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1.
Eur J Neurol ; 22(1): 142-9, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25142748

ABSTRACT

BACKGROUND AND PURPOSE: Earlier studies suggested an association between idiopathic restless legs syndrome (RLS) and cardiovascular diseases. However, the risk of cardiovascular events in patients with secondary RLS due to end-stage renal disease (ESRD) is unclear. Our aim was to examine whether ESRD patients with RLS had an increased risk of cardio/cerebrovascular events and mortality. METHODS: In all, 1093 ESRD patients were recruited between 2009 and 2010. The diagnosis and severity of RLS were assessed in a face-to-face interview. The occurrence of cardio/cerebrovascular events and death were confirmed by medical record review. The association between RLS and the outcomes of interest was examined using an adjusted multivariate Cox regression model. RESULTS: After a mean follow-up period of 3.7 ± 0.8 years, ESRD patients with RLS had a significantly higher risk of developing cardiovascular events and strokes [adjusted hazard ratio (aHR) 2.82, 95% confidence interval (CI) 2.02-4.11, and aHR 2.41, 95% CI 1.55-3.75, respectively] compared with patients without RLS. Increasing RLS severity was associated with an increasing likelihood of cardiovascular events [mild RLS severity, aHR 1.71 (95% CI 1.02-2.87); moderate, 2.79 (1.64-4.66); severe, 2.85 (1.99-4.46)] and strokes [mild, 1.89 (0.87-4.16); moderate, 2.42 (1.50-3.90); severe, 2.64 (1.49-4.91)] in a dose-dependent manner. RLS also increased the risk of total mortality in patients with ESRD [aHR 1.53 (95% CI 1.07-2.18), P = 0.02]; this association attenuated slightly after stratification by individual RLS severity category [mild RLS severity, aHR 1.44 (95% CI 0.78-2.67); moderate, 1.49 (0.98-2.55); severe, 2.03 (0.93-4.45)]. CONCLUSIONS: ESRD patients with RLS demonstrated an increased likelihood of cardio/cerebrovascular events and mortality.


Subject(s)
Cardiovascular Diseases/epidemiology , Kidney Failure, Chronic/epidemiology , Restless Legs Syndrome/epidemiology , Aged , Cardiovascular Diseases/mortality , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/mortality , Comorbidity , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Restless Legs Syndrome/etiology , Severity of Illness Index
2.
Eur J Neurol ; 21(3): 492-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24433515

ABSTRACT

BACKGROUND AND PURPOSE: Recent genome-wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients. METHODS: Sixteen RLS-related genetic variants at six loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259 subjects with and 734 subjects without RLS) were genotyped using TaqMan genotyping assays. Multivariate logistic regression analysis was used to test for associations between the genotypes and RLS in ESRD. Power calculations were completed using the CATs Genetic Power Calculator with settings of a multiplicative genetic model. RESULTS: A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03-2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97-3.11, P = 0.06). No associations between other genetic variants and risk and severity of RLS were observed in our ESRD cohort. CONCLUSIONS: The genetic variants of primary RLS candidate genes did not play a major role in our uremic RLS populations. The ethnic difference and heterogeneous etiologies underlying renal failure may partly explain the minor genetic contribution to uremic RLS in our populations. Further studies for other ethnicities will be of worth.


Subject(s)
Genetic Variation/genetics , Kidney Failure, Chronic/complications , Receptor-Like Protein Tyrosine Phosphatases, Class 2/genetics , Receptors, Progesterone/genetics , Restless Legs Syndrome/etiology , Restless Legs Syndrome/genetics , Aged , Apoptosis Regulatory Proteins , Chromosomes, Human, Pair 2/genetics , Female , Genetic Association Studies , Genotype , High Mobility Group Proteins , Humans , Kidney Failure, Chronic/genetics , Linkage Disequilibrium , Logistic Models , Male , Middle Aged , Retrospective Studies , Taiwan/epidemiology , Trans-Activators
3.
Eur J Neurol ; 20(7): 1025-31, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23369046

