bluuebunny/crossref_metadata_2025 huggingface dataset:
Grammatical dissociation during acquired childhood aphasia
Authors: MARTINS ISABEL PAVÃO , LOUREIRO CLARA , RAMOS SARA , MORENO TERESA
Published: April 2009

Aim  We report the case of a 6‐year‐old female who suffered a left hemisphere stroke attributed to a genetically determined prothrombotic state. She presented a fluent speech pattern with selective difficulty in retrieving names but not verbs. An evaluation was designed to clarify whether her symptoms represented a specific impairment of name retrieval.

Method  The child undertook an experimental battery of visual naming tasks requiring the production of 52 nouns (belonging to nine different semantic categories) and 44 verbs. Her performance was compared with that of 12 healthy children, matched for age and IQ, attending a local kindergarten.

Results  The child retrieved significantly more verbs than nouns (χ2=16.27, p<0.01) and had a significantly lower score in noun (t=−7.2, p<0.005), but not in verb retrieval than the comparison group. This pattern persisted when verbs and nouns were matched for oral word frequency, showing that the results could not be explained by stimuli difficulty.

Interpretation  To our knowledge, this is the first report of a grammatical dissociation in a child. It suggests that nouns and verbs are subject to different processing early in development, at least before the formal acquisition of grammar. It contradicts theories that postulate a common processing of different grammatical categories early in life.
Socio‐economic achievements of individuals born very preterm at the age of 27 to 29 years: a nationwide cohort study
Authors: MATHIASEN RENÉ , HANSEN BO M , NYBO ANDERSON ANNE‐MARIE , GREISEN GORM
Published: April 2009

Aim  To describe the socio economic achievement of individuals born very preterm (VPT) at the age of 27 to 29 years.

Method  Demographic and social data were extracted from national registers for all individuals born between 1974 and 1976 in Denmark (n=208 656). Of these, 203 283 individuals were alive in 2006. We compared VPT individuals (gestational age <33wks, n=1422; 51.8% males, n=736) with individuals born at term (>36wks, n=192 223; 51.1% males, n=98 240), of whom 4.08% (n=58) of the VPT and 0.19% (n=373) of the term individuals had a diagnosis of cerebral palsy (CP).

Results  Overall results in the two groups were similar, but significant differences appeared. The VPT group had a lower educational level than the term group: 23.9% versus 16.3% had a basic education (corresponding to attendance at basic school for 9y or less; odds ratio [OR] =1.61, 95% confidence interval [CI] 1.42–1.82). Similarly, 31.9% versus 37.6% had a tertiary education (corresponding to different levels of professional education; OR=0.77, CI 0.69–0.86). Net income was 11% lower in the VPT group and 10.8% versus 5.3% were receiving welfare support (OR=2.14, CI 1.81–2.55). In the VPT group 59% versus 52% did not have children (p<0.001) and there were more individuals living alone without children (28.8% vs 21.8%; OR=1.45, CI 1.29–1.63).

Interpretation  VPT birth in the 1970s in Denmark is associated with a highly statistically significant educational and social disadvantage persisting into young adulthood. CP increased the relative risk of social disadvantage in VPT individuals. However, the majority of the survivors are well integrated in society.
Tumor necrosis factor receptor‐associated protein 1 regulates cell adhesion and synaptic morphology via modulation of N‐cadherin expression
Authors: Kubota Kyoko , Inoue Kiyoshi , Hashimoto Ryota , Kumamoto Natsuko , Kosuga Asako , Tatsumi Masahiko , Kamijima Kunitoshi , Kunugi Hiroshi , Iwata Nakao , Ozaki Norio , Takeda Masatoshi , Tohyama Masaya
Published: April 2009

An increase in serum tumor necrosis factor‐α (TNF‐α) levels is closely related to the pathogenesis of major depression. However, the underlying molecular mechanism between this increase and impairment of brain function remains elusive. To better understand TNF‐α/TNF receptor 1 signaling in the brain, we analyzed the brain distribution and function of tumor necrosis factor receptor‐associated protein 1 (TRAP1). Here we show that TRAP1 is broadly expressed in neurons in the mouse brain, including regions that are implicated in the pathogenesis of major depression. We demonstrate that small interfering RNA‐mediated knockdown of TRAP1 in a neuronal cell line decreases tyrosine phosphorylation of STAT3, followed by a reduction of the transcription factor E2F1, resulting in a down‐regulation of N‐cadherin, and affects the adhesive properties of the cells. In addition, in cultured hippocampal neurons, reduced expression of N‐cadherin by TRAP1 knockdown influences the morphology of dendritic spines. We also report a significant association between several single nucleotide polymorphisms in the TRAP1 gene and major depression. Our findings indicate that TRAP1 mediates TNF‐α/TNF receptor 1 signaling to modulate N‐cadherin expression and to regulate cell adhesion and synaptic morphology, which may contribute to the pathogenesis of major depression.
Phosphorylation status of the NR2B subunit of NMDA receptor regulates its interaction with calcium/calmodulin‐dependent protein kinase II
Authors: Raveendran Rajeevkumar , Devi Suma Priya Sudarsana , Mayadevi Madhavan , Steephan Mathew , Santhoshkumar Thankayyan R. , Cheriyan John , Sanalkumar Rajendran , Pradeep Kurup K. , James Jackson , Omkumar Ramakrishnapillai V.
Published: April 2009

