A 15-year-long Southern blotting analysis of FMR1 to detect female carriers and for prenatal diagnosis of fragile X syndrome in Taiwan.

Here, we review the results of Southern blotting analyses of the FMR1 gene performed in our reference laboratory in Taiwan over a 15-year period. In total, 725 high-risk women with a family history of fragile X syndrome (FXS) or idiopathic intellectual disability, 3911 low-risk pregnant women without such family history, and prenatal diagnosis data for 32 foetuses from 24 carrier mothers were included. Only 2 carriers were in the low-risk group, which indicated a prevalence of 1 of 1955 women (95% confidence interval: 1/7156-1/539). A total of 100 carriers were found to be in the high-risk group, thus revealing a significantly higher frequency than the low-risk group (100/725 vs 2/3911, P<0.0001). Eight of the 14 foetuses that inherited the maternal mutant allele were verified to have a full mutation, with the smallest maternal pre-mutation allele carrying 56 CGG repeats. The overall findings confirmed that the carrier prevalence among low-risk women in Taiwan is significantly lower than that reported in western countries. Therefore, the most important step for preventing FXS in Taiwan would be to focus on high-risk women by promoting general awareness of this disease and spreading knowledge regarding the benefits of carrier screening and prenatal testing.

Associations between genetic variants and the severity of metabolic syndrome in subjects with type 2 diabetes.

Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features of MetS. The etiology of MetS is complex, involving both environmental and genetic factors. In this study, we examined the role of specific candidate genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D subjects aged 35-64 years were recruited. Waist circumstance, plasma triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure were measured to define MetS. Subjects were divided into 4 groups according to MetS components. Target genes involved in fibrotic and inflammatory processes, insulin and diabetes, cell growth and proliferation, and hypertension were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms (SNPs) were analyzed to evaluate their genetic association with MetS severity in T2D subjects. Univariate ordinal logistic regression using a dominant model (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP markers within 4 genes with genotypes associated with MetS risk. For the SNP genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R), and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the reference group. In addition, the CC genotype was comparable to the TT genotype for rs3777411. There was no gender-specific effect. In conclusion, our results suggest that among the Han Chinese population, several SNPs increase the risk of severe MetS in T2D subjects. Further study in a large population should be conducted.

Kidney-targeting Smad7 gene transfer inhibits renal TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice.

AIMS/HYPOTHESIS: The TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes. METHODS: We delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF-ß/SMAD2/3-mediated fibrosis and NF-κB-dependent inflammation were evaluated. RESULTS: In this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-ß/SMAD and NF-κB signalling pathways in the kidney. CONCLUSIONS/INTERPRETATION: Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-ß/SMAD and NF-κB signalling pathways.

Combined effect of C-reactive protein gene SNP +2147 A/G and interleukin-6 receptor gene SNP rs2229238 C/T on anthropometric characteristics among school children in Taiwan.

OBJECTIVE: The purpose of this study was to explore the combined effect of the C-reactive protein (CRP) +2147 A/G (rs1205) and interleukin (IL)-6R rs2229238 C/T single-nucleotide polymorphisms (SNPs) on the anthropometric variables of school children in Taiwan. SUBJECTS AND DESIGN: Cross-sectional analyses were performed using the data from the Taipei Children Heart Study-II. After multi-stage sampling, we selected 430 boys and 463 girls with an average age of 13.1 years. We genotyped these individuals for the CRP +2147 A/G and IL-6R rs2229238 C/T SNPs using a TaqMan 5' nuclease assay. Anthropometric characteristics, which included body height, body weight (BW), body mass index (BMI), waist circumference (WC), hip circumference (HC), body fat percentage (BF), and waist circumference to height ratio (WHtR), were measured/calculated. RESULTS: When considering the CRP +2147 A/G polymorphism, GG genotype boys were heavier and had larger BMI, WC, HC, BF and WHtR than A allele carriers. The odds ratio (OR) of larger WHtR in GG genotype boys was 2.14 (95% CI: 1.09-4.21). For the IL-6R rs2229238 C/T polymorphism, T allele carrier girls had larger WC and WHtR than those carrying the CC genotype. The OR of a larger HC for T allele carrier boys was 2.33 (95% CI: 1.16-4.68). Boys with the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T had higher OR for BW, BMI, WC, HC, BF and WHtR than boys who were carriers of the A allele of CRP +2147 A/G and had the CC genotype of IL-6R rs2229238 C/T (OR range=3.86-8.04, all P<0.05). CONCLUSION: Boys who carry the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T have a greater risk of having abnormal BW, BMI, WC, HC, BF and WHtR and of developing obesity than individuals who do not have these genotypes.

