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H J Gurland

Publications and source records attributed to H J Gurland.

At least 19 recordsLinked to original sources
PubMed1999

Platelet-leukocyte aggregates during hemodialysis: effect of membrane type.

Hemodialysis is associated with the formation of platelet-leukocyte aggregates. Whether this phenomenon is hemodialysis (HD) membrane dependent is unclear. To evaluate this process, we examined respectively platelet activation (anti-CD41, anti-CD62, and antifibrinogen monoclonal antibodies [MoAb] binding), leukocyte activation (CD11b expression), and the appearance of platelet specific antigens on leukocytes as an index of platelet-leukocyte aggregation during HD using 3 different membrane materials, Cuprophan, Hemophan, and polysulfone. Flow cytometric techniques and specific MoAb were used. All parameters were assayed 5 min after initiation of HD to avoid the confounding variable of leukopenia and resultant cell subpopulation analysis. Platelet activation (anti-CD62 and antifibrinogen binding) occurred only with Cuprophan. All 3 membranes induced equivalent increases in CD11b expression on neutrophils and similarly increased the binding of anti-CD41 to neutrophils, reflecting an increment in the formation of platelet neutrophil aggregates. However, only Cuprophan induced an increase in anti-CD62 binding to neutrophils, suggesting that the aggregated platelets linked to neutrophils were activated. Increased anti-CD41 binding by monocytes was similarly observed with all 3 membranes. However, only polysulfone induced an increase in CD11b expression and fibrinogen binding to monocytes. We conclude that while the formation of platelet leukocyte aggregates appears to be a universal phenomenon in HD occurring with a variety of membrane types, subtypes of this phenomenon consisting of activated platelets and fibrinogen binding may be membrane dependent. This phenomenon may serve as a new biocompatibility parameter and may shed light on some of the biologic consequences of hemodialysis.

Antibodies, Monoclonal↗
PubMed1997

A comparison of dialysers with low-flux membranes: significant differences in spite of many similarities.

The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross-over clinical trial. While all four dialysers provided comparable removal of urea and creatinine, the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane. Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane, whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations. The ability to activate complement, measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex, and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three. The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation. Neutrophil degranulation, as indicated by the release of elastase-alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes. None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex. Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes, there are also significant differences. These differences may enable improvements in therapy, while allowing continued use of low-flux dialysers.

Adult↗
PubMed1997

LDL hemoperfusion--a new procedure for LDL apheresis: first clinical application of an LDL adsorber compatible with human whole blood.

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.

Acrylic Resins↗
PubMed1996

Microspheres based detoxification system: a new method in convective blood purification.

A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.

Adsorption↗
PubMed1996

The significance of adhesion molecules in nephrology.

Our knowledge of adhesion molecules has exploded over the last 5 years and has swamped most fields of medicine including nephrology. This is not surprising because adhesion molecules play a pivotal role in all aspects of cell to cell contact. Thus, they are involved in important issues, such as fetal development, in any kind of inflammatory or immune response including allograft rejection, as well as thrombus formation, and in tumor growth and metastasis (1-3). This short overview briefly reports some aspects of the biology of relevant adhesion molecules and their significance in inflammatory kidney diseases and in hemodialysis and renal allograft rejection. Finally, new therapeutic opportunities that arise by blocking adhesion molecule function are discussed.

E-Selectin↗
PubMed1995

[Internal medicine complications of ventriculoatrial shunt].

BACKGROUND: Ventriculo-atrial shunts (VASs) and ventriculo-peritoneal shunts (VPSs) are the symptomatic treatment of choice for hydrocephalus. Bacterial contamination of the atrial part of VASs (usually with Staphylococcus epidermidis) can result in further organ complications, in most instances immune complex mediated glomerulonephritis ("shunt-nephritis") or direct microbial heart valve destruction. PATIENTS AND METHODS: In a retrospective study, we analyzed clinical and laboratory data of 11 patients with VAS associated complications as well as the course of the disease. RESULTS: The following complications were observed: glomerulonephritis (n = 9), glomerulonephritis and aortic valve destruction (n = 1), pulmonary embolism, pulmonary hypertension and tricuspid valve insufficiency (n = 1). Out of the 11 patients, 8 suffered from unexplained fever. All 11 patients had elevated circulating immune complexes. In 3 of 4 patients initially requiring dialysis, renal function improved which allowed to stop hemodialysis. Renal function also improved in 3 of 5 patients who presented with elevated serum creatinine. Unfortunately, the patient with multiple pulmonary embolisms and tricuspid valve insufficiency died of progressive pulmonary hypertension. CONCLUSION: The prognosis for impaired renal function is good only if the VAS infection is diagnosed early and an immediate surgical and antibiotic treatment leads to an eradication of the underlying chronic infection.

