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Biomedical subjects

G Hooper

Publications and source records attributed to G Hooper.

At least 19 recordsLinked to original sources
PubMed2000

Interhemispheric switching mediates perceptual rivalry.

BACKGROUND: Binocular rivalry refers to the alternating perceptual states that occur when the images seen by the two eyes are too different to be fused into a single percept. Logothetis and colleagues have challenged suggestions that this phenomenon occurs early in the visual pathway. They have shown that, in alert monkeys, neurons in the primary visual cortex continue to respond to their preferred stimulus despite the monkey reporting its absence. Moreover, they found that neural activity higher in the visual pathway is highly correlated with the monkey's reported percept. These and other findings suggest that the neural substrate of binocular rivalry must involve high levels, perhaps the same levels involved in reversible figure alternations. RESULTS: We present evidence that activation or disruption of a single hemisphere in human subjects affects the perceptual alternations of binocular rivalry. Unilateral caloric vestibular stimulation changed the ratio of time spent in each competing perceptual state. Transcranial magnetic stimulation applied to one hemisphere disrupted normal perceptual alternations when the stimulation was timed to occur at one phase of the perceptual switch, but not at the other. Furthermore, activation of a single hemisphere by caloric stimulation affected the perceptual alternations of a reversible figure, the Necker cube. CONCLUSIONS: Our findings suggest that interhemispheric switching mediates perceptual rivalry. Thus, competition for awareness in both binocular rivalry and reversible figures occurs between, rather than within, each hemisphere. This interhemispheric switch hypothesis has implications for understanding the neural mechanisms of conscious experience and also has clinical relevance as the rate of both types of perceptual rivalry is slow in bipolar disorder (manic depression).

Adolescent↗
PubMed2000

Gastrointestinal spread of oral prolonged-release mesalazine microgranules (Pentasa) dosed as either tablets or sachet.

BACKGROUND: There is increasing interest in using higher dosages of mesalazine for the treatment of inflammatory bowel disease; however, with current mesalazine products this involves the use of 8-16 tablets per day. AIM: To evaluate the disposition, dispersion and movements of Pentasa prolonged-release microgranules following single dosing of either tablets (2 x 500 mg) or a new 1 g sachet (unit dose, microgranules in a foil bag). METHODS: A randomized crossover study in eight healthy volunteers was undertaken. Both formulations were radiolabelled by neutron activation and dosed in the fasted state. Location of the preparations in the bowel was assessed over 24 h by scintigraphy. RESULTS: Dissolution testing at pH 7.5 showed comparable in vitro mesalazine release properties for the tablet and sachet preparations. In vivo disposition of the microgranules administered as either tablets or sachet was comparable in terms of gastric emptying, small intestinal transit and colon arrival. CONCLUSIONS: Pentasa sachets 1 g unit dose offers the same release of mesalazine as Pentasa 500 mg tablets. Drug release occurs throughout the gastrointestinal tract from stomach to colon, with the advantage of fewer oral doses and ease of swallowing.

Administration, Oral↗
PubMed2000

Histological appearances in post-partum de Quervain's disease.

Six patients who developed de Quervain's disease during pregnancy or within 12 months of childbirth were treated surgically. Histopathological examination of the tendon sheaths using alcian blue stain showed that myxoid degeneration was responsible for the thickening observed in the sheath. Characteristic intramural deposits of mucopolysaccharides were present, predominantly in the subsynovial region. Acute or chronic inflammatory changes were not seen. These findings were the same as those described in patients with de Quervain's disease unrelated to pregnancy or childbirth.

Adult↗
PubMed2000

Volar metacarpophalangeal joint dislocation.

Volar dislocation of the metacarpophalangeal joint is a very rare clinical finding. A volar dislocation of the metacarpophalangeal joint of the left index finger in a 44 year old man is reported. Closed reduction proved unsuccessful requiring subsequent open reduction and internal fixation via a combined dorsal and volar approach. The presentation, mechanism of injury and treatment of this case and other previously reported cases are discussed.

Adult↗
PubMed1999

Improved targeting of beclomethasone diproprionate (250 micrograms metered dose inhaler) to the lungs of asthmatics with the Spacehaler.