Ca2+ influx through NMDA‐type glutamate receptor at excitatory synapses causes activation of post‐synaptic Ca2+/calmodulin‐dependent protein kinase type II (CaMKII) and its translocation to the NR2B subunit of NMDA receptor. The major binding site for CaMKII on NR2B undergoes phosphorylation at Ser1303, in vivo. Even though some regulatory effects of this phosphorylation are known, the mode of dephosphorylation of NR2B‐Ser1303 is still unclear. We show that phosphorylation status at Ser1303 enables NR2B to distinguish between the Ca2+/calmodulin activated form and the autonomously active Thr286‐autophosphorylated form of CaMKII. Green fluorescent protein–α‐CaMKII co‐expressed with NR2B sequence in human embryonic kidney 293 cells was used to study intracellular binding between the two proteins. Binding in vitro was studied by glutathione‐S‐transferase pull‐down assay. Thr286‐autophosphorylated α‐CaMKII or the autophosphorylation mimicking mutant, T286D‐α‐CaMKII, binds NR2B sequence independent of Ca2+/calmodulin unlike native wild‐type α‐CaMKII. We show enhancement of this binding by Ca2+/calmodulin. Phosphorylation or a phosphorylation mimicking mutation on NR2B (NR2B‐S1303D) abolishes the Ca2+/calmodulin‐independent binding whereas it allows the Ca2+/calmodulin‐dependent binding of α‐CaMKII in vitro. Similarly, the autonomously active mutants, T286D‐α‐CaMKII and F293E/N294D‐α‐CaMKII, exhibited Ca2+‐independent binding to non‐phosphorylatable mutant of NR2B under intracellular conditions. We also show for the first time that phosphatases in the brain such as protein phosphatase 1 and protein phosphatase 2A dephosphorylate phospho‐Ser1303 on NR2B.
Soil metal immobilization and ryegrass uptake of lead, copper and zinc as affected by application of organic materials as soil amendments in a short‐term greenhouse trial
Authors: Nwachukwu O. I. , Pulford I. D.
Published: April 2009

Green waste compost, peat, coir and wood bark were applied to metal‐contaminated mine waste at the rates of 1%, 10% and 20% on dry weight basis, and perennial ryegrass grown over a period of 6 weeks. Addition of amendments led to increased biomass yield in all soils when compared with the non‐amended soil. EDTA extractable Pb, Cu and Zn was significantly reduced in amended soil, while leaf and root metal concentrations were also significantly reduced by the application of amendments, especially at applied rates of 10% and 20%. Coir, green waste compost and wood bark stood out as amendments which were consistent in reducing soil extractable and plant tissue Pb, Cu and Zn; while peat rates above 10% enhanced solubility of Cu and Zn because of a lowering of the soil pH.
From convex feasibility to convex constrained optimization using block action projection methods and underrelaxation
Authors: De Pierro Alvaro R. , Helou Neto Elias Salomão
Published: April 2009

We describe the evolution of projection methods for solving convex feasibility problems to optimization methods when inconsistency arises, finally deriving from them, in a natural way, a general block method for convex constrained optimization. We present convergence results.
A hybrid genetic algorithm for the phylogeny problem using path‐relinking as a progressive crossover strategy
Authors: Ribeiro Celso C. , Vianna Dalessandro S.
Published: April 2009

A phylogenetic tree relates taxonomic units using their similarities over a set of characteristics. Given a set of taxonomic units and their characteristics, the phylogeny problem under the parsimony criterion consists in finding a phylogenetic tree with a minimum number of evolutionary steps. We developed a hybrid genetic algorithm for the problem of building a phylogenetic tree minimizing parsimony. The algorithm combines local search with a crossover strategy based on path‐relinking, an intensification technique originally used in the context of other metaheuristics such as scatter search and GRASP. Computational experiments on benchmark and randomly generated instances show that the proposed algorithm is very robust and outperforms other heuristics in terms of solution quality and running times.
Increased Children's Access to Fluoride Varnish Treatment by Involving Medical Care Providers: Effect of a Medicaid Policy Change
Authors: Okunseri Christopher , Szabo Aniko , Jackson Scott , Pajewski Nicholas M. , Garcia Raul I.
Published: April 2009

Background. In 2004, the State of Wisconsin introduced a change to their Medicaid Policy allowing medical care providers to be reimbursed for fluoride varnish treatment provided to Medicaid enrolled children.

Objective. To determine the extent by which a state‐level policy change impacted access to fluoride varnish treatment (FVT) for Medicaid enrolled children.

Data Source. The Electronic Data Systems of Medicaid Evaluation and Decision Support database for Wisconsin from 2002 to 2006.

Study Design. We analyzed Wisconsin Medicaid claims for FVT for children between the ages of 1 and 6 years, comparing rates in the prepolicy period (2002–2003) to the period (2004–2006) following the policy change.