Adult↗
PubMed1995

Synthetic modification of PAN membrane: biocompatibility and functional characterization.

A disturbing interaction of PAN membranes and the bradykinin generation system particularly in the presence of angiotensin converting enzyme inhibitors has been described. A modified new membrane, SPAN (special PAN), was produced by varying the polymer components in type and composition, in particular by a reduction in Na-Methallylsulfonate. Although the SPAN membrane successfully averted the bradykinin generating ability of PAN, it was important to determine whether such a modification did not lead to a loss of the satisfactory biocompatibility profile characteristic of the parent membrane. For this purpose, we conducted the present clinical study in nine patients comparing 3 membranes; (i) a polysulphone membrane (F60S); (ii) PAN; and (iii) SPAN, to examine the clinical biocompatibility profile and performance of the new membrane. A small increase in C5a with F60S and SPAN was found which is in the range expected for highly biocompatible synthetic membranes. The three dialysers had a similar inert profile for terminal complement complex arterial values, and had similar venous values. A minimal nonsignificant decline in white cell count was observed at 15 min for all dialysers, but otherwise WBC counts were unchanged. Platelet counts were unchanged throughout treatment for the three dialysers. Arterial and venous thrombin-anti-thrombin complex values were similar for all three dialysers. F60S and SPAN dialysers had similar urea clearances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure.

This study focuses on the role of platelet membrane glycoproteins and platelet-leucocyte adhesion in patients with sepsis and multiple organ failure (MOF). Specifically, the study raises the following issues: (1) the influence of sepsis and MOF on platelet activation as assessed by surface expression of platelet membrane glycoproteins GPIIb-IIIa and thrombospondin; and (2) the effect of sepsis and MOF on platelet adhesion to circulating leucocytes. In addition, platelet activation and platelet-leucocyte adhesion are evaluated according to clinical outcome. Forty-five patients with suspected sepsis or MOF were evaluated by intensive care scoring systems (APACHE II and Elebute) to assess severity of disease. Flow cytometric techniques were used to examine platelet membrane expression of various adhesion molecules on circulating platelets and the appearance of platelet specific antigen (CD41) on leucocytes as an index of platelet-leucocyte adhesion. The results were compared with severity of disease and according to outcome in patients. Twenty-eight patients of the total study population were septic and 17 were non-septic. Twenty-two of the 28 septic patients suffered from severe MOF (APACHE II > or = 20) whereas in six septic patients MOF was absent. Eleven of the non-septic group suffered from moderate MOF whereas in six, severe MOF was present. In septic patients fibrinogen receptor activity on platelets was significantly above normal values (P < 0.001). When MOF was present, thrombospondin surface expression on circulating platelets also increased significantly (P < 0.05). Concomitantly, platelet-leucocyte adhesion was increased in sepsis (P < 0.05) and decreased in patients with MOF (P < 0.05). Significant lower levels of circulating platelet-leucocyte aggregates occurred in non-survivors (P < 0.05). We conclude that sepsis is associated with increased surface expression of platelet adhesion molecules and an increased occurrence of circulating platelet-leucocyte aggregates. The decrease in circulating platelet-leucocyte peripheral sequestration. An increased platelet-leucocyte adhesion and sequestration might account for development of MOF in the course of sepsis.

Adolescent↗
PubMed1995

Efficacy of lipid apheresis: definitions and influencing factors.

The comparison of efficiency of currently available lipid apheresis systems has been hampered by different definitions of efficacy and poorly controlled apheresis conditions. This paper suggests definitions of efficacy and standardization of its determinants. The acute efficacy of risk factor reduction reflects the relative decrease of pathogen by a single treatment session compared to preapheresis levels. Standardization of treated plasma volume in relation to the patients plasma volume and correction of changes in plasma volume during the procedure are mandatory. Its determination is most useful in the technical evaluation of new systems. The long-term efficacy of risk factor reduction as compared to baseline is determined by mean interapheresis levels of e.g. LDL-C in the pseudo-steady-state after about 3 months of regular treatment. It is the major criterion for potential regression of coronary artery disease and absolute average plasma levels of 120 < or = mg/dl LDL-C should be attained. It is influenced by the acute efficacy of the system, apheresis frequency and rebound kinetics. The clinical efficacy is defined by apheresis induced reduction of coronary morbidity and mortality. It is influenced by long-term risk factor reduction, the selectivity of the system as well as the control of non-lipid risk factors. Apheresis related effects on coronary artery disease comprise functional improvements of hemorheology and vasomotion as well as morphological benefits like regression of luminal narrowing and plaque stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1994

Platelet-leukocyte aggregation during hemodialysis.

