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1.
Artigo em Inglês | MEDLINE | ID: mdl-31287546

RESUMO

CONTEXT: Familial hyperaldosteronism type I or glucocorticoid-remediable aldosteronism (FH-I; GRA) is caused by unequal crossing-over of the steroid 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. Somatic KCNJ5 mutations have not been reported in patients with GRA; therefore, the appropriate treatment and prognosis of such concurrent cases remain unknown. CASE DESCRIPTION: Two siblings of a Taiwanese family with GRA were found to have adrenal adenomas and somatic KCNJ5 mutations. Complete clinical cure was achieved after unilateral adrenalectomy. Furthermore, the conversion site of the chimeric gene was identified by direct sequencing. CONCLUSIONS: We report for the first time the coexistence of a somatic KCNJ5 mutation and GRA. GRA patients whose blood pressure management develops resistance to glucocorticoid treatment could therefore benefit from a lateralization test. The promising outcomes after unilateral adrenalectomy presented in this report offer new perspectives for further research into various PA subtypes.

2.
Curr Pharm Des ; 25(6): 627-634, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931851

RESUMO

BACKGROUND: Methotrexate (MTX) is one of the leading chemotherapeutic agents with the bestdemonstrated efficacies against childhood acute lymphoblastic leukemia (ALL). Due to the narrow therapeutic range, significant inter- and intra-patient variabilities of MTX, non-effectiveness and/or toxicity occur abruptly to cause chemotherapeutic interruption or discontinuation. The relationship between clinical outcome and the systemic concentration of MTX has been well established, making the monitoring of plasma MTX levels critical in the treatment of ALL. Besides metabolizing enzymes, multiple transporters are also involved in determining the intracellular drug levels. In this mini-review, we focused on the genetic polymorphisms of MTX-disposition related transporters and the potential association between the discussed genetic variants and MTX pharmacokinetics, efficacy, and toxicity in the context of MTX treatment. METHODS: We searched PubMed for citations published in English using the terms "methotrexate", "transporter", "acute lymphoblastic leukemia", "polymorphisms", and "therapeutic drug monitoring". The retrieval papers were critically reviewed and summarized according to the aims of this mini-review. RESULTS: Solute carrier (SLC) transporters (SLC19A1, SLCO1A2, SLCO1B1, and SLC22A8) and ATP-binding cassette (ABC) transporters (ABCB1, ABCC2, ABCC3, ABCC4, ABCC5, and ABCG2) mediate MTX disposition. Of note, the influences of polymorphisms of SLC19A1, SLCO1B1 and ABCB1 genes on the clinical outcome of MTX have been extensively studied. CONCLUSION: Overall, the data critically reviewed in this mini-review article confirmed that polymorphisms in the genes encoding SLC and ABC transporters confer higher sensitivity to altered plasma levels, MTX-induced toxicity, and therapeutic response in pediatric patients with ALL. Pre-emptive determination may be helpful in individualizing treatment.

3.
Curr Pharm Des ; 25(3): 343-351, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931853

RESUMO

BACKGROUND: Valproic acid (VPA) as a widely used primary medication in the treatment of epilepsy is associated with reversible or irreversible hepatotoxicity. Long-term VPA therapy is also related to increased risk for the development of non-alcoholic fatty liver disease (NAFLD). In this review, metabolic elimination pathways of VPA in the liver and underlying mechanisms of VPA-induced hepatotoxicity are discussed. METHODS: We searched in PubMed for manuscripts published in English, combining terms such as "Valproic acid", "hepatotoxicity", "liver injury", and "mechanisms". The data of screened papers were analyzed and summarized. RESULTS: The formation of VPA reactive metabolites, inhibition of fatty acid ß-oxidation, excessive oxidative stress and genetic variants of some enzymes, such as CPS1, POLG, GSTs, SOD2, UGTs and CYPs genes, have been reported to be associated with VPA hepatotoxicity. Furthermore, carnitine supplementation and antioxidants administration proved to be positive treatment strategies for VPA-induced hepatotoxicity. CONCLUSION: Therapeutic drug monitoring (TDM) and routine liver biochemistry monitoring during VPA-therapy, as well as genotype screening for certain patients before VPA administration, could improve the safety profile of this antiepileptic drug.

