Search PubMed⌕ Search

Biomedical subjects

T Weinreich

Publications and source records attributed to T Weinreich.

36 records · Page 2Linked to original sources
PubMed1995

Low dialysate calcium in continuous ambulatory peritoneal dialysis: a randomized controlled multicenter trial. The Peritoneal Dialysis Multicenter Study Group.

Hypercalcemia is a common complication in continuous ambulatory peritoneal dialysis (CAPD) patients treated with calcium-containing phosphate binders and using the standard dialysate calcium concentration of 3.5 mEq/L (SCa). Lowering the dialysate calcium was proposed to overcome this problem. The current randomized controlled multicenter study was designed to investigate efficiency and safety of a low calcium dialysate (2.00 mEq/L; LCa) compared with SCa (3.5 mEq/L) in CAPD patients. After an 8-week run-in period, 103 stable CAPD patients, 68 men, 35 women, aged 54.5 years (range, 20 to 77)) were randomly allotted to treatment with either LCa or SCa. All patients received calcium carbonate as oral phosphate binder to achieve serum phosphate levels < 6.2 mg/dL. If persistent hypercalcemia arose, CaCO3 was replaced by Al(OH)3 until normocalcemia was achieved. All patients received 0.25 microgram calcitriol/d. Parameters monitored included total and ionized serum calcium, serum phosphate, phosphate binder intake, incidence of hypercalcemia, serum aluminium, intact parathyroid hormone (1,84PTH), osteocalcin, alkaline phosphatase, bone mineral density and hand skeletal x-ray. Primary end points were (a) number of hypercalcemic episodes, (b) tolerated doses of calcium-containing phosphate binders, and (c) 1,84PTH. After 6 months of therapy, total and ionized calcium were lower in LCa patients (total Ca:9.6 v 10.08 mEq/L, P = 0.005; iCa: 4.76 v 5.15 mg/dL; P = 0.013). In the LCa group, significantly fewer episodes of hypercalcemia were recorded (total S-calcium > 10.8 mg/dL: LCa 24 v SCa 86 episodes; P < 0.005). Use of LCa permitted the administration of more CaCO3 (mean daily tablet number: LCa, 5.9 v SCa, 4.2; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1995

[Does the primary disease recur in kidney transplantation?].

Improved graft survival is accompanied by complications which interfere with the long-term function of the allograft. Recurrence of the primary renal disease in the graft is well recognized and is found in 10 to 20% of all recipients; however, graft loss due to recurrent disease is reported in less than 5% of all cases. The most frequent cause of recurrence is glomerulonephritis: Membrano-proliferative GN type II, IgA nephritis and focal sclerosis are frequently observed. Among metabolic disorders linked to graft disease, diabetic nephropathy has to be mentioned first. Primary oxalosis is a rare disorder, but it is related to a very high risk of recurrent disease in the transplant. Combined kidney-liver transplantation seems to offer a valuable alternative for these patients. The high risk of recurrence of certain diseases, i.e. membrano-proliferative GN type II, focal-segmental glomerulosclerosis, primary oxalosis, should prevent living donation. In addition, there are some reports suggesting that living-related donation might increase the recurrence rate of hemolytic-uremic syndrome, membranous GN and Schönlein-Henoch purpura. Recurrent disease might not only affect the outcome of the transplant, but can provide insight into the nature and pathogenesis of the primary disease. Currently there are no conclusive reports indicating that chronic immunosuppression, especially cyclosporin-A treatment, reduces recurrence rates; however the clinical course might be ameliorated.

Glomerulonephritis↗
PubMed1994

Inhibition of growth by calcitriol in a proximal tubular cell line (OK).

