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Biomedical subjects

E Persson

Publications and source records attributed to E Persson.

At least 73 records · Page 4Linked to original sources

Whitacre or Quincke needles--does it really matter.

BACKGROUND: Postdural puncture headache (PDPH) and backache are well known complications of spinal anaesthesia. The incidence of PDPH may be significant in young people (< 50 years). The present study was undertaken in order to compare the utility and complication rate of the Whitacre and Ouincke spinal needles. METHODS: During three years all patients who could comply, and who were to undergo spinal anaesthesia at the Department were asked to join this quality control study. Each one received a questionnaire including questions about discomfort and other possible side effects attributed to spinal anaesthesia. In each case, an extended anaesthetic record was filled out by the anaesthesiologist. About 50 anaesthesiologists at different educational levels were involved. RESULTS: The study includes 2598 cases, of which questionnaires were returned by 66%. Needles of the 25 G gauge size were used in over 90% of the cases. Multiple skin punctures were required more frequently in the Quincke than in the Whitacre group (P < 0.01). The number of insufficient blocks was also higher in the Quincke group (P < 0.01). There was a higher incidence of backache in the Quincke group (P < 0.05). In patients under 50 years, PDPH was more frequent following use of the Quincke needle (P < 0.05), whereas no difference between the needles in this regard was found among those over 50 years (P > 0.05). CONCLUSIONS: For routine clinical use the Whitacre needle appears to be associated with better performance and increased reliability. In younger patients the Whitacre needle have the additional advantage of decreasing the risk of postdural puncture headache.

Adolescent↗

Polychlorinated biphenyl (PCB) exposure produces placental vascular and trophoblastic lesions in the mink (Mustela vison): a light and electron microscopic study.

Polychlorinated biphenyls (PCBs) cross the placenta and cause fetal death in mink. No indications of impaired implantation have been reported. To study the effects of PCB on mink placental morphology, 2 groups each of 10 animals were orally exposed to Clophen A50 at 0.65 mg (low dose) and 1.3 mg (high dose) per day for 54 days, starting before mating, with 10 control animals. Placentae from mid to late gestation were examined by light and electron microscopy. In the controls, 11% of placentae were degenerate compared to 31% (low dose) and 64% (high dose) in PCB-exposed mink. All control animals exhibited implantation sites, while one animal in the low dose and four in the high-dose group exhibited none. However, there was no difference between PCB-exposed and control animals in the number of placentation sites in implanted animals. Fetal death was markedly increased in PCB-exposed mink, with only four animals (low dose) having all viable fetuses and eight (low and high dose) having a mixture of viable and dead fetuses. Nine exposed animals displayed maternal vascular lesions in the placental labyrinthine zones of viable fetuses, comprising loss and degeneration of endothelial cells, thrombi and haemorrhages. Extracellular fluid was present between the interstitial layer of maternal vessels and the syncytiotrophoblast, and there was focal degeneration of the trophoblast and fetal vasculature. It appears, therefore, that exposure of the mink placenta to PCBs affects maternal vasculature and produces degenerative changes in the trophoblast and fetal vessels, leading to fetal growth retardation or death.

Animals↗

Appearance of glucose-induced insulin release in fetal rat beta-cells.

Fetal rat pancreatic cells were isolated from pancreatic primordia on days 12-14 of pregnancy and cultured for 48 h in the presence of 5 mmol/l glucose. Insulin accumulation in the medium over the next 24 h was measured. Cultured cells from day 12 fetuses secreted about 1 fmol insulin per pancreas in response to 5 or 15 mmol/l glucose irrespective of whether 1 mmol/l tolbutamide, 400 mumol/l diazoxide, 5 mmol/l theophylline or 10 mmol/l mannoheptulose was present. In contrast, insulin released from day 13 cultured cells increased significantly from 3.0 +/- 0.6 to 6.2 +/- 2.2 fmol per pancreas, when the glucose concentration was raised. Tolbutamide increased, diazoxide and mannoheptulose decreased and theophylline had no effect on insulin release. Even more pronounced effects were found on insulin release from day 14 cultured cells, in which theophylline also increased the release. In addition, insulin release from cells from pregnancy day 14 was 75 +/- 16 amol/min per pancreas when the cells were perifused for 15-20 min in the presence of 5 mmol/l glucose within 3 h of isolation. Increasing the glucose concentration to 15 mmol/l or adding tolbutamide increased, whereas diazoxide decreased, insulin release in the freshly isolated cells. The insulin content of rat pancreata from pregnancy day 13 was 0.06 +/- 0.01 pmol per pancreas and increased approximately 10-fold every second day up to 6.7 +/- 0.9 pmol on day 17 of pregnancy. Between day 17 and 19 the pancreatic insulin content increased about fivefold to 39 +/- 2 pmol. The present data suggest that critical components of the insulin-secretory machinery, including ATP-regulated K+ channels, glucokinase and adenylate cyclase activities, are present in the developing beta-cell earlier than hitherto thought.

