29 results on '"Norman TR"'
Search Results
2. A double blind placebo controlled randomised pilot study of nocturnal melatonin in tracheostomised patients
- Author
-
Egi, M, Bates, S, Norman, TR, Hart, GK, Bellomo, R, Ibrahim, MG, and Goldsmith, D
- Published
- 2006
Catalog
3. Antidepressant Treatment of Depression in the Elderly: Efficacy and Safety Considerations
- Author
-
Norman, TR and Norman, TR
- Abstract
Depression in the elderly is a significant clinical problem which is likely to endure as an ongoing issue as the cohort of individuals aged over 65years continues to increase as a proportion of the total population. While there are a multiplicity of approaches to the treatment of depression, the mainstay for moderate to severe cases is pharmacotherapy. The majority of extant antidepressants have demonstrated efficacy, at least in short term (6-12weeks) clinical evaluations. There is demonstrable efficacy over and above that of placebo in the majority of clinical trials for most agents. Within the classes of antidepressants there is no difference between individual agents, while between classes differences have not been demonstrated consistently. Thus, there appears to be little to choose between the various agents. However, considerations other than efficacy play a role in the choice of an antidepressant for an individual patient. A systematic review of the efficacy of antidepressant agents based on trials in elderly populations is presented. Factors influencing the choice of a medication over and above efficacy are presented along with a brief review of adverse events of particular concern in elderly patients. A considerable proportion of elderly patients have comorbid medical conditions, which may also influence the choice of agent due to drug-drug interaction considerations. A brief overview of interactions likely to influence medication selection is also canvassed. While there is every reason to be optimistic about outcomes in elderly patients, there are still unanswered questions about antidepressant efficacy in this population: effectiveness in long-term treatment and in the population of so-called ‘old-old’ elderly are principal among them. more...
- Published
- 2021
4. The H163A mutation unravels an oxidized conformation of the SARS-CoV-2 main protease
- Author
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Norman Tran, Sathish Dasari, Sarah A. E. Barwell, Matthew J. McLeod, Subha Kalyaanamoorthy, Todd Holyoak, and Aravindhan Ganesan
- Subjects
Science - Abstract
Abstract The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted Mpro’s susceptibility to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the mechanisms of conformational change and its functional consequences are poorly understood. Here, we present the crystal structure of an Mpro point mutant (H163A) that shows an oxidized conformation with the catalytic cysteine in a disulfide bond. We hypothesize that Mpro adopts this conformation under oxidative stress to protect against over-oxidation. Our metadynamics simulations illustrate a potential mechanism by which H163 modulates this transition and suggest that this equilibrium exists in the wild type enzyme. We show that other point mutations also significantly shift the equilibrium towards this state by altering conformational free energies. Unique avenues of SARS-CoV-2 research can be explored by understanding how H163 modulates this equilibrium. more...
- Published
- 2023
- Full Text
- View/download PDF
5. A substrate-induced gating mechanism is conserved among Gram-positive IgA1 metalloproteases
- Author
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Jasmina S. Redzic, Jeremy Rahkola, Norman Tran, Todd Holyoak, Eunjeong Lee, Antonio Javier Martín-Galiano, Nancy Meyer, Hongjin Zheng, and Elan Eisenmesser
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Cryo-EM reveals the structure of the IgA1 metalloprotease (IgA1P) from the pathogen, G. haemolysans in the absence and presence of IgA substrate, which suggests a conserved gating mechanism for IgA1P enzymes and provides a basis for therapeutic strategies. more...
- Published
- 2022
- Full Text
- View/download PDF
6. Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease
- Author
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Zhiming Wang, Jeremy Rahkola, Jasmina S. Redzic, Ying-Chih Chi, Norman Tran, Todd Holyoak, Hongjin Zheng, Edward Janoff, and Elan Eisenmesser
- Subjects
Science - Abstract
Pathogenic IgA1 metalloproteases block the initial host immune response by cleaving host IgA1. Using cryoEM, the authors here provide structural insights into the substrate recognition mechanism of Streptococcus pneumoniae IgA1 protease, and develop a protease-inhibiting antibody. more...
