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Biomedical subjects

N H Andersen

Publications and source records attributed to N H Andersen.

At least 19 recordsLinked to original sources

NT-proBNP in normoalbuminuric patients with Type 2 diabetes mellitus.

OBJECTIVE: To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes. RESEARCH DESIGN AND METHODS: The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings. RESULTS: Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function. CONCLUSIONS: NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters.

Albuminuria↗

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.

Blood Flow Velocity↗

Relation between plasma amino-terminal propeptide of procollagen type III and left ventricular longitudinal strain in essential hypertension.

OBJECTIVE: To investigate whether myocardial fibrosis assessed non-invasively is related to left ventricular (LV) longitudinal systolic function in patients with essential hypertension. DESIGN: The study consisted of 30 control subjects and 40 patients with hypertension with normal LV ejection fraction. Tissue Doppler echocardiography was performed to assess LV longitudinal systolic strain from the apical views. Mean strain was calculated from the basal and mid segments. Plasma concentrations of the amino-terminal propeptide of type III procollagen (PIIINP) were measured. RESULTS: In the hypertension group, mean strain was significantly reduced (mean (SD) 13 (6)% v 21 (6)%, p < 0.01) and plasma PIIINP were increased compared with controls (3.0 (0.7) microg/l v 2.1 (0.3) microg/l, p < 0.001). A significant correlation was found between mean strain and PIIINP (r = -0.56, p < 0.001). In patients with abnormal diastolic filling (n = 21) mean strain was reduced compared with patients with normal LV filling (n = 19) (10 (6)% v 15 (6)%, p < 0.01) and the serological marker PIIINP was increased (3.5 (0.6) microg/l v 2.5 (0.5) microg/l, p < 0.001). CONCLUSIONS: There is a significant association between the extent of myocardial fibrosis and reduced LV longitudinal contractility.

Case-Control Studies↗

Impact of essential hypertension and diabetes mellitus on left ventricular systolic and diastolic performance.

AIMS: To investigate left ventricular systolic and diastolic function in patients with essential hypertension and diabetes mellitus associated with hypertension by the myocardial performance index (MPI). METHODS AND RESULTS: The study included 45 patients with essential hypertension, 45 patients with diabetes mellitus and hypertension and 45 normal subjects, who underwent a complete two-dimensional and Doppler echocardiography including assessment of the isovolumetric Doppler time intervals for the estimation of the Doppler-derived MPI. The MPI was significantly higher in patients with essential hypertension and diabetes with hypertension, compared to controls (Essential hypertension=0.51+/-0.12; Diabetes=0.51+/-0.12 vs. controls 0.40+/-0.05, P=0.001). The isovolumetric contraction time was significantly prolonged in essential hypertension (56+/-26 msec vs. 40+/-17 msec, P<0.01 respectively) and among diabetes patients isovolumetric relaxation time was prolonged compared to normal subjects (100+/-20 ms vs. 87+/-16 ms, P<0.01, respectively). The index was not related to left ventricular mass, age or ejection fraction, but significantly correlated to E-wave deceleration time (rho=0.48, P<0.001). CONCLUSIONS: The MPI is increased, in both essential hypertensive patients and diabetes patients with associated hypertension, despite normal ejection fraction.

Diabetes Complications↗

Decreased left ventricular longitudinal contraction in normotensive and normoalbuminuric patients with Type II diabetes mellitus: a Doppler tissue tracking and strain rate echocardiography study.

Type II diabetes mellitus is associated with congestive heart failure with preserved ejection fraction. This group of patients has been assumed to have isolated diastolic dysfunction; however, the longitudinal systolic contraction of the left ventricle has not been studied previously. The objective of the present study was to investigate the longitudinal contraction of the left ventricle in normotensive Type II diabetes mellitus patients with normal ejection fraction. We examined 32 normotensive patients with Type II diabetes mellitus with ejection fraction >0.55 and fractional shortening >0.25. Exclusion criteria were angina pectoris, cardiac valve disease, albuminuria, retinopathy or neuropathy. Normal subjects (n =32) served as controls. A 16 segment model of motion amplitude assessed left ventricular longitudinal contraction and the average of the segments was calculated as the tissue tracking score index. Peak systolic velocity and strain rate was also obtained in each segment. Patients with Type II diabetes mellitus had a significantly lower tissue tracking score index compared with normal subjects (5.8+/-1.6 mm compared with 7.7+/-1.1 mm; P <0.001). Mean peak systolic velocity was also significantly lower (4.3+/-1.5 cm/s compared with 5.4+/-1.0 cm/s; P <0.001), as well as peak systolic strain rate (-1.2+/-0.3 s(-1) compared with -1.6+/-0.4 s(-1); P <0.001). Patients with Type II diabetes mellitus and preserved diastolic function had a significantly lower tissue tracking score index compared with normal subjects (6.6+/-1.5 mm; P <0.001), but patients with diastolic dysfunction had an even more profound decrease in tissue tracking score index compared with patients without diastolic dysfunction (4.9+/-0.9 mm; P <0.01). In conclusion, the longitudinal systolic contraction was significantly decreased in normotensive patients with Type II diabetes mellitus with normal ejection fraction, which was most profound in patients with concomitant diastolic dysfunction.

