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Biomedical subjects

K Danielson

Publications and source records attributed to K Danielson.

At least 19 recordsLinked to original sources
PubMed2002

Polymer/alginate amalgam for cartilage-tissue engineering.

Marrow stroma-derived cells (MSC) are highly proliferative, multipotential cells that have been considered as ideal candidate cells for autologous tissue engineering applications. In this study, we have characterized the chondrogenic potential of human MSCs in both a PLA/alginate amalgam and pure PLA macrostructure as model three-dimensional constructs to support both chondrogenic differentiation and proliferation following TGF-beta treatment. MSCs were seeded in experimental groups that consisted of PLA-loaded constructs and PLA/alginate amalgams with and without recombinant human TGF-beta1. Chondrogenesis of the PLA and the PLA/alginate amalgam cultures was assessed at weekly intervals by histology, immunohistochemistry, scanning electron microscopy, sulfate incorporation, and RT-PCR. Chondrogenic differentiation occurs within a polymeric macrostructure with TGF-beta1 treatment as indicated by histological, immunohistochemical, sulfate incorporation, and gene expression profiles. This macrostructure can be further encased in an alginate gel/solution to optimize cell shape and to confine growth factors and cells within the polymer construct, while the polymeric scaffold provides appropriate mechanical/tissue support. The stable three-dimensional PLA/alginate amalgam represents a novel candidate system of mesenchymal chondrogenesis, which is amendable to investigation of mechanical and biological factors that normally modulate cartilage development and formation as well as a potential tissue engineering construct for cartilage repair.

Alginates↗
PubMed2001

Application of mesenchymal stem cells in the regeneration of musculoskeletal tissues.

Mesenchymal stem cells are a rare population of undifferentiated cells, isolated from adult tissue sources, that have the capacity to differentiate into mesodermal lineages, including bone, fat, muscle, cartilage, tendon, and marrow stroma. These cell populations may be expanded in culture and subsequently permitted to differentiate into the desired lineage. This directed differentiation may be reached by the application of bioactive molecules, specific growth factors, and signaling molecules. Understanding the functional potential of these cells and the signaling mechanisms underlying their differentiation should lead to innovative protocols for clinical orthopaedic interventions. Clinically applicable techniques to isolate, expand, and reimplant these autogenous cells will become part of the repertoire of orthopaedic therapy. In the presence of extrinsic signaling molecules, provided by both the clinician and the local cellular environment, the intrinsic multipotential nature of the stem cells may be realized for applications such as the replacement of bone graft for segmental defects, nonunions, and spinal fusions. Additional applications may include treatment of full-thickness articular defects and articular resurfacing by site-specific delivery of stem cells. The ultimate goal is directed cellular regeneration of damaged or diseased musculoskeletal tissue. Currently, the limitation is our knowledge and ability to direct this differentiation, but with further study molecular orthopaedic interventions should become a reality.

Animals↗
PubMed1995

Phenytoin causes phalangeal hypoplasia in the rabbit fetus at clinically relevant free plasma concentrations.

New Zealand White rabbits were treated orally with 0 (controls), 50, 100, or 150 mg/kg phenytoin on days 14-16 of pregnancy. Total and free plasma concentrations of phenytoin were determined in maternal plasma 2, 6, and 24 hr after the final dose in all animals. In addition, after administration of 150 mg/kg maternal plasma concentrations were also determined after 12 and 48 hr, the concentrations in amniotic fluid after 6 hr, and those in fetal tissue 6 and 24 hr after the final treatment. A high degree of plasma protein binding was observed in maternal blood. Treatment with 50 mg/kg resulted in free plasma concentrations of up to 5.0 mumol/l during the 24 hr period following the final dose. Significantly higher free plasma concentrations were observed at the two higher dose levels; up to 9.7 mumol/l at 100 mg/kg and 12.7 mumol/l at 150 mg/kg. Digital hypoplasia was not seen in the control group or the animals treated with 50 mg/kg. However, treatment with 100 mg/kg resulted in hypoplasia in a single or a few digits in approximately 50% of the fetuses, and 150 mg/kg provoked hypoplasia in almost all digits in all fetuses. These results show that even though the doses which caused digital defects in rabbits are much higher than those used therapeutically, the resulting free concentrations of phenytoin are similar to those which are associated with the same type of defects in humans. These data indicate that the pharmacologically induced fetal hypoxia/ischemia and vascular disruption preceding malformations of this type, which were observed in a previous study in rabbits, may be of human relevance.

Abnormalities, Drug-Induced↗
PubMed1993

Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration.