Association between retinoid-X receptor-gamma genetic polymorphisms and diabetic retinopathy.

Retinoid-X receptor (RXR) is one of the members of the nuclear hormone receptor superfamily. It forms heterodimers with many nuclear receptors, such as the peroxisome proliferative-activated receptor, which has been proposed to be involved in diabetic complications, including retinopathy. A recent study revealed that RXR-alpha has antioxidant properties and is associated with diabetic retinopathy. We found that the RXR-gamma gene is involved in the pathogenesis of diabetic nephropathy. We also hypothesized that the RXR-gamma gene has a role in the development of diabetic retinopathy. We examined 213 diabetic patients, who were divided into retinopathy or no retinopathy groups. Nine selected single nucleotide polymorphisms (SNPs) in the RXR-gamma gene were evaluated. The diabetic retinopathy group had longer diabetes duration, higher body mass indexes, and higher systolic blood pressure, as well as higher concentrations of fasting plasma glucose, blood urine nitrogen, and creatine. One SNP--rs3818569 of the RXR-gamma gene was found to be associated with increased risk for diabetic retinopathy in both allele and genotype frequencies (P = 0.0023 and 0.0057, respectively). Analysis with multivariate logistic regression revealed that the dominant RXR-gamma GG genotype is a risk factors for the development of diabetic retinopathy (odds ratio = 2.388; 95% confidence interval = 1.17-4.875). We conclude that the RXR-gamma rs3818569 SNP is associated with diabetic retinopathy development in the Taiwanese population.

Polarity-variable birefringence on hyperlens structure.

A variable birefringence effect has been observed with 1D PMMA surface gratings on a gold film substrate. By changing the operation wavelength on the Au film, the birefringence value Δn(eff) changes from positive to negative. The result verified that this uniaxial crystal-like plasmonic surface gratings showed good superlensing effect at 515 nm when PMMA width:Air width=1:1 where the absolute value of Δn(eff) is relatively large.

Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report.

We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.

Surrogate estimates of insulin sensitivity in subjects with hypertension.

The purpose of the study is to compare surrogate estimates of insulin sensitivity with a directly measured insulin sensitivity index, steady-state plasma glucose (SSPG) from insulin suppression test (IST), in subjects with hypertension. Two hundred and twenty-eight hypertensive patients who received IST for SSPG were included for analysis. Estimates from fasting measurements alone, homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)), and indices from fasting and/or 2 h samples (ISI(0,120) and ISI(TX)) were calculated. In addition to Pearson and partial correlations, variance-component models were used to test the relationship between surrogate estimates of insulin sensitivity and SSPG. A large proportion of variance owing to covariates in the variance-component models indicated the goodness of model fit, irrespective of the independence among variables. SSPG was positively correlated with logarithmic transformation (Log) (HOMA-IR) and negatively correlated with QUICKI, Log (ISI(0,120)) and ISI(TX) (all P<0.0001). Log (ISI(0,120)) seemed to have a better correlation with SSPG (r=-0.72) than other measures in partial correlation. The proportion of variance owing to all covariates of Log (ISI(0,120)) and ISI(TX) were larger than those of Log (HOMA-IR) and QUICKI in the variance-component models. After adjustments for demographic and obesity covariates, the proportion of variance explained by Log (ISI(0,120)) were largest among the surrogate measures in the variance-component models. Our results showed that ISI(0,120) and ISI(TX) correlated better with SSPG than those used fasting measures alone (HOMA-IR and QUICKI). Log (ISI(0,120)) currently showing the strongest association with SSPG than other estimates is adaptable for use in large studies of hypertension.

The Role of Uric Acid for Predicting Future Metabolic Syndrome and Type 2 Diabetes in Older People.

