Cardiac troponin T vs other biochemical markers in patients with congestive heart failure.

BACKGROUND: Several pathologic processes can cause myocardial injury, which is followed by cardiac remodeling and congestive heart failure (CHF). Cardiac troponin T (cTnT), a specific and sensitive marker of myocardial injury, has been related to long-term outcome in patients with CHF, so the relationship between cTnT and other biochemical markers associated with the pathophysiology of CHF was investigated in the present study. METHODS AND RESULTS: Between February 2004 and December 2005, 145 consecutive hospitalized patients (mean left ventricular ejection fraction (LVEF) 31.6+/-0.9%) with CHF were divided into low (<0.01 ng/ml) and high (> or =0.01 ng/ml) serum cTnT groups. Correlations with other prognostic biochemical markers, including brain natriuretic peptide (BNP), type I collagen C-terminal telopeptide (ICTP), procollagen type III peptide (PIIIP), renin, norepinephrine (NOREPI), C-reactive protein (CRP), cholesterol, hemoglobin (Hb), uric acid and HbA1c were examined. cTnT was high in 46 (32%) and low in 99 (68%) patients at baseline. Patients with high cTnT had abnormally high blood concentrations of BNP (p<0.0001), ICTP (p<0.0001), PIIIP (p=0.0006), NOREPI (p=0.0119), CRP (p=0.0003), uric acid (p=0.0026) and HbA1c (p=0.0361). In contrast, concentrations of cholesterol and Hb were significantly lower in patients with high cTnT (p=0.0319 and 0.0005, respectively). Death from or rehospitalization for CHF occurred in 41% in the high vs 9% in the low cTnT group (p=0.0002). Univariate analysis showed that high cTnT (p=0.0005), BNP (p=0.0001), renin (p=0.0158), NOREPI (p=0.0094), old age (p=0.0390), low LVEF (p=0.0231) and high New York Heart Association (NYHA) class (p=0.0006) were predictors of death from or rehospitalization for CHF. By multivariate analysis including BNP, NOREPI, age, LVEF and NYHA class, high cTnT and renin remained as significant predictors. CONCLUSIONS: Patients with ongoing myocardial injury and high cTnT had associated findings consistent with activation of the sympathetic system, synthesis of cardiac fibrosis, inflammation and metabolic abnormalities. By multivariate analysis, high cTnT and renin remained significant predictors of death or rehospitalization.     

Extracellular-to-intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis: results from the Nagahama Study

Introduction/objectives

To test the hypothesis that greater extracellular-to-intracellular water (ECW/ICW) ratios in lower-limb muscles are associated with worsened functional abilities in patients with knee osteoarthritis (OA).

Methods

We analyzed data from 787 participants (82.2% female; mean age, 69.6 ± 5.3 years) from the Nagahama Prospective Cohort who were ≥60 years old and had radiographically confirmed bilateral knee OA. The Knee Scoring System (KSS) was used to assess functional abilities. Lower-limb ECW/ICW ratios and skeletal mass index values were determined with multi-frequency bioelectrical impedance analysis (BIA). Multiple linear regression analysis was used to test for associations between ECW/ICW ratios and functional abilities. Subgroup analyses based on OA severities and symptomaticity were also conducted.

Results

Increased ECW/ICW ratios were associated with a 4.38-point decrease in the KSS function scores (95% confidence interval [CI], 3.15–5.62 points) after adjusting for covariates. This association varied according to the degree of knee symptoms, especially in individuals with radiologically mild OA. ECW/ICW ratios in individuals with asymptomatic mild OA were associated with a 2.14-point decrease in the KSS function score (95% CI, 0.32–3.96 points), whereas those in individuals with severe symptomatic mild OA were associated with a 6.16-point decrease (95% CI, 2.13–10.19 points).

Conclusions

Our findings indicate that higher ECW/ICW ratios are associated with greater functional disability in patients with knee OA. Therefore, ECW/ICW ratio measurements with multi-frequency BIA can serve as valuable indicators for functional disability in patients with knee OA.

Plasma matrix metalloproteinase-8 concentrations are associated with the presence and severity of coronary artery disease.

BACKGROUND: Interstitial collagen, especially type I, is a major component of atherosclerotic plaques and the matrix metalloproteinases (MMP) 1, 8 and 13 can initiate collagen breakdown. MMP-8 degrades type I collagen preferentially and more potently than MMP-1 or MMP-13. Although MMP-8 was thought to be produced only by neutrophils, it was recently reported to also be produced by endothelial cells, smooth muscle cells and macrophages in plaques. METHODS AND RESULTS: Plasma MMP-8 concentrations were measured in 250 patients undergoing coronary angiography for coronary artery disease (CAD: >50% stenosis), which was found in 181 patients, of whom 69 had 1-vessel, 66 had 2-vessel, and 46 had 3-vessel disease. Compared with 69 patients without CAD, the 181 with CAD had higher MMP-8 concentrations (3.5 vs 3.0 ng/ml, p < 0.001). There was a stepwise increase in MMP-8 concentration depending on the number of stenotic vessels: 3.2 in 1-vessel, 3.6 in 2-vessel, and 4.3 ng/ml in 3-vessel disease (p < 0.001). Multivariate analysis showed that MMP-8 concentration was independently associated with CAD. The odds ratio for CAD was 1.22 (95%confidence interval = 1.07-1.39) for a 1 ng/ml increase in MMP-8 concentration. CONCLUSIONS: Plasma MMP-8 concentration is associated with the presence and severity of CAD.     