ABSTRACT

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end-stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently reported to associate with RLS. We aim to perform a large-scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world. METHODS: From October 2009 to October 2011, we constitutively recruited 1130 patients with ESRD from 17 hemodialysis centers. Demographic, laboratory data, presence and severity of RLS were collected. Odds ratios (ORs) were estimated by logistic regression models. RESULTS: We found the prevalence of RLS to be 25.3% in patients with ESRD. Having type 2 diabetes [OR = 3.61 (2.27-5.77), P < 0.01], low serum transferrin saturation [OR = 1.42 (1.01-2.03), P < 0.05] and duration of dialysis [OR = 1.09 (1.03-1.14), P < 0.01] were associated with RLS. In contrast, high serum hemoglobin level was inversely associated with RLS [OR = 0.61 (0.40-0.89), P < 0.05]. RLS has a significant impact on sleep quality in dialysis patients. Among patients with RLS, history of type 2 diabetes [OR = 4.04 (1.65-10.79), P < 0.05], low serum hemoglobin level [OR = 5.41 (2.43-13.12), P < 0.01] and duration of dialysis [OR = 1.01 (1.01-1.02), P < 0.01] were associated with increased severity of RLS. CONCLUSIONS: Our findings demonstrated that RLS is common in Taiwanese dialysis patients. Clinicians should have a high suspicion for the presence of RLS symptoms in patients with ESRD, especially those with type 2 diabetes, anemia, low serum iron status and long duration of dialysis.


Subject(s)
Kidney Failure, Chronic/epidemiology , Restless Legs Syndrome/epidemiology , Female , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged , Prevalence , Renal Dialysis/statistics & numerical data , Restless Legs Syndrome/complications , Risk Factors , Taiwan/epidemiology
4.
Intern Med J ; 40(1): 30-6, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20561363

ABSTRACT

BACKGROUND: Proteinuria reflects disrupted renal function in which enhanced immuno-inflammation activity plays a key role. So far, information concerning the relations between proteinuria and peripheral different leucocyte counts is limited. We thereby conducted this study aiming to obtain comprehensive information of the issue. METHODS: Study subjects were participants of a health check programme from 2000 to 2002. Additional two enrolment criteria were (i) leucocyte analysis was checked with a same blood cell counter and (ii) urinalysis showed no pyuria or haematuria. Data of subjects were retrospectively collected and analysed by using sas program. RESULTS: Higher neutrophil and monocyte counts, but not lymphocyte count, were significantly associated with both the presence and the severity of proteinuria (all P < 0.0001, n= 12 225). Such associations maintained significant after adjustments of age, sex, body mass index, mean blood pressure and blood levels of glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides and creatinine (all P< or = 0.001, n= 12 225). There was a sharp increase in the incidence of proteinuria in association with a neutrophil count > or =4.50 x 10(9)/L (P< or = 0.0001). CONCLUSION: Our study showed that in apparently normal adults the presence and the severity of proteinuria could be reflected by the peripheral neutrophil and monocyte counts, but not the lymphocyte count. These findings, together with the documented inflammatory basis of proteinuria and the diverse pathophysiological roles of differential leucocytes, suggest that peripheral differential leucocyte counting may be useful in predicting the course of an existing proteinuria. Perspective longitudinal follow-up studies are needed to test this presumption.


Subject(s)
Monocytes/cytology , Neutrophils/cytology , Proteinuria/blood , Proteinuria/pathology , Severity of Illness Index , Adult , Female , Humans , Leukocyte Count/methods , Male , Monocytes/metabolism , Neutrophils/metabolism , Retrospective Studies
5.
Clin Nephrol ; 71(1): 96-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19203559

ABSTRACT

Gram-negative pathogen-induced continuous ambulatory peritoneal dialysis- (CAPD) related peritonitis is increasing, especially that caused by enteric pathogens. We describe a 54-year-old Taiwanese man with a case of Campylobacter jejuni-mediated CAPD-related peritonitis and bacteremia. Positive Campylobacter jejuni dialysate and blood cultures confirmed the diagnosis of CAPD-mediated systemic infection. We initially administered intraperitoneal ceftazidime, amikacin and oral azithromycin, but the patient did not recover. We then administered i.v. ciprofloxacin and replaced the hemodialysis (HD). The patient recovered and was discharged with maintenance HD. Treatment of Campylobacter jejuni-mediated CAPD peritonitis is a challenge in areas with high antibiotic resistance.


