). The diabetic patients with decreased low-frequency vasomotor responses were associated with increased odds ratio of peripheral neuropathy [odds ratio = 3.51 (95% confidence interval = 1.19-10.31), p = 0.02]. This study elucidated possible interaction between impaired microvascular flow motion and diabetic peripheral neuropathy. The vasomotor changes of skin microcirculation could be detected even in the absence of overt cardiovascular dysfunction.
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Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/fisiopatología , Regulación hacia Abajo , Endotelio Vascular/fisiopatología , Microcirculación , Piel/irrigación sanguínea , Sistema Vasomotor/fisiopatología , Estudios Transversales , Neuropatías Diabéticas/diagnóstico , Diagnóstico Precoz , Endotelio Vascular/inervación , Femenino , Hospitales de Veteranos , Humanos , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/inervación , Músculo Liso Vascular/fisiopatología , Índice de Severidad de la Enfermedad , Piel/inervación , TaiwánRESUMEN
BACKGROUND: Diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a rare variant of papillary thyroid carcinoma (PTC). We report a 61-year-old female of DSPC whose course was complicated by multiple metastases and an elevated serum carcinoembryonic antigen (CEA) level. SUMMARY: The patient presented with upper back pain. X-ray showed an osteolytic lesion of the sixth cervical spinous process. She had a hard, nonmovable mass with fixed enlarged lymph nodes (LNs) over right neck. Fine-needle aspiration cytology revealed PTC with LNs metastasis. Positron emission tomography demonstrated multiple brain, bone, liver, and lung metastases. However, the patient had an elevated serum CEA level. She underwent a total thyroidectomy and 200 mCi radioactive (131)I therapy. The pathological findings were diffuse sclerosing variant of PTC with capsular and lymph vessel invasion. A double staining of tumor specimen appeared concomitantly positive for CEA and thyroglobulin. CONCLUSIONS: To our knowledge, DSPC with an elevated CEA level is extremely rare.
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Antígeno Carcinoembrionario/sangre , Carcinoma Papilar/secundario , Carcinoma/patología , Neoplasias de la Tiroides/patología , Carcinoma/radioterapia , Carcinoma Papilar/patología , Terapia Combinada , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Esclerosis , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/radioterapiaRESUMEN
In this study, we performed all-atom long-timescale molecular dynamics simulations of phospholipid bilayers incorporating three different proportions of negatively charged lipids in the presence of K(+), Mg(2+), and Ca(2+) ions to systemically determine how membrane properties are affected by cations and lipid compositions. Our simulations revealed that the binding affinity of Ca(2+) ions with lipids is significantly stronger than that of K(+) and Mg(2+) ions, regardless of the composition of the lipid bilayer. The binding of Ca(2+) ions to the lipids resulted in bilayers having smaller lateral areas, greater thicknesses, greater order, and slower rotation of their lipid head groups, relative to those of corresponding K(+)- and Mg(2+)-containing systems. The Ca(2+) ions bind preferentially to the phosphate groups of the lipids. The complexes formed between the cations and the lipids further assembled to form various multiple-cation-centered clusters in the presence of anionic lipids and at higher ionic strength-most notably for Ca(2+). The formation of cation-lipid complexes and clusters dehydrated and neutralized the anionic lipids, creating a more-hydrophobic environment suitable for membrane aggregation. We propose that the formation of Ca(2+)-phospholipid clusters across apposed lipid bilayers can work as a "cation glue" to adhere apposed membranes together, providing an adequate configuration for stalk formation during membrane fusion.
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Cationes/química , Membrana Dobles de Lípidos , Fusión de Membrana , Simulación de Dinámica Molecular , Fosfolípidos/química , Modelos Moleculares , Agua/químicaRESUMEN
Impaired cutaneous blood flow and sweating dysfunction might be among the earliest manifestations of diabetic autonomic neuropathy. This study assessed the pathophysiological basis underlying skin vasomotion changes and their relation with progressive sudomotor dysfunction and other autonomic and somatic measures in subclinical diabetic feet. Laser Doppler skin perfusion was assessed on 68 diabetic and 25 control subjects. The low-frequency vasomotion was transformed into three frequency intervals 0.0095-0.021, 0.021-0.052 and 0.052-0.145 Hz, respectively, for the investigation of endothelial, neurogenic and myogenic effects on microcirculatory alterations. The diabetic patients were categorized into three groups by increasing severity of sudomotor dysfunction: SSR+ (sympathetic skin response present; 27 patients), SSR- (SSR absent; 23 patients) and at-risk (SSR absent and of preulcerative cracked skin; 18 patients). All diabetic patients underwent nerve conduction and cardiovascular autonomic studies. The total spectral and endothelial activity was significantly decreased only in the at-risk group. The SSR- group had lower neurogenic vasomotion than the SSR+ group (p<0.05). Although no statistical difference was noted between any group in absolute myogenic spectrum, the SSR- group had higher normalized myogenic activity than the SSR+ group (p<0.01). The larger drop in orthostatic pressure was paralleled by a reduction in the myogenic amplitude (r=-0.33, p<0.01). These results suggested that early impairment of low-frequency flow motion correlated closely with the presence of sudomotor dysfunction of subclinical feet mainly in neurogenic and endothelial components. Impaired systemic vascular tone as manifested by orthostatic hypotension was proportional to the degree of myogenic dysregulation in diabetic patients.
