Prescribing dialysate bicarbonate concentrations for hemodialysis patients

A rearranged equation of Sargent and Gotch (1) was used to determine dialysate bicarbonate concentrations for hemodialysis patients. Parameters in this equation include an estimate of the acid generated by each patient between treatments, an estimate for the dialyzer dialysance for bicarbonate, ultrafiltration rate, blood flow rate and a targeted mid-dialysis plasma bicarbonate concentration of 25 mEq/L. Nine patients were studied over a 35 week period to verify this method of determining each patient's dialysate bicarbonate concentration. Prescribed dialysate bicarbonate concentrations for the nine patients varied from 29 to 38 mEq/L with five patients having a prescribed value of 35 mEq/L. After a baseline period of five weeks, five patients switched from a 37 mEq/L acetate dialysate to their prescribed dialysate bicarbonate concentration. Four patients who had already been on bicarbonate dialysis at a concentration of 35 mEq/L were dialyzed with their prescribed dialysate bicarbonate concentrations. Patients were then followed for a study period of 30 weeks. The prescribed dialysate bicarbonate concentration resulted in more normal acid/base chemistries for both groups of patients. The results also demonstrate that chronic hemodialysis patients require individualization of dialysate bicarbonate concentrations.     

Super high flux hemodialysis at high dialysate flows: an ex vivo assessment

BACKGROUND AND OBJECTIVES: The removal of cytokines by standard hemofiltration is limited. Super high flux membranes may significantly improve removal even when used in dialysis mode. We sought to measure cytokine clearance using a large surface super high-flux membrane and a standard hemodialysis setting. SETTING: ICU laboratory of a tertiary institution. SUBJECTS: Six healthy volunteers. METHODS: Blood form healthy volunteers was incubated for 4 hours with E. coli endotoxin to stimulate cytokine production. Cytokine containing blood was then circulated through a dialysis circuit at 3 different dialysate flow rates. Blood and dialysate were sampled for cytokine and albumin measurements and calculation of clearances. RESULTS: Super high-flux dialysis achieved high median cytokine clearances (IL-1 clearance of 106 ml/min, IL-6 clearance of 66.8 ml/min, IL-8 clearance of 61.7 ml/min and TNF clearance of 36.1 ml/min). Increasing dialysate flow rate from 300 to 500 ml/min did not significantly increase cytokine clearances. Albumin clearances however were between 2.7 and 5.4 ml/min. CONCLUSIONS: Cytokine dialysis is feasible at high dialysate flow rates yielding high cytokine clearances. Albumin loss, however, is appreciable and may require separate supplementation in the clinical setting.     

Needle biopsy‐derived myofascial tissue samples are sufficient for quantification of myofibroblast density

Quantification of myofibroblasts is a promising method for assessing tissue properties in the field of fascia research. This is commonly performed by immunohistochemistry for α‐smooth muscle actin. However, usually larger tissue samples sizes are required for quantification. The aim of this investigation was to explore whether a microscopic quantification of myofibroblasts can be conducted with fascial tissue samples derived via percutaneous needle biopsy. Fascial tissues were derived via percutaneous needle biopsy from the fascia lata of 11 persons (aged 19–40 years). Following immunohistochemistry, selected fields for photomicroscopic analysis were chosen by a Monte Carlo method based randomization procedure. On these fields, a digital quantification for the relative density of α‐smooth muscle actin was attempted. The newly developed quantification method could successfully be applied in all tissue samples. The median α‐smooth muscle actin density in the selected tissue samples ranged between 0% and 1.7% (median 0%, IQR 0%–0.001%). The applied protocol proved to be workable for the purpose of an estimation of the α‐smooth muscle actin density in fascial tissue samples derived via percutaneous needle biopsy. Since this type of biopsy is less invasive than the commonly performed open muscle biopsy, this offers a new and useful perspective for future histological investigations of fascial tissue properties in living patients. Clin. Anat. 31:368–372, 2018. © 2018 Wiley Periodicals, Inc.     

A new technique for low-volume continuous sampling of spent dialysate: a validation study

Journal of Artificial Organs - The measure of hemodialysis (HD) adequacy recommended nowadays by most guidelines, Kt/V-urea, presents significant drawbacks. Direct dialysis quantification (DDQ)...     

