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Biomedical subjects

R Fünfstück

Publications and source records attributed to R Fünfstück.

At least 19 recordsLinked to original sources

Tissue factor expression in an animal model of hydronephrosis.

BACKGROUND: Hydronephrosis is associated with interstitial fibrosis and occlusion of renal capillaries by fibrin. However, the mechanisms leading to fibrin formation is unknown. METHODS AND RESULTS: Twenty days after unilateral ligation of the ureter, interstitial fibrosis occurred in the ligated kidney. Fibrosis was preceded by infiltration of inflammatory cells (macrophages, B and T lymphocytes). Staining with an antibody against von Willebrand factor demonstrated newly formed capillaries in the fibrosing tissue as well as prominent fibrin deposition. Fibrin staining was found around vessels, in the interstitium, the glomeruli, and tubuli. Fibrin deposition was less prominent in the non-ligated kidney and almost absent in sham-operated animals. The expression of tissue factor, the central initiator of coagulation, was induced within 5 days after ligation in the operated kidney but not in the sham-operated animals. Tissue factor positivity was observed by immunohistochemistry in vascular endothelial cells, the vessel wall, tubular epithelial cells, glomerular capsular cells, Bowman's space and in the interstitium. Tissue factor induction was due to increased transcription, since in-situ hybridization showed increased levels of mRNA in the ligated kidney compared to sham-operated rats. The tissue factor gene is under control of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappa B). When extracts of operated organs were compared with kidneys of sham-operated rats or contralateral kidneys in electrophoretic mobility shift assays, an increase in AP-1 and NF-kappa B binding activity to their respective binding sites in the tissue factor gene was observed in the operated, but not in the contralateral kidney or kidneys of sham-operated animals. CONCLUSION: Ureteral ligation leads to infiltration of inflammatory cells, increased AP-1 and NF-kappa B expression in the kidney, resulting in increased tissue factor transcription and translation, and ultimately in increased fibrin deposition.

Animals

Dysmorphic erythrocytes in glomerulonephritis. 1. Electron microscopical and histochemical investigation.

Dysmorphic erythrocyte malformation in urine is characteristic of glomerulonephritis. The mechanisms leading to this phenomenon are still unknown. To obtain evidence of the site as well as of the process of erythrocyte damage, electron microscopical and histochemical investigations of renal biopsy materials from 19 patients with histologically defined glomerulonephritis were performed. The results suggest that the initial damage of erythrocytes in the glomerular area is reasoned by enzymatic glycocalyx destruction. On passage through the tubular system the osmotically sensitized surface altered cells undergo rapid hemolysis and losses of membrane skeletal proteins leading to dysmorphic shape transformations.

Adult

Dysmorphic red cell formation in glomerulonephritis. 2. In vitro generation of dysmorphic erythrocytes.

In the present study influences leading to in vitro formation of dysmorphic erythrocytes were studied. Fresh and surface altered erythrocytes pretreated with several proteases were passed through different solutions representing distinct nephronís fluids. After passage of intact erythrocytes only 12-15% dysmorphic cells were observed. In case of protease treated cells the number of dysmorphic cells rose to 35-80%. The hemoglobin content was decreased. PAGE and electron microscopical findings demonstrated substantial losses of transmembrane and membrane skeleton proteins. It is assumed that surface protein degradation, loss of membrane skeleton proteins and hemolysis seem to be closely associated with dysmorphic malformation of urinary erythrocytes characteristical for glomerulonephritis.

Anisotropy

Haemodialysis-associated beta 2M amyloidosis: current controversies.

Beta 2M amyloidosis is a major complication of long-term haemodialysis. Beta 2M, the precursor molecule of amyloid fibrils, accumulates in renal failure because of diminished renal excretion. Whether, in addition, a minor increase of synthesis occurs in dialysed patients is still controversial. Beta 2M amyloidosis differs from most other forms of amyloid by its preferential osteoarticular location. This points to some peculiar role of the microenvironment in the synovial space, which is currently poorly defined. A finding which remains so far unexplained is the more delayed appearance of beta 2M amyloidosis in patients dialysed with polyacrylonitrile membranes. In principle, however, beta 2M amyloidosis is seen with all dialysis modalities and possibly even before maintenance dialysis. Differences between treatment modalities relate either to removal of beta 2M or some aspect of bioincompatibility, e.g. proteolytic processing. Finally, the exact chemical nature of amyloid fibrils, i.e. whether they constitute native beta 2M molecules or processed molecules, is currently controversial.

Amyloid

Beta-2-microglobulin-derived amyloidosis: onset, distribution and clinical features in 13 hemodialysed patients.