Principal Findings. Medicaid claims for FVT in 2002–2003 totaled 3,631. Following the policy change, claims for FVT increased to 28,303, with 38.0 percent submitted by medical care providers. FVT rates increased for children of both sexes and all ages, rising from 1.4 per 1,000 person‐years of enrollment in 2002–2003 to 6.6 per 1,000 person‐years in 2004–2006. Overall, 48.6 percent of the increase in FVT was attributable to medical care providers. The largest increase was seen in children 1–2 years of age, among whom medical care providers were responsible for 83.5 percent of the increase.

Conclusions. A state‐level Medicaid policy change was followed by both a significant involvement of medical care providers and an overall increase in FVT. Children between the ages of 1 and 2 years appear to benefit the most from the involvement of medical care providers.
Intra‐abdominal hypertension in two adult horses
Authors: Brosnahan Margaret M. , Holbrook Todd C. , Gilliam Lyndi L. , Ritchey Jerry W. , Confer Anthony W.
Published: April 2009

Objective
– To describe the clinical and pathological findings in 2 adult horses with documented increases in intra‐abdominal pressure (IAP), and to describe the direct puncture technique used to measure this pressure.

Series Summary
– Two adult horses developed increases in IAP secondary to large‐volume abdominal effusion. A 9‐year‐old Quarter Horse cross gelding was presented for evaluation of urinary and neurologic signs. Abdominal ultrasonographic examination showed a hepatic abscess along with abdominal effusion. A 4‐year‐old Quarter Horse gelding was presented for evaluation of castration complications. A castration site infection extended into surrounding tissues, resulting in peritonitis, abdominal effusion, and severe cellulitis of the limbs. IAP measured in both horses was increased relative to reported equine reference values. Changes in hemodynamic parameters in both horses, notably increased central venous pressure, were consistent with those seen in other species in which intra‐abdominal hypertension (IAH) and its sequellae have been documented.

New or Unique Information Provided
– Extensive research and clinical literature guides management of humans with IAH and abdominal compartment syndrome. Knowledge of these conditions in companion animal and large domestic species is less well developed. Recent research has established reference values for standing, sedated and recumbent, anesthetized horses. Detailed reports of equine clinical cases of IAH have not been reported in the literature. This report provides information on the clinical, hemodynamic, and pathologic characteristics of 2 horses with measured increases in IAP, and describes the direct puncture technique used to perform these measurements.
Characteristics and outcomes in surgical management of severe acute pancreatitis: 37 dogs (2001–2007)
Authors: Thompson Lisa J. , Seshadri Ravi , Raffe Marc R.
Published: April 2009

Objective –Describe clinical characteristics and outcomes associated with canine patients undergoing surgical intervention for treatment of acute pancreatitis.

Design –Retrospective outcome study from 2001 to 2007.

Animals –Thirty‐seven dogs.

Interventions –None.

Measurements and Main Results –The following data were collected for dogs who underwent surgical intervention in the course of treatment for severe acute pancreatitis: preoperative clinicopathologic and physical data, ultrasonographic findings, surgical procedure detail, histopathologic findings, and transfusion requirements. The survival rate was 80.8% in dogs with extrahepatic biliary obstruction, 64.3% in dogs undergoing necrosectomy, and 40.6% with pancreatic abscess. Overall survival was 63.6%. Surgical complications included intraoperative and postoperative hemorrhage in 12 dogs, postoperative development of diabetes mellitus in 3 dogs, exocrine pancreatic insufficiency in 1 dog, and bacterial peritonitis in 2 dogs.

Conclusion –Surgical intervention and aggressive postoperative care may be pursued in select dogs with severe acute pancreatitis. In dogs with extrahepatic biliary obstruction secondary to acute pancreatitis, surgical intervention may be associated with a good prognosis whereas dogs with pancreatic abscess formation may have a more guarded prognosis.
Effects of probiotic therapy on portal pressure in patients with cirrhosis: a pilot study
Authors: Tandon Puneeta , Moncrief Karli , Madsen Karen , Arrieta Marie C. , Owen Richard J. , Bain Vince G. , Wong Winnie W. , Ma Mang M.
Published: April 2009

Background: Recent literature has supported the role of bacterial translocation as a mediator of splanchnic vasodilatation and portal hypertension. The objective of this study was to determine whether the probiotic VSL#3 would reduce portal pressure in patients with cirrhosis.

Methods: Eight patients with compensated or very early decompensated cirrhosis and hepatic venous pressure gradient (HVPG) >10 mmHg, received 2 months of VSL#3 (3600 billion bacteria daily). The HVPG, intestinal permeability, endotoxin, tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐8, renin and aldosterone were measured at baseline and study end.

Results: There was no change in the HVPG or intestinal permeability from baseline to study end but there was a trend to reduction in plasma endotoxin (P=0.09), a mild but significant increase in serum TNF‐α (P=0.02) and a significant reduction in plasma aldosterone (P=0.03).

