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Background: Regional anticoagulation in hemodialysis avoids the use of heparin, which is responsible for both hemorrhagic and non-hemorrhagic complications. Typically, blood is decalcified by injecting citrate into the arterial line of the extracorporeal circuit. Calcium-free dialysate improves anticoagulation efficacy but requires injection of a calcium-containing solution into the venous line and strict monitoring of blood calcium levels. Recent improvements have made regional anticoagulation with calcium-free dialysate safer and easier., Observations: (1) Adjusting the calcium injection rate to ionic dialysance avoids the risk of dyscalcemia, thus making unnecessary the monitoring of blood calcium levels. This adjustment could be carried out automatically by the hemodialysis monitor. (2) As calcium-free dialysate reduces the amount of citrate required, this can be supplied by dialysate obtained from currently available concentrates containing citric acid. This avoids the need for citrate injection and the risk of citrate overload. (3) Calcium-free dialysate no longer needs the dialysate acidification required for avoiding calcium carbonate precipitation in bicarbonate-containing dialysate., Conclusions: Regional anticoagulation with calcium-free dialysate enables an acid- and heparin-free procedure that is more biocompatible and environmentally friendly than conventional bicarbonate hemodialysis. The availability of specific acid-free concentrates and adapted hemodialysis monitors is required to extend this procedure to maintenance hemodialysis., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

