Biomedical subjects

Christian Meier

Publications and source records attributed to Christian Meier.

27 records · Page 2Linked to original sources

PubMed2003

Diffusion in compartmental systems. II. Diffusion-weighted measurements of rat brain tissue in vivo and postmortem at very large b-values.

Diffusion-weighted single-voxel (1)H spectroscopic measurements were performed on rat brain tissue in vivo and postmortem. Diffusion weighting was achieved by varying the diffusion time from 23 ms to 1.18 sec via the mixing time in a stimulated echo sequence. A series of constant gradient (cg-) experiments of eight effective gradient strengths q(2)(q(2) = gamma(2)delta(2)g(2)) from 24.2 x 10(3) to 490.2 x 10(3) mm(-2) was performed, resulting in a maximum attenuation factor of b = 580,000 s/mm(2). A fit of three exponential terms was found to be appropriate to represent the attenuation signal over the whole b-range. The behavior of the slowest decaying component can be fully understood in terms of a long time limit of a modified Kärger formalism for a two-compartment system. This allowed estimation of the transmembrane water exchange rate: the intracellular exchange time was determined to be 622 +/- 29 ms and 578 +/- 20 ms in vivo and postmortem, respectively.

Animals↗

PubMed2003

Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial.

Hypothyroidism is associated with premature atherosclerosis and cardiovascular disease. Recently, total homocysteine (tHcy) and C-reactive protein (CRP) emerged as additional cardiovascular risk factors. We first investigated CRP and tHcy in different severities of primary hypothyroidism and in a second study we evaluated the effect of L-thyroxine treatment in patients with subclinical hypothyroidism (SCH) in a double-blind, placebo-controlled trial. One hundred and twenty-four hypothyroid patients (63 with subclinical, 61 with overt hypothyroidism, OH) and 40 euthyroid controls were evaluated. CRP was measured using a latex-based high sensitivity immunoassay; tHcy was determined by a fluorescence polarization immunoassay. tHcy values were significantly elevated in OH (P=0.01). In SCH tHcy levels were not augmented as compared to controls. CRP values were significantly increased in OH (P=0.016) and SCH (P=0.022) as compared to controls. In a univariate analysis tHcy correlated significantly with fT4, vitamin B12, folic acid and creatinine levels. In multiple regression analysis only fT4 (beta=0.33) had a significant effect on tHcy. CRP did not correlate with thyroid hormones. In SCH, L-T4 replacement had no significant effect on either tHcy or CRP levels. This is the first paper to show that CRP values increase with progressive thyroid failure and may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. In contrast to overt disease, only CRP, but not tHcy values, are affected in SCH, yet without significant improvement after L-thyroxine therapy.

Aged↗

PubMed2003

Prolactin dysregulation in women with subclinical hypothyroidism: effect of levothyroxine replacement therapy.

This study investigated the effect of levothyroxine treatment on serum prolactin (PRL) levels in women with subclinical hypothyroidism. Sixty-six women (mean age, 58.5 +/- 1.3 years) with confirmed subclinical hypothyroidism (mean thyrotropin [TSH], 11.7 +/- 0.8 mIU/L) were randomly assigned to receive levothyroxine or placebo for 48 weeks. Based on blinded TSH monitoring, physiologic levothyroxine replacement (85.5 +/- 4.3 microg/d; TSH, 3.1 +/- 0.3 mIU/L) was ascertained throughout the study. PRL levels were measured before and after administration of thyrotropin-releasing hormone (TRH) at baseline, after 24 and 48 weeks. Sixty-three of the 66 women completed the study. At baseline, basal PRL levels were elevated in 19% of the patients. None of the patients reported menstrual disturbances, infertility, or galactorrhea. In the levothyroxine group (n = 31) basal and peak PRL levels were significantly reduced after 24 and 48 weeks (p = 0.03 and p = 0.001). Mean changes in PRL levels differed significantly between the two treatment groups after 24 weeks (p = 0.03 and p = 0.01). The treatment effect was more pronounced in patients with PRL and TSH levels above the median at baseline (i.e., PRL > 16 ng/mL; TSH > 11 mIU/L). Based on this double-blinded, placebo-controlled study we demonstrate that in subclinical hypothyroidism PRL regulation is altered with elevated basal and stimulated PRL levels, and that physiologic levothyroxine treatment restores PRL concentrations.

Double-Blind Method↗

PubMed2003

Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysis.

