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Biomedical subjects

P Duffy

Publications and source records attributed to P Duffy.

At least 19 recordsLinked to original sources

Calf vein anatomy and flow: implications for colour Doppler imaging.

Early experience has suggested that colour flow Doppler ultrasound may have a diagnostic role in calf vein thrombosis. Before its accuracy within the calf can be adequately assessed, normal calf vein flow and anatomy needs to be understood. We, therefore, studied 40 normal volunteers, age range 24-75 years (mean 45.4), M:F 22:18, and assessed both flow and venous diameter in each of the three sets of calf veins in the supine and erect positions and once again in both these positions following the application of an above knee band. Paired sets of veins were present in all posterior tibial and common peroneal sets, but in only 85% of the anterior tibial group. Significant flow variations were present between different sets of veins, there being relatively less appreciable flow within the common peroneal (p < 0.05). Both band application and erect posture produced significant increases in venous diameter (p < 0.01, p < 0.001) in the posterior tibial and common peroneal veins, aiding visualization but at the cost of reducing flow following band application (p < 0.05, p < 0.01). The erect posture had no deleterious effect on calf vein flow. We, therefore, recommend that when the patency of calf veins is being assessed scanning should be performed in both a supine and erect position as this will help vein visualization without a reduction in flow, and thus avoid misinterpretation.

Adult

Colour flow imaging of calf vein thrombosis.

Ultrasound and more recently colour Doppler ultrasound has been successfully used in the diagnosis of lower limb venous occlusive disease. Colour Doppler ultrasound has shown promise in the diagnosis of calf vein thrombosis but to date there has been no prospective trial to specifically evaluate its potential. In view of this, we carried out a prospective trial of 50 patients comparing the accuracy of colour Doppler ultrasound with venography in the diagnosis of deep venous thrombosis both above and below knee but in particular with respect to the detection of calf vein clot. Of the 50 patients studied, 10 had only one imaging modality performed as there were eight venographic failures and two ultrasonic failures. Comparison was only thus possible in 40 cases. As in previous studies, colour Doppler ultrasound was shown to be accurate in the diagnosis of thrombosis within the femoro-popliteal veins and had a sensitivity and specificity of 100% respectively. With respect to calf vein lesions, there was one false negative scan using the ultrasonic technique giving a sensitivity of 95%, specificity of 100% and accuracy of 97.5%. We feel colour Doppler ultrasound can and should be used as a first line alternative to venography and can be employed for the exclusion of both above and below knee deep venous thrombosis. Venography should now be reserved for those patients who are unsuitable for ultrasound examination or who have an equivocal ultrasound scan.

Adult

Effects of 5-hydroxytryptophan on extracellular serotonin in the spinal cord of rats with experimental allergic encephalomyelitis.

Serotonin (5-HT) and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were collected by in vivo dialysis in the lumbar spinal cord of control rats and rats with hindlimb paralysis induced by experimental allergic encephalomyelitis (EAE). Both 5-HT and 5-HIAA were significantly decreased in baseline samples from EAE rats compared to controls. This decrease in extracellular 5-HT and 5-HIAA in the EAE rats was accompanied by marked morphological changes in spinal cord axons and axon terminal plexuses that were stained for 5-HT-like immunoreactivity. The 5-HT precursor, 5-hydroxytryptophan (5-HTP)-increased 5-HT and 5-HIAA levels in dialysate samples from both control and EAE animals. However, the 5-HTP-induced increase in extracellular 5-HT was significantly greater in the EAE rats than in the controls, despite a lower baseline 5-HT level in the EAE animals. In contrast to 5-HT, both baseline and post-5-HTP levels of 5-HIAA were significantly higher in control animals than in EAE animals. The decreased extracellular 5-HT and 5-HIAA in baseline samples from the EAE rats compared to controls is probably a consequence of the damage to descending 5-HT axons and axon terminals that occurs during the disease. The larger increase in extracellular 5-HT in EAE animals after precursor injection may reflect both decreased 5-HT reuptake from the extracellular space by damaged 5-HT terminals and disruption of the blood-brain barrier that allows entry into the central nervous system of 5-HT that was synthesized from 5-HTP in the periphery.