4.
Crit Care ; 22(1): 313, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30463626

RESUMO

BACKGROUND: The interaction between hyperaldosteronism and immune dysfunction has been reported and glucocorticoid co-secretion is frequently found in primary aldosteronism (PA). The aforementioned conditions raise the possibility of the infection risk; however, clinical episodes of sepsis have not been reported in PA. METHODS: Using Taiwan's National Health Insurance Research Database between 1997 and 2009, we identified PA and aldosterone-producing adenoma (APA) matched with essential hypertension (EH) at a 1:1 ratio by propensity scores. The incidences of sepsis and mortality after the index date were evaluated, and the risk factors of outcomes were identified using adjusted Cox proportional hazards models and taking mortality as a competing risk. RESULTS: We enrolled 2448 patients with PA (male, 46.08%; mean age, 48.4 years). There were 875 patients who could be ascertained as APA. Taking mortality as the competing risk, APA patients had a lower incidence of sepsis than their matched EH patients (hazard ratio (HR) 0.29; P < 0.001) after target treatments. Patients receiving adrenalectomy showed a benefit of decreasing the risk of sepsis (PA vs EH, HR 0.14, P = 0.001; APA vs EH, HR 0.16, P = 0.003), but mineralocorticoid receptor antagonist treatment may differ. Compared with matched control cohorts, patients with APA had a lower risk of all-cause mortality (PA, adjusted HR 0.84, P = 0.050; APA, adjusted HR 0.31, P < 0.001) after target treatments. CONCLUSIONS: Our study demonstrated that patients with PA/APA who underwent adrenalectomy could attenuate the risk of sepsis compared with their matched EH patients. We further found that APA patients with target treatments could decrease all-cause mortality compared with EH patients.

5.
Surgery ; 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30473204

RESUMO

BACKGROUND: An elevated plasma aldosterone level has been reported as an independent risk factor for severe erectile dysfunction in men. The aim of this study was to explore whether primary hyperaldosteronism patients experience erectile dysfunction after targeted treatment. METHODS: We conducted a population-based cohort study of men with newly identified primary hyperaldosteronism/aldosterone-producing adenoma from January 1, 1997, to December 31, 2009. Men with essential hypertension and normotension were matched to the primary hyperaldosteronism group according to propensity score matching. RESULTS: We identified 1,067 men with primary hyperaldosteronism (mean age, 46.7 ± 12.8 years) and matched them with the same number of men with essential hypertension or normotension. During the mean follow-up interval of 5.4 years, the incident rates of total erectile dysfunction were 5.7, 3.9, and 3.1 per 1,000 person-years for the primary hyperaldosteronism, essential hypertension, and normotension groups, respectively. Men with primary hyperaldosteronism exhibited a higher risk of erectile dysfunction compared with men with normotension (competing risks hazard ratio, 1.83), and no difference was seen in comparison with men who have essential hypertension. After adrenalectomy, men who have primary hyperaldosteronism had a higher risk of exhibiting severe erectile dysfunction compared with men who have essential hypertension (competing risks hazard ratio, 2.44) or normotension (competing risks hazard ratio, 2.90). CONCLUSION: Men with primary hyperaldosteronism reported a higher incidence of severe erectile dysfunction than normotension controls despite targeted treatment. The risk of severe erectile dysfunction increased after men who have primary hyperaldosteronism underwent adrenalectomy. This result raises the possibility of severe erectile dysfunction after adrenalectomy and calls for a prospective large-scale study of men who have aldosterone-producing adenoma regarding their erectile function both before and after adrenalectomy.

7.
J Clin Med ; 7(10)2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332741

RESUMO

Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening ARR in PA patients with diabetes. The study enrolled consecutive patients and they underwent ARR testing at screening. Then the diagnosis of PA was confirmed from the Taiwan Primary Aldosteronism Investigation registration dataset. Generalized additive model smoothing plot was used to validate the performance of screening ARR in PA patients with or without diabetes. During this study period, 844 PA patients were confirmed and 136 (16.0%) among them had diabetes. Other 816 patients were diagnosed with essential hypertension and used as the control group and 89 (10.9%) among them had diabetes. PA patients with diabetes were older and had a longer duration of hypertensive latency, higher systolic blood pressure and lower glomerular filtration rate than those PA patients without diabetes. The cut-off value of ARR in the generalized additive model predicting PA was 65 ng/dL per ng/mL/h in diabetic patients, while 45 ng/dL per ng/mL/h in non-diabetic patients. There was a considerable prevalence of diabetes among PA patients, which might be capable of interfering with the conventional screening test. The best cut-off value of ARR, more than 65 ng/dL per ng/mL/h in PA patients with diabetes, was higher than those without diabetes.