In plasma exchange (PE), contrary to dialysis, there is no ultrafiltration, and the volume of anticoagulant contributes to volume overload of the patient and might also reduce PE efficiency through dilution. To reduce the volume of citrate, we compared 4 and 15% citrate anticoagulation protocols in PE in a randomized study, aiming to evaluate PE efficacy, anticoagulation efficiency, and overall safety. In addition to standard biochemical analyses during PE treatments, the elimination rate (ER) of immunoglobulins was calculated to evaluate PE efficacy. Anticoagulation was evaluated by postfilter ionized calcium, visual evaluation of the extracorporeal system, and change in the sieving coefficient (SC) during PE. Accumulation of citrate was determined by calculating the total-to-ionized calcium ratio and measuring the citrate concentration after PE. One hundred forty procedures (70 in each group) were performed in 37 patients. The mean citrate infusion rate was 197 ± 10 mL/h in the 4% and 59 ± 5.5 mL/h in the 15% groups, respectively; the total volume of infused citrate was 502 ± 77 mL versus 164 ± 52 mL (P < 0.001). ER for immunoglobulin G (0.57 ± 0.06 vs. 0.55 ± 0.1, P = 0.18), M, and A were comparable. Ionized calcium was stable during the procedures, and there were no significant side effects. Although postfilter ionized calcium was on the upper limit of the target range (0.41 ± 0.16 vs. 0.37 ± 0.14 mmol/L, P = 0.38), the visual assessment score was excellent, and even a rise in SC was observed during the procedures in both groups. The total-to-ionized calcium ratio was increased in 20 versus 22% of procedures, and citrate concentrations after PE were also similar (1306 ± 441 vs. 1263 ± 405 μmol/L). To conclude, we were unable to show superior PE efficacy in the 15% citrate group, but we significantly reduced the infused volume, which is important in patients with fluid overload. Both citrate protocols were found to provide excellent anticoagulation without significant metabolic disturbances or other side effects, confirming the safety of 15% citrate as anticoagulant during PE. , (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Hemodynamic effects related to changes in serum ionized calcium (iCa) are difficult to determine during conventional hemodialysis (HD) using a fixed dialysate concentration of calcium. Regional citrate anticoagulation (RCA) allows the study of the effects of predefined iCa changes on arterial stiffness and blood pressure (BP) during a single dialysis session. In a crossover study, 15 patients with end-stage renal disease underwent two HD sessions with RCA. Each session was divided into two study phases in which iCa was titrated either to 0.8-1.0 mm or to 1.1-1.4 mm. The sequence of phases was randomly chosen and alternated for the second session. After reaching a stable iCa level, pulse wave velocity (PWV), arterial BP, and heart rate were measured. iCa levels were modified during sequence 1 (iCa low-high) from a predialysis baseline value of 1.15 ± 0.09 mm, first to 0.92 ± 0.05 mm (time point 1; P < 0.001 vs. baseline) and then to 1.18 ± 0.05 (time point 2; ns). During sequence 2 (iCa high-low), iCa levels were modified from 1.15 ± 0.12 mm first to 1.20 ± 0.05 mm (time point 1; ns vs. baseline) and then to 0.93 ± 0.03 (time point 2; P < 0.001). Assuming a basic linear repeated measures model, PWV was positively related to iCa levels (P < 0.03) independent of systolic or diastolic BP, heart rate, or ultrafiltration rate. PWV is closely related to acute changes in serum iCa levels in HD patients using RCA. RCA provides an interesting opportunity to study the effects of acute iCa changes during one dialysis procedure., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Selective cytopheretic inhibitory device (SCD) therapy is an immunomodulatory treatment provided by a synthetic biomimetic membrane in an extracorporeal circuit, which has shown promise in preclinical large animal models of severe sepsis as well as in clinical trials treating patients with acute kidney injury and multiple organ failure. During SCD therapy, citrate is administered to lower ionized calcium levels in blood for anticoagulation and inhibition of leukocyte activation. Historically, citrate has been known to interfere with sorbent dialysis, therefore, posing a potential issue for the use of SCD therapy with a portable dialysis system. This sorbent dialysis SCD (sorbent SCD) would be well suited for battlefield and natural disaster applications where the water supply for standard dialysis is limited, and the types of injuries in those settings would benefit from SCD therapy. In order to explore the compatibility of sorbent and SCD technologies, a uremic porcine model was tested with the Allient sorbent dialysis system (Renal Solutions Incorporated, Fresenius Medical Care, Warrendale, PA, USA) and concurrent SCD therapy with regional citrate anticoagulation. The hypothesis to be assessed was whether the citrate load required by the SCD could be metabolized prior to recirculation from systemic blood back into the therapeutic circuit. Despite the fact that the sorbent SCD maintained urea clearance without any adverse hematologic events, citrate load for SCD therapy caused an interaction with the sorbent column resulting in elevated, potentially toxic aluminum levels in dialysate and in systemic blood. Alternative strategies to implement sorbent-SCD therapy will be required, including development of alternate urease-sorbent column binding chemistry or further changes to the sorbent-SCD therapeutic circuit along with determining the minimum citrate concentration required for efficacious SCD treatment., (© 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Low-volume bowel preparations with polyethylene glycol (PEG) have been shown to provide an equivalent cleansing with improved tolerability as compared with standard PEG bowel preparation for colonoscopy. A new iso-osmotic sulphate-free formulation of PEG-Citrate-Simethicone (PEG-CS) in combination with bisacodyl has been recently developed., Aim: To compare the quality of bowel cleansing with PEG-CS with bisacodyl vs. PEG-Ascorbate (PEG-ASC) in adult out-patients undergoing colonoscopy., Methods: Randomised, observer-blind, parallel group study in adult out-patients undergoing colonoscopy in five Italian centres. Both preparations were taken the evening before the procedure. Subjects were instructed to take 2-4 tablets of 5 mg bisacodyl at 16:00 hours and 2 L of PEG-CS at 20:00 hours or 2 L of PEG-ASC plus 1 L of additional water the day before colonoscopy. Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale (≥6 scores were considered as 'clinical success'), and mucosal visibility according to a 3-point scale. Tolerability, acceptability and compliance were also evaluated., Results: Four hundred and eight patients were randomly allocated to PEG-CS and bisacodyl (n = 204, male patient 48%, mean age 59.1 years) or PEG-ASC (n = 204, male patient 51%, age 59.4 years). In the planned per-protocol analysis, the rate of successful preparation was 79.1% following PEG-CS with bisacodyl, and 70% following PEG-ASC (P < 0.05). Mucosal visibility was evaluated as optimal in 56.1% in the PEG-CS and bisacodyl and 46.3% in the PEG-ASC group (P < 0.05). There were no serious adverse events (AE) in each of the two experimental groups. Two subjects in the PEG-ASC group discontinued the study because of AE., Conclusions: Polyethylene glycol-Citrate-Simethicone in combination with bisacodyl was more effective for bowel cleansing than PEG-ASC for out-patient colonoscopy. Tolerability, safety, acceptability and compliance of the two low-volume bowel preparations were similar., (© 2012 Blackwell Publishing Ltd.)