- Published
- 2020
- Full Text
- View/download PDF
7. Continuation treatment of major depressive disorder: is there a case for duloxetine?
- Author
-
Norman, TR, Olver, JS, Norman, TR, and Olver, JS
- Abstract
Duloxetine is a serotonin-noradrenaline reuptake inhibitor with established efficacy for the short-term treatment of major depressive disorder. Efficacy in continuation treatment (greater than six months of continuous treatment) has been established from both open and placebo-controlled relapse prevention and comparative studies. Seven published studies were available for review and showed that in both younger and older populations (aged more than 65 years) the acute efficacy of duloxetine was maintained for up to one year. Response to treatment was based on accepted criteria for remission of depression and in continuation studies remission rates were greater than 70%. Comparative studies showed that duloxetine was superior to placebo and comparable to paroxetine and escitalopram in relapse prevention. Importantly a study of duloxetine in patients prone to relapse of major depressive disorder showed that the medication was more effective than placebo in this difficult to treat population. Side effects of duloxetine during continuation treatment were predictable on the basis of the known pharmacology of the drug. In particular there were no significant life-threatening events which emerged with continued use of the medication. On the other hand vigilance is required since the data base on which to judge very rare events is limited by the relatively low exposure to the drug. Duloxetine has established both efficacy and safety for continuation treatment but its place as a first-line treatment of relapse prevention requires further experience. In particular further comparative studies against established agents would be useful in deciding the place of duloxetine in therapy. more...
- Published
- 2010
8. Duloxetine in the treatment of generalized anxiety disorder.
- Author
-
Norman, TR, Olver, JS, Norman, TR, and Olver, JS
- Abstract
Duloxetine, a medication with effects on both serotonin and noradrenaline transporter molecules, has recently been approved for the treatment of generalized anxiety disorder. The evidence for its efficacy lies in a limited number of double blind, placebo controlled comparisons. Statistically significant improvements in the Hamilton Anxiety Rating Scale from baseline were demonstrated in all studies at doses of 60 to 120 mg per day. The significance of such changes in terms of clinical improvements compared to placebo is less certain, particularly when the effect size of the change is calculated. In comparative trials with venlafaxine, duloxetine was as effective in providing relief of anxiety symptoms. In addition to improvements in clinical symptoms duloxetine has also been associated with restitution of role function as measured by disability scales. Duloxetine use is associated with nausea, dizziness, dry mouth, constipation, insomnia, somnolence, hyperhidrosis, decreased libido and vomiting. These treatment emergent side effects were generally of mild to moderate severity and were tolerated over time. Using a tapered withdrawal schedule over two weeks in the clinical trials, duloxetine was associated with only a mild withdrawal syndrome in up to about 30% of patients compared to about 17% in placebo treated patients. Duloxetine in doses of up to 200 mg twice daily did not prolong the QTc interval in healthy volunteers. Like other agents with dual neurotransmitter actions duloxetine reduces the symptoms of generalized anxiety disorder in short term treatments. Further evidence for its efficacy and safety in long term treatment is required. more...
- Published
- 2008
9. Mianserin in breast milk [letter]
- Author
-
Buist, A, primary, Norman, TR, additional, and Dennerstein, L, additional
- Published
- 1993
- Full Text
- View/download PDF
10. Pharmacokinetics of nomifensine after a single oral dose [letter].
- Author
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McIntyre, IM, Norman, TR, Burrows, GD, and Maguire, KP
- Published
- 1982
- Full Text
- View/download PDF
11. Determination of nomifensine plasma concentrations: a comparison of radioimmunoassay and gas chromatography.
- Author
-
McIntyre, IM, Norman, TR, Burrows, GD, and Maguire, KP
- Abstract
1 A gas-liquid chromatography (g.l.c.) method for measurement of the antidepressant nomifensine was developed and compared for precision, accuracy, sensitivity and convenience with radioimmunoassay (RIA). 2 No significant difference was found between the two techniques for unconjugated nomifensine (y = 1.07x = 2.7; r = 0.996) or total nomifensine (y = 1.;02x + 0.02; r = 0.999). 3 RIA proved more sensitive than g.l.c. (detection limit of RIA being 1 microgram/l and g.l.c. 5 micrograms/l). 4 RIA was found to be a more convenient technique (up to 50 samples per day with RIA, and 16 samples with g.l.c.). [ABSTRACT FROM AUTHOR] more...
