Intradialytic hypotension is often caused by a discrepancy between ultrafiltration and plasma refilling. Increasing the plasma refill rate could therefore reduce intradialytic hypotension. We used a recently developed method to measure the effect of cool dialysate and sodium (Na) profiling on refill during hemodialysis (HD). Using a Gambro AK200 with blood volume (BV) sensor plus computer-guided external pump, a high ultrafiltration rate quickly induced a preset BV reduction. A software feedback mechanism subsequently adjusted the ultrafiltration rate continuously to maintain BV between very narrow preset boundaries. The continuously changing, software-generated ultrafiltration rate then quantitatively equalled refill. Absolute plasma refill rate was measured in six stable patients without intradialytic hypotension, undergoing HD without intervention, with cool dialysate (1 degrees C below core temperature), and with Na profiling (gradually declining from 150 to 140 mmol/l). Baseline refill rate was 20.1 + or - 4.0 ml/min (mean + or - SD). Although cool dialysate did not affect refill (22.2 + or - 4.1 ml/min, p = 0.27 vs. baseline), Na profiling induced a significant improvement (26.8 + or - 3.7 ml/min, p = 0.006 vs. baseline). Using our method to measure absolute plasma refill rate during HD, we demonstrated that Na profiling indeed improves the plasma refill rate. A potential effect of cool dialysate could not be established.

Toxic-shock syndrome is primarily caused by the Toxic-shock syndrome toxin 1 (TSST-1), which is secreted by the Gram-positive bacterium Staphylococcus aureus. The toxin belongs to a family of superantigens (SAgs) which exhibit several shared biological properties, including the induction of massive cytokine release and V(beta)-specific T-cell proliferation. In this study we explored the possibility to use monoclonal Variable domains of Llama Heavy-chain antibodies (VHH) in the immuno capturing of TSST-1 from plasma. Data is presented that the selected VHHs are highly specific for TSST-1 and can be efficiently produced in large amounts in yeast. In view of affinity chromatography, the VHHs are easily coupled to beads, and are able to deplete TSST-1 from plasma at very low, for example, pathologically relevant, concentrations. When spiked with 4 ng/mL TSST-1 more than 96% of TSST-1 was depleted from pig plasma. These data pave the way to further explore application of high-affinity columns in the specific immuno depletion of SAgs in experimental sepsis models and in sepsis in humans.

Methods to continuously measure absolute refill during dialysis are not available. It would be useful to have such a method because it would allow investigating the mechanism of refill the effect of interventions. We designed a feedback algorithm that adjusts ultrafiltration rate (QUF) according to hemoglobin (Hb) concentration changes in such a way that relative blood volume (BV) remains constant within a narrow target range. In this situation, the generated QUF quantitatively reflects refill. Refill patterns were studied in five hypotension prone patients. In addition, on separate occasions, we studied the effect of antiembolism stockings (AES) and infusion of hydroxy-ethylated starch (HAES) on refill in these patients. Refill during the first hour fell significantly from 21 +/- 3 ml/min to 9 +/- 2 ml/min (p < 0.05). In the second hour, refill decreased further and became zero in four out of five patients. Neither AES nor HAES measurably affected refill. The marked and rapid fall in refill in the early stages of dialysis suggests untimely depletion of the interstitial compartment and underestimation of dry weight. We propose that continuous, online measurement of refill patterns may be of value for accurate estimation of dry weight in dialysis patients.

The postprandial glycemic response is an important metabolic health factor, which, from laboratory studies, is known to change from low to high over the course of the day, and from which negative health outcomes have been linked to nightly eating. We applied interstitial continuous glucose monitoring to examine the glycemic response to a standardized carbohydrate-rich snack (198 kcal) across the day in a real-life setting. Twenty-four healthy participants (12 men, 12 women, 27–61 y old) consumed the snack nine times during 6 d in a crossover design, altering the time of consumption between morning, afternoon and evening. The snack was consumed in the participant’s own environment with a preceding fast of at least 2.5 h between their customary main meals and practices. Linear mixed models were used with fixed effect of timing, and participant as random effect, to assess incremental area under the curve, peak value and time-to-peak of the glycemic response. Overall, the highest glycemic excursions were observed in the morning, while a more dampened but prolonged response was observed in the evening. These findings do not concur with previously published laboratory studies. This implies that results obtained under controlled experimental conditions in laboratories cannot be generalized directly to predict chrononutritional effects on the glycemic response in healthy individuals and their daily routines.

Severe sepsis is characterized by rapid development of multiple organ failure associated with high mortality. Bacterial toxin release triggers a sequence of events that activates intracellular pathways to produce inflammatory mediators and nitric oxide. There have been numerous attempts to interrupt this devastating cascade by removing toxins, removing or inhibiting mediators, and by blocking receptors of mediators. This review considers toxin properties with a strong focus on toxic shock syndrome toxin 1 and the potential of various removal technologies in relation to these properties. The distribution of toxins in vivo forms a key issue but is nevertheless poorly defined. For toxic shock syndrome toxin 1, either a high clearance or a high degree of compartmentalization to a space not accessible by pheresis or immunoabsorption technologies seems likely. Attempts to remove toxins to treat sepsis may appear futile if we cannot access this space or when the level of induced clearance is too low compared with natural clearance. The impact of these considerations is highly dependent on the exact toxin biology in vivo. Extrapolated to other toxins, we indicate a set of general requirements to be met to facilitate successful toxin removal by a pheresis technique.