Calcitriol has been shown to inhibit (i) cell proliferation of renal carcinoma cell lines and of cultured adult human mesangial cells in vitro, and (ii) renal compensatory growth in vivo. In the present study we examined the effects of calcitriol on DNA synthesis and cell replication in an immortalized cell line showing the phenotypic characteristics of proximal tubular cells (opossum kidney, OK cells). The viability of OK cells was not affected by calcitriol (Trypan-blue exclusion, LDH and K+ release), but the cells did not convert 3H-25(OH)2D3 to 3H-1,25(OH)2D3. In the log growth phase, calcitriol (but not alternative vitamin D metabolites) caused dose-dependent (10(-12) to 10(-6) M) inhibition of radiothymidine incorporation. Inhibition was calcium dependent, i.e. it was more pronounced at the lower nominal calcium concentration in tissue culture media (0.9 versus 1.8 mmol/l) and amplified by coincubation with nifedipine (1 microM). Inhibition of DNA synthesis was paralleled by inhibition of cell replication (growth curve) under basal conditions and after stimulation with EGF (10 ng/ml). In conclusion, calcitriol inhibits proliferation of proximal tubular cells which normally express 1-alpha-hydroxylase activity.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1993

Transperitoneal calcium mass transfer using dialysate with a low calcium concentration (1.0 mM).

Lower dialysate calcium concentrations were recently proposed to overcome the risk of hypercalcemia in continuous ambulatory peritoneal dialysis (CAPD) patients on calcium-containing phosphate binders and/or vitamin D metabolites using the standard dialysate calcium concentration (SCa) of 1.75 mM. To assess transperitoneal calcium mass transfer (CaMT) in CAPD patients using a dialysate with a low calcium concentration (LCa, 1.00 mM), 18 stable patients were randomly allocated to receive either LCa or SCa. CaMT was assessed over 4 hours using 2L dialysate bags with three different dialysate glucose concentrations (1.5%, 2.3%, 4.25%). Total serum calcium (tCa), ionized calcium (iCa), and the exact dialysate volume were measured before and after the 4-hour dwell. A sample of the drained dialysate was obtained to measure the dialysate calcium concentration. The tCa and iCa levels were not significantly different in both groups prior to and did not change throughout the test. CaMT (median/range) was -0.64 mmol/exchange (-0.35(-)-1.29 mmol/exchange) using LCa with 1.5% glucose compared to 0.23 mmol (-0.18-0.87 mmol) with SCa (p < 0.0001). CaMT was negatively correlated to iCa and ultrafiltration volume [4.25%: LCa-1.22 (-0.84(-)-1.9); SCa -0.43 (-1.35-0.13); p < 0.001]. In summary, LCa results in a loss of calcium into the dialysate even at low ultrafiltration volumes and serum iCa levels. This might facilitate the prevention and therapy of renal osteodystrophy with calcium-containing phosphate binders and calcitriol. However, patients using LCa must be carefully monitored for calcium homeostasis and bone turnover.

Aged↗
PubMed1992

Severe hemorrhagic complications from infection with nephropathia epidemica strain of Hantavirus.

In the following we describe a case of severe hemorrhagic fever with renal syndrome (HFRS) caused by Puumala infection. The diagnosis was made by immunofluorescence technique and by solid phase enzyme immunoassay using recombinant nucleocapsid antigen of a Puumala serotype strain. Such a clinical course with severe bleeding complications is considered untypical for Puumala induced HFRS.

Aged↗
PubMed1991

Single cell analysis of changes in cytosolic calcium induced by vitamin D3 metabolites in cultured rat mesangial cells.

The acute effects of 1,25-Dihydroxy-vitamin D3 [1,25(OH)2D3] on the concentration of cytoplasmic ionized calcium [Ca2+] of cultured rat mesangial cells were studied at the single cell level by microspectrofluorometry of fura-2-loaded cells. Addition of 1,25(OH)2D3 produced an immediate increase of [Ca2]+. This rise in [Ca2+] was sustained and similar to that caused by the Ca2+ channel agonist BAY K 8644. Comparable changes were also observed in cultured human mesangial cells. The effects of the hormone (10 (-10)-10(-7) M) were dose-dependent (62% and 285%). Only 30-40% of the cells responded to stimulation with 1,25(OH)2D3. 25OHD3 also increased Ca2+ whereas 24,25(OH)2D3 and 1aOHD3 were inactive. Addition of 1 mM CoCl2 or 2-5 microM nifedipine largely blocked the effects of 1,25(OH)2D3 suggesting the involvement of Ca2+ channel activation in the rapid 1,25(OH)2D3-induced increase in mesangial cell [Ca2+]. 45Ca uptake studies are consistent with This interpretation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Actions of 1,25-dihydroxyvitamin D3 on human mesangial cells.

