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Biomedical subjects

J G Hardy

Publications and source records attributed to J G Hardy.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

Quantitative assessment of the response to therapy in achalasia of the cardia.

Radionuclide oesophageal transit studies and manometry have been carried out in 15 patients with achalasia of the cardia, before treatment, after a course of nifedipine and after pneumatic bag dilatation. Transit studies were also done in 10 patients after cardiomyotomy and in 10 normal subjects. Images were recorded with the subjects seated in front of a gamma camera while swallowing a 10 ml bolus of 99Tcm-tin colloid and then after a further drink of 50 ml water. There was marked retention of tracer in the oesophagus in patients with achalasia compared with rapid clearance in control subjects. Bag dilatation significantly reduced lower oesophageal sphincter pressure but there was no significant difference in the 50% clearance time or percentage dose retained at 100s before and after the treatments. Oesophageal clearance of tracer after the additional drink of water, was improved by bag dilatation. Oesophageal transit in the patients after cardiomyotomy was similar to that in patients who had undergone bag dilatation. There was considerable retention of the tracer in the oesophagus overnight, but this did not result in pulmonary aspiration. Radionuclide oesophageal transit studies provided a quantitative assessment of therapy in achalasia and the proportion of tracer retained after the additional drink proved to be a sensitive measure of response to treatment. Nifedipine proved ineffective as a treatment for achalasia. Bag dilatation and cardiomyotomy were of similar value.

Administration, Sublingual↗
PubMed1989

Gastrointestinal transit of Sinemet CR in healthy volunteers.

The gastrointestinal transit and systemic absorption of Sinemet CR (50/200) and standard Sinemet (25/100) have been studied in fasting and "fed" healthy human subjects. Both formulations were labeled with a gamma-emitting radionuclide, and their gastric emptying, colon arrival, and in vivo dissolution profiles were monitored using gamma scintigraphy. The standard dosage forms were found to disperse soon after administration and to empty rapidly from both the fasting and the "fed" stomach. The erosion of the controlled-release (CR) system was independent of food. Dosing after a light breakfast altered the gastric emptying profile of the CR formulation and led to significant differences in the plasma levels of levodopa.

Antiparkinson Agents↗
PubMed1988

Monitoring pulmonary vascular permeability using radiolabeled transferrin.

A simple, noninvasive technique for monitoring pulmonary vascular permeability in patients in critical care units is discussed. High vascular permeability is observed in patients with clinically defined adult respiratory distress syndrome (ARDS) but not in patients with hydrostatic pulmonary edema or in patients with minor pulmonary insults who are considered to be at risk of developing ARDS. The technique has been used in the field of therapeutics and pharmacology to test the effects of the putative antipermeability agents methylprednisolone and terbutaline sulfate. There appears to be a good correlation between the acute inhibitory effect of either drug on transferrin exudation and patient prognosis. Thus, a byproduct of such drug studies may be an index of survival in patients with established ARDS.

Burns, Inhalation↗
PubMed1988

Lung vascular permeability in patients with acute pancreatitis.

Acute pancreatitis may be complicated by acute lung injury associated with increased lung vascular permeability to plasma protein. The pulmonary accumulation of the plasma protein transferrin, radiolabelled in vivo with indium-113m, was monitored using a portable probe radiation detector in sixteen patients with acute pancreatitis. Plasma protein accumulation (PPA) indices were within normal limits (less than 0.5 X 10(-3)min-1) in all survivors (n = 10) and elevated in all but one of the non-survivors. All non-survivors had severe acute pancreatitis as judged by standard criteria. Thus increased lung vascular permeability was not a constant feature of uncomplicated acute pancreatitis and was only observed in patients with multisystem failure accompanied by clinically evident acute lung injury.

Acute Disease↗
PubMed1988

A comparison between magnetic resonance imaging and scintigraphic bone imaging in the diagnosis of disc space infection in an animal model.

In a controlled prospective study, 33 rabbits were used to compare the efficacy of magnetic resonance imaging (MRI) to scintigraphy in diagnosing pyogenic infection of the intervertebral disc. A suitable inoculum of Staphylococcus aureus (10(8) organisms) was injected into a test level while a similar volume of sterile culture medium was injected into a control disc in each animal. Plain radiographs, MRI, and scintigraphic bone images then were performed at regular intervals after operation. The imaging studies were interpreted blind, as was the final histologic assessment. Five animals died of respiratory complications following sedation. In the remaining 28 animals, 23 developed infection at the test level, and four developed infection at the control disc. Magnetic resonance imaging was found to be more sensitive than scintigraphy in diagnosing discitis, particularly in the early stages of the disease. The overall results showed MRI had a sensitivity of 93%, specificity of 97%, and accuracy of 95%. There were two false-negative results and one false-positive. In contrast, scintigraphy had a sensitivity of 41%, specificity of 93%, and accuracy of 68%. There were two false-positive and 16 false-negative results. Plain radiographs had a sensitivity of 82%, specificity of 93%, and accuracy of 88%. There were two false-positive and five false-negative results. The MRI appearance of discitis was characteristic from an early stage in the disease, and preceded the changes on scintigraphy and plain radiographs by several days in the majority of cases.

