Biomedical subjects

C G Wilson

Publications and source records attributed to C G Wilson.

At least 19 recordsLinked to original sources

PubMed1992

Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit.

Although lactulose, a widely used cathartic, is known to increase stool frequency, details of its site of action in the colon are obscure. In the present study a noninvasive scintigraphic technique was used to closely follow the movements of proximal colonic contents. Lactulose, 10-20 mL three times daily, significantly accelerated mean transit through the ascending colon from 12.9 +/- 3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the occurrence of mass movements, with six such events seen during lactulose treatment whereas only one was seen during the control study (P less than 0.05). Lactulose also accelerated movement through the rest of the colon so that at 24 hours after dosing the geometric center of the isotope bolus was distal to that seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than 0.001). This model of diarrhea in otherwise normal subjects was subsequently used to study the effects of viscous gels in diarrhea. The viscous and relatively poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements and was associated with a small but significant increase in proximal colonic transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P less than 0.05). By contrast, the viscous but readily fermentable gelling agent guar gum, 5 g three times daily, further accelerated the cathartic effect of lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7 hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by lactulose may be a useful model to study diarrhea and its modification by therapy.

Adolescent↗

PubMed1992

Ocular surface residence times of artificial tear solutions.

Solutions of hydroxypropylmethylcellulose (HPMC) and polyvinyl alcohol (PVA) are widely used as artificial tears. However, their usefulness is limited by the short duration of their effect. Dilute sodium hyaluronate (SH) solutions exhibit non-Newtonian rheology with high viscosities at low shear rates, which would be expected to enhance their ocular surface residence time. Using quantitative gamma scintigraphy, estimates of the ocular surface residence times of 0.3% HPMC, 1.4% PVA, and 0.2% SH were made in six patients with keratoconjunctivitis sicca. The sodium hyaluronate solution had a mean half-life on the ocular surface of 321 s, significantly longer than hydroxypropylmethylcellulose (44 s; p = 0.012) and polyvinyl alcohol (39 s; p = 0.013).

Biological Availability↗

PubMed1992

Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery System (NODS): rate of clearance of a soluble marker in relation to duration of pharmacological action of pilocarpine.

1. A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS) containing pilocarpine nitrate in 12 healthy volunteers. 2. The NODS was radiolabelled with the soluble marker technetium-99m labelled diethylenetriaminepentaacetic acid, to mark the release characteristics of soluble drugs contained within the matrix. 3. The relationship between the precorneal residence time of the marker and the duration of drug effect on intraocular pressure and pupil diameter was monitored. Results obtained following administration of the NODS were compared with those obtained after administration of a 25 microliters drop of a 2% w/v pilocarpine nitrate solution. Each formulation was administered to one eye only, the other eye acting as a control. 4. Dissolution of the radiolabel from the NODS in vivo showed considerable intersubject variation with half-times of dissolution ranging from 46 s to 833 s (mean +/- s.d. -280 +/- 217 s), the mean (+/- s.d.) half-time of clearance of the radiolabel from the NODS and corneal region of interest was 406 +/- 214 s whereas the radiolabelled solution had a mean (+/- s.d.) ocular surface residence time of 2.9 +/- 1.5 s. 5. Pupil diameter and intraocular pressure were measured for 5 h post-administration of the NODS and the solution. After both treatments pupil diameter was significantly constricted in the test eye when compared with the control eye (P less than 0.001; Student's paired t-test). Pupil diameter was constricted by 52% after administration of the NODS and by 35% after administration of the solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

A comparison of the precorneal residence of an artificial tear preparation in patients with keratoconjunctivitis sicca and normal volunteer subjects using gamma scintigraphy.

The precorneal residence of an artificial tear preparation has been compared in twelve patients with keratoconjunctivitis sicca (KCS) and twelve normal healthy volunteers. The artificial tear solution was radiolabelled by the inclusion of 1 MBq technetium-99m diethylenetriaminepentaacetic acid (99Tcm-DTPA), and 25 microliters was instilled into one eye only. Deposition of the preparation was followed by gamma scintigraphy. Precorneal clearance of the solution was found to follow bi-exponential kinetics in all subjects with no significant differences in clearance rates between the two study populations. There was also no significant difference in the area under the time-activity profile for the two study groups. This suggests that the reduced reflex tearing and basal lacrimation in KCS patients, indicated by the Schirmer's test, are not important in the clearance of isotonic solutions from the eye surface.

Adult↗

PubMed1991

The use of a radiolabelled saccharin solution to monitor the effect of the preservatives thiomersal, benzalkonium chloride and EDTA on human nasal clearance.

The effect of thiomersal, benzalkonium chloride and ethylenediaminetetraacetic acid (EDTA) on the nasal mucociliary clearance of healthy volunteers has been investigated using a modified saccharin test and gamma scintigraphy concomitantly. A significant correlation was found between the two techniques. Using each subject as his/her own control, none of the preservatives significantly altered the rate of clearance or proportion cleared from the nasal cavity after the administration of a single dose. This result is at variance with some in-vitro findings.

