Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4.

OBJECTIVE: Abundant evidence has demonstrated that long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous study reveals a significant association between promoter polymorphisms of Th2-derived cytokine interleukin-4 (IL-4) and T2DM, which suggests possible roles of IL-4 in metabolism. In this study, we focused on examining the putative regulation of glucose and lipid metabolism by IL-4. METHODS: C57BL/6 mice were intraperitoneally injected with either adenovirus containing full-length IL-4 encoding gene (AdIL-4) or recombinant IL-4 for mimicking the status of transient and long-term IL-4 overexpression, respectively, and the effects of the overexpressed IL-4 to glucose/lipid metabolism and insulin sensitivity were subsequently investigated. RESULTS: Our results reveal that IL-4 improves insulin sensitivity and glucose tolerance through upregulating Akt phosphorylation while attenuating GSK-3ß activities. IL-4 is also involved in lipid metabolism by inhibiting lipid accumulation in fat tissues, which lead to decreased weight gain and fat mass. CONCLUSIONS: Our results suggest that IL-4 regulates glucose and lipid metabolism by promoting insulin sensitivity, glucose tolerance and inhibiting lipid deposits. This study uncovers the novel roles of IL-4 in metabolism and provides new insights in the interaction between cytokines/immune responses, insulin sensitivity and metabolism.

Polymorphisms of cytotoxic T lymphocyte-associated antigen-4 and cytokine genes in Taiwanese patients with ankylosing spondylitis.

Cytokines, costimulatory and counter-regulatory molecules play important roles in the regulation of inflammatory response, and are good candidates involved in the development of ankylosing spondylitis (AS). This study investigated the genotypic distribution of proinflammatory cytokines and T-cell negative regulator cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in healthy subjects and AS patients. Genomic DNA was extracted from 143 AS patients and 166 ethnic-matched healthy subjects. Nine polymorphisms within the genes of interleukin-4 (IL-4) (-34T>C, -81A>G, -285C>T and -589T>C), interleukin-6 (IL-6) (-174G>C), interleukin-10 (IL-10) (-592A>C and -819T>C) and CTLA-4 (-318C>T and +49A>G) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Significantly less AS patients carried the CTLA-4 high-expressing -318 T allele (P = 0.040). The CTLA-4 +49A>G genotypes were associated with circulatory levels of the inflammatory marker C-reactive protein (CRP) (P = 0.022). Our study documented the most complete genetic information of Taiwanese AS patients. The observations that CTLA-4 +49A>G genotypes are associated with circulatory CRP levels and significantly less AS subjects carrying CTLA-4 higher-secretor -318 T allele suggest the level and regulation of inflammation in AS subjects may be pre-determined by and associated with CTLA-4 genotypes.

Assessment of regional left ventricular function by dual source computed tomography: interobserver variability and validation to laevocardiography.

OBJECTIVE: Assessment of left ventricular function is possible in contrast-enhanced cardiac CT data sets. However, rapid ventricular motion especially in systole can lead to artifacts. Dual Source Computed Tomography (DSCT) has high temporal resolution which effectively limits motion artifact. We therefore assessed the accuracy of DSCT to detect regional left ventricular wall motion abnormalities in comparison to invasive cine angiocardiography. METHODS: We analyzed DSCT data sets of 50 patients (39 male, 11 female, mean age: 61+/-10 years) which were acquired after intravenous injection of 55-70 mL contrast agent (rotation time: 330 ms, collimation: 2 mm x 64 mm x 0.6 mm, 120 kV, 380 mAs, ECG-correlated tube current modulation). 10 data sets consisting of transaxial slices with a slice thickness of 1.5 mm, an increment of 1.0 mm and a matrix of 256 x 256 pixels were reconstructed at 10 time instants during the cardiac cycle (0-90% in 10% increments). The data sets were analyzed visually by two independent readers, using standard left ventricular planes, concerning regional wall motion abnormalities. DSCT was verified in a blinded fashion against cine ventriculography performed during cardiac catheterization (RAO and LAO projection), using a 7-segment model. Analysis was performed on a per-patient (presence of at least one hypo-, a- or dyskinetic segment) and on a per-segment basis. RESULTS: Concerning the presence of a wall motion abnormality, the two observers agreed in 340/350 segments (97%) and 48/50 patients (96%). In invasive cine angiocardiography, 22 of 50 patients displayed at least one segment with abnormal contraction. To detect these patients, DSCT showed a sensitivity of 95% (21/22), specificity of 96% (27/28), positive predictive value of 95% and negative predictive value of 96%. Out of a total of 350 left ventricular segments, 66 segments had abnormal contraction in cine angiocardiography (34 hypokinetic, 26 akinetic, 6 dyskinetic). For detection of these segments, DSCT had a sensitivity of 88% (58/66), specificity of 98% (278/284), positive predictive value of 91% (58/64) and negative predictive value of 97% (278/286). CONCLUSION: DSCT allows the detection of regional wall motion abnormalities with high interobserver agreement as well as high sensitivity and specificity. Whereas sensitivity and positive predictive value were higher in a per-patient- in comparison to a per-segment-based analysis, specificity, negative predictive value and interobserver agreement did not differ considerably between both analyzing methods.

