Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

Introduction: This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.Methods: IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogen

Interobserver variability between experienced and inexperienced observers in the histopathological analysis of Wilms tumors:a pilot study for future algorithmic approach

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Enterohepatic circulation of triiodothyronine (T3) in rats:Importance of the microflora for the liberation and reabsorption of T3 from biliary T3 conjugates

In normal rats, T3 glucuronide (T3G) is themajor biliary T3 metabolite, but excretion of T3 sulfate (T3S) isgreatly increased after inhibition of type I deiodinase, e.g. with6-propyl-2-thiouracil (PTU). In this study, the fate of the T3conjugates excreted with bile was studied to assess the significance of a putative enterohepatic circulation of T3 in rats.Conventional (CV) or intestine-decontaminated (ID) rats received iv [125I]T3G or [125I]T3S, the latter usually after pretreatment with PTU (1 mg/100 g BW). Radioactivity in plasma andbile or feces was analyzed by Sephadex LH-20 chromatographyand HPLC. Within 1 h, 88% of injected T3G was excreted inbile of CV or ID rats, independent of PTU. About 75% of theinjected T3S was excreted within 4 h in PTU-treated rats, incontrast to only 20% in controls. Up to 13 h after iv administration of T3G or T3S (+PTU) to intact ID and CV rats, fecalradioactivity consisted of more than 90% T3 in all CV rats, 95%of T3S in T3S-injected ID rats, and 30% T3 and 67% T3G inT3G-injected ID rats. In overnight-fasted CV rats injected withT3G, total plasma radioactivity rapidly declined until a nadir of0.10% dose/ml at about 2.5 h, but radioactivity reappeared witha broad maximum of 0.12% dose/ml between 5.5-10 h. In thelatter phase, plasma radioactivity consisted of predominantly I"and T3 in a ratio of 2:1. Reabsorption was diminished in fed CVrats and prevented in ID rats. Plasma T3 4-10 h after iv T3Ginjection to overnight-fasted CV rats was 12, 2, and 3 timeshigher than that in bile-diverted rats, fed CV rats, and ID rats,respectively, and similar to that 4 h after the injection of T3itself. Total plasma radioactivity as well as plasma T3 6-13 hafter iv administration T3S in PTU-treated rats were significantly increased in CV us. ID rats, e.g. T3 0.016% us. 0.005%dose/ml. These results demonstrate a significant enterohepaticcirculation of T3 in rats in which bacterial hydrolysis of T3conjugates excreted with bile plays an important role. {Endocrinology 125: 2822-2830,1989

On the enterohepatic circulation of triiodothyronine in rats: importance of the intestinal microflora.

Until 70 h after a single iv injection of I0 uCi [1251]trllodothyronine (T3) , normal rats excreted 15.8+2.8 % of the radioactivitywith the feces and 17.5+2.7 % with the--urlne, while in intestinedecontaminated rats fecal and urinary excretion over this periodamounted to 25.1+7.2 % and 23.6+4.0 % of administered radioactivity, respeetlvely--(mean~SD, n=4)~ In fecal extracts of decontaminated rats 11.5+6.8 % of the excreted radioactivity consisted of T 3glueuronide ~T3G) and 10.9+2.8 % of T 3 sulfate (T3S) , whereas noconjugates were detected ~n feces from normal rats. Until 26 hafter ig administration of I0 uCi [1251]T3, integrated radioactivity in blood of decontaminated rats was 1.5 times higher than thatin normal rats. However, after ig administration of I0 uCi[1251]T3G or [1251]T3S , radioactivity in blood of decontaminatedrats was 4.9- and 2.8-fold lower, respectively, than in normalrats. The radloactlvlty in tbe serum of control animals was composed of T 3 and iodide in proportions independent of the tracerinjected, while T 3 conjugates represented <I0 % of serum radloactivity. These results suggest an important role of the intestinalmicroflora in the enterohepatlc circulation of T 3 in rats

The learning curve of the direct anterior approach is 100 cases: an analysis based on 15,875 total hip arthroplasties in the Dutch Arthroplasty Register

Background and purpose — In the last decade, the direct anterior approach (DAA) for total hip arthroplasty (THA) has become more popular in the Netherlands. Therefore, we investigated the learning curve and survival rate of the DAA in primary THA, using data from the Dutch Arthroplasty Register (LROI). Patients and methods — We identified all patients who received a primary THA using the DAA in several highvolume centers in the Netherlands between 2007 and 2019 (n = 15,903). Procedures were ordered per surgeon, using date of operation. Using the procedure number, operations were divided into 6 groups based on the number of previous procedures per surgeon (first 25, 26–50, 51–100, 101–150, 151–200, > 200). Data from different surgeons in different hospitals was pooled together. Revision rates were calculated using a multilevel time-to-event analysis. Results — Patients operated on in group 1–25 (hazard ratio [HR] 1.6; 95% CI 1.1–2.4) and 26–50 (HR 1.6; CI 1.1–2.5) had a higher risk for revision compared with patients operated on in group > 200 THAs. Between 50 and 100 procedures the revision risk was increased (HR 1.3; CI 0.9–1.9), albeit not statistically significant. From 100 procedures onwards the HR for revision was respectively 1.0 (CI 0.6–1.6) and 0.8 (CI 0.5–1.4) for patients in operation groups 101–150 and 151–200. Main reasons for revision were loosening of the stem (29%), periprosthetic infection (19%), and dislocation (16%). Interpretation — We found a 64% increased risk of revision for patients undergoing THA using the DAA for the first 50 cases per surgeon. Between 50 and 100 cases, this risk was 30% increased, but not statistically significant. From 100 cases onwards, a steady state had been reached in revision rate. The learning curve for DAA therefore is around 100 cases