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Biomedical subjects

H Klinkmann

Publications and source records attributed to H Klinkmann.

At least 37 records · Page 2Linked to original sources
PubMed1993

Extracorporeal endotoxin removal by immobilized polyethylenimine.

The neutralization of bacterial endotoxins (ET) is still an unsolved problem in therapeutic medicine. The efficacy of anti-endotoxin antibodies or receptor antagonists and other substances interfering with the endotoxin-induced pathomechanisms is dependent on an intact cellular degradation system of the host. However, the phagocytosis function of that system seems to be impaired regularly in patients with intense or long-lasting endotoxemia or septic shock and in patients undergoing hemodialysis. Extracorporeal adsorption of ET might well be an effective support in the anti-ET therapy by lowering the amount of circulating ET and thus relieving the defense system of the body. In this work a new ET-adsorbent based on macroporous cellulosic beads with immobilized polyethylenimine (PEI) was tested for its ET-removal capacity in vitro. A test solution with 100 ng/ml ET from Escherichia coli 055:B5 was recirculated in a system containing the adsorbent beads. Polymyxin B immobilized to the same carrier was used for comparison. PEI as well as polymyxin B showed complete removal of ET from plasma and water as was measured by the Limulus Amebocyte Lysate (LAL) test (Chromogenix). The biocompatibility of the PEI absorber was superior to that of polymyxin B. The results indicate that the PEI absorber is of high efficacy and possibly of interest for the treatment of endotoxemia.

Adsorption↗
PubMed1993

Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins.

The removal of protein-bound substances of pathogenetic relevance from blood is of therapeutic interest for drug intoxications, renal and liver failure, and metabolic disorders. Current methods using adsorbents are effective but often not specific enough. This work presents an alternative method that enables the dialyzability of albumin-bound toxins from plasma by the use of a high-flux dialyzer (F 60 Fresenius) and an albumin solution circulating on the dialysate side to increase selectively the affinity for albumin-bound toxins. This method resulted in effective removal of unconjugated bilirubin, drugs with a high protein-binding ratio (sulfobromophthalein, theophylline), and a protein-bound toxin (phenol). The additional removal of PBS could extend the applicability of dialysis, for example, to drug intoxications and liver failure or could improve the elimination of protein-bound uremic toxins in chronic renal failure.

Adsorption↗
PubMed1993

Endothelium: the next frontier in biocompatibility.

Vascular endothelium plays a central role in two specific functional systems. It controls vascular tone, hemostasis, and substance transport. The endothelium is the "docking station" for trapping, deactivation, and regeneration of activated blood compounds and provides the principal clearance mechanism for biologically active mediators released by different cell types. The second function is a regenerational one. During the period between insults (or between dialysis sessions), the endothelium has to restore the "first line of defense," that is, to regenerate the injured athrombogenic surface of the vessel wall and its antioxidative potential, defoliate damaged endothelial cells, and interpolated new ones. These two important endothelial activities are required over and above its basic functions. Future research in artificial organs must take into account that continuous or intermittent blood-membrane contact creates an altered endothelial response. These altered responses may result in adaptional reactions that may differ substantially in the acutely ill patient on continuous venovenous hemofiltration (CVVH) or in a stable patient on maintenance hemodialysis. By a reduction in such factors as immediate or delayed cell-cell interactions (direct or indirect), it may be possible to influence the long-term outcome of chronic hemodialysis patients. Other research should strive to enhance those factors of endothelial function that are essential in the defensive and restorative properties of endothelial tissue. This is especially important in such continuous therapies as CVVH, long-term membrane oxygenation, and artificial heart and blood vessels. Currently, there are more unanswered questions than possible answers concerning endothelial functions in long-term hemodialysis patients, but it is clear that excluding endothelial cell behavior from investigation of extracorporeal therapy in the future would be a substantial omission.

Animals↗
PubMed1993

Prolonged biochemical and morphological stability of encapsulated liver cells--a new method.

In this work a new type of polyelectrolyte complex capsules is introduced as an artificial housing for liver cells. Male Wistar rat hepatocytes were encapsulated using cellulose sulphate and polydimethyldialyllammonium chloride as polyelectrolytes. Amino acid metabolism rate and urea synthesis of the cells increased over the investigation period in contrast to the decrease observed in control monolayer cultures. The encapsulated cells were morphologically characterized. The described procedure represents a sufficient method for the cultivation of living cells in mechanically stable semipermeable microcapsules.

Amino Acids↗
PubMed1993

2,3 diphosphoglycerate-haemoglobin binding in uraemic patients treated with erythropoietin. A 31P-nuclear magnetic resonance study.