- Published
- 1981
- Full Text
- View/download PDF
12. Metabolism and pharmacokinetics of dothiepin.
- Author
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Maguire, KP, Burrows, GD, Norman, TR, and Scoggins, BA
- Abstract
1 Seven healthy volunteers received a single oral dose of 75 mg dothiepin. Plasma concentrations of dothiepin were measured by gas chromatography-mass fragmentography. 2 The plasma concentrations obtained were fitted to the equation Ct = Ae-a(t-tau) + Be-beta(t-tau) - Ce-ka(t-tau). The mean peak concentration was 47(33-71) microgram/l at 3(2-5) h. Mean estimates were as follows: absorption half life 1.2(0.07- 3.0) h, distribution half-life 2.6(1.1-3.8) h, elimination half-life 22(14-40) h, apparent volume of distribution 45(20-92) l/kg, and oral clearance 1.36(0.88-1.8) l kg-1 h-1. 3 Blood concentrations of dothiepin were measured in comparison in five of the volunteers. The mean blood/plasma ratio was 0.7(0.6-0.8). 4 Plasma and blood concentrations of northiaden and blood concentrations of dothiepin S- oxide, two metabolites of dothiepin, were also measured. Dothiepin S- oxide was the major metabolic reaching a peak level of 81(34-150) microgram/l at 5(4-6) h. In comparison, northiaden reached a peak concentration of only 10 (3-21) microgram/l at 5 (4-9) h. The mean half- life of elimination of dothiepin S-oxide was 19 (13-35) h while that for northiaden was 33 (22-60) h. [ABSTRACT FROM AUTHOR] more...
- Published
- 1981
- Full Text
- View/download PDF
13. Determination of viloxazine in plasma by GLC.
- Author
-
Norman, TR, primary, Burrows, GD, additional, Davies, BM, additional, and Wurm, JM, additional
- Published
- 1979
- Full Text
- View/download PDF
14. Editorial: Role of the serotonergic system in pathology of major depressive disorders.
- Author
-
Norman TR
- Abstract
Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2022
- Full Text
- View/download PDF
15. Duloxetine in the acute and continuation treatment of major depressive disorder.
- Author
-
Bochsler L, Olver JS, and Norman TR
- Subjects
- Antidepressive Agents pharmacology, Clinical Trials as Topic, Duloxetine Hydrochloride, Humans, Thiophenes pharmacology, Antidepressive Agents therapeutic use, Depressive Disorder, Major drug therapy, Thiophenes therapeutic use
- Abstract
Duloxetine is a serotonin-noradrenaline reuptake inhibitor with indications for use in the short term, continuation and maintenance treatment of major depression. Although clinicians currently have access to a range of medications for the treatment of depression, a significant number of patients fail to respond or remit from their illness despite adequate trials of treatment with multiple agents. A developing concept is that antidepressant strategies that combine multiple mechanisms of action may have advantages over agents with single mechanisms (i.e., selective serotonin reuptake inhibitors). As a dual-acting agent, duloxetine offers the promise of advantages in terms of efficacy over selective serotonin reuptake inhibitors while retaining a favorable safety and tolerability profile in comparison to older agents. Likewise, duloxetine is of interest in the treatment of certain conditions commonly seen in conjunction with major depression, particularly anxiety and pain, both of which may respond more favorably to agents that act on both serotonin and noradrenaline neurotransmitter systems. more...
