Search PubMed⌕ Search

Biomedical subjects

S E Smith

Publications and source records attributed to S E Smith.

At least 145 records · Page 8Linked to original sources
PubMed1990

The effect of impaired renal function on the pharmacokinetics of metoprolol after single administration of a 14/190 metoprolol OROS system.

Renal function is known to sometimes have a significant effect on the pharmacokinetics of drugs or drug metabolites, which are eliminated in appreciable amounts by the kidneys. For this reason, we conducted a study to compare the plasma concentration profiles of metoprolol and its metabolite, alpha-hydroxymetoprolol (OH-metoprolol), in healthy volunteers and in renally impaired patients. Following a single oral dose of a 14/190 metoprolol OROS (oral osmotic) tablet, plasma metoprolol profiles were shown to be similar for both subject groups. However, in renally impaired patients, renal clearance of OH-metoprolol was reduced and mean plasma levels of OH-metoprolol were increased approximately two- to threefold in comparison with healthy volunteers. The accumulation of OH-metoprolol in plasma, however, is unlikely to contribute to the beta-blocking effect of metoprolol, since OH-metoprolol possesses only one tenth the activity of its parent compound.

Administration, Oral↗
PubMed1990

Prenatally diagnosed reflux: a follow-up study.

This report analyses the characteristics and outcome of 25 infants with vesicoureteric reflux detected prenatally on the basis of dilatation of the fetal urinary tract. Sixteen infants had bilateral reflux--a total of 41 refluxing units. The high proportion of males (84%) contrasts with clinically presenting reflux, which is dominated by females. Prenatally diagnosed reflux is generally of a higher grade--usually grade IV. Eight children (32%) had coexistent congenital abnormalities. Chemoprophylaxis was completely effective in 17 children (68%), who remained infection-free; 3 children (12%) had a single urinary infection and were managed conservatively whilst 5 (20%) experienced 2 or more infections and required reimplantation or vesicostomy. Spontaneous cessation of reflux was observed in 6 (35%) of 17 refluxing ureters reassessed after a mean interval of 2.1 years. The significance of isotope findings was sometimes difficult to assess but results in 30 refluxing units support the concept that focal renal scarring is usually a consequence of infected reflux in postnatal life.

Female↗
PubMed1990

Ultrastructural morphometric analysis of the uterine epithelium during early pregnancy in the sheep.

Stereological techniques were used to quantify ultrastructural changes in the caruncular epithelium during the pre- (Day 13), peri- (Day 16) and post- (Days 19 and 22) attachment periods of placentation. Tissues from Day-13 non-pregnant ewes were used as controls. Uteri for stereological evaluation were perfused via the uterine artery with 3% glutaraldehyde and separated into proximal, middle and distal regions. Tissues from caruncular areas were processed for electron microscopy. Volume fractions (Vv) of nuclei, mitochondria, lipid and cytoplasmic granules were estimated by point-counting volumetry. Surface areas per unit tissue volume (Sv) of mitochondrial membranes and cristae, Golgi, plasmalemma, endoplasmic reticulum and nuclear membranes were estimated by line-intersection counting. The only significant difference between pregnant and non-pregnant uterine epithelium at Day 13, a time before attachment, was a lower Sv of smooth endoplasmic reticulum (SER) in tissue from pregnant ewes. This value returned to control (non-pregnant Day 13) levels at Day 16, and was again significantly reduced at Days 19 and 22. The Vv of lipid decreased significantly at Day 16 and remained at reduced levels thereafter. These changes may reflect the effects of conceptus products on lipid storage and mobilization. The Sv of rough endoplasmic reticulum (RER) significantly increased on Day 16 of gestation, and remained elevated on Day 19. These results may reflect increased synthesis of protein for export at these times. In general, several of the values measured which may be indicative of cellular metabolism were reduced at Day 22 of pregnancy, perhaps suggesting diminished metabolism by the uterine epithelium after attachment of the trophoblast.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Scavenging by alginate of free radicals released by macrophages.

