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Biomedical subjects

C Bieglmayer

Publications and source records attributed to C Bieglmayer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Is there a role of cyclosporine A on total homocysteine export from human renal proximal tubular epithelial cells?

BACKGROUND: Immunosuppressive therapy may influence homocysteine metabolism in allograft recipients. We examined whether cyclosporine A influences the in vitro formation of homocysteine as determined by the measurement of total homocysteine (tHcy) concentrations in supernatants of human renal proximal tubule epithelial cells (hRPTEC), an important site of homocysteine metabolism. METHODS: Cells were incubated with and without vitamins in the presence of low or high methionine concentrations at different cyclosporine A concentrations for 24, 48 and 72 hours (N = 7 for each experiment). The concentration of tHcy in culture supernatants was measured by a fluorescence polarization immunoassay. Data were analyzed by four-way ANOVA, three-way ANOVA and t tests. RESULTS: The Hcy export from hRPTEC (tHcy in the culture supernatant) was 2.69 micromol/L during standard cell culture conditions at time point 24 hours and increased by 28.3% at 48 hours and by 44.6% at 72 hours. Comparisons of tHcy levels in culture supernatants over time by four way ANOVA showed that cyclosporine A at 200 or 800 ng/mL had no influence on tHcy export from hRPTEC (P = 0.67991). In contrast, the presence of vitamins in the medium (P = 0.000001), in vitro methionine loading (P < 0.000001), and prolonged incubation time (P < 0.000001) were associated with an increase of tHcy export from hRPTEC. Significant interactions in this analysis were "vitamins x methionine" (P = 0.001804), "vitamins x time" (P = 0.001478), "methionine x time" (P < 0.000001), and "vitamins x methionine x time" (P = 0.018128), pointing to a combined effect of vitamins in the presence of high methionine concentrations at the later time points. CONCLUSION: Our study shows that hRPTEC export Hcy into the cell culture medium, an effect that is enhanced by in vitro methionine loading and modulated by the presence of vitamins. Cyclosporine A had no major influence on Hcy export from tubule cells. Therefore, our findings do not support the assumption that cyclosporine A elevates total homocysteine plasma levels in organ transplant patients.

Biological Transport, Active↗
PubMed2001

Molecular and clinical characterisation of homocystinuria in two Austrian families with cystathionine beta-synthase deficiency.

The influence of the genotype on the phenotypic expression of homocystinuria due to cystathionine beta-synthase (CBS) deficiency is frequently unclear. We therefore investigated the genotype and the phenotype of CBS deficiency in two Austrian families also considering genetic polymorphisms with a putative association with vascular disease (MTHFR 677C-->T, MTHFR 1298A-->C, F5 1691G-->A, F2 20210G-->A) and response to therapy. We identified the CBS 833T-->C/1058C-->T and CBS 828ins104/1358del134 compound heterozygous genotype in our index patients. Both patients showed mental retardation and ectopia lentis. CBS 833T-->C/1058C-->T was associated with severe vascular complications, which was not the case for CBS 828ins104/1358del134. The patient with CBS 828ins104/1358del134 was negative for F5 1691G-->A, F2 20210G-->A, MTHFR 677C-->T, and MTHFR 1298A-->C, while the patient with CBS 833T-->C/1058C-->T was heterozygous for MTHFR 1298A-->C. A combination therapy including pyridoxine, folic acid, hydroxycobalamin, and betaine failed to lower total homocysteine plasma levels below 50 mumol/L in both patients. In summary, our study demonstrates that the CBS 833C/1058T-MTHFR 1298AC genotype can be related to severe vascular disease, while the CBS 828ins104/1358del134-MTHFR 1298AA genotype presents with a somewhat milder clinical phenotype. Both genotypes do not allow for normalisation of total homocysteine plasma levels following vitamin therapy.

Adult↗
PubMed2001

Characterization of a vitamin D receptor knockout mouse as a model of colorectal hyperproliferation and DNA damage.

