Comparison of Three ß-Glucan Tests for the Diagnosis of Invasive Candidiasis in Intensive Care Units.

The (1→3)-ß-d-glucan (BDG) is a marker of invasive fungal infection that can be detected in serum by different commercial kits. In this study, we compared the performance of the Fungitell assay (FA), the Fungitell STAT assay (STAT), and the Wako ß-glucan test (WA) for the diagnosis of invasive candidiasis (IC) in the intensive care unit (ICU). Patients for whom at least one BDG testing was required for a clinical suspicion of IC were retrospectively enrolled. A total of 85 serum samples from 56 patients were tested by the three BDG tests. The rate of IC was 23% (13/56) with a predominance of noncandidemic (intra-abdominal) IC. STAT and WA results exhibited overall good correlation with those obtained by FA (Spearman's coefficient R = 0.90 and R = 0.89, respectively). For the recommended cutoffs of positivity, sensitivity and specificity for IC diagnosis were 77%/51% (FA, 80 pg/mL), 69%/53% (STAT, ratio 1.2), and 54%/65% (WA, 7 pg/mL), respectively. Optimal performance was obtained at 50 pg/mL (FA), ratio 1.3 (STAT), and 3.3 pg/mL (WA) with sensitivity/specificity of 85%/51%, 69%/57%, and 77%/58%, respectively. Overall, the three BDG tests showed comparable but limited performance in this setting with positive and negative predictive values for an estimated IC prevalence of 20% that were in the range of 30 to 35% and 85 to 95%, respectively.

Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland.

Echinocandins represent the first-line therapy of candidemia. Echinocandin resistance among Candida spp. is mainly due to acquired FKS mutations. In this study, we report the emergence of FKS-mutant Candida albicans/glabrata in Switzerland and provide the microbiological and clinical characteristics of 9 candidemic episodes. All patients were previously exposed to echinocandins (median 26 days; range 15-77). Five patients received initial echinocandin therapy with persistent candidemia in 4 of them. Overall mortality was 33%.

Link between Heat Shock Protein 90 and the Mitochondrial Respiratory Chain in the Caspofungin Stress Response of Aspergillus fumigatus.

Aspergillus fumigatus is an opportunistic mold responsible for invasive aspergillosis. Triazoles (e.g., voriconazole) represent the first-line treatment, but emerging resistance is of concern. The echinocandin drug caspofungin is used as second-line treatment but has limited efficacy. The heat shock protein 90 (Hsp90) orchestrates the caspofungin stress response and is the trigger of an adaptive phenomenon called the paradoxical effect (growth recovery at increasing caspofungin concentrations). The aim of this study was to elucidate the Hsp90-dependent mechanisms of the caspofungin stress response. Transcriptomic profiles of the wild-type A. fumigatus strain (KU80) were compared to those of a mutant strain with substitution of the native hsp90 promoter by the thiA promoter (pthiA-hsp90), which lacks the caspofungin paradoxical effect. Caspofungin induced expression of the genes of the mitochondrial respiratory chain (MRC), in particular, NADH-ubiquinone oxidoreductases (complex I), in KU80 but not in the pthiA-hsp90 mutant. The caspofungin paradoxical effect could be abolished by rotenone (MRC complex I inhibitor) in KU80, supporting the role of MRC in the caspofungin stress response. Fluorescent staining of active mitochondria and measurement of oxygen consumption and ATP production confirmed the activation of the MRC in KU80 in response to caspofungin, but this activity was impaired in the pthiA-hsp90 mutant. Using a bioluminescent reporter for the measurement of intracellular calcium, we demonstrated that inhibition of Hsp90 by geldanamycin or MRC complex I by rotenone prevented the increase in intracellular calcium shown to be essential for the caspofungin paradoxical effect. In conclusion, our data support a role of the MRC in the caspofungin stress response which is dependent on Hsp90.

Near-infrared scanning cavity ringdown for optical loss characterization of supermirrors.

