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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 199 records · Page 11Linked to original sources
PubMed1989

Optimization of blood sampling time after intravenous bolus doses of gentamicin.

Comparisons were made, based on a one-compartment model, between predicted serum concentrations obtained at various sampling times after i.v. bolus and i.m. injections of gentamicin. Post-dose concentrations 1 h after i.m. injection were within 3% of the maximum concentration at steady-state, indicating that this was the optimal sampling time. Serum concentrations 1 h post-i.v. bolus were less than 7% different from those 1 h post-i.m. injection. In a clinical trial, blood samples taken earlier during the distribution phase of the drug, after an i.v. bolus, resulted in serum concentrations which were up to 74% higher than concentrations at 1 h. A survey of a sample of U.K. hospitals showed that only 41% were taking samples at 1 h post i.v. bolus of gentamicin. The majority of hospitals recommended a range of post-dose serum concentrations between 4 and 12 mg/l for patients with septicaemia, but when adjusted for errors related to sampling time, 36% of hospitals recommended a minimum which was equivalent to less than 4 mg/l at 1 h post dose. Post-dose concentrations of gentamicin should be measured in samples taken 1 h after either i.v. bolus and i.m. injections.

Gentamicins↗
PubMed1989

Improved medium for recovery and enumeration of the farmer's lung organism, Saccharomonospora viridis.

A new medium, which we propose to call R8, was developed for the isolation and enumeration of the thermophilic actinomycete, Saccharomonospora viridis. This organism has been implicated in a range of hypersensitivity pneumonitides, including farmer's lung, but is generally isolated in small numbers from contaminated environments. Recovery of S. viridis from moldy hay and mushroom compost on R8 medium was compared with recovery on conventional media. S. viridis was isolated from both substrates but in highest numbers and most consistently on the R8 medium. The selectivity of this medium was best observed when the sedimentation chamber method was used for hay samples. Here S. viridis accounted for up to 80% of the total number of actinomycetes recovered on R8 and could not be recovered on rifampin selective medium under the same conditions. R8 was also found to be an efficient recovery medium for a range of thermophilic actinomycetes from mushroom compost and for another allergenic species, Faenia rectivirgula, from moldy hay. Contamination of isolation plates by thermophilic bacilli was reduced on R8 compared with the activity on half-strength tryptone soy agar, supplemented with 0.2% casein hydrolysate, and this, together with specific improvements in S. viridis growth, accounts for the selective effect. It is possible that the occurrence of S. viridis and its role as a causative agent of hypersensitivity pnuemonitis have been underestimated by the use of suboptimal recovery protocols. It is hoped that use of R8 in conjunction with dilution plate techniques will generate information on the ecology of S. viridis and contribute to health risk assessment studies.

Actinomycetales↗
PubMed1989

The use of indium-111 labeled platelet scanning for the detection of asymptomatic deep venous thrombosis in a high risk population.

Five hundred indium-111 labeled platelet imaging studies (387 donor and 113 autologous) were performed postoperatively in 473 patients who had undergone total hip replacement, total knee replacement, or internal fixation of a hip fracture to detect occult deep venous thrombosis. All patients had been anticoagulated prophylactically with aspirin, warfarin sodium (Coumadin), or dextran. Thirty-four possible cases of proximal deep venous thrombosis were identified in 28 asymptomatic patients. To verify the scan results, 31 venograms were performed in 25 patients (three refused). In 21 of 31 cases, totally occlusive thrombi were detected; in 5 cases, partially occlusive thrombi were detected; in 5 cases, no thrombus was seen. No patient who had a negative scan nor any patient who had a verified positive scan (and received appropriate heparin therapy) subsequently developed symptoms or signs of pulmonary embolism. One hundred forty-one indium study patients also underwent Doppler ultrasonography/impedance plethysmography (Doppler/IPG) as a comparative non-invasive technique. In 137 cases, the results of the indium study and Doppler/IPG studies were congruent. The indium study had no false negative results that were detected by Doppler/IPG. No patient had any clinically evident toxicity. These results suggest that indium-111 labeled platelet scanning is a safe, noninvasive means for identifying DVT in high risk patients.

Adult↗
PubMed1989

Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments.

Adenocarcinoma↗
PubMed1989

Exocytosis of bovine chromaffin granules in Ficoll captured by rapid freezing.