The vitamin D receptor knockout (VDR-KO) mouse presents with a skeletal phenotype typical for complete lack of genomic 1,25-dihydroxycholecalciferol effects. Our previous data from human colorectal tissue suggest that the steroid hormone and its receptor may have protective function against tumour progression. In order to investigate the relevance of the vitamin D system for pre-malignant site-directed changes in the colon, we characterized the amount and site-specific distribution of the VDR along the large intestine in wild-type (WT), heterozygote (HT) and KO mice. We also evaluated expression of proliferating cell nuclear antigen (PCNA), of cyclin D1 and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress. In colon ascendens, proliferative cells were dispersed all along the crypt and expression levels of all three markers were high in WT mice. A decrease of VDR expression did not affect expression significantly. In colon descendens, however, fewer proliferative cells were solely located in the lower third of the crypt, and an inverse relationship between VDR reduction, PCNA positivity and cyclin D1 expression was found in HT and KO mice. In parallel to enhanced proliferation a highly significant increase of 8-OHdG positivity occurred. Therefore, the sigmoid colon of VDR-KO mice, fed on an appropriate lactose/calcium-enriched diet to alleviate impaired calcium homeostasis-related phenotypic changes, is an excellent model for investigating induction and prevention of pre-malignant changes in one of the hotspots for human colorectal cancer incidence.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Markers of bone turnover in postmenopausal women receiving hormone replacement therapy.

We investigated the effects of hormone replacement therapy (n = 27) on biochemical markers of bone turnover in a cross-sectional study of 127 postmenopausal women (according to WHO guidelines 18 patients had normal bone mineral density and 109 suffered from bone loss). Urinary excretion of free deoxypyridinoline and C- or N-telopeptide fragments of type I collagen served as bone resorption markers, serum osteocalcin as a bone formation marker. In women with no hormone replacement therapy, only C- and N-telopeptides correlated significantly with the lumbal T-score as an index for bone mineral density. Patients with bone loss receiving hormone replacement therapy exhibited significantly lower C-telopeptide, N-telopeptide and osteocalcin levels than those with no therapy (mean -45%, -43% and -26%, respectively), while deoxypyridinoline showed no significant differences. Among the markers investigated, C- and N-telopeptides seemed to be more reliable to detect therapeutic effects on bone metabolism. We present a preliminary model to evaluate bone turnover and resorption/formation rate.

Aged↗
PubMed2000

Prevalence of C-cell hyperplasia in patients with normal basal and pentagastrin-stimulated calcitonin.

The prevalence of thyroid C-cell hyperplasia (CCH) was investigated prospectively in 57 patients with normal preoperative pentagastrin-stimulated plasma concentrations of calcitonin (hCT, range, 1-60 pg/mL; normal, 100 pg/mL) who subsequently underwent total thyroidectomy due to thyrotoxicosis (n = 18) or to nodular thyroid disease in the presence (n = 9) or absence (n = 30) of cytological follicular neoplasia. CCH was seen in 28 of 57 (49%) of all patients. CCH was more common in hyperthyroid (12/18 [66%]) than in euthyroid (16/39 [41%] patients. No age- or gender-related differences in the occurrence of CCH was seen. There was no histological evidence of medullary thyroid carcinoma (MTC) in any patient. CCH classified histologically as neoplastic was encountered in two instances. It was concluded that CCH may be expected in almost 50% of normocalcitonemic patients with various thyroid disorders. Although the potential clinical importance of this histological finding and specifically its neoplastic variety remains unknown, these results are in keeping with the assumption that pentagastrin-stimulated plasma concentrations of hCT within the normal range do not exclude the presence of CCH.

Adult↗
PubMed2000

High prevalence of hyperhomocysteinemia in critically ill patients.