Conclusions: Within the limitations of small sample size, there does not appear to be a benefit of probiotic therapy for portal pressure reduction in patients with compensated or early decompensated cirrhosis. The reductions in endotoxin and aldosterone suggest possible beneficial effects of probiotics for this patient population. The clinical significance of the small but unexpected increase in TNF‐α is unclear. Future studies are planned in patients with decompensated cirrhosis.
Cross‐species immunohistochemical investigation of the activation of the liver progenitor cell niche in different types of liver disease
Authors: Schotanus Baukje A. , Van Den Ingh Ted S. G. A. M. , Penning Louis C. , Rothuizen Jan , Roskams Tania A. , Spee Bart
Published: April 2009

Background: When hepatocyte replication during liver disease is insufficient for regeneration, liver progenitor cells (LPCs) are activated. The cells and stroma in the immediate environment of LPCs, together termed the LPC niche, are thought to play an important role in this activation. Among these cells are the hepatic stellate cells (HSCs)/myofibroblasts (MFs).

Aims/Methods: We assessed the activation of HSC/MFs and LPCs in relation to the histological location and extent of liver disease in immunohistochemically (double) stained serial sections. Markers of HSC/MFs [α‐smooth muscle actin, glial fibrillary acidic protein (GFAP), neurotrophin 3 and neural‐cell adhesion molecule], markers of LPCs (keratin 7 and keratin 19) and a proliferation marker (Ki67) were used. A very relevant spontaneous model to evaluate LPC niche activation in a translational approach seems to be the dog. Therefore, both human and canine liver diseases with different degree of fibrosis and disease activity were included.

Results: In human and canine liver disease, type and extent of LPC niche activation depended on type and severity of disease (P<0.05) and corresponded to the main location of disease. Activated HSCs surrounded the activated LPCs. In chronic hepatitis and non‐alcoholic steatohepatitis lobular‐type HSCs were activated, while during biliary disease portal/septal MFs were mainly activated. In canine liver, GFAP further presented as an early marker of HSC activation. Activation of the LPCs correlated with disease location and severity (P<0.01), and was inversely related to hepatocyte proliferation, as was previously shown in man.

Conclusion: A shared involvement of HSC/MFs, LPCs and disease severity during hepatic disease processes is shown, which is highly similar in man and dog.
Genetic differences in oxidative stress and inflammatory responses to diet‐induced obesity do not alter liver fibrosis in mice
Authors: Syn Wing‐Kin , Yang Liu , Chiang Dian Jung , Qian Yue , Jung Youngmi , Karaca Gamze , Choi Steve S. , Witek Rafal P. , Omenetti Alessia , Pereira Thiago A. , Diehl Anna Mae
Published: April 2009

Objective:To determine how genetic factors might influence the progression of nonalcoholic fatty liver disease (NAFLD).

Design/Intervention:Beginning in adolescence, male C57BL6 (BL6) and 129/SVJ mice were fed control (n=15/group) or high‐fat (HF) diets (n=30/group) for 6 months.

Main Outcome Measures:Assessed were body weight, insulin resistance, hepatic production of free radicals, expression of cytokines and fibrosis‐related genes and severity of hepatic steatosis, injury and fibrosis.

Results:High‐fat diets induced comparable obesity, hepatic steatosis and insulin resistance in the two strains. Compared with BL6 mice, 129/SVJ mice had impaired induction of antioxidant genes, generated three‐ to four‐fold more free radicals and exhibited two‐fold greater induction of profibrogenic cytokines (interleukin‐4 and transforming growth factor‐β1) and fibrosis‐related genes (fibronectin and tissue inhibitor of metalloproteinase‐1) (allP<0.05 for 129 vs BL6). Surprisingly, however, induction of collagen I α1 mRNA and accumulation of Sirius red‐stained fibrils and hepatic hydroxyproline were similar in BL6 and 129/SVJ mice, and although patchy sinusoidal fibrosis emerged in both strains, neither developed bridging fibrosis.

Conclusions:Although BL6 and 129/SVJ mice with diet‐induced obesity, insulin resistance and steatosis differed with respect to several factors that are thought to influence human NAFLD progression, they developed comparable liver fibrosis. Moreover, none of the risk factors for NAFLD‐related cirrhosis in humans, including obesity, insulin resistance, chronic inflammatory and oxidant stress, steatohepatitis or activation of fibrogenic genes, proved to be sufficient to cause cirrhosis in these mice, even when exposure to one or more of these insults was very prolonged.
ASDIN: Establishing Learning Curve for Tenckhoff Catheter Insertion by Interventional Nephrologist Using CUSUM Analysis: How Many Procedures and in Which Situation?
Authors: Goh Bak Leong , Ganeshadeva Yudisthra M. , Lim Teck Onn
Published: April 2009

Peritoneal dialysis (PD) catheter insertion success rate is known to vary among different operators, and peritoneoscope PD catheter insertion demands mastery of a steep learning curve. Defining a learning curve using a continuous monitoring tool such as a Cumulative Summation (CUSUM) chart is useful for planning training programs. We aimed to analyze the learning curve of a trainee nephrologist in performing peritoneoscope PD catheter implantation with CUSUM chart. This was a descriptive single‐center study using collected data from all PD patients who underwent peritoneoscope PD catheter insertion in our hospital. CUSUM model was used to evaluate the learning curve for peritoneoscope PD catheter insertion. Unacceptable primary failure rate (i.e., catheter malfunction within 1 month of insertion) was defined at >40% and acceptable performance was defined at <25%. CUSUM chart showed the learning curve of a trainee in acquiring new skill. As the trainee became more skillful with training, the CUSUM curve flattened. Technical proficiency of the trainee nephrologist in performing peritoneoscope Tenckhoff catheter insertion (<25% primary catheter malfunction) was attained after 23 procedures. We also noted earlier in our program that Tenckhoff catheters directed to the right iliac fossae had poorer survival as compared to catheters directed to the left iliac fossae. Survival of catheters directed to the left iliac fossae was 94.6% while the survival for catheters directed to the right iliac fossae was 48.6% (p < 0.01). We advocate that quality control of Tenckhoff catheter insertion is performed using CUSUM charting as described to monitor primary catheter dysfunction (i.e., failure of catheter function within 1 month of insertion), primary leak (i.e., within 1 month of catheter insertion), and primary peritonitis (i.e., within 2 weeks of catheter insertion).
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Selection of Modality of Renal Replacement Therapy
Authors: Antoun Tania Abi , Palevsky Paul M.
Published: April 2009