The growth hormone-releasing hormone analogue GHRH(1-29)-NH2 was administered intravenously or intranasally to 30 healthy men aged 19-43 years. Intravenous injection of the lowest dose tested, 0.25 microgram/kg body weight, elicited significant release of growth hormone (GH). Maximal release (mean GH peaks of about 90 mU/l) was obtained with a dose of 1-2 micrograms/kg. Although GHRH(1-29)-NH2 was rapidly eliminated after intravenous injection, GH levels were elevated for about 3 hours. Absorption of GHRH(1-29)-NH2 through the nasal mucosa was found to be low, and the bioavailability was only 3-5%. There was a dose-dependent release of GH after intranasal administration of GHRH(1-29)-NH2, with the maximal response obtained with about 50 micrograms/kg; this dose was approximately as potent as 1 microgram/kg injected intravenously. The GH response after repeated intranasal administration of GHRH(1-29)-NH2 was sustained; there was no suppression of GH secretion during the night following a day when GHRH(1-29)-NH2 had been given three times intranasally. Based on these findings and the obvious convenience of intranasal administration compared with injections, it would be justified to test intranasal therapy for treatment of short stature in children with GH deficiency caused by hypothalamic damage.

Administration, Intranasal↗
PubMed1993

Intranasal administration of growth hormone-releasing hormone(1-29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth.

The growth-promoting potential of growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 micrograms/l in two stimulation tests (arginine, insulin), but above 12 (24-90) micrograms/l after intravenous GHRH, 1 microgram/kg. GHRH, 50 micrograms/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRH insufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 micrograms/l and from 10 to 85 mIU/l, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate rose from 0.24 to 0.48 mm/week after 6 weeks of treatment (p = 0.03) and then rapidly declined; the mean 6-month stadiometric height velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions.

Administration, Intranasal↗
PubMed1990

Plasma concentrations of lidocaine and prilocaine and analgesic effect after dermal application of EMLA cream 5% for surgical removal of mollusca in children.

The plasma concentrations of lidocaine and prilocaine after dermal application of EMLA cream 5% were determined in two clinical studies. The cream (10-16 g) was applied to a total surface area of 100-160 cm2. Each area was covered by a Tegaderm dressing (3M) in order to obtain occlusion. An application time of 2 hours was used. Two age groups of ten children were studied: 2-3 years and 6-8 years. In both groups venous blood samples were drawn prior to application and at 2, 3, 4 and 5 hours. In addition, in one of the studies, the cream was used during the surgical removal of mollusca in order to study the analgesic effect of the cream. The absorption of the local anaesthetics as indicated by plasma concentrations was far below toxic levels. The highest individual concentration of lidocaine was 315 ng/ml and of prilocaine 215 ng/ml. The analgesic effect was sufficient--eight out of ten patients experienced no or slight pain. Transient local reactions (paleness, redness) were frequently observed. In one patient with eczema present at the application site prior to the application, a reaction persisted for one week. Dermal analgesia provided by EMLA is a safe and effective method for alleviation of pain from removal of mollusca and the plasma concentrations are innocuous.

Analgesia↗
PubMed1990

Inverse relationship between age-dependent erythrocyte activity of methaemoglobin reductase and prilocaine-induced methaemoglobinaemia during infancy.

We have measured plasma concentrations of local anaesthetics, and the substance fraction of methaemoglobin (MetHb), in infants less than 3 months of age, after application of a lignocaine-prilocaine cream (EMLA). A total of EMLA 2 g was applied over four different skin areas, totalling 16 cm2, for 4 h before anaesthesia for a minor surgical procedure. Sampling was carried out before and 4, 8 and 12 h after application. Maximum MetHb values (median = 2.24%) were obtained usually at 8 h and were significantly (P less than 0.001) higher than before application (median 1.32%). The plasma concentrations of local anaesthetics were low (maximum values: prilocaine 78 ng ml-1, lignocaine 412 ng ml-1). The activity of erythrocyte MetHb reductase (cytochrome b5 reductase) was analysed. Data from a previously studied group of infants aged 3-12 months were included also. Enzyme activity did not reach adult levels until after the age of 3 months. It showed a good inverse correlation with the maximum MetHb values after application of EMLA. Although the MetHb concentrations in the infants younger than 3 months were small, the enzyme capacity may be overloaded when EMLA is administered at the same time as other MetHb-inducing agents. It is concluded that the use of EMLA should be restricted in this age group.

Age Factors↗
PubMed1990

Administration of growth hormone by disposable preloaded syringes.

