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Biomedical subjects

J Bommer

Publications and source records attributed to J Bommer.

At least 37 records · Page 2Linked to original sources

Acute effects of haemodialysis on cutaneous microcirculation in patients with peripheral arterial occlusive disease.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is an increasing problem in patients on maintenance haemodialysis. Alterations in microvascular perfusion accompany and complicate arteriosclerosis of large vessels and might contribute to the disease process. The aim of the study was to investigate the acute effects of haemodialysis on the cutaneous microcirculation in 26 patients with and without intermittent claudication. METHODS: Cutaneous perfusion was assessed by measuring transcutaneous oxygen pressure (tcPO2) and skin temperature at the dorsum of the foot. After standardized cooling to 15 degrees C of a 2cm2 skin area, the time to reach baseline skin temperature was evaluated as an indirect parameter of reactive hyperaemia. RESULTS: During haemodialysis, tcPO2 dropped significantly in both groups. The decrease in tcPO2 was more pronounced in patients with PAOD (20% vs 15% n.s.). The reactive hyperaemia response was reduced significantly in patients with intermittent claudication indicated by a prolonged time to reach baseline skin temperature after cooling. Values of tcPO2 and reactive hyperaemia did not reach baseline values at the end of haemodialysis in either group. CONCLUSIONS: Nutritive skin perfusion is impaired during haemodialysis. These changes are more pronounced in patients with PAOD and persist after dialysis. These findings are relevant for the treatment of patients with vascular disease on maintenance haemodialysis.

Adult↗

D-thyroxine reduces lipoprotein(a) serum concentration in dialysis patients.

Uremia raises lipoprotein(a) (Lp(a)) serum concentration and the risk of arteriosclerosis in dialysis patients. The treatment of high Lp(a) levels is not satisfactory today. The decrease of Lp(a) in hypothyroid patients on L-T4 therapy raised the question of whether dextro-thyroxine (D-thyroxine) reduces not only serum cholesterol, but also Lp(a) serum concentration. In a single-blind placebo-controlled study, the influence of D-thyroxine therapy on Lp(a) serum concentration was evaluated in 30 hemodialysis patients with elevated Lp(a) serum levels. Lp(a) was quantified in parallel by two methods, i.e., rocket immunoelectrophoresis and nephelometry, and apo(a) isoforms were determined by a sensitive immunoblotting technique. Regardless of the apo(a) isoforms, 6 mg/d D-thyroxine reduced elevated Lp(a) levels significantly by 27 +/- 13% in 20 dialysis patients (P < 0.001) compared with 10 control subjects (-9.9 +/- 8.4%). In parallel, D-thyroxine therapy significantly lowered total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and LDL cholesterol/HDL cholesterol ratio (P < 0.01); raised T4 and T3 serum levels; and suppressed thyroid-stimulating hormone secretion without causing clinical symptoms of hyperthyroidism in any of the patients. D-Thyroxine reduces elevated serum Lp(a) concentration in dialysis patients. The effect in nondialysis patients can be expected but remains to be proven.

Aged↗

Potential transfer of endotoxin across high-flux polysulfone membranes.

It has been postulated that synthetic membranes, such as polysulfone membranes, are rather impermeable for endotoxin or endotoxin fragments and can be used for sterile filtration of dialysate. It has never been investigated, however, whether endotoxin permeability may be different in commercially available polysulfone membranes. In vitro, we found a significantly different permeability for endotoxin in two standard dialyzers and one test dialyzer with high-flux polysulfone membranes. In contrast to the F-60 dialyzer with a very low permeability for endotoxin, a stepwise increasing load of endotoxin concentration in the dialysate compartment of the PN 1913 test dialyzer and Primus 1350 polysulfone dialyzer was followed by a stepwise increase of endotoxin in the blood compartment. A significant transfer across the membranes was found when the endotoxin concentration in the dialysate compartment was > 10 ng/mL in the PN 1913 and > 0.5 ng/mL in the Primus 1350. In the latter, about 0.5% of the endotoxin concentration of the dialysate compartment was found in the blood compartment. The data suggest that manufacturers have to evaluate the performance and other properties of their synthetic membranes in detail.

Biocompatible Materials↗

Arteriosclerosis in dialysis patients.

Arteriosclerosis is a constant problem in long-term hemodialysis patients. Computer tomography of the abdominal aorta allows a well-defined and reproducible evaluation of aortosclerosis. In the cross-sectional study, aortosclerosis was significantly accelerated in 84 chronic hemodialysis patients and was comparable to the results found in 20-year older control patients without renal disease. The increase of aortosclerosis correlated significantly with age of the patient, smoking, and duration of dialysis therapy. Furthermore, increased VLDL cholesterol and decreased HDL cholesterol seem to enhance aortosclerosis in our dialysis patients. In the longitudinal study (two CT scans with a time interval of 87 +/- 62.7 months) in 36 dialysis patients, progressed aortosclerosis correlated significantly with the long duration of hypertriglyceridemia, VLDL cholesterol, uric acid, and calcium phosphate products. Progression of aortosclerosis was reduced in parathyroidectomized patients. The study suggests that premature aortosclerosis is found in dialysis patients. In addition to the common risk factor of aortosclerosis disturbed calcium phosphate and parathyroid hormone metabolism seem to enhance aortosclerosis in patients under maintenance hemodialysis.

