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Biomedical subjects

P Ostwald

Publications and source records attributed to P Ostwald.

At least 19 recordsLinked to original sources
PubMed1999

Solvent for etomidate may cause pain and adverse effects.

We tested the hypothesis that the solvent for etomidate was a factor in the incidence of pain and other side effects after injection, and that these were associated with histamine release. Nine of 10 volunteers who received etomidate in a propylene glycol formulation reported moderate to severe pain on injection; only one of 10 subjects who received a lipid emulsion formulation reported mild pain (P < 0.05). The incidence of venous sequelae in the injected vein over the next 8 days was 50% in the propylene glycol group and 0% in the lipid emulsion group (P < 0.05). In one volunteer in the propylene group, there was a 13-fold increase in histamine concentrations and in one subject a four-fold increase. In the lipid emulsion group, no volunteer had an increase in histamine concentrations > 1 ng ml-1. We conclude that etomidate formulated in propylene glycol may cause direct injury to vascular endothelium resulting in pain and venous sequelae, whereas etomidate in lipid emulsion does not. There was no relationship between pain or venous sequelae and histamine release.

Adult↗
PubMed1999

Reducing myoclonus after etomidate.

BACKGROUND: The authors hypothesized that myoclonus after etomidate is dose-related, could be suppressed when small doses of etomidate were administered before induction, and is unassociated with seizure-like activity on electroencephalogram (EEG). METHODS: Three studies were performed. In the first study, 36 men were randomly assigned to receive 0.025, 0.050, 0.075, 0.100, 0.200, or 0.300 mg/kg of etomidate. In a second crossover study, eight men were randomly allocated to receive either a pretreatment dose of 0.050 mg/kg etomidate or placebo 50 s before 0.300 mg/kg etomidate was injected. EEG was recorded for subjects in the first two studies. In a third study, 60 patients were randomly allocated to one of three pretreatment doses of etomidate: 0.030, 0.050, or 0.075 mg/kg before 0.300 mg/kg was given. RESULTS: In Study 1, myoclonus was not observed after 0.025 or 0.050 mg/kg etomidate. One volunteer had myoclonus after 0.075 mg/kg and another after 0.100 mg/kg etomidate; three had myoclonus after 0.200 mg/kg; and five after 0.300 mg/kg. Incidence of myoclonus was dose-related (P < or = 0.01). In Study 2, two volunteers (25%) with etomidate pretreatment had mild myoclonus compared to six (75%) with placebo pretreatment (P < or = 0.05). EEG changes, other than delta waves, were not seen during myoclonic epochs. In Study 3, myoclonus was less likely after the small pretreatment doses (0.030 or 0.050 mg/kg) than after the large dose (0.075 mg/kg, P < or = 0.01). CONCLUSIONS: Incidence and intensity of myoclonus after induction with etomidate are dose-related, suppressed by pretreatment, and unassociated with seizure-like EEG activity.

Adult↗
PubMed1998

Do inflammatory processes contribute to radiation induced erythema observed in the skin of humans?

BACKGROUND: Two prospective trials were designed to determine whether there may be a role for inflammatory mediators in human skin erythema at both high and low doses per fraction and for 'out of field' effects. METHODS: Trial 1. Effects of topical indomethacin (1%) and hydrocortisone (1%) applied before and during radiotherapy were compared for erythema induced by 20 Gy in four fractions (n = 26, 6 MV). Trial 2. Effects of topical hydrocortisone (1 %) applied before and during radiotherapy and no medication were compared for erythema induced by 1, 3, 5 and 7 Gy in five fractions (n = 21, 120 kV). Erythema was measured using reflectance spectrophotometry (RFS) and laser Doppler (LD) on a weekly basis. RESULTS: Trial 1. A bi-phasic reaction time course was suggested in two-thirds of the cases. The first phase did not appear to be influenced by hydrocortisone cream but the second was significantly attenuated. Indomethacin had no effect on either reaction phase. Erythema measured several centimetres outside of the field was reduced by hydrocortisone but not by indomethacin. Trial 2. Trial 2 confirmed the presence of measurable erythema, invisible to the eye, that coincided in its time course to the first phase of erythema noted in trial 1. This reaction was more intense than predicted by the LQ formula and was non-significantly attenuated by topical hydrocortisone. RFS readings proved to be less subject to inter- and intra-patient variations than the LD unit used. CONCLUSION: Inflammatory responses may play a role in the mediation of the erythematous response to radiation in human skin. Further studies are warranted.