5-Hydroxytryptophan

Colour Doppler ultrasound of the post-phlebitic limb: sounding a cautionary note.

Colour Doppler ultrasound is accurate in the diagnosis of acute lower limb venous thrombosis. Some patients, however, will re-present with recurrent lower limb swelling following the acute event, and ultrasound may also become the primary imaging modality in these patients. We, therefore, undertook a prospective study of 20 patients with a diagnosis of deep venous thrombosis proven initially on both venography and ultrasound. Sixteen patients had thrombosis in the femoro-popliteal segment and four patients had isolated calf vein thrombosis. Patients with above knee thrombosis were scanned at 1, 3 and 6 months and those with isolated calf lesions at intervals of 1 week, 1 and 3 months. Results showed that in cases of above knee thrombosis, only 50% of patients showed complete recanalization by 6 months. The remaining 50%, by this time, showed only partial recanalization of thrombus, the features of which cannot be distinguished from acute non-occlusive thrombus. With respect to the four cases of isolated calf vein thrombosis, one case showed evidence of popliteal extension of thrombus, which by 3 months had fully recanalized. The remaining three cases recanalized completely without further thrombus extension. These results show that interpretation of the ultrasonic features of the post-phlebitic limb may be difficult in patients who re-present with lower limb swelling. Based on this study, we would advise routine scanning of all patients with above knee venous thromboses at 6 months to provide a baseline scan, permitting more accurate ultrasonic assessment of any future thrombotic events. This study also highlights the question of whether isolated calf vein thrombosis can safely be regarded as a benign entity.

Adult

Plant cardiac glycosides and digoxin Fab antibody.

The potential application of the Digoxin Fab antibody (Wellcome Digibind) in the clinical management of plant poisoning was investigated. The cardiac glycoside contents of various Australian plants were studied using immunoassay techniques. The cross-reactions of the Fab antibody and two digoxin assay antibodies against extracts of these plants were also studied. Results obtained indicated that the Digibind antibody cross-reacted with a wide range of glycosides contained in Australian plants and therefore could be of use in the treatment of life-threatening plant poisoning.

Adult

A comparison of axonal and somatodendritic dopamine release using in vivo dialysis.

The release of endogenous dopamine from the axon terminal field in the nucleus accumbens and from the A10 dopamine cell bodies of conscious rats was measured using intracranial dialysis. Release of dopamine from both areas was calcium-dependent and markedly inhibited by the presence of the D2 agonist, quinpirole, in the dialysis buffer. However, the addition of tetrodotoxin to the buffer produced less of a decrease in dopamine in the A10 region than in the nucleus accumbens. When dopamine release was examined by substituting K+ for Na+ or by adding amphetamine to the buffer, the evoked release was significantly less in the A10 region than in the nucleus accumbens. Likewise, enhanced extracellular dopamine following blockade of reuptake by nomifensine addition to the dialysis buffer was not as great in the A10 region as in the nucleus accumbens. These data argue that, in general, axonal and somatodendritic dopamine release are regulated by similar factors, although somatodendritic release is less influenced by action potential generation and less responsive to some releasing agents.

Amphetamine

Caffeine consumption decreases the response to bronchoprovocation challenge with dry gas hyperventilation.

OBJECTIVE: To determine whether caffeine consumption affects bronchoprovocation challenge (BPC). DESIGN: A prospective, double-blind, placebo-controlled, randomized, crossover trial. PATIENTS: Eleven nonsmoking men, aged 18 to 42 years, with normal baseline spirometry and evidence of exercise-induced bronchospasm. INTERVENTION: On three separate test days, each individual received, in random order, either placebo, 5 mg/kg caffeine, or 10 mg/kg caffeine, and then underwent BPC with eucapnic voluntary hyperventilation (EVH). RESULTS: Caffeine (10 mg/kg) significantly reduced bronchoconstriction compared to placebo (p = 0.02). The reduction in bronchoconstriction correlated with the serum level of caffeine (p = 0.014). CONCLUSIONS: Caffeine decreases bronchoconstriction due to EVH. Caffeine should be eliminated from diet prior to BPC.

