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Biomedical subjects

H K Stummvoll

Publications and source records attributed to H K Stummvoll.

At least 19 recordsLinked to original sources

[Aerobic and anaerobic capacity of chronic hemodialysis patients under continuous therapy with recombinant human erythropoietin].

In earlier studies we have shown that partial correction of anemia by recombinant human erythropoietin (r-HuEPO) already after 12 weeks results in a significant increase of exercise capacity in patients on chronic hemodialysis. As causative effect increased oxygen availability with improved oxygen delivery to the tissues was assumed. To elucidate the long-term effects of a partial correction of anemia with r-HuEPO on exercise capacity, oxygen uptake at maximum exercise and at the anaerobic threshold was measured by repetitive spiroergometry. Measurements were done before, 3 months and 6 months after initiation of r-HuEPO therapy. The results are summarized below: (table; see text) Our results show that a long-term improvement of peripheral oxygen availability leads to a further increase of anaerobic threshold in patients on chronic hemodialysis even without a further increase of hemoglobin levels and without exercise training. It appears that elimination of the chronic hypoxic condition results in a restoration of previously diminished mitochondrial enzymes in muscle, particularly for aerobic glycolysis. Besides acute improvement of aerobic and anaerobic exercise capacity, the long-term administration of r-HuEPO with its increased anaerobic threshold enhances the patients' everyday life working capacity.

Erythropoietin

[Ethylene oxide-induced antibodies and hypersensitivity reactions in hemodialysis].

The presence of antibodies against ethylene oxide, which is used for sterilization of dialyzers, was evaluated in 52 hemodialysis patients (30 male, 22 female). The aim of the prospective study was to evaluate a possible correlation of these antibodies with hypersensitivity reactions during hemodialysis. By means of a radio-allergo-sorbent-test (RAST) only 3.9% (2 patients) were detected to have ethylene oxide antibodies. There was no significant correlation between antibodies on the one hand, and symptoms, eosinophilia and IgE-elevation on the other hand. We could not find ETO-induced hypersensitivity reactions in our study population. Thorough rinsing and sufficient storage time of the dialyzers might be the reasons for these findings.

Adult

Working capacity is increased following recombinant human erythropoietin treatment.

To investigate the effect of partial correction of anemia in patients maintained by chronic intermittent hemodialysis on aerobic and anaerobic working capacity, eight patients underwent a bicycle spiro-ergometry before and after treatment with recombinant human erythropoietin (r-HuEPO). the initial mean (+/- SD) hemoglobin value was 5.9 mg/dl +/- 0.61 and increased during treatment to 10.9 +/- 0.59 mg/dl, P less than 0.0001). This partial correction of anemia resulted in a significant increase of both oxygen uptake at the anaerobic threshold and peak peripheral oxygen uptake at subjective exhaustion (P less than 0.01 and P less than 0.0002, respectively). The increase in oxygen uptake corresponded to significant increases in Watts, both at the anaerobic threshold and at maximum workload (P less than 0.02 and P less than 0.0004). These data show that partial correction of renal anemia results in a significant increase of both exercise capacity and maximum work.

Adult

Acute oliguria associated with chlorprothixene overdosage.

The occurrence of acute reversible oliguria is described in a 23-year-old male after ingestion of 1,500 mg of chlorprothixene in a suicidal attempt. In contrast to earlier reports hypothesizing that the pathophysiology of the renal insufficiency associated with chlorprothixene intoxication may be attributed to direct nephrotoxic effects of the compound or to ischaemia owing to transitory unrecognized shock, a careful diagnostic work-up including renal biopsy, disclosed the presence of acute interstitial nephritis.

Acute Disease

[Effectiveness of recombinant human erythropoietin in the treatment of transfusion-dependent anemia in patients on chronic dialysis].

Recombinant human erythropoietin (r-HuEPO) has recently become available for clinical trial and has been used for the first time in Austria for the treatment of transfusion dependent patients on chronic haemodialysis. Inclusion criteria into the study were baseline haemoglobin levels of less than or equal to 6 g/dl and transfusion requirements of greater than or equal to 1 unit of blood per month. r-HuEPO (CILAG/AMGEN/ORTHO) was administered intravenously 3 times weekly at the end of dialysis. The initial dose was 100 U/kg body weight at each administration and was increased by 25 U/kg if Hb levels failed to increase by greater than 5% of baseline at intervals of 3 weeks. All 9 patients studied showed an increase in Hb values to the desired value at least greater than or equal to 10 g/dl within 6 to 16 weeks and none of the patients required further blood transfusions. All patients reported subjective improvement of life quality and markedly increased working ability. Apart from minor episodes of bone pain and subfebrile temperatures after r-HuEPO administration no major side effects were noted. These preliminary results show that r-HuEPO (CILAG/AMGEN/ORTHO) is a safe and effective form of therapy for renal anaemia and one which opens new horizons in the management of patients on chronic haemodialysis.

Anemia

Abnormalities in the hypothalamic-pituitary-adrenocortical axis in patients with chronic renal failure.

