Whole body Kt/V from dialysate urea measurements during hemodialysis

A new method for the calculation of dialysis dose from continuous measurements of dialysate urea concentrations has been developed. It is based on urea mass in the patient instead of plasma concentrations, and results in a measure of dialysis dose that has been named whole body Kt/V. The measured urea mass removal rate and the slope of the dialysate urea concentration curve are the key parameters needed for the calculations. No assumptions have to be made about urea distribution in the body (single or double pool, etc.). Blood sampling is not needed. This simplifies the logistics and eliminates the problems with rebound and timing in taking samples. The total urea mass present in the body before treatment is also obtained. It can be used directly, or in relation to body weight or water volume, as a measure of the level of urea in the body. This may serve as an alternative to pretreatment plasma concentration. If a pretreatment plasma urea concentration is available, the urea distribution volume can be calculated, which may be of separate clinical interest.     

Assessment of dialysis adequacy using the dialysate urea monitor: preliminary experience of the dialysate urea monitor

Numerous studies have identified a strong linkage between the delivered dialysis dose (Kt/V) and the survival of hemodialysis (HD) patients. However, the current method used to calculate Kt/V requires multiple blood samples and the process is complex and time consuming. We evaluate the performance of a recently developed on-line monitor (Biostat 1000 dialysate urea monitor, Baxter) that measures the urea concentration in the effluent dialysate and displays Kt/V and nPCR immediately after hemodialysis. To verify the performance of the urea monitor, we selected 21 hemodialysis patients, calculated their Kt/V and nPCR values from blood samples obtained during each hemodialysis, and compared the results with data obtained using the urea monitor. The Kt/V and nPCR values calculated by the urea monitor were both significantly correlated with those obtained using blood samples (R = 0.804, p < 0.001 in Kt/V and R = 0.749, p < 0.001 in nPCR). Our results suggest that the urea monitor may be used for on-line assessment of dialysis adequacy and obviates the need for blood sampling.     

Changes in [K+]o evoked by baclofen in guinea pig hippocampus

OBJECTIVE: Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. METHODS: Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. RESULTS: Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. CONCLUSIONS: In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using similar format and treatments. Potassium citrate was not hypocalciuric in children, a response differing from that for adults, who have shown a decrease in acute urinary calcium excretion in response to alkaline potassium treatment. Further characterization of calciuric responses to dietary factors is required for children, who may differ from adults in many respects.     

Delta9-tetrahydrocannabinol activates [Ca2+]i increases partly sensitive to capacitative store refilling

Delta9-tetrahydrocannabinol induces [Ca2+]i increases in DDT1MF-2 smooth muscle cells. Both Ca2+ entry and release from intracellular Ca2+ stores were concentration dependently activated. The Ca2+ entry component contributed most to the increases in [Ca2+]i. Stimulation with delta9-tetrahydrocannabinol after functional downregulation of intracellular Ca2+ stores by longterm thapsigargin treatment, still induced a major Ca2+ entry and a minor Ca2+ release component. Thapsigargin sensitive influx and release were selectively inhibited by the cannabinoid CB1 receptor antagonist SR141716A. No effects on [Ca2+]i were obtained after stimulation with the CB2 receptor agonist palmitoylethanolamide. This study is the first demonstration of (1) Ca2+ release from thapsigargin sensitive intracellular stores and capacitative Ca2+ entry via CB1 receptor stimulation and of (2) an additional delta9-tetrahydrocannabinol induced thapsigargin insensitive component, mainly representing Ca2+ influx which is neither mediated by CB1 nor CB2 receptor stimulation.     

Cardiac sympathetic stimulation increases cardiac contractility but decreases contractile efficiency in canine hearts in vivo

The effect of cardiac sympathetic stimulation on cardiac contractile efficiency was studied in dogs. In 19 anesthetized and open-chest dogs, left ventricular (LV) pressure, LV volume, coronary blood flow and coronary venous oxygen saturation were measured simultaneously. The LV end-systolic pressure volume relations (ESPVR) and the relation between myocardial oxygen consumption (VO2)-pressure volume area (PVA) were obtained during a transient occlusion of the inferior vena cava before and after sympathetic stimulation (9V, 6 Hz, 40 sec) both with and without 50 mg/kg of 2,3-butanedione monoxime (BDM). Without BDM, sympathetic stimulation increased the slope of ESPVR by 62% (p<0.05), the slope of the VO2-PVA line by 19% (p<0.05) and the y-axis intercept of the VO2-PVA by 65% (p<0.05). With BDM, the increase in the slope of the VO2-PVA line became insignificant although other responses were similarly preserved. These data imply that cardiac sympathetic stimulation decreases cardiac contractile efficiency through mechanisms by which norepinephrine-induced beta-adrenergic activation enhances myosin ATPase-operating ATP hydrolysis in crossbridge formation.     

