bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Src in ligand‐specific regulation of δ‐opioid receptor desensitization and internalization
Authors: Hong Min‐Hua , Xu Chi , Wang Yu‐Jun , Ji Jing‐Li , Tao Yi‐Min , Xu Xue‐Jun , Chen Jie , Xie Xin , Chi Zhi‐Qiang , Liu Jing‐Gen
Published: November 2008

The opioid receptors are a member of G protein‐coupled receptors that mediate physiological effects of endogenous opioid peptides and structurally distinct opioid alkaloids. Although it is well characterized that there is differential receptor desensitization and internalization properties following activation by distinct agonists, the underlying mechanisms remain elusive. We investigated the signaling events of δ‐opioid receptor (δOR) initiated by two ligands, DPDPE and TIPP. We found that although both ligands inhibited adenylyl cyclase (AC) and activated ERK1/2, only DPDPE induced desensitization and internalization of the δOR. We further found that DPDPE, instead of TIPP, could activate GRK2 by phosphorylating the non‐receptor tyrosine kinase Src and translocating it to membrane receptors. Activation of GRK2 led to the phosphorylation of serine residues in the C‐terminal tail, which facilitates β‐arrestin1/2 membrane translocation. Meanwhile, we also found that DPDPE promoted β‐arrestin1 dephosphorylation in a Src‐dependent manner. Thus, DPDPE appears to strengthen β‐arrestin function by dual regulations: promoting β‐arrestin recruitment and increasing β‐arrestin dephosphorylation at the plasma membrane in a Src‐dependent manner. All effects initiated by DPDPE could be abolished or suppressed by PP2, an inhibitor of Src. Morphine, which has been previously shown to be unable to desensitize or internalize δOR, also behaved as TIPP in failure to utilize Src to regulate δOR signaling. These findings point to the existence of agonist‐specific utilization of Src to regulate δOR signaling and reveal the molecular events by which Src modulates δOR responsiveness.
Understanding your inhibitions: effects of GABA and GABAAreceptor modulation on brain cortical metabolism
Authors: Nasrallah Fatima A. , Griffin Julian L. , Balcar Vladimir J. , Rae Caroline
Published: November 2008

A targeted neuropharmacological,1H/13C NMR spectroscopy and multivariate statistical approach was used to examine the effects of exogenous GABA and ligands at the GABAAreceptor family on brain metabolism in the Guinea pig cortical tissue slice. All ligands at GABAAreceptors generated metabolic patterns which were distinct from one another with the major variance in the data arising because of metabolic work (shown by net flux into Krebs cycle byproducts and increased metabolic pool sizes). Three major clusters of metabolic signatures were identified which corresponded to: (i) activity at phasic (synaptic) GABAAreceptors, dominated by α1‐containing receptors and responsive to GABA at 10 μmol/L; (ii) activity at perisynaptic receptors, dominated by response to high (40 μmol/L) GABA and the superagonist 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridine‐3‐ol hydrochloride, and C, activity at extrasynaptic receptors, dominated by response to low (0.1–1.0 μmol/L) GABA, zolpidem (400 nmol/L) and the non‐specific allosteric modulator RO19‐4603 (1 nmol/L). These results highlight the utility of a different but robust approach to study of the GABAergic system using metabolic systems analysis.
Activation of P2X7 receptors induces CCL3 production in microglial cells through transcription factor NFAT
Authors: Kataoka Ayako , Tozaki‐Saitoh Hidetoshi , Koga Yui , Tsuda Makoto , Inoue Kazuhide
Published: November 2008

Microglia are implicated as a source of diverse proinflammatory factors in the CNS. Extracellular nucleotides are well known to be potent activators of glial cells and trigger the release of cytokines from microglia through purinergic receptors. However, little is known about the role of purinoceptors in microglial chemokine release. In this study, we found that high concentrations of ATP evoked release of CC‐chemokine ligand 3 (CCL3)/macrophage inflammatory protein‐1α from MG‐5 cells, a mouse microglial cell line, and rapid up‐regulation of CCL3 mRNA was elicited within 30 min of ATP stimulation. The release of CCL3 was also stimulated by 2′‐ and 3′‐O‐(4‐benzoylbenzoyl) ATP, an agonist of P2X7 receptors. Brilliant Blue G, an antagonist of P2X7 receptors, strongly inhibited this ATP‐induced CCL3 release. Similar pharmacological profile was observed in primary microglia. In MG‐5 cells, ATP caused de‐phosphorylation and nuclear translocation of the transcription factor nuclear factor of activated T cells (NFAT). ATP‐induced NFAT de‐phosphorylation was also dependent on P2X7 receptor activation. Furthermore, ATP‐induced CCL3 release and production were prevented by a selective inhibitor of NFAT. Taken together, the results of this study demonstrate an involvement of NFAT in the mechanism underlying P2X7 receptor‐mediated CCL3 release.
Fibronectin stimulates TRPV1 translocation in primary sensory neurons
Authors: Jeske Nathaniel A. , Patwardhan Amol M. , Henry Michael A. , Milam Stephen B.
Published: November 2008