The proliferation of new technologies has led to the availability of a broad range of options for the management of renal replacement therapy (RRT) in patients with acute kidney injury. We provide a review of the published literature comparing the continuous RRTs (CRRT) with other modalities of renal support, including intermittent hemodialysis and the more recently described “hybrid” therapies such as sustained, low efficiency dialysis as well as compare arteriovenous and venovenous and convective and diffusive modalities of CRRT. While there is clear evidence that venovenous therapies are superior to arteriovenous therapies, current evidence does not support superiority of convective when compared with diffusive therapies or greater survival or recovery of kidney function with any individual modality of RRT. Selection of modality of RRT should therefore rely on the resources and expertise available.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Drug Dosing During Continuous Renal Replacement Therapy
Authors: Churchwell Mariann D. , Mueller Bruce A.
Published: April 2009

Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Intensity of Continuous Renal Replacement Therapy in Acute Kidney Injury
Authors: Palevsky Paul M.
Published: April 2009

The intensity of continuous renal replacement therapy (CRRT) is generally assessed on the basis of small solute clearance with dosing usually expressed in terms of total effluent volume per unit time (e.g., ml/kg/hour). Although several clinical trials have suggested an improvement in survival with higher doses of CRRT, results have not been consistent across all studies. The results of recent trials of intensity of CRRT are reviewed. The largest and most recent trials suggest that there is no additional benefit to using effluent flow rates in excess of 20 ml/kg/hour, although earlier studies suggested improved survival with doses of 35 to 45 ml/kg/hour.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Machines for Continuous Renal Replacement Therapy
Authors: Cruz Dinna , Bobek Ilona , Lentini Paolo , Soni Sachin , Chionh Chang Yin , Ronco Claudio
Published: April 2009

A significant number of advancements have taken place since the beginning of continuous renal replacement therapy (CRRT). In particular, high volume hemofiltration and high permeability hemofiltration have been successful extensions of the technique. The additional and combined use of sorbent has also been tested successfully. Specific machines have now been designed to permit safe and reliable performance of the therapy. These new devices are equipped with a friendly user interface that allows for easy performance and monitoring. The apparent complexity of the circuit is made simple by a self‐loading circuit or a cartridge which includes the filter and the blood and dialysate lines. Priming is performed automatically by the machine and pre‐ or postdilution (reinfusion of substitution fluid before or after the filter) can easily be performed by changing the position of the reinfusion line. These new machines permit all CRRT methodologies to be performed by programming the flows and the total amounts of fluid to be exchanged or circulated as a countercurrent dialysate at the beginning of the session. Progress has been made not only in technology in this area but also on our understanding of the pathophysiology of acute renal failure. New biomaterials and new devices are now available with new frontiers are on the horizon. We might, however, speculate that although improvements have been made, a lot remains to be done. There is no doubt that technology has progressed enormously in critical care nephrology and that more progress will come in the near future. The goal, and likely outcome, is an improvement in the morbidity and mortality of the most severely ill patients.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Anticoagulation for Continuous Renal Replacement Therapy
Authors: Tolwani Ashita J. , Wille Keith M.
Published: April 2009

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury, particularly those with hemodynamic instability. Anticoagulation is necessary for effective delivery of CRRT, but this requirement can also present challenges, as many critically ill patients with sepsis and inflammation already have a higher risk of bleeding as well as clotting. Without anticoagulation, CRRT filter and circuit survival are diminished, and therapy becomes less helpful. Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin‐induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods of anticoagulation have been investigated, including regional heparin/protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat). Each of these techniques has unique advantages and disadvantages, and anticoagulation for CRRT should be adapted to the patient’s characteristics and institution’s experience. Of the alternative methods, citrate anticoagulation is gaining wider acceptance with the development of simplified and safer protocols.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Continuous Renal Replacement Therapies in Patients with Acute Neurological Injury
Authors: Davenport Andrew
Published: April 2009