Objectives/hypothesis: This study tested the hypotheses that swallowing apnea duration (SAD) will increase given barium versus water, chemesthetic stimuli (i.e., water < ethanol, acid, and carbonation) mixed with barium, age (older > younger), and genetic taste differences (supertasters > nontasters)., Study Design: Prospective group design., Setting: University Medical Center., Methods: Eighty healthy women were identified as nontasters and supertasters, equally comprising two age groups: 18 to 35 years and 60+ years. The KayPentax Swallowing Signals Lab was used to acquire SAD via nasal cannula during individually randomized swallows of 5 mL barium, 2.7% w/v citric acid with barium, carbonation with barium, and 50:50 diluted ethanol with barium. Data were analyzed using path analysis, with the mediator of chemesthetic perception, adjusted for repeated measures., Results: Significant main effects of age (P = .012) and chemesthetic stimuli (P = .014) were found, as well as a significant interaction between chemesthetic stimuli and age (P = .028). Older women had a significantly longer SAD than younger women. Post hoc analyses revealed that barium mixed with ethanol elicited a significantly longer SAD than other bolus conditions, regardless of age group. There were no significant differences in SAD between barium and water conditions, and no significant effect of chemesthetic perception (P > .05)., Conclusions: Ethanol added to barium elicited longer SAD compared to plain barium, but not the other chemesthetic conditions. Older women had a longer SAD than younger women in all conditions. These findings may influence design of future studies examining effects of various stimuli on SAD., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

The aims of this study were to determine the effects of pH and acid concentration on the dissolution of enamel, dentine, and compressed hydroxyapatite (HA) in citric acid solutions (15.6 and 52.1 mmol l(-1) ; pH 2.45, 3.2, and 3.9), using a pH-stat system. After an initial adjustment period, the dissolution rates of enamel and HA were constant, while that of dentine decreased with time. The dissolution rate increased as the pH decreased, and this was most marked for enamel. To compare substrates, the rate of mineral dissolution was normalized to the area occupied by mineral at the specimen surface. For a given acid concentration, the normalized dissolution rate of HA was always less than that for either dentine or enamel. The dissolution rate for dentine mineral was similar to that for enamel at pH 2.45 and greater at pH 3.2 and pH 3.9. The concentration of acid significantly affected the enamel dissolution rate at pH 2.45 and pH 3.2, but not at pH 3.9, and did not significantly affect the dissolution rates of dentine or HA at any pH. The variation in response of the dissolution rate to acid concentration/buffer capacity with respect to pH and tissue type might complicate attempts to predict erosive potential from solution composition., (© 2010 Eur J Oral Sci.)

Background: Aim of this study was to investigate the effect of idiopathic burning mouth syndrome (BMS) on both, the pain perception within trigeminal lingual nerve distribution and gustatory sensitivity using capsaicin threshold test, and regional taste tests, respectively., Methods: Pain thresholds for capsaicin were assessed using capsaicin-impregnated filter-paper strips. The strips were placed midline on the tongue tip for whole mouth testing with the mouth closed, and on the left or right edge of the extended anterior tongue for lateralized testing. Measures of gustatory function were obtained by validated "taste strips" test kit and electrogustometry. The tests were applied to 13 patients with BMS. Results were compared with those from 28 healthy subjects., Results: Patients with BMS exhibited a decreased gustatory and somatosensory perception compared with healthy controls. These changes were found for lateralized tests but not for the whole mouth test procedure. Duration of disorder showed an effect on the capsaicin threshold, with patients being less sensitive to capsaicin exhibiting an increased duration of disorder., Conclusion: Both pain-related and gustatory sensitivies of the tongue are found to be decreased in BMS.