Extracellular matrix (ECM) molecules are highly variable in their composition and receptor recognition. Their ubiquitous expression profile has been linked to roles in cell growth, differentiation, and survival. Recent work has identified certain ECM molecules that serve as dynamic signal modulators, versus the more‐recognized role of chronic modulation of signal transduction. In this study, we investigated the role that fibronectin (FN) plays in the dynamic modulation of transient receptor potential family V type 1 receptor (TRPV1) translocation to the plasma membrane in trigeminal ganglia (TG) sensory neurons. Confocal immunofluorescence analyses identify co‐expression of the TRPV1 receptor with integrin subunits that bind FN. TG neurons cultured upon or treated with FN experienced a leftward shift in the EC50 of capsaicin‐stimulated neuropeptide release. This FN‐induced increase in TRPV1 sensitivity to activation is coupled by an increase in plasma membrane expression of TRPV1, as well as an increase in tyrosine phosphorylation of TRPV1 in TG neurons. Furthermore, TG neurons cultured on FN demonstrated an increase in capsaicin‐mediated Ca2+ accumulation relative to neurons cultured on poly‐d‐lysine. Data presented from these studies indicate that FN stimulates tyrosine‐phosphorylation‐dependent translocation of the TRPV1 receptor to the plasma membrane, identifying FN as a critical component of the ECM capable of sensory neuron sensitization.
Assessing burden of illness following acute deep vein thrombosis: data quality, reliability and validity of the Norwegian version of VEINES‐QOL/Sym, a disease‐specific questionnaire
Authors: Enden Tone , Garratt Andrew Malcolm , Kløw Nils‐Einar , Sandset Per Morten
Published: November 2008

The data quality, reliability and validity of the Norwegian version of VEINES‐QOL/Sym were assessed in 74 patients with deep vein thrombosis (DVT). This patient‐reported questionnaire produces two scale scores of venous disease‐specific quality of life and venous symptoms. Items had low levels of missing data. Item‐total correlations ranged from 0.41 to 0.78 with the exception of 0.29 for the symptom item ‘night cramps’. Internal consistency was supported by Cronbach’s alpha of 0.88 and 0.94 for VEINES‐Sym and VEINES‐QOL, respectively. Test–retest reliability assessed for 40 patients gave intraclass correlation coefficients of 0.83 and 0.88 for VEINES‐Sym and VEINES‐QOL, respectively. Assessment of correlation between the two scales and other clinical measures supports the construct validity of the scales. The results indicate acceptable internal consistency, test–retest reliability and validity of the Norwegian version of the VEINES‐QOL/Sym questionnaire in patients with DVT. The results follow those of previous studies, and support the use of VEINES‐QOL/Sym in the evaluation of patient outcomes and burden of illness in clinical studies of venous thrombosis.
Hernofiltration for the Treatment of Hypertensions Associated with End‐Stage Renal Failure
Authors: Henderson Lee W.
Published: November 2008

Six patients with chronic renal failure and hypertension have been studied with a crossover protocol involving three months on hemodialysis followed by three months on predilution hemofiltration and concluded by a return to hernodialysis for three months. Half of the patients showed improved blood pressure control in the absence of measurable changes in plasma renin activity, blood volume, and body weight. A fall in dopamine‐β‐hydroxylase activity in the plasma and a reduction in the lability of blood pressure in these three patients suggest that improved blood pressure control is the result of improvement in the defective baroreceptor reflex noted to be present in patients with chronic renal failure and hypertension.
Selective Plasma Component Removal: Alternatives to Plasma Exchange
Authors: Pineda Alvaro A. , Taswell Howard F.
Published: November 2008

Plasma exchange, the unselective removal of all plasma constituents, has been applied, with varying degrees of success, to an increasing number of disorders. Because of the high cost of plasma exchange, largely the result of expensive homologous replacement solution, and other reasons, alternatives have been sought. Selective removal of plasma components permits the use of autologous plasma as replacement which is less costly, more physiologic, and in some cases, a more efficient alternative to plasma exchange. The selective removal of plasma components whose presence is associated with a disease process can be accomplished presently by physical or chemical means with either on‐line or off‐line systems. A state‐of‐the‐art review of currently available alternatives to plasma exchange is described. This includes hemoperfusion and plasmaperfusion over affinity columns or filters with immobilized sorbents. On‐line separation of macromolecules by membrane filtration and cryoprecipitation as well as off‐line chemical precipitation and cryoprecipitation are also described. The potential and limitations of the techniques are emphasized.
Dialyzer Ultrafiltration Coefficients: Comparison Between In Vitro and In Vivo Values
Authors: Keshaviah Prakash R. , Constantini Edward G. , Luehmann Douglas A. , Shapiro Fred L.
Published: November 2008

This study describes a simple, convenient method for the in vivo measurement of the ultrafiltration coefficient of hemo‐dialyzers. The method is based on a scheme of isolated ultrafiltration, i.e., ultrafiltration without dialysate flow through the dialyzer. Results with this method indicate that it is more accurate than the conventional bed scale technique. Measurements on three different dialyzers demonstrate that the in vivo ultrafiltration coefficient is only between 1% and 10% lower than the corresponding in vitro value. This is in contrast to the rule of thumb used by some manufacturers that in vivo coefficients are 30% lower than in vitro values. The deviation of the in vivo value from the in vitro one seems to be higher with higher dialyzer ultrafiltration coefficients. Based on these results, it is recommended that to estimate ultrafiltration ratres in the clinical setting, the in vitro ultrafiltration coefficient be used, transmembrane pressures being corrected for the colloid osmotic pressure of plasma proteins.
Hemodynamic Effects of Hemodialysis and Hemofiltration
Authors: Chaignon M. , Aubert Ph. , Martin M. F. , Lucsko M. , Guedon J.
Published: November 2008

The hemodynamic effects (n=8) of hemodialysis (HD) and hemofiltration (HF) were compared in the same group of dialyzed patients. The two procedures induced the same decrease in body weight, total blood volume, and blood pressure; however, hemodynamic alterations were different. Cardiac index and stroke index decreased markedly with HD and did not change significantly with HF, and peripheral resistance remained stable after HD and decreased significantly after HF.