The convenience of Genotropin KabiQuick, a novel single-use disposable injection system for growth hormone (GH) administration, was studied in 20 GH-treated children aged 8-16 years. The convenience of the device and tolerance to it were assessed by means of a questionnaire, which was completed by the patients and their families after a treatment period of 2 weeks. The families were asked to compare the new device with the conventional system of GH administration, involving the use of standard ampoules and ordinary syringes. The majority of patients considered the new device superior to the conventional system; 85% of patients found reconstitution easier and 70% found dosing easier. Sixty-five per cent of patients expressed a preference for using Genotropin KabiQuick for future therapy. It is concluded that Genotropin KabiQuick is well tolerated and that the majority of patients prefer it to conventional injection systems for GH administration.

Adolescent↗
PubMed1990

Genotropin 16 IU KabiVial is more convenient than conventional administration systems for children on growth hormone therapy.

The use of a new device for reconstitution and storage of growth hormone (GH), Genotropin KabiVial, was studied in 20 children, aged 9-17 years, who had been receiving GH therapy using conventional administration systems. After 2 weeks of treatment, the convenience of the device and the patients' tolerance of it were assessed by the patients/families through a questionnaire. They were asked to compare the new device with the conventional method (standard vials and syringes). Most of the patients found the new device superior to the conventional method; they found that it was easier to reconstitute the GH and considered the multi-dose system and the smaller injection volume to be advantageous. Ninety per cent of the patients (p less than 0.001) expressed a preference for Genotropin 16 IU KabiVial for their future therapy.

Adolescent↗
PubMed1990

EMLA for pain relief during arterial cannulation. A double-blind, placebo-controlled study of a lidocaine-prilocaine cream.

The aim of the study was to evaluate the effect of a lidocaine-prilocaine cream (EMLA cream, Astra) in relieving pain during arterial cannulation. The study had a random, double-blind, placebo-controlled design and included altogether 90 patients. All the patients were premedicated with an opioid before cannulation. An EMLA application time of 60 minutes was used in 60 patients (30 EMLA/30 placebo) and there was no difference in the pain reaction measured on a visual analogue scale (VAS) or on an observer's verbal scale. The study was extended with a further 30 patients (15 EMLA/15 placebo) with an application time exceeding 90 minutes. Between these groups pain experience measured by VAS did not show any significant difference although the mean value was lower in the EMLA group. Observer ratings showed a significant (p less than 0.01) difference in distribution towards lower ratings in the EMLA group. In conclusion EMLA was found to have a weak, but measurable effect when the application time exceeded 90 minutes but not after 60 minutes.

Anesthetics, Local↗
PubMed1989

Local anaesthetic cream for the alleviation of pain during venepuncture in Tanzanian schoolchildren.

The analgesic effect and the usefulness of EMLA cream 5% in connection with venous blood-sampling was investigated in 42 Tanzanian schoolchildren. Approximately 2.5 g EMLA was applied to the right cubital fossa for a minimum of 120 min. The analgesic effect was pronounced--93% of the venepunctures were pain-free and no child experienced severe pain. No adverse reactions were observed and the children could continue normal school work during the application time.

Adolescent↗
PubMed1987

Plasma concentrations of prilocaine and lidocaine and methaemoglobin formation in infants after epicutaneous application of a 5% lidocaine-prilocaine (EMLA).

The aim of the study was to measure the plasma levels of lidocaine and prilocaine after dermal application of EMLA in infants and to evaluate whether this procedure increases the levels of methaemoglobin (Met-Hb). Two groups of infants, 3-6 (n = 12) and 6-12 months (n = 10) of age, were studied. In total, 2 ml of EMLA was applied to 4 x 4 cm of skin surface for 4 h and blood samples for detection of Met-Hb and plasma levels of local anaesthetics were taken at 0, 2, 4 and 8 h after the application. After removal of the cream the infants were operated mainly for minor procedures under general anaesthesia. The plasma concentrations of lidocaine and prilocaine were in all cases below toxic levels and there were only minor increases in Met-Hb in a few infants. In conclusion, EMLA can be used safely in infants above 3 months of age provided that the recommendations with regard to dose, application area and time are followed. The use of EMLA in smaller infants and in children taking other Met-Hb-inducing drugs needs further evaluation.

Administration, Topical↗
PubMed1978

Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects.

The single-dose kinetics of D-propoxyphene, acetyl salicylic acid and phenazone, given in a combination tablet (Doleron), were compared in young and elderly subjects. Serial blood samples were taken 0--48 hours after administration. The plasma concentrations of propoxyphene and of its major metabolite, norporpoxyphene, were assessed by mass fragmentography, those of phenazone by gas chromatography, and those of acetyl salicylic acid plus salicylic acid by spectrofluorometry. Neither for propoxyphene, norpropoxyphene, acetyl salicylic acid nor phenazone did the areas under the concentration curves or the elimination half-lives differ between young and elderly subjects. These data do not provide pharmacokinetic support for a general reduction of the Doleron dosage in elderly subjects.

Administration, Oral↗