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Biomedical subjects

J Proudfoot

Publications and source records attributed to J Proudfoot.

At least 19 recordsLinked to original sources
PubMed2006

The effectiveness of computerized cognitive behavioural therapy in routine care.

OBJECTIVES AND DESIGN: The efficacy of a Computerized Cognitive Behavioural Therapy (CCBT) package, Beating the Blues, has been demonstrated in a large randomized controlled trial. The current study tests the generalizability of this finding in a naturalistic non-randomized trial. METHOD: 219 patients with anxiety and/or depression were recruited to receive CCBT in routine care. The Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) and Work and Social Adjustment scale (WSA) were administered pre-treatment, immediately on completing treatment and at 6 months post-treatment. Single-item self-report measures of anxiety and depression were also collected during each treatment session. RESULTS: Completer and intention-to-treat analysis demonstrated statistically and clinically significant improvements on the CORE-OM, WSA and in self-reported anxiety and depression. Intention-to-treat analysis indicated an average 0.29-point drop on the CORE-OM, equating to an uncontrolled pre-post effect size of 0.50. Research completers achieved an average 0.61-point drop equating to an uncontrolled pre-post size of 1.00 on the same measure. Where data was available (18%), these benefits were maintained at week 32 (6 months follow-up). CONCLUSION: CCBT can be an effective first line tool within a stepped care framework for the management of common mental health problems.

Adult↗
PubMed2003

Computerized, interactive, multimedia cognitive-behavioural program for anxiety and depression in general practice.

BACKGROUND: Cognitive-behavioural therapy (CBT) brings about significant clinical improvement in anxiety and depression, but therapists are in short supply. We report the first phase of a randomized controlled trial of an interactive multimedia program of cognitive-behavioural techniques, Beating the Blues (BtB), in the treatment of patients in general practice with anxiety, depression or mixed anxiety/depression. METHOD: One hundred and sixty-seven adults suffering from anxiety and/or depression and not receiving any form of psychological treatment or counselling were randomly allocated to receive, with or without medication, BtB or treatment as usual (TAU). Measures were taken on five occasions: prior to treatment, 2 months later, and at 1, 3 and 6 months follow-up using the Beck Depression Inventory, Beck Anxiety Inventory and Work and Social Adjustment Scale. RESULTS: Patients who received BtB showed significantly greater improvement in depression and anxiety compared to TAU by the end of treatment (2 months) and to 6 months follow-up. Symptom reduction was paralleled by improvement in work and social adjustment. There were no interactions of BtB with concomitant pharmacotherapy or duration of illness, but evidence, on the Beck Anxiety Inventory only, of interaction with primary care practice. Importantly, there was no interaction between the effects of BtB and baseline severity of depression, from which we conclude that the effects of the computer program are independent of starting level of depression. CONCLUSIONS: These results demonstrate that computerized interactive multimedia cognitive-behavioural techniques under minimal clinical supervision can bring about improvements in depression and anxiety, as well as in work and social adjustment, with and without pharmacotherapy and in patients with pre-treatment illness of durations greater or less than 6 months. Thus, our results indicate that wider dissemination of cognitive-behavioural techniques is possible for patients suffering from anxiety and/or depression.

Adult↗
PubMed2001

Establishment of assisted reproduction technologies in female and male African wild dogs (Lycaon pictus).

Transrectal ultrasonography, electroejaculation and cryopreservation of spermatozoa were applied to the African wild dog (Lycaon pictus) to establish non-invasive protocols for assessing the reproductive health of one of the most endangered African canids. Transrectal ultrasonography was performed on immobilized male (n = 2) and female (n = 5) captive wild dogs. The testes and epididymides of the male dogs were imaged transcutaneously, followed by electrostimulation and cryopreservation of spermatozoa. The sonomorphology of the female and male urogenital tracts was characterized. In females, the vagina, cervix, non-pregnant uterus and ovary were imaged and the reproductive health of each female was evaluated. The sonographic assessment helped to identify one pyometra and extensive abdominal fat deposits in two other individuals in which pyometra had been suspected. Images of the adrenal glands showed differences in size among individuals of the same breeding group. Whether these differences were related to the dominance hierarchy remains to be determined. In males, visualization of the prostate gland, testis and epididymis indicated sexual maturity. Three ejaculatory fractions (1.0, 1.5 and 0.5 ml, with 50, 95 and 95% motility, respectively; 1.125 x 10(8) spermatozoa per ejaculate) were collected from one male. The motility of each of these fractions after thawing was 0, 30 and 40%, respectively. Electrostimulation of the second male, in which a cystic structure in a testis had been identified by sonography, resulted in an aspermic ejaculate (0.5 and 1.0 ml). These technologies provided basic data on reproduction in female and male African wild dogs and were an efficient way to evaluate reproductive health.