These results suggest that the maintenance of a high cardiac output may account for the lack of acute hypotensive episodes Reported during HF. The reduction of blood pressure after HF is related to the decrease in total peripheral resistance. Thus, the arterial vasodilator effect induced by HF might explain the improvement of severe hypertension on long‐term treatment with HF, as Reported previously.
Efficacy of Charcoal Hemoperfusion in Paraquat Poisoning
Authors: Tabei Kaoru , Asano Yasushi , Hosoda Saichi
Published: November 2008

We studied the efficiency of in vitro and in vivo charcoal hemoperfusion for the removal of paraquat. At a flow rate of 200 ml/min, 93–99% of paraquat in 4 L of solution (5, 10, 100 ppm) was removed in less than 160 min. The disappearance half‐time was 16 min 10 sec. At 100 ml/min, it was 49 min 30 sec.

Of 23 paraquat poisoning cases, 15 patients underwent hemoperfusion (HP) of which 10 died of respiratory failure within 28 days (7.6 ± 2.9) and 5 survived without pulmonary complications. Of eight patients who did not receive HP, six died of respiratory failure within 97 days (33.4 ± 18.8), even when their general condition was good upon admission. Two who vomited the ingested paraquat immediately survived without HP, and their paraquat concentration in urine was less than one ppm on admission. In one patient, whose paraquat concentration in blood was followed serially, 99% of the paraquat was removed from circulating blood by a single hemoperfusion.

We conclude that charcoal hemoperfusion is effective for the removal of paraquat from blood in vivo and from solution in vitro. Hemoperfusion may also improve survival after paraquat ingestion, but further data are needed.
Polytetrafluoroethylene and Anodized Aluminum Surfaces in an Extracorporeal Circuit: Scanning Electron Microscopic Study
Authors: W.‐O Eva Berglin , Hansson Hans‐Arne , William‐Olsson Göran
Published: November 2008

Tubes with polytetrafluoroethylene (PTFE) or anodized aluminum surfaces were inserted in an extracorporeal circuit which was connected to mongrel dogs. The tubes were removed at regular intervals during the perfusions and their inner surfaces were examined by scanning electron microscopy. The anodized aluminum tubes were covered with platelets, fibrin, and other blood elements in a thick layer. In contrast, the PTFE tubes were mainly uncovered.
Mechanical Techniques of Circulation Support: A Percutaneous Intra‐aortic Balloon Device
Authors: Bregman David , Cohen Steven R.
Published: November 2008

Summary: As medical indications for intra‐aortic balloon (IAB) pumping expand, many physicians without surgical expertise are faced with the decision to institute circulatory support. Accordingly, to facilitate rapid establishment of cardiac assist and to obviate the need for operative insertion and removal, a 40‐cc single‐chambered device was designed for percutaneous insertion by the Seldinger technique. Hemodynamic augmentation produced by the percutaneous balloon is similar to that obtained with conventional IAB. It appears that complications related to IAB insertion may be decreased by the percutaneous method.
Development and Evaluation of Pulsatile Roller Pump and Tubing for Cardiac Assistance
Authors: Noon George P. , Harrell James E. , Feldman Louis , Peterson Julie , Kent Patricia M. , DeBakey Michael E.
Published: November 2008

Summary: In our laboratories we have developed a roller pump for cardiopulmonary bypass and circulatory assistance that has the ability to produce steady or pulsatile flow. The pulsatile mode can also be used for counterpulsation. The roller pump has been tested both experimentally and clinically. Studies have also been performed in vitro and in vivo to evaluate and select the best medical‐grade roller pump tubing to be used in the pump for shortand longterm support. In vitro tests included rebounding of tubing volume versus revolutions per minute, rebounding over time with continuous pumping, flex life, and spallation. In vivo testing was performed in mongrel dogs using heparinless left heart bypass pumping for 6 h. Hematologic studies were performed during the procedure. Postmortem examination was performed, looking especially for thromboembolism. The tubing and connectors were also inspected. The results of the in vivo and in vitro tests of all tubings were then compared.
Numerical Modeling of Blood Flow in the Ventricular Cavity of the Artificial Heart
Authors: Starobin Iosif M. , Zaiko Valeriy M.
Published: November 2008

Summary: The flow of blood as a viscous, Newtonian, incompressible liquid in an expanding spherical cavity with a ball‐type inlet valve was examined. This type of flow can serve as a model of the phase of ventricular diastole in a sac‐type artificial heart. The critical values of Reynolds numbers at which flow interruption behind the valve occurs were found. The optimum geometric ratios of the dimensions of the ventricular cavity and valve that permit a decrease in the input resistance of the cavity, the size of the valve, and the surface tensions in the bloodstream were determined.
Charcoal Hemoperfusion for Treatment of Ethchlorvynol Overdose
Authors: Kathpalia Satish C. , Haslitt Joseph H. , Lim Victoria S.
Published: November 2008