OBJECTIVE: To test the hypothesis that the prevalence of hyperhomocysteinemia is increased in critically ill patients and correlates with disease severity and mortality in these patients. DESIGN: A prospective study. SETTING: Three medical intensive care units at the University of vienna Medical School serving both medical and surgical patients. PATIENTS: All consecutive admissions (n = 56) during a period of 4 wks. A total of 112 age- and gender-matched healthy individuals constituted the control group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn within 24 hrs after admission for analysis of total homocysteine (tHcy), folate, vitamin B6 levels, and vitamin B12 levels as well as to identify the 677C-->T polymorphism in the gene coding for the enzyme 5,10-methylenetetrahydrofolate reductase. Acute Physiology and Chronic Health Evaluation III scores at admission and 24 hrs after admission as well as 30-day survival were documented in all patients. Hyperhomocysteinemia was more prevalent in critically ill patients (16.1%; 95% confidence interval, 7.6% to 28.3%) compared with age- and gender-matched healthy individuals (5.4%; 95% confidence interval, 2.0% to 11.3%; chi-square test; p = .022). There was no difference in tHcy plasma concentrations in the first 24 hrs after admission to an intensive care unit between survivors and nonsurvivors. The 5,10-methylenetetrahydrofolate reductase 677C-->T polymorphism had no influence on tHcy levels and survival of intensive care unit patients. CONCLUSIONS: The prevalence of hyperhomocysteinemia is increased in critically ill patients compared to age- and gender-matched healthy individuals. The clinical significance of this finding remains to be determined.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2000

Epinephrine application via an endotracheal airway and via the Combitube in esophageal position.

OBJECTIVE: To compare plasma concentrations and cardiovascular effects of epinephrine after application via a conventional endotracheal airway and via the esophageal lumen of a new emergency airway, the esophageal tracheal Combitube. DESIGN: Prospective, randomized study. SETTING: Center for Biomedical Research, University of Vienna. SUBJECTS: Fourteen juvenile swine received either an endotracheal tube (Group A) or a Combitube in esophageal position (Group B). INTERVENTIONS: In Part I of the study, epinephrine was administered during spontaneous beating of the heart; in Part II, epinephrine was administered during cardiopulmonary resuscitation, using a ten-fold higher dosage in Group B, respectively. MEASUREMENTS: Plasma epinephrine levels were measured 1, 2, 3, 5, 7, 10, 15, and 30 mins after application. Systolic arterial blood pressure and cardiac output in Part I, and end-tidal CO2 and coronary perfusion pressure in Part II were recorded. MAIN RESULTS: In Part I, increased levels of plasma epinephrine and systolic arterial pressure were maintained significantly longer in Group B when compared with Group A. In Part II, no significant differences between the groups were found with regard to plasma epinephrine levels and hemodynamic variables. CONCLUSION: Epinephrine applied via the esophageal lumen of the Combitube in a ten-fold higher dosage has similar effects on plasma epinephrine levels and hemodynamic variables compared to endotracheal administration.

Animals↗
PubMed1999

Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the antipyretic efficacy of aspirin and acetaminophen (INN, paracetamol) in 30 male volunteers with the use of endotoxin (lipopolysaccharide) to elicit a standardized febrile response. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in parallel groups. Subjects received an intravenous endotoxin bolus of 4 ng/kg after premedication with either placebo, 1000 mg aspirin, or 1000 mg acetaminophen by mouth. RESULTS: Peak body temperatures were 38.5 degrees C +/- 0.2 degrees C in the placebo group, 37.6 degrees C +/- 0.2 degrees C in the acetaminophen group (P = .001 versus placebo), and 38.6 degrees C +/- 0.2 degrees C in the subjects treated with aspirin (P = .001 versus acetaminophen; P = .570 versus placebo) at 4 hours after lipopolysaccharide infusion. Subjective symptom scores for chills and perception of fever were higher in the placebo group than in the acetaminophen group (chills, 2.5 +/- 0.3 versus 1.0 +/- 0.2, P = .009 and fever, 2.5 +/- 0.2 versus 2.0 +/- 0.2, P = .021). Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 levels rose by several orders of magnitude (P < .001 versus baseline in all groups), without significant intergroup differences. CONCLUSIONS: Acetaminophen was the superior antipyretic drug in endotoxemia compared with aspirin. Treatment with acetaminophen ameliorates subjective symptoms induced by endotoxemia without compromising the humoral response of a subject to endotoxin. This observation has clinical interest and may also help to improve the lipopolysaccharide model, which can be used to test anti-inflammatory and anticoagulatory drugs.