A cavity ringdown system for probing the spatial variation of optical loss across high-reflectivity mirrors is described. This system is employed to examine substrate-transferred crystalline supermirrors and to quantify the effect of manufacturing process imperfections. Excellent agreement is observed between the ringdown-generated spatial measurements and differential interference contrast microscopy images. A 2-mm diameter ringdown scan in the center of a crystalline supermirror reveals highly uniform coating properties with excess loss variations below 1 ppm.

Efficacy of Antifungal Monotherapies and Combinations against Aspergillus calidoustus.

Invasive fungal infections due to Aspergillus calidoustus with decreased azole susceptibility are emerging in the setting of azole prophylaxis and are associated with poor outcomes. We assessed the in vitro activity of antifungal drugs used alone or in combinations against A. calidoustus and found a synergistic effect between voriconazole and terbinafine at concentrations within the therapeutic range. An invertebrate Galleria mellonella model of A. calidoustus infection tended to support the potential benefit of this combination.

In vitro differentiation of near-unlimited numbers of functional mouse basophils using conditional Hoxb8.

BACKGROUND: Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought-after tool for diagnostic and drug testing purposes. METHODS: A method is described to massively expand bone marrow-derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin-3 (IL-3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. RESULTS: IL-3-dependent, conditional Hoxb8-immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near-unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end-differentiated and short-lived and express basophil-specific surface markers and proteases. Upon IgE- as well as C5a-mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2-type cytokines (IL-4, IL-13) and leukotriene C4. IL-3-deprivation induces apoptosis correlating with upregulation of the BH3-only proteins BCL-2-interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM-1). CONCLUSION: A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.

Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.

BACKGROUND AND STUDY AIMS: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn's disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model. METHODS: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm (2); delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4 (+) T cells, percentage of apoptotic CD4 (+) T cells, body weight, and systemic side effects were evaluated. RESULTS: LDPDT improved the MEIC ( P = 0.011) and the histological score ( P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 ( P = 0.042), interleukin-17 ( P = 0.029), and interferon-gamma ( P = 0.014), decreased the number of mucosal CD4 (+) T cells, and increased the percentage of apoptotic CD4 (+) T cells compared with the disease control group. No local or systemic side effects occurred. CONCLUSION: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4 (+) T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

Mid-infrared interference coatings with excess optical loss below 10 ppm.

We present high-reflectivity substrate-transferred single-crystal GaAs/AlGaAs interference coatings at a center wavelength of 4.54 µm with record-low excess optical loss below 10 parts per million. These high-performance mirrors are realized via a novel microfabrication process that differs significantly from the production of amorphous multilayers generated via physical vapor deposition processes. This new process enables reduced scatter loss due to the low surface and interfacial roughness, while low background doping in epitaxial growth ensures strongly reduced absorption. We report on a suite of optical measurements, including cavity ring-down, transmittance spectroscopy, and direct absorption tests to reveal the optical losses for a set of prototype mirrors. In the course of these measurements, we observe a unique polarization-orientation-dependent loss mechanism which we attribute to elastic anisotropy of these strained epitaxial multilayers. A future increase in layer count and a corresponding reduction of transmittance will enable optical resonators with a finesse in excess of 100 000 in the mid-infrared spectral region, allowing for advances in high resolution spectroscopy, narrow-linewidth laser stabilization, and ultrasensitive measurements of various light-matter interactions.

Accuracy of Sensititre YeastOne echinocandins epidemiological cut-off values for identification of FKS mutant Candida albicans and Candida glabrata: a ten year national survey of the Fungal Infection Network of Switzerland (FUNGINOS).