In a randomized study, sequential anticoagulation for hemodialysis (citrate for the first 3.5 h, switching to 30-min anticoagulation-free hemodialysis) was compared to standard citrate anticoagulation. Fifty-two hemodialysis procedures were randomized either to sequential (n = 27) or standard citrate group (n = 25). The antithrombotic effect in the circuit was visually assessed after hemodialysis using a score from 1 (total clotting) to 5 (no clotting). The antithrombotic score for sequential versus standard group was as follows: dialyzer, 4.0 +/- 1.1 versus 4.8 +/- 0.4 (P < 0.01); arterial bubble trap, 4.0 +/- 1.2 versus 4.7 +/- 0.6 (P = 0.013); venous bubble trap, 4.0 +/- 1.3 versus 4.8 +/- 0.6 (P < 0.01). Serum citrate levels during sequential versus standard citrate anticoagulation (micromol/L) were as follows: at the beginning, 143 +/- 65 versus 148 +/- 77 (not significant [NS]); after 2 h, 317 +/- 157 versus 354 +/- 111 (NS); at the end, 125 +/- 81 versus 405 +/- 133 (P < 0.01). Sequential anticoagulation reduces the final serum citrate concentration to predialysis level. It can be a good anticoagulation strategy for patients in whom the reduction of citrate load is desired.

Unlabelled: We report a 40-d-old female infant who presented to our clinic with afebrile generalized convulsive episodes due to severe hypomagnesaemia with secondary hypocalcaemia. Laboratory investigations revealed mild hypoparathyroidism, which was to return normal following magnesium (Mg) treatment, and normal fractional renal excretion of Mg (0.8%). After the diagnosis of primary hypomagnesaemia was established, the patient was discharged with oral Mg subcarbonate and intramuscular Mg sulphate. On regular follow-up until the age of 4 y, the child was asymptomatic. Mean serum calcium levels remained normal, while mean serum Mg levels remained subnormal. During this 4-y period, oral Mg dose was gradually increased while the doses and frequency of administration of parenteral Mg were decreased. Additionally, oral Mg subcarbonate was switched to Mg citrate because of its side effects. Finally, parenteral Mg was discontinued as the dosage of oral Mg supplementation reached a level of 90 mg/kg/d elemental Mg citrate, without any gastrointestinal side effects. Some screening tests were performed to evaluate the complications of chronic hypomagnesaemia. Bone age, bone densitometry, ECG and renal sonography were all normal. Our patient is now 5 y old and symptom free., Conclusion: Treatment with high doses of oral Mg was successful in keeping our patient symptom free and normocalcaemic, but cannot fully normalize serum Mg concentrations. Thus, during the regular follow-up of patients with primary hypomagnesaemia, the main target must be to increase oral Mg supplementation to a dosage which can maintain normocalcaemia rather than normomagnesaemia.

Alpha-hydroxy acid (AHA) agents, such as glycolic acid and lactic acid, have been used as therapeutic agents for more than a quarter of a century. Recently, they have been used as agents to rejuvenate photo-aged skin. It is believed that these AHA agents induce the epidermis to remodel and accelerate desquamation, thus exerting their therapeutic effects. In this study, we investigated the histological differences in skin treated with glycolic, lactic, citric and acetic acids once daily for 6 weeks. The melanin pigments in the basal layer were less prominent in the glycolic and lactic acid-treated skin than in the citric and acetic acid-treated skin. The melanin deposits in the horny layers were equal for all AHA. However, the melanin deposits in the squamous layers were less prominent in the glycolic and lactic acid-treated skins than in the citric and acetic acid-treated skins; this was analogous to observations of the basal layers. Collagen I and procollagen I were increased after treatment with glycolic, lactic and citric acid in the upper dermis, but were not increased with acetic acid treatment. However, the staining of the epidermis and dermis for matrix metalloproteinase-1 (MMP-1) after treatment was not significantly different among the agents. Our data suggest that longer treatment intervals with glycolic and lactic acid can cause improvements in both the epidermal and dermal components and support the usefulness of AHA for rejuvenating photo-damaged skin.

