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Biomedical subjects

C G Wilson

Publications and source records attributed to C G Wilson.

At least 73 records · Page 4Linked to original sources

ECG changes in asphyxia neonatorum.

Twenty five asphyxiated neonates had ECG changes consistent with degree of asphyxia. Equivocal changes were found in mild asphyxia and changes suggestive of myocardial infarction were seen with severe asphyxia. In most cases, the changes reverted to normal within two weeks signifying great ability of the neonatal heart to withstand hypoxic insult. Four babies with severe asphyxia having ECG changes suggestive of acute myocardial infarction expired within 48 hours of birth.

Asphyxia Neonatorum↗

The effect of eating on transit through the small intestine.

The effect of eating on the transit of radiolabelled particles through the small intestine has been monitored in eight healthy subjects dosed after an overnight fast. Each subject participated on three occasions and either remained fasting for 9 h after dosing or consumed a meal at 1.5 h or 4 h. The mean +/- 1 S.D. small intestinal transit time during the fasting study was 5.5 +/- 2.1 h and during the 1.5h and 4 h fed studies 4.8 +/- 2.9 h and 4.7 +/- 2.2 h, respectively. These times were not significantly different, nor were the rates of entry of the particles into the colon. These findings indicate that once in the small intestine the efficacy of orally administered pharmaceutical preparations is unlikely to be affected by eating.

Administration, Oral↗

The effect of capsule size and density on transit through the proximal colon.

Colonic transit of radiolabelled capsules has been monitored in 18 healthy subjects using gamma scintigraphy. The capsules ranged in volume from 0.3-1.8 cm3 and in density from 0.7-1.5 gcm-3. The capsules were administered after an overnight fast and entered the colon, on average, 5 h after dosing. Transit rates through the proximal colon were independent of capsule density. Any effect due to capsule volume was small when compared with intersubject variations in transit rates. Within 10 h of entering the colon 80% of the units had reached the splenic flexure. These findings have implications in the design of non-disintegrating, sustained release dosage forms.

Adult↗

Nasal delivery of a vasopressin antagonist in dogs.

The dosage form (drop or spray) and site of administration (dorsal or ventral surface of the nostril) profoundly affect the distribution and clearance of a gamma-emitting 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) solution in dogs. The slowest nasal clearance was observed for dorsally administered drops. Administration of drops to the ventral surface or sprays to either dorsal or ventral surface results in rapid clearance and little deposition in the turbinates. The octapeptide vasopressin antagonist, SKF 101926, was administered intravenously (0.3, 1.0, 3.0, and 10 micrograms/kg) and then on separate occasions intranasally (10, 25, and 50 micrograms/kg as a drop to the ventral surface) to four conscious, trained, female, water-loaded, vasopressin-infused dogs. SKF 101926 reversed the antidiuretic response to vasopressin after administration by either the intravenous or intranasal route in a dose-dependent fashion. Peak dilution of urine occurred within 50- to 60-min postdosing by both routes. Estimated doses to reduce vasopressin antidiuresis by 50% were 1.4 micrograms/kg intravenously and 23 micrograms/kg intranasally. After recovery to at least 70% of antidiuretic base line, and then administration of a second dose of SKF 101926 (3 micrograms/kg), subsequent dilution of urine osmolality was inversely related to the magnitude of the previously administered dose. It is concluded that the estimated relative effectiveness of intranasally administered SKF 101926 is 3-21%, compared with intravenous administration. Acute tachyphylaxis to repeated dosing was observed. The mechanism of the apparent tachyphylaxic response was not elucidated. No tachyphylaxis to less frequent (weekly) dosing was observed.

Administration, Intranasal↗

An investigation into the floating behaviour of a pectin-containing anti-reflux formulation (FF5005) by means of gamma scintigraphy.

The gastric distribution and residence time of a new pectin-containing formulation, FF5005 (Farma Food A/S, Denmark), was investigated by using the technique of gamma scintigraphy in six healthy volunteers after administration with a radiolabelled meal. The formulation and test meal were radiolabelled with indium-113m and technetium-99m, respectively, and the formulation was administered to the subjects 30 min after the labelled meal. FF5005 was shown to float and form a discrete phase on top of the stomach contents and emptied from the stomach more slowly than the food (p less than 0.05, Wilcoxon signed rank test). The times taken for the formulation and test meal to half-empty from the stomach (T50) were 4.13 +/- 0.69 h (mean +/- SD) and 2.17 +/- 0.15 h (mean +/- SD), respectively. Greater than 50% of the formulation remained in the fundal region of the stomach for 3 h. FF5005 produced in vivo behaviour similar to that of established alginate-containing anti-reflux agents, and the pectin content of the formulation was shown to decrease the rate of emptying of the meal.

Antacids↗

Exercise and small intestinal transit.

The transit of 99Tcm-labelled particles through the small intestine has been monitored in nine healthy subjects undergoing three levels of exercise. The mean +/- 1S.D. small intestine transit times under conditions of minimal, moderate and strenuous activity were 4.5 +/- 1.7 h, 5.4 +/- 2.5 h and 4.1 +/- 1.8 h, respectively. These findings indicate that the bioavailability of drugs from controlled release preparations passing through the small intestine is unlikely to be affected by variations in normal daily activity.

Adult↗

The effect of Mucodyne on nasal clearance in healthy adults.

A randomized double-blind cross-over trial in healthy young adults compared the effect of S-carboxymethylcysteine (2.25 g per day for 7 days) against placebo on nasal mucociliary clearance. The clearance rate of a radio-labelled aqueous test spray was measured by gamma scintigraphy. Analysis of the data revealed no significant effect of the drug compared to placebo.