OBJECTIVE: Although it is known that high uric acid (UA) level is associated with type 2 diabetes (T2DM) and metabolic syndrome (MetS), most of the previous studies were focused on adults. Since aging becomes a major problem for many societies, in this longitudinal study, we investigated the role of UA in future T2DM and MetS in a large cohort of people who were older than 65 years. DESIGN: A cross-sectional and longitudinal study. SETTING/PARTICIPANTS: 18,907 elderly (9,732 men, 9,175 women) aged above 65 years, enrolled from health check-up centers, were classified into three subgroups by 10-year intervals (young old 65-74 years, YO; old old 75-84 years, OO; and oldest old 85-94 years, ODO), with the average follow-up period of 4.3 years. MEASUREMENTS: The optimal cut-off values (CoVs) of baseline UA to predict future MetS and T2DM were determined by receiving operating characteristic (ROC) curve analysis. Using these CoVs of UA, the participants were divided into normal- and high-level groups of UA. Cox proportional hazard analysis was used to calculate hazard ratios (HRs) for the subjects with a high level of UA for the risk of future MetS and T2DM. In addition, Kaplan-Meier plots and log rank test were used to evaluate the time effect on the incidence of developing MetS and T2DM between the two groups. RESULTS: In ROC curve analysis, the optimal CoVs of baseline UA were 6.0, 6.3 and 6.7 mg/dl in YO, OO, and ODO men, respectively; 5.5 and 4.9 mg/dl in YO and OO women, respectively (all p < 0.05). However, the CoVs of UA in ODO women (6.1 mg/dl) failed to show its discriminant power (p = 0.13). The Cox regression analysis showed the YO subjects with a higher baseline level of UA had a higher risk of developing MetS (HRs 1.56 and 1.58 for men and women, respectively, both p < 0.001); as for T2DM the HRs were 1.39 and 1.57. In OO men, the HRs was 1.89 for developing future MetS. However, no significant findings could be noted in the ODO group. Kaplan-Meier plots and log rank test also showed the same findings. CONCLUSION: Our study showed that old subjects with high levels of UA will have a higher chance to have MetS and T2DM, particularly in the YO group (6.0 mg/dl for men and 5.5 mg/dl for women, respectively). Using UA as one of the metabolic biomarkers may help clinicians to early detect and prevent MetS and diabetes.

Normal fasting plasma glucose predicts type 2 diabetes and cardiovascular disease in elderly population in Taiwan.

BACKGROUND: Hyperglycemia increases prevalence of metabolic syndrome (MetS), type 2 diabetes (T2D) and cardiovascular disease (CVD). But the role of normoglycemia on the development of T2D and CVD in elderly population remains unclear. AIM: To determine an optimal cut-off for fasting plasma glucose (FPG) to predict MetS and subsequent risk of T2D and CVD in an elderly Taiwanese population with normal FPG levels. DESIGN: Two stages included cross-sectional (Stage 1) and prospective (Stage 2) cohort study. METHODS: In Stage 1 18 287 subjects aged ≥60 years were enrolled; of these, 5039 without T2D and CVD advanced to Stage 2 and a mean follow-up of 3.8 years. MetS components were analysed, and in Stage 1, FPG cut-offs for MetS risk were calculated using receiver operating characteristic (ROC) curve analyses. In Stage 2, subjects without T2D and CVD in Stage 1 were classified into high-FPG and low-FPG groups based on cut-offs, and sex specific differences in incidence for T2D and CVD were calculated. RESULTS: ROC curve analysis gave an optimal FPG cut-off for MetS of 93 mg/dl and 92 mg/dl for males and females, respectively. The high-FPG group had a 1.599- and 1.353-fold higher chance of developing T2D compared with the low-FPG group for males and females, respectively (95% CI: 1.606-2.721 and 1.000-1.831, P = 0.015 and 0.05). The high-FPG group had a 1.24-fold higher chance of developing CVD for females (95% CI: 1.015-1.515, P = 0.035); however, there was no difference for males. CONCLUSIONS: Our results suggest that FPG within the normal range was associated with MetS, and elderly subjects with high normal levels have a higher incidence of developing T2D for both sexes, and CVD for females, over the short-term.

The glycine allele of a glycine/arginine polymorphism in the beta2-adrenergic receptor gene is associated with essential hypertension in a population of Chinese origin.

BACKGROUND: Several studies implicate polymorphisms in the human beta-adrenergic receptor gene (ADRB2) in the susceptibility to hypertension. We sought to replicate these results in a population of Chinese origin primarily from Taiwan and the San Francisco Bay area. METHODS: We genotyped >800 hypertensive subjects and individuals with low-normal blood pressure that were derived largely from the same families as the hypertensive patients for three polymorphisms in the ADRB2 gene: a C/T transition at position 47 (C-47T) in the 5' leader cistron; another C/T transition that results in a glycine/ arginine substitution at codon 16 (Gly16Arg), and a G/C transversion that causes a glutamate/glutamine substitution at codon 27 (Glu27Gln). RESULTS: The Gly16Arg was significantly associated with hypertension (P < .03). Under a dominant model, for hypertension the relative risk for the Gly/Gly and Gly/Arg genotypes versus the Arg/Arg genotype was 1.35 (95% confidence limits [CL] 1.08, 1.70); for low-normal blood pressure the relative risk was 0.79 (95% CL 0.66, 0.94). This polymorphism explained approximately 1% of the variance in systolic and diastolic blood pressures in our study population. There was no evidence of association between the C-47T and Glu27Gln polymorphisms and hypertension in this population. CONCLUSIONS: The Glyl6 allele in the beta2-adrenergic receptor gene is a susceptibility allele for essential hypertension in a population of Chinese origin.

Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol.

Insulin resistance is associated with hypertriglyceridemia, low serum high-density lipoprotein cholesterol (HDL-C) concentrations and high serum total cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either lovastatin or gemfibrozil may favorably lower serum lipid concentrations. However, their effects on insulin sensitivity are unknown. The primary aim of this study was to compare the effects of lovastatin and gemfibrozil on insulin sensitivity and serum leptin concentrations in subjects with high TC/HDL-C ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day. Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose tolerance test (OGTT) and a modified insulin suppression test were performed before and after 3 months of treatment. The study showed the mean plasma TC, low-density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were significantly reduced in the lovastatin-treated group, but no obvious effects on plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma TG and HDL-C were markedly lowered, but no significantly different effects in other plasma lipids were found. Gemfibrozil did not affect steady-state plasma glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG concentrations. Neither drug affected the serum leptin concentration during the OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio, and TC/HDL-C concentrations and adversely affects insulin sensitivity, while gemfibrozil markedly reduces plasma TG concentrations without altering insulin sensitivity in subjects with high TC/HDL-C ratios.

Alstrom syndrome in two siblings.

Alstrom syndrome is a very rare autosomal recessive inherited disorder. Only 50 cases have been reported since the syndrome was first described in 1959. This syndrome is characterized by obesity, impaired glucose tolerance with insulin resistance, retinal degeneration, neurosensory deafness, acanthosis nigricans, hepatic dysfunction, and some endocrine disorders. The index case of this report was a 12-year-old girl who became blind at the age of 6 years as the result of progressively impaired vision. At the age of 12, diabetes mellitus was diagnosed and acanthosis nigricans presented in the neck, axilla, and groin regions. Her 10-year-old brother had similar symptoms. Electroretinography and audiometry disclosed generalized pigmentary epithelial change, decreased to absent cone and rod responses, and moderate sensorineural hearing loss in both siblings. Biochemistry and oral glucose tolerance tests showed diabetes mellitus, dyslipidemia, and hepatic dysfunction in the index case. Elevations of insulin, C-peptide, and leptin concentrations were found in both siblings. Insulin resistance was also demonstrated in both siblings using the modified insulin suppression test with constant infusion of somatostatin and exogenous insulin.

Effect of foot position on electromyographic activity of the vastus medialis oblique and vastus lateralis during lower-extremity weight-bearing activities.

STUDY DESIGN: Repeated measures analysis of the effects of foot wedges on quadriceps muscle function. OBJECTIVES: To investigate the relationship between foot position and 2 quadriceps muscle activation conditions: maximum voluntary isometric quadriceps muscle contractions with the knee extended and 1-leg short squats with a knee flexion range of motion of 0 degree to 50 degrees. BACKGROUND: Abnormal foot position has been suggested as an important factor which may lead to patellofemoral malalignment. No previous studies have examined the effects of foot position on activation of the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles using weight-bearing exercises. METHODS AND MEASURES: Sixteen healthy volunteers performed the 2 exercises under 3 foot conditions: level surface, a 10 degrees medial wedge, and a 10 degrees lateral wedge. Subjects' electromyographic data for the VMO and VL were analyzed using ANOVA. RESULTS: The normalized VMO/VL ratio was significantly greater during the short squat than during the maximum voluntary isometric muscle contractions, but no significant differences were identified across the 3 foot positions. CONCLUSIONS: Clinicians should understand that the benefit of using a foot orthotic to correct a pronated or supinated foot might not result from a change in quadriceps muscle activation intensity but from other mechanical factors.

Oral midazolam versus meperidine, atropine, and diazepam: a comparison of premedicants in pediatric outpatients.