Acute neurological injury may occur in patients with end‐stage kidney disease on dialysis. Less frequently, acute kidney injury requiring renal dialytic support develops following acute neurological injury. Surrounding any site of neurological injury there is a penumbra of damage which is potentially reversible. To maximize full potential neurological recovery in patients requiring renal dialytic support, it is important that treatments do not themselves cause further cerebral ischemia. Standard intermittent hemodialysis is associated with cerebral swelling even in healthy outpatients and often with episodes of intradialytic hypotension. Continuous modes of renal replacement therapy have been shown to cause fewer surges in intracranial pressure and greater stability of cerebral perfusion pressure than standard intermittent techniques. In patients with acute neurological injury, renal replacement therapy should be carefully adapted to minimize cardiovascular instability and reduce the rate of change of serum osmolality.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Modalities of Continuous Renal Replacement Therapy: Technical and Clinical Considerations
Authors: Cerdá Jorge , Ronco Claudio
Published: April 2009

Continuous renal replacement therapies (CRRT) are continuous forms of renal functional replacement used to manage acute kidney injury (AKI) in the critically ill patient. Depurative mechanisms include convection, diffusion, and membrane adsorption utilizing high‐flux highly permeable biocompatible dialysis membranes. The simultaneous infusion of replacement fluid permits fluid removal without intravascular volume contraction and better hemodynamic stability, metabolic control to almost normal parameters, and removal of large‐size toxins and cytokines. Moreover, CRRT allows better long‐term clearance of small and middle molecules than other dialysis modalities. This article focuses on the different modalities of CRRT and reviews both the basic concepts and the newest approaches to the management of the critically ill patient with AKI.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Complications of Continuous Renal Replacement Therapy
Authors: Finkel Kevin W. , Podoll Amber S.
Published: April 2009

Continuous renal replacement therapy (CRRT) is commonly used in critically ill patients with acute kidney injury. Many studies show that compared with intermittent hemodialysis, continuous therapy has superior hemodynamic stability, metabolic clearance, and volume control. Despite these benefits, no survival advantage can be demonstrated with its use. Although study design explains much of this paradox, it is also quite plausible that the complications associated with CRRT negate its potential benefits in the critically ill patient. We summarize the common complications associated with the use of CRRT.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Selection of Dialysate and Replacement Fluids and Management of Electrolyte and Acid‐Base Disturbances
Authors: Kraus Michael A.
Published: April 2009

Often, too little consideration is given to the fluids used in all forms of continuous renal replacement therapy (CRRT). However, errors in fluid prescription, delivery, or creation can be rapidly fatal; in addition, fluid associated expenses can be the overriding cost in continuous renal replacement therapies. While a standard solution is frequently acceptable in most clinical circumstances, specific electrolyte and acid‐base disturbances may direct changes in fluid delivery and composition. Decisions regarding fluids, whether dialysate versus replacement, including generation and composition of therapy are discussed in this review.
THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Volume Management in Continuous Renal Replacement Therapy
Authors: Bouchard Josée , Mehta Ravindra L.
Published: April 2009

Volume management is an integral component of the care of critically ill patients to maintain hemodynamic stability and optimize organ function. The dynamic nature of critical illness often necessitates volume resuscitation and contributes to fluid overload particularly in the presence of altered renal function. Diuretics are commonly used as an initial therapy to increase urine output; however they have limited effectiveness due to underlying acute kidney injury and other factors contributing to diuretic resistance. Continuous renal replacement techniques (CRRT) are often required for volume management. In this setting, successful volume management depends on an accurate assessment of fluid status, an adequate comprehension of the principles of fluid management with ultrafiltration, and clear treatment goals. Complications related to excessive ultrafiltration can occur and have serious consequences. A careful monitoring of fluid balance is therefore essential for all patients. This review provides an overview of the appropriate assessment and management of volume status in critically ill patients and its management with CRRT to optimize organ function and prevent complications of fluid overload.
Decreased Sensitivity to Ethanol Reward in Adolescent Mice as Measured by Conditioned Place Preference
Authors: Dickinson Shelly D. , Kashawny Sarah K. , Thiebes Karen P. , Charles Dean Y.
Published: April 2009

Background:  Many preclinical studies have demonstrated age‐related differential sensitivity to various effects of ethanol between adolescent and adult animals. However, published data addressing possible differences in ethanol’s motivational effects are sparse, particularly in mice. The present study examined age‐related differences in the conditioned rewarding effects of ethanol in DBA/2J mice.

Methods:  In the first experiment an unbiased place conditioning procedure was used to determine the rewarding effects of 2 g/kg ethanol in adult and adolescent DBA/2J mice. In a subsequent place conditioning experiment, the effects of 2 and 4 g/kg were assessed in adolescent mice.

Results:  Adolescents demonstrated a place preference with the high dose of 4 g/kg but not with a more moderate dose of 2 g/kg. In contrast, 2 g/kg was sufficient to produce place preference in adult mice.

Conclusions:  Adolescents are less sensitive than adults to the rewarding effects of ethanol but can experience reward with high doses. These results extend the current literature on ethanol’s effects in adolescent animals.
Effects of Pregnanolone and Dehydroepiandrosterone on Ethanol Intake in Rats Administered Ethanol or Saline during Adolescence
Authors: Gurkovskaya Olga V. , Leonard Stuart T. , Lewis Peter B. , Winsauer Peter J.
Published: April 2009

Background: Adolescent alcohol use may contribute to long‐term changes in the receptors and neuroactive steroids that may mediate its effects and to subsequent alcohol abuse and dependence as an adult. Therefore, in this study, ethanol preference and intake as an adult were examined after adolescent ethanol or saline administration. In addition, ethanol intake in the same groups was examined after administration of 2 neuroactive steroids with modulatory effects at GABAAreceptors.