K(+)- and transmitter-induced rises in [Ca2+]i in auditory neurones of developing rats

Ca2+ ions are thought to play important roles in processes underlying neuronal plasticity such as synapse stabilization. We employed the Fura-2 technique on brainstem slices of neonatal rats to measure changes in intracellular Ca2+ ([Ca2+]i) in neurons of the lateral superior olive (LSO) in order to analyse whether these cells have functional Ca2+ channels when synaptic maturation takes place. Rises in intracellular Ca2+ could be induced by KCl-evoked depolarizations or by glutamate, but not by glycine or GABA. These results show that Ca2+ channels are present in developing LSO neurones and that many of them, if not all, belong to the voltage-sensitive type. We speculate that these channels play a role during ontogeny by mediating Ca(2+)-dependent mechanisms of synapse stabilization.     

CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion

Increases in [Ca2+]i in pancreatic beta cells, resulting from Ca2+ mobilization from intracellular stores as well as Ca2+ influx from extracellular sources, are important in insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated in beta cells by glucose stimulation, has been postulated to serve as a second messenger for intracellular Ca2+ mobilization for insulin secretion, and CD38 is thought to be involved in the cADPR accumulation (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here we created "knockout" (CD38(-/-)) mice by homologous recombination. CD38(-/-) mice developed normally but showed no increase in their glucose-induced production of cADPR in pancreatic islets. The glucose-induced [Ca2+]i rise and insulin secretion were both severely impaired in CD38(-/-) islets, whereas CD38(-/-) islets responded normally to the extracellular Ca2+ influx stimulants tolbutamide and KCl. CD38(-/-) mice showed impaired glucose tolerance, and the serum insulin level was lower than control, and these impaired phenotypes were rescued by beta cell-specific expression of CD38 cDNA. These results indicate that CD38 plays an essential role in intracellular Ca2+ mobilization by cADPR for insulin secretion.     

Effects of barium on stimulus-induced rises in [K+]o in juvenile rat hippocampal area CA1

Immature glia may not be able to buffer K+ ions released during neuronal activity. Therefore, we investigated entorhinal-hippocampal slices of juvenile rats (ages P15-18 and P22-26) using a perfusion medium containing 2 mM BaCl2 in order to block glial inward rectifying and leak potassium channels. In contrast to adult animals, rises in [K+]o in slices from juvenile animals elicited by repetitive alvear stimulation were not augmented by Ba2+. Ba2+ effects on fast field potentials, slow field potentials and the applied current sink source distribution were roughly similar as in adult rats. We conclude that the capacity to buffer large quantities of K+ ions by mechanisms involving Ba2+-sensitive K+ channels has not yet developed in juveniles.     

Fluorescence and laser photon counting: measurements of epithelial [Ca2+]i or [Na+]i with ciliary beat frequency

We describe a system we developed that enabled simultaneous measurements of either epithelial calcium ion concentration ([Ca2+]i) or sodium ion concentration ([Na+]i) with the ciliary beat frequency (CBF) in native ciliated epithelia using either Fura-2 (AM) or SBFI (AM) ratiometric fluorescence photon counting along with nonstationary laser light scattering. Studies were performed using native epithelial tissues obtained from ovine tracheae. The dynamic range of the laser light-scattering system was determined by a simulated light "beating" experiment. The nonstationary CBF was demonstrated by the time-frequency analysis of the raw photon count sequences of backscattered heterodyne photons from cultured and native epithelia. Calibrations of calcium and sodium ion concentrations were performed using the respective Fura-2 and SBFI impermanent salts as well as in native epithelia. The cumulative responses of 10(-6), 10(-5), and 10(-4) M nifedipine on [Ca2+]i together with the CBF as well as the cumulative responses of 10(-5), 10(-4), and 10(-3) M amiloride on [Na+]i together with the CBF were also determined. Nifedipine decreased [Ca2+]i but had no effect on CBF. Amiloride decreased [Na+]i and CBF. Stimulation of CBF corresponded with either an increase of [Na+]i or an increase of [Ca2+]i. Decreases of [Na+]i or substantial decreases of [Ca2+]i were associated with decreases in the CBF. These data demonstrate the utility of this system for investigating the regulatory mechanisms of intracellular ions dynamics and the CBF in native epithelia.     

