bluuebunny/crossref_metadata_2025 huggingface dataset:
Conventional PKCs regulate the temporal pattern of Ca2+ oscillations at fertilization in mouse eggs
Authors: Halet Guillaume , Tunwell Richard , Parkinson Scott J. , Carroll John
Published: March 2004

In mammalian eggs, sperm-induced Ca2+ oscillations at fertilization are the primary trigger for egg activation and initiation of embryonic development. Identifying the downstream effectors that decode this unique Ca2+ signal is essential to understand how the transition from egg to embryo is coordinated. Here, we investigated whether conventional PKCs (cPKCs) can decode Ca2+ oscillations at fertilization. By monitoring the dynamics of GFP-labeled PKCα and PKCγ in living mouse eggs, we demonstrate that cPKCs translocate to the egg membrane at fertilization following a pattern that is shaped by the amplitude, duration, and frequency of the Ca2+ transients. In addition, we show that cPKC translocation is driven by the C2 domain when Ca2+ concentration reaches 1–3 μM. Finally, we present evidence that one physiological function of activated cPKCs in fertilized eggs is to sustain long-lasting Ca2+ oscillations, presumably via the regulation of store-operated Ca2+ entry.
Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins
Authors: Peden Andrew A. , Oorschot Viola , Hesser Boris A. , Austin Cary D. , Scheller Richard H. , Klumperman Judith
Published: March 2004

The adaptor protein (AP) 3 adaptor complex has been implicated in the transport of lysosomal membrane proteins, but its precise site of action has remained controversial. Here, we show by immuno-electron microscopy that AP-3 is associated with budding profiles evolving from a tubular endosomal compartment that also exhibits budding profiles positive for AP-1. AP-3 colocalizes with clathrin, but to a lesser extent than does AP-1. The AP-3– and AP-1–bearing tubular compartments contain endocytosed transferrin, transferrin receptor, asialoglycoprotein receptor, and low amounts of the cation-independent mannose 6-phosphate receptor and the lysosome-associated membrane proteins (LAMPs) 1 and 2. Quantitative analysis revealed that of these distinct cargo proteins, only LAMP-1 and LAMP-2 are concentrated in the AP-3–positive membrane domains. Moreover, recycling of endocytosed LAMP-1 and CD63 back to the cell surface is greatly increased in AP-3–deficient cells. Based on these data, we propose that AP-3 defines a novel pathway by which lysosomal membrane proteins are transported from tubular sorting endosomes to lysosomes.
The J-domain protein Rme-8 interacts with Hsc70 to control clathrin-dependent endocytosis in Drosophila
Authors: Chang Henry C. , Hull Michael , Mellman Ira
Published: March 2004

By screening for mutants exhibiting interactions with a dominant-negative dynamin, we have identified the Drosophila homologue of receptor-mediated endocytosis (Rme) 8, a J-domain–containing protein previously shown to be required for endocytosis in Caenorhabditis elegans. Analysis of Drosophila Rme-8 mutants showed that internalization of Bride of sevenless and the uptake of tracers were blocked. In addition, endosomal organization and the distribution of clathrin were greatly disrupted in Rme-8 cells, suggesting that Rme-8 participates in a clathrin-dependent process. The phenotypes of Rme-8 mutants bear a strong resemblance to those of Hsc70-4, suggesting that these two genes act in a common pathway. Indeed, biochemical and genetic data demonstrated that Rme-8 interacts specifically with Hsc70-4 via its J-domain. Thus, Rme-8 appears to function as an unexpected but critical cochaperone with Hsc70 in endocytosis. Because Hsc70 is known to act in clathrin uncoating along with auxilin, another J-protein, its interaction with Rme-8 indicates that Hsc70 can act with multiple cofactors, possibly explaining its pleiotropic effects on the endocytic pathway.
The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cells
Authors: Snapp Erik L. , Reinhart Gretchen A. , Bogert Brigitte A. , Lippincott-Schwartz Jennifer , Hegde Ramanujan S.
Published: March 2004

Protein translocons of the mammalian endoplasmic reticulum are composed of numerous functional components whose organization during different stages of the transport cycle in vivo remains poorly understood. We have developed generally applicable methods based on fluorescence resonance energy transfer (FRET) to probe the relative proximities of endogenously expressed translocon components in cells. Examination of substrate-engaged translocons revealed oligomeric assemblies of the Sec61 complex that were associated to varying degrees with other essential components including the signal recognition particle receptor TRAM and the TRAP complex. Remarkably, these components not only remained assembled but also had a similar, yet distinguishable, organization both during and after nascent chain translocation. The persistence of preassembled and complete translocons between successive rounds of transport may facilitate highly efficient translocation in vivo despite temporal constraints imposed by ongoing translation and a crowded cellular environment.
Organic Osmolyte Permeabilities of the Malaria-induced Anion Conductances in Human Erythrocytes
Authors: Duranton Christophe , Huber Stephan M. , Tanneur Valerie , Brand Verena B. , Akkaya Canan , Shumilina Ekaterina V. , Sandu Ciprian D. , Lang Florian
Published: March 2004

Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces new permeability pathways (NPPs) in the host cell membrane. Isotopic flux measurements demonstrated that the NPP are permeable to a wide variety of molecules, thus allowing uptake of nutrients and release of waste products. Recent patch-clamp recordings demonstrated the infection-induced up-regulation of an inwardly and an outwardly rectifying Cl− conductance. The present experiments have been performed to explore the sensitivity to cell volume and the organic osmolyte permeability of the two conductances. It is shown that the outward rectifier has a high relative lactate permeability (Plactate/PCl = 0.4). Sucrose inhibited the outward-rectifier and abolished the infection-induced hemolysis in isosmotic sorbitol solution but had no or little effect on the inward-rectifier. Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC50s in the range of 0.1 and 1 μM, respectively. In contrast, the IC50s of NPPB and furosemide for the inward-rectifying current were >10 μM. Osmotic cell-shrinkage inhibited the inwardly but not the outwardly rectifying conductance. In conclusion, the parasite-induced outwardly-rectifying anion conductance allows permeation of lactate and neutral carbohydrates, whereas the inward rectifier seems largely impermeable to organic solutes. All together, these data should help to resolve ongoing controversy regarding the number of unique channels that exist in P. falciparum–infected erythrocytes.
Gating Dynamics of the Acetylcholine Receptor Extracellular Domain
Authors: Chakrapani Sudha , Bailey Timothy D. , Auerbach Anthony
Published: March 2004

We used single-channel recording and model-based kinetic analyses to quantify the effects of mutations in the extracellular domain (ECD) of the α-subunit of mouse muscle–type acetylcholine receptors (AChRs). The crystal structure of an acetylcholine binding protein (AChBP) suggests that the ECD is comprised of a β-sandwich core that is surrounded by loops. Here we focus on loops 2 and 7, which lie at the interface of the AChR extracellular and transmembrane domains. Side chain substitutions in these loops primarily affect channel gating by either decreasing or increasing the gating equilibrium constant. Many of the mutations to the β-core prevent the expression of functional AChRs, but of the mutants that did express almost all had wild-type behavior. Rate-equilibrium free energy relationship analyses reveal the presence of two contiguous, distinct synchronously-gating domains in the α-subunit ECD that move sequentially during the AChR gating reaction. The transmitter-binding site/loop 5 domain moves first (Φ = 0.93) and is followed by the loop 2/loop 7 domain (Φ = 0.80). These movements precede that of the extracellular linker (Φ = 0.69). We hypothesize that AChR gating occurs as the stepwise movements of such domains that link the low-to-high affinity conformational change in the TBS with the low-to-high conductance conformational change in the pore.
Molecular Surface of Tarantula Toxins Interacting with Voltage Sensors in Kv Channels
Authors: Wang Julia M. , Roh Soung Hun , Kim Sunghwan , Lee Chul Won , Kim Jae Il , Swartz Kenton J.
Published: March 2004

The venom from spiders, scorpions, and sea anemone contain a rich diversity of protein toxins that interact with ion channel voltage sensors. Although atomic structures have been solved for many of these toxins, the surfaces that are critical for interacting with voltage sensors are poorly defined. Hanatoxin and SGTx are tarantula toxins that inhibit activation of Kv channels by interacting with each of the four voltage sensors. In this study we set out to identify the active surface of these toxins by alanine-scanning SGTx and characterizing the interaction of each mutant with the Kv2.1 channel. Examination of the concentration dependence for inhibition identified 15 mutants with little effect on the concentration dependence for toxin inhibition of the Kv2.1 channel, and 11 mutants that display moderate to dramatic perturbations. Mapping of these results onto the structure of SGTx identifies one face of the toxin where mutations with pronounced perturbations cluster together, and a backside of the toxin where mutations are well tolerated. The active surface of SGTx contains a ring-like assembly of highly polar residues, with two basic residues that are particularly critical, concentrically arranged around a hydrophobic protrusion containing critical aliphatic and aromatic residues. These results identify the active surface of the toxin and reveal the types of side chains that are important for interacting with voltage sensors.
Mouse Bestrophin-2 Is a Bona fide Cl− Channel
Authors: Qu Zhiqiang , Fischmeister Rodolphe , Hartzell Criss
Published: March 2004