The association of severe erosion with certain habits of consuming soft drinks prompted a study of erosion in relation to fluid flow. In the main experiments, citric acid solution (pH 3.2) was directed at polished enamel surfaces at flow rates of 26, 67 or 126 ml min(-1) through outlets of diameters 1.0, 2.6 or 5.0 mm for up to 20 min. Erosion depth increased with time of exposure and total volume of solution, with increasing flow rate and with decreasing outlet diameter. Scanning electron microscopy of acid-treated surfaces and of the subsurface enamel indicated that the clearance of dissolution products, rather than the mechanical dislodgement of partly dissolved crystal bundles, was the main process involved. For an exposure time of 20 min, erosion increased with (liquid velocity)(1/4). In a secondary experiment, it was found that the erosive potential of a low-erosive drink did not increase with increasing liquid velocity. The rapid increase in the rate of erosion caused by citric acid at low liquid velocities shows that reproducible stirring is essential for precision and intercomparison of in vitro studies. It also accounts for the rapid erosion seen when erosive drinks are consumed from a straw placed labial to the anterior teeth, or are "swished" between the teeth., ((c) Eur J Oral Sci, 2005)

Background: We studied the effects of famotidine, sodium bicarbonate, and citric acid on the 13C-urea breath test (UBT)., Methods: Helicobacter pylori-infected volunteers received a UBT, 40 mg of famotidine at bedtime, and a second UBT (pudding test meal, 648 mg NaHCO3 tablet then 125 mg of urea in 200 ml of water containing 650 mg of NaHCO3). Experiment 2 consisted of four UBTs. Two were standard citric acid UBTs with 75 mg of urea and 2 g citric acid and two were sequential bicarbonate-citric acid UBTs. Sequential UBTs consisted of administration of a 648 mg bicarbonate tablet with 50 g of Polycose in 200 ml of water. Five minutes later, 125 mg of 13C-urea was given in 75 ml of water containing 650 mg of NaHCO3. Breath samples were collected after 15 minutes. Then, to acutely acidify the stomach, 4 g of citric acid was given in 200 ml of water. A second breath sample was collected 15 minutes after the citric acid. The standard UBTs were done before and after 6 days of famotidine (40 mg b.i.d.). Sequential UBTs were done after 1 and 6 days of famotidine therapy. Gastric biopsies for histology, culture, and mucosal cytokines were assessed before and after 6 days of famotidine., Results: Eighteen subjects participated, 10 in each experiment; seven had endoscopy with biopsy. Famotidine/ bicarbonate resulted an approximately 50% fall in UBT values (p = .021) with 10% becoming negative. The gastric pH increased from 5.1 +/- 0.5 to 6.7 +/- 0.2 (p = .03) although no pH value predicted the occurrence of false negative results. Under famotidine acid suppression, NaHCO3 reduced the delta over baseline (DOB) by 63% (p = .021). This was reversed with citric acid. Histology showed a H2-receptor antagonist-associated increase in the depth of gastric corpus inflammation., Conclusions: H2-receptor antagonists differ from proton pump inhibitors as high intragastric pH may cause a reduction in urease activity, unrelated to a reduced bacterial load and reversed by citric acid.

Background: Recently, a rapid-release 100-mg 13C-urea tablet with citrate supplement (Diabact UBT) showed excellent performance in a European population., Aim: To investigate the accuracy of a 50-mg tablet-based 13C-urea breath test protocol., Methods: : Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-Urea breath test was performed using a 50-mg 13C-urea tablet (Diabact UBT) and compared with the gold standard (rapid urease test and histology). Baseline, 10-min, 20-min and 30-min breath samples were collected in all cases. The cut-off values at each measurement interval were determined by three standard deviations above the mean excess delta 13CO2 excretion of Helicobacter pylori-negative patients., Results: Two hundred patients (150 before therapy and 50 after therapy) were available for analysis, with a mean age of 48.4 years, and 99 patients (50%) were H. pylori positive. The sensitivity and specificity of the 50-mg tablet-based 13C-urea breath test at 10 min, 20 min and 30 min were 100% and 98%, 100% and 100%, and 100% and 98%, respectively., Conclusion: A 20-min, 50-mg tablet-based 13C-urea breath test (Diabact UBT) protocol is highly accurate for the diagnosis of H. pylori infection.