Subject(s)
Bacteremia/etiology , Campylobacter Infections/etiology , Campylobacter jejuni , Kidney Failure, Chronic/therapy , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Peritonitis/etiology , Bacteremia/diagnosis , Bacteremia/therapy , Campylobacter Infections/diagnosis , Campylobacter Infections/therapy , Humans , Male , Middle Aged , Peritonitis/diagnosis , Peritonitis/therapy , Taiwan
6.
Clin Nephrol ; 71(4): 451-3, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19356381

ABSTRACT

Total or near-total rupture of the pectoralis major muscle is rare. It has mainly occurred in male patients between 20 - 40 years of age while performing weight-lifting. Major tendon rupture is a rare but well-documented complication of long-term dialysis. However, rupture of pectoralis major in dialysis patients had never been reported before. Here, we present a pectoralis major rupture in an elderly patient receiving maintenance hemodialysis. Both old age and long-term dialysis could be risk factors of rupture. The clinicians should pay more attention to this complication when taking care of elderly patients on hemodialysis.


Subject(s)
Pectoralis Muscles/injuries , Renal Dialysis/adverse effects , Renal Dialysis/instrumentation , Aged, 80 and over , Female , Humans , Pectoralis Muscles/diagnostic imaging , Rupture , Tomography, X-Ray Computed
7.
QJM ; 101(1): 13-22, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18203722

ABSTRACT

BACKGROUND: Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. AIM: To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. DESIGN: Retrospective record review. METHODS: From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. RESULTS: Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. DISCUSSION: Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.


Subject(s)
Adenoma/metabolism , Adrenal Cortex Neoplasms/metabolism , Adrenal Glands/pathology , Aldosterone/biosynthesis , Adenoma/diagnostic imaging , Adenoma/pathology , Adrenal Cortex Neoplasms/diagnostic imaging , Adrenal Cortex Neoplasms/pathology , Adrenal Glands/metabolism , Adult , Aged , Case-Control Studies , Female , Humans , Hyperaldosteronism/metabolism , Hyperaldosteronism/pathology , Hyperplasia/metabolism , Hyperplasia/pathology , Male , Middle Aged , Radiography , Retrospective Studies
8.
Clin Nephrol ; 70(3): 233-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18793565

ABSTRACT

BACKGROUND: Dyslipidemia and residual renal function (RRF) have a significant impact on the cardiovascular mortality in dialysis patients, but their association in patients on chronic peritoneal dialysis (PD) has not been completely studied. METHODS: 170 PD patients were divided into 2 groups based on the RRF (Group I had no RRF and Group II had RRF >0 ml/min/1.73 m2 BSA). An observational, longitudinal study was performed to elucidate the dyslipidemic state in PD patients with different levels of RRF and the association of dyslipidemia and deterioration of RRF during 3 years. RESULTS: Patients' basic characteristics and lipid profiles at the initiation of study were similar between the groups. At the end of study, Group I patients had a lower T-CHO (p=0.001), LDL-C (p=0.018), HDL-C (p=0.05) and non-HDL-C (p=0.003) than Group II. There was a significant correlation between a change in HDL-C and the decline of RRF (r=0.177, p=0.048) and it was independent of PD duration and levels of highly sensitive C-reactive protein (r=0.233, p=0.04). CONCLUSION: Our results clearly demonstrate the different longitudinal changes of lipid profiles in PD patients with different RRF and an association between decline of HDL-C and deterioration of RRF.