Case-Control Studies↗

Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications.

OBJECTIVE: Osteoprotegerin (OPG) is a newly identified inhibitor of bone resorption. Recent studies indicate that OPG also acts as an important regulatory molecule in the vasculature. Plasma levels of OPG seem to be elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. The aim of the present study was to examine the association between plasma OPG levels and microvascular complications and glycemic control in patients with type 2 diabetes. DESIGN AND METHODS: Four groups of 20 subjects in each, individually matched for age and gender, were included in the study: (i) subjects with normal glucose tolerance (NGT); (ii) subjects with impaired glucose tolerance (IGT); (iii) type 2 diabetic patients without retinopathy; and (iv) type 2 diabetic patients with diabetic maculopathy (DMa). Plasma concentration of OPG was measured in duplicate by a sandwich ELISA method. Furthermore, fundus photography, flourescein angiography, and measurements of urinary albumin excretion rate (RIA) were performed. RESULTS: Plasma OPG was significantly higher in diabetic (iii+iv) than in NGT (i) subjects (3.04+/-0.15 vs 2.54+/-0.16 ng/ml, P<0.05). Plasma OPG was significantly higher in the DMa (iv) group than in the NGT (i) group (3.25+/-0.23 vs 2.54+/-0.16 ng/ml, P=0.01). Moreover, plasma OPG was significantly higher (3.61+/-0.36 ng/ml) in the group of diabetic subjects with both microalbuminuria and DMa (n=7) than in the NGT (i) (2.54+/-0.16 ng/ml, P<0.01), IGT (ii) (2.82+/-0.21 ng/ml, P<0.05), and no retinopathy (iii) groups (2.83+/-0.20 ng/ml, P<0.05). CONCLUSIONS: We found increased levels of OPG in plasma from diabetic patients with microvascular complications. This finding indicates that OPG may be involved in the development of vascular dysfunction in diabetes [corrected].

Albuminuria↗

Exendin-4 and glucagon-like-peptide-1: NMR structural comparisons in the solution and micelle-associated states.

Exendin-4, a 39 amino acid peptide originally isolated from the oral secretions of the lizard Heloderma suspectum, has been shown to share certain activities with glucagon-like-peptide-1 (GLP-1), a 30 amino acid peptide. We have determined the structuring preferences of exendin-4 and GLP-1 by NMR in both the solution and dodecylphosphocholine (DPC) micelle-associated states. Based on both chemical shift deviations and the pattern of intermediate range NOEs, both peptides display significant helicity from residue 7 to residue 28 with greater fraying at the N-terminus. Thornton and Gorenstein [(1994) Biochemistry 33, 3532-3539] reported that the presence of a flexible, helix-destabilizing, glycine at residue 16 in GLP-1 was an important feature for membrane and receptor binding. Exendin-4 has a helix-favoring glutamate as residue 16. In the micelle-associated state, NMR data indicate that GLP-1 is less helical than exendin-4 due to the presence of Gly16; chemical shift deviations along the peptide sequence suggest that Gly16 serves as an N-cap for a second, more persistent, helix. In 30 vol-% trifluoroethanol (TFE), a single continuous helix is evident in a significant fraction of the GLP-1 conformers present. Exendin-4 has a more regular and less fluxional helix in both media and displays stable tertiary structure in the solution state. In the micelle-bound state of exendin-4, a single helix (residues 11-27) is observed with residues 31-39 completely disordered and undergoing rapid segmental motion. In aqueous fluoroalcohol or aqueous glycol, the Leu21-Pro38 span of exendin-4 forms a compact tertiary fold (the Trp-cage) which shields the side chain of Trp25 from solvent exposure and produces ring current shifts as large as 3 ppm. This tertiary structure is partially populated in water and fully populated in aqueous TFE. The Leu21-Pro38 segment of exendin-4 may be the smallest protein-like folding unit observed to date. When the Trp-cage forms, fraying of the exendin-4 helix occurs exclusively from the N-terminus; backbone NHs for the C-terminal residues of the helix display H/D exchange protection factors as large as 10(5) at 9 degrees C. In contrast, no tertiary structure is evident when exendin-4 binds to DPC micelles. An energetically favorable insertion of the tryptophan ring into the DPC micelle is suggested as the basis for this change. With the exception of exendin-4 in media containing fluoro alcohol cosolvents, NMR structure ensembles generated from the NOE data do not fully reflect the conformational averaging present in these systems. Secondary structure definition from chemical shift deviations may be the most appropriate treatment for peptides that lack tertiary structure.