Aged↗
PubMed1998

Etomidate revisited.

The major advantage of etomidate is its lack of cardiovascular side effects. In addition, etomidate is supposed to be neuroprotective. The side effects of etomidate include adrenal suppression and myocloni. A review of the recent literature on etomidate, its clinical use, its side effects and its mechanism of action was performed. Among others, major recent advances include a new drug preparation devoid of propylene glycol and its side effects, a new pretreatment technique that may reduce the incidence of myocloni, and the identification of its site of action in the central nervous system.

Journal Article↗
PubMed1997

Administration of H1 and H2 antagonists for chemoprophylaxis: a double-blind, placebo-controlled study in healthy volunteers.

A double-blind, placebo-controlled trial was performed to establish the duration of action of antihistamines and their ability to attenuate the adverse affects associated with histamine release. Thirty volunteers were assigned randomly to receive either placebo or a combination of the H1 blocker dimetindene maleate (0.1 mg/kg) and the H2 blocker cimetidine (5 mg/kg). A bolus dose of histamine (450 ng/kg) was given 15 minutes after antihistamine or placebo treatment and repeated after 2, 4, and 6 hours. Cardiovascular variables, plasma histamine levels, cutaneous manifestations, and objective and subjective signs and symptoms associated with histamine release were determined before and after each histamine injection. Although many of the signs of histamine release, including erythema and metallic taste, could be attenuated effectively for 6 hours with antihistamine treatment, the protection against histamine-induced flush and headache diminished after 2 hours. Statistically significant protection against histamine-mediated tachycardia persisted for only 2 hours. Antihistamine treatment significantly reduced the increase in plasma histamine levels after the first histamine injection but did not alter the levels after subsequent histamine injections. The currently recommended administration regimen for prophylaxis with antihistamines is insufficient to prevent histamine-mediated side effects, and additional doses may be required after 4 hours to achieve appropriate chemoprophylaxis.

Adult↗
PubMed1997

Adenosine receptor blockade and nitric oxide synthase inhibition in the retina: impact upon post-ischemic hyperemia and the electroretinogram.

We preformed this study to determine the effect on ocular blood flow and the electroretinogram of either nitric oxide synthase (NOS) inhibition, adenosine receptor blockade or the combination of both after 1 hr of ocular ischemia. Thirty-seven cats under general anesthesia were subjected to 1 hr of complete ischemia in one eye by raising the intraocular pressure above systolic blood pressure. The other eye in each animal served as a non-ischemic control. Arterial blood gas tension, systemic arterial pressure, body temperature, hematocrit, and anesthetic level were controlled in each experiment. Cats were divided into four groups. Group 1 received normal saline injections [intravenous (i.v.) and intravitreal], Group 2 adenosine receptor blockade (0.1 ml of 0.01 M 8-sulfophenyltheophylline intravitreal) and saline i.v., Group 3 NOS inhibition (30 mg/kg l-NG-nitroarginine-methyl-ester i.v.) and saline intravitreal, and Group 4 intravitreal adenosine receptor blockade and NOS inhibition i.v. A subset of Group 3 received l-arginine to investigate the reversibility of NOS inhibition, after the blood flow measurements were completed. Five minutes after the end of ischemia, blood flows in retina and choroid were measured using injections of radioactively labeled microspheres. Electroretinographic (ERG) studies were carried out before treatment, before ischemia, during ischemia, and 1, 2, 3, and 4 hr after ischemia ended. NOS inhibition significantly reduced basal blood flow in the choroid, and in the retina when combined with adenosine receptor blockade. Adenosine receptor blockade completely attenuated post-ischemic hyperemia in the retina, but retinal hyperemia reappeared when adenosine receptor blockade and NOS inhibition were combined. Adenosine receptor blockade had no effect on ERG recovery after ischemia. NOS inhibition led to a reduction of ERG a- and b-wave amplitudes in control eyes, that could be reversed by l-arginine. Nitric oxide (NO) appears to be a significant factor in the regulation of basal blood flow in the choroid. Adenosine appears to be a major mediator of retinal hyperemia after 60 min of ischemia. Since NOS inhibition appeared to have direct effects on ERG wave amplitudes, short-term ERG studies may be of limited use in assessing the role of NO in postischemic recovery of the retina. Our observations correlate well with the emerging role of NO as a neurotransmitter in the retina.

