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Biomedical subjects

P Kurz

Publications and source records attributed to P Kurz.

17 recordsLinked to original sources

Evidence for abnormal calcium homeostasis in patients with adynamic bone disease.

To investigate whether the derangements in calcium kinetics in patients with renal osteodystrophy are similar in the various histologic forms of this metabolic bone disease, 43 patients on chronic maintenance dialysis underwent calcium kinetic studies using the double isotope technique, iliac crest bone biopsies for mineralized bone histology and histomorphometry and determinations of serum indices of calcium and bone metabolism. Intestinal calcium absorption was not different among the three histologic groups. However, women exhibited lower calcium absorption in each histologic form (P < 0.01). Patients with predominant hyperparathyroid bone disease showed plasma calcium efflux, calcium accretion rate and calcium retention markedly above normal values. Patients with low turnover bone disease exhibited a normal or slightly decreased plasma calcium efflux and calcium accretion rate together with a disproportionately low calcium retention. Patients with mixed uremic osteodystrophy presented with a calcium kinetic profile intermediary to the two other forms. Good relationships existed between plasma calcium efflux, calcium accretion rate, calcium retention and histomorphometric parameters of bone turnover as well as serum levels of parathyroid hormone. However, no serum parameter could indicate with certainty the underlying bone disease. These findings demonstrate that adynamic bone disease does not merely represent an academic finding but is characterized by a very low bone capacity to buffer calcium and inability to handle an extra calcium load. This is particularly relevant for the daily care of end-stage renal failure patients presently receiving higher than ever amounts of vitamin D and calcium salts.

Adolescent

Effect of recombinant human erythropoietin on iron balance in maintenance hemodialysis: theoretical considerations, clinical experience and consequences.

Iron deficiency is the main reason for insufficient response to rEPO therapy. Serum ferritin and transferrin saturation give valuable information on storage iron and iron transport. Iron demand for correction of anemia can easily be estimated after HCT (vol%) x average blood volume (dl) = mg iron. Inadequate iron supply of the bone marrow in the presence of sufficient storage iron in the RES develops frequently under rEPO, possibly explaining the improvement of bone marrow response to rEPO by concomitant intravenous iron supply. The reasons of functional iron deficiency are still speculative.

Anemia

Bactericidal activity of human peritoneal macrophages from patients undergoing peritoneal dialysis.

Peritoneal macrophages (PM) play an essential role in the pathogenesis of bacterial peritonitis, the main complication of peritoneal dialysis (PD). We determined the antibacterial activity of PM from 31 PD patients using gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative (Escherichia coli, Pseudomonas aeruginosa) test organisms. In an 8-hour test assay, PM revealed the highest antibacterial activity against E. coli [median bactericidal index (Bi) = 5.46 representing 0.74 log growth inhibition compared to controls] and the lowest against P. aeruginosa (Bi = 1.63, 0.21 log growth inhibition, p less than 0.05). The antibacterial activity against S. aureus (Bi = 1.99, 0.3 log growth inhibition) and S. epidermidis (Bi = 2.0, 0.31 log growth inhibition) was within this range. When compared to peripheral blood polymorphonuclear leukocytes, PM reached only 4% (S. aureus) and 8.1% (E. coli) of their antibacterial activity (p less than 0.05). Using E. coli as a test organism, PM isolated after a 4-hour dialysis period revealed the highest antibacterial activity when compared to PM isolated after longer dialysis periods (p less than 0.05). Increasing the duration of PD to 6 and 8 h subsequently decreased the antibacterial activity of PM, suggesting that unphysiologic concentrations of toxic metabolites in the peritoneal effluent might have a harmful influence on PM functions.

Bacteria

CAPD in elderly patients with cardiovascular risk factors.

Twenty-nine elderly patients (greater than 70 years) on CAPD treatment were compared with 30 younger patients (less than 55 years). Biochemical parameters did not differ between the two groups, apart from blood sugar which was higher in the older patient group. Ultrafiltration rates were almost identical. CAPD-specific complications also did not differ in the two patient groups. Arterial hypertension was well-controlled on CAPD and the proportion of patients requiring antihypertensives fell significantly. 8% of the old patients and 52% of the young patients required antihypertensive medication after 12 months of therapy compared to 38% and 81% before commencement of CAPD. Improvement of hemodynamic parameters was especially pronounced in older patients, who had cardiac risk factors in a high percentage of cases. Age and cardiac risk factors had the highest impact on the outcome, thus explaining the higher mortality in the older patient group. Older patients with renal insufficiency can be treated with CAPD leading to equally good results as those documented for younger patients.

Actuarial Analysis

Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses.