Subject(s)
Dyslipidemias/complications , Kidney Failure, Chronic/physiopathology , Kidney/physiopathology , Peritoneal Dialysis , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dyslipidemias/blood , Female , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , Triglycerides/blood
9.
Int J Clin Pract ; 62(9): 1441-6, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18564200

ABSTRACT

BACKGROUND: Subjects with the metabolic syndrome are accompanied by insulin resistance (IR). However, it is not clear how well the newly defined metabolic syndrome identifies IR specifically in hypertensive subjects. AIMS: The purpose of the study was to evaluate the performance of the metabolic syndrome, defined by the American Heart Association (AHA) and the International Diabetes Federation (IDF) definitions, in identifying IR in hypertension. METHODS: The analysis is a cross-sectional study. Totally, 228 hypertensive patients and 92 non-diabetic normotensive controls who received insulin suppressive tests for direct evaluation of their insulin sensitivity were included from the Stanford Asia and Pacific Program for Hypertension and IR. McNemar's tests were used to compare sensitivity and specificity of the AHA-defined with the IDF-defined metabolic syndrome in diagnosis of IR. RESULTS: The sensitivity of the metabolic syndrome for IR in hypertension was 89.7% and the specificity 45.9% by the AHA definition. Using the IDF definition, the sensitivity was 77.6%, and the specificity increased to 63.5%. The diagnostic power of individual components of the syndrome was also modest. The predictive discrimination of wider waist circumference was similar to that of the AHA-defined metabolic syndrome. CONCLUSIONS: Use of the metabolic syndrome by the AHA definition provided good sensitivity, but low specificity to diagnose IR in hypertension. The IDF definition improved in false-positive rate, but it was still not specific enough to identify IR in hypertension.


Subject(s)
Hypertension/complications , Insulin Resistance/physiology , Metabolic Syndrome/diagnosis , Adult , Case-Control Studies , Cross-Sectional Studies , False Positive Reactions , Female , Humans , Male , Metabolic Syndrome/complications , Middle Aged , Sensitivity and Specificity , Waist Circumference
10.
Article in Zh | MEDLINE | ID: mdl-29798423

ABSTRACT

An aged female complained intermittent hoarse 10 years, without swallowing and breathing difficulties. A month ago, this patient's voice hoarse became worse, she also had sore throat and pharyngeal foreign body sensation at the same time. There are visible lesions on the right side of the vocal cords, anterior commissure and on the left side of the ventricular bands. Laryngeal CT: the right side of the vocal cords has increased thickness, and hyper density with mild enhancement.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Laryngeal Neoplasms/diagnosis , Aged, 80 and over , Carcinoma, Squamous Cell/complications , Female , Hoarseness/etiology , Humans , Laryngeal Neoplasms/complications , Larynx , Vocal Cords/pathology
11.
Clin Nephrol ; 66(4): 291-6, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17063997

ABSTRACT

Spontaneous renal or peri-renal bleeding or so-called Wunderlich's syndrome is a rare but potentially life-threatening condition. Most reported cases are Caucasian and caused by ruptured renal tumors, either benign or malignant. The syndrome has never been documented in Orientals with underlying autoimmune diseases. We report 3 cases of spontaneous renal bleeding with concurrent systemic lupus erythematosus and vasculitis presenting with flank or abdominal pain, anemia, leukocytosis, and a high C-reactive protein. All were diagnosed by computerized tomography, magnetic resonance imaging or angiography, and treated successfully with glucocorticoids and cytotoxic agents without surgical intervention.


Subject(s)
Vasculitis/complications , Vasculitis/therapy , Adult , Aged , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/complications , Female , Hemorrhage/complications , Hemorrhage/therapy , Humans , Kidney Diseases/complications , Kidney Diseases/diagnostic imaging , Kidney Diseases/therapy , Lupus Erythematosus, Systemic/complications , Middle Aged , Radiography , Renal Artery/diagnostic imaging , Syndrome
12.
Electromyogr Clin Neurophysiol ; 45(3): 139-44, 2005.
Article in English | MEDLINE | ID: mdl-15981684