8.
Ci Ji Yi Xue Za Zhi ; 30(3): 169-175, 2018 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30069126

RESUMO

Objectives: Adrenocortical scintigraphy for patients with primary aldosteronism (PA) without discontinuation or modification of antihypertensive medications is of concern because of drug interference with the renin-angiotensin-aldosterone system. We report the surgical outcomes of patients with PA lateralized with adrenocortical scintigraphy without drug discontinuation or modification. Materials and Methods: We retrospectively reviewed 34 patients with PA with computed tomography (CT)-documented adrenal tumors who had undergoing subsequent I-131-6 ß-iodomethyl-norcholesterol (NP-59) single photon emission CT (SPECT)/CT followed by unilateral adrenalectomy according to the results of NP-59 uptake between May 2005 and December 2014. All enrolled patients underwent standard confirmatory tests and lateralization with NP-59 SPECT/CT without discontinuation of existing antihypertensive medications, including spironolactone. The pathological findings, hypertension outcomes, and biochemical changes were reported. The accuracy of NP-59 SPECT/CT without drug discontinuation or modification was also evaluated. Results: None of the 34 enrolled patients (M:F = 16:18) had complications such as a hypertensive crisis, life-threatening hypokalemic event, or cardiac arrhythmia. Pathology disclosed 31 (91%) adenomas and three cases of hyperplasia. Hypertension cure and improvement were observed in 12 (35%) and 18 (53%) patients, respectively. All of the 30 patients (100%) without postoperative use of beta-blockers and with an available postoperative aldosterone/renin ratio achieved a biochemical cure. The positive predictive values of NP-59 SPECT/CT were 91%, 88%, and 100% for the pathological findings, hypertension outcomes, and biochemical changes, respectively. Conclusion: Noninvasive NP-59 SPECT/CT without discontinuation or modification of antihypertensive medications not only provided accurate lateralization and safety but also resulted in a high improvement rate for PA-associated hypertension.

9.
PLoS One ; 13(6): e0198677, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29944661

RESUMO

In order to solve the problem of Meshing Efficiency of spur-face gear sliding friction, a method for calculating the Meshing Efficiency of Spur-Face gear is proposed based on Elastohydrodynamic lubrication (EHL) theory. Through the Tooth Contact Analysis (TCA) and Loaded Tooth Contact Analysis technique (LTCA) method, the meshing process of the Spur-Face gear was simulated. The calculation model of Sliding friction coefficient was established by using non Newtonian quasi steady thermal Elastohydrodynamic lubrication (TEHL) theory, and the calculation model of Meshing Efficiency of Spur-Face gear was established. The influence of input torque and rotational speed on Meshing Efficiency is analyzed. The results show that Sliding friction coefficient is an important factor affecting the Meshing Efficiency of gears. Sliding friction coefficient is not the same at different positions of the tooth surface. Sliding friction coefficient is affected by input speed and input torque. This method provides a theoretical basis for further optimization calculation of Spur-Face gear.

10.
J Formos Med Assoc ; 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29506889

RESUMO

BACKGROUND/PURPOSE: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. METHODS: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management. RESULTS: In patients with lateralized PA, including aldosterone producing adenoma (APA), laparoscopic adrenalectomy is the 'gold standard' of treatment. Mini-laparoscopic and laparoendoscopic single-site approaches are feasible only in highly experienced surgeons. Patients with bilateral adrenal hyperplasia or those not suitable for surgery should be treated by mineralocorticoid receptor antagonists. The outcome data of PA patient management from the literature, especially from PA patients in Taiwan, are reviewed. Mental health screening is helpful in early detection and management of psychopathology among PA patients. CONCLUSION: We hope this consensus will provide a guideline to help medical professionals to manage PA patients in Taiwan to achieve a better quality of care.