Adult↗

Apolipoprotein E phenotypes and hyperlipidemia in patients under maintenance hemodialysis.

Apolipoprotein E phenotypes and gene frequencies were determined in 560 patients receiving long-term hemodialysis. In addition, fasting plasma lipid- and apolipoprotein-concentrations were evaluated in 245 of these individuals. The distribution of the three major apolipoprotein E alleles (epsilon 4, epsilon 3, and epsilon 2) and that of the six common apolipoprotein E phenotypes (E4/4, E3/3, E2/2, E4/2, E4/3, and E3/2) in the dialysis group was nearly identical to that of healthy controls. Patients with the apolipoprotein E phenotypes E2/2, E4/4 and E4/3 (comprising 24% of the whole group) had higher mean plasma cholesterol- and triglyceride-concentrations than those with the apolipoprotein E phenotypes E3/3 and E3/2 (72% of the whole group). Thus, the genetic polymorphism of apolipoprotein E may contribute to the individual risk of accelerated atherosclerosis in patients under maintenance hemodialysis.

Adult↗

Severe type III hyperlipoproteinemia in two patients maintained on chronic hemodialysis.

Two patients with severe hyperlipidemia receiving long-term hemodialysis were classified as type III hyperlipoproteinemic subjects. They are homozygous for apolipoprotein E2 and have an elevated VLDL-cholesterol/plasma-triglyceride ratio. The dyslipoproteinemia was severely aggravated by the renal failure, but careful treatment with bezafibrate was able to effectively lower elevated serum lipids. Accurate diagnosis of lipid abnormalities in patients with chronic renal failure seems to be necessary to plan appropriate therapeutic interventions and to lower the risk for accelerated atherosclerosis.

Apolipoproteins E↗

Fluid phase generation of terminal complement complex as a novel index of bioincompatibility.

Blood membrane interactions in hemodialysis have been shown to trigger complement (C) activation. As indicators of C-activation the anaphylatoxins (C3a and C5a) are problematical because of methodological difficulties and their kinetic properties. We developed a sensitive and specific micro-ELISA using a monoclonal antibody against neoantigens on the terminal complement complex (TCC); highly purified human TCC served as standard. Concentrations of TCC were measured in single-path perfusion systems (in vitro) and in the blood lines (arterial inlet; venous outlet) of patients on hemodialysis using steam-sterilized or ETO-sterilized dialyzers with the following membranes: cuprophan (CU), hemophan (HE) and polysulfone F6 (PS), respectively. All dialyzers with identical geometry were run under identical conditions. All membranes tested caused continuously ongoing net generation of TCC. In vitro, contact of serum with CU minidialyzers resulted in fivefold higher net release of TCC compared with HE and PS. In vivo TCC concentration-time profiles differed significantly between membranes in the rank order CU much much greater than HE greater than PS (mean basal concentration 58 x 10(-11) M; peak increase over baseline with CU 40-fold, HE fourfold, PS threefold). In addition, more TCC was generated from the same dialyzers with ETO than steam sterilization. TCC differed from C3a and C5a in the following respects: (i) lower detection limit (4 x 10(-11) vs. less than 5 x 10(-9) M for both C-anaphylatoxins); (ii) higher relative increment (inlet) during CU dialysis (25-fold vs. eightfold and twofold, respectively); (iii) C-anaphylatoxins yielded the same ranking (CU much greater than HE greater than PS), but TCC concentrations were not a linear function of C3a or C5a concentrations, respectively. Kinetic analysis (Bateman function) showed significant differences of invasion constants between membranes, that is, CU 0.088 min-1, HE 0.09, PS 0.168. The net amount of TCC released from the dialyzer was calculated under certain assumptions. It was 75.5 mg/4 hr for CU, 7.3 for HE and 5.0 for PS. The elimination constant was also dependent on the type of membrane. Using flow cytofluorometry and immunohistochemical methods (APAAP), TCC was demonstrated on membranes of granulocytes obtained during dialysis; this is compatible with potential in vivo cell activation. Generation of PGE2 and TNF alpha by adherent monocytes induced by cuprophan was C8 dependent: levels were significantly increased by addition of C8 to C8 deficient human serum concomitantly with generation of TCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improved sexual function during recombinant human erythropoietin therapy.

