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P Duffy

Publications and source records attributed to P Duffy.

At least 73 records · Page 4Linked to original sources
PubMed1993

Transfection of the malaria parasite and expression of firefly luciferase.

The goal of this work is to develop a method for the functional analysis of malaria genes using the method of DNA transfection. We have developed a transient transfection vector by constructing a chimeric gene in which the firefly luciferase gene was inserted in frame into the coding region of the pgs28 gene of Plasmodium gallinaceum. This plasmid DNA was introduced into P. gallinaceum gametes and fertilized zygotes by electroporation, and luciferase expression was assayed after 24 hr. This report of successful introduction and expression of a foreign gene in a malaria parasite demonstrates the feasibility of this approach to developing methods for the functional analysis of parasite genes.

Animals↗
PubMed1993

Regulation of the polyspermy block in the mouse egg: maturation-dependent differences in cortical granule exocytosis and zona pellucida modifications induced by inositol 1,4,5-trisphosphate and an activator of protein kinase C.

Germinal vesicle (GV)-intact fully grown mouse oocytes do not undergo cortical granule (CG) exocytosis in response to A23187 treatment, whereas metaphase II (MII)-arrested eggs do. This differential response may reflect the development of the ability of the egg to undergo CG exocytosis, which is responsible for the biochemical modification of the glycoprotein ZP2 in the zona pellucida. Accordingly, we compared in these two stages the ability of 12-O-tetradecanoyl phorbol 13-acetate (TPA) or inositol 1,4,5-trisphosphate (IP3) to promote CG exocytosis and/or the ZP2 to ZP2f conversion; these agents are known to stimulate early events of mouse egg activation. TPA (10 ng/ml) treatment for 60 and 120 min resulted in a 25% and 52% CG loss in GV-intact oocytes and a 38% and 76% loss in MII eggs, respectively; fertilization resulted in a CG loss of approximately 70-80%. Although a similar extent of ZP2 to ZP2f conversion was observed in oocytes and eggs after a 120-min TPA treatment (approximately 70-80%), a greater extent of conversion was observed in oocytes after a 60-min treatment (80% for oocytes, 50% for eggs). Microinjection of IP3 (final concentration 1 microM) into MII eggs resulted in an extent of ZP2 conversion similar to that observed following fertilization, whereas little conversion occurred in GV-intact oocytes similarly injected. These results indicate that a protein kinase C sensitivity develops prior to meiotic maturation, whereas responsiveness to IP3 develops after maturation has resumed. We propose that the regulatory mechanism involving an IP3-mediated calcium release is deficient in GV-stage oocytes.

Animals↗
PubMed1993

Carotid colour Doppler.

Following the introduction of a carotid colour duplex Doppler service, a retrospective survey of the second 100 patients examined was undertaken to determine the accuracy of the examination compared with angiography and surgery, and to assess the clinical efficacy of the results with a review of the final diagnosis, how that diagnosis was achieved and whether the test had helped assess the patient's illness or altered the medical management and/or the outcome of the patient's illness. The results indicated the expected accuracy of over 94% and that the examination helped assess the patient's illness in 92%, altered the management plan in 40% and altered the outcome of the patient's illness in 14% where the disease prevalence was 16%.

Aged↗
PubMed1993

IgG subclass concentrations and Gm allotypes in IgA-deficient and normal pregnant women.

IgG subclass concentrations were measured in the serum of 40 IgA-deficient (IgA concentration < 0.01 milligram) and 38 normal women in the second trimester of pregnancy. In the IgA-deficient group, 2 women were also deficient in IgG2 and IgG4, while a further 10 had very low concentrations of serum IgG4 only. These low IgG4 values were unrelated to the presence of anti-IgA antibodies. The incidence of low IgG4 values was significantly greater (p < 0.01) than in the control group where only 1 woman had low IgG4 and none had low IgG2. Mean values for total IgG, IgG1 and IgG3 were very significantly higher (p < 0.001) in the IgA-deficient group than in the control group. These differences were unrelated to Gm phenotype.

Female↗
PubMed1993

Time course of extracellular dopamine and behavioral sensitization to cocaine. II. Dopamine perikarya.

