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Biomedical subjects

D Lundberg

Publications and source records attributed to D Lundberg.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pharmacokinetics and absolute bioavailability of epristeride in healthy male subjects.

The objective of the current investigation was to describe the pharmacokinetics and absolute oral bioavailability of epristeride. Twelve healthy male subjects (mean (SD) age, 27 (6.2) years) received a single oral dose of 5 mg and an intravenous infusion of 4.5 mg over 30 min in a crossover fashion. Blood samples were obtained over 72h for the determination of epristeride plasma concentrations using a sensitive high-performance liquid chromatography assay. The lower limit of quantification was 5 ng mL-1. Pharmacokinetic analysis of the plasma concentration-time data was performed by both non-compartmental and compartmental methods. Absolute bioavailability was determined using dose-normalized AUC values following oral and intravenous administration. Epristeride plasma concentrations declined in a biexponential fashion with secondary peaks evident around 24 h in a majority of subjects following both routes of administration. Maximal plasma concentrations were typically achieved approximately 4 h after oral dosing. The mean apparent terminal elimination half-life estimates were similar following intravenous and oral administration and were 27.3 and 26.2 h, respectively. The mean plasma clearance and steady-state volume of distribution were 0.33 (0.09) mL min-1 kg-1 and 0.54 (0.17) L kg-1, respectively. The mean absolute bioavailability was 93% (95% CI: 84%, 104%). Following compartmental analysis of the intravenous data, the mean (SD) lambda 1 and lambda 2 half-life estimates were 2.74 (0.48) and 31.8 (19.5) h, respectively. The % AUC associated with the lambda 2 exponential phase was approximately 68%. This long half-life allows for once-daily dosing of epristeride.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Intensive care syndrome: a literature review.

The aim in this literature review is to describe the definitions, denominations, clinical signs and symptoms, explanations, causative factors and interrelationships of the intensive care syndrome discussed since 1950. It was found that there is no agreement about which symptoms should be included in the syndrome, when the syndrome may appear and how many patients may be affected. Furthermore, it is unclear what causes the development of the syndrome; most authors conclude that there are many reasons for it. The syndrome has generally been examined by using a medical or psychological approach, but during the last few years it has also been described and analysed from a nursing care perspective. From this nursing perspective the syndrome may be seen as an individual pattern developed by patients during their stay in an intensive care unit (ICU) and sometimes this pattern of clinical signs and symptoms lasts for a shorter or longer period even after discharge from the unit. From a wider viewpoint the development of the syndrome can be seen as an increase by degrees or as a vicious circle. finally, most authors agree that the ICU syndrome consists of, and is caused by, a complex interaction between many factors.

Critical Care↗
PubMed1995

A prospective survey of postoperative nausea and vomiting with special regard to incidence and relations to patient characteristics, anesthetic routines and surgical procedures.

We performed a prospective study on 421 patients subjected to routine general-, orthopaedic-, urologic-, gynecological and paediatric surgery to estimate the current incidences of nausea and vomiting during the first 24 hours after surgery. The overall incidences of postoperative nausea or vomiting were 17% and 28%, respectively. Postoperative emetic symptoms were not related to age in adults. Women had more often emetic symptoms than men (P < 0.01). In general, opiate premedication was more frequently associated with postoperative nausea and vomiting than benzodiazepines (P < 0.01), but in otherwise comparable subgroups of patients undergoing major surgery, this difference was not confirmed. Balanced general anaesthesia caused more nausea (23%) and vomiting (53%) than face-mask anaesthesia (13% and 15%, respectively) or regional blocks (12% and 7%, respectively) (P < 0.001). There was a positive correlation between the duration of anaesthesia and the incidence of postoperative emetic symptoms (P < 0.001). The incidences of postoperative nausea and vomiting after abdominal surgery were 23% and 58% respectively. Corresponding figures for orthopaedic surgery were 25% and 34%, other kinds of extra-abdominal surgery 18% and 32% and for laparoscopy 21% and 25%. After minor gynecological-, urological- and paediatric surgery the incidences were less than 20%. In conclusion female gender, balanced anaesthesia, lengthy duration of anaesthesia, and abdominal and orthopaedic operations appeared to be most frequently associated with postoperative emetic symptoms.