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events.

OBJECTIVE: To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). METHODS: Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. RESULTS: A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. CONCLUSIONS: Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive treatment strategies should be directed to both smoking cessation and control of disease activity in patients with SLE.

Use of zeolite for removing ammonia and ammonia-caused toxicity in marine toxicity identification evaluations.

Ammonia occurs in marine waters including effluents, receiving waters, and sediment interstitial waters. At sufficiently high concentrations, ammonia can be toxic to aquatic species. Toxicity identification evaluation (TIE) methods provide researchers with tools for identifying aquatic toxicants. For identifying ammonia toxicity, there are several possible methods including pH alteration and volatilization, Ulva lactuca addition, microbial degradation, and zeolite addition. Zeolite addition has been used successfully in freshwater systems to decrease ammonia concentrations and toxicity for several decades. However, zeolite in marine systems has been used less because ions in the seawater interfere with zeolite's ability to adsorb ammonia. The objective of this study was to develop a zeolite method for removing ammonia from marine waters. To accomplish this objective, we performed a series of zeolite slurry and column chromatography studies to determine uptake rate and capacity and to evaluate the effects of salinity and pH on ammonia removal. We also assessed the interaction of zeolite with several toxic metals. Success of the methods was also evaluated by measuring toxicity to two marine species: the mysid Americamysis bahia and the amphipod Ampelisca abdita. Column chromatography proved to be effective at removing a wide range of ammonia concentrations under several experimental conditions. Conversely, the slurry method was inconsistent and variable in its overall performance in removing ammonia and cannot be recommended. The metals copper, lead, and zinc were removed by zeolite in both the slurry and column treatments. The zeolite column was successful in removing ammonia toxicity for both the mysid and the amphipod, whereas the slurry was less effective. This study demonstrated that zeolite column chromatography is a useful tool for conducting marine water TIEs to decrease ammonia concentrations and characterize toxicity.

Relationship between adherence to study and clinic visits in systemic lupus erythematosus patients: data from the LUMINA cohort.

The aim of this study was to examine the relationship between nonadherence with study visits and with regularly scheduled clinic visits after adjusting for other patient and disease characteristics. One hundred and forty-one LUMINA patients with appointment data in the institutions' computerized systems (UAB and UTH) were studied. 'No shows' were assessed as the percentage of appointments not attended for either rheumatology, other clinics and LUMINA visits (from zero to 100%). Eighty-nine percent of the patients were women, 40% were Caucasians, 55% African-Americans and 5% Hispanics. 'No shows' to rheumatology were associated with non-Caucasian ethnicity, younger age, single marital status, lack of home ownership, 'no shows' to other clinics and to the LUMINA study, greater disease activity and to some disease manifestations (serositis, renal involvement, positive anti-dsDNA antibodies). In multivariable analyses, features predictive of rheumatology 'no shows' were lack of home ownership, 'no shows' to LUMINA study visits, renal involvement and serosal manifestations. Nonadherence with study visits and with regularly scheduled care at rheumatology clinics were associated. Other factors predictive of nonadherence to recommended care were lack of home ownership (a measurement of low socioeconomic status) and the presence of disease manifestations (i.e., renal or serosal involvement). These data should be considered when caring for patients with SLE.

Coronary artery ectasia: a ten-year experience in a tertiary hospital in Singapore.