11.
Surg Endosc ; 32(3): 1449-1455, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28916965

RESUMO

BACKGROUND: Laparoendoscopic single-site (LESS) adrenalectomy is a novel challenging technique which is still under clinical evaluation. Initial reports have revealed its superiority in patient convalescence. In addition, it has been reported that some patient or anatomic factors might affect the ergonomics of LESS adrenalectomy. The aim of this study is to investigate the possible factors that might affect procedural efficiency and patient convalescence in LESS adrenalectomy. METHODS: Between October 2009 and July 2015, 105 consecutive adult patients with benign adrenal tumors, who underwent LESS retroperitoneal adrenalectomy were enrolled in this study. All the relevant peri-operative parameters were prospectively collected for later analysis. By using stepwise linear regression and stepwise selection of these peri-operative parameters, those that might affect the operative efficiency and patient convalescence were analyzed. RESULTS: Finally, 78 patients who completed follow-up and were eligible for stepwise linear regression were enrolled for final analysis. For parameters affecting operative efficiency, the fitted model revealed that patients with a pre-operative diagnosis of pheochromocytoma, a higher BMI, and an associated co-morbidity of heart disease are associated with a longer operative time. In addition, the fitted model revealed that patients with a lower post-operative pain score, a delayed oral intake, and a diagnosis of non-functioning adrenal tumor were associated with a lengthier period before returning to normal activity. CONCLUSION: A higher BMI is the only anatomic factor that affects procedural efficiency in LESS adrenalectomy. In addition, post-operative pain score, time to oral intake, and a diagnosis of non-functioning adrenal tumor are the factors affecting patient convalescence.

12.
J Formos Med Assoc ; 116(12): 993-1005, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28735660

RESUMO

BACKGROUND/PURPOSE: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. METHODS: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. RESULTS: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. CONCLUSION: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA.


Assuntos
Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/terapia , Adosterol/administração & dosagem , Adrenalectomia , Aldosterona/sangue , Consenso , Humanos , Cintilografia , Renina/sangue , Sociedades Médicas , Taiwan , Tomografia Computadorizada por Raios X
13.
J Hypertens ; 35(8): 1698-1708, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28661412

RESUMO

OBJECTIVE: Abnormal glucose metabolism due to insulin resistance has been linked to aldosterone overproduction. However, the long-term incidence of new-onset diabetes mellitus (NODM) among patients with primary aldosteronism after targeted treatment has not been well documented. METHODS: The diagnosis of primary aldosteronism and essential hypertension were identified, and then the occurrence of NODM, all-cause mortality among these patients, was ascertained by a validated algorithm from a 23-million population insurance registry. RESULTS: From 1999 to 2007, 2367 primary aldosteronism patients without previously diabetes mellitus were identified and propensity score-matched with 9468 patients with essential hypertension. Among those primary aldosteronism patients, 754 aldosterone-producing adenomas patients were identified and matched with 3016 essential hypertension controls. After a mean 5.2 years of follow-up, primary aldosteronism patients who underwent adrenalectomy had an attenuated NODM incidence (hazard ratio = 0.60, P < 0.01, versus essential hypertension); whereas those treated with mineralocorticoid receptor antagonist had augmented risk of NODM (hazard ratio = 1.16, P < 0.001, versus essential hypertension). Among the aldosterone-producing adenoma patients, adrenalectomy is also protective from developing NODM (hazard ratio = 0.61, P < 0.001, versus essential hypertension), however, mineralocorticoid receptor antagonist treatment did not alter the risk of NODM (P = 0.10, versus essential hypertension). Adjusted hazard ratios for long-term risk of mortality from this analysis revealed that adrenalectomy is protective, but NODM and major cardiovascular disease are deleterious. CONCLUSION: The primary aldosteronism patients who underwent adrenalectomy had reduced risk for incident NODM and all-cause of mortality, compared with matched hypertensive controls. This observation adds more evidence on the association of primary aldosteronism with a higher risk of metabolic syndrome and long-term mortality.


Assuntos
Diabetes Mellitus/epidemiologia , Hiperaldosteronismo , Adrenalectomia , Diabetes Mellitus/etiologia , Grupos Diagnósticos Relacionados/estatística & dados numéricos , Feminino , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgia , Hipertensão/tratamento farmacológico , Incidência , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pontuação de Propensão , Fatores de Risco , Taiwan/epidemiologia
14.
Respir Res ; 18(1): 111, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28558721

