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Michael Joannidis

Publications and source records attributed to Michael Joannidis.

17 recordsLinked to original sources

Mechanisms of neutrophil transmigration across renal proximal tubular HK-2 cells.

BACKGROUND: Adhesion of intratubular leukocytes to proximal tubules in biopsies of patients with rapidly progressive glomerulonephritis and the appearance of leukocytes in the urine in interstitial nephritis suggest interactions between leukocytes and tubular epithelia in renal diseases. The aim of this study was to investigate the effect of cytokines and endotoxin on leukocyte migration through proximal tubular epithelial cells and also to determine the role of the transmembrane adhesion molecules ICAM-1 and CD47 in this process. METHODS: Experiments determined transepithelial migration (TEM) of PMN (polymorphonuclear) leukocytes through monolayers of HK-2. Expression of ICAM-1 and CD47 was assessed via confocal immunofluorescence, FACS analysis and western blotting. The effect of antibodies against ICAM-1 and CD47 on TEM was examined. Furthermore measurements of cytokine release (IL- 6 and IL-8) were performed. RESULTS: Preincubation of HK-2 cells with either TNFalpha or LPS resulted in stimulation of PMN migration through monolayers of HK-2 cells. There was no preferred direction of transmigration. ICAM-1 was expressed by HK-2 cells and expression was increased after 4 h stimulation with TNFalpha or LPS. Application of ICAM-1 antibodies inhibited TEM. CD47 was expressed in both HK-2 cells and PMN. CD47 antibodies inhibited predominantly basolateral-to-apical TEM. HK-2 cells released IL-8 and IL-6 preferably into the apical compartment. Additionally, we showed that fMLP induced transmigration through monolayers of HK-2 cells was associated with significant increased CD47 expression on PMN cell surfaces. CONCLUSIONS: Inflammatory mediators stimulate TEM of PMN through monolayers of HK-2 cells without a clearly discernible preference of direction. Mechanisms involved in TEM stimulated by cytokines or endotoxin appear to be mainly changes in surface receptor densities of HK-2 cells with ICAM-1 and CD47 playing an essential role.

Antibodies, Monoclonal↗

Pharmacokinetics of liposomal amphotericin B during extracorporeal albumin dialysis.

Extracorporeal blood purification techniques such as hemofiltration or albumin dialysis can exert a significant, but not easily predictable influence on plasma pharmacokinetics of antimicrobial agents. The effect of albumin dialysis on the pharmacokinetics of liposomal amphotericin B (AMB) and other lipid-formulated drugs has not been investigated so far. Therefore, plasma concentrations of liberated and liposomal AMB were measured in a patient, who obtained liposomal AMB for suspected invasive mycosis and required albumin dialysis because of cholestatic liver failure caused by graft versus host disease after bone marrow transplantation. Liberated and liposomal AMB were separated by solid phase extraction and measured by high performance liquid chromatography. No excessive AMB elimination took place during albumin dialysis. Plasma levels of liposomal AMB exceeded those of liberated AMB. Pharmacokinetic data were comparable to those obtained previously in patients on hemofiltration and in critically ill patients without extracorporeal blood purification.

Adult↗

Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis.

INTRODUCTION: In acute disseminated intravascular coagulation, the effect of antithrombin (AT) administration on elevated levels of D-dimer is not well established. In the present study, we report on changes in circulating levels of D-dimer in response to administration of AT in a series of patients with acquired AT deficiency due to severe sepsis. METHODS: Eight consecutive critically ill medical patients presenting with acute disseminated intravascular coagulation associated with severe sepsis/septic shock received a single bolus infusion of AT over 30 minutes, aiming to achieve physiological AT levels. Haemostatic parameters including D-dimer were assessed prior to, 6 and 24 h after AT administration. An average of 42 +/- 9 U/kg body weight was infused. RESULTS: Following AT substitution, elevated levels of D-dimer fell whereas AT levels rose. CONCLUSION: These observations support the notion that AT can favourably affect fibrin degradation accompanying disseminated intravascular coagulation of severe sepsis.