Carboxyeosin decreases the rate of decay of the [Ca2+]i transient in uterine smooth muscle cells isolated from pregnant rats

We assessed whether using the tracheal diameter to predict the correct size of the left double-lumen endobronchial tube (DLT) could be used for our generally smaller sized Asian patients. Sixty-six consecutive adult patients under anesthesia for elective surgery requiring the use of a DLT were studied. The size of the left-sided DLT used was based on the width of patients' trachea measured from the preoperative posterior-anterior chest radiograph. The placement of the DLT was standardized and confirmed with fiberoptic bronchoscopy. The correct size of the DLT was the largest size tube inserted into the left bronchus with a small air leak detectable when the endobronchial cuff was deflated but not exceeding the recommended resting volume when inflated for lung isolation. Using this method of choosing our DLT, we found that an oversized DLT was often chosen especially among our female Asian patients. The overall positive predictive values for the male and female patients were 77.3% and 45.5%, respectively. We postulate that this could be due to our criteria for correct DLT size or that our local Asian patients, especially the females, were smaller and shorter. IMPLICATIONS: This study assessed whether the correct double-lumen endobronchial tube size could be predicted from tracheal diameter measurements taken from the chest radiograph. We found that this method of choosing the double-lumen endobronchial tubes was not always reliable.     

Overestimation of hemodialysis dose depends on dialysis efficiency by regional blood flow but not by conventional two pool urea kinetic analysis

In 26 patients, a linear relationship between delta Kt/V (equilibrated minus single pool) and dialysis efficiency K/V was noted (r = -0.72). To determine if such a relationship would be supported by formal urea kinetic analysis, t, Kd, and V were randomly varied in 1,400 simulations using both intracellular/extracellular and regional blood flow 2 pool variable volume models. In the intracellular/extracellular model, delta Kt/V was best correlated with Kd/Kc (r = -0.96), where Kc is the intercompartmental clearance. Kc was not correlated with V, which translated into a lack of correlation between delta Kt/V and V, and a better correlation between delta Kt/V and Kd than between delta Kt/V and K/V. In the regional blood flow model delta Kt/V was best correlated with Kd/QL (r = -0.99), where QL is the perfusion of the low flow compartment. QL was correlated with V because QL is a function of cardiac output, which varies with surface area and therefore with V. In the regional blood flow model, delta Kt/V did correlate with V (r = 0.49), and better with K/V (r = -0.76) than with K (r = -0.47), similar to the results in patients. The slope of delta Kt/V on K/V depended upon fQL (the fractional perfusion of the low flow compartment) and on cardiac index. At an fQL of 0.15 and a cardiac index of 2.85, the theoretical slope was similar to that seen in observational data: delta Kt/V = -0.6 x K/V + 0.03. The results show that the regional blood flow model predicts the observed relation between delta Kt/V and K/V, whereas the intracellular/extracellular model fails in this task unless one arbitrarily ties Kc to V.     

Playing prosocial video games increases empathy and decreases schadenfreude.

Past research provided abundant evidence that exposure to violent video games increases aggressive tendencies and decreases prosocial tendencies. In contrast, research on the effects of exposure to prosocial video games has been relatively sparse. The present research found support for the hypothesis that exposure to prosocial video games is positively related to prosocial affect and negatively related to antisocial affect. More specifically, two studies revealed that playing a prosocial (relative to a neutral) video game increased interpersonal empathy and decreased reported pleasure at another's misfortune (i.e., schadenfreude). These results lend further credence to the predictive validity of the General Learning Model (Buckley & Anderson, 2006) for the effects of media exposure on social tendencies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Developmental increases and decreases in solutions of conditional syllogism problems.

281 students (Grades 8, 10, and 12 and college sophomores) were given a 16-item conditional reasoning test which contained 1 each of the arguments generated by the orthogonal arrangement of (a) stating the major premise in each of the 4 combinations of positive and negative instances of the antecedent or consequent, and (b) stating the 2nd premise in each of the 4 cases of affirming or denying the antecedent or consequent. Analysis of results indicated little development after Grade 8 for the easy affirm-antecedent problems, substantial increase on the deny-antecedent and affirm-consequent problems from below chance at the 8th grade to mediocre performance levels for college sophomores and a surprising monotonic decrease in performance on the deny-consequent problems from Grade 8 to the college sophomore year. An error analysis was performed which revealed that the poor performance of younger Ss and even adults may be partially an artifact of students misinterpreting the "if, then" conditional statements as biconditional ("if and only if, then") propositions. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Different mechanisms for [Ca2+]i oscillations induced by carbachol and high concentrations of [Ca2+]o in the rat ventricular myocyte