OBJECTIVES: Echinocandins represent the first-line treatment of candidaemia. Acquired echinocandin resistance is mainly observed among Candida albicans and Candida glabrata and is associated with FKS hotspot mutations. The commercial Sensititre YeastOne™ (SYO) kit is widely used for antifungal susceptibility testing, but interpretive clinical breakpoints are not well defined. We determined echinocandins epidemiological cut-off values (ECV) for C. albicans/glabrata tested by SYO and assessed their ability to identify FKS mutants in a national survey of candidaemia. METHODS: Bloodstream isolates of C. albicans and C. glabrata were collected in 25 Swiss hospitals from 2004 to 2013 and tested by SYO. FKS hotspot sequencing was performed for isolates with an MIC≥ECV for any echinocandin. RESULTS: In all, 1277 C. albicans and 347 C. glabrata were included. ECV 97.5% of caspofungin, anidulafungin and micafungin were 0.12, 0.06 and 0.03 µg/mL for C. albicans, and 0.25, 0.12 and 0.03 µg/mL for C. glabrata, respectively. FKS hotspot sequencing was performed for 70 isolates. No mutation was found in the 52 'limit wild-type' isolates (MIC=ECV for at least one echinocandin). Among the 18 'non-wild-type' isolates (MIC>ECV for at least one echinocandin), FKS mutations were recovered in the only two isolates with MIC>ECV for all three echinocandins, but not in those exhibiting a 'non-wild-type' phenotype for only one or two echinocandins. CONCLUSION: This 10-year nationwide survey showed that the rate of echinocandin resistance among C. albicans and C. glabrata remains low in Switzerland despite increased echinocandin use. SYO-ECV could discriminate FKS mutants from wild-type isolates tested by SYO in this population.

Latency of cathepsin B secreted by human colon carcinoma cells is not linked to secretion of cystatin C and is relieved by neutrophil elastase.

The lysosomal cysteine proteinase cathepsin B is shown to be secreted by ten human colon carcinoma cell lines and to accumulate in culture media as a latent enzyme. The cell lines also secrete a physiological inhibitor of cathepsin B, cystatin C. A significant correlation was found between secretion of the latent enzyme and the inhibitor (r = 0.755, P < 0.01). The aim of the present study was to modulate the respective secretion of the two antagonists to test whether or not latency of cathepsin B was due to the concomitant secretion of the inhibitor. SW480 colon carcinoma cells were treated with the acidotropic agent ammonium chloride, phorbol 12-myristate 13-acetate, and the inflammatory cytokines TGF-beta, TNF-alpha, and IL-1 beta. Ammonium chloride significantly increased latent cathepsin B levels without affecting the constitutive secretion of cystatin C. Phorbol 12-myristate 13-acetate induced a 4- to 5-fold increase in secreted latent cathepsin B, but did not alter significantly the accumulation of cystatin C in media. The cytokines, TGF-beta, TNF-alpha, and IL-1 beta, had no major effect on the expression of these two antagonists. Latent cathepsin B released from human carcinoma cells could be efficiently activated by neutrophil elastase at neutral pH. It is concluded that latent cathepsin B is a true proenzyme rather than an enzyme-inhibitor complex. In addition, our data from neutrophil elastase activation experiments indicate that a proteolytic system for activation of the tumor cell-secreted latent enzyme may exist in vivo.

Troponin-I for prediction of early postoperative course after pediatric cardiac surgery.

OBJECTIVES: It was the aim of the study to test the prognostic value of cardiac troponin-I (cTnI) concerning the early postoperative course after pediatric cardiac surgery. BACKGROUND: Cardiac troponin-I is a very specific and sensitive marker of myocardial damage in adults and children. As perioperative myocardial damage may be a significant factor of postoperative cardiac performance, serial cTnI values were analyzed in children undergoing open heart surgery. METHODS: Seventy-three children undergoing elective correction of congenital heart disease including atrial and ventricular surgical manipulation were studied. Cardiac troponin-I levels were measured serially and correlated with intra- and postoperative parameters (such as doses and length of inotropic support, renal and hepatic function, duration of intubation). Patients with prolonged postoperative recovery were analyzed with special attention to the cTnI levels. RESULTS: The cutoff point for the definition of a high and a low risk group of cTnI values was set at 25 microg/liter, 4 h after admission to the intensive care unit (ICU) and at 35 microg/liter considering the maximal value of cTnI in the first 24 h in the ICU. The results showed a highly significant correlation between the need for inotropic support, the severity of renal dysfunction and the duration of intubation in relation to the serum levels of cTnI. CONCLUSIONS: Cardiac troponin-I serum levels after open heart surgery in children and infants 4 h after admission to the ICU allowed anticipation of the postoperative course and correlated with the incidence of significant postoperative complications.