Postmortem examinations were carried out in 13 patients (6 males, 7 females, age 58 +/- 9 years) who had been on regular hemodialysis treatment for 10-90 months using disposable regenerated cellulose membrane dialyzers. The prevalence of beta 2-microglobulin (beta 2m)-derived AB-amyloid deposits in different sites was determined. At autopsy, specimens were obtained from different joints, paravertebral tissue, intervertebral discs and from visceral organs. During life, routine laboratory parameters and radiographic studies had been carried out at 6-month intervals. Serum levels of beta 2m were elevated in all patients (57.5 +/- 13.4 mg/l). Synovial AB-amyloid deposits were shown in different joints of 4 patients, aged between 59 and 73 years, and dialysed for 10-90 months, respectively. All had been unremarkable by X-ray and asymptomatic. No amyloid could be detected in the intervertebral discs of 2 further patients suffering from destructive spondylarthropathy. In 11 of the 13 patients, extracellular beta 2m deposits were observed by immunohistochemistry in different tissues. The results document that (a) AB-amyloidosis may occur in elderly patients even when dialysed for less than 5 years; (b) most cases are completely asymptomatic; the appearance of symptoms must be dependent on additional factors, e.g., site of AB-amyloid deposition and intensity of inflammatory reaction, and (c) AB-amyloid is not the exclusive cause of destructive spondylarthropathy, as 2 typical cases were observed who were devoid of amyloid.

Amyloidosis

[Comparative studies of the effectiveness of 1-day treatment and 7-day treatment with sulfamerazine/trimethoprim (Berlocombin) of patients with urinary tract infection].

Insights into the pathogenesis of urinary tract infections warrant reflections on new therapeutic strategies. Of particular interest is the phenomenon of bacterial adherence to cells, as the adhesion of microorganisms to uroepithelial cells plays an important role in the development of the disease. In 21 women with an acute episode of lower urinary tract infection who were known of having chronic pyelonephritis, we studied the influence of a one-day (n = 7) and a seven-day treatment by administering the regular sulfamerazine/trimethoprime (Berlocombin) dose (2 X 2 tablets from the 2nd day, n = 7) or a reduced amount (2 X 1 tablet from the 2nd day, n = 7). All treatment regimes led to a disappearance of the clinical symptoms; however, in one case of the group receiving one-day treatment, dysuric complaints recurred as early as on day 3 after therapy. Only when employing the regular schedule of therapy, the controls of the urine cultures revealed sterility of the urine for all cases still on the 21st day after treatment. This treatment regimen most clearly influenced the ability of the microorganisms to adhere to the uroepithelial cells of the probands (in-vivo adherence). The one-day treatment was not able to reduce the rates of bacterial adherence to the cells. In all patients, the acute disease resulted in an increase in microorganisms coated with antibodies; on day 21 following therapy, however, the findings registered were as before onset of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Virulence of Escherichia coli strains in relation to their hemolysin formation, mannose-resistant hemagglutination, hydroxamate production, K 1-antigen and the plasmid profile in patients with chronic pyelonephritis.

Microorganisms initiating infections of the kidneys and the upper urinary tract are characterized by specific properties. In 96 patients with non-obstructive chronic pyelonephritis, Escherichia coli strains were isolated and their virulence properties studied. Most frequently hemolysin formation and mannose-resistant hemagglutination (n = 39/40%), less frequently the ability to produce hydroxamate/aerobactin (n = 18/19%) and the K 1-antigen (n = 13/14%) were detected. In 34 E. coli strains (35%) two and more virulence factors were found. A statistically significant correlation exists between mannose-resistant hemagglutination (evidence of P- and F7-F14 fimbriae) and hemolysin formation on the one hand and hydroxamate production and K 1-antigen on the other (confidence intervals are 0.56-0.75 and 0.75-0.89, respectively). Disease activity and pathogenicity of E. coli strains showed a statistically significant association (chi 2-value, DF 1: hemolysin 29.5, mannose-resistant hemagglutination 17.1, K 1-antigen 4.8, hydroxamate 0.5). The analysis of the plasmid profile yielded species in molecular weight range from 0-170 Md. A correlation between single virulence features and certain plasmid combinations failed to be demonstrated. The results revealed a close connection between certain virulence properties of E. coli strains and a specific uropathogenicity. The clinical significance of this observation should be further elucidated.

Adolescent

[The significance of erythrocyte morphology in glomerular and non-glomerular hematuria].

By the judgement of erythrocyte morphology in urinary sediment it is possible to recognize the origin of hematuria. In glomerular hematuria the cells show destructive changes so that a differentiation is possible contrary to the regular formed erythrocytes from bleeding sources of the urinary tract. The urinary sediments of 325 patients (185 cases with glomerulonephritis and 140 cases with urolithiasis) are judged independently by two study groups. In glomerulonephritis 90.5 +/- 7.4% dysmorphic erythrocytes were found, whereas in urolithiasis the portion of destructed cells was 5.7 +/- 5.4%. In 95% of the patients the origin of hematuria could be verified by microscopical erythrocyte analysis.