OBJECTIVES: The aim of this study was first to investigate whether early total thyroidectomy (ETT; 1-5 years of age) can prevent medullary thyroid carcinoma with persistent or recurrent disease (PRD) in pediatric patients with multiple endocrine neoplasia type 2A (MEN-2A) and second, to evaluate the strength of codon analysis in children with MEN-2A as prognostic parameter. METHODS: Case reports and review of the literature for pediatric patients with MEN-2A were conducted. Inclusion criteria were age (0-20 years) and histologic degree of C-cell disease (normal = N, C-cell hyperplasia = CCH, medullary thyroid carcinoma = MTC, metastatic MTC = MMTC). To evaluate therapeutic results of ETT (1-5 years) versus late total thyroidectomy (LTT; 6-20 years), age-dependent histologic stages of C-cell disease and postoperative occurrence of PRD were compared. Prognostic value of specific codons, age-dependent histologic distribution, and long-term outcome were analyzed. RESULTS: In a total of 260 cases, 42 (16%) underwent ETT, and 218 (84%) underwent LTT. Histologic analysis showed significant difference between ETT versus LTT (57% vs 76%) regarding malignant stage of C-cell disease (of combined rate of MTC and MMTC). Long-term outcome was documented in 74 patients (28%). During a median follow-up period of 2 years (range: 0-15 years), 21 of 65 of the LTT group versus 0 of 9 of the ETT group suffered PRD. Information about codon analysis was available in 150 patients (58%). Mutated codons were c634 (63%), c618 (19%), c620 (9%), and c804 (6%). Codon-related histologic analysis resulted in prognostic differences: 81% of patients with c634-mutation had MCT or MMTC in contrast to c804 (44%), c618 (34%), and c620 (7%). Fifteen of 17 MMTC and 7 of 9 PRD occurred in patients with c634-mutation. CONCLUSIONS: 1) ETT until 5 years of age in MEN-2A gene carriers results in significant reduction of MTC and MMTC in favor of CCH and improved disease-free long-term outcome. 2) Codon analysis is an important prognostic factor. Timing of TT could be individualized based on codon-specific prognosis. Until more detailed knowledge is available, consequent genetic and biochemical screening is mandatory for appropriate individual timing of ETT before age of 5 years.

Adolescent↗

PubMed2002

Activation of system L heterodimeric amino acid exchangers by intracellular substrates.

System L-type transport of large neutral amino acids is mediated by ubiquitous LAT1-4F2hc and epithelial LAT2-4F2hc. These heterodimers are thought to function as obligatory exchangers, but only influx properties have been studied in some detail up until now. Here we measured their intracellular substrate selectivity, affinity and exchange stoichiometry using the Xenopus oocyte expression system. Quantification of amino acid influx and efflux by HPLC demonstrated an obligatory amino acid exchange with 1:1 stoichiometry. Strong, differential trans-stimulations of amino acid influx by injected amino acids showed that the intracellular substrate availability limits the transport rate and that the efflux selectivity range resembles that of influx. Compared with high extracellular apparent affinities, LAT1- and LAT2-4F2hc displayed much lower intracellular apparent affinities (apparent K(m) in the millimolar range). Thus, the two system L amino acid transporters that are implicated in cell growth (LAT1-4F2hc) and transcellular transport (LAT2-4F2hc) are obligatory exchangers with relatively symmetrical substrate selectivities but strongly asymmetrical substrate affinities such that the intracellular amino acid concentration controls their activity.

Amino Acids↗

PubMed2002

Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies.

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4-6/>6-12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03). This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0-15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.

Autoantibodies↗

PubMed1998

Synthesis and Characterization of Neutral Hexanuclear Iron Sulfur Clusters Containing Stair-like [Fe(6)(&mgr;(3)-S)(4)(&mgr;(2)-SR)(4)] and Nest-like [Fe(6)(&mgr;(3)-S)(2)(&mgr;(2)-S)(2)(&mgr;(4)-S)(&mgr;(2)-SR)(4)] Core Structures.