Using 31P-nuclear magnetic resonance (NMR) measurements of relaxation rate for 2,3 diphosphoglycerate (DPG) phosphorus atoms, we showed previously that in uraemic red blood cells the DPG-haemoglobin binding is stronger, thus stabilizing the deoxyhaemoglobin form and hence facilitating oxygen release. Here we verified if these modifications of spatial environment of DPG remain in uraemic patients treated by human recombinant erythropoietin (rHuEpo). Simultaneously we measured the intraerythrocytic ATP concentration (ATPi) and pH (pHi) of patients. Our results show a slight decrease on pHi and ATPi values during rHuEpo treatment. For the DPG relaxation rates, we observed a very weak but statistically significant increase 6 months after the beginning of treatment, but we cannot attribute a physiopathological significance to these results because of the lack of accuracy of the NMR determination of relaxation rate in red blood cells. Therefore, the DPG-haemoglobin binding is always stronger than in normal subjects.

2,3-Diphosphoglycerate↗
PubMed1992

Three years with a national apheresis registry.

The large number of unsolved problems in plasma exchange therapy makes an apheresis registry appear useful. The results of such an open prospective observational study from 1987 to 1989 in East Germany are presented in this paper. With 1,945 procedures in a total of 419 patients (on average 4.1 treatments per patient) about 80% of all treatments in the country were registered. Exchange volume averaged 2.7 (+/- 0.78) l or 43 (+/- 13.9) ml/kg body weight. Substitutes were albumin (51% of the cases), FFP (22%), and both (22%). Nephrological (25%) and neurological (23%) diagnoses prevailed among the treated diseases. Haematologic diseases (12%) were underrepresented and hepatic coma (20%) was overrepresented. Minor side effects occurred in 22% of all treatments and severe complications in 38 treatments (2%). Four fatalities probably resulted from plasmapheresis therapy. The registry permits an assessment of the treatment results and of several trends during the period of observation.

Adolescent↗
PubMed1991

Immunoadsorption and plasma exchange in multiple sclerosis: complement and plasma protein behaviour.

Three groups of patients suffering from acute attacks or progressive multiple sclerosis (MS) are under investigation. First results revealed remarkable clinical improvements of patients with acute attacks in the groups treated by therapeutic plasma exchange (TPE) and immunoadsorption (IA). Only slight or no improvements were seen in the patients of the control group treated only with steroids. Plasma protein levels (IgG, IgM, IgA, fibrinogen) were considerably reduced in patients of the TPE group after each treatment procedure as expected. The same holds true concerning the total hemolytic capacities (THC) of the complement of the classic (CP) and the alternative (AP) pathway. On the other hand in the IA group only slight decreases of plasma proteins (about 20%) were observed, but the behaviour of THC's were quite similar than those seen in the patients of the TPE group. The THC decreases in both groups can be explained by removal of all complement factors (TPE group) or by the adsorption of single factors (IA group) of both complement pathways according to earlier in vitro investigations. The THC decreases in patients of both groups suffering from acute MS attacks could mean an "antiinflammatory" effect and could--at least partially--contribute to the clinical improvements of these patients.

Blood Proteins↗
PubMed1991

Detection of charges and their distribution on dialysis membranes with cationic/anionic dyes using confocal laser scanning microscopy.

Methods for the detection of positive or negative charges on the surface of biomaterials/membranes and inside a membrane are important for the characterisation of such materials. We tested different dyes and optimized staining procedures. Under standardized conditions negatively charged membranes were stained with cationic triarylmethane compounds such as crystal violet and positively charged membranes with the anionic anthraquinone dye anthralan blue B. There was no staining of uncharged cellulose membranes. The applicability of these methods was demonstrated on membranes coated to varying degrees with charged compounds such as heparin, these changes in charge being detectible quantitatively by photometry. The distribution of charges inside a membrane was detected by optical sectioning across the stained (FITC labelled poly-L-lysine) membrane using confocal laser scanning microscopy (LSM). LSM offers a completely new application possibility in biomaterial and biocompatibility research.

Biocompatible Materials↗
PubMed1991

Importance of endotoxins in high-flux dialysis.

Endotoxins are not only important for inducing pyrogenic reactions during haemodialysis but also for the stimulation of different blood cells. This is followed by the release of interleukin-1 and other powerful biological active substances, resulting in a broad spectrum of biological activities. Permeation of LPS (endotoxins) through dialysis and haemofiltration membranes is of great importance. Using a quantitative turbidimetric method based on the LAL (limulus amoebocyte lysate) test LPS concentrations were measured in a closed in vitro system for 11 different dialysers and haemofilters. To assess the passage of endotoxin through the membrane, permeation was measured from the dialysate to the blood side as well as from the blood compartment to the dialysate side.

Endotoxins↗