Cocaine was administered daily (15 mg/kg, i.p. x 1 d followed by 30 mg/kg, i.p. x 5 d) to produce behavioral sensitization. Using microdialysis in the ventral tegmental area and medial substantia nigra, the effect of repeated cocaine was examined on the extracellular levels of dopamine. One day after discontinuing repeated cocaine injections, an acute challenge with cocaine (15 mg/kg, i.p.) produced a significant elevation in extracellular dopamine compared to rats pretreated with daily saline (x6 d). The augmentation in extracellular dopamine persisted longer than the sensitized behavioral response. In contrast, 14 d after discontinuing daily cocaine, the increase in extracellular dopamine produced by an acute cocaine challenge was not augmented, although behavioral sensitization was present. In separate animals, the basal concentration of dopamine in the ventral tegmental area/medial substantia nigra was measured by determining the concentration of dopamine at which no net flux occurred across the dialysis membrane in vivo. One day after discontinuing daily treatments, the basal level of extracellular dopamine in the cocaine pretreated rats was significantly elevated over the level in saline-pretreated animals (1.3 nM vs. 0.8 nM). By 14 d after the last daily injection, the basal levels of dopamine were equivalent in cocaine- and saline-pretreated animals. It is concluded that daily cocaine injections produce a transient alteration in the regulation of somatodendritic dopamine release. While such changes are not responsible for the long-term behavioral sensitization produced by repeated cocaine administration, they may be involved in the initiation of behavioral sensitization.

Animals↗
PubMed1993

Time course of extracellular dopamine and behavioral sensitization to cocaine. I. Dopamine axon terminals.

Repeated administration of cocaine to rodents produces a progressive augmentation in motor activity known as behavioral sensitization. By using microdialysis in the ventral striatum, some studies have found that the development of behavioral sensitization is associated with a similar augmentation in dopamine release, while others have not. It was postulated that differences in doses and withdrawal periods may account for the discrepancies between studies. Rats were behaviorally sensitized to daily peripheral injections using two cocaine treatment regimens (15 mg/kg, i.p. x 5 d or 30 mg/kg, i.p. x 5 d). Using in vivo microdialysis in the ventral striatum, the effect of acute cocaine (15 mg/kg, i.p.) on extracellular dopamine content and motor behavior was examined at various times after discontinuing daily treatments. Twenty-four hours after discontinuing the low dose of daily cocaine, the increase in motor activity and extracellular dopamine elicited by an acute cocaine challenge was significantly elevated. In contrast, following the higher daily treatment regimen there was a significant augmentation in motor activity, but the increase in extracellular dopamine produced by cocaine was significantly reduced. When rats were challenged 10-14 d after discontinuing either dosage regimen of daily cocaine, the increase in both motor activity and extracellular dopamine was augmented. In general, the increase in extracellular dopamine by an acute cocaine challenge increased over time when rats were challenged between 1 and 22 d after discontinuing daily cocaine. Basal concentrations of extracellular dopamine were determined by measuring the in vivo flux of dopamine across the dialysis membrane, and there was no significant difference at 24 hr or 2 weeks following the last daily injection of saline or cocaine. It is concluded that behavioral sensitization to cocaine is generally associated with an augmentation in extracellular dopamine in the ventral striatum, but that high doses of daily cocaine produce apparent tolerance to the augmentation in extracellular dopamine during the early withdrawal period.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Understanding computers or some of the things you always wanted to know about computers ... but were afraid to ask.

Criteria for computer systems evaluation are changing. No longer can we rely on an evaluation based solely on what the combination of hardware and software does for the user (functional criteria). Significant improvements in software productivity have occurred in recent years as a result of the availability of tools such as relational database management systems and fourth-generation languages. Meanwhile new technologies such as image processing and graphical user interfaces, e.g. MS-Windows and X Window, are coming onstream. Most of these technologies and capabilities require substantially more computing resources than traditional character-based systems. Fortunately, the open systems revolution is creating a more competitive marketplace and computer price/performance ratios are soaring, making the additional computing resources readily available at reasonable prices. But the opportunities of the future will not be for everyone. They will exist only for those medical record practitioners who recognize that a shift away from purely functional evaluation is necessary. Those that make the shift successfully will not become computer technicians, but they will understand the few technical criteria that are truly essential in systems evaluation. They will, in short, apply the 80/20 principle successfully to make future system selections. Medical record professionals must take steps to upgrade their computer system knowledge in order to accommodate the needs of technical criteria evaluation. For the active practitioner this means taking the time to learn from the many sources available in print, educational programs, and knowledgeable persons. Students should seek out courses that will give them a balanced view of the computer sciences, without being overloaded with specifics. AMRA should look for ways to augment the computer sciences requirements in the student's curriculum. Development of study tracks that concentrate on combining standard curricula with computer science would both create a new breed of practitioner and expand the horizons of the profession. The medical record profession must actively work to keep pace with the ever-changing information management environment in order to maintain its position of healthcare information management leadership.

Computer User Training↗