1. The purpose of the present study was to explore the different mechanisms of [Ca2+]i oscillations induced by high concentrations of either carbachol (CCh) or extracellular Ca2+ ([Ca2+]o). First, we compared the oscillations induced by CCh at concentrations of 100-300 micromol/L and [Ca2+]o (5 mmol/L) in the single rat ventricular myocyte. Second, we studied CCh- and [Ca2+]o-induced [Ca2+]i oscillations following either interference with the production of inositol trisphosphate (IP3), reductions in cytosolic Ca2+ ([Ca2+]i), inhibition of Ca2+ influx and Na+-Ca2+ exchange or depletion of Ca2+ from its intracellular store. 2. The [Ca2+]i oscillations induced by CCh were frequent and were superimposed on [Ca2+]i transients in electrically stimulated cells, whereas those induced by high [Ca2+]o were occasional and occurred in quiescent cells and between [Ca2+]i transients in electrically stimulated cells. In both cases, [Ca2+]i oscillations were preceded by an increase in resting levels of [Ca2+]i. 3. Carbachol-induced [Ca2+]i oscillations were accompanied by an increase in amplitude and prolongation of the time of decline to 80% of the peak of the [Ca2+]i transient, while high [Ca2+]o-induced [Ca2+]i oscillations were the opposite. 4. A reduction of [Ca2+]o to 0.1 mmol/L and treatment with Ni2+ or ryanodine or 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid AM (BAPTA-AM) abolished the [Ca2+]i oscillations induced by both CCh and high [Ca2+]o. 5. The calcium channel blockers verapamil and nifedipine and inhibitors of phospholipase C (neomycin and U-73122) abolished the [Ca2+]i oscillations induced by CCh; Li+ accelerated the onset of the [Ca2+]i oscillations induced by CCh. 6. These observations suggest that the mechanisms responsible for the [Ca2+]i oscillations induced by CCh and high [Ca2+]o are different from each other. Other than an increase in extracellular Ca2+ influx as a mechanism common for both CCh- and high [Ca2+]o-induced [Ca2+]i oscillations, the CCh-induced [Ca2+]i oscillations involve influx of Ca2+ via L-type Ca2+ channels, Na+-Ca2+ exchange, mobilization of intracellular Ca2+ and IP3 production.     

Time course of the initial [Ca2+]i response to extracellular ATP in smooth muscle depends on [Ca2+]e and ATP concentration

In response to extracellular application of 50 microM ATP, all individual porcine aortic smooth muscle cells respond with rapid rises from basal [Ca2+]i to peak [Ca2+]i within 5 s. The time from stimulus to the peak of the [Ca2+]i response increases with decreasing concentration of ATP. At ATP concentrations of 0.5 microM and below, the time to the [Ca2+]i peak varies more significantly from cell to cell than at higher concentrations, and each cell shows complicated initiation and decay kinetics. For any individual cell, the lag phase before a response decreases with increasing concentration of ATP. An increase in lag time with decreasing ATP concentration is also observed in the absence of extracellular Ca2+, but the lag phase is more pronounced, especially at concentrations of ATP below 0.5 microM. Whole-cell patch-clamp electrophysiology shows that in porcine aortic smooth muscle cells, ATP stimulates an inward current carried mainly by Cl- ion efflux with a time course similar to the [Ca2+]i changes and no detectable current from an ATP-gated cation channel. A simple signal cascade initiation kinetics model, starting with nucleotide receptor activation leading to IP3-mediated Ca2+ release from IP3-sensitive internal stores, fits the data and suggests that the kinetics of the Ca2+ response are dominated by upstream signal cascade components.     

Sequential increases and decreases in blood flow stimulates progressive intimal thickening

Exfoliative toxins of approximately 30 kDa produced by Staphylococcus hyicus strains NCTC 10350, 1289D-88 and 842A-88 were purified and specific polyclonal antisera were raised against each of the toxins. It was shown by immunoblot analysis and ELISA that three exfoliative toxins from S. hyicus were antigenically distinct. The three toxins were designated ExhA, ExhB and ExhC. From 60 diseased pigs, each representing an outbreak of exudative epidermitis, a total of 584 isolates of S. hyicus were phage typed and tested for production of exfoliative toxin. ExhA-, ExhB- and ExhC-producing S. hyicus isolates were found in 12 (20%), 20 (33%) and 11 (18%), respectively, of the 60 pig herds investigated. Production of the different types of exfoliative toxin was predominantly associated with certain phage groups. However, toxin production was found in all of the six phage groups defined by the phage typing system. Some changes in the distribution of isolates between phage groups were observed when the results of this study were compared to previous investigations. In this study two new antigenically distinct exfoliative toxins were isolated and tools for in vitro detection of toxin producing S. hyicus isolates and for further studies on the exfoliative toxins from S. hyicus have been provided.     