The binuclear iron complex [{Fe("EtN(2)S(2)")}(2)] (1b, "EtN(2)S(2)" = N,N'-diethyl-3,7-diazanonane-1,9-dithiolate) was prepared from the free ligand and ferrous bis[bis(trimethylsilyl)amide] in toluene. In dichloromethane 1b reacts with the [Fe(4)S(4)I(4)](2-) cubane cluster to displace two iodo ligands and to form the neutral hexanuclear cluster [{Fe("EtN(2)S(2)")}(2)Fe(4)S(4)I(2)] (2), which is isolated as black crystals in 87% yield. As elucidated by an X-ray structure analysis, 2 contains the novel hexanuclear stair-like [Fe(6)(&mgr;(3)-S)(4)(&mgr;(2)-SR)(4)] core, which exhibits crystallographic inversion symmetry. The compound crystallizes as a solvate with two molecules of CH(2)Cl(2) per formula unit in the monoclinic space group P2(1)/n with a = 1570.5(2) pm, b = 1060.2(1) pm, c = 1604.0(2) pm, beta = 114.93(1) degrees, and Z = 2. In the aprotic polar solvents DMF, 1,2-propylenecarbonate, and DMSO, 2 dissolves with decomposition and formation of the cluster [{Fe("EtN(2)S(2)")}(2)Fe(4)S(5)] (3), which is isolated as black needles from DMF. 3.2DMF crystallizes in the triclinic space group P&onemacr; with a = 950.9(1) pm, b = 1086.0(1) pm, c = 2381.5(2) pm, alpha = 101.81(1) degrees, beta = 91.94(1) degrees, gamma = 97.01(1) degrees, and Z = 2. The neutral compound contains a nest-like [Fe(6)(&mgr;(4)-S)(&mgr;(3)-S)(2)(&mgr;(2)-S)(2)(&mgr;(2)-SR)(4)] core of idealized C(2)(v)() symmetry that is closely related to that of other well-known clusters, e.g., the cluster anion [Fe(6)S(9)(SR)(2)](4-). The zero-field (57)Fe Mössbauer spectrum of 3 is in accordance with four Fe(2.5+)S(4) centers (delta = 0.46 mm/s; DeltaE(Q) = 1.14 mm/s) and two N(2)S(3)-bound high-spin Fe(2+) sites (delta = 0.83 mm/s; DeltaE(Q) = 3.64 mm/s). A total cluster spin of 0 is deduced from the Mössbauer spectrum at 4.2 K and 5.3 T, which yields magnetic splitting from the applied field only. For 2, three subspectra are observed in the Mössbauer spectrum (a, delta = 0.45 mm/s, DeltaE(Q) = 1.05 mm/s; b, delta = 0.55 mm/s, DeltaE(Q) = 1.61 mm/s, c, delta = 0.80 mm/s; DeltaE(Q) = 3.83 mm/s) reflecting different coordination environments of the iron atoms rather than different oxidation states. The electrochemical properties of 1b, 2, and 3 were determined by cyclic voltammetry. 1b can be quasi-reversibly oxidized in dichloromethane solution at -75 mV (vs SCE). Whereas 2 shows only an irreversible redox behavior in N,N'-dimethylimidazolidin-2-one solution, 3 in the same solvent can be quasi-reversibly reduced in two consecutive steps at -830 and -1630 mV (vs SCE) to the dianion, which consists entirely of Fe(II).

Journal Article↗

PubMedDate not supplied

Cardiovascular flow measurement with phase-contrast MR imaging: basic facts and implementation.

Phase-contrast magnetic resonance (MR) imaging is a well-known but undervalued method of obtaining quantitative information on blood flow. Applications of this technique in cardiovascular MR imaging are expanding. According to the sequences available, phase-contrast measurement can be performed in a breath hold or during normal respiration. Prospective as well as retrospective gating techniques can be used. Common errors in phase-contrast imaging include mismatched encoding velocity, deviation of the imaging plane, inadequate temporal resolution, inadequate spatial resolution, accelerated flow and spatial misregistration, and phase offset errors. Flow measurements are most precise if the imaging plane is perpendicular to the vessel of interest and flow encoding is set to through-plane flow. The sequence should be repeated at least once, with a high encoding velocity used initially. If peak velocity has to be estimated, flow measurement is repeated with an adapted encoding velocity. The overall error of a phase-contrast flow measurement comprises errors during prescription as well as errors that occur during image analysis of the flow data. With phase-contrast imaging, the overall error in flow measurement can be reduced to less than 10%, an acceptable level of error for routine clinical use.

Aorta↗

PubMedDate not supplied

Effect of restoration of euthyroidism on peripheral blood cells and erythropoietin in women with subclinical hypothyroidism.

BACKGROUND: In overt hypothyroidism (OH) anemia is common, while less frequently basophilia has been described. In subclinical hypothyroidism (SCH), however, data on the distribution of peripheral blood cells are lacking. Therefore, we evaluated the effects of L-T4 replacement therapy on peripheral blood elements in female patients with SCH before and after restoration of euthyroidism in a randomized, double-blind and placebo-controlled study. PATIENTS AND METHODS: Sixty-six women with SCH (TSH 12.9 +/- 8.2 mU/L) were randomly assigned to receive L-thyroxine or placebo for 48 weeks. 63 of the 66 women completed the study. Peripheral blood cells were measured at baseline and 48 weeks after L-thyroxine or placebo treatment, respectively. RESULTS: The percentage of lymphocytes decreased (p<0.05), whereas percent of monocytes (p<0.05) and eosinophiles (p<0.05) increased significantly upon restoration of euthyroidism after 48 weeks. Hemoglobin and hematocrit remained unchanged throughout the study period. However, erythropoietin levels increased significantly (p<0.01) during L-T4 treatment. In the placebo group all parameters remained unchanged throughout the study. CONCLUSIONS: Overall, we observed subtle alterations of the leuco-lympho-monocytic distribution of the peripheral blood cells upon restoration of euthyroidism in patients with SCH. Hemoglobin and Hematocrit remained unchanged; however, the increasing level of erythropoietin during L-T4 treatment suggests an already stimulated, yet compensated erythropoietic system in mild thyroid failure.

Journal Article↗