Hemodialysis is associated with simultaneous changes in leukocytes and platelets, but it is unclear whether these alterations affect the interactions between these cell types. To evaluate this process, we examined the appearance of platelet specific antigens (CD41) on leukocytes as an index of platelet-leukocyte aggregation during hemodialysis using three different synthetic membranes. Patients with end-stage renal disease (ESRD) on long-term hemodialysis treatment were enrolled. Flow cytometric techniques and platelet specific monoclonal antibodies (MoAb) that recognize the glycoprotein complex on resting and activated platelets (anti-CD41), the activated GPIIb-IIIa complex receptor (anti-LIBS1), and the p selectin GMP140, that is exposed on platelet plasma membrane after activation and platelet degranulation (anti-CD62), were used. Subjects with ESRD had a lower predialysis platelet surface expression of CD41 and LIBS1 compared to normal controls, but unchanged CD62 expression. In parallel, patients with ESRD manifested a uniformly reduced platelet-leukocyte microaggregates predialysis compared to normal controls. When examined across the dialyzer, however, an increase in platelet-neutrophil and platelet-monocyte microaggregates was observed with all three synthetic membranes at both 15 and 30 minutes after initiation of dialysis. This phenomenon could be duplicated in vitro by physiologic concentrations of the platelet specific agonist ADP, but not by the complement factors C3a or C5a. We conclude that platelet-leukocyte aggregates occur during dialysis likely related to a primary platelet activation mechanism. This phenomenon may serve as a new biocompatibility parameter and may shed light on some of the biologic consequences of hemodialysis.

Adolescent↗
PubMed1994

Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.

Impaired platelet function and a bleeding tendency are well-recognized complications of chronic renal failure. Because the fibrinogen receptor GPIIb-IIIa plays a central role in platelet aggregation and adhesion to the subendothelium, it was reasoned that a defect in this receptor may underlie the impaired platelet function in uremia. To test this hypothesis, the function of this receptor in the platelets of 11 uremic patients was studied. Aggregation studies were performed with flow cytometric techniques with anti-GPIIb-IIIa conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1). Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets from patients with chronic renal failure showed significantly decreased binding of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or RGD-peptide stimulation compared with normal controls, suggesting a defect related to the ability of the fibrinogen receptor to undergo a conformational change. Moreover, antifibrinogen and antithrombospondin binding to activated platelets were reduced in uremic patients, implying impairment of both ligand-binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa function, which may account for the observed effects of this therapy in restoring platelet aggregation. These findings indicate that platelets of patients with chronic renal failure reveal an aggregation defect at least partially due to an intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that inhibits fibrinogen binding to GPIIb-IIIa.

Adenosine Diphosphate↗
PubMed1993

Biocompatibility of a new high-permeability modified cellulose membrane for haemodialysis.

The biocompatibility and solute permeability characteristics of a high-permeability modified cellulose membrane (Hemophan-HP) (He-HP) were compared with those of two synthetic membranes (poly(ethylene-co-vinyl alcohol) (EVAL) and poly(acrylonitrile-co-sodium methallyl sulphonate) (AN69)) and Cuprophan in a multicentre, four-way cross-over clinical trial. Cuprophan membranes caused significant complement activation, leukopenia, and granulocyte elastase release. He-HP membranes demonstrated a lesser effect, which was similar to that observed for the EVAL membrane, although less than that seen with the AN69 membrane. A similar order for the four membranes was seen for their effect on platelets. Cuprophan membranes provided superior small-molecule removal to the other three membranes. In contrast, Cuprophan was essentially impermeable to beta 2-microglobulin, whereas He-HP, EVAL, and AN69 allowed the removal of 60-90 mg of beta 2-microglobulin per treatment. However, a decrease in the plasma concentration of beta 2-microglobulin was observed only with the AN69 membrane, most probably as a result of the ability of that membrane to adsorb proteins. Our results demonstrate that high-permeability membranes of comparable biocompatibility to some synthetic membranes can be fabricated from cellulose derivatives.

Adult↗
PubMed1993

Lipid apheresis by hemoperfusion: in vitro efficacy and ex vivo biocompatibility of a new low-density lipoprotein adsorber compatible with human whole blood.