Analysis of Variance↗
PubMed1997

Response of human hair cortical cells to fractionated radiotherapy.

Hair cortical cell counting (HCCC) represents a non-invasive, in-vivo measure of cell kill in the human integument. Sixty-six patients undergoing conventionally fractionated, external beam radiotherapy for early stage carcinoma of the prostate had groin hair samples counted. This technique is a sensitive and reproducible measure of radiation effect and may have applicability as an in-vivo prediction tool or in the field of biological dosimetry. A repopulative follicular response occurring at 3-4 weeks may explain flattening of the dose response curve.

Dose-Response Relationship, Radiation↗
PubMed1997

Haemolysis after etomidate: comparison of propylene glycol and lipid formulations.

We sought to determine if the solvent in the formulation of etomidate is responsible for haemolysis in patients. In a randomized, prospective, double-blind study of 49 patients undergoing otolaryngological surgery, patients received etomidate dissolved in propylene glycol or in lipid emulsion. Concentrations of free haemoglobin and haptoglobin were measured before and for up to 360 min after injection of etomidate. Free haemoglobin concentrations increased by 216.8 mg litre-1 in patients who received the propylene glycol formulation and by 11.8 mg litre-1 in the lipid emulsion group (P < or = 0.0004). Correspondingly, reductions in haptoglobin concentrations were significantly greater in the propylene glycol group (P < or = 0.002). We conclude that with respect to haemolysis, lipid emulsion is superior to propylene glycol as a solvent for etomidate.

Anesthetics, Intravenous↗
PubMed1997

The usefulness of three biallelic restriction fragment length polymorphisms versus a polymorphic dinucleotide tandem repeat polymorphism at the low-density-lipoprotein receptor gene locus for diagnosis of familial hypercholesterolemia.

Indirect molecular diagnosis of familial hypercholesterolemia is possible based on genetic linkage analysis of DNA polymorphisms at the low-density-lipoprotein receptor gene locus in family studies. The use of biallelic restriction fragment length polymorphisms, however, is restricted by their low degree of heterogeneity, and therefore several of these markers have to be combined. To overcome these restrictions we examined the value and applicability of an (AT)n tandem repeat polymorphism at the 3' untranslated region of the gene, alone and in combination with three biallelic restriction fragment length polymorphisms in 35 independent healthy subjects and in familial hypercholesterolemia families with 23 parents and 52 children. For each family one of the parents had the clinical diagnosis of familial hypercholesterolemia. The probands were genotyped using the TaqI, HincII and NcoI restriction fragment length polymorphism and the (AT)n tandem repeat polymorphism of the gene. The heterozygosity index (0.60) and the polymorphism information content (PIC value) (0.53) of the ATn repeat polymorphism were higher compared to each single biallelic restriction fragment length polymorphism (heterozygosity index 0.26-0.54; PIC value 0.24-0.36). The combined PIC value of all three biallelic restriction fragment length polymorphisms (0.79) was comparable to the combination of the HincII and the ATn polymorphism (0.74). Using these two markers, a definitive molecular diagnosis could be made in 36 children from 15 parents compared to just 12 parents and their children using the three biallelic restriction fragment length polymorphisms. We conclude that the ATn tandem repeat polymorphisms is useful for indirect molecular diagnosis of familial hypercholesterolemia in affected families.