Erythrocyte Count

Vitamin status in patients with chronic renal failure.

Many factors complicate the effort for a recommendation on individual vitamin requirements in CRF. On the basis of our present incomplete knowledge about the handling of vitamins in uremia, suggestions for appropriate supplementation only of water-soluble vitamins are given. Patients with advanced CRF without dialysis treatment should receive daily supplements of vitamin B6 (5 mg), ascorbic acid (70-100 mg), and the normal recommended daily allowance of the other water-soluble vitamins in addition to the vitamin intake from the diet. We give folic acid only in patients taking antifolate drugs or in combination with iron in iron deficiency state and anemia (1 tablet of Folicombin contains 0.5 mg folic acid and 0.4 g elemental iron). There is still a pressing need for more data on the vitamin status, on vitamin requirements, and on long-term effects of vitamin administration in CRF.

Humans

[Changes in the pharmacokinetics of gentamycin during nephrotoxic therapy].

Nephrotoxicity secondary to aminoglycoside antibiotic therapy is a well-known complication in clinical medicine. We have analysed the influence of a 10-day gentamicin treatment with 3.40 mg/d on pharmacokinetic parameters and renal excretion of electrolyses and beta-NAG in 10 patients (9 female, 1 males) with UTJ. Using compartment-independent methods the following kinetic parameters at the first and 10th day of treatment were estimated: total body clearance from 100 to 80 ml/min (-20%), mean residence time from 2.7 to 3.5 h (+28%) and AUC from 6.7 to 9.4 mg/l.h (+41%). Similar results could be obtained using a linear two-compartment model: k13 is changed from 0.74 to 0.54 h-1 (-27%). Vdss approximately 16 1, k12 and k21 are not significantly influenced. There was no significant difference between the first and 10th day for renal excretion electrolyses, urine volume and osmolality with the exception of beta-NAG, which increased from 7.2 to 11.7 U/l (p less than 0.05). From the results it can be concluded that even a ten day gentamicin treatment with normal doses and serum concentrations in the therapeutic range less than 5 mg/l induce nephrotoxic effects at the glomerular and tubular side of the nephron. For quantification of the nephrotoxic effects we propose a nonlinear two-compartment model with a new pharmacokinetic parameter for renal damage. This new model allows to predict and to compare the nephrotoxic effects for different aminoglycoside antibiotics and different modes of treatment.

Electrolytes

[Pathogenetic aspects of chronic urinary tract infections].

Infections of the urinary tract belong to the most frequent bacterially caused diseases. Strains of bacteria which are able to evoke an infection of the urinary tract distinguish themselves by particular properties. Hereby the existence of O- and K-antigens, the demonstration of adhesins (F-antigens), the ability of the formation of haemolysin and production of colicin V (aerobactin), the serum resistance as well the plasmid profile an important role is ascribed. The ability of uropathogenic bacteria to the adhesion to the epithelial cells of the urinary tract is significant for the development and the course of a disease. A connection is to be established between the rate of bacterial attachment of the epithelial cells and the activity of a pyelonephritis. The defence of an infection of the urinary tract takes place above all in the local area, in which cases among others the phenomenon of the antibody coated bacteria and disturbances of the formation of the secretory IgA are of interest. Various pathogenetic aspects of chronic infections of the urinary tract are discussed on the basis of reports from literature and findings of own investigations.

Bacterial Adhesion

The influence of selected urinary constituents on the adhesion process of Escherichia coli to human uroepithelial cells.

In the pathogenesis of infectious diseases, great importance is attached to the problem of adhesion of bacteria to cells. In 100 urine specimens from normal test persons, patients with infections of the lower urinary tract, with chronic pyelonephritis and glomerulonephritis were studied. The adhesion of strains of Escherichia coli to human uroepithelial cells depended on the concentration of single urinary factors. While increased concentrations of urea and creatinine favored the adhesion process, a statistically significant negative influence was found with regard to potassium, immunoglobulins and pH value. Considering the multifactorial effects of the urinary constituents, we found in a multivariate comparison that none of the studied physiological features alone exerts a fundamental influence upon adhesion, but in their entirety they determine the environmental conditions for the adhesion of bacteria to cells in the urine.

Adult

[Comparative studies of calcium resorption modified by vitamin D2 and D3 in patients with chronic renal failure and dialysis patients].