Postnatal development of low [Mg2+] oscillations in neocortex

One form of rhythmic activity intrinsic to neocortex can be induced in slices of adult somatosensory cortex by lowering [Mg2+]o to unblock N-methyl--aspartate (NMDA) receptors. It has been suggested that a population of intrinsically burst-firing (IB) neurons that are unique to cortical layer 5 may play a role in the rhythmic activity seen under these conditions. Whole cell patch-clamp and field-potential recordings in slices of somatosensory cortex from neonatal rats were used to study the development of IB cells and the development of 0 [Mg2+] oscillations. IB cells were not encountered before postnatal day 12 (P12) in layer 5, but from P13 to P19 an increasing proportion of cells had IB properties. Recordings from cells at P7, P17, and P19 in 0 [Mg2+] indicate that dramatic changes occur postnatally in 0 [Mg2+]-induced activity. At P7, cells largely showed trains of single action potentials. In contrast, at P19, cells showed organized bursts of rhythmic activity lasting 0.5-5 s separated by periods of relative quiescence. Cells recorded at P17 were found to have less organized rhythmic activity than cells from P19 cortex. Field-potential recordings in 0 [Mg2+] made at P7 showed infrequent and slowly occurring field depolarizations, whereas field-potential recordings at P19 consisted of spontaneous bursts of 4-12 Hz oscillations identical to those observed in the adult. Application of NE, which inhibits burst-firing of layer 5 IB cells, significantly altered the discharge pattern of 0 [Mg2+] oscillations at P19. These data suggest that the maturation of one type of rhythmic network activity intrinsic to neocortex is influenced by the development of the membrane properties of a single cell type.     

Effects of barium on stimulus-induced changes in [K+]o and field potentials in dentate gyrus and area CA1 of human epileptic hippocampus

Congenital para-oesophageal hiatal hernia (PEHH) is a rare problem in infancy, however, it constitutes a clinical entity that mandates surgical repair once the diagnosis is made. In the paediatric age group, acquired PEHH has been described as a major complication in a number of patients who were treated surgically for gastro-oesophageal reflux (GER) by Nissen fundoplication. PEHH is a frequently encountered condition in elderly patients; it accounts for 5% of diaphragmatic hiatal hernias. In both paediatric and adult patients PEHH, whether congenital or acquired in origin, is usually associated with potentially lethal complications such as gastric volvulus, incarceration, and perforation. In clinical practice true PEHH is extremely rare. The term has been expanded to include large gastric hiatal hernias where most of the stomach and the gastro-oesophageal junction are in the chest. Six infants with congenital PEHH are presented, together with an attempt to understand its possible aetiology and a review of its current surgical management.     

Quantitating dialysis using two dialysate samples: a simple, practical and accurate approach for evaluating urea kinetics

AIM: Factors which influence the accuracy of the field application during daily irradiation routine are not well known. The aim of this prospective analysis was to determine the significance of these factors on the occurrence of field misadjustments in irradiation without immobilization and to evaluate their clinical relevance. PATIENTS AND METHODS: Fifty-three patients received external cobalt-60 beam irradiation without fixation. Once weekly portal images of all treatment fields were carried out. In addition to objective patient data (age, weight, height, general condition, irradiation indication), the psychological situation of the patient during treatment (anxiety, restlessness, pain) and work circumstances of the medical staff during treatment were evaluated once weekly. The distance of clearly visible anatomic structures to the field borders of the portal images were measured and the deviation to the corresponding simulator images was calculated. Patient data were correlated to the number of field misadjustments (deviation larger than 1 cm). RESULTS: Patients whose condition is generally poor and patients being treated palliatively, patients with feeling of anxiety, restlessness or pain during simulation or irradiation and heavy patients (90 kg and more) were more often misadjusted. The number of field misadjustments increased with the stress of the medical staff. CONCLUSIONS: The problem of reproducibility of external beam irradiation without fixation in palliative treatment is of clinical relevance. Effective analgesic therapy and a comfortable and painfree patient set-up reduce misadjustments. In curative treatment, immobilization techniques should be used.