The Spacehaler (Evans Medical Ltd, Leatherhead, U.K.) is a new, compact, inhaler device containing the same aerosol canister as a conventional metered dose inhaler (MDI). However, the design of the Spacehaler has been shown to reduce the velocity of the aerosol, thus reducing the proportion of non-respirable particles delivered to the patient. This study compared radioaerosol deposition patterns following inhalation of 250 micrograms of beclomethasone dipropionate from the Spacehaler and a conventional MDI (Beclazone, Norton Health Care, Harlow, U.K.). After rigorous in vitro validation of the radiolabelling technique, 12 asthmatic subjects (seven men aged 20-69 years, mean baseline FEV1 2.59 1 (SD 0.55 1) received one dose of 99mTc-labelled beclomethasone dipropionate 250 micrograms via either a Spacehaler or MDI on each of two study days in a randomized cross-over manner. All subjects had been taught the required inhalation technique before the dose was administered. Inhalation details were recorded using a spirometer connected in series with the device. Lung and oropharyngeal depositions were measured by gamma scintigraphy. The mean percentage of the metered dose deposited in the lungs was 23.0% (SD 8.3%) for the Spacehaler and 12.8% (SD 6.8%) for the MDI (P < 0.01). However, there was no significant difference in the distribution patterns within the lungs between the two devices. Oropharyngeal deposition was significantly lower (P < 0.01) for the Spacehaler than for the MDI [mean (SD) 27.9% (16.4%) and 73.6% (8.7%), respectively] whilst the percentage of the metered dose remaining on the Spacehaler actuator was significantly greater than that on the MDI actuator [mean (SD) 48.0% (11.8%) and 12.4% (8.5%) respectively, P < 0.01]. There was evidence from the inhalation recordings that some patients experienced the 'cold Freon effect' whilst using the metered dose inhaler which may have contributed to the lower lung deposition seen with this device. This study demonstrates that the proportion of a 250 micrograms dose of beclomethasone dipropionate that is delivered to the lungs is significantly greater with the Spacehaler than the MDI. The Spacehaler also reduces the proportion of the does that is deposited in the oropharynx to less than half that observed with the MDI, and reduces the total dose of drug received by the patient.

Administration, Inhalation↗
PubMed1998

Analysis of the human Sonic Hedgehog coding and promoter regions in sacral agenesis, triphalangeal thumb, and mirror polydactyly.

The human Sonic Hedgehog gene (SHH) is one of the vertebrate homologs related to the Drosophila segment polarity gene hedgehog. The entire coding and promoter region of the SHH gene, including 2 kb 5' of the transcriptional start site has been screened for mutations in families with autosomal dominant sacral agenesis and autosomal dominant triphalangeal thumb, two conditions previously known to be linked to 7q36. We have also studied the SHH gene in five families with mirror polydactyly associated with tibial hemimelia and in 51 unrelated patients with neural tube defects. Except for two sequence variants in exon 3, no mutations were found in these disease categories. OFF

Abnormalities, Multiple↗
PubMed1997

A scintigraphic study to evaluate the deposition patterns of a novel anti-asthma drug inhaled from the Cyclohaler dry powder inhaler.

A scintigraphic study was performed, in 10 healthy volunteers, to determine the deposition patterns of a novel anti-asthma drug, LAS 31025, inhaled from a dry powder inhaler, the Cyclohaler. In addition, plasma concentrations of drug following inhalation were determined to investigate their relationship to the deposition patterns. Increasing doses of LAS 31025 were inhaled by the volunteers on four separate study days; 2.25, 4.5, 9.0 and 18.0 mg. The average lung deposition values corresponding to these dose levels were 19.1, 20.9, 19.5 and 17.5%, respectively. Deposition patterns within the lungs were similar on each of the four study days, with slightly more of the dose deposited in the central and intermediate regions compared to the peripheral lung region. The scintigraphic data were supported by the pharmacokinetic measurements as there was an increase in the maximum plasma concentration and area under the concentration-time curve corresponding to the increased doses of LAS 31025 on successive study days.

Journal Article↗
PubMed1997

The distribution of fibrous flexor sheath ganglions.

The distribution of fibrous flexor sheath ganglions was studied in 57 patients. They were found to be more common in the third decade and in the middle finger. Both hands were equally affected. There was no clear relationship to occupation or repeated trauma. The striking finding in our study was the male predominance.

Adult↗
PubMed1997

Neonatal compression ischaemia of the forearm.

A case of neonatal compartment syndrome of the forearm is reported. The cause was thought to be compression during delivery. It not only caused muscle contractures but also affected bone growth. Conservative treatment was given. At the age of 6 years, the muscle contracture had recovered and there was full hand function, but there was growth arrest of the distal radial epiphysis and the affected forearm was shorter than the other.

