Biomedical subjects

Christian Bieglmayer

Publications and source records attributed to Christian Bieglmayer.

15 recordsLinked to original sources

PubMed2005

Colon-specific regulation of vitamin D hydroxylases--a possible approach for tumor prevention.

Epidemiological data suggest a protective role of calcium and vitamin D against colorectal tumor pathogenesis. 1,25-dihydroxyvitamin D3 (1,25-D3) is a key determinant of calcium homeostasis, cell proliferation and differentiation. Calcium in the intestinal lumen functions as a growth regulator and may prevent cancer by direct reduction of colonocyte proliferation. While calcium or vitamin D can counteract proliferation by itself, they could also interact if nutritional calcium were to modulate colonic vitamin D synthesis. In this paper we demonstrate that colonic and renal vitamin D hydroxylases are regulated independently. When mice were fed a modified AIN-76 diet containing low dietary calcium (0.1 or 0.04%) fecal calcium content was as low as 5% of that found in mice on a 0.9% calcium containing diet. Low fecal calcium concentration enhanced proliferating cell nuclear antigen expression in the colon mucosa and reduced that of the cyclin dependent kinase inhibitor p21. While low dietary calcium did not affect colonic expression of VDR or 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) mRNA, it influenced their renal expression in the expected manner by elevating the CYP27B1 expression and reducing VDR and 25-hydroxyvitamin D3 24-hydroxylase (CYP24) expression. In contrast, low calcium diets significantly augmented colonic CYP24 mRNA expression, but only in the ascending colon. This might result in reduced colonic accumulation of 1,25-D3 during hyperproliferation caused by low dietary calcium and might support site-specific tumorigenesis. The important realization that low dietary calcium by itself is a risk factor for colorectal carcinogenesis and that colonic and renal vitamin D hydroxylases indeed are regulated differently from each other will provide novel approaches for colon cancer prevention.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed2005

Low total vitamin C plasma level is a risk factor for cardiovascular morbidity and mortality in hemodialysis patients.

Hemodialysis patients are prone to deficiency of vitamin C, which constitutes the most abundant nonenzymatic antioxidant in blood. Because antioxidants are involved in the pathogenesis of atherosclerosis, the authors examined the association of total vitamin C plasma level with cardiovascular outcomes in such patients. One hundred thirty-eight consecutive maintenance hemodialysis patients (median age 61 yr, 90 males) were enrolled in a single-center study. At baseline, routine laboratory parameters were recorded, and predialysis total vitamin C plasma levels were measured by high-pressure liquid chromatography. Patients were prospectively followed-up for the occurrence of a primary composite endpoint consisting of fatal and nonfatal major adverse cardiovascular events (MACE) and for all-cause and cardiovascular mortality. MACE occurred in 35 patients (25%) over a period of median 30 mo, and 42 patients (30%) died [29 cardiovascular deaths (21% of total)]. Using Cox proportional hazards modeling, adjusted hazard ratios for the occurrence of MACE were 3.90 (95% confidence interval [CI]: 1.42 to 10.67; P = 0.008) and 3.03 (95% CI: 1.03 to 8.92; P = 0.044) for patients in the lower (<32 micromol/L) and middle (32 to 60 micromol/L) tertile of total vitamin C levels, compared with patients in the upper tertile (>60 micromol/L). Hazard ratios for cardiovascular death were 3.79 (95% CI: 1.23 to 11.66; P = 0.020) and 2.89 (95% CI: 0.89 to 9.37; P = 0.076). Total vitamin C levels were not independently associated with all-cause mortality. This study concludes that low total vitamin C plasma levels predict adverse cardiovascular outcomes among maintenance hemodialysis patients. Future studies should address the potential protective effect of an adequate vitamin C supplementation.

Aged↗

PubMed2005

Quick PTH assay cannot predict incomplete parathyroidectomy in patients with renal hyperparathyroidism.

BACKGROUND: Contradictory reports on the value of intraoperative quick parathyroid hormone (PTH) monitoring in renal hyperparathyroidism have been published. METHODS: Thirty-five consecutive patients underwent total parathyroidectomy, central neck dissection, bilateral thymectomy, and immediate autotransplantation. PTH levels were measured by PTH assay at induction of anesthesia (baseline level) and in 5-minute intervals after excision of the last parathyroid gland. Parathyroidectomy was considered "total" in patients with PTH levels <10 pg/mL (subgroup 1), "subtotal" between 10 and 65 pg/mL (subgroup 2) and "insufficient" at >65 pg/mL (subgroup 3) within the first postoperative week. RESULTS: Fifteen minutes after excision of the last gland, PTH levels dropped to 19.4 +/- 15.7% (subgroup 1), 14.9 +/- 5.9% (subgroup 2), and 18 +/- 6.7% (subgroup 3) from baseline among 22 patients on hemodialysis, to 22.1 +/- 18.7% and 17.5% in 9 patients (subgroups 1 and 2) after successful kidney transplantation, and to 10.7% and 17.5% (subgroup 1) and 12.8% and 31.4% (subgroup 2) in 4 patients with reduced renal function after kidney transplantation. CONCLUSIONS: Currently available QPTH assays are not useful to predict insufficient resection of hyperfunctioning parathyroid tissue.