Abstract: Charcoal hemoperfusion is commonly employed to treat overdose of a number of drugs. There are varying Reports of its efficacy in the treatment of ethchlorvynol overdose. Herein is Reported a case of ethchlorvynol overdose successfully treated with charcoal hemoperfusion within 5 h of ingestion of 12.5 g of the drug. The patient was deeply comatose at that time but recovered consciousness at the end of 4 h of hemoperfusion. Ethchlorvynol clearance over the charcoal varied from 118 to 147 ml/min. There were no bleeding complications. Prompt charcoal hemoperfusion may be an effective mode of treatment in cases of ethchlorvynol intoxication.
Five‐Year Trial of Dialytic Treatment for Schizophrenia
Authors: Splendiani Giorgio , Bruno Vittorio , Marinangeli Giancarlo , Cupillari Maurizio , Cirelli Carla , Tancredi Maurizio
Published: November 2008

Abstract: Thirty schizophrenic patients were treated with hemodialysis for 4–36 months. The clinical results were evaluated using two psychiatric scales: the Brief Psychiatric Rating Scale and the Inpatient Multidimensional Psychiatric Scale. In 13 schizophrenic patients psychiatric symptoms disappeared completely, and complete social reintegration followed. Eight patients showed no significant modification of schizophrenic disease after more than 30 dialysis sessions. Nine patients were not considered because their treatment was interrupted during the first month. Dialysis improved the psychotic attitude in one group of schizophrenic patients. The best results were obtained using polyacrylonitrile membranes.
Levomepromazine Elimination in Patients During Active and Sham Hemodialysis
Authors: Andersson S.‐B. , Forshell G. Plym , Schulman A. , Wetterberg L. , Asaba H.
Published: November 2008

Abstract: The effect of active and sham dialysis on the plasma concentration of levomepromazine was studied in seven schizophrenic patients undergoing hemodialysis treatment in a double‐blind crossover study. Samples of blood were collected before, after 2 h and 5 h of treatment, and once a week during the treatment program. The plasma concentrations decreased during both active and sham dialysis. The data indicate that there was no significant difference in the elimination of the drug between active and sham hemodialysis.
Chromatographic Analysis of Urine and Dialysate from Schizophrenic Patients Undergoing Hemodialysis
Authors: Foss Irene , Schulman Abraham , Trygstad Olav , Wetterberg Lennart
Published: November 2008

Abstract: Maladjustments in the central nervous system may result in altered concentrations of neuropeptides in cerebrospinal fluid and urine. Urinary protein‐peptide precipitates from psychiatric patients have previously been observed to have different chromatographic profiles with regard to the ultraviolet absorbancy at 280 nm. Hemodialysis has previously been Reported to improve some schizophrenic patients and has been recommended in treatment trials. Seven chronic schizophrenic patients were selected for hemodialysis in a double‐blind crossover study. Specimens of 24‐h urine collections were obtained the day before, the day of, and the day after active and sham dialysis. The chromatographic profiles obtained on Sephadex G‐25 gel columns did not change with active dialysis. Materials with ultraviolet absorbancy at 280 nm also precipitated from dialysates and showed the same pattern following active and inactive dialysis. Thus, no biochemical evidence for removal of any pathogenetic humoral substance during hemodialysis could be provided.
Polyanions and Glucose as Osmotic Agents in Simulated Peritoneal Dialysis
Authors: Twardowski Zbylut J. , Nolph Karl D. , McGary Terry J. , Moore Harold L.
Published: November 2008

Abstract: Peritoneal dialysis solutions contain glucose as an osmotic agent to obtain ultrafiltration. Due to rapid absorption, glucose does not sustain high ultrafiltration during long exchanges. Nonabsorbable polyanions might be effective as osmotic agents when suspended in electrolyte solution. Concentrations of freely diffusible ions should be in Gibbs‐Donnan equilibrium with plasma electrolytes. The ideal proportion of diffusable to polymerbound cation concentrations is unknown. To obtain concentrations of free ions in equilibrium with plasma, it is assumed that the polymer solution dialyzed against a polyelectrolyte solution of the desired composition (with hydraulic pressure higher on the polymer side) will approach the same thermodynamic activity as the electrolyte solution. Subsequently, if transmembrane pressure is released, osmotic ultrafiltration will occur in proportion to the hydrostatic pressure applied during polymer solution preparation. Polyacrylate solution so prepared was compared with a commercial dextrose dialysis solution in an in vitro simulation of peritoneal dialysis. With dwell times up to 24 h, sustained ultrafiltration with polymer was observed, whereas, with dextrose, ultrafiltration ceased after 8 h. Concentrations of diffusible bivalent cations in polyacrylate were lower than intended due to avid polymer complexing; however, dextran sulfate solutions were developed to contain desired concentrations of diffusible electrolytes. The conclusion is that some polymer solutions might be useful in clinical settings when high sustained ultrafiltration is needed.
Development and In Vivo Testing of a Chronic Percutaneous Prosthesis
Authors: Daly Benedict D. T. , Dasse Kurt A.
Published: November 2008

Abstract: Significant progress has been made in the development of a percutaneous energy transmission system (PETS) designed to provide energy to intracorporeally implanted blood pumps for up to 2 years. The mean survival of our six most recent PETS implantations was 351 ± 33 days. Four of these were explanted electively after a full year of implantation. Sinus formation around each prosthesis was limited by a biomaterial seal at the sinus termination point. The results support the hypothesis that collagen inhibits epidermal downgrowth. Continued development of systems based on this hypothesis is desirable.
U.S. Clinical Studies of the Treatment of Anemia with Fluosol‐DA 20%
Authors: Tremper Kevin K. , Cullen Bruce F.
Published: November 2008