Adrenal Glands↗
PubMed2000

Mechanisms of transport and structure-permeability relationship of sulfasalazine and its analogs in Caco-2 cell monolayers.

PURPOSE: To investigate the mechanisms involved in transport of sulfasalazine in Caco-2 cells. METHODS: Permeability coefficients of sulfasalazine and its analogs across Caco-2 cell monolayers were measured as a function of direction of transport, energy and concentration dependence, and in the presence of inhibitors of various cellular efflux pumps and transporters. RESULTS: Permeability coefficients of sulfasalazine across Caco-2 cell monolayers were approximately 342-, 261-, and 176-fold higher from basolateral to apical direction (BL-->AP) than from apical to basolateral direction (AP-->BL) at 100, 200, and 500 microM, respectively. Carrier permeability coefficient, non-saturable membrane permeability coefficient, and Michaelis constant were estimated to be 1.4x10(-5) cm/s, 1.9x10(-8) cm/s, and 369 microM, respectively. The efflux of sulfasalazine was completely blocked at 4 degrees C and in the presence of an uncoupler of oxidative phosphorylation. Using cellular efflux inhibitors, the permeability of sulfasalazine was shown to depend on multidrug resistance-associated protein and anion sensitive transport mechanisms. Structure-permeability studies showed that the affinity of sulfasalazine for the cellular efflux pumps and transporters in Caco-2 cells depended strongly on the carboxylic acid functional group. CONCLUSIONS: The permeability of sulfasalazine across Caco-2 cell monolayer is very low due to its strong interaction with multiple cellular efflux pumps and transporters. This may partially explain its low absorption in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin.

Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity.

Antioxidants↗
PubMed1999

Measurement of urinary F(2)-isoprostanes as markers of in vivo lipid peroxidation-A comparison of enzyme immunoassay with gas chromatography/mass spectrometry.

This study aimed at comparing the two most commonly utilized methods for measuring urinary F(2)-isoprostanes, currently considered one of the best available markers of in vivo lipid peroxidation. The F(2)-isoprostanes were measured in 24-h urine samples from 14 male subjects using electron capture negative ionization gas chromatography-mass spectrometry (ECNI-GCMS) with 8-iso-PGF(2alpha)-d(4) as an internal standard and compared with levels obtained using an enzyme immunoassay (EIA, 8-iso-PGF(2alpha) kit, Cayman Chemical Co.). The methods were compared using Pearson correlation coefficients, and Bland-Altman plots were constructed for the difference in F(2)-isoprostane against the average F(2)-isoprostane measured by either method. Weighted least-products regression was used to determine fixed bias (where there is a consistent difference between the methods) and proportional bias (where one method gives values higher or lower than the other method by an amount proportional to the size of the measurement). The correlation between F(2)-isoprostane levels obtained using EIA and GCMS methods, although significant, was poor (r = 0.628, P < 0.02). Comparison of the methods using the Bland-Altman analysis showed that there were wide limits of agreement between the two methods with only 28% of the values falling within the 95% confidence limits for the difference. The GCMS gave higher values with a mean difference of 298.1 pM (636.6, -40.2; P = 0.079), and a near significant linear association between the differences and the mean F(2)-isoprostane level (r = -0.559, P = 0.05). Weighted least-product regression analysis confirmed the presence of both significant fixed and proportional bias with the EIA giving lower levels of F(2)-isoprostanes at low concentrations and higher levels at higher concentrations. The cross-reactivity in the EIA of 8-iso-15(R)-PGF(2alpha) and 9beta-PGF(2alpha) which coelute with the F(2)-isoprostane peak measured by GCMS was very low, 0.2 and 0.1%, respectively. The proportional bias observed between the methods may in part be due to differences in the relative amounts of 8-iso-15(R)-PGF(2alpha), 9beta-PGF(2alpha), and 8-iso-PGF(2alpha) with increasing lipid peroxidation. This study shows that the measurements of F(2)-isoprostanes by EIA and GCMS are not equivalent. Therefore, comparison of levels derived using a GCMS method which estimates concentration from a peak encompassing a number of F(2)-isoprostane isomers, and levels derived from enzyme immunoassay measuring a specific isoprostane, may be inappropriate.