In seven male haemodialysis patients, living with a constant sexual partner, sexual life (self-administered questionnaire) and sex hormones were evaluated before and 3 or 10 months after commencement of recombinant human erythropoietin (rHuEpo) therapy respectively. Haematocrit increased from 22.2 +/- 2.1% to 30.6 +/- 1% with a maintenance dose of 140 +/- 55 U/kg per week. Two patients were hypertensive before and after rHuEpo therapy; antihypertensive medication was kept constant during the study. Self-reported sexual function improved in four of seven patients, including libido and erection. This was paralleled by improved indices of wellbeing (physical fitness, mental alertness). In contrast, serum values of sexual hormones (testosterone or oestradiol) and of basal and stimulated (LHRH/TRH), prolactin and LH, and FSH were not significantly changed during rHuEpo therapy.

Adult↗

Particles from dialysis tubing stimulate interleukin-1 secretion by macrophages.

Loading of tissue macrophages with dialysis-tubing-derived particles may occur during chronic haemodialysis. Previous studies have demonstrated that these particle-laden macrophages release significant quantities of prostaglandins. In these experiments, the effects of dialysis-tubing-particle loading on the release of the central inflammatory mediator, interleukin 1 (IL 1), was examined. Rats received daily injections of silicone or polyvinylchloride (PVC) particles, and were compared to animals given saline alone. The silicone and PVC groups received a total of 3 x 10(9) particles over a 4-week period. Non-stimulated peritoneal macrophages from control animals released a median of 4.1 (range 1.2-10.3) U IL 1 per 10(6) cells. In contrast, macrophages from silicone- and PVC-loaded animals spontaneously released high levels of IL 1 (median 21.8; range 10-36.7) and 94 (range 36-336) U per 10(6) cells respectively). Following in vitro stimulation with bacterial lipopolysaccharide (LPS), peritoneal macrophages from silicone- and PVC-treated animals released large amounts of IL 1 (median 538 (range 359-2017) U and median 653 (range 326-1134) U per 10(6) cells, respectively) as compared to LPS-stimulated macrophages from control animals (median 332 (range 130-306) U per 10(6) cells]. Zymosan or LPS stimulation of splenic cells from silicone- and PVC-loaded animals also secreted increased quantities of IL 1 as compared to controls. The chronic loading of tissue macrophages in dialysis patients with tubing-derived particles may result in augmented release of IL 1, with subsequent activation of inflammatory processes.

Animals↗

Doppler echocardiographic findings in dialysis patients.

We used Doppler echocardiographic techniques firstly to examine left ventricular (LV) filling patterns in dialysis patients, secondly to analyse whether Doppler echocardiographic left ventricular filling pattern is different in patients with recurrent intradialytic hypotension, and thirdly to study the relation between blood pressure decrease during volume subtraction and left ventricular filling pattern. Indices of left ventricular filling patterns of 47 dialysis patients were consistently different when compared to normotensive healthy controls. To further assess the relation of left ventricular filling pattern to blood pressure stability on dialysis, we first compared 24 patients with stable intradialytic blood pressure (BP) and 23 patients with one or more episodes or intradialytic hypotension per month. Patients with recurrent intradialytic hypotension had lower predialysis blood pressure (MAP 89 +/- 13 vs 96 +/- 14 mmHg), more severe concentric hypertrophy (left ventricular mass/volume ratio 2.7 +/- 1.4 vs 2.0 +/- 0.7), and impaired left ventricular filling (Doppler) as indicated by the ratio of early diastolic vs late (atrial) filling (0.66 +/- 0.2 vs 0.95 +/- 0.22). Subsequently we assessed by Doppler technique the effect of a predetermined rate of volume subtraction (during one dialysis session) in patients with or without recurrent intradialytic hypotension. Diastolic filling indices deteriorated consistently prior to the reduction in blood pressure (early diastolic filling 26.8 +/- 15.2 vs 45.4 +/- 10.9% of diastolic filling). It is suggested that impaired left ventricular filling, presumably reflecting disturbed left ventricular compliance, is common in dialysis patients. Findings by noninvasive Doppler techniques suggest a role of abnormal left ventricular distensibility in recurrent dialysis hypotension.

Adult↗

Mechanisms of improved physical performance of chronic hemodialysis patients after erythropoietin treatment.

Correction of the anemia that is common among chronic hemodialysis patients by treatment with human recombinant erythropoietin (rHuEPO), even if incomplete, improves physical performance of patients. Oxygen uptake and physical work capacity at maximal work loads and at the anaerobic threshold increase by approximately 20%. Analysis of underlying mechanisms by pulmonary function tests and ergospirometry demonstrate that improved oxygen transport in the blood and its concomitant changes of the anaerobic threshold and heart rate appear to be main causes of improvement. Parameters of respiratory mechanics and gas exchange remain essentially unaltered.

Adult↗