Bestrophins have recently been proposed to comprise a new family of Cl− channels. Our goal was to test whether mouse bestrophin-2 (mBest2) is a bona fide Cl− channel. We expressed mBest2 in three different mammalian cell lines. mBest2 was trafficked to the plasma membrane as shown by biotinylation and immunoprecipitation, and induced a Ca2+-activated Cl− current in all three cell lines (EC50 for Ca2+ = 230 nM). The permeability sequence was SCN−: I−: Br−: Cl−: F− (8.2: 1.9: 1.4: 1: 0.5). Although SCN− was highly permeant, its conductance was ∼10% that of Cl− and SCN− blocked Cl− conductance (IC50 = 12 mM). Therefore, SCN− entered the pore more easily than Cl−, but bound more tightly than Cl−. Mutations in S79 altered the relative permeability and conductance for SCN− as expected if S79 contributed to an anion binding site in the channel. PSCN/PCl = 8.2 ± 1.3 for wild-type and 3.9 ± 0.4 for S79C. GSCN/GCl = 0.14 ± 0.03 for wild-type and 0.94 ± 0.04 for S79C. In the S79 mutants, SCN− did not block Cl− conductance. This suggested that the S79C mutation altered the affinity of an anion binding site for SCN−. Additional evidence that S79 was located in the conduction pathway was provided by the finding that modification of the sulfhydryl group in S79C with MTSET+ or MTSES− increased conductance significantly. Because the effect of positively and negatively charged MTS reagents was similar, electrostatic interactions between the permeant anion and the channel at this residue were probably not critical in anion selectivity. These data provide strong evidence that mBest2 forms part of the novel Cl− conduction pathway in mBest2-transfected cells and that S79 plays an important role in anion binding in the pore of the channel.
A Genomic Analysis of Rat Proteases and Protease Inhibitors
Authors: Puente Xose S. , López-Otín Carlos
Published: April 2004

Proteases perform important roles in multiple biological and pathological processes. The availability of the rat genome sequence has facilitated the analysis of the complete protease repertoire or degradome of this model organism. The rat degradome consists of at least 626 proteases and homologs, which are distributed into 24 aspartic, 160 cysteine, 192 metallo, 221 serine, and 29 threonine proteases. This distribution is similar to that of the mouse degradome but is more complex than that of the human degradome composed of 561 proteases and homologs. This increased complexity of rat proteases mainly derives from the expansion of several families, including placental cathepsins, testases, kallikreins, and hematopoietic serine proteases, involved in reproductive or immunological functions. These protease families have also evolved differently in rat and mouse and may contribute to explain some functional differences between these closely related species. Likewise, genomic analysis of rat protease inhibitors has shown some differences with mouse protease inhibitors and the expansion of families of cysteine and serine protease inhibitors in rodents with respect to human. These comparative analyses may provide new views on the functional diversity of proteases and inhibitors and contribute to the development of innovative strategies for treating proteolysis diseases.
The relationship between plasma levels of leptin and androgen in healthy and preeclamptic pregnant women
Authors: Atamer Yildiz , Erden Ali Ceylan , Demir Bulent , KoÇyigit Yuksel , Atamer AytaÇ
Published: April 2004

Background.  To clarify the role of leptin and androgens in the pathogenesis of preeclampsia, we wanted to assess role of maternal leptin in women with severe and mild preeclampsia and the effects of sex steroid hormones on leptin production.

Methods.  The groups consisted of 40 healthy pregnant women (HPW) as well as 55 pregnant women with severe preeclampsia (SPE) and 41 pregnant women with mild preeclampsia (MPE). No significant differences were observed between the three groups regarding age, gestational age and body mass index (BMI). Plasma leptin, total testosterone (T), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A) levels were measured. Statistical analysis was achieved with one‐way analysis of variance (anova) followed by post hoc multiple comparisons with the Tukey honestly significant difference (HSD) test by using SPSS for Windows statistical computer program, and the Pearson's coefficient of correlation was calculated.

Results.  The plasma level of leptin was significantly increased in the SPE and MPE groups (p < 0.001), whereas the plasma level of T was significantly increased only in the SPE group (p < 0.001). However, there was no significant difference in plasma levels of DHEAS among the three groups (p < 0.05). The plasma level of A was significantly decreased in the MPE group (p < 0.05). There was no significant difference in the plasma level of E2 in the MPE and SPE groups (p < 0.05). There was a significant positive correlation between the plasma levels of leptin and E2 in the MPE group (r = 0.41, p < 0.001).

Conclusion.  We concluded that the elevated plasma levels of leptin and testosterone could contribute to the endothelial dysfunction involved in the pathogenesis of preeclampsia, and that estradiol might lead to an increase in the plasma levels of leptin.
Ambulatory labor analgesia: what does an obstetrician need to know?
Authors: Kuczkowski Krzysztof M.
Published: April 2004

A simple statement that describes the degree of the patient's satisfaction with the pain relief from her labor epidural analgesia has often assessed the quality of labor analgesia as perceived by the patient. Many laboring parturients, midwives, obstetricians and anesthesiologists are increasingly concerned by the limitations of traditional epidural labor analgesia. In general, women dislike the inability to void, the often‐dense motor block, the feeling of numbness of the lower body, the total lack of the urge to bear down, and the complete perineal anesthesia. Continuous search for balanced labor analgesia that provides relief from pain, while preserving motor function, has led to the development of an ambulatory labor analgesia technique. This article assesses the validity of various strongly advocated opinions as to whether parturients benefit from ambulation in labor and also reviews the current trends in ambulatory labor analgesia.
Cutting Power Lines within the Palace? Countering Paternity and Eurocentrism in the ‘Geographical Tradition’
Authors: McEwan Cheryl
Published: April 2004

This paper attempts to combine critical feminist and post‐colonial approaches to suggest how more inclusive histories of geography may be written. Drawing on the specific example of women travellers in West Africa during the late nineteenth century, the paper proposes strategies to disrupt the masculinist and eurocentric construction of ‘the geographical tradition’. These strategies include moving beyond a disciplinary focus, disrupting essentialisms, interrogating whiteness and authority, and attempting to reveal the historical agency and resistance of colonized others. The problematic and antagonist relationship between the recovery of the agency of white women and the recovery of non‐Western agency and resistance is recognized, and it is suggested that countering eurocentrism requires a rethinking of current forms of countering paternity.
Questionnaire survey on the use of rotary nickel–titanium endodontic instruments by Australian dentists
Authors: Parashos P. , Messer H. H.
Published: March 2004

Aim  To ascertain the extent of the adoption and use of rotary nickel–titanium (NiTi) instruments and techniques in general dental practice and specialist endodontic practice in Australia in 2001.