Troglitazone induces p27Kip1-associated cell-cycle arrest through down-regulating Skp2 in human hepatoma cells

Increasing evidence has confirmed that ligands for peroxisome proliferator-activated receptor gamma (PPARgamma) exhibit antitumoral effects through inhibition of cell proliferation and induction of cell differentiation in several malignant neoplasms. Recently, we have documented the accumulation of a cyclin-dependent kinase inhibitor, p27(Kip1), as well as an unexpected accumulation in cyclin E in G1-arrested human hepatoma cells treated with the PPARgamma ligand troglitazone. Simultaneous accumulations in both p27(Kip1) and cyclin E are known to be characteristic phenotypes in cells derived from mice lacking Skp2, an F-box protein component of the SCF ubiquitin-ligase complex. Thus, the aim of the present study was to assess whether Skp2 might be involved in the down-regulation of p27(Kip1) in troglitazone-treated human hepatoma cells. A striking decrease in Skp2 expression and a reciprocal increase in p27(Kip1) expression were found in troglitazone-treated hepatoma cells but not in those cells treated with other PPARgamma ligands such as pioglitazone and ciglitazone. Quantitative real-time RT-PCR analysis showed that troglitazone down-regulated Skp2 at the mRNA levels. Consistently, ectopic overexpression in Skp2 brought resistance to troglitazone, resulting in a decreased population of arrested cells at the G1 phase compared with that in the mock-transfected cells. In surgically resected hepatocellular carcinoma (HCC) tissue, an increased expression in Skp2 was found in both the moderately differentiated HCCs and the poorly differentiated HCCs. In conclusion, troglitazone attenuated Skp2 expression, thereby promoting p27(Kip1) accumulation in human hepatoma cells. This therapeutic potential of the ligand may lead to new cell-cycle-based antitumor strategies for advanced HCCs.     

Case of adult genotype C HBV carrier after acute hepatitis B, losing HBsAg and acquiring HBsAb after IFN and lamivudine treatment.

Here we report the case of a 48-year-old man, carrier of genotype C HBV for longer than 6 months after contracting sexually transmitted acute hepatitis B, who eventually lost HBsAg and acquired HBsAb by IFN/lamivudine therapy. The patient had been negative for HBsAg in 2001, but, during his stay in China from January to July in 2003, he developed acute hepatitis B after having an extra-marital sexual contact there. HBsAg was still positive and a liver biopsy indicated chronic hepatitis when he was admitted to our hospital in December 2003 for detailed examination of liver dysfunction. HBV DNA in his serum, revealed to segregate to genotype C by sequencing on admission, decreased to undetectable levels at the end of a 3-month IFN therapy, and remained undetectable during and after the successive 6-month lamivudine therapy. HBeAg seroconverted to HBeAb during the therapy, and HBsAb appeared after the therapy. To our knowledge, this is the first case of genotype C chronic hepatitis B occurring after acute hepatitis.     

Relationship between Helicobacter pylori Colonization and Acute Inflammation of the Duodenal Mucosa

A relationship between Helicobacter pylori colonization and acute inflammation of the duodenal mucosa was studied in 75 patients with duodenal ulcer and nine with endoscopically normal duodenal mucosa. A biopsy of the duodenal bulb in each patient was used for both detection of H. pylori and histological assessment of acute inflammation [polymorphonuclear leukocyte (PMN) infiltration and regenerative changes of the duodenal epithelial cells). Biopsies with regenerative changes showed a marked PMN infiltration, regardless of the duodenal H. pylori status. In biopsies without regenerative changes, H. pylori colonization was closely associated with PMN infiltration. Acute inflammation in the duodenal mucosa surrounding ulcers is caused mainly by acid, hut our data suggest that H. pylori is another important factor in the development of PMN infiltration in the duodenal mucosa.     

Lower serum free thyroxine (T4) levels in painless thyroiditis compared with Graves' disease despite similar serum total T4 levels

Serum total T4 (T4), total T3 (T3), free T4 (FT4), free T3 (FT3), and T4-binding globulin concentrations and T3 resin uptake values were measured in 17 women with thyrotoxicosis due to painless thyroiditis (PT) and compared with the same parameters in 17 women with thyrotoxicosis due to Graves' disease (GD) with similar serum T4 levels. The mean serum T3 resin uptake value and T3, FT4, and FT3 concentrations in the PT patients were significantly lower than those in the GD patients. The mean serum T4-binding globulin concentration [20.2 +/- 4.2 (+/- SD) microgram/mL] in patients with PT did not differ significantly from those in patients with GD (18.0 +/- 2.6 micrograms/mL) and normal euthyroid women (21.9 +/- 4.0 micrograms/mL). The serum T3 to T4 (nanogram per microgram) ratio was higher than 20 in 14 GD patients, but lower than 20 in all patients with PT, whereas the individual serum FT3 to FT4 ratio values considerably overlapped in the 2 groups. In patients with PT, FT4 correlated well with T4 at various times during the clinical course. These findings indicate that the elevation in serum FT4 in patients with PT is mostly due to the increase in circulating T4 levels, whereas GD patients also have some diminution in T4 binding. The serum T3 to T4 ratio, but not the FT3 to FT4 ratio, may be helpful for differentiation between the two diseases.