INTRODUCTION: Coronary artery ectasia (CAE) is a well-recognised, albeit rare, angiographic finding of abnormal coronary dilatation. To our best knowledge, its incidence has never been described in Singapore. We aimed to determine the incidence of CAE at our teaching hospital and to describe patient and angiographic characteristics. MATERIALS AND METHODS: Cases were identified through a search of our hospital's computer database and all records were reviewed. RESULTS: Over the 10-year study period (1992-2001), 8641 patients underwent coronary angiography. CAE was diagnosed in 104 patients, giving an incidence of 1.2%. The majority (74%) were male. The median age was 54 years (range, 25 to 79 years). Sixty-six per cent of patients were Chinese, 19% Malays, 12% Indians and 3% other races. Concomitant diabetes mellitus was present in 31%, hypertension in 58% and dyslipidaemia in 63% of patients. Co-existent obstructive coronary artery disease was present in 82% of cases. The frequency of arterial involvement was: right coronary artery (RCA), 65%; left anterior descending artery (LAD), 48%; circumflex artery (CX), 43%; and left main artery (LM), 2%. CAE affected only 1 major vessel in 62% of cases and all 3 vessels in 20%. Eighteen patients were advised to undergo bypass surgery, while percutaneous coronary intervention was recommended in 26 patients. CONCLUSIONS: The incidence of ectasia was 1.2%. The majority of patients were males in their sixth decade with underlying dyslipidaemia or hypertension. CAE was associated with obstructive coronary artery disease in more than 80% of cases. The RCA was most commonly affected and most patients had single vessel involvement.

Removal of ammonia toxicity in marine sediment TIEs: a comparison of Ulva lactuca, zeolite and aeration methods.

Toxicity Identification Evaluations (TIEs) can be used to determine the specific toxicant(s), including ammonia, causing toxicity observed in marine sediments. Two primary TIE manipulations are available for characterizing and identifying ammonia in marine sediments: Ulva lactuca addition and zeolite addition. In this study, we compared the efficacy of these methods to (1) remove NH(x) and NH(3) from overlying and interstitial waters and (2) reduce toxicity to the amphipod Ampelisca abdita and mysid Americamysis bahia using both spiked and environmentally contaminated sediments. The utility of aeration for removing NH(x) and NH(3) during a marine sediment TIE was also evaluated preliminarily. In general, the U. lactuca and zeolite addition methods performed similarly well at removing spiked NH(x) and NH(3) from overlying and interstitial waters compared to an unmanipulated sediment. Toxicity to the amphipod was reduced approximately the same by both methods. However, toxicity to the mysid was most effectively reduced by the U. lactuca addition indicating this method functions best with epibenthic species exposed to ammonia in the water column. Aeration removed NH(x) and NH(3) from seawater when the pH was adjusted to 10; however, very little ammonia was removed at ambient pHs ( approximately 8.0). This comparison demonstrates both U. lactuca and zeolite addition methods are effective TIE tools for reducing the concentrations and toxicity of ammonia in whole sediment toxicity tests.

Comparisons of coarse and fine versions of two carbons for reducing the bioavailabilities of sediment-bound hydrophobic organic contaminants.

Coarse (whole) and finely ground Ambersorb 1500 and coarse and fine coconut charcoal were compared as to their efficiencies in scavenging organic contaminants desorbed from sediment. Aqueous slurries of a test sediment spiked (1 ppm) with p,p(')-DDE (DDE), 2,2('),5,5(')-tetrachlorobiphenyl (TCB), naphthalene (NAP), or phenanthrene (PHEN), and containing 1% levels of the test carbons were treated by shaking at 35 degrees C while exposed to clusters of low-density polyethylene membrane (detox spiders). Controls consisted of spiked sediments and detox spiders but no added carbon of any kind and thus represented unimpeded bioavailabilities (to the spiders). After the treatments--agitation periods from 2.5 to 60 h, depending on contaminant hydrophobicity--the exposed detox spiders were analyzed. The fine carbon of either type was more effective than its coarser variant in obstructing contaminant bioavailabilities. The finer variants of both carbons obstructed the bioavailabilities of NAP and PHEN equally well as did the coarser variants of both. Whole Ambersorb 1500 and coarse coconut charcoal were similarly ineffective in intercepting TCB and DDE. Ground Ambersorb 1500 obstructed virtually all bioavailability of all four contaminants and was far more effective than fine coconut charcoal in intercepting DDE and TCB. An additional experiment compared the effectiveness of ground Ambersorb 1500 and fine coconut charcoal in obstructing the bioavailabilities from sediment of a broad array of spiked organochlorine pesticides. The performance of ground Ambersorb 1500 was again found to be superior; the bioavailable levels of each of the 27 pesticides were markedly lower in the presence of ground Ambersorb 1500 than in the presence of fine coconut charcoal.