Abstract: This article describes the progress of clinical studies of the perfluorochemical (PFC) emulsion Fluosol‐DA 20% in the United States. To date, two studies have been completed and one is in progress. All three studies have been restricted to the treatment of acute anemia in patients who refused blood transfusions on religious grounds, i.e., Jehovah's Witnesses. The first protocol, referred to as the “Humanitarian Protocol“ (no. 79006), was initiated in November 1979. Jehovah's Witness patients who were considered to have a lethal degree of anemia were treated with Fluosol to supplement oxygen transport. Collection of specific data was not mandated in this protocol. Six patients were treated under this protocol until it was replaced by the “Medical Use Protocol“ (no. 79007). In this second study, hemodynamic and oxygen transport data were collected while patients breathed room air and 100% inspired oxygen before and after a Fluosol infusion. Seven patients were treated under this protocol and it was concluded that the PFC was transporting the expected amount of oxygen based on its known oxygen solubility. This increased oxygen transport by the PFC resulted in increased oxygen consumption and arterial and mixed venous blood oxygenation. Two of the seven patients had adverse reactions to a 0.5‐ml test dose of Fluosol, manifested by an increase in pulmonary artery systolic pressure. The third and current anemia protocol as of this writing is a randomized controlled study with data collection similar to the Medical Use Protocol. This third protocol, called “Anemia Protocol“ (no. 8105), stipulates that cardiac filling pressures be normalized before Fluosol treatment and then data collected (filling pressures should be similar before and after Fluosol treatment). This modification should permit a separation of the oxygen transport effects of Fluosol from its volume loading effects when compared with a control group.
Development of a Perfluorochemical Emulsion as a Blood Gas Carrier
Authors: Mitsuno Takao , Ohyanagi Harumasa , Yokoyama Kazumasa
Published: November 2008

Abstract: Over 10 years of research has led to the development of a perfluorochemical (PFC) emulsion that can be utilized clinically as a blood gas carrier. The physiochemical properties of this PFC emulsion and their bio‐physiological effects on animals meet the minimum requirements of an oxygen transport medium. As PFC is chemically and biochemically inert, its toxicity is extremely low. Acute toxicity was related chiefly to the particle size of the emulsion. PFC particles injected intravenously are phagocytized in the reticuloendothelial system as foreign bodies and are excreted from the lungs. The excretion rate was roughly proportional to the vapor pressure of each PFC. An emulsion consisting of 7 parts perfluorodecalin and 3 parts perfluorotripropylamine, 20% (wt/vol) PFC final, Fluosol‐DA 20%, was selected as the best formulation in view of efficacy, stability, and excretion rate. No untoward reactions were observed after administration of this emulsion. More than 400 patients have received intravenous Fluosol‐DA 20% in Japan.
Prevention of Platelet Deposition and Thrombus Formationon Hemodialysis Membranes: A Double‐Blind Randomized Trial of Aspirin and Dipyridamole
Authors: Salter M. C. P. , Crow M. J. , Donaldson D. R. , Roberts T. G. , Rajah S. M. , Davison A. M.
Published: November 2008

Abstract: A double‐blind crossover study comparing low‐dose aspirin (ASA) and dipyridamole (DPM) (100 mg ASA+75 mg DPM, t.d.s.), high‐dose ASA and DPM (300 mg ASA+75 mg DPM, t.d.s.), and placebo on platelet deposition and thrombus formation on hemodialysis membranes was undertaken in 17 long‐term dialysis patients. The high‐dose combination significantly reduced the fall in platelet count during dialysis and also significantly increased postdialysis heparin concentrations. Scanning electron microscopy of the Cuprophan membranes showed a reduction in platelet desposition and fibrin formation during both treatment schedules, but this was most marked with the high‐dose combination. The results of this study indicate that there is a graded response to combined ASA‐DPM treatment and that this can significantly reduce platelet consumption and contact activation of fibrin during hemodialysis with Cuprophan membranes.
Effect of Hemodialysis on Intraocular Pressure
Authors: Gutmann S. M. , Vaziri N. D.
Published: November 2008

Abstract: Intraocular pressure (IOP) was determined in 13 dialysis patients before, during, and after dialysis. The values were compared with those obtained in an age‐, sex‐, and time‐matched normal control group. The IOP values obtained in dialysis patients were significantly lower than those in the control group. An insignificant decrease in IOP was noted during the first 2 h of dialysis. This was followed by a slight rise above the base line by the end of dialysis. Although the middialysis IOP was significantly lower than the postdialysis value, the latter was not significantly different from the predialysis value. Our results are at variance with several earlier studies demonstrating marked increase in IOP during dialysis. Lack of significant rise in IOP during dialysis in our study seems to be due to improved dialytic technique and better uremia control employed here as compared with the earlier studies.
Plasticizer Migration from Blood Lines in Hemodialysis
Authors: Ljunggren L.
Published: November 2008

Abstract: Polyvinylchloride (PVC) is the most commonly used material for tubing in extracorporeal circulation. It is usually plasticized by the addition of di‐2‐ethylhexyl‐phthalate (DEHP). The plasticizer is physically mixed into the PVC. The potential danger of DEHP migration into blood has been discussed. It has been suggested that the polyurethane (PUR) coating should reduce this transport. Eight different types of PVC tubing sets for hemodialysis were investigated for migration of DEHP. In general, they contained ‐40% by weight of plasticizer. It was shown that ‐60 mg placticizer could be extracted from complete tubing sets during a 6‐h period. The release rate of DEHP from the PUR coating compared with PVC was increased. The results show that in contrast to previously published information, PUR coating of PVC tubing is not an effective method forreducing migration.
Evaluation of the Influence of Peritoneal Dialysis on Cellular Immunity by the E‐Rosette Inhibition Test
Authors: Giacchino F. , Pozzato M. , Piccoli G.
Published: November 2008