Follow-Up Studies↗

PubMed2004

Dynamic contrast-enhanced MR imaging of the stimulated pituitary gland.

Apoplexy due to infarction and/or hemorrhage is a frequent complication of pituitary adenoma, occurring either spontaneously or precipitated by several factors, among them pituitary function test with hypothalamic releasing hormones. The mechanism by which releasing hormones cause pituitary apoplexy is unclear. It has been proposed that increase in pituitary size and/or alterations in blood flow could be responsible. The aim of this study was to explore the effects of intravenous administration of hypothalamic releasing hormones on pituitary size and hemodynamics in healthy subjects. Gadolinium-DTPA-enhanced dynamic magnetic resonance imaging (MRI) was performed in eight healthy volunteers under basal conditions and 20 min after injection of releasing hormones. Mean upslopes of Gadolinium-DTPA enhancement curves showed good correlation between basal and stimulated conditions (R = 0.89) and were significantly steeper after stimulation (P = 0.017). In contrast, pituitary height, width and length did not differ significantly between basal and stimulated conditions. In conclusion, the pituitary does not swell in healthy subjects in response to stimulation with hypothalamic releasing hormones, whereas transfer of contrast agent to tissue (blood flow and/or vessel permeability) is enhanced.

Adenoma↗

PubMed2004

Vitamin C plasma level and response to erythropoietin in patients on maintenance haemodialysis.

BACKGROUND: Intravenous vitamin C supplementation to haemodialysis patients might ameliorate responsiveness to recombinant human erythropoietin (rHuEpo). This study was performed to analyse the relation between vitamin C plasma concentration and response to rHuEpo. METHODS: In a cross-sectional, single-centre observational study including all haemodialysis patients, pre-dialysis plasma vitamin C concentrations were measured by high-performance liquid chromatography and response to rHuEpo (haemoglobin concentration/international units rHuEpo/kg/week) was recorded together with baseline laboratory data. RESULTS: Univariate analysis yielded a significant correlation between vitamin C plasma levels and response to rHuEpo (n = 130, r = 0.25, P = 0.004), which still persisted after adjustment for transferrin saturation, C-reactive protein, malondialdehyde, parathyroid hormone, route of rHuEpo administration, residual renal function and diabetes mellitus (adjusted r = 0.23, P = 0.014). Analysis per quartiles of vitamin C plasma level revealed a significantly lower response to rHuEpo with decreasing vitamin C values (P = 0.026). CONCLUSIONS: In unselected haemodialysis patients, vitamin C plasma levels account, at least partially, for the response to rHuEpo. Larger-sized interventional studies are needed to find out whether vitamin C plasma levels may or may not appropriately reflect the potential beneficial effect of vitamin C supplements on rHuEpo responsiveness.

Aged↗

PubMed2004

Frequency and relevance of elevated calcitonin levels in patients with neoplastic and nonneoplastic thyroid disease and in healthy subjects.

Routine measurement of serum calcitonin (CT) has been recently proposed for all patients with neoplastic thyroid disease to detect clinically occult medullary thyroid carcinoma (MTC). Data on the prevalence of elevated CT levels in nonneoplastic thyroid disease or in healthy subjects have not been reported to date. Four hundred and fourteen consecutive patients with suspected thyroid disease and 362 healthy controls underwent thyroid examination with measurement of basal serum CT. Whenever serum CT was 10 pg/ml or more, a pentagastrin (PG) stimulation test was performed. Twenty-eight of 414 patients (6.8%) showed elevated basal serum CT levels, 15 of them with nonneoplastic thyroid disease, and the remaining 13 subjects with neoplastic thyroid disease. Four patients with abnormal PG testing (stimulated CT, > or = 100 pg/ml) were identified. Three of them had biochemical and sonographical evidence of thyroiditis. Elevated basal CT levels were significantly more frequent in patients with Hashimoto's thyroiditis (HT; P < 0.05). One female patient with HT had a 5-mm nodule, which was classified as MTC. None of the 6 out of 362 healthy controls with elevated basal CT (1.7%) presented an abnormal PG test. Our data suggest that basal CT measurements can be of use in the detection/screening of MTC not only in subjects with neoplastic thyroid disorders, but also in patients with immunological evidence of HT. They also confirm earlier reports on the essential value of PG stimulation testing, even when basal plasma CT levels are only modestly elevated, with regard to establishing the diagnosis of MTC or its premalignant associated conditions (micro-MTC and neoplastic C cell hyperplasia).