Exocytosis of cultured bovine adrenal chromaffin cells was examined in a balanced salt solution containing Ficoll using rapid freezing followed by freeze-substitution. In solution without Ficoll, exposure to Ba2+ produced many exocytotic lumina between the cells; in most cases, these lumina were large and empty. When chromaffin cells were exposed to Ba2+ in Ficoll, it was possible to observe a small pore between the plasmalemma and each granule. The granule retained the dense contents when the pore was approximately 20 nm in diameter, and became empty when the pore was widened in 14% Ficoll. The addition of Ficoll made it easy to catch the events occurring during exocytosis of individual bovine chromaffin granules.

Animals↗
PubMed1988

Sequencing and synthesis of pardaxin, a polypeptide from the Red Sea Moses sole with ionophore activity.

Pardaxin, an amphipathic polypeptide secreted by the Red Sea flatfish Pardachirus marmoratus whose sequence is NH2-G-F-F-A-L-I-P-K-I-I-S-S-P-L-F-K-T-L-L-S-A-V-G-S-A-L-S-S-S-G-G-Q-E, was synthesized by the solid-phase method. The structure was verified by sequencing. The synthetic polypeptide changed the resistance of lipid bilayers by forming pores. At 10(-7)-10(-8) M, the synthetic pardaxin increased the frequency of the spontaneous release of quanta of acetylcholine at the neuromuscular junction by up to 100-fold, resembling the native product. Synthetic pardaxin seems to be a suitable tool for investigating the molecular structures underlying channel selectivity.

Acetylcholine↗
PubMed1988

Aberrant growth of regenerating retinotectal axons subsequent to optic tract ablation in goldfish.

This study examined the effect of optic tract ablation on retinotectal fiber regeneration in goldfish. Approximately two-thirds of the left optic tract was removed, and, at various times post lesion (10-75 days), the course of regenerating retinotectal fibers was traced using horseradish peroxidase. In all experimental animals, axons were observed regenerating through the visual pathway but at the brachia most of the fibers were channeled through the ventral brachium. We present evidence that fibers in the ventral brachium originated from ganglion cells in all regions of retina and that these fibers grew almost exclusively into ventral half tectum even though some of these fibers would normally synapse in dorsal half tectum. These observations suggest that optic tract ablation does not prevent retinal fiber regeneration but results in aberrant growth through the brachia and significant inhibition of exploratory fiber growth within the tectum.

Animals↗
PubMed1988

Differences in the pore sizes of the N-methyl-D-aspartate and kainate cation channels.

The cation channels in central nervous system neurons gated by the glutamate agonists N-methyl-D-aspartate (NMDA) and kainate have been shown to be similar, but not identical. To analyze the differences in more detail, the permeabilities of the channels to cations of different sizes have been measured. The kainate channel appears to be larger, and the cation permeabilities are similar to those of the acetylcholine gated channel at the neuromuscular junction. The NMDA channel appears to be about 10% smaller in size.

Animals↗
PubMed1988

A reexamination of the role of the RAD52 gene in spontaneous mitotic recombination.

The RAD52 gene is required for much of the recombination that occurs in Saccharomyces cerevisiae. One of the two commonly utilized mutant alleles, rad52-2, increases rather than reduces mitotic recombination, yet in other respects appears to be a typical rad52 mutant allele. This raises the question as to whether RAD52 is really necessary for mitotic recombination. Analysis of a deletion/insertion allele created in vitro indicates that the null mutant phenotype is indeed a deficiency in mitotic recombination, especially in gene conversion. The data also indicate that RAD52 is required for crossing-over between at least some chromosomes. Finally, examination of the behavior of a replicating plasmid in rad52-1 strains indicates that the frequency of plasmid integration is substantially reduced from that in wild type, a conclusion consistent with a role for RAD52 in reciprocal crossing-over. Analysis of recombinants arising in rad52-2 strains suggests that this allele may result in the increased activity of a RAD52-independent recombinational pathway.

Alleles↗
PubMed1988

Development of a surgical case review system.

Quality assurance professionals at Wayne County (Pennsylvania) Memorial Hospital have successfully implemented a surgical case review system for evaluating all inpatient surgical and same-day surgical procedures (including those where no tissue is removed) as well as post-hospitalization infections or complications that may signal unusual events or potential risk factors. The occurrence of such an event triggers a review of the case. Physician members of a surgical case review committee review and evaluate the surgical procedure in such cases and take immediate action to resolve quality of care issues.

