Reliability of the novel 7-joint ultrasound score: results from an inter- and intraobserver study performed by rheumatologists.

OBJECTIVE: To assess the inter- and intraobserver reliability of 26 rheumatologists when performing the 7-joint ultrasound score (US7). METHODS: Six patients with rheumatoid arthritis were examined by 26 sonographers in 12 rater groups who performed the US7 score. The US7 score includes the clinically dominant wrist, the second and third metacarpophalangeal (MCP) and proximal interphalangeal joints, and the second and fifth metatarsophalangeal (MTP) joints, which were evaluated for synovitis, tenosynovitis/paratenonitis, and erosions from the dorsal side and palmar/plantar aspects by gray-scale and power Doppler (PD) ultrasound. Additional lateral scans were performed at the MCP2 and MTP5 joints. All of the groups repeated the examination in 4 patients in order to calculate the intraobserver reliability. The results of one group that included 2 expert sonographers were considered as the reference standard. Kappa values, median agreement rates (interobserver), and P values (intraobserver evaluation) were calculated. RESULTS: The median overall kappa value for detecting synovitis was 0.51, for tenosynovitis/paratenonitis was 0.57, and for erosions was 0.45. In detail, the best interobserver results were found for the detection of erosions in the MTP2 joint from the plantar aspect (κ = 1; median agreement rate 89.4%) and for PD signal detection in the palmar wrist region (κ = 0.79; median agreement rate 78.8%). Good agreement was found for detecting erosions in the MCP2 joint from the radial side (κ = 0.67; median agreement rate 77.3%). CONCLUSION: The inter- and intraobserver reliability of the US7 score shows moderate to substantial kappa values and good agreements. Therefore, this ultrasound score has the potential to be an important imaging tool, including multicenter analysis to assess structural changes.

Improved estimation of GFR by serum cystatin C in patients undergoing cardiac catheterization.

Clinical assessment of glomerular filtration rate (GFR) mainly relies on single determinations of serum creatinine (crea) which is commonly insensitive to mild renal dysfunction. Serum cystatin C (cysC) has been proposed as an alternative endogenous marker of GFR showing higher correlation to standard clearance methods such as inulin or iohexol clearance. We compared serum crea and cysC levels in n=127 patients undergoing cardiac catheterization. The clearance of the iodinated contrast dye iopromide served as reference method for GFR. Serum cysC was determined by a particle-enhanced immunonephelometric method. CysC showed higher non-parametric correlation (r=0.805) to the iopromide clearance compared to crea (r=0.652) and to the estimated GFR according to the Cockcroft-Gault formula (r=0.690), which underestimated true GFR systematically. Receiver operating curves revealed a greater area-under-the-curve (AUC) for cysC (0.957 vs. 0.801, p<0.05). At a cut-off level of >1.3 mg/l cysC exhibited an 88% sensitivity and a 96% specificity for detecting renal dysfunction which was defined as an iopromide clearance less than 80 ml/min/1.73 m2; best values for crea were 63% for sensitivity and 80% for specificity at a cut-off of >1.2 mg/dl. In conclusion, cysC detected reduced GFR more reliably and at an earlier stage in patients undergoing cardiac catheterization allowing a better identification of patients with renal dysfunction and those at risk for contrast damage.

Sensitive high-performance liquid chromatographic assay for the determination of eugenol in body fluids.

The high-performance liquid chromatographic assay described permitted a simple, rapid, sensitive, selective and precise quantitative determination of eugenol in body fluids (serum, urine and bile) without derivatization. Amounts in the range 0.02-100 micrograms of eugenol per millilitre of body fluid were determined with intra-assay coefficients of variation below 4% (3.72-1.13%). The short analysis time for each sample and the selectivity even at low concentrations made this assay suitable for pharmacokinetic studies. Eugenol undergoes a pronounced first-pass effect; in serum, unconjugated eugenol was not detected after an oral dose of 150 mg. The kinetics of eugenol conjugates were measured. More than 80% of the dose was excreted within 6 h after oral administration.

The metabolism of eugenol in man.

1. The metabolism of eugenol (4-hydroxy-3-methoxy-allylbenzene) was investigated in male and female healthy volunteers. It was rapidly absorbed and metabolized after oral administration and was almost completely excreted in the urine within 24 h. Unmetabolized eugenol excreted in urine amounted to less than 0.1% of the dose. 2. The urine contained conjugates of eugenol and of nine metabolites. The structures of these metabolites, elucidated using g.l.c.-mass spectrometry, and by comparison with synthetic reference compounds, were identified as: eugenol, 4-hydroxy-3-methoxyphenyl-propane, cis- and trans-isoeugenol, 3-(4-hydroxy-3-methoxyphenyl)-propylene-1,2-oxide, 3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol, and 3-(4-hydroxy-3-methoxyphenyl)-propionic acid. 3. The structures of the following metabolites were tentatively deduced from mass spectra only, as reference compounds were not available: 3-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-allylbenzene, 3-(6?-mercapto-4-hydroxy-3-methoxyphenyl)-propane, and 2-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-propionic acid. 4. The amounts of the individual metabolites excreted were determined by g.l.c. Some 95% of the dose was recovered in the urine, most of which (greater than 99%) consisted of phenolic conjugates; 50% of the conjugated metabolites were eugenol-glucuronide and sulphate. Other metabolic routes observed were the epoxide-diol pathway, synthesis of a thiophenol and of a substituted propionic acid, allylic oxidation, and migration of the double bond.