Methodology  A questionnaire survey comprising 43 questions was developed by first creating questions, then pilot testing with 10 postgraduate students in endodontics, followed by a final revision. The final series of questions covered demographics, patterns of rotary NiTi usage, issues associated with NiTi usage and training in NiTi use. The sampling frame was 908, comprising 64 endodontists and 844 general dentists.

Results  The overall response rate was 87%. Rotary NiTi instruments were used by 22% of general dentists and 64% of endodontists. The two main reasons for not using rotary NiTi were ‘no perceived advantage’ and ‘too fragile’. Instrument fracture had been experienced by 74% of respondents, and 72% of these had fractured one to five files for the two main perceived reasons of ‘excessive pressure on the file’ and ‘over‐usage’. The next two most common problems encountered were ‘binding’ (53%) and ‘ledging’ (45%). Very high proportions of positive experiences were noted. Most respondents (73%) had attended one or more continuing education courses, most of which were provided by dental supply companies (64%).

Conclusions  The results indicate a sensible and responsible approach to the incorporation of rotary NiTi instruments and techniques into root canal treatment. Dentists were aware of the limitations of the new technology, but were taking steps to become familiar with the properties and behaviour of the instruments. Instrument fracture was common, but it was of low frequency and did not deter dentists from using the technology.
Comparative investigation of two rotary nickel–titanium instruments: ProTaper versus RaCe. Part 1. Shaping ability in simulated curved canals
Authors: Schäfer E. , Vlassis M.
Published: March 2004

Aim  To compare the shaping ability of ProTaper with Reamer with Alternating Cutting Edges (RaCe) instruments. Part 1 of this two‐part report describes the efficacy of these two nickel–titanium instruments in simulated curved root canals.

Methodology  Simulated canals with 28° and 35° curves in resin blocks were prepared with ProTaper and RaCe instruments using a crown‐down preparation technique (n = 24 canals in each case). Pre‐ and postinstrumentation images were recorded, and assessment of canal shape was completed with a computer image analysis program. Material removal was measured at 20 measuring points, beginning 1 mm from the apex. Incidence of canal aberrations, preparation time, changes of working length and instrument failures were also recorded. The data were analysed statistically using the Mann–Whitney U‐test or the chi‐square test.

Results  On average, canals prepared with RaCe instruments remained better centred compared with those enlarged with ProTaper files. Three RaCe instruments and two ProTaper files fractured during preparation (P > 0.05). Between both the canal types, RaCe was significantly faster (P < 0.001) than ProTaper and maintained working length significantly better (P < 0.05).

Conclusion  Both instruments prepared curved canals rapidly and were relatively safe. RaCe respected original canal curvature better than ProTaper, which tended to transport towards the outer aspect of the curve.
A standard for radiopacity of root‐end (retrograde) filling materials is urgently needed
Authors: Tagger M. , Katz A.
Published: March 2004

Aim  To assess the radiopacity of materials used, or recommended for use, as apical root‐end (retrograde) fillings.

Methodology  The radiopacity of 14 materials falling into the category of root‐end filling materials was measured in equivalent millimetres of aluminium (mm Al) using a new computerized method. These included temporary or intermediate sealing materials; composite, compomer and GIC filling materials; EBA‐derived cements; amalgam, etc. Gutta‐percha cone material was added as a control. Samples of 1 mm thickness were radiographed on periapical film alongside an aluminium step wedge calibrated in millimetres, and the opacity of the materials, in greyscale or pseudo‐colour, was compared with the equivalent step.

Results  The radiopacity ranged from 1.75 mm Al to >10 mm Al. The lower range appears insufficient for routine clinical detection when it is compared with the minimal requirement for intracanal fillings.