In 16 patients with a chronic renal insufficiency at the stage of the compensated retention and 13 test persons of the chronic haemodialysis programme determinations of the total calcium and of the ionized calcium fraction as well as investigation of the intestinal calcium absorption by means of the isotope 47Ca were performed. In these cases the influence of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) on these parameters of the calcium metabolism was compared. Under the treatment with vitamin D a normalization of the serum calcium levels concerning the total calcium concentration as well as with regard to the ionized calcium fraction was achieved; this effect took place parallel to the improvement of the intestinal calcium absorption. Vitamin D3, had a more favourable effect than vitamin D2. The necessary doses are below 40,000 U a day.

Blood Urea Nitrogen

No tissue level abnormality of vitamin A concentration despite elevated serum vitamin A of uremic patients.

In 57 patients with chronic renal failure (CRF) [44 patients on regular dialysis treatment (RDT), 33 renal transplant patients (RT) and 26 normal patients (NP)] and in a further 11 patients with CRF (8 patients on RDT and 17 patients without any renal disease in the post mortem) the vitamin A content of the serum obtained from the tissue of the liver, the stomach, the subcutaneous adipose tissue and the bone were analyzed. The vitamin A content of the serum was increased significantly for all groups of patients in comparison with the control group, but hypervitaminotic ranges were not reached in any case. The vitamin A content decreased depending on the time of dialysis treatment and the period after kidney transplantation. The retinol-binding protein accumulated even more than vitamin A in CRF and RDT. This statement is not in conformity with that of a hypervitaminosis A, of which normal respectively decreased RBP levels are characteristic. The serum prealbumin concentration was near the upper limit of the normal range in all groups of patients. The serum content of beta-carotene in patients with CRF and RDT was raised in comparison with NP and RT patients. As to the vitamin A content of the organs, a distinctive decrease appeared in the liver, so that a marginal supply must be assumed. In the stomach and the subcutaneous adipose tissue no changes, in comparison with the control patients, resulted. Due to renal insufficiency the results indicated an unphysiological situation in the vitamin A metabolism. Connections with disturbances of the fat-household could not be set up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Morphometric and histochemical studies of the skeletal muscles of patients with chronic renal failure and dialysis patients].

In 19 patients with chronic renal insufficiency in the stage of compensated retention, 20 patients undergoing dialysis and 24 patients with normal renal function muscle tissue was taken by an open biopsy and investigated histologically, histochemically as well as morphometrically. A neurogenic atrophy stood in the foreground of the histologic changes of the striated musculature in uraemia, a pure type II atrophy was found more infrequently. In the patients undergoing dialysis frequency and size of these disturbances were more distinct. Except for a possible influence of a disturbed calcium metabolism other pathogenetic factors supposed in literature could not be found.

Adult

[Desferal treatment of aluminum poisoning; effect on serum concentrations of aluminum (Al), iron (Fe) and copper (Cu)].

In 2 patients with a progressive dialysis encephalopathy and increased serum aluminium concentrations a Desferal-treatment with 500 mg per week was performed and in these cases the kinetics of Al, Fe, Cu was investigated. After the application of Desferal an increase of the serum levels, the ultrafiltrable proportion, the dialysance and the eliminated quantity of aluminium developed. In the course of the treatment in the two patients the aluminium level could be reduced to approximately normal values. Nevertheless one patient died of a severe course of a progressive dialysis encephalopathy. An increase of the copper concentration independent of Desferal-treatment after the dialysator passage remained without influence on the course of concentration of the serum copper in the examination period. A remarkable effect of the Desferal-therapy on the iron metabolism could not be established. Since in the dosage used there did not appear any side effects the Desferal-application is to characterized as a distinct and effective technique for the decrease of the serum-aluminium-concentration in patients undergoing dialysis.

Adult

[Vitamin A status of patients with chronic renal failure in relation to renal osteodystrophy].

In patients with chronic renal insufficiency and dialysis patients as well as in normal persons determinations of vitamin A in the serum and in the bone were performed and related to the parameters of the bone metabolism and to the histomorphometric investigation of the bone. The vitamin A serum levels were significantly increased in the two groups of patients, however, did not show any differences between the patients with an osteoidosis or the combination of osteoidosis and fibroosteoclasia. There were no correlations to calcium, phosphorus, PTH and to the alkaline phosphatase as well as to the individual histomorphometric data. The vitamin A content of the bone was low and did not show any differences to the normal persons. On the other hand, there were significant relations between the parathormone and the parameters of the regeneration and the absorption of the bones. An additional influence of vitamin A on the bone disturbance, eventually by the activation of the osteoclasts cannot be excluded.

Adult

[Massive corpus luteum hemorrhage in a dialysis patient].

A 17-year old patient who was continuously dialyzed due to Fanconi-anemia and bilateral renal insufficiency developed an acute and severe bleeding from a ruptured Graafian follicle (corpus luteum). The bleeding was life-threatening, most likely due to the continuous treatment with heparin necessary for hemodialysis procedure. Differential-diagnostic considerations and interdisciplinary therapeutic measurements are reported.

Adolescent