Adolescent

Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens.

The behavioral stimulant effect of peripheral cocaine injection into rats is augmented following daily administration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the increased behavioral response following daily cocaine administration is associated with an increase in extracellular dopamine concentration. Acute injection of cocaine (15 mg/kg, ip) produced an elevation in extracellular dopamine concentration in the nucleus accumbens. Following daily pretreatment with cocaine (15 mg/kg, ip X 4 days), a subsequent acute injection of cocaine (15 mg/kg, ip) significantly elevated the extracellular dopamine levels compared to that produced by a single acute injection. Although the levels of extracellular dopamine metabolites was significantly lowered by both acute cocaine and daily cocaine, no difference between these two groups of animals was measured. The increase in extracellular dopamine following a single acute injection of cocaine was not correlated to the motor stimulant response. However, after daily pretreatment with cocaine the motor stimulant response to acute cocaine was positively correlated with the increased extracellular concentration of dopamine in the nucleus accumbens. These data demonstrate that enhanced dopamine release into the nucleus accumbens may mediate the behavioral sensitization produced by daily injections of cocaine, but that other neural systems are influential in mediating the acute motor stimulant effect of cocaine.

3,4-Dihydroxyphenylacetic Acid

Colour Doppler ultrasound in deep venous thrombosis: a comparison with venography.

Colour Doppler ultrasound is a new technical development allowing simultaneous grey scale imaging and a dynamic colour flow vascular image. To date, many real time ultrasonic studies have been assessed in the diagnosis of lower limb venous thrombosis and have been shown to be accurate in the femoral and popliteal segments. A double blind prospective study comparing colour Doppler with contrast venography in the diagnosis of lower limb thrombosis was performed in a group of 40 patients. Of the study group, 26 venograms were negative and 27 ultrasound examinations were negative. Of the 14 positive venograms there was one false negative colour doppler scan which missed a calf and lower popliteal thrombosis. Two cases of isolated calf vein thrombosis were successfully detected by colour Doppler. Overall, the sensitivity and specificity for detection of lower limb venous thrombosis, including calf vein assessment, were 93% and 100% respectively. Colour Doppler is easy to perform; the average scanning time being 15 minutes for complete assessment of a unilateral lower limb venous system. Spontaneous flow is evident in the femoropopliteal segment, whilst proximal calf vein flow can only be appreciated with the aid of distal compression. Eccentric thrombus and partially recanalized thrombus can be shown. Although the number of isolated calf vein thromboses was small, early experience suggests colour Doppler may be useful in the assessment of proximal calf vein patency.

Adult

Changes in the distribution of mouse oocyte cortical granules and ability to undergo the cortical reaction during gonadotropin-stimulated meiotic maturation and aging in vivo.

Mouse oocyte cortical granule (CG) activation and distribution were investigated during in vivo meiotic maturation to determine the onset of competence to undergo the cortical reaction, which is considered responsible for the block to polyspermy. In the present study, the resumption of oocyte maturation was stimulated by hCG administration. Competence to undergo the cortical reaction (assessed with calcium ionophore A23187) was undetectable (0% loss) in germinal vesicle-stage oocytes 0.5 h after hCG administration. When germinal vesicle breakdown and metaphase I had taken place (3 and 7 h post hCG, respectively), approximately 30% CG loss was observed. Maximal (A23187-inducible) levels of CG loss, 67% and 72%, were present at 10 and 13 h, respectively, during metaphase II. Cortical granule distribution changed dramatically during metaphase I, polar body formation, metaphase II, and post-ovulatory aging in vivo. A stable metaphase II distribution was present from 13 to 18 h. After 24 and 32 h, 28% and 83% of the eggs, respectively, exhibited major alterations in the cortical distribution of CGs, some of which did not appear to be susceptible to release by A23187. These data support the hypothesis that just before ovulation the egg cortex completes the development of its normal structure and physiological competence, which are maintained for only a brief period of time afterward. The implications are discussed for normal fertilization and polyspermy in mammals, including humans.