- Published
- 2011
- Full Text
- View/download PDF
16. Continuation treatment of major depressive disorder: is there a case for duloxetine?
- Author
-
Norman TR and Olver JS
- Subjects
- Antidepressive Agents adverse effects, Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Clinical Trials as Topic, Depressive Disorder, Major prevention & control, Duloxetine Hydrochloride, Humans, Thiophenes adverse effects, Thiophenes pharmacology, Depressive Disorder, Major drug therapy, Thiophenes therapeutic use
- Abstract
Duloxetine is a serotonin-noradrenaline reuptake inhibitor with established efficacy for the short-term treatment of major depressive disorder. Efficacy in continuation treatment (greater than six months of continuous treatment) has been established from both open and placebo-controlled relapse prevention and comparative studies. Seven published studies were available for review and showed that in both younger and older populations (aged more than 65 years) the acute efficacy of duloxetine was maintained for up to one year. Response to treatment was based on accepted criteria for remission of depression and in continuation studies remission rates were greater than 70%. Comparative studies showed that duloxetine was superior to placebo and comparable to paroxetine and escitalopram in relapse prevention. Importantly a study of duloxetine in patients prone to relapse of major depressive disorder showed that the medication was more effective than placebo in this difficult to treat population. Side effects of duloxetine during continuation treatment were predictable on the basis of the known pharmacology of the drug. In particular there were no significant life-threatening events which emerged with continued use of the medication. On the other hand vigilance is required since the data base on which to judge very rare events is limited by the relatively low exposure to the drug. Duloxetine has established both efficacy and safety for continuation treatment but its place as a first-line treatment of relapse prevention requires further experience. In particular further comparative studies against established agents would be useful in deciding the place of duloxetine in therapy. more...
- Published
- 2010
- Full Text
- View/download PDF
17. Duloxetine in the treatment of generalized anxiety disorder.
- Author
-
Norman TR and Olver JS
- Abstract
Duloxetine, a medication with effects on both serotonin and noradrenaline transporter molecules, has recently been approved for the treatment of generalized anxiety disorder. The evidence for its efficacy lies in a limited number of double blind, placebo controlled comparisons. Statistically significant improvements in the Hamilton Anxiety Rating Scale from baseline were demonstrated in all studies at doses of 60 to 120 mg per day. The significance of such changes in terms of clinical improvements compared to placebo is less certain, particularly when the effect size of the change is calculated. In comparative trials with venlafaxine, duloxetine was as effective in providing relief of anxiety symptoms. In addition to improvements in clinical symptoms duloxetine has also been associated with restitution of role function as measured by disability scales. Duloxetine use is associated with nausea, dizziness, dry mouth, constipation, insomnia, somnolence, hyperhidrosis, decreased libido and vomiting. These treatment emergent side effects were generally of mild to moderate severity and were tolerated over time. Using a tapered withdrawal schedule over two weeks in the clinical trials, duloxetine was associated with only a mild withdrawal syndrome in up to about 30% of patients compared to about 17% in placebo treated patients. Duloxetine in doses of up to 200 mg twice daily did not prolong the QTc interval in healthy volunteers. Like other agents with dual neurotransmitter actions duloxetine reduces the symptoms of generalized anxiety disorder in short term treatments. Further evidence for its efficacy and safety in long term treatment is required. more...