Animals↗
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

Oesophageal transit of small tablets.

Oesophageal transit has been studied in six asymptomatic subjects aged 29-80 years. Using gamma scintigraphy, the transit of a liquid and five small tablets was monitored in each subject. All the subjects exhibited normal liquid swallowing, with 50% oesophageal clearance times of less than 5 s. In three subjects all the tablets passed through the oesophagus within 6 s, but transit was prolonged in 60% of the swallows in the other subjects. Tablet hold up occurred more frequently in the elderly. An additional drink of water cleared all lodged tablets into the stomach. To minimize possible mucosal irritation, the taking of even small tablets should be followed by an additional drink of water.

Adult↗
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

Gastrointestinal transit of an enteric-coated delayed-release 5-aminosalicylic acid tablet.

Gastrointestinal transit of an enteric-coated, delayed-release 5-aminosalicylic acid tablet radiolabelled with indium-111 has been monitored in a preliminary study with eight healthy subjects using gamma scintigraphy. Gastric emptying of the tablet was delayed by the presence of food in the stomach. Disintegration occurred about 5 hours after the tablet left the stomach. There was close agreement between the tablet disintegration times and the initial detection of drug in the blood. The site of disintegration could be established in most instances; approximately 80% of the doses resulted in drug dispersion within the ascending colon. The coated tablets provide an effective means of drug delivery to the proximal colon.

Adult↗
PubMed1987

Evaluation of an enteric-coated delayed-release 5-aminosalicylic acid tablet in patients with inflammatory bowel disease.

Gastrointestinal transit of an enteric coated delayed release 5-aminosalicylic acid tablet radiolabelled with 111indium has been monitored in a total of 13 patients with Crohn's disease and ulcerative colitis. More than 70% of the tablets disintegrated in the small intestine, on average 3.2 hours after emptying from the stomach. Dispersed preparation was detected in the proximal colon of all the patients, except one with an ileostomy. Mean peak plasma concentrations of 5-aminosalicylic acid and its metabolite acetyl-5-aminosalicylic acid occurred 3-4 hours after gastric emptying. The tablets provide a reliable means of drug delivery to the ileum and proximal colon.

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↗
PubMed1986

Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man.

Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS)--an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with 113mIn. Ten patients with ARDS exhibiting increased PPA indices (greater than 1.0 x 10(-3)/min) were given an intravenous infusion of terbutaline (7 micrograms/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0 x 10(-3)/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n = 5) and non-survivor (n = 5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p less than 0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implications for beta-2-agonists in ARDS.

Adrenergic beta-Agonists↗
PubMed1986

Non-invasive investigation of lower limb revascularisation using resting thallium peripheral perfusion imaging.

Resting thallium thigh and calf imaging was performed in 11 patients with lower limb ischaemia before and after revascularisation. Eight patients had successful revascularisation but in the other three the procedure failed to improve the circulation. Despite symptomatic improvement and increases in ankle systolic pressures after successful revascularisation there was no change in thallium uptake. Thallium imaging was compared with radionuclide angiography and blood pool imaging in six patients. Radionuclide angiograms confirmed the presence of well developed collateral circulation in some patients with increased thallium uptake in the symptomatic limb and in all cases the angiograms were clinically useful. There was no correlation between thallium and blood pool images. Resting lower limb blood flow did not change after revascularisation and thallium peripheral perfusion imaging did not aid the assessment of the response to lower limb revascularisation.

Adult↗
PubMed1986

Colonic motility and enema spreading.

Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents.

Adult↗
PubMed1986

Whole-bowel transit in patients with the irritable bowel syndrome.

The transit of radiolabelled preparations through the stomach, small intestine and colon was monitored in ten patients with the irritable bowel syndrome. Five patients complained of diarrhoea, and five complained of constipation. The preparations comprised a non-disintegrating capsule and a multiparticulate system. Both preparations emptied from the stomach together and at the same rates in both groups of patients. In the patients complaining of constipation, the transit times through the small intestine were the same for both preparations. In the patients complaining of diarrhoea, the capsule passed through the small intestine slightly faster than the particles, but there were no significant differences in the small-intestinal transit rates of the two patient groups. Within the colon, the transit of the capsule was faster than that of the small particles. Although movement through the colon was, on average, faster in the group of patients complaining of diarrhoea, there was considerable intersubject variability, and the differences in transit rates between the two patient groups were not statistically significant.

Adult↗
PubMed1986

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↗