Animals↗

Ca2+ in the first epidermal growth factor-like domain of activated factor VII.

Activated factor VII (FVIIa) needs to be bound to tissue factor (TF) to express biological activity, and biochemical and structural data show that the first epidermal growth factor (EGF)-like domain of FVIIa contributes essential contacts with TF. To investigate the role of Ca2+ binding to this domain in FVIIa we used site-directed mutagenesis to replace Asp46 and Asp63 by Asn, which abolished Ca2+ binding, and characterized the double mutant (D46,63N-FVIIa) with respect to its TF-binding properties and the functional status of its complex with TF. D46,63N-FVIIa had a lower amidolytic activity than FVIIa at optimal Ca2+ concentrations. A slightly lower amidolytic activity was also observed in complex with soluble TF, apparently due to a lower catalytic turnover rate of D46,63N-FVIIa. However, D46,63N-FVIIa and FVIIa bound to lipidated TF were equally efficient activators of factor X. The dissociation constant for the interaction between D46,63N-FVIIa and soluble TF, derived from amidolytic activity and direct binding measurements, was approximately 20-fold higher than that for the interaction between FVIIa and soluble TF. The same difference was observed in the affinity for lipidated TF. These findings suggest that a functional Ca2+-binding site in the first EGF-like domain adds approximately 7 kJ/mol to the total binding energy of the interaction with both lipidated and soluble TF.

Amino Acid Sequence↗

Characterization of the interaction between the light chain of factor VIIa and tissue factor.

Factor VIIa (fVIIa) consists of a heavy chain (serine protease domain) and a light chain (gamma-carboxyglutamic acid (Gla)-rich and epidermal growth factor (EGF)-like domains). The light chain, primarily the first EGF-like domain, appears to provide most of the binding energy in the interaction with tissue factor (TF). The Ca2+-binding sites in the protease domain and in the first EGF-like domain influence activity and interaction with TF, but the contribution from the Ca2+-binding sites in the Gla domain has not been established. We have compared the soluble TF (sTF)-binding properties of intact fVIIa to those of a fragment comprising almost the entire light chain and a small disulphide-linked peptide from the protease domain. Half-maximal binding of fVIIa and the light chain to sTF occurred around 0.3 and 1 mM Ca2+, respectively. The Ca2+ dependence of light-chain binding indicates an influence of Ca2+ binding to the Gla domain on the interaction between fVIIa and sTF. Comparison of the sTF-binding properties of fVIIa and a truncated variant lacking the Gla domain suggests that this domain interferes with sTF association at suboptimal Ca2+ concentrations. The light chain of fVIIa associated 5-fold slower with sTF than did fVIIa at saturating Ca2+ concentrations, whereas the dissociation of its complex with sTF was at least 100-fold faster than that of fVIIa:sTF. This gave a dissociation constant of 1-2 microM for the interaction between the light chain and sTF compared to about 3 nM for the fVIIa:sTF interaction.

1-Carboxyglutamic Acid↗

Ca2+ binding to the first epidermal growth factor-like domain of factor VIIa increases amidolytic activity and tissue factor affinity.

Coagulation factor VIIa belongs to a family of homologous enzymes, including factors IXa and Xa and activated protein C, composed of two epidermal growth factor-like domains located between an N-terminal domain rich in gamma-carboxyglutamic acid residues and a C-terminal serine protease domain. The first epidermal growth factor-like domain in factor VIIa contains a Ca2+ binding site, the function of which is largely unknown. Site-directed mutagenesis of two Ca2+-liganding Asp residues in this domain abolished Ca2+ binding and resulted in a 2-3-fold decrease in amidolytic activity at optimal Ca2+ concentrations. The lower amidolytic activity persisted in complex with soluble tissue factor, apparently due to a lower kcat of the mutant factor VIIa. Mutant and wild-type factor VIIa bound to lipidated tissue factor were equally efficient activators of factor X. The dissociation constants, derived from amidolytic activity and surface plasmon resonance measurements, were 2-5 nM and 50-60 nM for the interactions between wild-type and mutant factor VIIa, respectively, and soluble tissue factor. Binding to lipidated tissue factor was characterized by dissociation constants of 7.5 pM for factor VIIa and 160 pM for the factor VIIa mutant. Hence, a functional Ca2+ binding site in the first epidermal growth factor-like domain added 7-8 kJ/mol to the total binding energy of the interaction with both lipidated and soluble tissue factor.

