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Biomedical subjects

J Bommer

Publications and source records attributed to J Bommer.

At least 19 recordsLinked to original sources

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

[Vitamin D metabolism in kidney insufficiency: disorders of an endocrine regulatory zone].

The vitamin metabolite 25(OH)D is transformed into the active secosterole 1.25(OH)2D3 in the proximal tubular epithelium of the kidney. This transformation is disturbed in patients with renal insufficiency. However, this review shows that presumably not all vitamin D dependent disturbances in patients with renal insufficiency are explicable merely as the consequence of reduced renal synthesis of 1.25(OH)2D3 secondary to nephronal loss. In incipient renal failure, vitamin D dependent functions (calcemic action of PTH, intestinal absorption of Ca) are disturbed. Yet, circulating 1.25(OH)2D3 levels are slightly elevated. This finding is compatible with an inadequate response of the renal 1-alpha-hydroxylase system to activating stimuli (hyperparathyroidism, hypocalcemia, fasting hypophosphatemia) and/or end-organ resistance to the action of 1.25(OH)2D3. Osteomalacia in renal insufficiency cannot entirely be explained as the consequence of a reduction of the serum-concentration of any of the known vitamin D metabolites [25(OH)D3; 1.25(OH)2D3; 24.25(OH)2D3]. The relatively poor response of osteomalacia of uremic patients to the administration of 1.25(OH)2D3 leads to the question of whether other vitamin D metabolites or non-vitamin D related factors are important in its genesis. Critical information is lacking with respect to 1.25(OH)2D3 receptors, post receptor events and interaction between vitamin D metabolites and PTH in bone cells of such patients. A specific action of 1.25(OH)2D3 on longitudinal growth of uremic children has been described. However, several clinical and experimental studies failed to provide evidence of normalization of growth by 1.25(OH)2D3 and failed to show differences in this respect between vitamin D and 1.25(OH)2D3. Currently, it remains undecided whether vitamin D metabolites affect PTH secretion, and if so which vitamin D metabolite is involved. Clarification of this problem is of paramount importance for the therapeutic suppression of the parathyroids of uremic patients. Vitamin D metabolites play an important role in some organ functions unrelated to homeostasis of Ca-Pi-metabolism (e.g. muscle, testis, pancreas, etc). The loss of such function is of potential importance in the genesis of the uremic syndrome and its imcomplete reversal by hemodialysis.

Absorption

Improved sexual function in male haemodialysis patients on bromocriptine.

The effect of bromocriptine on sexual activity was studied in male haemodialysis patients in a single-blind placebo controlled trial with random cross-over. At a dose of 2.5 mg bromocriptine twice day, plasma-prolactin concentrations were consistently reduced, while sexual function as assessed by a questionnaire was markedly improved. At the doses used, side-effects, particularly hypotension, were common, but bromocriptine helped to restore sexual function in dialysed patients.

Bromocriptine

Urinary matrix calculi consisting of microfibrillar protein in patients on maintenance hemodialysis.

In seven patients on maintenance hemodialysis, de novo recurrent renal stone formation was observed. In all patients, the underlying disease was glomerulonephritis, with or without the nephrotic syndrome. All patients had considerable persistent proteinuria. The stones consisted predominantly of protein, as revealed by amino acid analysis, and had a negligible carbohydrate and lipid content. Only in some specimens, X-ray diffraction and scanning electron microscopy revealed the presence of small amounts of whewellit (calcium oxalate monohydrate) and/or uric acid. In semithin sections, the stones had a laminated texture and exhibited structural anisotropy under polarized light. With transmission electron microscopy, they were found to consist of peculair microfibrils. The proteinaceous material differed from fibrin or Tamm-Horsfall-protein, as indicated by ultrastructure, carbohydrate analysis, and amino acid analysis. Symptomatic de novo matrix stone formation constitutes another complication of dialyzed patients which has not been reported so far.

Adult

Skeletal X-ray findings and bone histology in patients on hemodialysis.

X-ray films of the hand skeleton (mammography technique), serum chemistry, and quantitative bone histology (micromorphometry of undecalcified sections, iliac crest spongiosa) were compared in 25 patients on maintenance hemodialysis. The X-ray findings correlated better with serum PTH levels than with bone histology. Of all radiological signs of renal osteodystrophy, pronounced subperiosteal resorption (radial aspect, second finger, middle phalanx) and periosteal new bone formation (middle phalanx) correlated best with histological indicators of osteitis fibrosa. These signs were never seen in control patients. Acroosteolysis (endphalanx) and intracortical or endosteal resorption (middle phalanx) were less specific (i.e., seen even in the absence of metabolic bone disease) and correlated less with bone histology. Osteosclerosis in iliac cancellous bone was paralleled by abnormal texture of spongy bone in the proximal metaphysis of the middle phalanx (second finger).

Adult