In the present study, we examined specific binding of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by an effects of 1,25(OH)2D3 on human mesangial cells (hMC), obtained from healthy portions of tumor-bearing kidneys. Receptors for 1,25(OH)2D3 were characterized by (1) sucrose density gradient analysis, (2) Scatchard analysis, and (3) DNA affinity of the receptor molecule. Specific binding occurred by a single class of macromolecules, sedimenting with 3.5 S in sucrose density gradients (5% to 20%). Receptors showed high affinity (Kd, 1.39 x 10(-10)), and specific binding capacity (Nmax) of 821 binding sites per cell. 1,25(OH)2D3 (10(-6) to 10(-10)) reduced both DNA synthesis (by [3H]thymidine incorporation) and cell growth (by cell counting) throughout the log-phase and confluence. Further evidence of functional effects of 1,25(OH)2D3 on hMC is provided by ultrastructural studies, which showed rapid increase of electron-dense lysosomal particles in hMC exposed to 1,25(OH)2D3. The data identify actions of 1,25(OH)2D3, a molecule with recently recognized immunoregulatory roles, on hMC. The results are consistent with a role of 1,25(OH)2D3 in control of mesangial cell function.

Calcitriol↗
PubMed1991

Is control of secondary hyperparathyroidism optimal with the currently used calcium concentration in the CAPD fluid?

Progression of hyperparathyroidism and bone disease on CAPD has been noted by several authors. In our CAPD patients we observed that aluminium-containing phosphate binders were often required because administration of CaCO3 was limited by the development of hypercalcaemia particularly in patients concomitantly requiring calcitriol. We propose that CAPD fluids with lower calcium concentration should be evaluated to facilitate control of plasma phosphate and secondary hyperparathyroidism.

Calcitriol↗
PubMed1990

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↗
PubMedDate not supplied

Angiotensin II induces hypertrophy and hyperplasia in adult human mesangial cells.

Several experimental studies point to a potential role of angiotensin II (Ang II) in the progression of glomerulosclerosis even in the absence of glomerular hypertension. We tested the hypothesis that Ang II acts as a growth factor for adult human mesangial cells (AHMC). AHMC were isolated from noninvolved parts of tumor nephrectomy specimens and grown in RPMI medium with the addition of fetal calf serum (FCS). All studies were performed with growth-arrested cells. Proliferation studies were done in serum-free standard growth medium (SF) with the addition of either various concentrations of insulin, plasma-derived serum, or FCS. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-thymidine uptake of AHMC up to 57 +/- 13% over solvent controls (p < 0.01). In parallel, the DNA content was 36 +/- 10% higher (p < 0.05) than in solvent controls after 2 days of culture. The cell numbers were higher up to 47 +/- 8% in Ang II (10(-6) M) stimulated cultures after 4 days of incubation (p < 0.01). The effect of Ang II was specific, since it was almost completely obliterated by the AT1 receptor antagonist DuP753. The effect of Ang II was particularly marked when cultures were incubated with SF plus high concentrations (1.7 x 10(-6) M) of insulin or SF plus 10% plasma-derived serum. In contrast, the effect was not significant when cultures were incubated with SF plus 10% FCS. Ang II, when added to platelet-derived growth factor at various concentrations, did not further increase the proliferation. The effect on protein synthesis was assessed in growth-arrested AHMC by 3H-methionine uptake and protein/DNA ratio in cell lysates. Ang II (10(-10) to 10(-6) M) dose dependently increased the 3H-methionine uptake of AHMC up to 47 +/- 10% over solvent controls (p < 0.01). In parallel Ang II (10(-8) to 10(-6) M) dose dependently increased the 3H-methionine uptake of the protein/DNA ratio by 24 +/- 6% after 48 h of incubation. DuP753 obliterated the stimulatory effect of Ang II. Ang II (10(-6) M) also increased the mRNA of the immediate-early growth-related gene Egr-1. We conclude that Ang II induces hypertrophy and proliferation in adult human mesangial cells. This result is of interest with respect to a potential role of Ang II in the pathogenesis of glomerulosclerosis in humans.