Failure to eradicate mucoid forms of P. aeruginosa has implicated bacterial alginate in a local evasion of host defence mechanisms within the lung of Cystic Fibrosis (CF) patients. We have found that purified bacterial alginate scavenges free radicals released by triggered macrophages as detected by lucigenin amplified chemiluminescence (CL) and reduction of cytochrome c. In agreement with this, alginate was also able to scavenge radicals generated by a chemical system (hydrogen peroxide and copper; detected by benzoate hydroxylation and chemiluminescence), and by an enzymatic system (hypoxanthine and xanthine oxidase; detected by chemiluminescence). All inhibitions were dose-related. Oxygen consumption by neutrophils (unlike that of macrophages) could be detected in a Clark electrode, and was not reduced by alginate, confirming that scavenging of radicals was responsible for the earlier observations. These data suggest that bacterial alginate by scavenging free radicals, may favour the survival of mucoid forms of P. aeruginosa, particularly in the CF lung.

Alginates↗
PubMed1989

Indomethacin as prophylaxis against ureteral colic following extracorporeal shock wave lithotripsy.

Ureteral colic occurs in 24 to 34 per cent of all patients following extracorporeal shock wave lithotripsy. Recent research has shown prostaglandin synthetase inhibitors to be effective in relieving the pain associated with ureteral colic. Our prospective, controlled, double-blind, randomized study was designed to test the efficacy of indomethacin in the prophylactic treatment of pain after extracorporeal shock wave lithotripsy. Patients undergoing extracorporeal shock wave lithotripsy were randomized into 2 groups. Group 1 received 100 mg. indomethacin suppositories twice daily and group 2 received placebo suppositories. After extracorporeal shock wave lithotripsy 2 analgesics were available to the patients: oral co-dydramol or intramuscular pethidine was offered in the normal manner by the nursing staff. The pre-extracorporeal shock wave lithotripsy x-ray was used to make a quantitative estimate of the total stone burden in each patient. The post-extracorporeal shock wave lithotripsy analgesic requirement was used to compare the 2 groups. Of 112 patients recruited to the study 55 received indomethacin and 57 received placebo. The request for analgesia in the 2 groups was not different (28 of 55 and 33 of 57, respectively). However, in the indomethacin group only 6 patients required pethidine (10 doses), compared to 18 (41 doses) in the placebo group. This difference is statistically significant (p less than 0.01). There was no difference between the 2 groups in the occurrence of ureteral steinstrasse. Indomethacin has been shown to be effective in the prophylactic treatment of ureteral colic after lithotripsy.

Adult↗
PubMed1989

Otrivine-antistin-pupil, corneal and conjunctival responses to topical administration.

The ocular effects of Otrivine-Antistin eyedrops have been measured in a placebo controlled single-blind study in sixteen healthy volunteers. The drops produced mild sympathomimetic responses in the eye but had no effect on corneal sensitivity or on intraocular pressure. The evidence indicates that use of Otrivine-Antistin imposes no risk to the subject.

Administration, Topical↗
PubMed1989

Cardiovascular responses to metipranolol and timolol eyedrops in healthy volunteers.

1. Intraocular pressure and cardiovascular responses to metipranolol 0.1% and 0.3% and timolol 0.25% eyedrops were measured in a balanced single dose placebo-controlled crossover study in eight healthy volunteers aged 34-58 years. 2. Timolol 0.25% and metipranolol 0.3% reduced intraocular pressure throughout the 6 h period of observation to a similar extent. Metipranolol 0.1% was marginally less effective, significantly reducing pressure up to 4 h only. 3. No drug treatment significantly altered resting heart rate or blood pressure. Timolol 0.25% significantly reduced exercise tachycardia (P less than 0.05), an effect which was not shown by metipranolol 0.1 or 0.3%. Exertional pain in the legs occurred more frequently after timolol 0.25% and metipranolol 0.3% than after metipranolol 0.1% or placebo eyedrops. 4. Octan-1-ol/pH 7.4 buffer distribution coefficients at 37 degrees C were found to be: metipranolol 5.19, timolol 0.84, indicating that metipranolol has an approximately 6-fold greater lipid solubility. 5. It is concluded that, by comparison with timolol, metipranolol in eyedrop concentrations up to 0.3%, despite its greater lipid solubility, reaches concentrations in the systemic circulation which are less likely to affect the heart.