RESUMO

BACKGROUND: The disruption and hyperpermeability of bronchial epithelial barrier are closely related to the pathogenesis of asthma. House dust mite (HDM), one of the most important allergens, could increase the airway epithelial permeability. Heat shock protein (Hsp) 90α is also implicated in the lung endothelial barrier dysfunction by disrupting RhoA signaling. However, the effect of extracellular Hsp90α (eHsp90α) on the bronchial epithelial barrier disruption induced by HDM has never been reported. METHODS: To investigate the involvement of eHsp90α in the bronchial epithelial barrier disruption induced by HDM, normal human bronchial epithelial cell line 16HBE14o- (16HBE) cells were treated by HDM, human recombinant (hr) Hsp90α and hrHsp90ß respectively and pretreated by1G6-D7, a specific anti-secreted Hsp90α monoclonal antibody (mAb). Hsp90α-silencing cells were also constructed. To further evaluate the role of RhoA signaling in this process, cells were pretreated by inhibitors of Rho kinase, GSK429286A and Y27632 2HCl. Transepithelial electrical resistance (TEER) and FITC-dextran flux (FITC-DX) were examined as the epithelial barrier function. Expression and localization of adherens junctional proteins E-cadherin and ß-catenin were evaluated by western blotting and immunofluorescence respectively. The level of eHsp90α was investigated by concentration and purification of condition media. RhoA activity was determined by using a Rho G-LISA® RhoA activation assay kitTM biochem kit, and the phosphorylation of myosin light chain (MLC), the downstream signal molecule of RhoA, was assessed by western blotting. RESULTS: The epithelial barrier disruption and the loss of adherens junctional proteins E-cadherin and ß-catenin in cytomembrane were observed in HDM-treated 16HBE cells, paralleled with the increase of eHsp90α secretion. All of which were rescued in Hsp90α-silencing cells or by pretreating 16HBE cells with 1G6-D7. Also, 1G6-D7 suppressed RhoA activity and MLC phosphorylation induced by HDM. Furthermore, inhibitors of Rho kinase prevented and restored the airway barrier disruption. Consistently, it was hrHsp90α instead of hrHsp90ß that promoted barrier dysfunction and activated RhoA/MLC signaling in 16HBE cells. CONCLUSIONS: The eHsp90α mediates HDM-induced human bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling, suggesting that eHsp90α is a potential therapeutic target for treatment of asthma.


Assuntos
Antiasmáticos/farmacologia , Brônquios/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/farmacologia , Cadeias Leves de Miosina/metabolismo , Pyroglyphidae/imunologia , Transdução de Sinais/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Antígenos CD , Brônquios/enzimologia , Brônquios/imunologia , Caderinas/metabolismo , Linhagem Celular , Dextranos/metabolismo , Impedância Elétrica , Células Epiteliais/enzimologia , Células Epiteliais/imunologia , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Permeabilidade , Fosforilação , Interferência de RNA , Fatores de Tempo , Transfecção , beta Catenina/metabolismo , Quinases Associadas a rho/metabolismo
15.
Oncotarget ; 8(18): 29984-29995, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28415786

RESUMO

The aim of this study was to show the effect of KCNJ5 mutational status on arterial stiffness in aldosterone-producing adenomas after adrenalectomy. Between February 2008 and January 2010, we prospectively enrolled 108 aldosterone-producing adenoma patients undergoing adrenalectomy. We conducted repeated measurements of pulse wave velocity at baseline, 6 months, and 12 months after adrenalectomy, grouped by KCNJ5 mutational status. Prognostic factors of arterial stiffness and risk for hypertension at 12 months after adrenalectomy were analyzed after propensity score matching in a 1:1 ratio. After matching for age, sex and body mass index, 88 patients were divided equally into KCNJ5-mutant and non-mutant groups. KCNJ5 mutational status was not an independent variable in either the generalized estimating equation model (p = 0.147) or the percentage change of brachial-ankle pulse wave velocity (p = 0.106). The generalized additive model smoothing plot showed that aldosterone-producing adenoma patients who carried the KCNJ5 mutation and were aged between 37 and 60 may have a hypertension recovery advantage. According to our observations during a 12-month follow-up after adrenalectomy, KCNJ5 mutational status was not associated with improvement in arterial stiffness.


Assuntos
Adenoma Adrenocortical/complicações , Adenoma Adrenocortical/genética , Pressão Sanguínea , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/fisiopatologia , Mutação , Rigidez Vascular , Adrenalectomia , Adenoma Adrenocortical/cirurgia , Análise Mutacional de DNA , Humanos , Hipertensão/etiologia , Hipertensão/fisiopatologia , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Pontuação de Propensão , Fatores de Risco
17.
Sci Rep ; 7: 39121, 2017 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-28102204

RESUMO

Constitutive activation of the Wnt pathway/ß-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of ß-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.