ABSTRACT

Carpal Tunnel Syndrome (CTS) is easily the most common focal peripheral nerve compression. The primary diagnostic tool is electrodiagnosis, although 13-27% of patients with symptoms and signs of CTS have normal electrodiagnostic results. The goal of this study was to create a more sensitive and specific latency difference criteria without any additional testing beyond the minimum. Statistical theory indicates that this would occur by comparing the latency most sensitive to CTS to the least sensitive latency. Data was evaluated from 68 normal hands, 23 hands of patients with symptoms and signs of CTS but normal standard results, and 88 hands of patients with CTS symptoms and signs of CTS with the diagnosis confirmed with standard criteria. The Median Sensory latency was the most sensitive parameter, while the Ulnar Motor Latency varied least in the presence of CTS, making the (Median Sensory-Ulnar Motor) latency difference the criteria of choice. Setting a cutoff value of 0.8 msecs for this difference correctly classified all normals, and all hands with CTS by standard criteria, and classified as abnormal 19/23 (82%) of hands with symptoms and signs of CTS but negative results by standard criteria. Overall the (Median Sensory-Ulnar Motor) Latency difference is a simple, easy, sensitive and specific test for CTS.


Subject(s)
Carpal Tunnel Syndrome/diagnosis , Electrodiagnosis/methods , Median Nerve/physiopathology , Neural Conduction/physiology , Reaction Time/physiology , Ulnar Nerve/physiopathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
13.
J Clin Endocrinol Metab ; 80(3): 783-9, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7883831

ABSTRACT

The different responses of plasma aldosterone to ACTH and angiotensin II in aldosterone-producing adenoma (APA) is thought to be due to the various cellular compositions of the tumors. To investigate whether the dopaminergic regulation of aldosterone in APA is also dependent on the cellular types, we studied the effects of metoclopramide on plasma aldosterone in six patients with APA. The messenger RNA (mRNA) levels of aldosterone synthase (P450aldo), 11 beta-hydroxylase (P450(11) beta), and 17 alpha-hydroxylase (P450(17) alpha) of APA and normal adrenal glands were determined by competitive polymerase chain reaction. After administration of metoclopramide (an antagonist of dopamine-2 receptor), the increment of plasma aldosterone correlated inversely with the percentage of zona fasciculata cells of APA. The mRNA level of P450aldo in the tumorous portion was much higher, whereas the levels of P450(11) beta and P450(17) alpha mRNAs were lower, than those of the nontumorous portion and normal adrenals. There was a correlation of the percentage of zona fasciculata cells in APA with the levels of P450aldo and P450(11) beta mRNAs, but not with P450(17) alpha mRNA. These results suggest that differential responsiveness of plasma aldosterone to metoclopramide may be due to various proportions of different cell types in APA that may have different expression of dopamine-2 receptor. In addition, this histologically dependent expression was present at the transcriptional level of the gene responsible for aldosterone biosynthesis.


Subject(s)
Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Aldosterone/blood , Cytochrome P-450 Enzyme System/genetics , Metoclopramide/pharmacology , RNA, Messenger/analysis , Steroid 11-beta-Hydroxylase/genetics , Zona Fasciculata/pathology , Adenoma/pathology , Adrenal Gland Neoplasms/pathology , Aldosterone/biosynthesis , Base Sequence , Cytochrome P-450 CYP11B2 , Female , Humans , Male , Molecular Sequence Data
14.
J Clin Endocrinol Metab ; 86(9): 4460-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11549694

