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Biomedical subjects

J G Hardy

Publications and source records attributed to J G Hardy.

At least 19 recordsLinked to original sources
PubMed1996

Intra-operative nuclear medicine in surgical practice.

The use of radionuclides for the intra-operative localization of tumours has increased steadily over the past 15 years. We reviewed more than 15 years experience of a peripatetic service using a sterilizable probe system in operating theatres throughout the UK for localizing bone and soft tissue lesions. The technique requires the positive concentration of an appropriate radiopharmaceutical, together with a suitably designed detector system which can be sterilized for use during surgery. All surgical procedures were undertaken following initial positive imaging studies. A well-collimated nuclear probe with a 5 mm diameter CdTe detector was sterilized with ethylene oxide gas and coupled to a digital counter and ratemeter for use in the operating theatre. A total of 68 surgical procedures have been undertaken at 35 hospitals. Fifty-eight patients underwent excision of osteoid osteoma subsequently proven by histology. The other lesions successfully resected included osteoblastoma, hamartoma, Brodie's abscess, chronic bone infection, ectopic parathyroid adenoma and metastatic neuroblastoma. The technique can now be regarded as the method of choice for the surgical localization of osteoid osteoma. The successful detection of lesions at surgery can be assured providing that clear localization of the radiopharmaceutical occurs on the pre-operative images. The intra-operative use of conventional and new tumour-specific radiopharmaceuticals is reviewed and we confirm an increasing role for the surgical-probe-guided localization of primary and metastatic tumours.

Adenoma↗
PubMed1995

Effect of 'antiembolism' compression hosiery on leg blood volume.

Blood volume in the legs of healthy volunteers and the ability of graduated compression hosiery to reduce that volume were investigated with gamma scintigraphy. Changing posture from supine to upright, or pneumatic thigh cuffs inflated to either 20 or 40 mmHg with the subject supine, significantly increased leg blood volumes; the mean increase was: upright 126 ml, 20 mmHg cuff 44 ml, and 40 mmHg cuff 113 ml. A significant trend in reducing these volumes was noted in three brands of commercially available stockings, with the subject supine and without thigh cuffs (Page's L trend 132.5, P < 0.01) and when cuffs were applied at 20 mmHg (Page's L trend 128, P = 0.05). Few of the commercially available stockings delivered the 'standard' compression profile of 18 mmHg at the ankle, 14 mmHg at the calf and 8 mmHg at the upper thigh. The effects of other compression profiles were assessed, using custom-made stockings, and pneumatic cuffs inflated to 20 mmHg applied to the upper thighs to impede venous return. There was no consistent reduction of blood volume in the popliteal region, although decreases were seen in the upper and lower calf. The major determinant of performance was compression at the calf; the ankle to calf compression gradient was not important. Stockings with a profile of 16.8 mmHg at the ankle, 14.5 mmHg at the calf and 6.4 mmHg at the upper thigh performed best.

Adult↗
PubMed1994

Evaluation of 153Sm-diethylenetriaminepentaacetic acid for radiolabelling of pharmaceutical dosage forms by neutron activation.

153Sm-DTPA provides a suitable alternative to 99mTc-DTPA and 111In-DTPA as a water soluble tracer for the evaluation of pharmaceutical preparations. The chelate was handled biologically in a similar way to 99mTc-DTPA and 111In-DTPA. The chelate can be incorporated into the formulation as a non-radioactive excipient and the intact dosage form can then be neutron activated to produce 153Sm.

Administration, Inhalation↗
PubMed1994

The distribution of an intranasal insulin formulation in healthy volunteers: effect of different administration techniques.

The initial deposition pattern in the nasal passages and subsequent clearance of an insulin formulation labelled with 99mTc-human serum albumin have been determined in 12 healthy male volunteers. Four different administration modes from a novel aqueous spray device were compared, involving delivered volumes of 80-160 microL, and with either gentle or vigorous inhalation while firing the device. The entire dose was deposited in the nasal cavity, and no significant radioactivity was deposited in the lungs. A mean 25-33% of the radiolabel remained in the nose after 4 h. A significantly smaller area of the nasal mucosa was covered by the smallest (80 microL) bolus, but subsequent clearance rates did not vary significantly with mode of administration. Blood glucose levels fell after administration of the insulin formulation, but no serious episodes of hypoglycaemia occurred.

Absorption↗
PubMed1993

Localization of drug release sites from an oral sustained-release formulation of 5-ASA (Pentasa) in the gastrointestinal tract using gamma scintigraphy.