Assuntos
Hiperaldosteronismo/genética , Hiperaldosteronismo/patologia , Hipertensão/epidemiologia , Mutação , beta Catenina/genética , Adrenalectomia , Citocromo P-450 CYP11B2/análise , Citocromo P-450 CYP11B2/genética , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Expressão Gênica , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento
18.
Asian J Surg ; 40(3): 221-226, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-26626099

RESUMO

OBJECTIVE: Laparoendoscopic single-site (LESS) adrenalectomy is a promising minimally invasive technique, however, the current evidence has not confirmed its long-term effectiveness in primary aldosteronism (PA). We conducted a study to analyze the long-term efficacy of LESS adrenalectomy in patients with PA. METHODS: A total of 49 patients who had been clinically confirmed with PA who had an indication for unilateral adrenalectomy were included in this study. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. The median follow-up was 16.5 months. RESULTS: No intra- or early post-operative complication occurred. All LESS adrenalectomies were completed successfully, except one with laparoscopic conversion. Hypokalemia was resolved in all cases and no patient required potassium supplements after surgery. Post-operative cure of hypertension was achieved in 63% of our patients. Overall, 84% of our PA patients had clinical improvement in blood pressure control after surgery. CONCLUSIONS: Our long-term experience revealed that LESS adrenalectomy is a safe and effective approach, which demonstrated comparable long-term cure and improvement of hypertension to a conventional laparoscopic series in treating PA.


Assuntos
Adrenalectomia , Hiperaldosteronismo/cirurgia , Laparoscopia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
19.
Biomed Res Int ; 2016: 6894381, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27975056

RESUMO

Objective. To compare laparoendoscopic single-site (LESS) and conventional multiport adrenalectomy in patients with aldosterone-producing adenoma (APA). Material and Methods. We retrospectively reviewed patients who had been clinically confirmed with unilateral APA and who underwent LESS or multiport adrenalectomy between 2009 and 2014. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. Results. We identified 45 APA patients in the LESS group and 71 in the multiport group. The baseline characteristics were matched between two groups. All adrenalectomies were completed successfully, except one with laparoscopic conversion in the single-port group and one open conversion in the multiport group. After a mean follow-up around one year, there were no significant group differences in the improvement of hypertension, number of types of medication taken, and cure of hypokalemia after operation. Conclusions. Our study confirm that LESS adrenalectomy achieved similar clinical and functional outcomes as conventional multiport adrenalectomy for management of unilateral APA.


Assuntos
Adenoma/etiologia , Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/etiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Hiperaldosteronismo/complicações , Laparoscopia/métodos , Adenoma/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Estudos de Viabilidade , Feminino , Humanos , Hiperaldosteronismo/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Estudos Retrospectivos , Resultado do Tratamento
20.
Sci Rep ; 6: 32103, 2016 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-27586402

RESUMO

There exists a great knowledge gap in terms of long-term effects of various surgical and pharmacological treatments on outcomes among primary aldosteronism (PA) patients. Using a validated algorithm, we extracted longitudinal data for all PA patients diagnosed in 1997-2010 and treated in the Taiwan National Health Insurance. We identified 3362 PA patients for whom the mean length of follow-up was 5.75 years. PA has higher major cardiovascular events (MACE) than essential hypertension (23.3% vs 19.3%, p = 0.015). Results from the Cox model suggest a strong effect of adrenalectomy on lowering mortality (HR = 0.23 with residual hypertension and 0.21 with resolved hypertension). While the need for mineralocorticoid receptor antagonist (MRA) after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5 and 50 mg may alleviate risk of death in a U-shape pattern. A specificity test identified patients who has aldosterone producing adenoma (HR = 0.50, p = 0.005) also confirmed adrenalectomy attenuated all-cause mortality. Adrenalectomy decreases long-term all-cause mortality independently from PA cure from hypertension. Prescription corresponding to a DDD between 12.5 and 50 mg may decrease mortality for patients needing MRA. It calls for more attention on early diagnosis, early treatment and prescription of appropriate dosage of MRA for PA patients.


Assuntos
Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/mortalidade , Adrenalectomia , Adulto , Feminino , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Taiwan/epidemiologia , Resultado do Tratamento
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