Ambulatory Surgical Procedures↗
PubMed1988

Growth hormone (GH) responses to arginine and L-dopa alone and after GHRH pretreatment.

In order to investigate the mechanisms by which arginine and L-dopa cause GH release in humans we measured the GH response to GHRH 1-44 (200 micrograms i.v.), arginine (30 g i.v. over 30 min) and L-dopa (500 mg orally) administered alone and 120 minutes following pretreatment with GHRH 1-44 (200 micrograms i.v.) in normal male subjects. Prior GHRH administration abolished the GH response to subsequent GHRH. Arginine infusion induced a rise in GH levels maximal at 45 min. Following GHRH pretreatment the GH response to arginine was enhanced, with peak values of 19.3 +/- 6.4 vs 53.3 +/- 16.5 mU/l (mean +/- SEM) respectively (P less than 0.02). L-dopa alone induced a rise in GH levels maximal at 90 min (17.6 +/- 7.4 mU/l, mean +/- SEM) but this rise was abolished by pretreatment with GHRH.

Adult↗
PubMed1988

Clinical assessment of an enzyme immunoassay (EMIT) for measurement of serum salicylate.

Salicylic acid concentrations in serum were compared using a homogenous enzyme immunoassay (EMIT) and an automated colorimetric analysis (ACA) technique. Analysis of samples showed similar within-day and day-to-day coefficients of variation (CV): 1.3% and 4.6% by EMIT and 1.0% and 2.6% by ACA, respectively. Quantification of serum containing added salicylate and serum from patients receiving salicylate therapy showed a slight positive bias towards the ACA method over the range of 0-600 mg/l. No significant difference in reliability was found between the two methods. The EMIT assay showed no interference from other antiflammatory drugs being taken by patients who were not taking salicylates. If decisions to alter salicylate dosage are made with due regard to the drug's saturation kinetics, measurements using either EMIT or ACA should allow the clinician to titrate patients' serum concentrations accurately within the narrow therapeutic range.

Colorimetry↗
PubMed1988

The effects of different anaesthetic agents on the estimation of uterine vascular permeability in mice.

Vascular permeability in the uterus and other tissues of mice was assessed using the accumulation of 125I-human serum albumin 30 min after its intravenous injection. The anaesthetic agent employed for the 125I-albumin injection differentially affected the estimates of vascular permeability: intraperitoneal (i.p.) tribromoethanol of pentobarbitone sodium produced significantly higher values for the uterus and body wall than ether. The i.p. administration of either Saffan or pentobarbitone sodium reduced estimates of vascular permeability in the duodenum. These results emphasize the importance of the choosing a suitable anaesthetic agent in vascular studies of the uterus and other abdominal tissues.

Alfaxalone Alfadolone Mixture↗
PubMed1988

Induction of luteal regression in the marmoset monkey (Callithrix jacchus) by a gonadotrophin-releasing hormone antagonist and the effects on subsequent follicular development.

Doses of 100 or 200 micrograms of a novel GnRH antagonist ([N-acetyl-D beta Na11-D-pCl-Phe2-D-Phe3-D-Arg6-Phe7-Arg8-D-Ala10]NH2 GnRH) (4 animals/dose) were administered on Days 10/11 of the luteal phase and induced a marked suppression of circulating bioactive LH and progesterone concentrations within 1 day of treatment (P less than 0.01). Thereafter, progesterone concentrations remained low or undetectable until after the next ovulation. Similar results were obtained when 200 micrograms antagonist were given on Days 5/6 of the luteal phase (N = 4). The interval from injection of antagonist (200 micrograms but not 100 micrograms) to ovulation (based on a rise in progesterone above 10 ng/ml) was significantly longer than that from prostaglandin-induced luteal regression to ovulation in control cycles (N = 4/treatment) (range, 13-15 days after antagonist vs 8-10 days after prostaglandin, P less than 0.01). This delay of 4-5 days was equivalent to the duration for which LH concentrations were significantly suppressed by 200 micrograms antagonist when administered to ovariectomized animals (N = 3). Corpus luteum function during the cycle after GnRH antagonist treatment appeared normal according to the pattern of circulating progesterone. These results show that corpus luteum function and preovulatory follicular development in the marmoset monkey are dependent on pituitary gonadotrophin secretion.

Animals↗
PubMed1988

Use of a single-injection tissue-sampling technique to study steroid uptake by the decidualized endometrium of the mouse.