Adult↗

Disturbances of electrolytes and blood chemistry in acute alcohol intoxication.

Prevalence of electrolyte disturbances and biochemical changes were determined in patients admitted to the emergency room of the Department of Internal Medicine in Innsbruck, Austria during a six-month period. The value of biochemical parameters for the detection of chronic alcohol abuse was also investigated. The most frequent electrolyte disturbances found were hypernatremia (41%), hyperchloremia (21%), hypermagnesemia (17%) and hypocalcemia (15%), whereas hypokalemia and hypophosphatemia were observed quite rarely (5% and 3.4%, respectively). The most frequent biochemical changes observed were consistent with signs of cellular toxicity i.e. increased liver enzymes (elevated gamma-glutamyltransferase (GGT), aspartate aminotransferase, alanine aminotransferase and lactic dehydrogenase) as well as signs of pancreatitis (elevated serum lipase and amylase) and muscle damage (elevated creatine kinase). The most frequent changes in blood counts were leucocytosis (23%), thrombocytopenia (14%), and anemia (12%). C-reactive protein showed only minimal elevation. Male sex and level of blood alcohol were detected as major risk factors for the diagnosis of chronic alcohol abuse in the patient sample investigated. When testing the value of routinely measured parameters for predicting the presence of chronic alcohol abuse, GGT and mean corpuscular volume of red blood cells (MCV) appeared to be of equal value. A combination of elevated blood alcohol with an increase in either of these markers may be interpreted as high risk for chronic alcohol abuse in this particular group of patients.

Adult↗

Epidemiology and natural history of acute renal failure in the ICU.

This article focuses on the incidence, risk factors, and mortality of acute renal failure (ARF) in critically ill patients. Accurate epidemiologic assessment of ARF is still a problem; as long as there is neither a uniquely accepted definition of ARF nor definitions for end points to measure, results will remain heterogeneous and hard to compare. Mortality of ARF has remained high throughout the last decades, despite further development of modern treatment modalities. This indicates that ARF is not just a matter of loss of organ function that can easily be replaced easily by extracorporeal therapies, but is a condition additionally accompanied by systemic consequences which significantly impact on prognosis.

Acute Kidney Injury↗

Comparison of different scoring methods for assessing the nutritional status of hospitalised patients.

OBJECTIVE: Despite intense clinical research, no commonly accepted diagnostic tool for assessment of nutritional status is yet available. In this study a comparison of four different methods for diagnosis of the nutritional status of patients admitted to a university hospital in Austria is presented. PATIENTS AND METHODS: Clinical data of 640 hospitalised patients were analysed in a prospective-descriptive study design. Four recommended methods, the Innsbruck nutrition score (INS), the Prideaux nutritional risk assessment (PNRA), the well established nutrition risk index (NRI), and the body mass index (BMI) were used to analyse nutritional status. RESULTS: The BMI showed 90.2% of the patients evaluated to have normal nutritional status, whereas the PNRA identified 48.9%, the NRI 40% and the INS 58.6% as well nourished. Patients were variously diagnosed with moderate malnutrition: 9% (BMI), 42% (PNRA), 54.8% (NRI) and 30% (INS). Severe malnutrition was detected in 0.5% (BMI), 9.1% (PNRA), 5.2% (NRI) and 11.4% (INS) of the patients evaluated. Cancer patients had the worst nutritional status. CONCLUSION: Malnutrition seems to be a common diagnosis among hospitalised patients in Austria. Screening and assessment of nutritional status should be integrated into clinical routine. The methods tested scored malnutrition at different frequencies. BMI seemed to underestimate the prevalence of malnutrition. The PNRA provided some information on clinical outcome, whereas the NRI had the best relationship between the degree of malnutrition and length of stay. Calculation of the INS may give correct diagnosis of severe malnutrition. Further prospective clinical studies are needed to validate the scoring systems used in this study and to provide accurate clinical diagnosis of malnutrition.