- Published
- 2008
- Full Text
- View/download PDF
18. Emerging treatments for major depression.
- Author
-
Norman TR and Burrows GD
- Subjects
- Animals, Humans, Antidepressive Agents therapeutic use, Depressive Disorder, Major drug therapy, Psychiatry trends
- Abstract
Antidepressant drugs were introduced into clinical practice in the mid-20th Century. While for the most part they have proven effective for the amelioration of depressive symptoms, they are associated with significant deficiencies. These well-recognized shortcomings have given impetus to the pursuit of new molecules that seek to improve on the efficacy, tolerability and safety of existing medications. The following article reviews several new compounds that may have antidepressant potential. Some are more advanced in development, having undergone clinical trials, whereas the clinical potential of others is yet to be explored. For this latter group of compounds, the antidepressant potential relies on their activity in validated animal models. Agomelatine and duloxetine are in the first category, having shown antidepressant efficacy in clinical trials. The blockade of cortisol secretion continues to be a focus of attention for the development of new antidepressants. Thus, synthesis inhibitors, nonpeptide antagonists of corticotropin-releasing factor and glucocorticoid receptor antagonists show some promise in clinical and preclinical tests. Antagonists of the neuropeptide substance P, vasopressin and neuropeptide Y represent a departure of approach from traditional monoamine receptor-based mechanisms. While the clinical results with one substance P antagonist have led to the cessation of further trials, other molecules are in development. Approaches to treatment based on glutamatergic transmission arose from observations in animal models. The clinical evaluation of such compounds awaits further development. The extent to which new agents can be judged to have met the goals of efficacy, tolerability and safety rely not only acute treatment trials but also on longer-term outcomes and postmarketing surveillance. Whether any of the new agents canvassed here prove to be significantly better than existing agents is clearly a judgement for the future. more...
- Published
- 2007
- Full Text
- View/download PDF
19. Human embryonic stem cells: a resource for in vitro neuroscience research?
- Author
-
Norman TR
- Subjects
- Drug Evaluation, Preclinical ethics, Drug Evaluation, Preclinical trends, Embryonic Stem Cells physiology, Humans, Models, Biological, Neurodegenerative Diseases chemically induced, Neurodegenerative Diseases drug therapy, Neurodegenerative Diseases physiopathology, Neurons physiology, Neuroprotective Agents pharmacology, Neurosciences ethics, Neurosciences legislation & jurisprudence, Neurotoxins antagonists & inhibitors, Drug Evaluation, Preclinical methods, Embryonic Stem Cells drug effects, Neurons drug effects, Neurosciences trends, Neurotoxins toxicity
- Published
- 2006
- Full Text
- View/download PDF
20. A double-blind placebo-controlled randomised pilot study of nocturnal melatonin in tracheostomised patients.
- Author
-
Ibrahim MG, Bellomo R, Hart GK, Norman TR, Goldsmith D, Bates S, and Egi M
- Subjects
- Aged, Double-Blind Method, Dyssomnias etiology, Female, Humans, Male, Middle Aged, Pilot Projects, Antioxidants therapeutic use, Dyssomnias prevention & control, Melatonin therapeutic use, Tracheostomy, Ventilator Weaning
- Abstract
Background and Aim: Patients in the intensive care unit often suffer from lack of sleep at night. We hypothesised that nocturnal melatonin may increase observed nocturnal sleep in tracheostomised patients., Design: Double-blind, randomised, placebo-controlled pilot study., Setting: ICU of a tertiary hospital., Participants: Thirty-two ICU patients with tracheostomy who were not receiving continuous sedation., Methods: We administered either oral melatonin (3mg) or placebo at 20:00. We collected pre- and post-dosage blood samples on Days 1 and 3 to confirm drug delivery. Primary outcome measure was number of hours of observed sleep at night, assessed by the bedside nurse. Secondary outcome measures included comparison of the incidence of agitation, assessed by score on the Riker Sedation-Agitation Scale, and requirement for sedatives or haloperidol to settle agitation., Results: Pre-treatment melatonin levels in the two groups were similarly low: 4.8 pg/mL (95% CI, 2.4-7.5) for melatonin versus 2.4 (95% CI, 1.6-3.2) for placebo (P=0.13). Post-treatment, melatonin levels increased significantly in the melatonin group compared with the placebo group (3543 pg/mL versus 3 pg/mL; P<0.0001). However, subsequent observed nocturnal sleep was similar in the two groups: 240 minutes (range, 75-331.3) for melatonin v 243.4 minutes (range, 0-344.1) for placebo (P=0.98). Observed diurnal sleep was also similar: 138.7 minutes (range, 50-230) with melatonin v 104 minutes (range, 0-485) for placebo (P=0.42). The incidence of agitation was non-significantly higher in the melatonin group (31% v 7%; P=0.11), while the requirement for extra sedation or use of haloperidol was slightly higher in the placebo group (57% versus 46%; P=0.56)., Conclusion: Melatonin is well absorbed, and a standard dose increases blood levels approximately 1000-fold. However, in this pilot assessment, these high levels failed to increase observed nocturnal sleep or induce other observable benefits in tracheostomised ICU patients. more...