Aspartic Acid↗

Incorporation of an active site inhibitor in factor VIIa alters the affinity for tissue factor.

Recent studies showed that the administration of active site-inhibited factor VIIa blocked factor VIIa/tissue factor-induced fibrin and thrombus formation in ex vivo and in vivo model systems. These studies suggest that inactivated factor VIIa competes efficiently with plasma factor VII(a) for a limited number of tissue factor sites. In the present study, we compared the interactions of factor VIIa and active site-inhibited factor VIIa with tissue factor. Competition studies of factor VIIa and active site-inhibited factor VIIa in a factor X activation assay showed that the affinity of the latter for relipidated tissue factor was 5-fold higher than that of factor VIIa. Radioligand binding studies with a human bladder carcinoma cell line (J82) and surface plasmon resonance studies using soluble tissue factor demonstrated a faster association and a slower dissociation for the active site-inhibited factor VIIa. Studies of equilibrium binding to cell surface tissue factor showed that the affinity of active site-inhibited VIIa was 5-fold higher than that of factor VIIa to non-functional tissue factor sites, whereas both inactivated factor VIIa and factor VIIa bound to functional tissue factor sites with the same high affinity. Comparison of the CD spectra of factor VIIa and active site-inactivated factor VIIa revealed structural differences in the protease domain. The potential physiological implications of these findings are discussed.

Amino Acid Chloromethyl Ketones↗

Insulin-like growth factor-I in the porcine endometrium and placenta: localization and concentration in relation to steroid influence during early pregnancy.

To initiate the establishment of an epitheliochorial placenta, the developing porcine conceptuses contact the maternal endometrium on its mesometrial side. The porcine conceptuses secrete estrogens which, together with circulating maternal hormones, govern variations in the structure as well as expression and levels of steroid receptors and growth factors during early pregnancy. Mesometrial samples of endometrium or placenta were collected from 15 early pregnant (8-30 days after the onset of estrus) and six cycling (days 1-14) gilts. The variations in tissue morphology and immunohistochemical localization of insulin-like growth factor-I (IGF-I) were related to the tissue levels (by enzyme immunoassay) of receptors for estrogen (ER) and progesterone (PR), as well as mRNA (by solution hybridization) concentrations for the two receptors and IGF-I. IGF-I immunoreactivity was present in samples from all animals, being principally located in maternal epithelium, trophoblast, endothelium and vascular smooth muscle; the latter showing the strongest labeling. The levels of receptor proteins, as well as mRNAs, were highest in the non-pregnant animals at estrus and metestrus. The pregnant animals showed decreasing concentrations to consistently low levels after day 14. Temporal changes in the studied parameters were clearly coincidental with the peak (days 13-14) in conceptus estrogen secretion, e.g. the more uniform IGF-I immunolabeling in the uterine glands (days 8-13) compared with the later stages studied; the conspicuous accumulation and release of secretory vesicles in the endometrial glands (days 8-13), marking the change in secretory quality and quantity, leading to a gradual shift from histotrophic to hemotrophic nutrition of the conceptuses, and finally, the peaking level of IGF-I mRNA in the pregnant endometrium (days 12-13) which decreased considerably thereafter. It is concluded that IGF-I activity in the porcine uterus changes with the early development of the placenta.

Animals↗

Formulation of enamel matrix derivative for surface coating. Kinetics and cell colonization.