Adolescent↗
PubMed1990

Membrane expression of platelet calpain.

Platelet calpain has many platelet substrates, including external membrane proteins. We thus investigated whether platelet calpain II was associated with platelet membranes in unstimulated and thrombin-activated platelets. A monospecific, goat polyclonal antibody was reared to purified platelet calpain II. Sixteen whole platelet lysates were found to contain 4.5 +/- 0.7 micrograms calpain antigen II per 10(8) platelets (mean +/- SEM) as determined by a competitive enzyme-linked immunosorbent assay. Using the dipeptide fluorogenic substrate, Suc-Leu-Tyr-MCA, 17 human platelet lysates contained 3.6 +/- 0.4 micrograms calpain activity per 10(8) platelets. Platelet calpain II was associated with the Triton X-100 insoluble platelet cytoskeletons from both unstimulated and thrombin-activated platelets. When compared with the total cell content of platelet calpain II, calpain antigen (10% to 13%) and calpain activity (24% to 28%) was associated with platelet cytoskeletons in unstimulated and thrombin-activated platelets, respectively. On immunoblot, the heavy chain (80 Kd) of calpain II was detected in platelet cytoskeletons. Subcellular fractionation studies on both unstimulated and thrombin-activated platelets, revealed that half of the total platelet calpain II antigen was associated with cytosol, and the other half was associated with the membrane fraction. Platelet calpain II was not seen on the surface of unstimulated, paraformaldehyde fixed platelets by immunofluorescence. However, on thrombin-activated platelets, rim immunofluorescence was seen, indicating that activated platelets externalize their calpain. This observation was confirmed by the finding that about 2,000 molecules per platelet of an 125I-anti-calpain II Fab' specifically bound to thrombin-activated but not unstimulated platelets. Both dibucaine (1 mmol/L) and platelet activating factor (1.86 mumol/L) in the absence of external Ca++, but not collagen (5 micrograms/mL) or ionophore A23187 (2.5 mumol/L) in the absence of external Ca++, were also able to externalize platelet calpain II antigen, as indicated by a similar level of specific 125I-anti-calpain II Fab'-platelet binding. These combined studies indicate that platelet calpain II is a major protein, comprising 2% of total platelet protein, a substantial portion of which is membrane-associated. When platelets are activated by thrombin and platelet activating factor, calpain II antigen also becomes present on the external platelet surface.

Antibodies↗
PubMed1990

Dopamine counteracts hypertension during general anesthesia and hypotension during combined thoracic epidural anesthesia for abdominal aortic surgery.

The influence of the degree of sympathetic nervous system activation on the cardiovascular effects of dopamine was studied during abdominal aortic surgery in 13 patients. The arterial plasma norepinephrine concentration (NE) was used as an index of sympathetic nervous system activity. During anesthesia with nitrous oxide and fentanyl, 7 patients (group 1) had a NE above 700 pg/mL and an increased mean arterial pressure (MAP) compared with the preanesthetic level (150 +/- 6 v 117 +/- 10 mm Hg; p less than 0.01, mean +/- SEM). The other 6 patients (group 2) had no significant change in MAP compared with the preanesthetic MAP (119 +/- 7 v 105 +/- 4 mm Hg). Dopamine, 4 micrograms/kg/min, decreased MAP in group 1 by 19% (150 +/- 6 to 121 +/- 8 mm Hg; P less than 0.05) because of a 32% +/- 9% decrease (P less than 0.05) in systemic vascular resistance. MAP was not altered by dopamine in group 2 (119 +/- 7 v 123 +/- 6 mm Hg; not significant). Following termination of dopamine, the anesthetic was supplemented with thoracic epidural anesthesia (TEA). This reduced MAP to 65 +/- 7 mm Hg (P less than 0.01) and 56 +/- 3 mm Hg (P less than 0.01), and NE to 441 +/- 76 (P less than 0.05) and 235 +/- 45 pg/mL (P less than 0.05) in groups 1 and 2, respectively. During TEA, dopamine increased MAP similarly in both groups, to 85 +/- 7 mm Hg (P less than 0.01) and 82 +/- 9 mm Hg (P less than 0.05), respectively. In conclusion, dopamine, at the same dosages, counteracted hypertension during general anesthesia and counteracted hypotension during general anesthesia combined with TEA.

