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Anders Nilsson

Publications and source records attributed to Anders Nilsson.

25 records · Page 2Linked to original sources
PubMed2003

Growth hormone increases bone mineral content in postmenopausal osteoporosis: a randomized placebo-controlled trial.

Eighty osteoporotic, postmenopausal women, 50-70 years of age, with ongoing estrogen therapy (HRT), were randomized to recombinant human growth hormone (GH), 1.0 U or 2.5 U/day, subcutaneous, versus placebo. This study was double-blinded and lasted for 18 months. The placebo group then stopped the injections, but both GH groups continued for a total of 3 years with GH and followed for 5 years. Calcium (750 mg) and vitamin D (400 U) were given to all patients. Bone mineral density and bone mineral content were measured with DXA. At 18 months, when the double-blind phase was terminated, total body bone mineral content was highest in the GH 2.5 U group (p = 0.04 vs. placebo). At 3 years, when GH was discontinued, total body and femoral neck bone mineral content had increased in both GH-treated groups (NS between groups). At 4-year follow-up, total body and lumbar spine bone mineral content increased 5% and 14%, respectively, for GH 2.5 U (p = 0.01 and p = 0.0006 vs. placebo). Femoral neck bone mineral density increased 5% and bone mineral content 13% for GH 2.5 U (p = 0.01 vs. GH 1.0 U). At 5-year follow-up, no differences in bone mineral density or bone mineral content were seen between groups. Bone markers showed increased turnover. Three fractures occurred in the GH 1.0 U group. No subjects dropped out. Side effects were rare. In conclusion, bone mineral content increased to 14% with GH treatment on top of HRT and calcium/vitamin D in postmenopausal women with osteoporosis. There seems to be a delayed, extended, and dose-dependent effect of GH on bone. Thus, GH could be used as an anabolic agent in osteoporosis.

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PubMed2002

Conformations and receptor activity of desmopressin analogues, which contain gamma-turn mimetics or a psi[CH(2)O] isostere.

Three analogues of the antidiuretic drug desmopressin ([1-desamino,8-D-arginine]vasopressin) have been prepared. In two of these, gamma-turn mimetics based on a morpholin-3-one framework have been inserted instead of residues Phe3-Asn5, whereas the third analogue has a methylene ether isostere in place of the amide bond between residues 3 and 4. The three analogues were used to probe if the structure determined for desmopressin in aqueous solution, which contains an inverse gamma-turn centered around Gln4, is important in interactions with the vasopressin V(2) receptor. Conformational studies revealed that the analogues that contain either an inverse gamma-turn mimetic or a methylene ether isostere mimicked the conformation of desmopressin fairly well and very well, respectively. Despite this, the analogues displayed only very low agonistic activities at the vasopressin V(2) receptor. Consequently, an inverse gamma-turn involving residues Phe3-Asn5 does not appear to be important when desmopressin is bound to the V(2) receptor. In addition, it was concluded that the amide bond between Phe3 and Gln4 in desmopressin is crucial for interactions with the antidiuretic V(2) receptor.

Animals↗
PubMed2002

Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn.

Oxytocin is a neurohypophyseal peptide hormone that induces labor and lactation in mammals. An inverse gamma-turn mimetic corresponding to the tripeptide Ile-Val-Asn has been synthesized and incorporated instead of residues 3-5 of oxytocin to probe the hypothesis that a gamma-turn involving these residues is found in the receptor bound conformation of oxytocin. In the turn mimetic, residues i and i + 1 are connected by a psi[CH(2)O] isostere while a covalent methylene bridge replaces the hydrogen bond that is often found between residues i and i + 2 in gamma-turns. The turn mimetic was assembled from three types of building blocks: an azido epoxide, an alpha-bromo acid, and a protected beta-amino alcohol. The oxytocin analogue did not induce contractions of the uterus nor did it inhibit oxytocin-induced contractions. It is suggested that the loss of bioactivity is mainly due to the presence of a psi[CH(2)O] isostere instead of an amide bond between residues i and i + 1 in the turn mimetic.