Enamel Matrix Derivative (EMD) contains a protein complex belonging to the amelogenin family. Enamel matrix as well as EMD have been found to promote periodontal regeneration when applied onto denuded root surfaces in dehiscence models. In the present studies it is shown that propylene glycol alginate (PGA) is a suitable vehicle for EMD for its local application. EMD can be dissolved in PGA at an acidic pH, resulting in a highly viscous solution. At neutral pH and body temperature the viscosity decreases and EMD precipitates. Multilayers of EMD on mineral or protein surfaces have been analysed using ellipsometry, total internal reflection fluorescence (TIRF) and biospecific interaction analysis (BIA). The studies show that EMD adsorbs both to hydroxyapatite and collagen and to denuded dental roots. It forms insoluble spherical complexes, and detectable amounts remain at the site of application on the root surface for two weeks, as shown with radiolabelled protein in rats and pigs. Scanning electron micrograph (SEM) studies on monkey teeth further indicate that EMD in PGA may promote repopulation of fibroblast-like cells during the first weeks after application.

Adsorption↗

Effects of prostaglandin treatment and paracervical blockade on postoperative pain in patients undergoing first trimester abortion in general anesthesia.

BACKGROUND: The postoperative analgesic efficacy of a paracervical blockade (PCB) as an adjunct to general anesthesia (GA) during outpatient abortion (dilatation and curettage) is unclear, and the present study was initiated to evaluate if PCB is of significant importance per- or postoperatively. METHODS: Two hundred women (aged 18-49 years) were assigned to one of four groups; group 1 received vaginal prostaglandin (PG) (PGE1, gemeprost 1 mg) for softening of the cervix preoperatively and surgery was performed in GA, group 2 received preoperative PG and surgery was performed in GA + PCB; group 3 did not receive PG treatment and surgery was performed in GA and group 4 were subjected to GA + PCB without preoperative PG. RESULTS: Women receiving preoperative prostaglandin treatment (groups 1 and 2) reported significantly higher pain intensity already preoperatively, but also postoperatively as compared to patients not treated with PG. The patients subjected to prostaglandin treatment (groups 1 and 2) also had a significantly higher consumption of analgesics as compared to non-PG treated groups (3 and 4). The addition of PCB did not influence pre- and postoperative pain intensity significantly or consumption of analgesics. Patients receiving PG also reported significantly more nausea than the others although nausea was of low intensity. Patients receiving PG were, however, discharged earlier than the others from the hospital. CONCLUSIONS: Preoperative treatment of the cervix with prostaglandins was associated with significantly higher pain intensity both pre- and postoperatively, and increased need for analgesics postoperatively and more intense nausea. PCB given just before surgery did not result in significant postoperative analgesia. More efficient techniques for pain control should be developed for women subjected to first trimester abortion with preoperative PG treatment.

Abortion, Induced↗

Site-directed mutagenesis but not gamma-carboxylation of Glu-35 in factor VIIa affects the association with tissue factor.

Factor VIIa is a vitamin K-dependent enzyme whose gamma-carboxyglutamic acid (Gla)-containing domain is important for calcium ion-dependent binding to the cofactor tissue factor and membrane surfaces. This domain contains 10 Gla residues, the individual roles and importance of which are not known. Comparisons with the homologous protein C, factor IX and prothrombin may provide functional information on the first nine Gla residues, whereas no data can be extrapolated to Gla-35 in factor VIIa. Therefore, the effects of posttranslational gamma-carboxylation and site-directed mutagenesis of Glu-35 were investigated. Mutations to Asp, Gln or Val all lead to a lower affinity for tissue factor by decreasing the rate of association, in the case of the Val mutant by a factor of 200, as measured by surface plasmon resonance. In contrast, Glu or Gla side chains at position 35 appear to fulfil the functional roles equally well.

1-Carboxyglutamic Acid↗

Structural changes in factor VIIa induced by Ca2+ and tissue factor studied using circular dichroism spectroscopy.

Factor VIIa (fVIIa) is composed of four discrete domains, a gamma-carboxyglutamic acid (Gla)-containing domain, two epidermal growth factor (EGF)-like domains, and a serine protease domain, all of which appear to be involved, to different extents, in an optimal interaction with tissue factor (TF). All except the second EGF-like domain contain at least one Ca2+ binding site and many properties of fVIIa, e.g., TF and phospholipid binding and amidolytic activity, are Ca(2+)-dependent. A CD study was performed to characterize and locate the conformational changes in fVIIa induced by Ca2+ and TF binding. In addition to intact fVIIa, derivatives lacking the Gla domain or the protease domain were used. Assignment of the Ca(2+)-induced changes in the far-UV region of the fVIIa spectrum to the Gla domain could be made by comparing the CD spectra obtained with these fVIIa derivatives. The changes primarily appeared to reflect a Ca(2+)-induced ordering of alpha-helices existing in the apo state of fVIIa. This was corroborated by models of the apo and Ca2+ forms of fVIIa, obtained as difference spectra between fVIIa derivatives, were very similar to those of isolated Gla peptides from other vitamin K-dependent plasma proteins. The near-UV CD spectrum of fVIIa was dominated by aromatic residues residing in the protease domain and specific bands affected by Ca2+ were indicative of tertiary structural alterations. The formation of a fVIIa:TF complex led to secondary structural changes that appeared to be restricted to the catalytic domain, possibly shedding light on the mechanism by which TF induces an enhancement of fVIIa catalytic activity.