Acetaminophen↗
PubMed1999

Relationship of serum levels of endogenous relaxin to cervical size in the second trimester and to cervical ripening at term.

OBJECTIVE: To assess whether cervical size in the early second trimester and cervical ripening at term may be related to serum levels of endogenous relaxin, 17beta-oestradiol or progesterone. DESIGN: A cross-sectional study investigating the relationship between hormone concentrations and cervical parameters as measured by ultrasound and Bishop score, respectively. PARTICIPANTS: Uncomplicated human pregnancies with normal fetal outcome, 72 women in the second trimester and 40 women at term. METHODS: Vaginal ultrasound and palpation were used to estimate cervical parameters. Hormones were analysed either by dissociation-enhanced fluoroimmunoassay (relaxin) or by automated electrochemiluminescent immunoassays. RESULTS: Cervical length and diameter correlated positively during mid-gestation and negatively at term. During mid-gestation, but not at term, relaxin was significantly associated with cervical length and volume, and with progesterone. Bishop score only correlated inversely with progesterone at term. CONCLUSION: Corpus luteum function is reflected by progesterone and relaxin in the early second trimester. An impact of relaxin on cervical growth, previously demonstrated by animal models and in vitro experiments, was confirmed during human mid-gestation. In contrast to many other species, human cervical ripening was not associated with endogenous relaxin at term, but with decreased progesterone.

Adult↗
PubMed1999

The role of oxytocin in relation to female sexual arousal.

Oxytocin is clearly involved in human reproduction and serves an important role in sexual arousal. Oxytocin serum levels were measured before and after sexual stimulation in 12 healthy women. Values of oxytocin 1 min after orgasm were significantly higher (p < 0.05) than baseline levels. This finding supports the hypothesis that oxytocin plays a major part in human sexual response both in neuroendocrine function and postcoital behavior.

Adult↗
PubMed1998

Adrenal function in patients with chronic renal failure.

Previous studies have reported divergent findings on the function of the hypothalamic-pituitary-adrenal axis in patients with chronic renal failure (CRF). The low-dose adrenocorticotropin (ACTH) test offers the possibility of unmasking adrenal dysfunction, which might remain undiscovered using the ACTH test with the standard 250-microg dose. Furthermore, the choice of renal replacement therapy (either hemodialysis or continuous ambulatory peritoneal dialysis [CAPD]) might have an impact on adrenal function. To investigate these possibilities, ACTH tests were performed with three different doses (ie, 1, 5, and 250 microg) in 14 CRF patients and in seven healthy controls. Seven of the CRF patients were receiving chronic hemodialysis and seven were receiving CAPD. Basal plasma concentrations of cortisol were comparable in the three groups tested (5.3+/-0.4 microg/dL in the controls, 6.6+/-0.7 microg/dL in the hemodialysis patients, and 7.9+/-1.0 microg/dL in the CAPD patients), whereas basal ACTH concentrations were significantly elevated in the CRF patients (28.5+/-3.8 pg/mL in the hemodialysis patients and 33.0+/-6.0 pg/mL in the CAPD patients) when compared with normal controls (17.0+/-1.4 pg/mL; P < 0.05). All three doses of ACTH resulted in a rapid increase of plasma cortisol concentrations that was comparable in all three groups. In the hemodialysis patients, a trend toward a diminished response to the lowest dose of 1 microg was noticed. We conclude, therefore, that adrenal response to ACTH in various doses is unaffected in CRF independent of whether hemodialysis or CAPD is chosen for renal replacement therapy.