Conclusions  Because of the proliferation of root‐end filling materials with a broad range of radiopacity, an international standard stipulating the required minimal radiopacity, as well as other properties, is needed urgently. It should be based on in vitro results and on large‐scale clinical radiographic surveys.
DAILY HEMODIALYSIS—SELECTED TOPICS: The London, Ontario, Daily/Nocturnal Hemodialysis Study
Authors: Lindsay Robert M. ,   the Daily/Nocturnal Dialysis Study Group
Published: March 2004

The London Daily/Nocturnal Hemodialysis Study, a prospective, comparative, nonrandomized study, directly compared outcomes of quotidian (daily) hemodialysis patients with conventional thrice‐weekly hemodialysis patients. Patients were assigned to either daily (short‐hours) hemodialysis (n = 11) or nocturnal hemodialysis (n = 12) and followed up for 5–36 months; all data were directly compared with matched control patients receiving conventional hemodialysis (n = 22). Outcomes evaluated were adequacy (urea kinetics), nutrition, anemia management, blood pressure and volume control, calcium/phosphorus control, and patient quality of life. In addition, a detailed economic analysis was undertaken. The study showed that both quotidian hemodialysis regimens are more effective than conventional hemodialysis in improving weekly urea clearance. Significant clinical improvements were seen with quotidian therapy in the areas of nutrition (short‐hours daily), blood pressure (both), volume control (short‐hours daily), calcium/phosphorus control (nocturnal), and quality of life (both). A nonsignificant trend for improvement in anemia management was suggested. The economic analysis showed substantial savings in annualized cost per quality‐adjusted life‐year in changing from conventional hemodialysis (carried out in‐center, in satellite units, or at home) to home quotidian hemodialysis. The substantial clinical benefits of home quotidian hemodialysis, combined with the economic advantage shown by this study, clearly justify its expansion. (The details of this study have recently been published in 11 articles in the American Journal of Kidney Diseases[2003;42(suppl 1)].
DAILY HEMODIALYSIS—SELECTED TOPICS: Short Daily Hemodialysis and Nutritional Status in Patients with Chronic Renal Failure
Authors: Galland Roula , Traeger Jules
Published: March 2004

Malnutrition is a frequent complication in hemodialysis patients and is associated with increased mortality and morbidity. Interventions such as oral or intravenous nutritional supplements have often failed to improve nutritional status. We report here the effect that daily dialysis, practiced in our center since 1997, has had on nutritional parameters. Seventeen patients treated with conventional hemodialysis (4–5 hours, three times per week, for 9.6 ± 8.4 years) were converted to short daily hemodialysis (2–2.5 hours, six times per week, for a mean of 39.1 ± 23.5 months). Dietary, anthropometric, and biochemical evaluations were performed during conventional hemodialysis, after 1 year on short daily hemodialysis (sDHDyear), and at the end of follow‐up (sDHDend). Daily protein intake increased from 1.21 ± 0.27 g/kg/day with conventional hemodialysis to 1.51 ± 0.47 g/kg/day at sDHDyear and 1.51 ± 0.37 g/kg/day at sDHDend. Energy intake increased from 33.6 ± 9.5 kcal/kg/day to 38.3 ± 10.9 kcal/kg/day at sDHDyear and 39.4 ± 9.4 kcal/kg/day at sDHDend. The normalized protein equivalent nitrogen appearance (nPNA) increased from 1.19 ± 0.34 g/kg/day with conventional hemodialysis to 1.34 ± 0.43 g/kg/day sDHDyear and 1.37 ± 0.37 g/kg/day sDHDend. Biochemical indicators also increased: serum albumin increased from 40.2 ± 3.3 g/L to 44.5 ± 4.6 g/L and 45.1 ± 4.1 g/L, and prealbumin increased from 0.32 ± 0.06 g/L to 0.38 ± 0.09 g/L and 0.36 ± 0.09 g/L, respectively. These improvements were accompanied by an increase in body weight from 62.0 ± 10.6 kg on conventional hemodialysis to 64.3 ± 10.2 kg at sDHDyear and 65.5 ± 9.7 kg at sDHDend. All the changes between conventional hemodialysis and short daily hemodialysis were statistically significant. Increased frequency is more important than increased dialysis dose. Short daily hemodialysis appears to be a suitable method to improve nutritional status in dialysis patients.
DAILY HEMODIALYSIS—SELECTED TOPICS: Sleep Apnea and Daytime Sleepiness in End‐Stage Renal Disease
Authors: Hanly Patrick
Published: March 2004

Sleep disorders are common in patients with end‐stage renal disease (ESRD). The prevalence of sleep apnea is 10 times greater in patients with ESRD than in the general population. Although sleep apnea is not improved by conventional modes of dialysis, it is corrected by nocturnal hemodialysis, which provides a new and unique model to study its pathophysiology in this patient population. In addition to causing sleep disruption and impairment of daytime function, sleep apnea may also increase the cardiovascular morbidity and mortality that is commonly found in patients with ESRD. “Pathological” daytime sleepiness is found in 50% of patients with ESRD. Although its pathogenesis has been related both to sleep apnea and periodic limb movements, it has also been attributed to a variety of metabolic factors, including the severity of uremia. Further research is required to evaluate the impact of sleep disorders on the clinical outcome of patients with ESRD.
DAILY HEMODIALYSIS—SELECTED TOPICS: Development of a Nocturnal Home Hemodialysis (NHHD) Program for Children
Authors: Geary Denis F. , Piva Elizabeth , Gajaria Mukesh , Tyrrel Jennifer , Picone Gail , Harvey Elizabeth
Published: March 2004