Animals↗
PubMed2002

Studies of polyurethane urea bands for ACL reconstruction.

The present report describes the mechanical tests, in vitro and in vivo studies of a poly(urethane urea) (PUUR) intended for clinical use in anterior cruciate ligament (ACL) reconstruction. In the mechanical tests, no evidence of severe fatigue was observed after repeated cyclic loading. Testings for mutagenicity and delayed contact hypersensitivity were found negative. Three in vivo studies were performed in rabbits and minipigs. Altogether 35 rabbits were operated upon in (1) an intraarticular implantation study, performed to evaluate the soft tissue response to woven bands and fiber bundles of PUUR and (2) a rabbit ACL study, examining the function of the PUUR ACL replacement and the tissue response to the material. In a third study, PUUR ACL replacement in minipigs was evaluated. Taken together, ingrowth of connective tissue in close contact with the PUUR fibers was detected both in rabbits and minipigs. The first clear histological signs of degradation of the polymer was detected after 24 months. In conclusion, the evaluated mechanical properties of the PUUR band correspond to those of the mature, human ACL. Furthermore, both from a histological and functional point of view, the PUUR woven band show interesting properties for future clinical ACL reconstructions.

Journal Article↗
PubMedDate not supplied

Diffusive-convective mass transfer rates for solutes present on both sides of a dialyzer membrane.

The transport (J) of waste products across dialyzer membranes is known to be proportional to the blood inlet concentration (Cbi) according to J = KCbi, where K is the clearance. For solutes present on both sides of the membrane, like sodium chloride, it has been shown that under certain conditions the transport rate will depend linearly also upon the dialysis fluid inlet concentration Cdi according to J = KbCbi -KdCdi. Kb and Kd are generalized clearances, which depend upon flow rates and membrane permeability but are independent of the concentrations. We have extended the results of Ross et al. in three ways. First, they only considered ultrafiltration (UF) that is equally distributed along the dialyzer. This is an unrealistic assumption, especially in hemodiafiltration and hemofiltration treatments with large UF rates (Quf) leading to large pressure drops along the dialyzer. Our approach allows for an arbitrary UF distribution. Second, it was possible to incorporate the more realistic model of Villaroel et al. for the local combination of diffusion and convection. Finally, we allow an arbitrary distribution of blood among the different fibers. All of these results are valid in both cocurrent and countercurrent configurations. With a sieving coefficient of 1, a good approximation for small solutes, we were also able to show that Kd = Kb - Quf, irrespective of the UF distribution along the dialyzer. This is an important result that, for example, provides a theoretical foundation for allowing a nonzero Quf in conductivity based clearance measurements.

Diffusion↗
PubMedDate not supplied

An electrocardiogram-based method for early detection of abrupt changes in blood pressure during hemodialysis.

Clinical techniques for early detection of acute hypotension during conventional hemodialysis treatment are lacking, even though intradialytic hypotension is the most common acute complication. In this article, intradialytic hypotension is identified by means of signal analysis of data recorded at two clinics. The database consists of 30 treatments with concurrently acquired signals: the 12-lead electrocardiogram, continuous blood pressure, hematocrit, oxygen saturation, relative blood volume, and important hemodialysis variables. This article presents two characteristics, a heart rate turbulence (HRT) measure called turbulence slope (TS), and the LF/HF ratio, which provide information, at the beginning of hemodialysis treatment, on the patient's propensity to hypotension (TS: p = 0.0038, and LF/HF ratio: p = 0.0028). The authors also present a novel dynamic echocardiography-based method for detecting intradialytic hypotension using complementary information on heart rate variability (HRV) and ectopic beat patterns. These two types of information reflect different mechanisms of cardiac activity. It is essential that both types are used for the detection of hypotension, because HRV analysis is inappropriate when several ectopic beats are present. The proposed dynamic echocardiography-based method offers early identification of the cases with acute intradialytic hypotension of the database.

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