Adrenal Glands↗
PubMed1998

Normal serum concentrations of sex hormone binding-globulin in patients with hyperthyroidism due to subacute thyroiditis.

Serum concentrations of sex hormone binding-globulin (SHBG) were determined in patients with hyperthyroidism (n = 94; 12 men, 82 women) due to either Graves' disease (n = 59; 11 men, 48 women), autonomous thyroid adenomas (n = 23; 1 man, 22 women), or subacute thyroiditis (n = 12; all women). Elevated serum concentrations of SHBG were initially seen in 57 of 82 patients (69%) with hyperthyroidism due to either Graves's disease or due to autonomous adenoma. Elevated serum SHBG concentration was more frequent in patients with serum total thyroxine (TT4) concentrations greater than 15.0 microg/dL (32/39 [82%]; including 3 patients with autonomous adenoma) compared to those with serum TT4 concentration between 11.0 and 15.0 microg/dL (21/27 [77%]; including 7 patients with autonomous adenoma), or patients with an isolated elevation of serum total triiodothyronine (TT3) concentration (4/16 [25%]; including 2 patients with autonomous adenoma). Serum SHBG concentration normalized when patients became euthyroid. Only 1 of 12 patients in the hyperthyroid phase of subacute thyroiditis had an elevated serum concentration of SHBG. Serum concentrations of thyroid binding globulin (TBG) and transcortin (CBG) were normal in all but 1 patient. In patients with hyperthyroidism as a result of Graves' disease or autonomous adenoma serum SHBG concentrations were elevated with the greatest elevation found in patients with the highest serum T4 concentrations. The normal concentrations of SHBG in the hyperthyroid phase of subacute thyroiditis most likely reflects the shorter duration of exposure to increased thyroid hormone in this condition.

Adenoma↗
PubMed1998

Hyperprolactinemia, a tool in treatment control of tetrahydrobiopterin deficiency: endocrine studies in an affected girl.

Severe tetrahydrobiopterin (BH4) deficiency is a naturally occurring model of cerebral catecholamine and serotonin shortage. Examination of the stimulated release and physiologic secretion pattern of several hormones in affected individuals permits certain conclusions concerning the involvement of these neurotransmitters in hormone regulation. Treatment, moreover, permits the ranking of the quality of the therapeutic regimens in use according to the degree of hormonal alteration. The 24-h secretion pattern of prolactin, GH, cortisol, and melatonin and the stimulated release of prolactin, GH, TSH, and gonadotropins were studied in an affected girl. Severe hyperprolactinemia with disruption of the pulsatile and circadian secretion pattern was the prevailing feature. The GH physiologic secretion pattern was not affected, but its stimulation was impaired. Melatonin displayed a normal circadian secretion pattern; the rhythm, however, was advanced by several hours. Conventional treatment of BH4 deficiency, i.e. BH4, 5-hydroxytryptophan, and L-DOPA/carbidopa (the last named given in three doses per day), suppresses prolactin levels merely for a few hours. L-DOPA/carbidopa given at shorter intervals or, even better, as a slow release preparation, is more effective in suppressing prolactin levels. Our data indicate immense hyperprolactinemia but few other hormonal disturbances in severe BH4 deficiency. Prolactin secretion may serve as an extremely sensitive marker for the hypothalamic dopamine content under different therapeutic regimens. Treatment with an L-DOPA/carbidopa slow release preparation produces virtually normal prolactin levels.

Adolescent↗
PubMed1998

Elecsys TSH, FT4, T4, T-uptake, FT3 and T3. Clinical results of a multicentre study.