Methods: Two groups of male Long‐Evans rats were administered 15 intraperitoneal (i.p.) injections of either ethanol (2 g/kg, 20% v/v) or saline between postnatal days 35 and 63. Starting on postnatal day 75, both groups were trained to consume 10% ethanol using a saccharin‐fading procedure, and ethanol intake and preference were measured after a series of manipulations involving food deprivation, changes in the duration of access to ethanol, and changes in the concentrations of ethanol presented. Following these manipulations, pregnanolone (1 to 10 mg/kg) and dehydroepiandrosterone (DHEA, 1 to 100 mg/kg) were administered prior to preference sessions with an 18% ethanol solution.

Results: Adult ethanol preference and intake did not differ significantly in subjects treated with either saline or ethanol as adolescents during training, the substitution of other ethanol concentrations (3.2 to 32%), ad‐lib feeding, or moderate food deprivation. Pregnanolone administration altered the intake of both adolescent‐treated groups after the first injection of 3.2 mg/kg and after repeated injections with 10 mg/kg, a dose that produced sedation. In contrast, multiple doses of DHEA consistently decreased intake of an 18% ethanol concentration in both groups after repeated injections and 3 doses of DHEA (10, 32, and 56 mg/kg) administered with various ethanol concentrations dose‐dependently shifted the ethanol‐concentration curves for the volume and dosage of ethanol consumed downward.

Conclusions: These results indicate that chronic intermittent ethanol (CIE) administration of 2 g/kg during adolescence did not alter preference or overall consumption of ethanol in outbred rats trained to drink ethanol as an adult under the conditions tested, and that DHEA may be more effective than pregnanolone at significantly decreasing ethanol consumption.
Projected Alcohol Dose Influences on the Activation of Alcohol Expectancies in College Drinkers
Authors: Read Jennifer P. , Lau‐Barraco Cathy , Dunn Michael E. , Borsari Brian
Published: April 2009

Background:  Alcohol expectancies have been linked to drinking behavior in college students, and vary according to a number of factors, including projected dose of alcohol. Research using Multidimensional Scaling (MDS) suggests that drinking may be influenced by activation of differing expectancy dimensions in memory, yet studies have not examined expectancy activation according to projected alcohol doses.

Methods:  The present study used Individual Differences Scaling (INDSCAL) to map expectancy networks of college students (n = 334) who imagined varied drinking at high and low alcohol doses. Expectancy activation was modeled by dose, as well as by gender and by drinking patterns (typical quantity, blood alcohol content, heavy episodic drinking, and alcohol consequences). Expectancies were organized along positive–negative and arousal–sedation dimensions. Anticipation of a high dose of alcohol was associated with greater emphasis on the arousal–sedation dimension, whereas anticipation of a lower dose was associated with greater emphasis on the positive–negative dimension.

Results:  Across heavy, medium, and light drinkers, expectancy dimensions were most distinguishable at higher doses; activation patterns were more similar across drinking groups at lighter doses. Modest evidence for the influence of gender on activation patterns was observed. Findings were consistent across alcohol involvement indices.

Conclusions:  These data suggest that both dimensionality and context should be considered in the refinement of interventions designed to alter expectancies in order to decrease hazardous drinking.
Circadian Timing of Ethanol Exposure Exerts Enduring Effects on Subsequent Ad Libitum Consumption in C57 Mice
Authors: Trujillo Jennifer L. , Roberts Amanda J. , Gorman Michael R.
Published: April 2009

Background:  There is a daily rhythm in the voluntary intake of ethanol in mice, with greatest consumption in the early night and lowest intake during the day. The role of daily timing of ethanol exposure on the development and control of long‐term ethanol self‐administration has been neglected. The present study examines these issues using C57BL/6J mice.

Methods:  Mice were repeatedly exposed to 10% ethanol for 2 hours early in the night or day for several weeks. Subsequently, ethanol was available at the opposite time (Expt 1) or 24 hours daily (Expts 1 and 2). Lick sensors recorded the patterns of drinking activity in Experiment 2.

Results:  Mice exposed to ethanol during the night drink more than mice exposed during the day. Prior history did not affect ethanol intake when the schedule was reversed. Under 24‐hour exposure conditions, mice with a history of drinking during the night consumed significantly more than mice drinking during the day. The circadian patterns of drinking were not altered.

Conclusions:  These results demonstrate that the daily timing of ethanol exposure exerts enduring effects of self‐administration of ethanol in mice. Understanding how circadian rhythms regulate ethanol consumption may be valuable for modifying subsequent intake.
Comparing Models of Frailty: The Health and Retirement Study
Authors: Cigolle Christine T. , Ofstedal Mary Beth , Tian Zhiyi , Blaum Caroline S.
Published: April 2009

OBJECTIVES: To operationalize and compare three models of frailty, each representing a distinct theoretical view of frailty: as deficiencies in function (Functional Domains model), as an index of health burden (Burden model), and as a biological syndrome (Biologic Syndrome model).

DESIGN: Cross‐sectional analysis.