Adult↗
PubMed1989

Relative bioavailability of pilocarpine from a novel ophthalmic delivery system and conventional eyedrop formulations.

Pupillary responses to pilocarpine following topical application in a novel ophthalmic delivery system (NODS) and a conventional eyedrop formulation have been compared in eight healthy subjects in a single dose crossover study. The magnitude of the miotic and light reflex responses to NODS 40, 80, and 170 micrograms and to a single 2% Minims eyedrop (delivering 518 micrograms) were recorded by infrared television pupillography over periods of 24 hours. Dosage comparisons of drug responses were obtained by interpolation and yielded the equivalence of one eyedrop to 67 +/- 11 micrograms pilocarpine from the NODS formulation. These findings indicate that in a comparison of total doses delivered pilocarpine has an approximately eight-fold greater bioavailability from NODS than from a conventional eyedrop formulation.

Adult↗
PubMed1989

Effect of cataract extraction on the pupil response to mydriatics.

Pupil diameters in the dark, in the light, and after mydriasis with tropicamide+ phenylephrine have been measured in 25 patients before and six months after cataract surgery. The aphakic pupil showed reduced mobility as evidenced by a smaller diameter in the and a larger one in the light. In patients who had intracapsular extraction or extracapsular extraction with intraocular lens implantation the pupils dilated less well than preoperatively. The difference in response to mydriatics is of practical importance in the assessment and treatment of peripheral retinal disorders in aphakic and pseudophakic eyes.

Aged↗
PubMed1988

Free-radical generation by copper ions and hydrogen peroxide. Stimulation by Hepes buffer.

Hydroxyl radicals (OH.), generated by a phosphate-buffered Cu2+/H2O2 system, were detected by lucigenin-amplified chemiluminescence, deoxyribose degradation and benzoate hydroxylation. In each system the buffer, Hepes, was found to stimulate radical generation significantly. There are two main reasons for this effect: Hepes increases Cu2+ solubility in phosphate-buffered systems, and forms a complex with Cu2+ that is effective in generating OH. from H2O2. Pipes, a structurally similar buffer, and histidine, a known Cu2+ chelator, were found to have a similar effect. These data suggest that the crucial factor in such free-radical-generating systems is the availability of Cu2+, and that these actions of Hepes should be considered in the design of studies utilizing such systems.

Benzoates↗
PubMed1988

A kinetic and equilibrium study of ligand binding to the monomeric and dimeric haem-containing globins of two chitons.

The radular muscles of the amphineuran molluscs Amaurochiton glaucus and Sipharochiton pelliserpentis contain both a dimeric and a monomeric form of myoglobin. The dimeric form of the protein is composed of two polypeptide chains covalently linked to each other via one or more disulphide bonds. The dimeric protein shows co-operative O2-binding curves. Kinetic investigations indicate that CO binding is co-operative in the dimeric protein, subsequent to full photolysis, but mono-exponential following 10% photolysis. O2 recombination following part photolysis is mono-exponential in the dimeric form, whereas O2 dissociation kinetics indicates the presence of chain heterogeneity. The monomeric form of the protein exhibits mono-exponential time courses in all the experimental situations explored. Although the rate constants associated with the reactions of individual dimer and monomer molecular species are very different, the two species of chiton investigated show remarkably similar properties when compared with each other. All the reactions studied are pH-independent in the range pH 6-8. Amino acid analysis indicates that the monomeric units that combine to form the dimeric species are not identical with the naturally occurring monomeric form. A comparison is made between the chiton myoglobins and other similar O2-binding proteins.

Amino Acids↗
PubMed1988

Enhanced pressor sensitivity to oral tyramine challenge following high dose selegiline treatment.

Blood pressure and heart rate responses to oral tyramine have been measured in healthy volunteers before and after administration of the selective monoamine oxidase B inhibitor selegiline at high dosage (30 mg/day). Treatment brought about a 2 to 4-fold increase in tyramine sensitivity and a concomitant small but significant reduction in plasma 4-hydroxy-3-methoxyphenylglycol concentration, pointing to the emergence of some degree of monoamine oxidase A inhibition. It is suggested that patients treated with selegiline 30 mg/day or more should be placed on a tyramine-free diet.