Adult↗
PubMedDate not supplied

Long-term dialysis with low-calcium solution (1.0 mmol/L) in CAPD: effects on bone mineral metabolism. Collaborators of the Multicenter Study Group.

OBJECTIVE: Peritoneal dialysate solutions with conventionally high-calcium (Ca) concentrations (1.75 mmol/L) are now widely replaced by solutions with a lower, more physiological calcium content to prevent hypercalcemia in patients treated with oral calcium-containing phosphate binders and/or calcitriol. While there is still debate on how far the dialysate calcium should be lowered (1.25 mmol/L or less), little information is available concerning the effects of a long-term treatment with low-calcium solutions on secondary hyperparathyroidism and bone mineral metabolism in general. DESIGN: A prospective, randomized, controlled multicenter study to compare the effects of low-calcium (LCa, dialysate calcium 1.0 mmol/L) versus standard-calcium dialysate solution (SCa, dialysate calcium 1.75 mmol/L) on bone mineral metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients over 2 years of treatment. SETTING: Nephrology and dialysis units of primary and tertiary hospitals in Germany and Switzerland. PATIENTS: All CAPD patients in the participating centers between 18 and 80 years of age, stable on CAPD for at least 1 month, free of aluminium bone disease or prior parathyroidectomy were invited to enter the study. Sixty-four patients could be randomly allotted to LCa (n = 35) or SCa (n = 29) treatment in a 2-year protocol; 34 finished the study as planned. INTERVENTIONS: Calcium carbonate (CaCO3) was given as oral phosphate binder to maintain serum phosphate < 2.0 mmol/L. If hypercalcemia supervened, CaCO3 was exchanged stepwise for aluminium hydroxide (Al(OH)3), until normocalcemia was obtained. Patients received calcitriol (0.25 microgram/day per os) if parathyroid hormone (PTH) exceeded the upper limit of normal by a factor of 2 or more. MAIN OUTCOME MEASURES: We assessed total and ionized serum calcium, phosphate, serum aluminum, alkaline phosphatase, osteocalcin, PTH (intact molecule), and phosphate binder intake at regular intervals. Measurements of bone mineral density and hand skeleton x-rays were obtained at the start and after 6 months and 2 years, respectively. RESULTS: With LCa, mean total and ionized serum calcium levels were within the normal range (total Ca: 2.0-2.6 mmol/L; ionized Ca: 1.19-1.32 mmol/L), but throughout the treatment period were significantly lower than with SCa. The incidence of hypercalcemia (> 2.8 mmol/L) was three times higher in patients on SCa, despite the significantly higher amount of Al(OH)3 and less CaCO3 given in this group. In parallel, serum aluminum increased with SCa throughout the study, whereas it was slowly decreasing with LCa. Median PTH levels remained stable at about two times the upper limit of normal over the 2 years of study with LCa. However, 23% of the patients on LCa developed severe hyperparathyroidism, with PTH levels exceeding ten times the upper limit of normal compared to only 10.3% of the patients on SCa. With SCa, median PTH decreased towards near normal levels. Alkaline phosphatase and serum osteocalcin correlated positively with PTH levels. Bone mineral density was in the lower normal range in both groups and remained unchanged at the end of the study. Skeletal x-ray films showed only minor alterations in very few patients in both groups with no correlation to serum PTH or treatment modality. CONCLUSION: In CAPD patients low-calcium dialysate solutions can be used successfully over prolonged periods of time with stable control of serum calcium. The risk of hypercalcemia resulting from calcium-containing phosphate binders and the need to use aluminum-containing phosphate binders is markedly diminished. However, there is a certain risk that severe secondary hyperparathyroidism with long-term LCa therapy will develop, even if normocalcemia is maintained. Thus, LCa dialysis requires close and continuous monitoring of PTH and bone metabolism.

Adult↗