SETTING: 2004 wave of the Health and Retirement Study, a nationally representative, longitudinal health interview survey.

PARTICIPANTS: Adults aged 65 and older (N=11,113) living in the community and in nursing homes in the United States.

MEASUREMENTS: The outcome measure was the presence of frailty, as defined according to each frailty model. Covariates included chronic diseases and sociodemographic characteristics.

RESULTS: Almost one‐third (30.2%) of respondents were frail according to at least one model; 3.1% were frail according to all three models. The Functional Domains model showed the least overlap with the other models. In contrast, 76.1% of those classified as frail according to the Biologic Syndrome model and 72.1% of those according to the Burden model were also frail according to at least one other model. Older adults identified as frail according to the different models differed in sociodemographic and chronic disease characteristics. For example, the Biologic Syndrome model demonstrated substantial associations with older age (adjusted odds ratio (OR)=10.6, 95% confidence interval (CI)=6.1–18.5), female sex (OR=1.7, 95% CI=1.2–2.5), and African‐American ethnicity (OR=2.1, % CI=1.0–4.4).

CONCLUSION: Different models of frailty, based on different theoretical constructs, capture different groups of older adults. The different models may represent different frailty pathways or trajectories to adverse outcomes such as disability and death.
The Effect of Age on the Association Between Blood Pressure and Cognitive Function Later in Life
Authors: Euser Sjoerd M. , Van Bemmel Thomas , Schram Miranda T. , Gussekloo Jacobijn , Hofman Albert , Westendorp Rudi G. J. , Breteler Monique M. B.
Published: April 2009

OBJECTIVES: To determine the prospective relationship between blood pressure (BP) and cognitive function across a wide age range.

DESIGN: Prospective population‐based cohort study.

SETTING: The Rotterdam Study and the Leiden 85‐plus Study.

PARTICIPANTS: Three thousand seventy‐eight men and women, initial age 55 to 84 from the Rotterdam Study and 276 men and women, initial age 85, from the Leiden 85‐plus Study.

MEASUREMENTS: Systolic BP (SBP) and diastolic BP (DBP) were measured at baseline, cognitive function was assessed at the end of follow‐up using a dedicated neuropsychological test battery. The association between baseline BP levels and cognitive function later in life was assessed in 10‐year age groups in the Rotterdam Study and in 85‐year‐olds of the Leiden 85‐plus Study.

RESULTS: In the youngest participants (<65), SBP and DBP were not associated with cognitive function 11 years later. For persons aged 65 to 74, higher baseline SBP and DBP were related to worse cognitive function 11 years later. In contrast, in older age (≥75), higher SBP and DBP seemed to be related to better cognitive function at the end of follow‐up. This effect appeared strongest in the highest age group (aged 85).

CONCLUSION: High BP was associated with greater risk of cognitive impairment in persons younger than 75 but with better cognitive function in older persons. Age‐specific guidelines for BP management are needed, because the current directive that “lower is better” may not apply to BP levels in the very old.
Effect of Two Methods of Reinforcement on the Fracture Strength of Interim Fixed Partial Dentures
Authors: Fahmy Nadia Z. , Sharawi Amr
Published: April 2009

Purpose: This study assessed the efficiency of reinforcing provisional restorations by adding a fine gauze metallic mesh or polyethylene fibers between the abutments spanning the pontic length.

Materials and Methods: Forty‐five resin fixed partial dentures (FPDs) were constructed using three provisional resins. The three resin groups were further divided into three subgroups depending on their reinforcement. Specimens were loaded compressively, and the load required to fracture the specimens was recorded in Newtons. Data were presented as means and standard deviation values. A regression model with two‐way ANOVA was used in testing significance. Duncan's post hoc test was used for pairwise comparison (p≤ 0.05).

Results: Duralay resin and Duralay fiber‐reinforced restorations showed the highest fracture‐resistance values, followed by Protemp and Snap, which showed statistically similar values. The three mesh‐reinforced resin restoration materials showed no statistically significant difference between their fracture resistance values. Reinforcement did not alter the fracture resistance of Duralay and Protemp resin subgroups, but significantly increased that of Snap, equalizing it with the other resins. The three resin materials had similar moduli. Significant alterations occurred after fiber reinforcement. Results showed that fiber‐reinforced Duralay resin showed the highest modulus values, while no statistical difference was found between the moduli of fiber‐reinforced Protemp and Snap. Regarding the mesh‐reinforced groups, Duralay had the highest modulus followed by Protemp and Snap. Reinforcements altered the modulus values of Duralay resin only. Mesh‐reinforced Duralay resin showed the highest mean modulus, but no statistically significant difference was apparent between fiber‐reinforced and control groups. As for Protemp and Snap resin subgroups, their moduli remained unchanged by reinforcements.

Conclusion: Initially, Duralay resin had higher fracture resistance values than Protemp II and Snap. Fiber and mesh reinforcements increased the fracture resistance of Snap. No statistically significant difference was evident among the fracture resistances of the three mesh‐reinforced resin FPD restorations. The three resins had similar moduli. Fiber and mesh reinforcement increased the modulus of Duralay resin but did not change that of Protemp and Snap. Fiber and metal mesh reinforcements may alter the fracture strength and modulus of some, but not all, provisional resins.