[Pediatric shock--pathophysiology, diagnosis and treatment]. / Das Kind im Schock--Pathophysiologie, Früherkennung und Therapie.

Shock remains a significant cause of morbidity and potential mortality in the pediatric population. It is defined as a impaired perfusion with a too high oxygen demand in comparison to oxygen delivery. The cause of hypoxia may be found in a hypovolemic condition due to hemorrhage or loss of gastro-intestinal fluids, a disorder in volume distribution or a cardiac dysfunction. Less frequent are patients with an obstruction in the outflow tract of the heart or disorders in binding oxygen to hemoglobin. Hypoxia leads to lactat-acidosis with the clinical signs of tachypnoea, tachycardia and restlessness. It is of greatest importance to recognize the ongoing dysfunction early, in spite of mechanism of compensation with a high cardiac output, warm periphery and dry skin (warm shock). Is there no adequate therapy decompensation will occur with vasoconstriction, cold periphery and low cardiac output. This will lead to multiple organ dysfunction syndrome with neurological, renal, further cardiac, pulmonary and metabolic disorders. If this point of no return is reached, cell death will continue to occur and the patient will die. Early and aggressive volume therapy is indicated, filling the cardiac system with crystalloids or colloids. Later on under clinical conditions inotropic drugs will improve cardiac output and oxygen delivery. Only by recognizing these patients as early as possible we will be able to reduce morbidity and mortality of this potentially dangerous syndrome.

Respiratory syncytial virus triggered adult respiratory distress syndrome in infants: a report of two cases.

Two infants with severe respiratory syncytial virus infection which resulted eventually in classical adult respiratory distress syndrome (ARDS) are presented. Both infants had severe apneic spells, necessitating intubation and mechanical ventilation (MV). Chest radiographs changed after a few days after institution of MV from initial bronchopneumonia like pattern to severe ARDS. Assessment of respiratory system mechanics (single breath occlusion technique) revealed severe restrictive disease in both cases. The first patient recovered with residual restrictive changes determined during a follow-up 2.5 months later, whereas the second infant died because of ARDS, pulmonary interstitial emphysema and hypoxemic hypoxia.

Pulmonary function after one-lung ventilation in newborns: the basis for neonatal thoracoscopy.

BACKGROUND: To maintain good exposure during major video-assisted thoracic surgery it is necessary to deflate completely the ipsilateral lung. However, little is known about the effects of one-lung ventilation (OLV) on pulmonary function in newborn patients. METHODS: Ten neonatal domestic pigs with a mean age of 6+/-0.6 days were intubated and ventilated in pressure-controlled mode (inspired oxygen fraction=1.0). One-lung ventilation was maintained for 120 minutes. Serial measurements of hemodynamics and gas exchange were done before, during, and until 90 minutes after OLV. Pulmonary function testing was performed before and after OLV for each lung separately. RESULTS: With the inspired oxygen fraction set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar-arterial oxygen tension gradient increased slightly from the baseline value of 2.6% +/-0.3% to 3.8%+/-0.3% during OLV (mean+/-standard error of the mean; p=0.02), and from 358+/-28 to 407+/-18 mm Hg (not significant), respectively. Both values returned to baseline during the subsequent ventilation of both lungs. Static compliance and resistance of the ventilated lung did not change. Compliance of the collapsed lung decreased after reexpansion from 0.42+/-0.07 to 0.29+/-0.06 mL x cm H2O(-1) x kg(-1), p=0.008). Resistance remained unchanged (0.22+/-0.02 versus 0.25+/-0.05 cm H2O x L(-1) x s(-1); not significant). CONCLUSIONS: There were only minor effects on pulmonary function during and after OLV in the neonatal piglet. Alterations in gas exchange during OLV were minimal. Prolonged collapse of the lung with subsequent reexpansion was associated with a slight decrease in compliance, indicating some mild lung injury.

Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism; biochemical studies.

Investigation of a psychomotorically retarded girl showed excretion of abnormal amounts of alpha-ketoadipic acid, alpha-hydroxyadipic acid, alpha-aminoadipic acid, 1,2-butenedicarboxylic acid and elevation of plasma alpha-aminoadipic acid levels. The identity of these metabolities was established by various methods. The excretion of alpha-aminoadipic acid correlated to the lysine intake. Degradation studies with cultured fibroblasts indicate a defect in the oxidative decarboxylation of alpha-ketoadipic acid (see Clin. Chim. Acta, 58 (1975) 271.

Acute toxicity and depression of phagocytosis in vivo by liposomes: influence of lysophosphatidylcholine.

Small unilamellar phospholipid vesicles (liposomes), intended as drug carriers, have recently been demonstrated to reversibly depress phagocytic activity in rats when injected in a single high dose (2g of lipid per kg body weight) as revealed by the carbon clearance test. Depression of the phagocytic function was found to vary widely depending on the lipid used [M. Brandl et al., Pharm. Pharmacol. Lett., 4 (1) 1-4, 1994]. This study has now been extended in two directions: Firstly, liposomes made of the same type of lipid but different batches of raw material were compared in terms of their influence on phagocytosis as well as for their contents of impurities. The test revealed great variability of RES suppression between different batches of hydrogenated soy PC, whereas the reproducibility of the carbon clearance test was satisfactory with liposomes made of a single batch of raw material. Thin layer chromatographic analyses of the used phosphatidylcholines (PCs) and limulus tests on lipopolysaccharides revealed lysophosphatidylcholine (lysoPC) as the only impurity which showed parallels with the observed differences in phagocytosis. Secondly by "spiking" phosphatidylcholine with increasing amounts of lysoPC the latter could be proven to enhance RES depression by liposomes in a dose-dependent manner. At the same time a strong and dose-limiting increase in acute toxicity of PC vesicles was observed with increasing contents of lysoPC. However, in cholesterol-containing vesicles lysoPC-spiking did not significantly alter their behaviour, for lysoPC contents of up to 10%. Only PC/cholesterol-vesicles containing lysoPC contents as high as 15% provoked enhanced RES depression and toxicity compared to lysoPC-free vesicles. LysoPC and cholesterol in liposomes are known to play a destabilizing and stabilizing role respectively within liposomal bilayers which might influence recognition and uptake of vesicles by macrophages and thus modulation of phagocytosis.

Lung mechanics and gas exchange in ventilated preterm infants during treatment of hyaline membrane disease with multiple doses of artificial surfactant (Exosurf)