Analysis of Variance↗
PubMed1990

Intestinal hemodynamics during laparotomy: effects of thoracic epidural anesthesia and dopamine in humans.

The effects of thoracic epidural anesthesia (TEA) and dopamine infusion (4 micrograms.kg-1.min-1) on superior mesenteric artery blood flow (SMABF), the mesenteric arteriovenous oxygen difference (AVDO2), and the mesenteric venous lactate concentration were studied in nine patients before abdominal aortic reconstruction. Thoracic epidural anesthesia reduced SMABF, as measured by electromagnetic flowmetry, to 77% +/- 8% (mean +/- SEM) of control (P less than 0.05), and mean arterial pressure to 46% +/- 4% of control (P less than 0.01). The mesenteric AVDO2 increased from 27 +/- 3 to 39 +/- 6 mL/L (P less than 0.05) and superior mesenteric venous lactate from 1.03 +/- 0.11 to 1.60 +/- 0.38 mmol/kg (P less than 0.05); systemic AVDO2 and lactate did not change. Dopamine had no significant effect on SMABF and mean arterial pressure before TEA. However, dopamine increased SMABF during TEA (from 77% +/- 8% to 137% +/- 21% of control; P less than 0.01), returned mesenteric AVDO2 to 27 +/- 3 mL/L (P less than 0.05), and elevated mean arterial pressure to 62% +/- 4% of control (P less than 0.05). It is concluded that the decrease in perfusion pressure during TEA reduces SMABF with resultant evidence of intestinal reductive metabolism. The intestinal blood flow during TEA was improved by dopamine.

Aged↗
PubMed1988

The expression of high molecular weight kininogen on human umbilical vein endothelial cells.

High molecular weight kininogen (HMWK) functions as a cofactor for activation of plasma serine zymogens and as an inhibitor of tissue cysteine proteases. Cell surfaces to which HMWK binds may provide sites for regulation of these systems. Localization of these HMWK-dependent processes at sites of vascular injury may depend on its binding to specific receptors on endothelial cells. In culture, passaged human umbilical vein endothelial cells (HUVEC) bind anti-HMWK antibody to the cell surface and contain 171 +/- 75 ng of HMWK/10(8) cells. [35S]Methionine-labeled HUVEC in culture synthesize a 120-kDa protein immunoisolated using an anti-kininogen antibody, and a 3500-nucleotide message for human HMWK was detected by Northern blot in RNA extracted from HUVEC. HUVEC also express unoccupied binding sites for HMWK on their surface. 125I-HMWK specifically binds to HUVEC in a reaction requiring Zn2+. 125I-HMWK binding to HUVEC is saturable at 4 degrees C but not at 23 degrees C. 125I-HMWK binds to HUVEC with equal affinity as unlabeled HMWK. Kallikrein, factor XII, fibrinogen, fibronectin, and thrombin do not inhibit 125I-HMWK binding to HUVEC. 125I-HMWK-HUVEC binding remains fully reversible at 60 min following the addition of a 50-fold molar excess HMWK. HUVEC express 9.3 +/- 2.0 X 10(5) (mean +/- S.E.) HMWK binding sites/cell (Kd = 52 +/- 13 nM). Both added and cell-bound 125I-HMWK migrate at 120 kDa on sodium dodecyl sulfate gel electrophoresis, suggesting that the protein remains uncleaved upon binding to the HUVEC surface. These studies indicate that HUVEC synthesize HMWK and the HUVEC surface has a site for its expression. By synthesizing and localizing HMWK to the cell surface, endothelial cells may contribute to the activation of plasma's contact serine zymogens and regulation of tissue cysteine proteases.

Blotting, Northern↗
PubMed1988

Premedication with intramuscular dixyrazine: (Esucos). A controlled double-blind comparison with morphine-scopolamine and placebo.