Abstract: Sera of patients on peritoneal dialysis and regular hemodialysis were analyzed over a follow‐up period of 8 months for the capacity of normal lymphocytes to inhibit E‐rosette formation. The percentage of inhibition in sera from peritoneal dialysis patients was significantly reduced (p < 0.02) only 1 month after treatment was started, whereas in hemodialysis patients the percentage of inhibition remained unchanged. No difference was observed between sera collected before and after the hemodialysis sessions. There was no significant positive correlation between the percentage of E‐rosette inhibition and p‐urea, p‐creatinine, s‐albumin, and s‐proteins, respectively. Statistical analysis of the E‐rosette inhibition test by uremic serum and spontaneous E‐rosettes in these patients showed a significant regression coefficient (p < 0.01) in both groups. The fact that, unlike ultrafiltrate from hemodialysis, peritoneal dialysate significantly (p < 0.05) inhibits the E‐rosette formation capacity of normal lymphocytes, confirms these findings, suggesting an inhibitory activity of serum factors on lymphocyte function.
Drug Interaction in Middle Molecule Analysis, with Special Reference to Acetylsalicylic Acid
Authors: Faguer Patrick , Man Nguyen‐Khoa , Cueille Georges , Funck‐Brentano Jean‐Louis
Published: November 2008

Abstract: Concerning the middle molecules in uremia and other diseases, the potential artifact that can impede an accurate quantitation of middle molecules and that is related to the absorption of a very commonly used drug, namely aspirin, is discussed. Peak 7c and peak b 4‐2 are two different middle molecules separated by gel permeation chromatography followed by anion‐exchange chromatography. Oral ingestion of acetylsalicylic acid modifies the chromatographic pattern of the middle molecule fraction in normal subjects and uremic patients. Peak 7c is increased in the urine of healthy subjects, whereas this is not the case for peak b 4‐2: With the b 4‐2 technique, ingestion of acetylsalicylic acid produces a higher peak b 5. This is consistent with the previous demonstration that peak 7c was eluted as peak b 5. Structural analogies between salicylate metabolites and orthohydroxyhippuric acid (ß‐glucuronate (i.e., the main component of peak 7c) could explain this drug‐related artifact.
Allergy to Ethylene Oxide in Chronic Hemodialysis Patients
Authors: Dolovich Jerry , Marshall Cheryl P. , Smith Edward K. M. , Shimizu Arthur , Pearson Frederick C. , Sugona Michael A. , Lee Wanda
Published: November 2008

Abstract: Almost a decade ago, a single chronic hemodialysis patient in Hamilton, Ontario, Canada, who was experiencing recurrent acute reactions during hemodialysis was found to have become allergic to ethylene oxide gas (EO). This observation recently provided a stimulus to examine the possibility that others exhibiting acute allergic‐type reactions during hemodialysis might be similarly sensitized. Serum was obtained from 27 reacting patients and tested in a radioallergosorbent test (RAST) for antibodies to EO. The test was positive for 22 of these sera. EO related specificity of the antibodies was confirmed. However, EO sensitization was not found in other hemodialysis patients with isolated eosinophilia. In a survey of the current Hamilton chronic hemodialysis population for EO‐related antibodies, 9% had a positive allergy skin test and 12% had a positive RAST. The sensitized individuals had no distinctive symptoms. The lesser sensitivity of the skin test contrasts with usual findings in allergic individuals; however, the use of histamine and codeine in chronic hemodialysis and peritoneal dialysis patients might well explain a reduced sensitivity of the EO‐related allergy skin test. Chronic peritoneal dialysis could not be invoked as a source of sensitization. None of these patients had a positive skin test or RAST for EO‐related antibodies that could be attributed to peritoneal dialysis.
Hemodynamic Changes During Acetate and Bicarbonate Hemodialysis
Authors: Leenen Frans H. H. , Buda Andrew J. , Smith Donna L. , Farrel Susan , Levine David Z. , Uldall P. Robert
Published: November 2008

Abstract: In a crossover, double‐blind comparison, circulatory changes induced by hemodialysis with bicarbonate versus acetate dialysate were evaluated at the first exposure as well as after 2 weeks of acclimatization to each dialysate. Hemodialysis with bicarbonate dialysate resulted in only minor changes in blood pressure and left ventricular (LV) function as assessed by M‐mode echocardiography. In contrast, the first exposure to acetate resulted in significant decreases in systolic (30 mm Hg) and diastolic (17 mm Hg) blood pressure as well as in LV end‐diastolic and end‐systolic dimensions (5–6 mm) and a rise in ejection fraction. After acclimatization, tolerance developed for the arterial vasodilatory effects of acetate, but not for the venous vasodilatory effect (persistent decrease in LV end‐diastolic dimension). These results indicate that some of the circulatory changes induced by hemodialysis may be related more to the acetate infused than to fluid losses or relative autonomic insufficiency
Optimal Routes for Chronic Insulin Infusion with Portable and Implantable Devices
Authors: Selam J. L. , Slingeneyer A. , Saeidi S. , Mirouze J.
Published: November 2008