- Published
- 2006
21. Effect of sodium valproate on nocturnal melatonin sensitivity to light in healthy volunteers.
- Author
-
Hallam KT, Olver JS, and Norman TR
- Subjects
- Adolescent, Adult, Area Under Curve, Circadian Rhythm physiology, Circadian Rhythm radiation effects, Female, Humans, Male, Photic Stimulation methods, Radioimmunoassay, Valproic Acid blood, Circadian Rhythm drug effects, GABA Agents pharmacology, Light, Melatonin blood, Valproic Acid pharmacology
- Abstract
Sensitivity of the pineal hormone melatonin to bright light at night has been proposed as a putative marker of bipolar affective disorder. Patients with bipolar disorder have a super-sensitive melatonin response to light. No studies have investigated whether super-sensitivity is due to agents used to treat the illness or is associated with the disorder per se. We investigated the effect of valproate on this phenomenon. Melatonin sensitivity to light was determined on two nights in 12 healthy volunteers (5M, 7F). Between testing nights participants received 200 mg of valproate b.d. for 5 days. Valproate significantly decreased the sensitivity of melatonin to light. On the other hand, valproate had no effect on overall melatonin secretion or dim light melatonin onset. The ability of valproate to decrease the sensitivity of melatonin to light may relate to its therapeutic effect in bipolar disorder--an ability to lengthen circadian period similar to that of lithium. more...
- Published
- 2005
- Full Text
- View/download PDF
22. Low doses of lithium carbonate reduce melatonin light sensitivity in healthy volunteers.
- Author
-
Hallam KT, Olver JS, Horgan JE, McGrath C, and Norman TR
- Subjects
- Adult, Area Under Curve, Female, Humans, Male, Melatonin metabolism, Photic Stimulation methods, Photophobia chemically induced, Antimanic Agents administration & dosage, Circadian Rhythm drug effects, Lithium Carbonate administration & dosage, Melatonin adverse effects, Photophobia drug therapy
- Abstract
Sensitivity of the pineal hormone melatonin to bright light at night has been posited as a putative marker of affective disorders. Research demonstrates melatonin supersensitivity to light in bipolar disorder, however the role that lithium carbonate plays in this response is unclear. This study assessed the effect of lithium on nocturnal melatonin secretion and sensitivity to light in healthy adults. Ten participants, tested on two nights, had blood samples drawn between 20:00 and 02:30 hours. On testing nights participants were exposed to 200 lux of light between 24:00 and 01:00 hours. Participants took 250 mg of lithium daily for 5 d between testing nights. The results indicated that lithium had a significant effect on sensitivity to light but not on overall melatonin synthesis. This finding has implications on the true magnitude of the melatonin light response in people with bipolar disorder and may elucidate possible mechanisms of action of lithium. more...