We investigated impaired cellular immune responses of individuals on chronic hemodialysis by using monoclonal antibodies that trigger differential pathways of T cell activation. Reduced cellular reactivity, which exists in a high proportion of such patients, can be attributed to a failure of the monocyte population to support the process of primary T cell activation in vitro. This defect results in a lack of interleukin 2 production, which is critically dependent on a monocyte-derived signal. In contrast, T lymphocyte function was found to be physiologic. Perhaps more important, the degree of monocyte dysfunction in vitro correlated with the same patients' in vivo responses to hepatitis B vaccination. Addition of recombinant human interleukin 2 fully reconstituted their deficient immune response in vitro.

Adult

Impaired cellular immune responses in chronic renal failure: evidence for a T cell defect.

Cellular immune responses in vitro were studied in 24 patients on chronic hemodialysis and 16 healthy volunteers with normal kidney function. Patients on maintenance hemodialysis had lymphopenia with diminished numbers of both T4+ and T8+ T-lymphocytes. The T4/T8 ratios were within the normal range. Peripheral blood lymphocytes (PBL) showed a diminished proliferative response upon stimulation with concanavalin A, phytohemagglutinin and pokeweed mitogen. When cell surface antigens were used for stimulation (mixed lymphocyte culture) uremic lymphocytes also showed a lower proliferation rate. Although without statistical conformation, there was a tendency by uremic PBL to produce less IL-2 as compared to healthy controls. Moreover, in a PWM driven system, peripheral blood lymphocytes from uremics produced significantly less IgG than PBL from normals. These results support the notion that a profound defect in lymphocyte function accounts at least, in part, for the observed immunodeficiency of uremic patients.

Adult

Alterations in microsomal drug metabolism and heme oxygenase activity in isolated hepatic parenchymal and sinusoidal cells in Murphy-Sturm lymphosarcoma-bearing rats.

Previous studies have demonstrated that Murphy-Sturm lymphosarcoma-bearing rats have significantly decreased hepatic microsomal cytochrome P-450 and NADPH-cytochrome c reductase activity, a consequent decreased capacity for oxidative microsomal drug metabolism, and increased microsomal heme oxygenase activity. Splenic microsomes obtained from tumor-bearing rats did not display similar changes. To define the cellular locus of these changes, preparations of hepatic parenchymal and hepatic sinusoidal cells were obtained from control and Murphy-Sturm lymphosarcoma-bearing rats and examined for alterations in microsomal parameters of drug metabolism and heme oxygenase. In hepatic parenchymal cell populations, heme oxygenase activity was significantly increased in tumor-bearing rats (0.046 nmol/mg/min vs. 0.019 nmol/mg/min, control, p less than 0.01) while other microsomal parameters were all significantly decreased in activity (cytochrome P-450, 0.25 nmol/mg vs 0.70 nmol/mg, control, p less than 0.001; NADPH-cytochrome c reductase, 24.4 nmol/mg/min vs 42.6 nmol/mg/min, control, p less than 0.005; benzo(a) pyrene hydroxylase, 0.230 nmol/mg/min vs. 0.518 nmol/mg/min, control, p less than 0.001). These results are similar to those obtained with microsomes from whole liver. Conversely, while hepatic sinusoidal cell preparations also demonstrated increased heme oxygenase activity (0.134 nmol/mg/min vs 0.079 nmol/mg/min, control, p less than 0.01), all other hepatic sinusoidal cell microsomal parameters were not appreciably altered in tumor-bearing animals. The results indicate that the major effect of the tumor-bearing state on hepatic microsomal heme and drug metabolism is on the parenchymal cell, and not the sinusoidal cell population.

Animals

Alterations in hepatic heme and cytochrome P-450 metabolism in Murphy-Sturm lymphosarcoma-bearing rats. Implications for drug metabolism.

Previous studies have shown that tumor-bearing rats have significantly decreased hepatic microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity with, consequently, significantly decreased capacity for microsomal oxidative drug metabolism. Subsequent investigations have revealed that the rates of hepatic cytochrome P-450 apo-protein synthesis and degradation are decreased significantly and hepatic microsomal heme oxygenase activity is increased significantly in rats bearing an extra-hepatic tumor. Further studies have been done to attempt to clarify the pathogenesis and significance of these observations. Hepatic delta-aminolevulinic acid (ALA) synthetase activity in male Wistar rats declined to a nadir of 162 +/- 34 (S.E.) pmoles ALA per mg protein per 30 min 6 days following i.m. transplantation of Murphy-Sturm lymphosarcoma (vs control = 218 +/- 36 pmoles per mg per 30 min). Turnover of 3H-labeled heme in microsomal CO-binding particles (i.e. cytochrome P-450 heme) was increased significantly 8 days following i.m. transplantation of Murphy-Sturm lymphosarcoma with a T 1/2 of 5.5 hr for the fast phase of hepatic cytochrome P-450 heme disappearance in tumor-bearing rats as compared with a T 1/2 of 7 hr in control rats. Hepatic cytochrome P-450 apo-protein concentration was slightly, but not significantly, increased in Murphy-Sturm lymphosarcoma-bearing rats as compared with control rats up to 10 days following tumor transplantation. These results suggest that, in Murphy-Sturm lymphosarcoma-bearing rats, decreased microsomal cytochrome P-450 concentration is the result of both decreased cytochrome P-450 apo-protein synthesis and increased cytochrome P-450 heme turnover. Apo-cytochrome P-450 concentration was not appreciably altered because increased cytochrome P-450 heme turnover and decreased cytochrome P-450 apo-protein degradation were balanced by decreased cytochrome P-450 apo-protein synthesis. Because of their effects on cytochrome P-450 concentration and action, these alterations in heme and hemoprotein metabolism may be of importance in regulating oxidative drug metabolism in the tumor-bearing state.