Adult↗
PubMed1999

Ligands for the tyrosine kinase p56lck SH2 domain: discovery of potent dipeptide derivatives with monocharged, nonhydrolyzable phosphate replacements.

p56lck is a member of the src family of tyrosine kinases. Through modular binding units called SH2 domains, p56lck promotes phosphotyrosine-dependent protein-protein interactions and plays a critical role in signal transduction events that lead to T-cell activation. Starting from the phosphorylated dipeptide (2), a high-affinity ligand for the p56lck SH2 domain, we have designed novel dipeptides that contain monocharged, nonhydrolyzable phosphate group replacements and bind to the protein with KD's in the low micromolar range. Replacement of the phosphate group in phosphotyrosine-containing sequences by a (R/S)-hydroxyacetic (compound 8) or an oxamic acid (compound 10) moiety leads to hydrolytically stable, monocharged ligands, with 83- and 233-fold decreases in potency, respectively. This loss in binding affinity can be partially compensated for by incorporating large lipophilic groups at the inhibitor N-terminus. These groups provide up to 13-fold increases in potency depending on the nature of the phosphate replacement. The discovery of potent (2-3 microM), hydrolytically stable dipeptide derivatives, bearing only two charges at physiological pH, represents a significant step toward the discovery of compounds with cellular activity and the development of novel therapeutics for conditions associated with undesired T-cell proliferation.

Crystallography, X-Ray↗
PubMed1999

Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain.

Src homology-2 (SH2) domains are noncatalytic motifs containing approximately 100 amino acid residues that are involved in intracellular signal transduction. The phosphotyrosine-containing tetrapeptide Ac-pYEEI binds to the SH2 domain of p56lck (Lck) with an affinity of 0.1 microM. Starting from Ac-pYEEI, we have designed potent antagonists of the Lck SH2 domain which are reduced in peptidic character and in which the three carboxyl groups have been eliminated. The two C-terminal amino acids (EI) have been replaced by benzylamine derivatives and the pY + 1 glutamic acid has been substituted with leucine. The best C-terminal fragment identified, (S)-1-(4-isopropylphenyl)ethylamine, binds to the Lck SH2 domain better than the C-terminal dipeptide EI. Molecular modeling suggests that the substituents at the 4-position of the phenyl ring occupy the pY + 3 lipophilic pocket in the SH2 domain originally occupied by the isoleucine side chain. This new series of phosphotyrosine-containing dipeptides binds to the Lck SH2 domain with potencies comparable to that of tetrapeptide 1.

Binding, Competitive↗
PubMed1999

Psychological training improves mental health and job-finding among unemployed people.

The negative psychological effects of unemployment are well documented: lowered self-esteem and confidence, social isolation, anxiety, depression, reduced life satisfaction, hopelessness about the future. Further, it has been established that these effects often prevent re-employment. The need for interventions to help unemployed people to minimise such psychological effects is clearly warranted, yet little psychological assistance is usually given. This paper describes a psychological intervention based on cognitive behavioural therapy (CBT), the principles of which have been successfully applied through individual psychotherapy to several psychiatric disorders. We adapted these principles to create a group-training programme for a non-psychiatric group--long term (>12 months) unemployed. The results demonstrated that significantly more of the CBT group than the control group improved on measures of mental health, as well as on success in job-finding: four months after the completion of training 34% of the CBT group c.f. 12% of the control group had found full-time work. Taking part-time and temporary work into account, these figures increased to 49% (CBT group) and 28% (control group), indicating the value of psychological interventions in reducing the negative psychological effects of unemployment, and helping the unemployed find jobs.

Adult↗
PubMed1997

Effect of cognitive-behavioural training on job-finding among long-term unemployed people.