To date, selective extracorporeal low-density lipoprotein (LDL) removal can only be performed from plasma; that is, a plasma-cell separation step using a centrifuge or a plasma membrane separator is necessary initially. This article characterizes a new polyacrylate-based LDL adsorber directly applicable to whole blood. In vitro single-pass hemoperfusion tests using pooled donor blood showed quantitative adsorption of atherogenic LDL-cholesterol (LDL-C) and complete recovery of protective high-density lipoprotein C. Fibrinogen, another independent risk factor of atherosclerosis, was also adsorbed to a lesser extent. Single-pass ex vivo biocompatibility using fresh donor blood on-line was excellent and resulted in minimal cell loss. Neither signs of hemolysis nor activation of monocytes (interleukin-1 production) were detected. Only slight activation of leukocytes (elastase release) and thrombocytes (platelet factor 4 secretion) as well as of coagulation (thrombin-antithrombin complex formation) and complement (C3a, C5a generation) was observed. Under the experimental conditions used, the optimal anticoagulation regimen was 0.5 IU heparin plus 0.375 mg citrate/ml blood. Priming the column with a buffer of pH 7.4 containing heparin, citrate, and Ca2+ is recommended. In conclusion, this new adsorber exhibited selective LDL-C adsorption in vitro combined with excellent ex vivo biocompatibility and thus holds great promise for a successful clinical application in a closed-loop system in patients.

Acrylic Resins↗
PubMed1993

Renal complications of infected ventriculoatrial shunts.

Contamination of a ventriculoatrial shunt (VAS) with skin organisms that are usually nonpathogenic may be followed by an immunologically mediated renal injury. The bacteria characteristically involved are coagulase-negative Staphylococci (e.g., Staphylococcus epidermidis), which strongly adhere to the plastic surface of the VAS. These bacteria are protected from the body's natural defense mechanisms and respond only poorly to antibiotics. As a result, their growth persists and produces a continuous antigenic stimulation. Circulating immune complexes (CIC) are an appropriate tool to screen for chronically infected VASs. We followed CIC in 138 VAS patients. An infected VAS was seen in 20 of the 24 patients with highly elevated CIC and in 1 of the 19 patients with moderately elevated CIC, but none of the 95 patients with normal CIC had evidence of shunt infection. Of the 21 patients with shunt infections, 8 had renal involvement (4 requiring dialysis, and 4 with proteinuria, hematuria, and/or elevated creatinine). Results from kidney biopsy specimens available from 4 patients confirmed glomerulonephritis. Of the 4 patients requiring dialysis at diagnosis, renal function recovered sufficiently to stop dialysis after successful VAS exchange in all but 1. In the other 4 patients, renal symptoms (proteinuria, creatinine) also improved after VAS revision. Chronic infection with S. epidermidis or other bacteria is a continuing problem in patients with VASs and can lead to an immune-mediated renal injury. However, the prognosis for reversal of the renal injury is relatively good if the VAS infection is treated promptly.

Adolescent↗
PubMed1993

Long-term efficiency, biocompatibility, and clinical safety of combined simultaneous LDL-apheresis and haemodialysis in patients with hypercholesterolaemia and end-stage renal failure.

Three hypercholesterolaemic patients on maintenance haemodialysis with angiographically proven coronary artery disease were treated in a once-a-week schedule by combined, synchronous lipid apheresis (using heparin-induced extracorporeal LDL precipitation) and haemodialysis (HELP/HD) for 65-104 weeks. Clinical side-effects were few and mostly related to high ultrafiltration rates in patients with low compliance regarding interdialytic fluid restriction. Biocompatibility of the procedure was shown to be good and blood cell losses, leukocyte (elastase release) and thrombocyte (beta-thromboglobulin extrusion) as well as complement (C3a formation) activation were minimal. Interestingly, most of the C3a generated in the extracorporeal HELP circuit was immediately removed again in the precipitate filter. In the pseudo-steady-state after 3 months of regular therapy, acute haematocrit-corrected reduction of plasma components after the session compared to pre values were about 55% for the risk factors LDL cholesterol (LDL-C), lipoprotein(a) (Lp(a)), and fibrinogen (FIB) with good recovery of HDL-C and other proteins. Urea, creatinine, and phosphate elimination was similar to normal haemodialysis. Mean interapheresis values of risk factors after one (n = 2) and two (n = 1) years of treatment were crucially dependent upon ultrafiltration (UF); thus, in two patients with high UF LDL-C concentrations amounting to 185 and 220 mg/dl at baseline and were reduced to about 135 mg/dl LDL-C, while in the patient with low UF the reduction was from 231 mg/dl to 80 mg/dl. The atherogenic index (LDL-C/HDL-C), was reduced from 6.4 and 5.1 to about 4.3 in patients with high UF, from 6.1 to 3.3 in the patient with low UF.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