Chromosome Mapping↗
PubMed1996

Nitric oxide: a review of its role in retinal function and disease.

Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and endothelial isoforms are constitutively expressed, and require calcium for activation. Both of these isoforms can be induced (i.e., new protein synthesis occurs) under appropriate conditions. The immunologic isoform is not constitutively expressed, and requires induction usually by immunologic activation; calcium is not necessary for its activation. Neuronal and immunologic NOS have been detected in the retina. Neuronal NOS may be responsible for producing nitric oxide in photoreceptors and bipolar cells. Nitric oxide stimulates guanylate cyclase of photoreceptor rod cells and increases calcium channel currents. In the retina of cats, NOS inhibition impairs phototransduction as assessed by the electroretinogram. Inducible nitric oxide synthase, found in Müller cells and in retinal pigment epithelium, may be involved in normal phagocytosis of the retinal outer segment, in infectious and ischemic processes, and in the pathogenesis of diabetic retinopathy. Nitric oxide contributes to basal tone in the retinal circulation. To date, findings are conflicting with respect to its role in retinal autoregulation. During glucose and oxygen deprivation, nitric oxide may increase blood flow and prevent platelet aggregation, but it may also mediate the toxic effects of excitatory amino acid release. This reactive, short-lived gas is involved in diverse processes within the retina, and its significance continues to be actively studied.

Animals↗
PubMed1996

Underprediction of human skin erythema at low doses per fraction by the linear quadratic model.

BACKGROUND AND PURPOSE: The erythematous response of human skin to radiotherapy has proven useful for testing the predictions of the linear quadratic (LQ) model in terms of fractionation sensitivity and repair half time. No formal investigation of the response of human skin to doses less than 2 Gy per fraction has occurred. This study aims to test the validity of the LQ model for human skin at doses ranging from 0.4 to 5.2 Gy per fraction. MATERIALS AND METHODS: Complete erythema reaction profiles were obtained using reflectance spectrophotometry in two patient populations: 65 patients treated palliatively with 5, 10, 12 and 20 daily treatment fractions (varying thicknesses of bolus, various body sites) and 52 patients undergoing prostatic irradiation for localised carcinoma of the prostate (no bolus, 30-32 fractions). RESULTS AND CONCLUSIONS: Gender, age, site and prior sun exposure influence pre- and post-treatment erythema values independently of dose administered. Out-of-field effects were also noted. The linear quadratic model significantly underpredicted peak erythema values at doses less than 1.5 Gy per fraction. This suggests that either the conventional linear quadratic model does not apply for low doses per fraction in human skin or that erythema is not exclusively initiated by radiation damage to the basal layer. The data are potentially explained by an induced repair model.

Aged↗
PubMed1996

Effect of oral antihistamine premedication on mivacurium-induced histamine release and side effects.

In this randomized, double-blind, placebo-controlled study, we have examined histamine release, haemodynamic and cutaneous effects of mivacurium administered in low (0.105 mg kg-1 = 1.5 x ED95) and high (0.21 mg kg-1 = 3 x ED95) doses and assessed if oral pretreatment with H1/H2 antagonists would blunt the effects of mivacurium-induced histamine release. Patients received either ranitidine 300 mg and dimethindene 0.1 mg kg-1 (H1 blocker) or placebo, orally 1 h before induction of anaesthesia. Twelve patients were allocated to each group. Although plasma concentrations of histamine increased significantly in three patients in the placebo group given low-dose mivacurium, the mean value for the group was unchanged. Plasma concentrations of histamine increased significantly in five patients in the placebo group after high-dose mivacurium and the mean value was increased. There was no consistent correlation between haemodynamic changes, cutaneous manifestations and histamine concentrations. Significant cardiovascular reactions occurred in six patients in the placebo groups and in only one patient treated with antihistamines.