BACKGROUND: The principles of cognitive-behavioural therapy (CBT) have been applied successfully through individual psychotherapy to several psychiatric disorders. We adapted these principles to create a group--training programme for a non-psychiatric group-long-term (> 12 months) unemployed people. The aim was to investigate the effects of the programme on measures of mental health, job-seeking, and job-finding. METHODS: 289 volunteers (of standard occupational classification professional groups) were randomly assigned to a CBT or control programme, matched for all variables other than specific content, that emphasised social support. 244 (134 CBT, 110 control) people started the programmes and 199 (109 CBT, 90 control) completed the whole 7 weeks of weekly 3 h sessions (including three CBT, seven control participants who withdrew because they obtained employment or full-time training). Questionnaires completed before training, on completion, and 3-4 months later (follow-up data available for 94 CBT, 89 control) assessed mental health, job-seeking activities, and success in job-finding. Analyses were based on those who completed the programmes. Participants were not aware that two interventions were being used. Investigators were aware of group allocation, but were accompanied in all programmes by co-trainers who were non-investigators. FINDINGS: Before training, 80 (59%) CBT-group participants and 59 (54%) controls scored 5 or more on the general health questionnaire (GHQ; taken to define psychiatric caseness). After training, 29 (21%) and 25 (23%), respectively, scored 5 or more (p < 0.001 for both decreases). Improvements in mean scores with training on the GHQ (between-group difference 3.91, p = 0.05) and in other measures of mental health were significantly greater in the CBT group than in the control group. There were no significant differences between the groups in job-seeking activity during or after training, but significantly more of the CBT group than of the control group had been successful in finding full-time work (38 [34%] vs 13 [13%], p < 0.001), by 4 months after completion of training. INTERPRETATION: These results suggest that group CBT training can improve mental health and produce tangible benefits in job-finding. Application of CBT among the unemployed is likely to benefit both individuals and society in general.

Adult↗
PubMed1995

Mangostin inhibits the oxidative modification of human low density lipoprotein.

The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. We investigated the possible antioxidant effects of mangostin, isolated from Garcinia mangostana, on metal ion dependent (Cu2+) and independent (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the lagtime to both metal ion dependent and independent oxidation of LDL in a dose dependent manner over 5 to 50 microM as monitored by the formation of conjugated dienes at 234 nm (P < 0.001). There was no significant effect of mangostin on the rate at which conjugated dienes were formed in the uninhibited phase of oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL were measured 4 and 24 hours after oxidation with 5 microM Cu2+ in the presence or absence of 50 microM or 100 microM mangostin. We observed an inhibition of TBARS formation with 100 microM mangostin at 4 hours (P = 0.027) but not at 24 hours (P = 0.163). Similar results were observed in the presence of 50 microM mangostin. Mangostin, at 100 microM, retarded the relative electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+ induced oxidation. Mangostin (100 microM) significantly inhibited the consumption of alpha-tocopherol in the LDL during Cu2+ initiated oxidation over a 75 minute period (P < 0.001). From these results, we conclude that mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in this in vitro system.

Amidines↗
PubMed1995

Analgesia, anesthesia, and conscious sedation.

Providing sedation and analgesia is an integral part of emergency care for children. To become facile at pediatric pain control and sedation, clinicians must develop expertise regarding proper monitoring, drugs and doses, potential side effects, and strategies to select the best agent for a given procedure and clinical setting. Currently available agents, methods, and monitoring guidelines are reviewed with an emphasis on conscious sedation.

Analgesia↗
PubMed1991

A novel dipyridodiazepinone inhibitor of HIV-1 reverse transcriptase acts through a nonsubstrate binding site.

A novel dipyridodiazepinone, 6,11-dihydro-11-cyclopropyl-4-methyldipyrido[2,3-b:2',3'-e]- [1,4]diazepin-6-one (BI-RG-587), is a selective noncompetitive inhibitor of HIV-1 reverse transcriptase (RT-1). An azido photoaffinity analogue of BI-RG-587 was synthesized and found to irreversibly inhibit the enzyme upon UV irradiation. BI-RG-587 and close structural analogues competitively protected RT-1 from inactivation by the photoaffinity label. A thiobenzimidazolone (TIBO) derivative, a nonnucleoside inhibitor of RT-1, also protected the enzyme from photoinactivation, which suggests a common binding site for these compounds. Substrates dGTP, template-primer, and tRNA afforded no protection from enzyme inactivation. A tritiated photoaffinity probe was found to stoichiometrically and selectively label p66 such that 1 mol of probe inactivates 1 mol of RT-1.