ABSTRACT

Aldosterone secretion is evidently regulated by a dopaminergic inhibitory mechanism. Pharmacological characterization and autoradiographic studies revealed D2-like receptors in the adrenal cortex, especially in the zona glomerulosa. However, the subtype of the dopamine receptors involving this regulation has not been elucidated. To investigate which subtype of receptors expresses in the adrenal cortex, we examined the messages of D2-like receptors, D2, D3, and D4, by RT-PCR and in situ hybridization of adrenal glands and adrenal neoplasm. Both D2 and D4 receptors were expressed in normal adrenal glands, pheochromocytoma, and aldosterone-producing adenoma. However, the D2 receptors were not universally expressed, in contrast with the D4 receptors that were detected in all cases of aldosterone-producing adenoma and adrenal remnant. No D3 receptor message was detected by RT-PCR in any adrenal sample. Both D2 and D4 receptors were expressed in significant amounts in the adrenal medulla and pheochromocytoma. In the adrenal cortex, the expression of the D2 receptors was in the zona glomerulosa and zona reticularis, with no different signal intensities between the two zones. D4 receptors were mainly localized in the zona glomerulosa and, to a lesser extent, in the zona reticularis. Both receptors were expressed at low levels in the zona fasciculata. In aldosterone-producing adenoma, the expression of D2 and D4 was especially found in nonzona fasciculata-like cells. To elucidate which dopamine receptor regulates aldosterone secretion, the effects of specific D2 and D4 antagonists, raclopride and clozapine, respectively, were examined in cultured NCI-H295 cells. Dopamine further increased angiotensin II-induced aldosterone secretion by 20%. In the presence of 1 microM dopamine and angiotensin II, 10(-5)-10(-7) M clozapine decreased aldosterone levels by 40-55%. The decrease in aldosterone secretion by clozapine was completely reversed when raclopride was added simultaneously. These data suggest that dopamine exerts dual effects on aldosterone secretion in NCI-H295 cells. Activation of D4 receptors can increase aldosterone secretion, whereas an inhibitory effect is mediated via D2 receptors. In summary, we demonstrated the existence of both D2 and D4 receptors in the human adrenal gland and adrenal neoplasm. Both receptors play significant roles in the modulation of aldosterone secretion, but in opposite directions.


Subject(s)
Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Adrenal Glands/metabolism , Aldosterone/biosynthesis , Pheochromocytoma/metabolism , RNA, Messenger/biosynthesis , Receptors, Dopamine D2/biosynthesis , Adrenal Cortex/metabolism , Blotting, Southern , Humans , In Situ Hybridization , Poly A/biosynthesis , Protein Biosynthesis , RNA Probes , Receptors, Dopamine D4 , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
15.
Am J Kidney Dis ; 38(6): 1185-90, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11728949

ABSTRACT

Platelet glycoprotein receptors play a role in the pathogenesis of chronic diabetic complications. Genetic polymorphisms of the alpha2beta1 integrin and glycoprotein IIIa (GPIIIa) have been associated with myocardial infarction, stroke, and diabetic retinopathy. To identify risk factors for their development in a cohort of patients with type 2 diabetes, we evaluated clinical variables and genetic polymorphisms in the alpha2beta1 integrin and GPIIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 patients with and 108 patients without diabetic nephropathy), as well as 217 nondiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, body mass index (BMI), and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), total cholesterol, and triglyceride levels. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. No difference in the Bgl II polymorphism of the alpha2beta1 integrin gene was found between patients with type 2 diabetes with or without nephropathy (11 [8.7%], 47 [37.3%], and 68 patients [54.0%] versus 10 [9.3%], 32 [29.6%], and 66 patients [61.1%] for Bgl II+/+, Bgl II+/-, and Bgl II-/-, respectively; P = 0.271). Multiple logistic regression analyses showed that duration of diabetes, BMI, hypertension, and poor glycemic control were four independent predictors for the development of diabetic nephropathy. No contribution of the Bgl II+ allele of the alpha2beta1 integrin was found for the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.655 to 2.418; P = 0.490). The Pl(A2) allele genotype was not found among our studied subjects. In conclusion, age, duration of diabetes, BMI, and HbA(1c) level are strong predictors for nephropathy in patients with type 2 diabetes. However, the Bgl II polymorphism of the alpha2beta1 integrin gene and the Apa I polymorphism of the platelet GPIIIa gene do not have a major role in the development of diabetic nephropathy in our population.