Whereas the success of nocturnal home hemodialysis (NHHD) as a treatment modality for adults has been clearly demonstrated, there is very little experience with NHHD in children. There are genuine concerns related to patient safety, as well as a potentially overwhelming burden on the parents of children, while supervising NHHD. Each of these issues has been considered in the development of the NHHD program for children in Toronto. The steps involved in the development of this program are outlined. The experience of Simonsen (4), that NHHD is feasible and provides excellent dialysis for children, is confirmed.
DAILY HEMODIALYSIS—SELECTED TOPICS: Reducing Hemodialysis Costs: Conventional and Quotidian Home Hemodialysis in Canada
Authors: McFarlane Philip A.
Published: March 2004

The cost of hemodialysis is a concern as the prevalence of end‐stage renal disease (ESRD) increases. While home hemodialysis has been described as less expensive than in‐center hemodialysis, the proportion of patients performing home hemodialysis has been declining. In Canada, there is increasing interest in daily (or quotidian) forms of home hemodialysis, such as nocturnal hemodialysis and short daily hemodialysis. We reviewed the recent Canadian experience with the costs of these modalities and identified four descriptive costing studies: two whole‐program comparisons of home conventional hemodialysis and unmatched in‐center hemodialysis patients, and two comparing quotidian home hemodialysis and matched in‐center hemodialysis patients. All costs are listed as per patient‐year in 2003 U.S. dollars. In the two whole‐program analyses, conventional home hemodialysis was less expensive than in‐center hemodialysis ($36,840 versus $100,198 [p < 0.001] and $34,466 versus $58,959 [p < 0.001]). Reductions in categories such as staffing and overhead are likely due to the modality, while reductions in medications and hospital admissions may be due to differences in the patient mix. The savings for quotidian home hemodialysis are significant, but less striking. In the two matched analyses, nocturnal hemodialysis cost less than in‐center hemodialysis ($48,656 versus $59,476 [p = 0.006]), and costs decreased by $8,046 in those converted to short daily hemodialysis and by $14,341 in those converted to nocturnal hemodialysis, while increasing by $2,521 in those who remained on in‐center hemodialysis. Home conventional hemodialysis is less expensive than in‐center hemodialysis. Much of these savings are lost when dialysis frequency increases; however, quotidian home hemodialysis remains less expensive than in‐center hemodialysis.
DAILY HEMODIALYSIS—SELECTED TOPICS: The Direction of End‐Stage Renal Disease Reimbursement in the United States
Authors: Lockridge Robert S.
Published: March 2004

In the 1960s, care of the end‐stage renal disease (ESRD) patient changed. Either through transplantation or intermittent hemodialysis ESRD patients were able to live longer. The Gottschalk Committee issued the “Report of the Committee on Chronic Kidney Disease” to the Bureau of Budget. This report established that hemodialysis and kidney transplantation were the standard of care for the treatment of ESRD patients. Section 2991 of the Social Security Amendment of 1972 provided that patients with ESRD who qualified for Medicare were entitled to receive dialysis and/or transplantation nationwide. The first Medicare hearing held in 1975 regarding the Medicare ESRD program found that the cost of the program was much greater than had been predicted in 1972. Ever since 1975, accelerating cost has been a concern of the government. Quality of care for ESRD patients has been a major focus of the renal community and the Centers for Medicare and Medicaid Services (CMS) over the past 10 years. Consensus for entitlement has remained, but the staggering cost of the program as a whole has become a major problem that must be addressed. Since 1978, Congress and the CMS have passed laws and developed demonstration projects to improve quality of care and reduce costs in the Medicare ESRD program. Kt/V, urea reduction ratio (URR), and hemoglobin levels have all improved, but hospital admissions have remained unchanged and mortality rates have increased. Do the renal community and CMS need to rethink how they will improve the quality of care for ESRD patients and reduce costs in the Medicare ESRD program?
DAILY HEMODIALYSIS—SELECTED TOPICS: An International Registry to Compare Quotidian Dialysis Regimens with Conventional Thrice‐Weekly Hemodialysis: Why, How, and Potential Pitfalls
Authors: Nesrallah Gihad E. , Moist Louise M. , Awaraji Christian , Lindsay Robert M.
Published: March 2004

Thrice‐weekly hemodialysis is the most commonly used form of renal replacement therapy, yet it is associated with unacceptably high morbidity and mortality. Attempts to improve outcomes for hemodialysis patients by increasing their per‐session dose of dialysis have recently proven unsatisfactory in the multicentered Hemodialysis (HEMO) study. Interest has thus turned to increasing dialysis frequency. Short daily and long nocturnal dialysis, which are typically performed 6 days per week, are gaining acceptance and are associated with significant improvements in secondary outcomes, including nutrition, left ventricular hypertrophy, hypertension, anemia, and calcium‐phosphorus balance. Studies to date have not been adequately powered to detect the survival benefits that these changes may confer. Large‐scale randomized studies are planned, but will likely not answer the survival question for several years. Until this issue is resolved, funding policies are unlikely to change, confining current dialysis patients to potentially suboptimal therapy. By capturing data from current and future daily dialysis patients using an international registry, a survival benefit might be demonstrated more quickly. Such a project will soon be undertaken by the London Daily/Nocturnal Study Group with endorsement from the International Society for Hemodialysis and the U.S. National Institutes of Health. This database will also provide useful descriptive data that will help develop methodologies in this growing field. Historically the interpretation of dialysis registry data has been plagued with various methodological problems. These are briefly reviewed, and some potential solutions and necessary precautions are discussed.
DAILY HEMODIALYSIS—SELECTED TOPICS: Evidence‐Based Medicine in the Dialysis Unit: A Few Lessons from the USRDS and the NCDS and HEMO Trials
Authors: Briggs Josephine P.
Published: March 2004