Affinity Labels↗
PubMed1991

The effect of lipoproteins on the release of some eicosanoids by stimulated human leukocytes. A possible role in atherogenesis.

Changes in eicosanoid generation have been examined in stimulated human peripheral leukocytes incubated with plasma lipoprotein fractions. Leukocytes (2.5 X 10(7) cells/ml, 90% neutrophils) were incubated with physiological concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL). No release of leukotriene B4 (LTB4) or platelet activating factor (PAF) was noted prior to cell stimulation with either calcium ionophore, opsonized zymosan or FMLP. After stimulation with ionophore, LDL led to a 40% enhancement of LTB4 release compared to control incubations while there was no effect on PAF production. HDL caused a small but not significant increase in LTB4 while VLDL had no effect on the release of LTB4. The formation of the other major lipoxygenase product 5-hydroxy-eicosatetraenoic acid (5-HETE) was decreased by 20% following LDL incubation and by more than 50% after VLDL incubation compared to controls. LTB4 release was also enhanced by 27% after incubation with LDL and stimulation with opsonized zymosan. LDL did not cause any increase in superoxide production by leukocytes stimulated with opsonized zymosan or PMA. PGE2 release was stimulated directly in cells incubated with lipoproteins, particularly LDL and VLDL. Oxidised LDL enhanced LTB4 production to an even greater extent than native LDL. The observed enhancement of LTB4 by LDL is not the result of LDL oxidation during incubation, the provision of arachidonic acid substrate by the lipoprotein nor the uptake of cholesterol by the cell. The effect is most likely associated with the binding of LDL to the cell membrane, since LTB4 enhancement was partially blocked by dextran sulphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid↗
PubMed1988

A reverse-phase liquid chromatographic assay for flavin-containing monooxygenase activity.

A rapid, convenient assay for flavin-containing monooxygenase activity is described. The method is based on direct analysis of quenched incubation mixtures by reverse-phase liquid chromatography, and utilizes p-nitrophenyl-1,3-oxathiolane as the substrate. The synthesis of the substrate and the product are described. The usefulness of p-nitrophenyl-1,3-oxathiolane S-oxide formation as a measure of flavin-containing monooxygenase activity was demonstrated using highly purified and microsomal hog and rat liver flavin-containing monooxygenase. The assay is especially useful for determining stereoselectivity of flavin-containing monooxygenase activity in small amounts of crude tissue preparations.

Animals↗
PubMed1981

Medical reporting in the lay press.

Medical articles appearing in The Age during the first half of 1978 were reviewed. Thirty-three per cent were warnings or reports of adverse reactions, and 27% were reports of "new discoveries". A sample of these two groups of news items was evaluated by panels of doctors and laymen, and also assessed in the light of current literature. Results suggest that medical news items which fall into these categories may be misleading, often contain unsubstantiated claims, and present routine practice as news.

Australia↗
PubMedDate not supplied

Outbreak of salmonellosis in a zoologic collection of lorikeets and lories (Trichoglossus, Lorius, and Eos spp.).

During August 2001, a syndrome characterized by acute lethargy and dyspnea was observed in a population of 45 lorikeets and lories in an open-air zoologic exhibit. The first death occurred on August 10, and within the next 12 days, nine more birds died (22% mortality rate). Hepatomegaly, reddening and congestion of the lungs, and injection of the serosal surface of the intestines were the common gross findings. Histologic changes, including fibrinonecrotic hepatitis and splenitis, bacterial emboli (liver, spleen, lung, kidney, proventriculus), pulmonary congestion and hemorrhage, and enteritis, were indicative of an acute, overwhelming bacterial septicemia. Salmonella typhimurium, with the same antibiogram, was isolated from four birds. Several birds had attacked and killed a snake on July 24, and Salmonella serogroup B (untypeable) was isolated from intestine and kidney samples of a garter snake caught in the open-air exhibit on August 28. Salmonella was also isolated from environmental samples of the exhibit but not from food preparation areas. After antimicrobial therapy, Salmonella spp. was not isolated from the surviving birds. The source of Salmonella in this outbreak remains unknown, but infection either directly or indirectly from snakes in the exhibit is possible. Contact between captive psittacine populations and reptiles should be avoided to prevent the risk of salmonellosis.

Animals↗