Eight premature infants ventilated for hyaline membrane disease and enrolled in the OSIRIS surfactant trial were studied. Lung mechanics, gas exchange [PaCO2, arterial/alveolar PO2 ratio (a/A ratio)], and ventilator settings were determined 20 minutes before and 20 minutes after the end of Exosurf instillation, and subsequently at 12-24 hour intervals. Respiratory system compliance (Crs) and resistance (Rrs) were measured by means of the single breath occlusion method. After surfactant instillation there were no significant immediate changes in PaCO2 (36 vs. 37 mmHg), a/A ratio (0.23 vs. 0.20), Crs (0.32 vs. 0.31 mL/cm H2O/kg), and Rrs (0.11 vs. 0.16 cmH2O/mL/s) (pooled data of 18 measurement pairs). During the clinical course, mean a/A ratio improved significantly each time from 0.17 (time 0) to 0.29 (time 12-13 hours), to 0.39 (time 24-36 hours) and to 0.60 (time 48-61 hours), although mean airway pressure was reduced substantially. Mean Crs increased significantly from 0.28 mL/cmH2O/kg (time 0) to 0.38 (time 12-13 hours), to 0.37 (time 24-38 hours), and to 0.52 (time 48-61 hours), whereas mean Rrs increased from 0.10 cm H2O/mL/s (time 0) to 0.11 (time 12-13 hours), to 0.13 (time 24-36 hours) and to (time 48-61 hours) with no overall significance. A highly significant correlation was found between Crs and a/A ratio (r = 0.698, P less than 0.001). We conclude that Exosurf does not induce immediate changes in oxygenation as does the instillation of (modified) natural surfactant preparations. However, after 12 and 24 hours of treatment oxygenation and Crs improve significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Survivors with bad outcome after hypoxic-ischaemic encephalopathy: full-term neonates compare unfavourably with children.

UNLABELLED: Hypoxic-ischaemic encephalopathy (HIE) is of major importance in neonatal and paediatric intensive care with regard to mortality and long-term morbidity. Our aim was to analyse our data in full-term neonates and children with special regard to withdrawal of life support and bad outcome. PATIENTS: All patients with HIE admitted to our unit from 1992-96 were analysed. Criteria for HIE were presence of a hypoxic insult followed by coma or altered consciousness with or without convulsions. Severity of HIE was assessed in neonates using Sarnat stages, and in children the duration of coma. In the majority of cases staging was completed with electrophysiological studies. Outcome was described using the Glasgow Outcome Scale. Bad outcome was defined as death, permanent vegetative state or severe disability, good outcome as moderate disability or good recovery. RESULTS: In the neonatal group (n = 38) outcome was significantly associated with Sarnat stages, presence of convulsions, severely abnormal EEG, cardiovascular failure, and multiple organ dysfunction (MOD). A bad outcome was observed in 27 cases with 14 deaths and 13 survivors. Supportive treatment was withdrawn in 14 cases with 9 subsequent deaths. In the older age group (n = 45) outcome was related to persistent coma of 24-48 h, severely abnormal EEG, cardiovascular failure, liver dysfunction and MOD. A bad outcome was found in 36 cases with 33 deaths and 3 survivors. Supportive treatment was withdrawn in 15 instances, all followed by death. CONCLUSIONS: Overall, neonates and older patients did not differ with regard to good or bad outcome. However, in the neonatal group there were significantly more survivors with bad outcome, either overall or after withdrawal of support. Possible explanations for this difference include variability of hypoxic insult, maturational and metabolic differences, and the more compliant neonatal skull, which prevents brainstem herniation.

Vigabatrin dosing during haemodialysis.

The antiepileptic drug vigabatrin has shown efficacy in the treatment of patients with refractory epilepsy. Unlike many other antiepileptics it is not bound to plasma protein and mainly eliminated by the kidney. Although the therapeutic and toxic serum concentration range is not clearly defined and efficacy and toxicity are not closely correlated with the dose, factors decreasing vigabatrin elimination such as advanced age or renal failure may pose risk of untoward effects. Thus far there are no dose recommendations available for patients on haemodialysis. We report on an epileptic patient who experienced severe, partially reversible renal failure as a consequence of near-drowning. In this patient serum concentrations of vigabatrin were measured repeatedly both during haemodialysis and after partial recovery of renal function. The terminal elimination half-life in this patient was 41 hours during the period of severe renal failure (creatinine clearance < 5 ml/min). As about 60% of vigabatrin was removed from the blood pool by haemodialysis in these patients the antiepileptic should be administered after dialysis. To maintain serum concentrations in the usual range and to control seizure activity only 500 mg vigabatrin every 3 days were necessary.