An effective premedicant minimizes the emotional trauma children experience when facing surgery and may facilitate a smoother induction with fewer airway complications. In a randomized, double-blind study, the preoperative sedative effects and the postoperative recovery profiles of two oral pediatric premedicants were compared. Children (n = 102) were randomly assigned to receive 0.5 mg/kg midazolam or .2 mL/kg of a combination of meperidine 6.0 mg/mL, atropine 0.08 mg/mL, and diazepam 0.6 mg/mL 15-45 minutes before separation from parents. A five-point behavioral score was assigned at premedication, separation, and induction. Demographic data, preoperative preparation, analgesics, side effects, and recovery times were recorded. Scoring was continued at 15 and 30 minute intervals in the postanesthesia care unit (PACU). A majority of children in both groups achieved acceptable separation and induction scores; however, the midazolam subjects showed significantly better improvement in scores at both separation and induction (P < .01). In midazolam subjects, the age of the child did not influence induction scores; but in the meperidine/atropine/diazepam group, unacceptable scores were strongly associated with younger subjects (P < .01). Attendance at a children's preoperative preparation program did not affect scores. Midazolam subjects initially arrived in the PACU sleepier than pediatric anesthesia medicine subjects, but all other recovery scores were similar. There were no differences in analgesic requirements, side effects, or time to discharge between groups. We conclude that both premedicants are effective in most children, but that midazolam may offer more effective sedation in younger, distressed children.

Two-dimensional metamaterial structure exhibiting reduced visibility at 500 nm.

Metamaterials provide unprecedented freedom and flexibility in the creation of new structures, which control electromagnetic wave propagation in very unusual ways. Very recently various theoretical designs for an electromagnetic cloak were suggested and an experimental realization of a partial cloak operating in a two-dimensional cylindrical geometry were reported in the microwave frequency range. We report on an experimental two-dimensional reduced visibility structure that approximates the distribution of the radial component of the dielectric permittivity necessary to achieve nonmagnetic cloaking in the visible frequency range.

Bivariate genome-wide scan for metabolic phenotypes in non-diabetic Chinese individuals from the Stanford, Asia and Pacific Program of Hypertension and Insulin Resistance Family Study.

AIMS/HYPOTHESIS: Hypertension, obesity, impaired glucose tolerance and dyslipidaemia are metabolic abnormalities that often cluster together more often than expected by chance alone. Since these metabolic variables are highly heritable and are at least partially genetically determined, the clustering of defects in these traits implies that pleiotropic effects, where a common set of genes influences more than one trait simultaneously, are likely. METHODS: We conducted bivariate linkage analyses for highly correlated traits, aiming to dissect the genetic architecture affecting these traits, in 411 Chinese families participating in the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Study. RESULTS: We confirmed the pleiotropic effects of the locus at 37 cM on chromosome 20 on the following pairs: (1) fasting insulin and insulin AUC (empirical p = 0.0006); (2) fasting insulin and homeostasis model assessment of beta cell function (HOMA-beta) (empirical p = 0.0051); and (3) HOMA of insulin resistance (IR) and HOMA-beta (empirical p = 0.0044). In addition, the peak logarithm of the odds (LOD) scores of linkage between a chromosomal locus and a trait for the pair fasting insulin and HOMA-IR rose to 5.10 (equivalent LOD score in univariate analysis, LOD([1]) = 4.01, empirical p = 8.0 x 10(-5)) from 3.67 and 3.42 respectively for these two traits in univariate analysis. Additional significant linkage evidence, not shown in single-trait analysis, was identified at 45 cM on chromosome 16 for the pair 1 h insulin and the AUC for insulin, with a LOD score of 4.29 (or LOD([1]) = 3.27, empirical p = 2.0 x 10(-4)). This new locus is also likely to harbour the common genes regulating these two traits (p = 1.73 x 10(-6)). CONCLUSIONS/INTERPRETATION: These data help provide a better understanding of the genomic structure underlying the metabolic syndrome.

The effect of thyroxine-suppressive therapy in patients with solitary non-toxic thyroid nodules -- a randomised, double-blind, placebo-controlled study.

The efficacy of thyroxine (T(4)) for solitary non-toxic thyroid nodule remains uncertain. In this study, 60 patients with solitary non-toxic thyroid nodule were divided randomly into two groups. Group I (n = 30) received thyroxine 100 microg/day for 6 months and group II (n = 30) received placebo. The volume of the thyroid nodules in 11 patients decreased more than 50% after thyroxine therapy (36.7%, responders). In these 11 patients, the mean serum thyroglobulin level decreased significantly (340 +/- 115 to 162 +/- 86 microg/l, p < 0.01). Compared with the non-responders (n = 19, 63.3%), the serum thyroglobulin level before treatment was significantly higher (340 +/- 115 vs. 220 +/- 102 microg/l, p < 0.05). Thyroxine-suppressive therapy is proved as a useful tool in reducing nodule size in some patients with solitary thyroid nodules. The patients with a higher serum thyroglobulin level generally respond better to thyroxine-suppressive therapy.