Biofeedback regulation of ultrafiltration and dialysate conductivity for the prevention of hypotension during hemodialysis

Intradialytic hypotension remains a frequent complication of dialysis, occurring in up to 33% of patients. We tested a fully integrated biofeedback system (the Hemocontrol system) that monitors and regulates blood volume contraction during hemodialysis. Seven hypotension prone patients were selected for the study. We conducted a prospective crossover study alternating dialysis sessions using the blood volume regulation system and standard dialysis sessions. Event free sessions were defined as dialysis sessions not requiring any therapeutic intervention for hypotension related signs or symptoms. There was a significant improvement in the number of event free sessions with blood volume regulation compared with standard dialysis (50.8% of sessions vs. 29.2%; p < 0.01). Percentages of event free sessions and mean postdialysis systolic blood pressure improved progressively over the course of the study, indicating improved hemodynamic stability over the study period. Therefore, the use of a biofeedback system to monitor and regulate blood volume during dialysis was helpful in restoring cardiovascular stability in a population of hypotension prone hemodialysis patients. Further studies are needed to confirm these preliminary results and to establish the role of blood volume regulation systems in reducing the incidence of hypotension during hemodialysis.     

Regional citrate anticoagulation for hemodialysis: calcium-free vs. calcium containing dialysate - a randomized trial

BACKGROUND: The majority of citrate protocols for hemodialysis (HD) use calcium (Ca)-free dialysate, a limited number use dialysate with Ca, aiming to simplify the procedure. This randomized clinical study sought to compare the anticoagulant effect of citrate using Ca-free dialysate and dialysate with Ca 1.25 mmol/L. METHODS: Fifty HD procedures (in 5 chronic HD patients treated by chronic citrate anticoagulation) were randomly assigned to Ca-free dialysate (25 procedures) or Ca-1.25 dialysate (25 procedures), both with Mg 0.5 mmol/L, Na 138 mmol/L, and bicarbonate 28 mmol/L. Ca-free HD: 15% Na3 citrate 80 ml/hour was infused into the arterial line, and 1 M CaCl2, 14 ml/hour into the venous line. Ca-1.25 group: 15% Na3 citrate 100 ml/hour, 1 M CaCl2 2-4 ml/hour. Polyflux H dialyzers were used. Antithrombotic effect was assessed visually after HD at 3 points: dialyzer, arterial, and venous bubble traps, using a score of 5 (no clotting) to 1 (total clotting). RESULTS: Ca-free group: arterial bubble trap score 4.7 +/- 0.5, dialyzer 4.5 +/- 0.6, venous bubble trap 4.8 +/- 0.6. Ionized calcium (iCa) at dialyzer inlet 0.34 +/- 0.17, outlet 0.21 +/- 0.06 mmol/L. All HDs were completed successfully. Ca-1.25 group: arterial bubble trap score 4.7 +/- 0.5 (NS), dialyzer 2.6 +/- 1.04 (p<0.01), venous bubble trap 2.4 +/- 0.9 (p<0.01). Volume of clot in venous bubble trap was 1.9 +/- 1.8 mL (range 0.5-6 mL). iCa at dialyzer inlet 0.24 +/- 0.05 mmol/L (p<0.05), outlet 0.63 +/- 0.11 mmol/L (p<0.01). Four of 25 HD procedures (16%) were prematurely terminated due to threatening dialyzer clotting, in 6/25 HD procedures (24%), the venous line was changed (p<0.01). CONCLUSION: Citrate anticoagulation with Ca-1.25 dialysate resulted in significantly worse anticoagulation of dialyzer and venous bubble trap compared with Ca-free dialysate, despite higher citrate dose.     

Temporal data mining for the quality assessment of hemodialysis services

OBJECTIVE: This paper describes the temporal data mining aspects of a research project that deals with the definition of methods and tools for the assessment of the clinical performance of hemodialysis (HD) services, on the basis of the time series automatically collected during hemodialysis sessions. METHODS: Intelligent data analysis and temporal data mining techniques are applied to gain insight and to discover knowledge on the causes of unsatisfactory clinical results. In particular, two new methods for association rule discovery and temporal rule discovery are applied to the time series. Such methods exploit several pre-processing techniques, comprising data reduction, multi-scale filtering and temporal abstractions. RESULTS: We have analyzed the data of more than 5800 dialysis sessions coming from 43 different patients monitored for 19 months. The qualitative rules associating the outcome parameters and the measured variables were examined by the domain experts, which were able to distinguish between rules confirming available background knowledge and unexpected but plausible rules. CONCLUSION: The new methods proposed in the paper are suitable tools for knowledge discovery in clinical time series. Their use in the context of an auditing system for dialysis management helped clinicians to improve their understanding of the patients' behavior.     