Aging

Effect of acute and daily neurotensin and enkephalin treatments on extracellular dopamine in the nucleus accumbens.

The injection of neurotensin or the enkephalin analog Tyr-D-Ala-Gly-MePhe-Gly(ol) (DAMGO) into the A10 region of rats produces a motor stimulant effect that is associated with an increase in the postmortem levels of dopamine metabolites in the nucleus accumbens. These behavioral and neurochemical effects are augmented following daily administration. In vivo dialysis in the nucleus accumbens of conscious rats was used to determine if the acute and augmented behavioral responses following neurotensin or DAMGO administration are associated with an increase in extracellular dopamine concentrations. The acute injection of DAMGO produced a dose-dependent (0.03-3.3 nmol) elevation in extracellular dopamine and its metabolites in the nucleus accumbens. Neurotensin also produced a dose-related (0.1-3.3 nmol) increase in dopamine and its metabolites. The elevation in extracellular dopamine produced by DAMGO, but not by neurotensin, was positively correlated with the increase in motor activity. Following daily treatment of either neurotensin (1.0 nmol X 4 d) or DAMGO (0.03 nmol X 4 d), a significant elevation in extracellular dopamine levels occurred in the nucleus accumbens compared to an acute injection. The time course of the change in extracellular dopamine after daily injections was similar to the time course of the behavioral stimulation for both compounds. These data demonstrate that enhanced dopamine release in the nucleus accumbens mediates the acute behavioral effect of DAMGO but does not entirely explain the motor effects of neurotensin. However, enhanced dopamine release may mediate the behavioral sensitization produced by daily injection of both peptides into the A10 region.

3,4-Dihydroxyphenylacetic Acid

Modulation of A10 dopamine neurons by gamma-aminobutyric acid agonists.

Microinjection of the gamma-aminobutyric acidA agonist, muscimol, into the A10 region of the rat produced a dose-dependent increase in motor activity. This effect was antagonized by intra-A10 administration of the gamma-aminobutyric acidA antagonist, bicuculline, and by peripheral administration of haloperidol, and was associated with an increase in extracellular levels of dopamine metabolites in the nucleus accumbens. Although microinjection of the gamma-aminobutyric acidB agonist, baclofen, into the A10 region did not alter motor activity, it abolished the capacity of intra-A10 injection of mu opioid agonist, Tyr-D-Ala-Gly-MePhe-Gly(ol), or muscimol to increase motor activity. Baclofen also prevented the motor stimulant response to peripheral injection of cocaine or amphetamine, but was ineffective in blocking caffeine-induced behavioral activity. Pretreatment with baclofen prevented the capacity of a mu opioid agonist to elevate dopamine metabolite levels in the nucleus accumbens and prefrontal cortex in postmortem tissue. Baclofen also prevented the elevation of extracellular dopamine content in the nucleus accumbens produced by injection of a mu opioid agonist into the A10 region, as measured in the conscious rat with in vivo dialysis. Finally, when dopamine metabolite levels were elevated in the prefrontal cortex by mild footshock, it was shown that pretreatment with baclofen in the A10 region abolished this response. These data support electrophysiological studies suggesting that activation of gamma-aminobutyric acidB receptors on dopamine perikarya inhibits dopaminergic activity, while activation of gamma-aminobutyric acidA receptors results in an indirect disinhibition of dopaminergic function.

Animals

Current status of echography (ultrasound).

Ultrasonic demonstration of the anatomy and pathology of solid and fluid-filled organs and structures of the upper abdomen, the retroperitoneum and the pelvis is now well established, as is its use for examination of the thyroid gland, breast, the orbit, the heart, the scrotum and soft tissue masses. Aspiration of cytological and histological material for tissue diagnosis and other purposes is performed in a number of centres. Echography and computed tomography of the abdomen are complementary and there is a trend towards combined units so that each service may be used more efficiently.

Abdomen