5-Aminolevulinate Synthetase

Xerophthalmia in vitamin A-deficient rabbits. Clinical and ultrastructural alterations in the cornea.

Xerophthalmia developed in the eyes of rabbits maintained on a vitamin A-deficient diet for 4 to 6 months. The earliest clinical change, a lusterless graying of the central corneal epithelium, was noted after 16 to 18 weeks on the diet. Multiple small punctate epithelial erosions appeared in the interpalpebral fissure zone within 7 to 10 days after the lusterless graying became evident. The erosions gradually became confluent, and a striking dry, glazed, peau d'orange appearance was noted. Polycystic microbullae appeared in the epithelium in some eyes. Thick keratinized epithelial plaques developed in all eyes 1 to 2 weeks after the appearance of severe peau d'orange. Electron microscopy of corneas with lusterless graying of the epithelium revealed swelling of the most superficial epithelial cells with flattened and shorter microvillous projections. In corneas with punctate epithelial erosions and keratinized plaques, microvilli were absent or decreased in number on superficial cells, and multilayered, keratinized epithelial cells were present on the surface of the cornea. The stroma appeared essentially normal with minimal edema at all stages when examined by electron microscopy. Intercellular edema was present in the endothelium in early- and late-stage xerotic corneas but could not be detected clinically. No significant clinical or microscopic alterations were seen in the corneas of control rabbits on normal diet or in rabbits on the vitamin A-deficient diet supplemented with vitamin A. The alterations seen in the corneas of vitamin A-deficient rabbits are similar to those which have been described in vitamin A-deficient humans. Rabbit therefore appears to be a good model for further studies of xerophthalmia.

Animals

Factors influencing transperitoneal calcium balance during CAPD.

A dialysate containing a calcium concentration of 1.75 mmol/L has been the standard in CAPD for a long time. This concentration was chosen to achieve a positive calcium balance to suppress hyperparathyroidism. In the measurement of peritoneal calcium mass transfer, conflicting results have been published, with positive and negative calcium balances reported. These differences have been explained by differences in the filtration rate, and a negative correlation between the filtration rate and the peritoneal calcium mass transfer can be found. Whereas nearly all patients in this study had a negative calcium balance using a glucose solution of 3.86%, a wide variation was found for the 1.36% glucose solution. There were several patients who had a positive calcium balance despite a positive filtration rate. The explanation for this finding lay in differences in serum concentrations of calcium, and especially differences in the size of the total exchangeable calcium pool that contains the plasma calcium compartment. A negative correlation between peritoneal calcium balance and the size of the total exchangeable calcium pool could be demonstrated. This finding may explain the differences in the peritoneal calcium flux reported in the literature. As an enlargement of the exchangeable calcium pool correlates with the progression of vascular calcification, therapeutic efforts should be directed toward prevention of an enlargement of this pool.

Adult

Combined LDL apheresis and hemodialysis in a patient with end-stage renal disease and accelerated coronary atherosclerosis.

The first long-term experience with lipid apheresis in a hemodialysis patient with refractory combined hyperlipidemia and coronary heart disease is described. Simultaneous treatment was performed once a week using two separate machines connected by parallel flow. Correction of hyperlipidemia was achieved, accompanied by inhibition of progressive coronary heart disease, enabling kidney transplantation.

Adult

Altered pattern of calcium kinetics in hemodialysis patients after parathyroidectomy.

Six HD patients with severe secondary hyperparathyroidism (sHPT) underwent studies of calcium kinetics prior to and after parathyroidectomy (PTX) with autotransplantation. Postoperatively, patients received vitamin D and calcium supplementation. Before PTX, a markedly elevated bone turnover was found, with increased fluxes of calcium from plasma into the exchangeable calcium pool. This pool was three times larger than normal, indicating a high risk of extraosseous calcifications. Despite a marked fall in parathyroid hormone (iPTH) levels after PTX, bone cell activity was maintained, as indicated by elevated values for Ca retention. Although Ca efflux from plasma into other compartments of the exchangeable pools remained above normal, the size of the total exchangeable calcium pool markedly decreased after PTX, indicating that PTX with autotransplantation, followed by vitamin D therapy, can normalize bone turnover and shift the balance of calcium flux towards mineralized bone. Reduction in the exchangeable calcium pool may explain the clinical finding that extraosseous calcifications regress in some patients after PTX.

Adult