Subject(s)
Blood Platelets/metabolism , Collagen/genetics , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/physiopathology , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Collagen Type I , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Polymorphism, Genetic
16.
Mol Cell Endocrinol ; 111(2): 139-46, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7556875

ABSTRACT

There exist conflicting data regarding the inhibitory effect of atrial natriuretic peptide on aldosterone production from aldosterone-producing adenoma (APA). Natriuretic peptides mediate their actions through natriuretic peptide receptors (NPRs). Whether or not NPRs are present in the tumors remains controversial. To elucidate this paradox, gene expression of NPRs was examined by Northern blot analysis and competitive polymerase chain reaction in tumorous and non-tumorous portions of APA, and in normal adrenal gland from patients with renal cell carcinoma. The results of Northern blot analysis showed the presence of messenger ribonucleic acid (mRNA) of three NPRs in all adrenal tissues, including APA. The proportional expression of NPR gene transcripts in APA was type A (0.6%), type B (18.7%), and type C (80.7%). The levels, but not the proportions, of type C and possibly type B NPR mRNAs were lower in tumorous and non-tumorous portions of APA compared to those in normal adrenal gland (type C 190.2 +/- 24.5 [means +/- SEM, normal adrenal gland] > 168.1 +/- 20.8 [non-tumorous portion] > 112.2 +/- 15.5 [tumorous portion] pg/10 micrograms total RNA, F = 3.82, P < 0.05; type B 45.2 +/- 8.5 [normal adrenal gland] > 30.0 +/- 5.2 [non-tumorous portion] > 25.1 +/- 4.1 [tumorous portion] pg/10 micrograms total RNA, F = 3.03, P = 0.065). The mRNA levels of type C, rather than type A or type B, NPR were correlated with the percentage of zona fasciculata-like cells in APA (r = 0.90, P < 0.05). In conclusion we have demonstrated the presence of mRNA encoding the three NPRs in APA.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Aldosterone/biosynthesis , RNA, Messenger/analysis , Receptors, Atrial Natriuretic Factor/genetics , Adenoma/pathology , Adrenal Gland Neoplasms/pathology , Aldosterone/blood , Base Sequence , Binding, Competitive , Blotting, Northern , Molecular Sequence Data , Polymerase Chain Reaction
17.
Mol Cell Endocrinol ; 152(1-2): 47-55, 1999 Jun 25.
Article in English | MEDLINE | ID: mdl-10432222

ABSTRACT

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.


Subject(s)
Adenoma/metabolism , Adrenal Gland Neoplasms/metabolism , Aldosterone/metabolism , Angiotensin II/pharmacology , Receptors, Angiotensin/biosynthesis , Angiotensin II/metabolism , Humans , Hyperandrogenism/metabolism , In Situ Hybridization , Polymerase Chain Reaction , RNA, Messenger/analysis
18.
Am J Hypertens ; 13(6 Pt 1): 704-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10912757

ABSTRACT

Recent studies have found the tryptophan allele of a glycine to tryptophan polymorphism at position 460 (G460W) of the alpha-adducin protein to be associated with essential hypertension in European populations. We examined whether the tryptophan allele is associated with hypertension in a different population, comprised of subjects of Chinese origin from Taiwan, and Chinese and Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5' allelic discrimination assay or TaqMan to type individuals for the G460W polymorphism, and using this method we typed more than 1000 individuals. The frequency of the W allele was slightly increased in the treated subjects in the Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v 0.558). We considered dominant, recessive, and additive models in our analysis. There was a significant result for a recessive model for systolic blood pressure in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese population, there was no evidence for a positive association under any model. For the combined Chinese and Japanese samples, the evidence for association with alpha-adducin was not significant.


Subject(s)
Asian People , Asian , Blood Pressure/physiology , Calmodulin-Binding Proteins/genetics , Cytoskeletal Proteins/genetics , Hypertension/genetics , Adult , Alleles , Asian/genetics , Asian People/genetics , Calmodulin-Binding Proteins/metabolism , Cytoskeletal Proteins/metabolism , DNA/analysis , DNA Primers/chemistry , Gene Frequency , Genotype , Glycine/genetics , Hawaii/ethnology , Humans , Hypertension/ethnology , Hypertension/metabolism , Hypertension/physiopathology , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , San Francisco/ethnology , Taiwan/ethnology , Tryptophan/genetics
19.
Spine (Phila Pa 1976) ; 23(7): 828-33, 1998 Apr 01.
Article in English | MEDLINE | ID: mdl-9563115