- Published
- 2005
- Full Text
- View/download PDF
23. Brain monoamines and early visual information-processing speed.
- Author
-
Harrison BJ, Olver JS, Norman TR, and Nathan PJ
- Subjects
- Adult, Amino Acids blood, Amino Acids metabolism, Cross-Over Studies, Discrimination, Psychological drug effects, Discrimination, Psychological physiology, Double-Blind Method, Female, Humans, Phenylalanine deficiency, Serotonin metabolism, Tryptophan deficiency, Tyrosine deficiency, Biogenic Monoamines physiology, Brain Chemistry physiology, Visual Perception physiology
- Abstract
Visual inspection time (IT) is a measure of information-processing speed, which correlates reliably with psychometric intelligence. Pharmacological research into IT indicates that manipulation of the cholinergic system modulates performance on the IT task, however the contribution of other neurotransmitters to this modality remains unclear. This study was designed to examine the effects of low brain serotonin and catecholamine availability on IT using the established method of amino-acid precursor depletion. Female participants (n=13) completed three experimental sessions; tryptophan depletion (TD); tyrosine/phenylalanine depletion (TPD); and a balanced control condition (B) in a randomized, double-blind cross-over design. IT assessments were performed at baseline and approx. 5 h post-mixture administration. IT scores were unaffected by either of the treatment conditions. These findings suggest that monoamines, whilst implicated in various forms of cognition are not central to IT, which measures the efficiency of perceptual intake and information-processing speed. more...
- Published
- 2002
- Full Text
- View/download PDF
24. Olanzapine excretion in human breast milk: estimation of infant exposure.
- Author
-
Croke S, Buist A, Hackett LP, Ilett KF, Norman TR, and Burrows GD
- Subjects
- Adult, Antipsychotic Agents blood, Antipsychotic Agents therapeutic use, Benzodiazepines, Depression, Postpartum drug therapy, Depression, Postpartum metabolism, Depression, Postpartum psychology, Female, Humans, Infant, Infant, Newborn, Olanzapine, Pirenzepine blood, Pirenzepine therapeutic use, Psychiatric Status Rating Scales, Antipsychotic Agents pharmacokinetics, Milk, Human metabolism, Pirenzepine analogs & derivatives, Pirenzepine pharmacokinetics
- Abstract
Newer antipsychotic drugs offer significant clinical advantages for the treatment of psychosis. In particular for the treatment of postpartum disorders newer agents may be suited due to their favourable side-effect profiles. Of concern is the passage of the drugs into breast milk and what potential risks this poses for an infant who is breastfed. The excretion of olanzapine into the breast milk of five lactating women with postpartum psychosis was examined in this study. Nine pairs of plasma and breast-milk samples were collected and the concentration of olanzapine determined by high-performance liquid chromatography. Single-point milk-to-plasma ratios were calculated and ranged from 0.2 to 0.84 with a mean of 0.46. The median relative infant dose was 1.6% (range 0-2.5%) of the weight-adjusted maternal dose. During the study period, there were no apparent ill effects on the infant as a consequence of exposure to these doses of olanzapine. As with other antipsychotic drugs this study demonstrates that olanzapine passes into breast milk. The long-term effects of exposure in infants exposed to olanzapine requires further investigation. more...
- Published
- 2002
- Full Text
- View/download PDF
25. Melatonin sensitivity to dim white light in affective disorders.
- Author
-
Nathan PJ, Burrows GD, and Norman TR
- Subjects
- Adolescent, Adult, Aged, Biomarkers blood, Humans, Middle Aged, Mood Disorders blood, Bipolar Disorder blood, Depressive Disorder, Major blood, Light, Melatonin blood, Seasonal Affective Disorder blood
- Abstract
Both dim and bright light has been shown to suppress the nocturnal secretion of the pineal hormone melatonin. Early reports suggests that an abnormal response to light occurs in patients with bipolar affective disorder, where as patients with major depressive disorder respond similarly to controls. It has been suggested that this abnormal sensitivity of the melatonin response to light could be a trait marker of bipolar affective disorder. However reports lack consistency. Hence, we investigated the melatonin suppression by dim light (200 lux) in patients with bipolar affective disorder, seasonal affective disorder and major depressive disorder. Results suggest that a supersensitive melatonin suppression to light in bipolar affective disorder (p < .005), and seasonal affective disorder (p < .05), whereas patients with major depressive disorder display similar suppression to controls. The supersensitivity may be a mechanism where by phase-delayed rhythms, are resynchronised to a new circadian position. Conversely, an abnormality may exist in the pathway from the retina to the suprachiamatic nucleus. more...