Prediction of severe coronary artery disease and long-term outcome in patients undergoing vasodilator SPECT.

BACKGROUND: Vasodilator perfusion imaging has not been extensively evaluated for predicting severe coronary artery disease (CAD) or long-term prognosis. METHODS AND RESULTS: The goals of this study were to develop a model to predict left main/3-vessel CAD in patients undergoing vasodilator thallium 201 imaging and coronary angiography (angiographic population) and to test the long-term prognostic value of this model in a separate cohort of patients who were not referred for angiography (prognostic population). In the angiographic population (n = 653) the chi2 value of the clinical model (containing the variables age, sex, and prior myocardial infarction) in the prediction of severe CAD was 32. The addition of 3 vasodilator Tl-201 variables (magnitude of ST-segment depression, summed reversibility score, and increased lung uptake) increased the model chi2 value to 114 (P <.001). Only 9% of predicted low-risk patients versus 57% of predicted high-risk patients had severe CAD. In the prognostic population (n = 521) survival rates free of cardiac death or myocardial infarction at 7 years were 91%, 73%, and 51%, respectively, for patient groups predicted to be at low, intermediate, and high risk of severe CAD (P <.001). CONCLUSIONS: Clinical and vasodilator Tl-201 variables can accurately predict the risk of severe CAD. Stress Tl-201 variables add incremental information to clinical variables. The same model also predicts patient outcome.

Use of Ulva lactuca to identify ammonia toxicity in marine and estuarine sediments.

Toxicity identification evaluation (TIE) methods are being developed for use with whole sediments. Although a phase I TIE method has been developed to characterize ammonia toxicity in aqueous samples using the marine macroalga Ulva lactuca, the relationship between amphipod and mysid mortality and uptake by U. lactuca of bedded sediment ammonia had not been explored. Additionally, it was not known how interactions in whole sediments between metal and organic contaminants with U. lactuca and ammonia would affect TIE interpretation. The current study showed that ammonia toxicity to amphipods and mysids was reduced significantly in marine sediments in the presence of U. lactuca. The alga slightly affected metal concentrations but did not alter the concentration of organic contaminants in either overlying or interstitial waters. Conversely, ammonia uptake by U. lactuca was not affected by the presence of metal or organic contaminants in the sediments. When used with other TIE manipulations, U. lactuca can be utilized in a whole-sediment, phase I TIE to remove toxicity due to ammonia.

Sediment toxicity assessment: comparison of standard and new testing designs.

Standard methods of sediment toxicity testing are fairly well accepted; however, as with all else, evolution of these methods is inevitable. We compared a standard ASTM 10-day amphipod toxicity testing method with smaller, 48- and 96-h test methods using very toxic and reference sediments. In addition we compared parallel exposures of single species, either the amphipod Ampelisca abdita or the mysid Americamysis bahia, to multiple species, mysid, and amphipod, cohabiting the same types of chambers. These comparisons were performed for both water-only and sediment-water tests. Results of the comparison of the standard ASTM 10-day amphipod test with the smaller, 48- and 96-h test chambers indicate that survival was high in both test designs using the reference sediment. With toxic sediments, complete mortality occurred in less than 48 h using the smaller experimental chambers and only after 96 h in the larger experimental chambers. We concluded that although time to death is shorter in the smaller, shorter exposure chambers, there was no overall change in mortality for the organisms, and that the smaller chambers were predictive of the results obtained with larger chambers and longer exposures. For multiple species testing in whole sediment exposures there was no change in toxicity to either the amphipod or the mysid when they cohabited the same chamber. In contrast, for water-only exposures, A. bahia demonstrated less sensitivity when cohabiting the same chamber as A. abdita. Therefore, during whole sediment testing we can add A. bahia and A. abdita to the same test chamber without changing the toxicity to either species; however, in our 10-ml water-only exposures, the species should be tested separately.

Selective removal of organic contaminants from sediments: a methodology for toxicity identification evaluations (TIEs).