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Sistema Nervioso Autónomo/fisiopatología , Pie Diabético/fisiopatología , Neuropatías Diabéticas/fisiopatología , Microcirculación , Piel/irrigación sanguínea , Piel/inervación , Sudoración , Análisis de Varianza , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Pie Diabético/diagnóstico , Pie Diabético/patología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/patología , Electromiografía , Femenino , Humanos , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Piel/patología , TaiwánRESUMEN
OBJECTIVES: Most patients with Cushing's disease (CD) respond to corticotrophin-releasing hormone (CRH) or desmopressin with increased corticotrophin (ACTH) and cortisol levels. Although the vasopressin receptor subtype located on normal corticotrophs is the V3 receptor (V3R), desmopressin is a selective V2 receptor (V2R) agonist and it is unclear whether corticotrophinomas exhibit aberrant V2R expression. Furthermore, no studies have determined the relationship between the in vivo response of CD patients to desmopressin and vasopressin receptor expression, or between the response to CRH and CRH receptor (CRHR) expression. Therefore, the aim of this study was to investigate the expression of vasopressin receptors (V1R, V2R, and V3R) and CRHR on corticotroph tumours and its possible relation to the in vivo response. DESIGNS: A prospective study of 29 patients with CD. METHODS: Patients underwent desmopressin and CRH stimulation tests before surgery. The expression of vasopressin receptors and CRHR on corticotrophinomas was determined by immunocytochemistry. RESULTS: Most of the corticotrophinomas exhibited abundant expression of V1R, V3R, and CRHR, whereas the expression of V2R varied greatly and was lower in macroadenomas than in microadenomas. Both the percentage increment of ACTH and net area under the curve (AUC) of ACTH in the desmopressin stimulation test were found to be correlated with tumour volume. After adjustment for tumour volume, a positive correlation was found between the percentage increment of ACTH and the degree of V2R expression, but not between that of V1R or V3R. No relationship between the level of expression of CRHR on tumour tissues and the percentage increment or netAUC of ACTH to CRH was observed in CD patients. CONCLUSIONS: We concluded that V2R was expressed on corticotrophinomas and that the level of its expression correlated well with the ACTH response to desmopressin in CD patients, although abundant expression of V1R and V3R was also found in almost all corticotroph tumours. Further studies are needed to elucidate the role of these receptors in the pathogenesis of CD.
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Hormona Adrenocorticotrópica/sangre , Desamino Arginina Vasopresina/farmacología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/metabolismo , Neoplasias Hipofisarias/metabolismo , Receptores de Vasopresinas/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Hormona Liberadora de Corticotropina/farmacología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
AIMS: We investigated dialysis duration, dose of erythropoietin (EPO), and clinical manifestations in peritoneal dialysis (PD) patients with subclinical hypothyroidism. METHODS: This cross-sectional study, performed in 3 centers, assessed 122 adult patients on PD for more than 6 months with regard to demographic data, dialysis duration, thyroid function, biochemical data, EPO dose, and clinical manifestations. Thyroid dysfunction was determined by serum thyroid-stimulating hormone, free thyroxine, total thyroxine, total triiodothyronine, antithyroid peroxidase antibodies, and auto-antibodies against thyroglobulin. RESULTS: Of the 122 study patients, 98 (80.3%) were assessed as having euthyroidism; 19 (15.6%), subclinical hypothyroidism; and 5 (4.1%), subclinical hyperthyroidism. The proportion of women (74.2% vs. 57.1%, p = 0.038), the mean duration of PD (58.1 months vs. 37.9 months, p = 0.032), and the weighted mean monthly EPO dose (1.22 µg/kg vs. 1.64 µg/kg, p = 0.009) were significantly higher in the subclinical hypothyroidism group than in the euthyroidism group, but the prevalences of coronary artery disease and cerebrovascular disease were not. From the multivariate model, PD duration was more significant than sex as a risk factor for subclinical hypothyroidism (p = 0.0132). CONCLUSIONS: Subclinical hypothyroidism is frequent in PD patients, especially female patients and patients with a longer PD duration. Compared with euthyroid patients, patients with subclinical hyperthyroidism need a higher dose of EPO to maintain a stable hemoglobin level.
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Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Enfermedades de la Tiroides/epidemiología , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Prevalencia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Taiwán/epidemiología , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/etiología , Tirotropina/sangre , Tiroxina/sangreRESUMEN
INTRODUCTION: Emphysematous pyelonephritis (EPN) is a rare but severe infection of renal parenchyma. Risk factors of renal failure in patients survived from EPN are not clear. METHODS: The authors retrospectively reviewed the patients with a diagnosis of EPN at Taipei Veterans General Hospital from January 1, 1995, to December 31, 2009. The authors analyzed the demographic, characteristics and the treatment modalities of those patients. The renal function of survivors after EPN episode had been followed for 1 year. RESULTS: A total of 23 patients with a mean age of 62.8 ± 17.1 years were enrolled. Mean hospital duration was 31.8 ± 21.6 days. Fifteen (65.2%) patients had a history of diabetes mellitus. Mean serum HbA1c level among the diabetic patients was 11.7 ± 3.3. More than half of patients had Escherichia coli in culture. Eleven (47.8%) patients received antibiotic treatment alone. Twelve (52.2%) patients received the concurrent percutaneous drainage and antibiotics. The overall mortality rate was 8.6%. Shock, long hospital duration and the extensive classes of computed tomography image were correlated with poor outcome. A higher initial serum creatinine level (2.8 ± 1.4 versus 1.6 ± 0.8, P = 0.015) and receiving invasive therapy (67.7% versus 12.5%, P = 0.017) significantly contributed to chronic kidney disease in the follow-up. Shock is also an independent predictor of the poor outcome in those patients (P = 0.026). CONCLUSIONS: In the current era, antibiotics alone provide a high success rate for the treatment of EPN. Invasive therapy is a predictor of development of chronic kidney disease. Initial resuscitation and antibiotic therapy are still the cornerstone and have the benefit of the preservation of renal function.