Adult↗

PubMed1991

Delivery of propellant soluble drug from a metered dose inhaler.

The deposition of particulate suspensions delivered from a metered dose inhaler has been investigated extensively. The distribution of propellant, delivered from a metered dose inhaler, was studied by radiolabelling it with technetium-99m hexamethylpropyleneamine oxime. Andersen sampler measurements indicated that half of the dose was associated with particles in the size range 0.5-5 microns diameter. The preparation was administered to healthy subjects by inhalation and deposition was monitored with a gamma camera. Each lung image was divided into an inner, mid, and peripheral zone. The effects on deposition of varying the size of the delivery orifice (0.46, 0.61, and 0.76 mm internal diameters) and the effect of attaching a spacer were assessed. Lung deposition was independent of the orifice size within the actuator. Without the spacer the average dose deposited in the lungs was 39%, with 15% penetrating into the peripheral part of the lungs. Attachment of the spacer to the mouth-piece increased the mean lung deposition to 57% and reduced oropharyngeal deposition. The study has shown that propellant soluble drugs can be delivered efficiently to the lungs from a metered dose inhaler.

Administration, Inhalation↗

PubMed1991

Effect of pretreatment with ranitidine on the pharmacokinetics and gastrointestinal transit of a sustained release theophylline preparation.

A scintigraphic and pharmacokinetic study of the behaviour of (Bronchoretard forte, CAS 58-55-9) was carried out in 8 healthy male volunteers to evaluate the sensitivity of the preparation to changes in gastric pH. Volunteers were pretreated with ranitidine (CAS 66357-35-5) (150 mg b.d.) or placebo for three days prior to and on the study day to reduce gastric acidity. The effect of the pretreatment with ranitidine on gastric pH was measured on the prestudy day and the mean pH was significantly reduced compared to the placebo (ranitidine pH 2.2 +/- 2.4; placebo pH 1.6 +/- 2.0, p less than 0.01 Wilcoxon Signed Rank test). All subjects were pretreated with theophylline for 3 days (500 mg b.d.) to achieve steady-state. On the study day the volunteers swallowed two theophylline sustained release capsules radiolabelled by inclusion of indium-111 micronised Amberlite resin and the gastrointestinal transit followed continuously for 14 h using gamma scintigraphy with a further image at 24 h. Blood samples were taken from each subject throughout the study to determine the pharmacokinetic profile of theophylline when presented in the sustained release formulation. No significant differences were found in the gastrointestinal transit of the labelled microparticulates between the data obtained from the group when treated with ranitidine or placebo. Plasma theophylline concentration profiles were identical for the two treatments. These data indicate that the theophylline sustained release formulation is not sensitive to the effects of major changes in gastric H+ concentration.

Adult↗

PubMed1990

Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy.

Sodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, formulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance. Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volunteers. Using several indices of residence time, mean values for the sodium hyaluronate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry.

Adhesiveness↗

PubMed1990

Effect of time of dosing relative to a meal on the raft formation of an anti-reflux agent.

Gamma scintigraphy was used in twelve healthy volunteers to establish whether the time of dosing of Liquid Gaviscon relative to a meal influenced its therapeutic action. Indium-113m labelled Liquid Gaviscon was administered to fasted subjects, 30 min after a technetium-99m labelled meal or immediately before ingestion of the meal. The time for 50% of the Gaviscon to empty from the stomach was 0.36 +/- 0.13 h, 3.10 +/- 0.31 h and 0.68 +/- 0.04 h (s.e.m.), respectively. The preparation was found to empty rapidly from the fasted stomach and could not be floated on a meal consumed subsequently. For raft formation to occur, Liquid Gaviscon should be taken 30 min after a meal.

Adult↗

PubMed1990

Scintigraphic assessment of an ophthalmic gelling vehicle in man and rabbit.

Studies of the rate of clearance of a gellan gum formulation (Gelrite) radiolabelled by the inclusion of technetium-99m labelled diethylenetriaminepentaacetic acid were carried out in volunteer subjects and in rabbits. Disposition was followed by gamma scintigraphy and compared with 0.5% w/v hydroxyethylcellulose (HEC) solution and isotonic saline administered to the same subjects. Clearance of all solutions was found to follow bi-exponential kinetics with differences in clearance rates between the two species studied. A significant retention of the gellan gum formulation compared to HEC (p = 0.006) or saline (p = 0.009) was noted in man, but not in the rabbit. In this latter species the HEC showed greater retention compared to Gelrite. The species-specific differences in the precorneal residence of the formulations are attributed to the different physiological responses following instillation of solutions into the eye.

Analysis of Variance↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1987

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↗