This short review argues for the importance of evidence‐based medicine in the evolution of improved dialysis care. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has supported two major randomized clinical trials in dialysis, the National Cooperative Dialysis Study (NCDS), completed in 1981, and the Hemodialysis (HEMO) study, completed in 2002, and supports a major body of ongoing observational research through the U.S. Renal Data System (USRDS). The main results from the two randomized clinical trials and their implications for clinical practice and subsequent research are discussed here. The importance of observational research in the formulation of hypotheses and improvement of quality of care is examined. A brief historical perspective is provided on the critical examination of dialysis care in the late 1980s that occurred following completion of the NCDS. Finally, the rationale for continued investment in dialysis research and the plans of NIDDK to launch studies of more intensive dialysis regimens are discussed.
DAILY HEMODIALYSIS—SELECTED TOPICS: Rationale and Experience with Short Daily Hemofiltration
Authors: Jaber Bertrand L. , Zimmerman Deborah L.
Published: March 2004

Patients with end‐stage renal disease (ESRD) have morbidity and mortality rates that are much higher than those found in the general population. The nonphysiologic nature of thrice‐weekly hemodialysis may be partially responsible for the poor outcomes in this patient population. In response to the problems encountered with conventional hemodialysis schedules, a number of investigators have explored potential solutions to the problem. One such solution is to increase the time and/or frequency of hemodialysis. With this approach, ESRD patients have been observed to have better anemia management and blood pressure control, as well as improvements in quality of life. Hemodialysis is based on diffusion of solutes across a semipermeable membrane such that only small molecules are readily removed. Therefore a second solution has been to utilize hemofiltration instead of hemodialysis. Hemofiltration utilizes convective clearance of molecules, resulting in an improvement in the removal of larger solutes, much like the glomerular basement membrane of the kidney. Despite the accumulated evidence that thrice‐weekly hemofiltration adds to the benefits seen with increasing hemodialysis time and/or frequency, the use of hemofiltration has been limited by the available technology, cost, and low access blood flows. However, current technological advances in equipment and access creation are addressing these problems. With these advances, a number of investigators have also explored the potential benefits of daily hemofiltration as a treatment option for ESRD. The preliminary results suggest that improvements in blood pressure, β2‐microglobulin (β2M) levels, and quality of life are possible.
APPROACHES TO QUOTIDIAN DIALYSIS: The Aksys Personal Hemodialysis System
Authors: Kjellstrand Carl M. , Blagg Christopher R. , Bower John , Twardowski Zbylut J.
Published: March 2004

The Aksys personal hemodialysis system empowers patients to dialyze where, when, and how they want. It allows them to easily do the best dialysis—daily hemodialysis—in the safest place—at home—by simplifying operation (almost anyone can do it), doing the drudgery work of dialysis (the patient is the master, not the slave of the dialysis machine, giving patients their lives back), needing no bulky disposables (patients have their homes back), reducing emergencies during dialysis, and performing immediate fluid resuscitation on demand.
APPROACHES TO QUOTIDIAN DIALYSIS: Baxter Aurora Dialysis System
Authors: Kelly Thomas D.
Published: March 2004

With the recent focus on the benefits of more frequent dialysis, the Baxter Aurora dialysis system provides maximum flexibility for therapy prescription, including short daily treatments, long nocturnal treatments, hemodialysis, hemofiltration, and online hemodiafiltration, all in a compact, reliable, easy to use system. A self‐prompting touch screen user interface mounted on a movable arm provides for comfortable operation, whether sitting and standing. An automatic treatment setup mode facilitates easy treatment setup. Complex menus are eliminated by the use of a hardware key that automatically selects only the prescribed options during power up, eliminating all menus associated with nonprescribed functions and modalities. This prevents the user from becoming confused or accidentally altering the dialysis treatment. Prior to dialysis the instrument goes through an automatic self‐test that confirms the operation of internal systems. The screen will dim when there is no action that the patient needs to attend to on the instrument. After dialysis, press the disinfect button and the instrument disinfects itself and shuts off. For patient safety, the “disinfect” menus are not available during dialysis. The instrument can also be programmed to automatically start and rinse at a set time. For remote treatment monitoring, the instrument connects to the Internet. The Aurora records information about the machine's technical status, providing a record of instrument history for easy servicing. The Aurora is a flexible platform that provides the desired renal therapy with ease of use and proper support for the hemodialysis patient when combined with Baxter's 24‐hour infrastructure and support.
APPROACHES TO QUOTIDIAN DIALYSIS: Bellco Formula Domus Home Care System
Authors: Trewin Elizabeth
Published: March 2004