Background: Currently available colon cleansing preparations are often poorly tolerated., Aim: To evaluate the efficacy of a low-volume, low-salt preparation for colonoscopy., Methods: This was a pilot study in patients scheduled for colonoscopy. The preparation consisted of 34 g of magnesium citrate and four bisacodyl tablets the day before the procedure, and one bisacodyl suppository on the morning of the procedure., Results: Twenty patients (age range, 49-81 years; all males) were entered into the study. There were no significant side-effects associated with the preparation. All rated the taste as 'tolerable or better'. The examination was considered to be adequate, with no limitations, in 17 patients (85%), and was scored as good to excellent (no solid stool) in 11 (55%), acceptable (small amounts of solid stool) in six (30%) and poor in three (15%: two in-patients and one out-patient). Importantly, two of the failures then received a standard polyethylene glycol preparation and again failed to show adequate colon preparation., Conclusions: This pilot study showed that the low-salt colon cleansing preparation was an effective alternative preparation for colonoscopy.

Background: In a previous study, the use of a citric acid test meal produced a rapid dose-dependent increase in urease activity that was significantly greater than that resulting from a pudding meal, ascorbic acid or sodium citrate. The mechanism was hypothesized to be related to the ability of citric acid to delay gastric emptying and possibly to enhance intragastric distribution of the urea., Objective: To compare the effects of sodium citrate, two doses of citric acid and a pudding meal on gastric motor function., Method: Eleven normal healthy volunteers were investigated using non-invasive techniques to measure gastric emptying and gastric motility. We evaluated gastric emptying using the Meretek 13Ceebiscuit solid phase gastric emptying breath test, which employs a 340-calorie biscuit containing 200 mg of the edible 13C-blue-green alga Spirulina platensis, after the administration of test meals of pudding, 2 g and 4 g of citric acid and 2 g of sodium citrate. Electrogastrograms (Digitrapper EGG) were also recorded for 30 min before and 180 min after the test meal., Results: Gastric emptying, as assessed by the half-time (T1/2), was delayed similarly with the pudding (136.8 +/- 9 min) and with 4 g of citric acid (144.5 +/- 7 min) (P > 0.7). Sodium citrate (108.7 +/- 6 min) and 2 g of citric acid (110.1 +/- 6 min) had similar effects on gastric emptying (P=0.986), and were significantly less effective in delaying gastric emptying (P < 0.01) compared to pudding or 4 g of citric acid. The electrogastrograms remained normal and there were no differences among meals and no relation with the gastric emptying results., Conclusions: The increased intragastric urea hydrolysis associated with citric acid test meals cannot be attributed to delayed gastric emptying. Changes in the intragastric distribution of urea or a direct effect of citric acid on the bacteria (e.g. via the cytoplasmic protein, UreI) are more likely to be responsible.

Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.

Heparin and saline are commonly used to fill hemodialysis central venous catheters to prevent their thrombosis during the interdialytic period. The purpose of this prospective clinical study was to evaluate whether replacing heparin with citrate or polygeline could ensure satisfactory catheter function without exposing patients to the risk of systemic heparinization. Thirty end-stage renal disease (ESRD) patients with subclavian or jugular single lumen catheters as temporary vascular access for hemodialysis were enrolled. After the insertion of the catheters, the patients were randomly assigned to one of the following three filling groups: Group A, heparin; Group B, citrate; Group C, polygeline. Before each dialysis, the filling solution was aspirated and clot volume, if present, was measured. The catheter usage time and the clot volume were 23 +/- 24 days and 0.052 +/- 0.035 ml in Group A, 51 +/- 36 days and 0.059 +/- 0.032 ml in Group B, and 32 +/- 10 days and 0.056 +/- 0.038 ml in Group C, respectively. Our results indicate that citrate or polygeline can replace heparin effectively as a filling solution for single lumen temporary hemodialysis catheters.