Release of 5-ASA from a sustained release formulation (Pentasa, Ferring A/S, Copenhagen, Denmark) was monitored with plasma sampling for up to 24 hours in nine volunteers under both fasted and fed conditions. Drug absorption was correlated with location of the sustained-release microgranules in the gastrointestinal tract by gamma scintigraphy. Disintegration of the labeled tablet preparation occurred in the stomach within 20 minutes and acetylated 5-ASA was detectable in the plasma less than 60 minutes after ingestion. No significant differences were detected in either transit times through the small intestine, peak plasma acetylated 5-ASA concentration or lag time to absorption between fasted and fed individuals. Peak plasma concentration of acetylated 5-ASA usually occurred when the microgranules were present in the small intestine or ascending colon. The pharmacoscintigraphic study confirmed that 5-ASA release from the formulation occurred throughout the gastrointestinal tract, and that food effects on the in vivo behavior of the preparation were minimal.

Administration, Oral↗
PubMed1993

Lung deposition from four nebulizers.

The total and regional deposition of aerosol has been compared using four nebulizers; the Pari Boy 37.80, Pari IS-2, RespirGard II and Penta-Sonic. The aerosol was radiolabelled with [99Tcm]DTPA, administered to ten healthy subjects and the distributions monitored by gamma scintigraphy. Median lung aerosol depositions expressed as percentages of the doses initially loaded into the nebulizers were: Pari IS-2 19%, Pari Boy 37.80 13%, RespirGard II 9% and Penta-Sonic 2%. The ratios of the peripheral to central lung deposition, however, were greater with the RespirGard II and Penta-Sonic nebulizers. The choice of the most appropriate nebulizer depends on the pharmaceutical being administered, since aerosol must be delivered to the required site in sufficient quantity, whilst minimizing the incidence of local or systemic side-effects.

Administration, Inhalation↗
PubMed1993

Postoperative limb compression in reduction of haemorrhage after varicose vein surgery.

In varicose vein surgery, significant postoperative morbidity results from subcutaneous haematoma formation and limb swelling after saphenous vein stripping. We investigated the effectiveness of a high-compression short-stretch adhesive bandage compared with non-adhesive crêpe in reducing haemorrhage after stripping of varicose veins. Using 99mTc-labelled red blood cells, the degree of postoperative bleeding was assessed in 10 patients with bilateral varicose veins allocated for stripping and ligation. High-compression adhesive bandaging was applied to the experimental limb and a non-adhesive bandage to the contralateral control limb. Results show that adequate compression bandaging can decrease subcutaneous haematoma formation after stripping of varicose veins.

Adult↗
PubMed1992

Gamma scintigraphy in the evaluation of pharmaceutical dosage forms.

Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 oxide or erbium-170 oxide followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application.

Diltiazem↗
PubMed1992

In vivo evaluation of enteric-coated naproxen tablets using gamma scintigraphy.

Seven healthy, male volunteers were entered into a randomized, open crossover study of the gastrointestinal transit of two enteric-coated 500-mg naproxen tablets. Two radiolabeled tablets were given to each volunteer on two occasions separated by 7 days, once in the fasted state and once after breakfast. Radiolabeling of tablets was achieved by the incorporation of samarium-152 oxide during manufacture, followed by neutron activation of the tablet to produce the gamma-emitting isotope samarium-153. No loss of tablet integrity was seen in the stomach and all tablets disintegrated in the small intestine. Onset of tablet disintegration was controlled predominantly by gastric emptying. Time in the small intestine prior to tablet disintegration was independent of food intake. Naproxen blood levels with time were consistent with the delayed release of naproxen from the tablets. Overall, transit, disintegration, and absorption were as expected from an enteric-coated tablet.

Adult↗
PubMed1992

New aerosol delivery system for neonatal ventilator circuits.