Abstract: The optimal route for chronic insulin infusion via portable or implantable pumps is still a subject of controversy. Through the literature Reports and personal experience the authors have found that the subcutaneous route is the ideal route in terms of comfort, safety, and cost. However, owing to sluggish and unpredictable insulin resorption, it appears that subcutaneous infusion is often not more effective than intensive conventional insulin therapy. The intravenous route gives the best diabetic control, but with a high risk of infection and obstruction. The intramuscular route, although more efficient than the subcutaneous, can be envisaged for only short periods because of its poor tolerance. The portal route is still at an experimental stage. The authors chose the intraperitoneal route because of the following advantages: near physiological insulin resorption kinetics; better diabetes control than subcutaneous infusion although comparable to intravenous; a 30% reduction of insulin requirements; and satisfactory local tolerance and acceptability with respect to severe asepsy precautions, patient selection, intensive education, and careful medical follow‐up. The intraperitoneal route is feasible for portable insulin pumps, but basically more adaptable to implantable devices.
A New Hollow‐Fiber Oxygenator for Clinical Cardiopulmonary Bypass
Authors: Golding Leonard A. R. , D. Loop Floyd , Meserko John , Sinkewich Martin , Nosé Yukihiko
Published: November 2008

Abstract: A new hollow‐fiber oxygenator has become available for clinical cardiopulmonary bypass. It is available in three sizes for adult use, ranging from 3.3 to 5.4 m2. The surface area is dependent on the number of fibers, with blood and oxygen effecting very efficient gas transfer throughout the length of each of the fibers. The clinical experience now covers 100 patients, using the 3.3‐m2 device in 16 patients, the 4.3‐m2 device in 12 patients, and the 5.4‐m2 device in 72 patients. In all cases, the oxygenator has proven highly efficient in gas transfer. The addition of an oxygen‐blending unit was found to be necessary to prevent overoxygenation. It is a safe and effective device to use in routine clinical practice.
Enzymatic Detoxification Using Lipophilic Hollow‐Fiber Membranes: II. Sulfation Reactions
Authors: Tegtmeier F. , Brunner G.
Published: November 2008

Abstract: A lipophilic hollow‐fiber technique was used in the enzymatic sulfation of lipophilic toxins. Endogenous and exogenous toxins, for which glucuronidation reactions already were demonstrated with this technique, were submitted to sulfate transferase reaction as an alternative phase‐II detoxification route. Native enzyme was circulated on the external side of a lipophilic hollow‐fiber membrane while the toxin‐containing media (serum or aqueous solution) were circulated inside the hollow fiber. Sulfation reactions were catalyzed by rabbit liver cytosol, with a specific sulfate transferase activity of 626 nmol/min‐mg protein. Clearance of the hollow‐fiber module for phenol, p‐cresol, paracetamol, 2‐amino‐phenol, and 5–hydroxyindol were determined to be 38.1, 47.2, 2.7, 5.3, and 3.2 pmol/mg protein/h/cm2 hollow‐fiber surface, respectively. This technique allows sulfation reactions with crude enzyme preparations over long periods without loss of activity from covalent immobilization and without immunological hazards.
Pharmacokinetic Monitoring of Heparin Therapy for Regular Hemodialysis
Authors: Khazine F. , Simons O.
Published: November 2008

Abstract: Using a pharmacokinetic model for heparin prescription during hemodialysis leads to a precise monitoring of the coagulation time (CT) with 25% less heparin required. Two different populations were distinguished: The first group maintained stable sensitivity and elimination constant, permitting a stable prescription and giving stable CT values for up to 2 years. The other group exhibited wide variations of these parameters, necessitating daily dose monitoring.
Use of Artificial Pancreas and Portable Insulin Infusion Pumps in Diabetes Therapy: Past, Present, and Future
Authors: Pfeiffer E. F. , Kerner W.
Published: November 2008

Abstract: The development of the artificial pancreas (AP) was an important contribution to modern diabetology. The practical and theoretical findings obtained by its application in type I diabetic patients gave rise to new forms of treatment, i.e., portable insulin pumps and intensified conventional insulin therapy. Although these therapies lead to better results than conventional insulin administration, there is no doubt that the problems of diabetes therapy can be solved only by an implantable AP or pancreas transplantation.
Intrinsic Coagulation Pathway in End‐Stage Renal Disease Associated with Spinal Cord Injury Treated with Hemodialysis
Authors: Vaziri N. D. , Winer R. L. , Toohey J. , Danviriyasup K. , Alikhani S. , Eltorai I. , Gordon S. , Paule P.
Published: November 2008

Abstract: Plasma procoagulant activities of factors XII, XI, IX, and VIII and plasma concentrations of factor XII antigen and high molecular weight kininogen (HMK) were determined in nine men with chronic renal failure (CRF) associated with long‐standing spinal cord injury (SCI) treated with hemodialysis. The results were compared with those obtained in a group of 10 ambulatory CRF patients and 8 normal volunteers (control group). Congenitally deficient plasmas were used as the substrate for the measurement of procoagulant activities in a one‐stage clotting assay. Monospecific antibodies were employed in the measurement of factor XII antigen and HMK using gradient plate immunodiffusion and rocket immunoelectrophoresis. Factor XII coagulant activity and antigen concentration were significantly increased in the SCI group. The mean values for plasma factor XI and IX activities in the SCI group were comparable with those observed in the ambulatory patients and normal control group. However, marked variations in factor XI and IX levels were noted among the SCI patients with a few instances of mild to moderate factor deficiencies and several cases of markedly elevated levels. Factor VIII activity was markedly increased, with only two of the nine patients exhibiting normal values. HMK concentration in the SCI group was comparable with values obtained for the other groups. Following dialysis, factor XII antigen concentration rose and factor XI activity fell slightly but signficantly. The results indicate that the combination of CRF and long‐standing SCI is associated with marked aberrations of intrinsic coagulation pathway. The underlying mechanisms and the clinical consequences of these abnormalities are not known and require further investigation.
What Is the Actual Incidence of Peritonitis in Maintenance Peritoneal Dialysis? A Prospective Study
Authors: Gotloib Lazaro , Shustak Abshalom , Varka Itzak , Haas Robert , Mines Miguel , Weiss Zwi
Published: November 2008