Current lipid apheresis techniques can remove atherogenic lipoproteins only from plasma. The initial mandatory separation of plasma and blood cells renders the extracorporeal circuit complex. We recently described the first clinical application of a new lipid adsorber that adsorbs low-density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) directly from whole blood. In continuation of our work, this paper describes the clinical biocompatibility of this new LDL hemoperfusion system. In a 2 center phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation protocol consisted of an initial heparin bolus followed by an acid citrate dextrose-A (ACD-A) infusion during the treatment. One patient blood volume was treated per session. All sessions were clinically uneventful. No signs of hemolysis or extracorporeal clot formation could be detected, and cell counts remained virtually constant. In a subgroup of patients (n = 4-6), further biocompatibility parameters were studied. Activation of leukocytes (elastase release), thrombocytes (beta-thromboglobulin [beta-TG] extrusion), and monocytes (interleukin (IL)-1beta and IL-6) were minimal. Complement activation (C3a and C5a generation) was negligible. The chosen anticoagulation protocol was both safe (constant ionized calcium levels) and effective (low thrombin-antithrombin formation). In summary, within the scope of a first pilot study, this new LDL hemoperfusion procedure combined the features of excellent clinical tolerance, good biocompatibility, and ease of handling. Phase III clinical trials will have to show whether these encouraging preliminary results can be corroborated in a larger patient population.

To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 +/- 8% and triglycerides by 23 +/- 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 +/- 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future.

Some triclosan and stannous fluoride toothpastes have been shown effective in reducing plaque and more particularly gingivitis in home use studies. There have been few comparisons of such products for their chemical plaque inhibitory action divorced from the indeterminate variable of toothbrushing. This study was a randomised, single-blind, cross-over comparison of 4 products, in a 4-day plaque regrowth design, balanced for residual effects and involving 12 healthy dentate subjects. The test agents were a stannous fluoride toothpaste, a triclosan/copolymer toothpaste, a triclosan/zinc citrate toothpaste and water. On day 1 of each study period, subjects were rendered plaque free. For the following 4 days, each subject suspended normal toothcleaning and rinsed 2 x daily with the allocated treatment for 60 s under supervision. On day 5, plaque was scored by index. Washout periods of 2 1/2 days brushing with water alone, followed each treatment period. Pseudo treatment periods of 4 days, involving 2 x daily rinsing with water in the absence of toothbrushing, followed the normal washouts after the stannous fluoride and triclosan/zinc citrate treatments, giving a total of 6 treatment periods. This design permitted analyses for 1st-order-carry-over. Intention to treat analyses revealed all toothpastes were more effective than water but that there were no differences between the active treatments. Per protocol analysis gave essentially similar findings except that the difference in plaque in favour of the triclosan/zinc citrate toothpaste over water did not reach significance. There was no evidence of 1st-order-carry-over effects for the stannous fluoride or triclosan/zinc citrate toothpastes. Consistent with other studies it appears that stannous fluoride and triclosan can be formulated into toothpaste vehicles to provide plaque inhibitory effects.

Effects of topical citric acid application on tissue maturation was studied in standardized periodontal defects in 6 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and recessed 0.5 mm into the dentin of maxillary canines. 1 defect in each dog was conditioned with a saturated solution of citric acid for 3 min and then rinsed with saline. Control defects in contralateral teeth were treated with saline only for the same length of time. The defects were covered with an expanded polytetrafluoroethylene membrane and the flaps repositioned and sutured. 14 days postsurgery, healing appeared more advanced along the defect walls and floor than in the center of the defect in all instances. Histometrically, citric acid-conditioned defects exhibited a higher density of collagen fibers along the defect walls and floor and adjacent to the barrier membrane as well as more advanced resolution of the residual blood clot than the surgical controls. Differences in fibroblast density within specimen pairs were non-significant. All control defects but none of the acid-conditioned defects showed an artifactual split between the dentin walls and the granulation tissue. This study failed to support the contention that topical application of citric acid to root surfaces may delay healing following periodontal surgery.