Explaining savings for visuomotor adaptation: linear time-invariant state-space models are not sufficient

Adaptation of the motor system to sensorimotor perturbations is a type of learning relevant for tool use and coping with an ever-changing body. Memory for motor adaptation can take the form of savings: an increase in the apparent rate constant of readaptation compared with that of initial adaptation. The assessment of savings is simplified if the sensory errors a subject experiences at the beginning of initial adaptation and the beginning of readaptation are the same. This can be accomplished by introducing either 1) a sufficiently small number of counterperturbation trials (counterperturbation paradigm [CP]) or 2) a sufficiently large number of zero-perturbation trials (washout paradigm [WO]) between initial adaptation and readaptation. A two-rate, linear time-invariant state-space model (SSM(LTI,2)) was recently shown to theoretically produce savings for CP. However, we reasoned from superposition that this model would be unable to explain savings for WO. Using the same task (planar reaching) and type of perturbation (visuomotor rotation), we found comparable savings for both CP and WO paradigms. Although SSM(LTI,2) explained some degree of savings for CP it failed completely for WO. We conclude that for visuomotor rotation, savings in general is not simply a consequence of LTI dynamics. Instead savings for visuomotor rotation involves metalearning, which we show can be modeled as changes in system parameters across the phases of an adaptation experiment.     

Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells

Staphylococcus aureus invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, critically depends on fibronectin bridging between S. aureus fibronectin-binding proteins (FnBPs) and the host fibronectin receptor integrin alpha(5)beta(1) (B. Sinha et al., Cell. Microbiol. 1:101-117, 1999). However, it is unknown whether this mechanism is sufficient for S. aureus invasion. To address this question, various S. aureus adhesins (FnBPA, FnBPB, and clumping factor [ClfA]) were expressed in Staphylococcus carnosus and Lactococcus lactis subsp. cremoris. Both noninvasive gram-positive microorganisms are genetically distinct from S. aureus, lack any known S. aureus surface protein, and do not bind fibronectin. Transformants of S. carnosus and L. lactis harboring plasmids coding for various S. aureus surface proteins (FnBPA, FnBPB, and ClfA) functionally expressed adhesins (as determined by bacterial clumping in plasma, specific latex agglutination, Western ligand blotting, and binding to immobilized and soluble fibronectin). FnBPA or FnBPB but not of ClfA conferred invasiveness to S. carnosus and L. lactis. Invasion of 293 cells by transformants was comparable to that of strongly invasive S. aureus strain Cowan 1. Binding of soluble and immobilized fibronectin paralleled invasiveness, demonstrating that the amount of accessible surface FnBPs is rate limiting. Thus, S. aureus FnBPs confer invasiveness to noninvasive, apathogenic gram-positive cocci. Furthermore, FnBP-coated polystyrene beads were internalized by 293 cells, demonstrating that FnBPs are sufficient for invasion of host cells without the need for (S. aureus-specific) coreceptors.     

Pregastric stimulation and cholecystokinin are not sufficient for the meal size-intermeal interval correlation in the rat

Male albino rats with gastric fistula ate liquid food at the midpoints of the day or night phases of a 12:12 cycle after 3-hr food deprivation. During normal eating with fistula closed, rats (n=18) ate a mean meal size (MS) of 5.1 ml followed by a mean intermeal interval (IMI) of 67.2 min during the day, and rats (n=7) ate a MS of 3.0 ml followed by an IMI of 26.8 min at night. The MS and subsequent IMI correlated positively both in the day and night. When rats sham fed the first time with fistula open, the sham-fed MS was larger and IMI was shorter than were MS and IMI, respectively, when the fistula was closed during the night and day, and the MS-IMI correlation was absent in the day and night. When rats sham fed after intraperitoneal injection of 20% pure cholecystokinin (CCK) (day: 30 U/kg; night: 60 U/kg), sham-fed MS and IMI were not different from normal MS and IMI, respectively, when the fistula was closed during the night and day, but CCK failed to restore a normal MS-IMI correlation in the day or night. These results show that while certain food-contingent stimuli are potent for eliciting postprandial satiety including intermeal interval, preabsorptive pregastric stimuli and cholecystokinin may not be of major importance for the correlation between meal size and postprandial intermeal interval in the rat.     

Skin-prick blood samples are reliable for estimating Hb mass with the CO-dilution technique

Investigation of the impact of environmental stimuli such as altitude exposure on hemoglobin mass currently rely on invasive techniques that require venous blood sampling. This study assessed the feasibility of lancet skin pricks as an alternative to venepuncture to estimate hemoglobin mass with the carbon monoxide (CO) dilution technique, with the intent of making the technique accessible to technicians without phlebotomy training. Sixteen healthy volunteers rebreathed CO via a small-volume rebreathing apparatus. Blood was sampled simultaneously with a glass syringe (VEN) from a superficial forearm vein and with a capillary tube from either a lanced fingertip or earlobe (CAP). As a control, VEN blood was then aliquoted into capillary tubes (CONTROL-CAP). Samples were assayed for carboxyhemoglobin (HbCO) using a diode-array spectrophotometer. Mean %HbCO was higher in CAP than VEN (bias 0.3?±?0.2%HbCO, p?p?=?0.55). Compared to VEN, Hb mass derived from CAP samples was overestimated by 1.7% (15?±?22?g Hb, p?=?0.01). CAP samples to estimate Hb mass demonstrated a technical error of measurement of 2.7%, which is comparable to the 1.9% reported previously with VEN samples. We conclude that using CAP samples gives a reliable measure of %HbCO, and will make the estimation of Hb mass with the CO-technique accessible to technicians without phlebotomy training.     