Calcium↗

A comparative study of breast feeding after traditional postnatal hospital care and early discharge.

OBJECTIVE: To provide quality assurance for the care plan and working structure within the early discharge unit at the Women's Clinic, Central Hospital, Helsingborg, Sweden. DESIGN: Survey, using postal questionnaire. SETTING: The Women's Clinic, Central Hospital, Helsingborg, Sweden. PARTICIPANTS: 304 women with babies of six months of age, delivered at the Central Hospital, Helsingborg, between September and December 1993 and who, together with their baby, met the criteria for early discharge. Early discharge is generally defined in Sweden as discharge before 72 hours postpartum. MEASUREMENTS AND FINDINGS: Of the participants 41% chose early discharge (ED) and 59% chose traditional hospital care (THC). Four groups were studied for breast feeding frequency - THC primiparae, ED primiparae, THC multiparae and ED multiparae. Further division was made for breast feeding at 2, 4 and 6 months of age. The four main groups were examined for demographic differences. A difference was found in education level; early discharge mothers had a lower level of education than THC mothers. No significant difference was found for the frequency or duration of breast feeding between the early discharge and the traditional hospital care groups, despite the higher education level in the traditional hospital care group. IMPLICATIONS FOR PRACTICE: A possible explanation for this finding is that a care plan aimed at supporting the individual's responsibility and participation, providing relevant knowledge and a subliminal communication of trust in the competence of parent and child, is of particular significance for women with less education. The presence and participation of the baby's father at an early stage may also be a factor.

Adult↗

Peroperative adenosine infusion reduces isoflurane concentrations during general anesthesia for shoulder surgery.

BACKGROUND: Adenosine (ADO), and stable analogs thereof, have been shown to exert antinociceptive action under experimental conditions in animals and in humans. The aim of this randomized double-blind placebo-controlled study was to evaluate if a low dose of intravenous (i.v.) ADO could reduce isoflurane requirements during joint-associated surgery, as an indication of antinociception in deep somatic pain. METHODS: Thirty-two patients, age 19-62 years, ASA I and II, scheduled for shoulder joint surgery, were assigned to receive an i.v. infusion of either adenosine, 80 micrograms.kg-1.min-1, or placebo, during the surgical procedure. Anesthesia was maintained with isoflurane/N2O/O2 inhalation. RESULTS: The peroperative isoflurane concentration was significantly reduced at 50 minutes of surgery in the group receiving adenosine infusion. Also, the systolic blood pressure level was peroperatively more stable during adenosine infusion than during placebo. Other clinical parameters, such as pain, postoperative analgesic requirements and nausea, were not different between groups. CONCLUSION: A peroperative infusion of a low dose of adenosine during shoulder joint surgery may reduce the peroperative isoflurane requirement.

Adenosine↗

Influence of the gamma-carboxyglutamic acid-rich domain and hydrophobic stack of factor VIIa on tissue factor binding.

Des (1-38)- and des(1-44)-factor VIIa (fVIIa) were inhibited with Phe-Phe-Arg-chloromethyl ketone (FFR-cmk). Des(1-38)-FFR-fVIIa inhibited tissue factor (TF)-enhanced fVIIa amidolytic activity with an IC50 value of 15 nM, whereas 3- and 6-fold higher values were obtained with des(1-44)-FFR-fVIIa using soluble and full-length TF, respectively. The value for FFR-fVIIa was 8-10 nM. Clotting time was prolongated with IC50 values for inactivated des(1-38)- and des(1-44)-fVIIa of 50 nM and 1 mu M, respectively, whereas FFR-fVIIa yielded a value of 10 nM. From binding experiments in a BIA-core instrument, dissociation constants for the complexes between TF1-218 and fVIIa, des(1-38)-fVIIa and des(1-44)-fVIIa of about 3, 20 and 70 nM, respectively, could be estimated.

1-Carboxyglutamic Acid↗