The recently described human corticotropin-releasing factor was administered to eight patients with chronic renal failure in order to assess hypothalamic-pituitary-adrenocortical (HPA) function. Acute administration of corticotropin-releasing factor lead to a diminished increase of the basally elevated levels of ACTH and beta-endorphin immunoreactivity in patients on chronic hemodialysis. Basal plasma cortisol concentration was normal in end-stage renal disease; however, considering the corresponding elevated ACTH concentrations, cortisol levels were inadequately low. Thus, the hypothalamus as well as the adrenal gland seems to contribute to the alterations in HPA function observed in patients with chronic renal failure; involvement of the pituitary gland and effects of metabolic alterations cannot be ruled out.

Adrenocorticotropic Hormone

Blood-membrane interaction in hemodialysis leads to increased cytokine production.

Recently much interest has been focused on the role of immunoregulatory cytokines such as interleukin 1 (IL 1) and interleukin 2 (IL 2) during the pathogenesis of immunological as well as inflammatory diseases. Therefore peripheral blood mononuclear cells (PBMC) of eight patients undergoing hemodialysis (HD) were tested for IL 1 and IL 2 production. Before starting HD, cytokine production by PBMC in culture was not altered in comparison to normal healthy controls, however, a significant increase of IL 1 and IL 2 production was observed within the first HD hour which lasted throughout the end of HD. Moreover direct effects of cellulose membranes on PBMC cytokine production as well as serum IL 1 levels have been investigated. Serum IL 1 levels were already elevated before onset of HD and increased further during HD. The discrepancy between PBMC IL 1 production and serum IL 1 levels may be due to the diminished excretion in patients with end-stage renal disease. Since addition of dialysis membrane particles enhanced monocytes to produce more IL 1 as well as lymphocytes to release more IL 2, a direct stimulatory membrane effect is postulated. The increased release of immunoregulatory cytokines may account for some of the pathologic findings observed during hemodialysis.

Adult

[Clinical value of endotoxin determination in infection. Comparison of the Limulus amebocyte lysate test with detection of bacterial pathogens].

To evaluate usefulness of Limulus amoebocyte lysate test and blood culture in the diagnosis of septicemia both tests were performed in 27 intensive care patients. Test results were compared with a clinical sepsis score. Ten (62%) out of 16 patients with clinical diagnosis of septicemia showed a positive endotoxin test and 11 (69%) a positive blood culture. In 14 patients (87%) either endotoxin test or blood culture revealed a positive result. Two out of 11 patients (20%) classified by the sepsis score as non-septic showed positive blood cultures as well as positive endotoxin tests. 4 patients with gram-positive bacteria in the blood cultures showed a positive endotoxin test. Due to lack of sensitivity and specificity the Limulus amoebocyte lysate test is of rather low value in the diagnosis of septicemia. Simultaneous performance of Limulus amoebocyte lysate test and blood culture is able to improve the sensitivity, which then over-rules the one obtained when only blood cultures are performed.

Bacteria

Decreased serum interleukin 1 activity and monocyte interleukin 1 production in patients with fatal sepsis.

The role of interleukin 1 (IL 1) in 16 patients with sepsis and 16 normal controls was investigated. Thymocyte costimulation was used to assay in vitro IL 1 levels produced by adherent cells in the peripheral blood, and in vivo IL 1 levels in the serum. Adherent cells (i.e., monocytes) from nonsurviving septic patients produced significantly less IL 1 activity than cells from healthy controls or surviving patients, either spontaneously or by silica stimulation. In contrast, in vitro IL 2 production by T lymphocytes was not altered in septic patients. Serum IL 1 activity was determined using serum fractions from high-pressure liquid chromatographic gel filtration. Suppressor factors in healthy subjects as well as septic patients usually eluted at molecular weights above 50 kilodaltons, while IL 1-like activity was normally present between 35 and 1 kilodaltons. Sera of nonsurviving septic patients contained significantly less IL 1 compared to that of controls or surviving patients. Thus, decreased serum IL 1 levels and diminished monocyte production of IL 1 appear to be negative prognostic indicators, possibly reflecting a breakdown of mononuclear phagocytes.

Adult

Center-specific variations of thyroid hormone serum levels in hemodialysis patients.

Thyroid hormone (free and total thyroxine, total 3,5,3'- and 3,3'5'-triiodothyronine, thyroxine-binding globulin, thyrotropin) serum concentrations were measured in 107 uremic patients of 4 hemodialysis centers, in order to study the prevalence of hypothyroidism in hemodialysis patients. In accordance with the clinical impression there was no laboratory evidence of thyroid dysfunction. In spite of the fact that all patients had the expected low-T3 syndrome, there were highly significant differences between the mean thyroid hormone concentrations of the 4 different centers. The center with the highest thyroid hormone levels (all normal except for borderline low 3,5,3'-triiodothyronine) also had the lowest urea levels, indicating the relatively best metabolic control. One center had significantly lower hormone levels than the other 3 centers (all hormones except free thyroxine were below normal) with urea levels that did not differ significantly from one of these centers. A retrospective analysis of patients and of the techniques of dialysis of 3 centers excluded factors like heparin or the length of time on dialysis to be the reason for the low values of this center. Finally, only the significantly higher proportion of unsuccessfully transplanted patients and some technical differences (lack of water treatment, regenerated cellulose as dialyser membrane, and low magnesium content in the dialysate) unique for this center remained as possible factors that may speculatively explain the observed low thyroid hormone values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Radioimmunoassay of atrial natriuretic peptides in human plasma.