Surrogate markers are not useful for identification of HCV carriers in chronic hemodialysis patients.

Several diagnostic hepatitis C assays have been developed for the detection of antibodies to different antigens of the virus. This virus is the major cause of non-A, non-B hepatitis. Seventy-nine patients undergoing chronic hemodialysis and/or hemofiltration were tested for the presence of anti-HCV antibodies (anti-C-100-3 antibodies and anti-core antibodies), anti-hepatitis B core antibodies (anti-HBc), and aminotransferases (ALT). Seven patients were positive by one or more of the anti-HCV enzyme linked immunoassays (EIAs), while HCV-RNA was detectable in only four patients. These four patients had at least one, but not necessarily the same, positive anti-HCV EIA. HCV-RNA was not detected in patients who had no antibodies as determined by all six anti-HCV EIAs. All patients with a marker for HCV infection had persistent normal levels of transaminases. Three patients had elevated ALT values without a marker for HCV infection and suffered from hepatitis B virus infection. Anti-HBc was detected in 27/72 patients without any marker and in four patients with a marker of HCV infection. However, HCV-RNA was detectable in only one of these four anti-HBc positive patients. It is concluded that surrogate markers (anti-HBc and serum transaminases) are not useful for identification of HCV carriers in chronic hemodialysis patients.     

Propriospinal neurons are sufficient for bulbospinal transmission of the locomotor command signal in the neonatal rat spinal cord

We recently showed that propriospinal neurons contribute to bulbospinal activation of locomotor networks in the in vitro neonatal rat brainstem–spinal cord preparation. In the present study, we examined whether propriospinal neurons alone, in the absence of long direct bulbospinal transmission to the lumbar cord, can successfully mediate brainstem activation of the locomotor network. In the presence of staggered bilateral spinal cord hemisections, the brainstem was stimulated electrically while recording from lumbar ventral roots. The rostral hemisection was located between C1 and T3 and the contralateral caudal hemisection was located between T5 and mid-L1. Locomotor-like activity was evoked in 27% of the preparations, which included experiments with staggered hemisections placed only two segments apart. There was no relation between the likelihood of developing locomotor-like activity and the distance separating the two hemisections or specific level of the hemisections. In some experiments, where brainstem stimulation alone was ineffective, neurochemical excitation of propriospinal neurons (using 5-HT and NMDA) at concentrations subthreshold for producing locomotor-like activity, promoted locomotor-like activity in conjunction with brainstem stimulation. In other experiments, involving neither brainstem stimulation nor cord hemisections, the excitability of propriospinal neurons in the cervical and/or thoracic region was selectively enhanced by bath application of 5-HT and NMDA or elevation of bath K⁺ concentration. These manipulations produced locomotor-like activity in the lumbar region. In total, the results suggest that propriospinal neurons are sufficient for transmission of descending locomotor command signals. This observation has implications for regeneration strategies aimed at restoration of locomotor function after spinal cord injury.     

Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development

Parental origin-specific DNA methylation regulates the monoallelic expression of the mammalian imprinted genes. The methylation marks or imprints are established in the parental germline and maintained throughout embryonic development. However, it is unclear how the methylation imprints are maintained through extensive demethylation in cleavage-stage preimplantation embryos. Previous reports suggested that DNA methyltransferase(s) other than Dnmt1 is involved in the maintenance of the imprints during cleavage. Here we demonstrate, by using conditional knockout mice, that the other known DNA methyltransferases Dnmt3a and Dnmt3b are dispensable for the maintenance of the methylation marks at most imprinted loci. We further demonstrate that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of all imprinted loci examined in blastocysts. Consistent with these results we find that zygotic Dnmt1 is expressed in the preimplantation embryo. Thus, contrary to the previous reports, Dnmt1 alone is sufficient to maintain the methylation marks of the imprinted genes.     

Two sibs who are double heterozygotes for achondroplasia and pseudoachondroplastic dysplasia.

We report a family in which two sibs have both achondroplasia and pseudoachondroplastic dysplasia. The mother has achondroplasia and the father has pseudoachondroplastic dysplasia, which he had inherited from his father. Both children appeared typical of achondroplasia at birth. By 1 1/2 years they had developed a fixed lumbar kyphosis with gibbus and had additional x ray changes unusual for just achondroplasia and suggestive of pseudoachondroplastic dysplasia. Subsequently both children have shown characteristic features of both conditions and have grown less well than expected for achondroplasia. Radiographs show the striking synergistic effects of the two conditions. MRI in both sibs confirmed brain stem compression at the foramen magnum. This may be an important complication and should be actively sought in any double heterozygote.