6 assays for the assessment of thyroid function (TSH, FT4, T4, T-uptake, FT3 and T3) were targets of the International Multicenter Study on the random access analyzer Elecsys 2010. The aim of the study was to characterize the clinical performance of the assay in method comparison and reference range studies. The assays under evaluation were compared to a broad variety of radio isotopic and non-radio isotopic assays. They are suitable for serum and plasma samples. In case of TSH the study include 2nd and 3rd generation TSH procedures. In general, good to excellent correlations were found between the Elecsys and the respective routine methods. Systematic deviations were extraordinary low in case of TSH, FT4 and T4. Regarding the analysis of T3 and FT3 some systematic deviations in terms of standardization have been observed. Results of Elecsys T4 and Elecsys FT4 were independent of the serum total protein or serum albumin concentrations. In T3 and FT3 Elecsys the results of samples from NTI (non-thyroidal-illness) patients were decreased, reflecting the physiological situation in these patients. Studies using samples from healthy euthyroid as well as untreated hypo- and hyperthyroid individuals enabled us to assess the assays reference ranges.

Humans↗
PubMed1998

Results of the multicentre evaluation of an electrochemiluminescence immunoassay for HCG on Elecsys 2010.

This study evaluated the performance of the HCG STAT Elecsys assay in 8 European laboratories using the Elecsys 2010 system. Analytical sensitivity was < 0.5 mlU/mL. The analysis of concentration series prepared by mixing serum pools with high and low HCG concentrations proved linearity up to 10.000 mIU/mL. A high-dose hook effect was not seen up to HCG concentrations of 430.000 mIU/mL. The medians of the within-run CVs (n = 21, 3 series) were 3.0% (2.1-5.8% CV; 10.4-14.4 mIU/mL), 2.4% (1.7-6.1% CV; 35.6-88.6 mIU/mL) and 2.3% (1.7-6.1% CV; 282.3-643.8 mIU/mL). The medians of the between-day imprecisions (n = 10-21) were 7.0% CV (5.2-12.0% CV; 4.0-14.0 mIU/mL), 5.5% CV (3.1-7.2% CV; 35.4-92.7% mIU/mL) and 4.1% CV (2.8-5.1% CV; 270.8-658.0 mIU/mL). The median recovery of two external quality control samples with assigned values of 9.39 and 10.40 mIU/mL) were 101.2 and 104.3% (ranges: 94.8-116.1%, 98.6-117.8%, n = 10). The assay was compared with five non-isotopic automated routine immunoassay systems (x). Slopes ranged from 0.87 to 1.15 and intercepts from-0.53 to 12.50 mIU/mL. The coefficients of correlation were with one exception (0.898) > or = 0.960. The distribution of HCG in samples from non-pregnant women and healthy men was very similar to that observed with other automated routine methods. The HCG Elecsys assay is very specific for the intact holo-hormone. Nicked HCG dimer, nicked and non-nicked beta-subunits are weakly recognised or not detected. Hemoglobin, bilirubin and lipemia (tested up to: Hb, 3.7 g/L; bilirubin, 500 mumol/L; triglyceride, 37.6 mmol/L) did not interfere the assay. The HCG Elecsys assay is well suited for the early and fast diagnosis of normal pregnancy and the detection of tubal pregnancy.

Adult↗
PubMed1997

Tissue polypeptide-specific antigen in pediatric patients: assessment of normal values.

Measurement of serum concentrations of tissue polypeptide-specific Antigen (TPS) has been demonstrated to the useful in diagnosis and monitoring of adult epithelial tumors. So far, no data have been available on normal or pathologic TPS values in children. Therefore, the present study was designed to evaluate the normal values of TPS in childhood. Using a commercial enzyme linked immunosorbent assay (ELISA) kit, serum TPS was determined in 361 healthy children. Median (M) TPS was found to be 107 U/l at birth (n = 124). By the end of the first week, the value rose to M = 150 U/l (n = 68) and then continuously decreased with age (1 week-1 year, n = 45, M = 88 U/l; 1-7 years, n = 75, M = 51 U/l) until reaching the adult level (8-18 years, n = 49, M = 34 U/l). Additionally, the serum TPS values of 45 mothers right after delivery (M = 161 U/l) were assessed, and there was no correlation to the marker levels determined in the cord blood of their children. The age-dependent distribution of serum TPS in healthy children must be taken into account in the clinical application of this tumor marker.

Adolescent↗