Adolescent↗

Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis.

Albumin dialysis has been shown to improve the outcome in patients with cholestatic liver failure caused by chronic liver disease. This study reports 7 liver transplant recipients who were treated with albumin dialysis for intractable pruritus of different origin (ductopenic graft rejection, non-anastomotic strictures, and recurrence of hepatitis C). Treatment with histamine (H1) blockers, opioid antagonists, and cholestyramine had not been effective. The Molecular Adsorbent Recirculating System (MARS; Teraklin, Rostock, Germany) was used for albumin dialysis. All patients presented with numerous scratch marks, 6 of whom had a pronounced icterus. Six patients (86%) responded to 3 consecutive treatments with significant reduction of pruritus. The mean pruritus score, which was quantified by a visual analog scale (VAS), decreased from 9.7 +/- 0.5 to 3.7 +/- 0.8 (SD). The mean duration of 1 treatment was 15.6 hours. The procedure was well tolerated by all patients. The mean total serum bilirubin in patients who responded to therapy declined from 19.11 +/- 16.96 mg/dL (SD) before MARS therapy to 9.24 +/- 3.52 mg/dL after treatment. The mean serum concentration of 3 alpha-hydroxy bile acids decreased from 192.67 +/- 58.12 micromol/L (SD) to 42.33 +/- 31.58 micromol/L (SD). Follow-up in 3 cases showed sustained improvement of pruritus lasting for more than 3 months. In 3 patients, however, pruritus relapsed. One patient, who showed severe pruritus, without relevant elevation of serum bile acids before treatment, did not respond to albumin dialysis. Our data indicate that MARS is an effective therapeutic option for patients with intractable cholestatic pruritus.

Aged↗

Neutrophil transmigration in renal proximal tubular LLC-PK1 cells.

BACKGROUND/AIMS: Adhesion of intratubular leukocytes to proximal tubules in biopsies of patients with rapidly progressive glomerulonephritis and the appearance of leukocytes in the urine in interstitial nephritis suggest interactions between leukocytes and tubular epithelia in renal disease. The present study was performed to investigate whether incubation of tubular epithelia with cytokines or endotoxin (LPS) does stimulate adhesion and migration of leukocytes through these epithelia in vitro. METHODS: Experiments determined adhesion of PMN to LLC-PK cells cultured on tissue culture plates and transepithelial migration (TEM) through LLC-PK monolayers cultured on microporous membranes. Measurements of transepithelial electrical resistance (TER), cytokine release into apical or basolateral compartments and chemotactic activities of apical and basolateral supernatants were performed. RESULTS: Preincubation of LLC-PK cells with either TNFalpha or LPS resulted in stimulation of PMN adhesion and consequently PMN migration through LLC-PK monolayers in both apical-to-basolateral and basolateral-to-apical direction. TEM was not associated with a reduction of TER. Although largely apical IL-8 secretion by LLC-PK cells was found, apical-to-basolateral migration occurred against a concentration gradient of IL-8 and could not be inhibited by IL-8 antibodies. Chemotactic activities of supernatants were slightly increased by TEM but did not show any significant differences between apical and basolateral compartments independent of the direction of PMN migration. TEM in basolateral-to-apical direction was about twice as efficient as in apical-to-basolateral direction (Transmigration Index = 3,92 +/- 0,55 and 2,28 +/-,21, respectively). Only basolateral-to-apical TEM could be partly inhibited by preincubation of basolateral membrane with IL-8 antibodies. CONCLUSION: Inflammatory mediators stimulate PMN adherence to LLC-PK cells and subsequently TEM. The mechanisms involved in TEM stimulated by cytokines or endotoxin appear to be rather changes in surface receptor properties of LLC-PK cells than chemotactic stimuli. Basolateral-to-apical TEM appears to be the favored direction most likely augmented by IL-8 associated haptotactic PMN stimulation.

Animals↗

Amphotericin B lipid formulations in critically ill patients on continuous veno-venous haemofiltration.