Administration, Intranasal↗

A gamma scintigraphic evaluation of the precorneal residence of liposomal formulations in the rabbit.

Multilamellar liposomes were prepared from dipalmitoyl phosphatidylcholine or egg lecithin in combination with cholesterol and either dicetyl phosphate or stearylamine. The size and charge of the colloidal preparations were characterized before labelling with [111In]8-hydroxyquinoline. Freshly labelled liposomes were instilled into the eyes of unanaesthetized NZW rabbits and their disposition and drainage followed using gamma scintigraphy. A positive surface charge was found to affect significantly liposomal drainage rate, whereas an increase in size restricted drainage from the inner canthal region. Drainage of the suspending medium was directly compared with liposomes by labelling the medium with [99mTc] sodium pertechnetate and following the simultaneous change in removal of 99mTc and 111In from the precorneal area. Slower drainage rates were obtained for the suspending medium compared with solutions of the isotopes suggesting that the liposomes restricted solution drainage.

1,2-Dipalmitoylphosphatidylcholine↗

Albumin microspheres for intra-articular drug delivery: investigation of their retention in normal and arthritic knee joints of rabbits.

The retention of 131I-labelled albumin microspheres and microsphere-entrapped [131I]rose bengal was investigated in normal and experimentally arthritic knee joints of rabbits. Albumin microspheres were cleared slowly from the joint cavity and no significant difference was observed between normal and inflamed joints. Entrapment of rose bengal within albumin microspheres was found to delay the clearance of the drug from the joint when compared with a solution of rose bengal. In addition, the retention time for entrapped rose bengal was dependent on the degree of inflammation present.

Albumins↗

A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man.

The precorneal drainage of radiolabelled solutions containing polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC) have been measured in rabbit and man by gamma scintigraphy. Concentration of the polymers was varied to produce solutions with a viscosity range between 10.2 and 102 mPas. Solution drainage was faster in man than in the rabbit with a more pronounced effect of viscosity. Significant retardation of drainage in man was noted at the higher polymer concentrations (0.9% HPMC or 5.85% PVA).

Adult↗

A comparison of the effects of hyperosmotic salicylate solutions in closed and perfused rectal in-situ loops of rats.

The effects of presentation of hyperosmotic solutions of sodium salicylate to the closed and perfused rectal loop preparations commonly used in assessing drug absorption have been compared. Epithelial cell loss was quantified in control and treated loops. Tissue damage was significantly greater (P less than 0.01) in treated perfused loops. Fluid efflux, which was associated with a small but significant change in the haematocrit value, was noted in both systems.

Animals↗

The effect of a week's beta-adrenoceptor antagonism on daytime heart-rates, subjective responses to exercise, and physical activity in normal subjects.

The effects on heart rate (HR) and physical activity of 1 week's treatment with three different beta-adrenoceptor antagonists (20 mg betaxolol (Lorex); 160 mg propranolol LA; or 100 mg atenolol daily) have been compared with placebo in a double-blind study of 12 normal men. On the fifth day of each treatment a body-borne tape-recorder was worn during waking hours for recording of ECG and footfall signals. Each record was calibrated in terms of the subject's response to laboratory ergometer exercise, and a computer analysis provided objective indices of physical activity. While on beta-adrenoceptor antagonists the subjects perceived standard exercise as significantly harder than on placebo and reported more side-effects (albeit mild and transient). Ambulatory monitoring of HR showed that subjects spent 13% of their waking day at heart rates below 50 beats min-1 while on propranolol, compared with 1% on placebo and 20% on atenolol and betaxolol. On these latter drugs, the group spent as much as 10% of their waking time with HR below 45 beats min-1. The lowest individual heart-rates recorded were below 35 beats min-1. Objective indices of physical activity, such as the duration of periods spent with heart rates above the HR found at 100 W in the ergometer test, showed no differences between the treatments. This negative finding was confirmed by pedometer step counts over the whole week.

Adrenergic beta-Antagonists↗

Gastrointestinal transit of an osmotic tablet drug delivery system.

The gastrointestinal transit of a radiolabelled osmotic tablet drug delivery system has been monitored in groups of young and elderly healthy subjects, using gamma scintigraphy. The gastric emptying and small intestinal transit times were similar for both groups of subjects. The units were observed to move through the gastrointestinal tract at about the same rate as the released contents, arriving at the caecum on average 7 h after dosing. The data suggest that tablet adhesion to the mucosal surface is unlikely to be the mechanism responsible for the side effects reported for the indomethacin formulation Osmosin.

Adult↗

Drug delivery to the proximal colon.

The transits of a capsule and a multiparticulate pellet system have been monitored through the gastrointestinal tract in six healthy volunteers. Both preparations moved together through the stomach and small intestine, reaching the colon, on average, 4 h after dosing. Within the colon the pellets dispersed and moved at a slower rate than the capsule. There was considerable intersubject variability in the large bowel transit times. The findings are discussed in terms of drug delivery to the colon.

Adult↗

The use of gamma scintigraphy to follow the gastrointestinal transit of pharmaceutical formulations.

The technique of gamma scintigraphy has been used to follow the transit of a solution and a pellet formulation in the gastrointestinal tract of healthy volunteers. The emptying of the formulations from the stomach and their arrival at the caecum could be quantified, thereby allowing calculation of transit times for the small intestine. Gastric emptying was affected by the nature of the formulation, i.e. liquid or solid. However, transit through the small intestine was independent of the nature of the administered material.

Adult↗