Birth Injuries↗
PubMed1997

Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy.

PURPOSE: In this paper we report on the first scintigraphic evaluation of vaginal dosage forms in post-menopausal women. To date, almost nothing is known about the in vivo performance of pharmaceutical formulations in the human vagina, which is a major deficiency in the rational design of drug delivery systems for both existing and new indications. METHODS: The vaginal spreading and clearance of a radiolabelled pessary formulation and Replens (polycarbophil) gel, was assessed in six healthy, post-menopausal female volunteers over a six hour period using the technique of gamma scintigraphy. RESULTS: In five out of the six subjects studied, clearance of the two formulations exhibited very little intra-subject variation. However, there was considerable inter-subject variability in clearance; in Subject 5 circa 80% of the products were retained whilst in Subject 2 less than 2% was present at the end of the six hour imaging period. Importantly, there was no evidence to suggest that either of the formulations dispersed material beyond the cervix, into the uterus, in any of the subjects studied. CONCLUSIONS: The lack of significant retention of these products in most of the volunteers has obvious implications for the delivery of therapeutic agents. This study shows that gamma scintigraphy is an invaluable technique with which to assess novel formulations aimed at optimising retention in the vagina for topical or systemic drug delivery.

Administration, Intravaginal↗
PubMed1997

Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation.

BACKGROUND: Colonic delivery of corticosteroids may reduce the side-effects commonly associated with their use. Therefore, we tested the ability of the naturally occurring polysaccharide guar gum to deliver a corticosteroid, dexamethasone, to the colon using pharmacoscintigraphy. Guar gum is metabolized in the colon by resident bacterial enzymes to trigger drug release. MATERIALS: Each subject (eight per group, parallel study design) was administered one of four dexamethasone (9 mg) tablet formulations, radiolabelled with 153Sm using neutron activation, under fasted conditions. One formulation was designed to release drug rapidly following ingestion while the other three formulations were designed to delay release of dexamethasone to varying degrees. Progression of the formulations down the gastrointestinal tract was followed by gamma scintigraphy. Serum concentrations were measured over time to relate disintegration profiles of the tablets with pharmacokinetic observations. RESULTS: The immediate release formulation disintegrated in the stomach, on average, within 20 min of dosing. One of the three delayed release preparations (CD1) began to disintegrate in the small intestine 1.7 +/- 1.0 h after dosing. The second and third delayed release preparations (CD2 and CD3) did not begin to disintegrate until 5.8 +/- 2.3 and 3.6 +/- 1.6 h after dosing, respectively. All three colonic delivery preparations completely disintegrated in the colon ranging from 7.8 +/- 2.7 h (CD1) to 12.4 +/- 3.2 h (CD2) following oral administration. Pharmacoscintigraphic data indicated that 72-82% of the dexamethasone was delivered into the colon although not all the dexamethasone delivered into the colon was absorbed. CONCLUSIONS: Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.

Adult↗
PubMed1996

Efficient delivery to the lungs of flunisolide aerosol from a new portable hand-held multidose nebulizer.

In order to provide asthmatic patients with an inhaler that does not use chlorofluorocarbon propellants, a novel multidose hand-held nebulizer (RESPIMAT, Boehringer Ingelheim Ltd.) has been developed. This device delivers 200 x 15 microL metered doses of drug solution, but does not use propellants of any kind. In this study of 10 healthy volunteers, the deposition pattern in the lungs and oropharynx of an ethanolic solution of flunisolide delivered via a prototype III multidose nebulizer has been determined by gamma scintigraphy. A comparison was made with the same dose (250 micrograms) of flunisolide delivered by a pressurized metered dose inhaler (MDI) and MDI plus Inhacort spacer. Mean (SD) whole lung deposition from the multidose nebulizer (39.7 (9.9) % of the metered dose) was significantly higher than that from either MDI (15.3 (5.1) %, P < 0.01) or MDI plus spacer (28.0 (7.0) %, P = 0.01). A mean 10.4% of the dose was recovered from an exhaled air filter for the multidose nebulizer, but less than 2% of the dose for MDI or MDI plus spacer. Oropharyngeal deposition was significantly reduced for the multidose nebulizer (39.9 (9.4) %) compared to MDI (66.9 (7.1) %), but was reduced further for the MDI plus spacer (27.3 (11.3) %). The multidose nebulizer delivers an unusually high percentage of an aerosol dose to the lungs, and it "targets" flunisolide to the lungs more effectively than the MDI. The multidose nebulizer could constitute a viable alternative to MDIs in asthma maintenance therapy.