Amino Acid Sequence↗

Coupled magnetic excitations in single crystal PrBa(2)Cu(3)O(6.2).

The dispersion of the low-energy magnetic excitations of the Pr sublattice in PrBa(2)Cu(3)O(6.2) is determined by inelastic neutron scattering measurements on a single crystal. The dispersion, which shows the effect of interactions with the Cu spin waves, is well described by a model of the coupled Cu-Pr magnetic system. This model enables values for the principal exchange constants to be determined. The results suggest that both Pr-Pr and Cu-Pr interactions are important in producing the anomalously high ordering temperature of the Pr sublattice. Measurements of the Cu optic spin wave mode show that the interlayer Cu-Cu exchange is significantly lower than in YBa(2)Cu(3)O(6.2).

Journal Article↗

Temperature dependence of the flux line lattice transition into square symmetry in superconducting LuNi2B2C.

We have investigated the temperature dependence of the H parallel to c flux line lattice structural phase transition from square to hexagonal symmetry, in the tetragonal superconductor LuNi2B2C ( T(c) = 16.6 K). At temperatures below 10 K the transition onset field, H2(T), is only weakly temperature dependent. Above 10 K, H2(T) rises sharply, bending away from the upper critical field. This contradicts theoretical predictions of H2(T) merging with the upper critical field and suggests that just below the H(c2)(T) curve the flux line lattice might be hexagonal.

Journal Article↗

Antiferromagnetic ordering in superconducting YBa2Cu3O6.5.

Commensurate antiferromagnetic ordering has been observed in the superconducting high- Tc cuprate YBa2Cu3O6.5 ( Tc = 55 K) by polarized and unpolarized elastic neutron scattering. The magnetic peak intensity exhibits a marked enhancement at Tc. Zero-field muon-spin-resonance experiments demonstrate that the staggered magnetization is not truly static but fluctuates on a nanosecond time scale. These results point towards an unusual spin density wave state coexisting with superconductivity.

Journal Article↗

Flux line lattice reorientation in the borocarbide superconductors with H parallel a.

Small angle neutron scattering studies of the flux line lattice in LuNi2B2C and ErNi2B2C induced by a field parallel to the a axis reveal a first order flux line lattice reorientation transition. Below the transition the flux line lattice nearest neighbor direction is parallel to the b axis, and above the transition it is parallel to the c axis. This transition cannot be explained using nonlocal corrections to the London model. In addition, the anisotropy of the penetration depth lambda and the coherence length xi change at the transition.

Journal Article↗

Applications of high-energy synchrotron radiation for structural studies of polycrystalline materials.

The large penetration power of high-energy X-rays (>60 keV) raises interesting prospects for new types of structural characterizations of polycrystalline materials. It becomes possible in a non-destructive manner to perform local studies, within the bulk of the material, of the fundamental materials physics properties: grain orientations, strain, dislocation densities etc. In favourable cases these properties may be mapped in three dimensions with a spatial resolution that matches the dimensions of the individual grains. Imbedded volumes and interfaces become accessible. Moreover, the high energies allow better in-situ studies of samples in complicated environments (industrial process optimization). General techniques for research in this energy range have been developed using broad-band angle-dispersive methods, on-line two-dimensional detectors and conical slits. Characterizations have been made at the level of the individual grains and grain boundaries as well as on ensembles of grains. The spatial resolution is presently of the order of 10-100 micom. Four examples of applications are presented along with an outlook.

Journal Article↗

Formation of a molten-globule-like state of myoglobin in aqueous hexafluoroisopropanol.