Abstract: Generally, the incidence of peritonitis in maintenance peritoneal dialysis programs is calculated as a percentage of the total number of treatments or as the number of episodes per patient‐months. Both statistical methods give the wrong impression that peritonitis is seldom observed. However, peritonitis is still the major and unsolved challenge to successful long‐term peritoneal dialysis. The lack of a standard and homogeneous definition of peritonitis is another critical point that prevents a rational interpretation of the published experiences. In the present study, dialysate cell counts of > 1,100 cells/mm3 were assumed to be the first sign of peritoneal infection. As long as more signs and symptoms are required for recognizing peritonitis (fever, abdominal pains, positive cultures), the statistical probability of making such a diagnosis shows the characteristics of a Poisson distribution. It is concluded that in long‐term peritoneal dialysis, the currently used statistical methodology for evaluation of the incidence of peritonitis, including the clinical definition of this complication, is misleading. Dialysate cell counts appear to be the more sensitive sign for early diagnosis of peritonitis.
A Survey on Hypersensitivity Reactions in Hemodialysis
Authors: Villarroel Fernando , Ciarkowski Arthur A.
Published: November 2008

Abstract: This survey was conducted from 1982 through 1984 by a cooperative effort among the Health Industries Manufacturers Association, seven dialyzer manufacturers, and the Food and Drug Administration. This article presents an analysis of the 1982‐83 survey data and a summary of the 1984 data. Most of the reactions reported (99%) were associated with hollow‐fiber dialyzers. About 50% of these reactions were experienced by patients using a dialyzer model for the first time, and >98% of the reactions were related to new (unused) dialyzers. On average, there were 180 reactions reported per year, with >90% being considered severe, including death, by the reporting center. A plot of the number of reactions versus time from 1982 through 1984 shows periods of 12–15 months in which the reaction rate remained practically constant. During these periods, the rate of reported reactions alternated from 60 to 150% of the average. Analysis of the survey data showed a strong correlation of the number of reactions with the race and age of the patients. Blacks and other minorities experience nearly three times as many reactions as white patients. Also, patients under 29 years of age seem to have nearly twice as many reactions as patients in the 30‐ to 49‐year‐old range, whereas patients over 50 years old have nearly half the number of reactions of the 30‐ to 49‐year‐old range. The average reactivity of the U.S. hemodialysis patient population was calculated to be 3.3 reactions per year per 1,000 patients exposed to hollow‐fiber dialyzers and 0.3 reaction per year per 1,000 patients exposed to flat‐plate dialyzers. No reactions were reported with coil dialyzers. Using the manufacturers' sales figures, the reactivity of hollow‐fiber and flat‐plate dialyzers was calculated to be 4.3 and 0.2 reactions per 100,000 dialyzers sold, respectively.
Acute Effect of Plasma Exchange on Arterial Blood Pressure and Plasma Renin Activity
Authors: Moriconi L. , Palombo C. , Fommei E. , Meconi P. , Puccini R. , Innocenti M. , Ferri C. , Pecori F. , Ghione S.
Published: November 2008

Abstract: Blood pressure (BP) decreases significantly in patients with immune complex nephritis and hypertension in the course of therapeutic plasma exchange (TPE). To investigate possible underlying mechanisms of this effect, the variations of supine and upright BP and plasma renin activity (PRA) acutely induced by PE (performed by isovolumetric replacement of plasma with 4% albumin in saline solution) were analyzed in six patients. On the average, both supine and upright BP decreased after TPE; however, statistical significance was obtained only for upright systolic BP. Supine and upright PRA did not change significantly, although a clearly blunted response to posture was observed in three patients. The changes of BP induced by TPE were apparently not due to a functional depression of the renin‐angiotensin system, since the more marked decrements in BP were observed in the patients with lower basal PRA.
Zinc Transport During Hemodialysis
Authors: Hosokawa Shinichi , Koike Tohru , Kawaji Akiko , Nishitani Hiroshi , Nishio Toshiji , Tomoyoshi Tadao , Sawanishi Kenji , Yoshida Osamu
Published: November 2008

Abstract: Zinc transfer during hemodialysis and plasma zinc concentrations in hemodialysis patients were examined. Fifteen volunteer outpatients undergoing hemodialysis showed significant increases in plasma zinc from 74.0 ± 7.8 to 88.1 ± 9.7 μg/dl after a 5‐h dialysis. The increase was mainly the result of hemoconcentration as evidenced by a significant increase in the hematocrit and total serum protein during dialysis, but was also due to diffusion. To study the changes resulting from diffusion, zinc was measured in the arterial blood and in the dialysate at the inflow and outflow sites of the dialyzer. There was a significant (p < 0.01) increase in the plasma zinc of the arterial blood from 74.7 ± 8.1 to 80.2 ± 6.5 μg/dl, but a nonsignificant decrease in the dialysate zinc from 10.6 ± 2.5 to 9.5 ± 5.9 μg/dl. Zinc diffused across the dialyzer from the dialysate to the blood in 12 cases and into the dialysate in three others.