There is mounting evidence that a variety of drugs delivered as aerosols are likely to be of benefit in neonatal units. To avoid many of the problems associated with the use of jet nebulisers in ventilator circuits, a chamber was designed to be used in conjunction with a metered dose inhaler (MDI). The dimensions (4 cm x 11 cm) were chosen in an attempt to maximise drug delivery. In vitro studies were subsequently performed in order to determine the optimum operating conditions. Sodium cromoglycate delivered via this system was collected on a filter placed between the tip of an endotracheal tube and a model lung. The dose delivered was determined by means of an ultraviolet spectrophotometric assay. Using a Draeger Babylog 8000 ventilator it was found that drug delivery as maximised by actuating the device just before the inspiratory cycle when the chamber was placed adjacent to the endotracheal tube and by using a long (one second) inspiratory time. Under these conditions 1.5-2% of the original dose was deposited upon the filter at tidal volumes of 11-22 ml. When considered in terms of body weight this is many times the equivalent dose delivered to adults from an MDI. Effective drug delivery to the filter was confirmed using a radiolabelled aerosol. Radiolabelled studies delivering aerosol to the lungs of intubated rabbits demonstrated that deposition aerosol was distributed uniformly between lobes when corrected for the weight of each lobe. In conclusion, the device appears likely to deliver significant, reproducible quantities of drug to the lower respiratory tract while being simple to use.

Aerosols↗
PubMed1991

Characterisation of the in vivo behaviour of a controlled-release formulation of levodopa (Sinemet CR).

The gastrointestinal transit and systemic absorption of Sinemet CR (50-200) controlled-release tablets and standard Sinemet (25-100) immediate-release (IR) tablets have been studied in fasted and fed healthy human subjects. Both formulations were labelled with a gamma-emitting radionuclide and their gastric emptying, colon arrival and in vivo disintegration profiles monitored using gamma scintigraphy. The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs. Erosion of the CR system was independent of food or stomach pH. The CR tablet was observed to disintegrate fully in the gastrointestinal (GI) tract, resulting in complete release of levodopa over a 3-4 h time period. Considerable intersubject variation was found to exist for levodopa absorption. Absorption was more protracted with Sinemet CR than with standard Sinemet, due to the controlled release characteristics of the tablet matrix. There was no rapid initial absorption phase and instead, a gradual build-up in the absorption profile occurred.

Adult↗
PubMed1991

Evaluation of an enteric-coated naproxen pellet formulation.

An enteric-coated, pellet formulation of naproxen has been evaluated in eight healthy subjects. Each volunteer was dosed with 153Sm-labelled, enteric-coated pellets on two occasions, once whilst fasted and once after breakfast. Gastrointestinal transit was followed using gamma scintigraphy and drug absorption compared with that from uncoated naproxen pellets dosed on a separate occasion. The pH in the stomach and intestines was monitored using radiotelemetry capsules. Gastric emptying was delayed by dosing after breakfast, but small intestinal transit of the enteric-coated formulation was the same on both occasions. The highest pH recorded from the stomach was 4.0 and in all subjects the pH rose to at least 7.3 in the small intestine. The onset of drug absorption was fastest from the uncoated formulation and slowest from the coated pellets taken after breakfast. The total amount of drug absorbed was the same on all three occasions.

Administration, Oral↗
PubMed1991

Relationship between systemic drug absorption and gastrointestinal transit after the simultaneous oral administration of carbamazepine as a controlled-release system and as a suspension of 15N-labelled drug to healthy volunteers.

1. Plasma drug concentrations after a single oral administration of a suspension of carbamazepine (CBZ) and a 20/200 CBZ Oros osmotic pump system were measured in eight healthy male volunteers. The oral suspension contained 100 mg CBZ labelled with the stable isotope nitrogen-15, whilst the Oros contained 200 mg unlabelled CBZ. Plasma concentrations of [15N]-CBZ and CBZ were measured simultaneously by gas chromatography-mass spectrometry. 2. The position of the CBZ Oros (labelled with indium-111) in the gastrointestinal tract was followed by gamma scintigraphy. Plasma drug concentrations after the two treatments were used to relate pharmacokinetic with transit data. 3. The Oros was taken after breakfast and gastric emptying occurred between 1.1- greater than h post-dosing (median, 5.3 h). Small intestinal transit times ranged from 1.5- greater than 3.6 h, with a median of 2.2 h. There were wide individual variations in colonic transit, and the total transit time ranged from 10-60 h (median, 22 h). 4. Relative systemic bioavailability of CBZ from the Oros was reduced compared with that from the suspension (mean dose normalised AUC ratio = 0.69 +/- 0.17; mean dose-normalised AUC ratio = 0.85 +/- 0.13, allowing for actual release from the Oros system). 5. The in vivo absorption of drug into the systemic circulation from the Oros was estimated using the Wagner-Nelson method. This showed that absorption of CBZ was rapid when the Oros was present in the stomach and small intestine, the rate being determined by the release of drug from the system.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
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↗
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↗