The effects of aqueous hexafluoroisopropanol (HFIP) media on the structure of myoglobin are reported. Circular dichroism (CD) spectra of this alpha-helical protein in as little as 4% (v/v) HFIP indicate that native-like amounts of secondary structure remain while rigid tertiary structure is lost. However, thermal studies suggest some residual cooperativity of unfolding in this state. At much higher HFIP concentrations, the helicity exceeds the native value and the protein behaves as a series of independent helices which do not interact with each other. We did not observe cold denaturation of myoglobin, even though this phenomenon has been observed for molten globule states of myoglobin, as well as for monomeric amphipathic alpha-helices when moderate quantities of HFIP are present. The pH dependence of trifluoroethanol-induced disruption of tertiary structure revealed that the degree of disruption increases as the enthalpic advantage of the folded state is diminished at low pH.

Animals↗

[Arthroscopic subacromial decompression].

The aim of this prospective study was to evaluate the results of arthroscopic subacromial decompression (ASAD) in the treatment of impingement syndrome in patients without full thickness rotator cuff tears. Sixty patients (64 operative procedures) underwent ASAD during the study period; 37 men and 23 women, average age 46 years (range 28-63), average duration of symptoms 37 months (range 8-132). Patients with calcifying tendintis were not included. Evaluation preoperatively and one year postoperatively included: Constant score, clinical examination and radiological evaluation (supraspinatus outlet view). All follow-up examinations were done by an independent observer. Fifty-six patients (60 procedures) were available for follow-up. The average length of follow-up was 13 months (range 10-23). Forty-six patients (77%) achieved a good or excellent result according to Constant score criteria. Preoperatively twenty-four patients had applied for worker's compensation benefits (WCB). Only half of the patients in the WCB group achieved a satisfactory result, whereas 94% of the non-WCB patients had a good or an excellent result. Arthroscopic subacromial decompression is an effective procedure for the majority of patients with stage II impingement syndrome. In this study WCB claims were associated with inferior results.

Adult↗

Empirical parameterization of a model for predicting peptide helix/coil equilibrium populations.

A modification of the Lifson-Roig formulation of helix/coil transitions is presented; it (1) incorporates end-capping and coulombic (salt bridges, hydrogen bonding, and side-chain interactions with charged termini and the helix dipole) effects, (2) helix-stabilizing hydrophobic clustering, (3) allows for different inherent termination probabilities of individual residues, and (4) differentiates helix elongation in the first versus subsequent turns of a helix. Each residue is characterized by six parameters governing helix formation. The formulation of the conditional probability of helix initiation and termination that we developed is essentially the same as one presented previously (Shalongo W, Stellwagen, E. 1995. Protein Sci 4:1161-1166) and nearly the mathematical equivalent of the new capping formulation incorporated in the model presented by Rohl et al. (1996. Protein Sci 5:2623-2637). Side-chain/side-chain interactions are, in most cases, incorporated as context dependent modifications of propagation rather than nucleation parameters. An alternative procedure for converting [theta]221 values to experimental fractional helicities ( ) is presented. Tests of the program predictions suggest this method may have some advantages both for designed peptides and for the analysis of secondary structure preferences that could drive the formation of molten-globule intermediates on protein folding pathways. The model predicts the fractional helicity of 385 peptides with a root-mean-square deviation (RMSD) of 0.050 and locates (with precise definition of the termini in many cases) helices in proteins as well as competing methods. The propagation and nucleation parameters were derived from NMR data and from the CD data for a 79 peptide "learning set" for which an excellent fit resulted (RMSD = 0.0295). The current set of parameter corrections for capping boxes, helix dipole interactions, and side-chain/side-chain interactions (coulombic, hydrogen bonding and hydrophobic clustering), although still under development provide a significant improvement in both helix/coil equilibrium prediction for peptides and helix location in protein sequences. This is clearly evident in the rms deviations between CD measures and calculated values of fractional helicity for different classes of peptides before and after applying the corrections: for peptides lacking capping boxes and i/i + 3 and i/i + 4 side-chain/side-chain interactions RMSD = 0.044 (n = 164) versus RMSD = 0.054 (0.172 without the corrections, n = 221) for peptides that required context-dependent corrections of the parameters. If we restrict the analysis to N-acylated peptides with helix stabilizing side-chain/side-chain interactions (including N-capping boxes), the degree to which our corrections account for the stabilizing interaction can be judged from the change in helicity underestimation, ( calc- CD): -0.15 +/- 0.10, which is reduced to -0.018 +/- 0.048 (n = 191) upon applying the corrections.

Algorithms↗