Ninety patients scheduled for general or orthopaedic surgical procedures were randomly assigned to receive one of three i.m. premedications: dixyrazine 0.5 mg kg-1; morphine 0.15 mg kg-1 and scopolamine 0.0065 mg kg-1; or placebo. The premedication was administered and evaluated in a double-blind fashion. The patients were anaesthetized with thiopentone, fentanyl, pancuronium, and ventilated with nitrous oxide in oxygen. The three premedications had no noticeable anxiolytic effect. Although there was no difference in the frequency of observed postoperative nausea and vomiting between the three groups, premedication with dixyrazine nonetheless reduced the patients' experience of postoperative nausea as well as their need for postoperative antiemetics. Although patients in the two treatment groups were significantly more sedated immediately before induction of anaesthesia than patients receiving placebo, the degree of postoperative sedation was similar in all three groups. Morphine-scopolamine caused more postoperative dizziness than dixyrazine and placebo. Lack of recall was produced by both morphine-scopolamine and dixyrazine. It is concluded that premedication with dixyrazine is a useful alternative, especially in patients who have previously experienced postoperative nausea and vomiting.

Adult↗
PubMed1987

Propofol vs thiopentone as anaesthetic agents for short operative procedures.

In a randomized open study, 120 healthy female patients were included. For short gynaecological procedures they were anaesthetized with either propofol 2.5 mg X kg-1 (n = 60) or thiopentone 5 mg X kg-1 (n = 60) in combination with nitrous oxide/oxygen (67%/33%). Supplementary doses of propofol (10-20 mg) or thiopentone (25-50 mg) were given when necessary during the procedure. Induction characteristics for propofol and thiopentone 1 min after start of induction were similar. Propofol seemed to have a more depressant effect than thiopentone on the circulatory response to anaesthesia. Recovery times from the end of the operative procedure until the patients opened their eyes on command and were orientated were shorter in the propofol patients compared to the thiopentone patients. In the propofol group, patients recalled discomfort on injection more often than patients anaesthetized with thiopentone. Otherwise, the side-effects were similar in both groups. We conclude that propofol is similar to thiopentone in its anaesthetic qualities during induction and maintenance of short anaesthetic procedures. Propofol was associated with a more rapid emergence from anaesthesia than thiopentone.

Anesthesia, Intravenous↗
PubMed1987

Septic shock in the rat: activation of plasma proteolytic systems and effects of a kallikrein inhibitor/bradykinin antagonist (S-2441).

Septic shock was induced in rats by intraperitoneal injection of live Escherichia coli. Plasma prekallikrein, antithrombin III and plasminogen levels were studied with chromogenic peptide substrate assays. Decrease of all the studied plasma components occurred in all rats, but not until late in shock. S-2441, a kallikrein inhibitor/kinin antagonist, slightly delayed the fall in plasma prekallikrein, but no other effects were found. Rat survival was neither enhanced nor prolonged.

Animals↗
PubMed1986

Clonidine and the sympatico-adrenal response to coronary artery by-pass surgery.

Clonidine was administered intravenously in an attempt to limit sympatico-adrenal activity and thereby reduce the incidence of arterial hypertension associated with coronary artery by-pass graft surgery (CABG). Forty patients scheduled for CABG were assigned to two groups. Twenty patients received clonidine 4 micrograms kg-1 before surgery, 2 micrograms kg-1 after cardiopulmonary by-pass and 1 microgram kg-1 when the skin was sutured. The other 20 patients served as controls. All patients were anesthetized with fentanyl, droperidol, nitrous oxide and alcuronium. During surgery 5 min after sternotomy, mean arterial pressure was 13 mmHg lower (P less than 0.01) in the clonidine group, while after operation the difference between the groups was negligible. Both during and after surgery the plasma catecholamine concentrations were significantly lower in the clonidine group (P less than 0.01). The greatest difference between the groups was seen 90 min after operation, when plasma noradrenaline and plasma adrenaline concentrations in the clonidine group were less than 1/3 of those in the control group (P less than 0.01). As judged by catecholamine concentrations clonidine was effective in attenuating sympatico-adrenal hyperactivity during and after surgery. Postoperative arterial hypertension was not reduced, however, and it is concluded that other factors besides sympatico-adrenal hyperactivity must be important.

Adrenocorticotropic Hormone↗