There are certain characteristics in a dialysis machine that would be desirable for use in home and limited care environments. These features relate to safety, ease of use, consideration of physical space, and reliability. The Bellco Formula Domus Home Care System was designed to meet all these requirements. Bellco's philosophy of patient treatment centers on global biocompatibility. This is evident in the design of the Formula Domus Home Care System. It has the smallest hydraulic fluid pathway of any dialysis machine on the market. Formula is capable of preparing ultrapure dialysate. The ultrafiltration measurement mechanism, the patented Coriolis flow meter, measures the mass of the dialysate, not the volume. For this reason it is the only dialysis machine that detects actual backfiltration, not just the theoretical possibility of it based on transmembrane pressure. The Coriolis flow meter also ensures that dialysate flow is a true single pass. The operator interface is a single window operating control. It is possible to select up to 14 different languages. There is an online help key to assist patients with troubleshooting. Programmable start‐up and shutdown times save time for the patient. Formula is the only dialysis machine to offer a backup battery feature. Formula is capable of communicating with any software available. The focus on global biocompatibility ensures the best quality dialysis treatments for a population of patients who will likely remain on dialysis for a longer period of time than conventional dialysis patients.
APPROACHES TO QUOTIDIAN DIALYSIS: The Fresenius Medical Care Home Hemodialysis System
Authors: Schlaeper Christian , Diaz‐Buxo Jose A.
Published: March 2004

The Fresenius Medical Care home dialysis system consists of a newly designed machine, a central monitoring system, a state‐of‐the‐art reverse osmosis module, ultrapure water, and all the services associated with a successful implementation. The 2008K@home hemodialysis machine has the flexibility to accommodate the changing needs of the home hemodialysis patient and is well suited to deliver short daily or prolonged nocturnal dialysis using a broad range of dialysate flows and concentrates. The intuitive design, large graphic illustrations, and step‐by‐step tutorial make this equipment very user friendly. Patient safety is assured by the use of hydraulic systems with a long history of reliability, smart alarm algorithms, and advanced electronic monitoring. To further patient comfort with their safety at home, the 2008K@home is enabled to communicate with the newly designed iCare remote monitoring system. The Aquaboss Smart reverse osmosis (RO) system is compact, quiet, highly efficient, and offers an improved hygienic design. The RO module reduces water consumption by monitoring the water flow of the dialysis system and adjusting water production accordingly. The Diasafe Plus filter provides ultrapure water, known for its long‐term benefits. This comprehensive approach includes planning, installation, technical and clinical support, and customer service.
APPROACHES TO QUOTIDIAN DIALYSIS: The Gambro System for Home Daily Dialysis
Authors: Ledebo Ingrid , Fredin Richard
Published: March 2004

Safety and reliability have been the main emphasis when developing our system for home daily dialysis. The AK 95 is part of a comprehensive system of appropriate products consisting additionally of a silent water treatment module, an ultrafilter, and a range of dry disposables for dialysis fluid preparation and disinfection. The dialyzer can be selected from a family of synthetic, biocompatible filters, both low and high flux. To complete the system, a modern data management tool for online or off‐line surveillance and multilingual training manuals in both conventional format as well as animated software are available.
APPROACHES TO QUOTIDIAN DIALYSIS: The Allient Dialysis System
Authors: Ash Stephen R.
Published: March 2004

The Allient is a dialysis system that combines various technologies to allow dialysis to be performed at sites outside of dialysis units (intensive care unit [ICU] or home) with ease and safety. A sorbent column regenerates dialysate, removing toxins and providing ultrapure dialysate from only 6 liters of tap water. The use of the sorbent column eliminates the need for costly and complex water purification systems. The Pulsar Blood Movement System provides blood flow at constant negative or positive pressure through single‐lumen or dual‐lumen accesses, maximizing blood flow rate while eliminating bothersome pressure alarms. Ultrasonic flow monitors control the operation of the pump and ensure adequate blood flow during each dialysis treatment. A completely disposable blood tubing and dialysate circuit eliminates the need for sterilization of the machine. The Allient should make dialysis in the ICU or home setting much more practical, reducing training requirements and increasing safety.
APPROACHES TO QUOTIDIAN DIALYSIS: The NxStage System One
Authors: Clark William R. , Turk Joseph E.
Published: March 2004

Given the results of recent randomized controlled trials as well as staffing and budget challenges that today face many institutions across North America, a novel therapeutic approach is likely necessary to enable improvements in clinical outcomes for renal failure patients. The NxStage System One was developed to address these challenges. The system is an innovative, flexible device that delivers hemodialysis, hemofiltration, and/or ultrafiltration therapies to patients with renal failure or fluid overload. The unique characteristics of this system include a highly automated system design with a drop‐in cartridge to facilitate training and simple operation; portable size and independence from dedicated infrastructure to minimize practical barriers to where therapy may be administered; use of high‐quality premixed treatment fluids to enable capture of the potential clinical benefits of fluid purity without the hassles of local water treatment; and wide operating ranges to allow clinician flexibility in patient therapy prescriptions. In both the chronic and acute care environments, the System One presents clinicians with a new platform for delivering patient therapy improvements within real‐world constraints.