The concentration of atrial natriuretic peptide (hANP) in plasma from venous blood of healthy subjects was measured by radioimmunoassay. hANP from 5 mL of EDTA-treated plasma was adsorbed onto Sep-Pak C18 cartridges, which were eluted with methanol/trifluoroacetic acid (5 mL/L), 90/10 by volume. The eluates were concentrated by evaporation under nitrogen and lyophilized. After redissolving the samples in 0.5 mL of sodium phosphate buffer, we incubated 100-microL aliquots with anti-alpha-hANP for 24 h, then added 125I-labeled alpha-hANP tracer; 24 h later, we separated the bound and free fraction by adding an antibody/polyethylene glycol complex as the second antibody. The sensitivity of the assay was 2 pg per tube (B0-3 SEM). In the useful range of B = 15 to 85% of B0, CVs for within-run and between-run precision did not exceed 8 and 12%, respectively. The 50% intercept of the standard curve was at 12 pg per tube. hANP concentrations for 36 healthy adults ranged from 8 to 68 ng/L.

Adult

A new algorithm for individual dialysis prescription based on urea kinetics.

Methods for calculating required dialysis time to maintain certain blood urea nitrogen levels predialytically thus far have neglected the influence of ultrafiltration during hemodialysis and of weight changes in the interdialytic period. We therefore have developed a new algorithm for individual dialysis prescription based on urea kinetics which further optimizes accuracy of dialysis prescription by considering these two factors. The accuracy of this new method was proven in a prospective follow-up of 3 patients during some 9 consecutive hemodialysis session. It was found that there was a very close relation between the measured and the predicted values of blood urea nitrogen, the difference being only due to variations in dietary protein intake as the patients were kept on liberal food intake. The new algorithm is easily implemented into a pocket calculator and thus can be used under arbitrary dialysis conditions.

Algorithms

[Individual dialysis using computer-controlled prescription].

The use of urea kinetics as basis for optimization and individualization of renal replacement therapy has become quite popular over the last decade. The rationale underlying the use of blood urea nitrogen for monitoring or targeting dialysis therapy is based on the report of an American multicentre cooperative dialysis study showing that blood urea nitrogen concentrations are closely correlated to the occurrence of morbidity and complications in dialysis patients. In order to further optimize the accuracy of dialysis prescription we have developed a new algorithm for estimation of the dialysis time needed to reach a certain blood urea nitrogen concentration, which--in contrast to all methods employed so far--enables accurate calculation of ultrafiltration during haemodialysis and of weight changes in the interdialytic period.

Blood Urea Nitrogen

[Intrapulmonary percussion. A new method of respiratory therapy].

Intrapulmonary percussion with a high-frequency jet system is a new method in the treatment of respiratory impairment. It imitates the conventional percussion massage of the thorax by introducing high-frequency gas oscillations (300 impulses per minute) into the tracheobronchial system. In 14 patients with abnormal alveolo-arterial oxygen differences due to bronchial mucostasis ventilation was satisfactorily improved by its application.

Humans

Iron removal by desferrioxamine in patients on chronic hemodialysis--kinetic study and long-term results.

Serum ferritin levels, cumulative number of administered blood transfusions, number of monthly transfused blood units and total months on hemodialysis (HD) treatment differed significantly in 7 patients on hemodialysis with clinical, biochemical and histological evidence of hemosiderosis, when compared to 37 controls (p less than 0.001 for all parameters). As a new treatment method desferrioxamine (DFO) therapy was introduced for iron detoxification in these hemosiderotic chronically hemodialyzed patients. Hence, to maximize the biological half-time, 30 mg/kg body weight DFO were given after the end of HD in the iron-loaded patients. Iron removal during the subsequent HD and the increase of iron excretion by the stool after DFO was measured by atomic absorption spectroscopy. Iron removal by the artificial kidney was calculated by investigating the function (QDi + QF)CDo over the duration of HD treatment, which equals the total amount of iron removal during HD. Using numerical integration of measured data this removal was found to be 21.8 +/- 6.9 mg whereas cumulative iron loss via the feces was found to be 36.5 +/- 14.6 mg. Therefore, total iron elimination was calculated to be on average 50-60 mg after administration of a single dose of DFO. Furthermore, long-term treatment of 5 patients resulted in a significant decrease of serum ferritin levels from 2,309 +/- 295 to 715 +/- 177 ng WHO/ml (p less than 0.001) after a period of 36 +/- 5 months. We conclude, that DFO in a dosage of 30 mg/kg body weight given at the end of HD is able to remove more than 500 mg iron/month if it is administered following each HD. Long-term results indicate negative iron balance without significant change of transfusion frequency if not more than 2 U of blood (500 mg iron) are administered within 1 month. This treatment schedule might be superior compared to the previously used methods of administration where DFO was given at the beginning or throughout HD.

Adolescent