- Published
- 1999
- Full Text
- View/download PDF
26. Subsensitive melatonin suppression by dim white light: possible biological marker of panic disorder.
- Author
-
Nathan PJ, Burrows GD, and Norman TR
- Abstract
Light is involved in providing entrainment of circadian rhythms and the suppression of the pineal hormone melatonin. In patients with affective disorders, there have been indications of circadian as well as seasonal variation in illness, which may be reflected in melatonin production. Varying sensitivity to light has been noted within healthy individuals as well as in some patients with affective disorders. Recent evidence suggests that patients with panic disorder may have an altered and phase-delayed melatonin rhythm. The present study examined the nocturnal plasma melatonin rhythm in patients with panic disorder, and also examined their melatonin sensitivity to dim light. The melatonin rhythm was examined in 6 patients with panic disorder and 8 controls. The melatonin sensitivity to dim white light (200 lx) was examined in 8 patients with panic disorder and 63 controls and was compared to that of a group of 7 patients with other anxiety disorders. Patients with panic disorder demonstrated a trend towards higher and delayed peak melatonin levels compared to controls. Patients with panic disorder also had a subsensitive melatonin suppression by dim white light, compared to controls and patients with other anxiety disorders (p<0.005). The phase-delayed circadian rhythm observed in patients with panic disorder may be secondary to the subsensitivity of the melatonin response to light. It is hypothesized that the subsensitivity may be due to abnormal neurotransmitter/receptor systems involved in regulation of melatonin suppression and circadian rhythmicity, and may lead to phase- delayed circadian rhythms. The melatonin subsensitivity to light may be used as a biological marker of panic disorder. more...
- Published
- 1998
- Full Text
- View/download PDF
27. Comparative bioavailability of orally and vaginally administered progesterone.
- Author
-
Norman TR, Morse CA, and Dennerstein L
- Subjects
- Administration, Oral, Adult, Analysis of Variance, Biological Availability, Female, Humans, Osmolar Concentration, Pessaries, Progesterone blood, Progesterone pharmacokinetics, Random Allocation, Progesterone administration & dosage
- Abstract
Objective: To study the pharmacokinetics of progesterone (P) in healthy premenopausal female volunteers to compare the bioavailability of orally or vaginally administered hormone., Design: Subjects were randomly allocated to receive either oral P or a vaginal pessary then crossed over to the alternate preparation 1 month later., Setting: The study was conducted in outpatient setting., Subjects: All subjects were healthy, normal female volunteers who underwent a physical and gynecological examination before the study. None were using oral contraceptives. Ten subjects (mean age 32.6 +/- 7.3 years) entered the study and all completed it., Interventions: Progesterone was administered as 200 mg of micronized hormone or as a pessary containing 400 mg., Main Outcome Measure: Plasma levels of P were measured by radioimmunoassay to test the apriori hypothesis of similar bioavailability., Results: Peak plasma P concentrations attained within 4 hours after oral administration ranged from 8.5 to 70.6 ng/mL, whereas after vaginal administration the peak levels were attained within 8 hours and ranged from 4.4 to 181.1 ng/mL. Considerable interindividual variation was noted. Area under the plasma concentration-time curve for the two formulations was not significantly different (F = 1.09; P greater than 0.1; ANOVA)., Conclusions: The two formulations had similar bioavailability. more...
- Published
- 1991
- Full Text
- View/download PDF
28. Safety of zimeldine in overdose.
- Author
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Judd FK, Norman TR, and Burrows GD
- Subjects
- Adult, Electrocardiography, Female, Humans, Nervous System Diseases chemically induced, Safety, Zimeldine blood, Zimeldine poisoning
- Published
- 1983
- Full Text
- View/download PDF
29. Amitriptyline plasma concentration and clinical response.
- Author
-
Norman TR, Burrows GD, Maguire KP, and Scoggins B
- Subjects
- Amitriptyline therapeutic use, Depression drug therapy, Female, Humans, Male, Amitriptyline blood, Depression blood
- Published
- 1979
- Full Text
- View/download PDF
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