A tissue-sampling paired-tracer method was used to investigate the effect of plasma proteins on uptake by the decidualized endometrium of [3H]progesterone, [3H]oestradiol and [3H]corticosterone. When injected arterially in protein-free Ringer, the extraction of progesterone and oestradiol was 100%, while that of corticosterone was only 60%. The addition of 4% albumin or injection in mouse plasma resulted in significant decreases in progesterone extraction to about 80% and 65% respectively. Injection in pregnant guinea-pig plasma reduced progesterone extraction further (to 33%). While neither 4% albumin nor mouse plasma had any significant effect on the uptake of oestradiol, neonatal rat plasma reduced oestradiol extraction to 40%. These results are consistent with high-affinity binding proteins having a limiting effect on the availability of steroids to target tissues.

Animals↗
PubMed1988

Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential.

Acarbose delays the production of monosaccharides (notably glucose) by inhibiting the alpha-glucosidases associated with the brush-border membrane of the small intestine which are responsible for the digestion of complex polysaccharides and sucrose. In healthy subjects acarbose 100 to 200 mg significantly inhibits postprandial glucose, insulin and triglyceride responses, with some evidence of carbohydrate malabsorption with the higher dose. Clinical trials in patients with non-insulin-dependent diabetes mellitus showed that acarbose improved diabetic control, especially postprandial blood glucose levels, independent of whether the patients were receiving concomitant oral antidiabetic drugs in addition to dietary management. In comparative studies acarbose was significantly superior to placebo, and comparable to biguanides, when used alone or as an adjuvant to sulphonylurea therapy. Trials in patients requiring insulin to control their diabetes demonstrated that acarbose significantly reduced postprandial blood glucose concentrations, resulting in a smoother diurnal blood glucose-time curve and improved symptoms associated with nocturnal hypoglycaemia. Daily insulin requirements were sometimes reduced. In large multicentre trials acarbose up to 600 mg/day for 3 to 12 months improved glycaemic control in approximately 55% of patients with non-insulin-dependent or insulin-dependent diabetes mellitus. Apart from its use in diabetes, encouraging preliminary results have been obtained with acarbose in other therapeutic areas such as dumping syndrome, reactive hypoglycaemia, and types IIb and IV hyperlipoproteinaemias--however, further clinical experience is needed in these settings before clear conclusions can be drawn. No serious side effects have been reported during treatment with acarbose, although it is associated with a high incidence of troublesome gastrointestinal symptoms such as flatulence, abdominal distension, borborygmus and diarrhoea. The incidence of these reactions usually decreases with time. Thus, acarbose represents the first of a new class of oral antidiabetic drugs--the alpha-glucosidase inhibitors. It has proven useful for improving glycaemic control when used as an adjunct to standard therapy involving dietary restriction, oral antidiabetic drugs and/or subcutaneous insulin. That being the case, acarbose should provide the clinician with an interesting treatment option which can be used in a broad range of patients with diabetes mellitus in whom 'traditional' management approaches produce suboptimal glycaemic control.

Acarbose↗
PubMed1988

A possible role for the acetylcholine transport system in non-quantal release of acetylcholine at the rodent myoneural junction.

The effects on the spontaneous, non-quantal release of acetylcholine (ACh) from motor nerve terminals of substances known to inhibit the ACh transport system present in cholinergic synaptic vesicles have been investigated. In mouse diaphragms, the hyperpolarization normally produced by d-tubocurarine (dTC) in muscle endplates that had been treated by an anticholinesterase was partly or completely abolished by 2-(4-phenylpiperidino) cyclohexanol (AH5183, 10(-7)-10(-6)M), quinacrine (10(-7)M) and tetraphenylborate (10(-6) M). Since the sensitivity of the endplate to ACh was not changed, the block of the dTC induced hyperpolarization indicated an inhibition of the spontaneous, non-quantal release of ACh. This was confirmed by direct measurement of the ACh released by rat diaphragm. The release of ACh from the innervated diaphragm was decreased by about 50% by AH5183 (10(-8)-10(-6) M) and by 42% by quinacrine (10(-7)-10(-6) M). The ACh released was presumably neural, since the release of ACh from 4-day denervated diaphragms was not diminished by either AH5183 or quinacrine. The results indicate that the spontaneous release of ACh from the motor nerve terminals is probably mediated by a carrier which may be the vesicular transport system responsible for moving ACh into the vesicle. The transport system is likely incorporated into the membrane of the nerve terminal during exocytosis.

Acetylcholine↗