Adult↗
PubMed1995

Angioleiomyomas of the hand. A report of 14 cases.

We have reviewed a series of 14 angioleiomyomas of the hand. Unlike angioleiomyomas elsewhere, those occurring on the hand are less commonly painful, have an equal sex distribution and are not predominantly of the solid type as seen in the lower limb. We were unable to find a strong association between histological appearance and clinical presentation. We were able to demonstrate nerve fibres within angioleiomyomas, which have not been reported previously.

Adolescent↗
PubMed1995

Scaphoid exostosis and radio-carpal osteoarthrosis.

We report seven patients (eight wrists) with osteoarthrosis of the wrist associated with an exostosis arising from the dorsal aspect of the scaphoid. We believe that the exostosis is secondary to impingement of the scaphoid on the radial styloid process and is a consequence rather than a cause of osteoarthrosis. Conservative management is advised.

Adult↗
PubMed1995

Comparison of gamma scintigraphy and a pharmacokinetic technique for assessing pulmonary deposition of terbutaline sulphate delivered by pressurized metered dose inhaler.

A comparison has been made of pulmonary deposition of terbutaline sulphate from a pressurized metered dose inhaler (pMDI), measured in 8 healthy male subjects by gamma scintigraphy and by a pharmacokinetic (charcoal-block) method, involving drug recovery in urine. Measurements were carried out with a pMDI at slow (27 l/min) and fast (151 l/min) inhaled flows and with Nebuhaler large volume spacer device (average inhaled flow 17 l/min). Overall, the two methods did not differ significantly in their estimates of whole lung deposition, although values obtained by gamma scintigraphy exceeded those from the charcoal-block method for the pMDI with fast inhalation. The regional distribution of drug within the lungs and deposition in the oropharynx could be assessed by gamma scintigraphy, but not by the charcoal-block method. It is concluded that either method may be used to assess whole lung deposition of terbutaline sulphate from pMDIs, both with and without a spacer, although each method has its own inherent advantages and disadvantages.

Adult↗
PubMed1995

Colonic spreading of a non-chlorofluorocarbon mesalazine rectal foam enema in patients with quiescent ulcerative colitis.

BACKGROUND: Rectal foam enemas provide for drug delivery to the distal colon for treatment of left sided ulcerative colitis. However, currently available formulations contain chlorofluorocarbons which are due to be phased out in the near future. The objective of this study was therefore to determine the degree of dispersion of a newly developed non-chlorofluorocarbon rectal foam preparation in ulcerative colitis patients. METHODS: This was an open label non-controlled study of a single administration of a mesalazine foam enema (two actuations containing 2 g of mesalazine in approximately 120 mL foam) in 10 patients with quiescent ulcerative colitis. Spreading of the 99mTc-labelled foam enema was assessed over a 4-h period by the non-invasive technique of gamma scintigraphy. RESULTS: All patients retained the enema for the full 4-h imaging period. In nine out of the 10 patients, the enema was observed to spread as far as the descending colon and on average 23% of the dose was present in the descending colon at 4 h post-dose. CONCLUSIONS: The extent of spreading observed in the study supports the use of the formulation in the treatment of left sided ulcerative colitis.

Aminosalicylic Acids↗
PubMed1995

Scintigraphic assessment of the oropharyngeal and nasal depositions of fusafungine from a pressurized inhaler and from a novel pump spray device.

The distributions of fusafungine (Locabiotal, Servier) radiolabelled with 99mTc, and delivered either orally or intranasally, have been assessed in healthy volunteers from a pressurized metered-dose aerosol inhaler (125 micrograms per dose) and from a novel mechanical pump spray device (500 micrograms per dose). More than 90% of the dose was initially deposited in the oropharynx for oral dosing (n = 8), and more than 90% in the nose for nasal dosing (n = 9), with no significant penetration of aerosol into the lungs. Although not statistically significant, the mean area of deposition, measured in terms of gamma camera picture elements (pixels), was greater with the pump spray for both oral and nasal dosing. The area of deposition with the nasal pump spray extended into the turbinates in six of nine subjects, compared with only three of nine subjects for the pressurized aerosol. The data suggest that the distribution patterns of pump sprays and pressurized aerosols of fusafungine in the oropharynx and in the nasal passages are similar, and that the former can be substituted for the latter with little change in drug delivery.

Administration, Inhalation↗