OBJECTIVES: The pharmacokinetics of lipid-formulated amphotericin B (AMB), and of AMB that has dissociated from its lipid moiety and bound to lipoproteins in plasma, were separately determined in critically ill patients. PATIENTS AND METHODS: Eleven patients required continuous veno-venous haemofiltration (CVVH). Five of them were treated with liposomal AMB (AmBisome) and seven with AMB colloidal dispersion (Amphocil). Six of the critically ill were not undergoing CVVH (three of them treated with liposomal AMB and three with AMB colloidal dispersion). RESULTS: Significant amounts of AMB are liberated from liposomes or colloidal dispersion during circulation in plasma, where pharmacokinetics mimic that of AMB deoxycholate. Elimination of the remaining lipid-formulated fraction is different and differentially affected by CVVH. Plasma levels of lipid-formulated AMB were significantly higher in patients treated with liposomal AMB than in those treated with AMB colloidal dispersion; clearance of liposomal AMB is enhanced by haemofiltration, whereas elimination of AMB colloidal dispersion is not significantly affected. CONCLUSIONS: The pharmacokinetics of AMB that has been liberated from its lipid moiety is similar under treatment with either liposomal AMB or AMB colloidal dispersion. Since no significant influence of haemofiltration on the pharmacokinetics of liberated AMB has been found, a standard dose of lipid-formulated AMB can be recommended for patients on haemofiltration.

Adolescent↗

Severe electrolyte disturbances and renal failure in elderly patients with combined diuretic therapy including xipamid.

UNLABELLED: Diuretics are among the most frequently prescribed substances in elderly patients, but they are also associated with the highest incidence of adverse effects in this group of patients. Xipamide is a sulfonamide-like diuretic whose action does not depend on transtubular secretion. This characteristic makes it suitable for situations in which the kidney is highly sodium avid. Because of the potency of this substance the risk of adverse reactions like electrolyte disorders or hypovolemia is increased as well. We report seven patients (age 65-85) admitted to the emergency room of the University Hospital of Innsbruck between 1998 and 2002 who had developed serious adverse reactions upon initiation of treatment with xipamide as an additional diuretic. Six of these patients had received combinations with loop diuretics. The disturbances observed were hyponatremia (lowest value 108 mmol/l), hypokalemia (lowest value 1.5 mmol/l) and prerenal azotemia (highest serum urea 269 mg/dl, highest serum creatinine 5.13). CONCLUSION: With the exception of diuretic resistance in severe heart failure or renal insufficiency a combination therapy of xipamide with a second diuretic appears to be associated with an unnecessarily high risk of serious adverse reactions and thus should be avoided. This is especially true for elderly patients.

Age Factors↗

Treatment of intractable pruritus in drug induced cholestasis with albumin dialysis: a report of two cases.

Cholestatic liver injury can be caused by a variety of drugs and is difficult to treat. We report two patients, a 22 year old male and a 55 year old female, with drug induced cholestasis caused by anabolic-androgenic steroids (silabolin and nandrolone) and by fluoxetine, respectively. Both patients presented with massive jaundice and severe pruritus resulting in sleep deprivation and suicide ideation. Laboratory examination revealed signs of cholestasis. Medical treatment was ineffective; therefore, extracorporeal albumin dialysis using the molecular adsorbent recirculating system (MARS) was started. Three treatments with a mean duration of 16 hours were performed in each patient. The procedure was well tolerated by the patients and resulted in a sustained relief of pruritus as well as in a decline of plasma bilirubin and serum 3alpha-hydroxy bile acid levels. The mean plasma bilirubin concentration decreased from 25.27 mg/dl to 10.7 mg/dl; the mean serum 3alpha-hydroxy bile acid concentration decreased from 299 micromol/L to 88 micromol/L. After 2 months, the pruritus had nearly vanished in both patients, and there was a further decline of bilirubin levels after discharge from hospital. In conclusion, extracorporeal albumin dialysis appears to be a therapeutic option in severe drug induced cholestasis refractory to medical treatment.

Adult↗