Aqueous slurries of a test sediment spiked with dibenz[a,h]anthracene, 2,4,5,2',4',5'-hexachlorobiphenyl, p,p'-DDE, or phenanthrene were subjected to decontamination experimentation. The spiked sediments were agitated at elevated temperatures for at least 96 h in the presence of either of the two contaminant-absorbing media: clusters of polyethylene membrane or lipid-containing semipermeable membrane devices (SPMDs). The effects of treatment temperature and surface area of media on the removal of contaminants were explored. This work is part of a larger methodology for whole-sediment toxicity identification evaluation (TIE). A method is being sought that is capable of detoxifying sediments with respect to organic contaminants while leaving toxicity attributable to inorganic contaminants unaffected.

Long-term prognostic value of Duke treadmill score and exercise thallium-201 imaging performed one to three years after percutaneous transluminal coronary angioplasty.

The value of exercise nuclear perfusion imaging performed beyond the 6-month restenosis window for percutaneous transluminal coronary angioplasty (PTCA) has not been explored. This study evaluates the long-term prognostic value of exercise thallium (Tl)-201 imaging after PTCA. We studied the late outcome of a series of 211 patients with tomographic Tl-201 exercise studies performed between 1 to 3 years after PTCA. Follow-up was 96% complete at a median duration of 7.3 years. Most (73%) had 1- or 2-vessel coronary artery disease and normal left ventricular function and 193 (91%) had successful PTCA. Two thirds of the patients were symptomatic at the time of testing. The mean Duke score was 5+/-6 and 125 (60%) patients had a low-risk Duke score. Mean summed stress score was 50+/-9 and mean summed reversibility score was 3+/-4. The 5-year overall survival was 95%, yielding a low annual mortality rate of 1%/year. The summed stress score exhibited a significant association (p = 0.047) with the end point of cardiac death or myocardial infarction. The Duke score was predictive of the combination end point of hard and soft cardiac events (p = 0.002). This study demonstrates that exercise Tl-201 perfusion imaging performed 1 to 3 years after PTCA was predictive of cardiac events.

Isolated right ventricular diverticulum with chest pain.

A 26-year-old man presented with severe chest pain. Subsequent investigations revealed a right ventricular diverticulum communicating with the right atrium. Surgery was performed, following which the chest pain disappeared completely.

Working party report of the Gastroenterological Society of Singapore. Part II--Helicobacter pylori and non-ulcer dyspepsia in Singapore.

Non-ulcer dyspepsia (NUD) is a common symptom whose cause is currently unclear. Helicobacter pylori (H pylori) infection is found in half of all patients with NUD but other pathophysiological abnormalities eg delayed gastric emptying, have also been described. NUD patients with or without H pylori infection have identical symptom patterns and pathophysiological parameters. Studies on the efficacy of H pylori treatment in NUD give equivocal results to date. We therefore do not recommend treatment for H pylori in NUD.

Working Party report of the Gastroenterological Society of Singapore. Part I--Helicobacter pylori and peptic ulcer disease in Singapore.

The Gastroenterological Society Working Party on Helicobacter pylori (H pylori) recommends eradication of H pylori in patients with peptic ulcer, provided H pylori infection has been demonstrated. H pylori treatment is not indicated for non-ulcer dyspepsia, histological gastritis or mere demonstration of H pylori infection. H pylori infection can be demonstrated by a urease test, culture or histological assessment on gastric antral biopsy or by a 13C and 14C urea breath test: serology is acceptable if validated in the local population. There are many eradication regimens for H pylori infection and follow-up assessments to demonstrate eradication is desirable.

Diagnostic and therapeutic colonoscopy - a review of 300 examinations.

In a period of twenty-two months, 300 patients were subjected to colonoscopic examinations. The proximal colon could be intubated in more than 90% of patients, when there was no distal obstruction or contraindications. Colonoscopy provided a more accurate diagnosis of colorectal diseases when correlated with barium enema examinations, and several unnecessary operations were thus avoided. However both procedures should be regarded as complementary rather than competitive. Colonoscopic polypectomy has revolutionised the management of colonic polyps, which are precursors to most colonic carcinomas. It has greatly reduced the need for laparotomy and surgical polypectomy. The morbidity, mortality, length of hospitalization and cost are significantly lower with colonoscopic polypectomy when compared with surgical polypectomy. In the present series, 45 colonic polyps were removed from 32 patients without any complications. The increased use of colonoscopic polypectomy may reduce the death rate from colonic carcinoma.