Adult↗

PubMed2004

Multicentre performance evaluation of the E170 module for modular analytics.

The E170 module was evaluated at 13 sites in an international multicentre study. The objective of the study was to assess the analytical performance of 49 analytes, and to collect feedback on the system's reliability and practicability. The typical, within-run coefficients of variation (CVs) for most of the quantitative assays ranged between 1 and 2% while a range of 2-4% was achieved with the infectious disease methods. Total precision CVs were found to be within the manufacturer's expected performance ranges, demonstrating good concordance of the system's measuring channels and a high reproducibility during the 2-4-week trial period. The functional sensitivity of 11 selected assays met the clinical requirements (e.g., thyreotroponin (TSH) 0.008 mU/l, troponin T 0.02 microg/l, total prostate-specific antigen (PSA) 0.03 microg/l). The E170 showed no drift during an 8-hour period and no relevant reagent carryover. Accuracy was confirmed by ring trial experiments and method comparisons vs. Elecsys 2010. The reliability and practicability of the system's hardware and software met with, or even exceeded, the evaluator's requirements. Workflow studies showed that E170 can cover the combined workload of various routine analysers in a variety of laboratory environment. Throughput and sample processing time requirements were achieved while personnel 'hands-on-time' could be reduced.

Calibration↗

PubMed2003

Pathogenesis of bone loss in heart transplant candidates and recipients.

BACKGROUND: Heart transplantation (HTX) is associated with decreased bone mineral density and changes in bone metabolism. We conducted this study to evaluate the pathophysiology of bone metabolism in HTX candidates and recipients. METHODS: Thirty-six HTX recipients were compared with 36 HTX candidates concerning biochemical parameters of bone metabolism and bone mineral density. RESULTS: Osteocalcin, bone-specific alkaline phosphatase, cross-linked-N-telopeptide of type I collagen, estradiol, serum creatinine, and blood urea nitrogen concentrations were significantly higher, whereas the calcium-creatinine ratio, thyrotropin, thyroxine, and bone mineral density were significantly lower in HTX recipients than in HTX candidates. Compared with a control group, HTX candidates had decreased renal function and increased bone resorption, whereas HTX recipients additionally had increased alkaline phosphatase and osteocalcin levels. In HTX recipients, we found positive correlations between creatinine clearance and bone mineral density; daily and cumulative cortisone doses were not associated with bone mineral density. CONCLUSIONS: In HTX candidates, disturbances in bone metabolism with increased bone resorption may be caused partly by existing low-grade renal insufficiency, regular intake of loop diuretics, and restriction of mobility. In HTX recipients, immunosuppressive therapy-glucocorticoids and cyclosporine-seem to be responsible for changes in bone metabolism.

Adult↗

PubMed2003

Reduction of adverse citrate reactions during autologous large-volume PBPC apheresis by continuous infusion of calcium-gluconate.

BACKGROUND: Citrate-related side effects are common adverse reactions during PBPC apheresis. To reduce the incidence of citrate-related reactions, the effect of a continuous calcium-gluconate infusion on the appearance of hypocalcemic symptoms and on the subjective tolerance toward large-volume leukapheresis (LVL) was tested. STUDY DESIGN AND METHODS: A double-blinded, placebo-controlled trial was carried out in 50 patients undergoing standardized LVL at a median ACD-A ratio of 1.99 mg per kg and minute. Patients were randomly assigned to receive a continuous IV infusion of either saline or calcium-gluconate at a dose of 1.8 mmol calcium per hour. Subjective tolerance toward LVL was determined by standardized rating systems. Further, hormonal and electrolyte changes were monitored to assess the effect of continuous calcium infusion on calcium homeostasis. RESULTS: Continuous IV administration of calcium-gluconate throughout LVL reduced the incidence of citrate-related effects by 65 percent. In patients who developed signs of hypocalcemia, the symptoms were weaker, and less medical intervention was needed to resolve clinical symptoms. The subjective tolerance toward LVL was superior in patients receiving calcium support compared to control patients. Continuous calcium infusion attenuated changes in serum phosphorus compared to patients receiving saline. No differences were observed in the variation of serum potassium and serum magnesium between the control group and the treatment group. The administration of calcium was not associated with technical problems related to the apheresis procedure, neither was any effect of calcium support on the total number of CD34+ cells collected observed. CONCLUSION: These results indicate that continuous support of calcium-gluconate during LVL is an effective means of reducing the incidence of citrate-related symptoms and improving subjective tolerance toward LVL, without affecting the technical performance or the number of CD34+ cells collected.