Adolescent↗
PubMed1995

Verification of surface dose on patients undergoing low to medium energy X-ray therapy.

About 5% of patients still undergo cancer treatment with superficial (peak energy < or = 120 kVp) X-ray radiation. Dosimetry of these beams is difficult since the maximum dose is delivered at the surface and backscatter contributes significantly to the dose. This is particularly a problem in the difficult geometries encountered in superficial treatments in the head and neck area. It has recently been shown that surface dose measurements in mega-voltage X-ray beams can be performed using TLD (Thermoluminescence Dosimetry) extrapolation. In this technique, LiF TLD chips with a surface area of 3.15 x 3.15 cm2 and three different thicknesses (0.230, 0.099, and 0.038 g/cm2) are used together in the same radiation beam which allows the extrapolation of the measured dose back to the true surface. The energy response curve of the three thicknesses of LiF chips was measured for the energy range of 60kVp, HVL 1.6 mm Al to 300kVp, 4 mm Cu. LiF was found to over respond by a factor of 1.7 at 60kVp HVL 1.6 mm Al with respect to a 6MV photon beam. A feasibility study was carried out on three patients undergoing treatment at 120kVp. Because of the small field sizes involved it was necessary to limit irradiation to one or two chips at a time. The dose fall off in the first millimetre of tissue could be clearly detected. TLD extrapolation, in low to medium energy beams, was found to be useful to assess the dose of patients undergoing treatment for superficial lesions.

Feasibility Studies↗
PubMed1995

Effect of nitric oxide synthase inhibition on blood flow after retinal ischemia in cats.

PURPOSE: To determine the effect of nitric oxide synthase inhibition on blood flow in the cat retina and on changes in the electroretinogram after 1 hour of ocular ischemia. METHODS: After the induction of general anesthesia, one eye in each of 18 cats was subjected to 60 minutes of ischemia by raising intraocular pressure above systolic arterial pressure. One group (n = 9) was administered 30 mg/kg L-NG-nitro-arginine-methylester (L-NAME) intravenously 60 minutes before ischemia. The other group (n = 9) was administered an equivalent volume of saline intravenously. Five minutes after the end of ischemia, blood flow in the retina, choroid, and iris-ciliary body was measured using injections of radioactively labeled microspheres. Electroretinographic studies were carried out before, during, and 1, 2, 3, and 4 hours after ischemia ended. Arterial blood gas tension, systemic arterial pressure, hematocrit, and anesthetic levels were controlled in each experiment. RESULTS: Basal blood flow in iris-ciliary body was decreased by L-NAME, whereas retinal and choroidal blood flow was unchanged. Postischemic hyperemia was unaltered in the choroid and reduced in the retina. There was enhancement of postischemic hyperemia in the iris-ciliary body, but this effect may have resulted from a decrease in basal flow in the L-NAME group. Electroretinographic a- and b-wave recoveries were not altered by L-NAME; L-NAME infusion significantly decreased b-wave amplitude. CONCLUSIONS: Nitric oxide appears to be a significant factor in the regulation of uveal circulation and may contribute to the regulation of retinal, but not choroidal, blood flow after ischemia. The authors could not detect a difference in outcome by electroretinography with or without nitric oxide synthase inhibition.

Animals↗
PubMed1993

Identification of the serine-156 to leucine mutation in the low-density lipoprotein receptor in a German family with familial hypercholesterolemia.

Familial hypercholesterolemia is caused by various mutations in the gene encoding the low-density lipoprotein receptor. To date more than 100 mutations have been identified, including insertions and deletions as well as single base changes. In the German population haplotype analysis using four restriction fragment length polymorphisms has recently suggested that there exist at least six different genetic defects. Screening 100 FH patients of German origin for the serine 156 to leucine mutation, originally described in a Puerto Rican family living in the United States, resulted in the identification of the mutation in one family. However, by haplotype analysis the mutation was found on a different haplotype from that reported originally. Based on comparison of the haplotypes and their frequencies we suggest that this mutation has occurred independently at least twice.

Adult↗