Adult↗
PubMed1988

Chronic paroxysmal hemicrania. XIII. The pupillometric pattern.

Pupillometric studies were carried out in eight patients with chronic paroxysmal hemicrania (CPH) and in age- and sex-matched controls in the basal condition and after instillation of 2% tyramine (CPH, n = 5; controls, n = 17), 1% OH-amphetamine (CPH, n = 6; controls, n = 12), and 1% phenylephrine (CPH, n = 6; controls, n = 17). The pupil on the symptomatic and non-symptomatic sides in CPH patients was significantly smaller in the basal condition than in controls, particularly on the symptomatic side. The mydriatic responses to pharmacologic stimulation were essentially similar on the symptomatic and non-symptomatic sides. An evaporimetric study of the forehead sweat glands, using the body heating and pilocarpine tests, was also carried out in these patients and in age- and sex-matched controls. "Early", "intermediate", and "late" measurements demonstrated symmetry of forehead sweating. The findings for both methods of examination thus contrast with those in cluster headache patients. Pupillometric and forehead sweating patterns therefore suggest differences in the pathogenesis of the two headache entities. These tests may be used to distinguish CPH and cluster headache clinically.

Adult↗
PubMed1988

Inhibition of adherence of Candida albicans by conventional and experimental antifungal drugs.

We tested the effects of antifungal drugs on adherence of Candida albicans in vitro. Significant reduction of adherence occurred after 2 h incubation with amphotericin B, nystatin, miconazole, econazole, ketoconazole, chlorohexidine and ICI 195,739. Significant inhibition of candida adherence by 5-fluorocytosine and amorolfin required 18 h incubation. Combinations of amphotericin B with 5-fluorocytosine, miconazole, ICI 195,739 and amorolfin resulted in synergistic inhibition of adherence. Adherence is an important pathogenic mechanism in candida infections and interference with this process may represent a major component of the mode of action of antifungal drugs.

Adhesiveness↗
PubMed1988

Alginate inhibition of the uptake of Pseudomonas aeruginosa by macrophages.

Pseudomonas aeruginosa alginate was purified and characterized in terms of uronic acid, carbohydrate and protein content, as well as by infra-red spectroscopy and gel electrophoresis. Added exogenous bacterial alginate inhibited the uptake and degradation of both viable and non-viable radiolabelled non-mucoid P. aeruginosa by resident mouse peritoneal macrophages. Alginic acid (from seaweed) inhibited the same parameters to almost the same degree. Bacterial alginate also inhibited the uptake of fluorescent-labelled zymosan and latex particles. Starch, at equivalent viscosity to the alginate, inhibited the uptake and degradation of radiolabelled nonviable P. aeruginosa to a greater extent, but Dextran T500 had no effect. This suggests that the viscous nature of alginate exerts a non-specific inhibitory effect on the uptake and subsequent degradation of phagocytosible particles.

Alginates↗
PubMed1988

Ocular and cardiovascular response to topical carteolol 2% and timolol 0.5% in healthy volunteers.

Ocular and cardiovascular effects of carteolol 2%, timolol 0.5%, and dummy eyedrops have been measured in a single dose double-blind crossover study in six healthy volunteers. Both drugs lowered intraocular pressure and reduced exercise-induced tachycardia. Neither produced a significant change in resting heart rate or blood pressure. The two agents appear comparable as regards ocular hypotensive and cardiovascular effects.

Adult↗
PubMed1988

Blindness from quinine toxicity.

We report a case of quinine overdose in a 47-year-old man who presented with blindness. Fundus photography demonstrates the acute and subsequent retinal changes, and his visual recovery to normal acuity with visual field constriction is documented. Pupillary and electrodiagnostic findings are recorded. Stellate ganglion block has been widely advocated as a helpful therapeutic measure, but out patient was treated with a unilateral stellate ganglion block without apparent benefit to that eye. From a review of the literature we believe that quinine produces its effects by toxicity on the retina rather than by vasoconstriction and that stellate ganglion block probably does not alter the natural history of the retinal toxicity.

Autonomic Nerve Block↗