Adolescent↗

PubMed2003

The effect of beta-receptor blockade on factor VIII levels and thrombin generation in patients with venous thromboembolism.

High factor VIII (FVIII) is a risk factor for venous thromboembolism (VTE). The pathomechanism by which high FVIII leads to an increased risk of VTE is unknown. Physical activity and infusion of adrenalin provoke a rise in FVIII, which can be blocked by a nonselective beta-blockade. We tested the hypothesis that in patients with a VTE beta-blockade decreases FVIII and inhibits coagulation activation. 17 male patients with high FVIII (> 170 IU/dL, n = 7) or low FVIII (<150 IU/dL, n = 10) and a history of VTE received 40 mg of propranolol thrice daily for 14 days. FVIII and vasopressin levels were measured before and during propranolol intake and 28 days thereafter. At the same time points, haemostatic system activation was investigated by measuring prothrombin fragment f1.2 (f1.2) and thrombin antithrombin complexes (TAT) in venous blood and in blood emerging from a skin incision (shed blood). The mean FVIII level before propranolol was 192 IU/dL and 115 IU/dL in patients with high and low FVIII, respectively. During and 28 days after propranolol, no significant change in FVIII was seen in both groups. Changes in f1.2 and TAT were not detectable in either venous blood or in shed blood. beta-receptor blockade did not lower FVIII or inhibit haemostatic system activation in patients with VTE and persistently high FVIII. Administration of propranolol cannot be recommended as secondary thromboprophylaxis in patients with high FVIII.

Adrenergic beta-Antagonists↗

PubMed2002

Screening for medullary thyroid carcinoma: experience with different immunoassays for human calcitonin.

Calcitonin measurements in patients with nodular thyroid disease are helpful for early diagnosis and therapy of medullary thyroid carcinoma. We compared three commercial calcitonin assays routinely used: "CIS" (France), "Medgenix" (Belgium) and "Nichols-Advantage" (USA). In addition, we evaluated a two-step modification of the Medgenix-test and an enzyme immunoassay from Sangui (Japan). Method comparison studies revealed deviations from linear relationships between all routine assays. While histograms of CIS and Nichols results were similar at low concentrations with their highest frequency below 1 pg/ml, Medgenix showed a broad peak around 3 pg/ml. Correlation coefficients were 0.69 (CIS versus Medgenix) and 0.91 (CIS versus Nichols). In thyroidectomized patients, calcitonin was not detectable with CIS and Nichols, but the Medgenix test, which was more susceptible to interference, measured about 6 pg/ml. The immunoassay of Sangui showed insufficient analytical sensitivity. About 70-80% of calcitonin levels initially > 10 pg/ml were reproduced in the basal levels of the subsequent pentagastrin test. Average ratios (stimulated/basal level) were slightly higher for CIS and Nichols than for Medgenix. Prediction of a pathological stimulation from basal calcitonin was insufficient with CIS and Medgenix assays. If a calcitonin concentration of > 100 pg/ml (CIS) is considered as an indication for surgery, equivalent values are 71 pg/ml for Medgenix, and 96 pg/ml for Nichols. Using these criteria, about one third of patients who underwent pentagastrin stimulation showed pathological reactions. Reliable and sensitive calcitonin assays used for the screening of sporadic medullary thyroid carcinomas in patients pre-selected by nodular goiter are important for health and economic reasons, because they enable early therapy.

Calcitonin↗

PubMed2002

Leptin induces endothelin-1 in endothelial cells in vitro.