ABSTRACT

STUDY DESIGN: A prospective evaluation of the incidence of low back pain in college athletes was undertaken. OBJECTIVES: To evaluate prospectively leg length discrepancy, hip flexor tightness, and lower extremity acquired laxity or overuse as predictive factors for low back pain in college athletes. SUMMARY OF BACKGROUND DATA: A pilot study found an association between low back pain and the factors to be studied. Several allusions to the kinetic chain theory appear in the literature, but little prospective research has been done in examining the effects of lower extremity involvement on the back. METHODS: Two-hundred fifty-seven college athletes representing nine varsity sports were screened during a preseason sports physical examination. Measures of flexibility, ligamentous stability, leg length discrepancy, and overuse syndromes were recorded. Athletes were observed throughout the ensuing year for low back pain requiring treatment by the athletic trainer. Those athletes with low back pain as the result of direct trauma to the region were excluded from the data. RESULTS: Twenty-four athletes (9.3%) received treatment for low back pain. Thirteen of 87 women (15%) compared with 11 of 170 men (6%) required treatment for low back pain (P = 0.048). Of 57 athletes with lower extremity acquired laxity or overuse, low back pain developed in 14 (P < 0.001). CONCLUSIONS: Athletes with lower extremity acquired ligamentous laxity or overuse may be at risk for the development of noncontact low back pain during athletic competition. Female athletes with lower extremity involvement appeared to have a higher incidence of low back pain treatment compared with their male counterparts. Inflexibility of the lower extremities or leg length discrepancy were not associated with future low back pain treatment.


Subject(s)
Ligaments/injuries , Ligaments/physiopathology , Low Back Pain/epidemiology , Sports , Adult , Ankle Joint/physiology , Female , Hip Joint/physiology , Humans , Knee Joint/physiology , Male , Predictive Value of Tests , Prospective Studies
20.
Perit Dial Int ; 21(2): 143-7, 2001.
Article in English | MEDLINE | ID: mdl-11330557

ABSTRACT

OBJECTIVE: Systemic lupus erythematosus (SLE) is the most common secondary glomerulonephritis resulting in end-stage renal disease (ESRD) among young adults in Taiwan. Studies of the infectious complications and outcomes among such SLE patients undergoing peritoneal dialysis (PD) are limited. DESIGN: A retrospective age- and gender-matched case control study. SETTING: A university teaching hospital. PATIENTS: There were 23 SLE patients with ESRD receiving PD for more than 3 months during the past 15 years. Another 46 age- and gender-matched non-SLE nondiabetic patients receiving PD were selected as the control group in this study. INTERVENTION: All patients underwent PD as renal replacement therapy and were regularly followed up at this hospital. MAIN OUTCOME MEASURES: Technique survival and incidences of exit-site infection (ESI) and peritonitis in these patients. RESULTS: The SLE patients had a lower predialysis serum albumin than the control group (3.16 +/- 0.50 g/dL vs 3.52 +/- 0.50 g/dL, p < 0.01). The incidences of exit-site infection (ESI) and peritonitis were higher for SLE patients than for control patients (p < 0.01 and p < 0.001, respectively). Kaplan-Meier survival analysis indicated that SLE patients had shorter time intervals to first infectious complications, and poorer technique survival. Infection was the major cause of dropout and mortality in the SLE patients. The SLE patients had a reduced chance of receiving a renal transplant. The use of steroids by SLE patients was associated with a higher incidence of peritonitis (p = 0.04), but association with ESI was insignificant. In a Cox regression model, the underlying SLE was the only risk factor for technique failure and time interval to first infectious complication. CONCLUSION: SLE patients undergoing PD are more susceptible to infection than age- and gender-matched non-SLE nondiabetic patients and have poorer technique survival. Systemic lupus erythematosus itself may further compromise the immunity of uremic patients.


Subject(s)
Infections/etiology , Kidney Failure, Chronic/therapy , Lupus Nephritis/therapy , Peritoneal Dialysis/adverse effects , Peritonitis/etiology , Adult , Catheters, Indwelling/adverse effects , Female , Humans , Infections/microbiology , Lupus Nephritis/mortality , Male , Peritonitis/microbiology , Retrospective Studies , Survival Rate , Treatment Outcome
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