ABSTRACT
The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 +/- 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A-V fistulas, was 7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 +/- 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.
Subject(s)
Anticoagulants/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Renal Dialysis , Anticoagulants/adverse effects , Bleeding Time , Blood Coagulation/drug effects , Female , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle Aged , TinzaparinABSTRACT
A series of analogs of glucagon-like peptide-1 (GLP-1) was made replacing each amino acid with L-alanine to identify side-chain functional groups required for interaction with the GLP-1 receptor. In the case of L-alanine being the parent amino acid, substitution was made with the amino acid found in the corresponding position in glucagon. Binding assays were performed using the cloned rat GLP-1 receptor, and receptor activation was monitored using RIN 2A18 plasma membranes. The analogs that showed the weakest receptor binding were further compared with native GLP-1 by circular dichroism spectroscopy to investigate possible conformational changes. We conclude that the side chains in positions 7, 10, 12, 13, and 15 are directly involved in the receptor interaction while positions 28 and 29 are important for GLP-1 to adapt the conformation recognized by the receptor.
Subject(s)
Alanine , Glucagon/chemistry , Glucagon/metabolism , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Protein Precursors/chemistry , Protein Precursors/metabolism , Receptors, Cell Surface/metabolism , Receptors, Glucagon , Adenylyl Cyclases/metabolism , Amino Acid Sequence , Animals , Binding, Competitive , Cell Line , Cell Membrane/metabolism , Circular Dichroism , Glucagon/pharmacology , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Kinetics , Molecular Sequence Data , Peptide Fragments/pharmacology , Peptides/chemical synthesis , Peptides/chemistry , Peptides/metabolism , Protein Conformation , Protein Precursors/pharmacology , Sequence Homology, Amino Acid , Structure-Activity RelationshipABSTRACT
Three populations in South- and North-Thingeyjarsýslas, Northeast Iceland, were surveyed for the presence of torus palatinus. A total of 987 schoolchildren (489 male and 487 female) were examined. A statistically significant difference was noted between the prevalence in South-Thingeyjarsýsla (33.3%) and North-Thingeyjarsýsla (14.6%). Prevalence and size were affected by age and population but not by sex. An association between torus palatinus and torus mandibularis was not found. Secular changes in the occurrence of torus palatinus in Icelanders emphasize the importance of environmental etiological factors and diminish the value of torus palatinus as a racial trait.
Subject(s)
Palate/anatomy & histology , Adolescent , Anthropology, Physical , Child , Female , Humans , Iceland , MaleABSTRACT
Two hundred Skolt Lapps aged 8 to 16 years were examined for malocclusion with the aid of intraoral radiography and dental casts. The frequency of loss of permanent teeth was high, particularly of the first molars. Also, many teeth were severely defective because of caries. Hypodontia was very common. The frequency of tipped and rotated teeth was high, probably as a consequence of the frequent loss of neighboring teeth. Space and occlusal anomalies were roughly as common as in urbanized Swedish and Danish materials. The need for orthodontic treatment, judged on a 5-grade scale by one examiner, was found to be greater than in Swedish materials.