Leptin, a protein encoded by the obese gene, is produced by adipocytes and released into the bloodstream. In obese humans, serum leptin levels are increased and correlate with the individual's body mass index and blood pressure. Elevated serum concentrations of endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, were also observed in obese subjects. The pathomechanisms underlying this ET-1 increase in obesity are poorly understood. In the present study, we investigated the influence of the ob gene product leptin on the expression of ET-1 in human umbilical vein endothelial cells (HUVECs). Binding studies using (125)I-radiolabeled leptin revealed high- and low-affinity leptin binding sites on HUVECs (Kd1=13.1+/-3.1 nmol/L and Kd2=1390+/-198 nmol/L, respectively), mediating a time- and dose-dependent increase of ET-1 mRNA expression and protein secretion after incubation of HUVECs with leptin. This leptin-induced ET-1 expression was inhibited by preincubation of HUVECs with 0.75 micromol/L antisense phosphorothioate oligonucleotides directed against the leptin receptor Ob-Rb. Furthermore, after incubation with leptin, increased nuclear staining of c-fos and c-jun, the major components of the transcription factor AP-1, and increased AP-1 DNA binding were observed. Transient transfection studies with ET-1 promoter constructs showed that leptin-induced promoter activity was abolished in the absence of AP-1 binding sites or by cotransfection with a plasmid overexpressing a mutated jun, which is able to bind c-fos but not DNA. Thus, leptin upregulates ET-1 production in HUVECs via a mechanism potentially involving jun binding members of the bZIP family.

Cells, Cultured↗

PubMed2002

Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis.

OBJECTIVES: To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy (RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. METHODS: Patients with PCa before RP (n = 49), those who underwent TURP for BPH (n = 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n = 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. RESULTS: No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P = 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P = 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P = 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P < 0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. CONCLUSIONS: Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH.

Aged↗

PubMed2002

Influence of mycophenolic acid and tacrolimus on homocysteine metabolism.

BACKGROUND: The effect of mycophenolate mofetil (MMF) on homocysteine (Hcy) metabolism is unknown. METHODS: This in vitro study examined whether mycophenolic acid or tacrolimus influences the formation of Hcy as determined by measuring the total Hcy (tHcy) concentrations in supernatants of human renal proximal tubule epithelial cells. Cells were incubated with and without vitamins (folate, vitamin B6 and B12) in the presence of low or high methionine concentrations at different mycophenolic acid (0, or 5, or 20 microg/mL) or tacrolimus (0, or 10, or 25 ng/mL) concentrations for 24, 48 or 72 hours. The concentration of tHcy in culture supernatants was measured by a fluorescence polarization immunoassay. The effect of MMF on tHcy plasma levels was also examined in 454 kidney graft recipients. RESULTS: Comparisons of tHcy levels in culture supernatants over time by four way ANOVA showed that methionine concentration (P < 0.00001), time (P < 0.00001), vitamins (P = 0.002728), and mycophenolic acid concentration (P = 0.000095) were all significant predictors of tHcy concentrations. This was due to significantly lower tHcy levels with using mycophenolic acid at a high concentration versus control at the 48- and 72-hour time points. By contrast, tacrolimus showed no effect in vitro. Among the kidney graft recipients, male patients on MMF therapy showed lower plasma tHcy concentrations as compared to those on azathioprine (P = 0.03). CONCLUSION: Our study suggests a tHcy lowering effect of MMF in male transplant recipients, which improves the cardiovascular disease risk profile, whereas tacrolimus showed no effect.

Adult↗

PubMed2002

Kinetic analyses of parathyroid hormone clearance as measured by three rapid immunoassays during parathyroidectomy.

BACKGROUND: Rapid intraoperative parathyroid hormone (PTH) measurements are an important prerequisite for minimally invasive parathyroidectomy, serving as a feasible marker for "cure" because of the short half-life of PTH. Because automated analysis may facilitate monitoring, two automated PTH assays were compared with an established manual method. METHODS: We collected 109 plasma samples during minimally invasive surgery on 20 patients with primary hyperparathyroidism and single-gland disease. PTH was analyzed manually with a test from Nichols and by two automated assays from Diagnostic Product Corporation (DPC) and Roche, respectively. PTH half-life and residual concentrations were calculated by two kinetic models. RESULTS: Despite good overall correlations between methods [DPC = 1.07(Nichols) - 12 ng/L; r = 0.95, S(y/x) = 26 ng/L and Roche = 1.16(Nichols) - 2.82 ng/L; r = 0.98; S(y/x) = 16 ng/L], marked interindividual differences were observed. The iterative kinetic model failed with a nonuniform PTH decrease, but the interpolative model produced valid results. The mean (SD) half-life of 3.7 +/- 1.4 min with DPC differed significantly (P <0.05) from the 4.3 +/- 1.6 min with Roche (Nichols, 4.0 +/- 1.6 min). DPC produced significantly lower mean residual PTH (15 ng/L) vs Roche (27 ng/L); Nichols results were between them (20 ng/L). However, these differences were clinically irrelevant. CONCLUSIONS: Automated methods are as suitable as the manual test. The preoperative baseline PTH is necessary but is insufficient for kinetic calculations.

Autoanalysis↗