Search PubMed⌕ Search

Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 109 records · Page 6Linked to original sources
PubMed2001

Sustained response to open-label venlafaxine in drug-resistant major depression.

The aim of this study was to evaluate the response to venlafaxine in patients with treatment-resistant depression during an extension phase of an open-label study of venlafaxine. After completing the initial 8 weeks of the study, patients could continue venlafaxine treatment for an additional period of up to 10 months. Efficacy results are given for 149 patients with treatment-resistant depression. Response was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale (MADRS); 69% were responders after 8 weeks of treatment in the initial study phase, and 73% were responders at their final extension-phase visit. The mean MADRS score was 32.8 before treatment, 12.9 by 8 weeks, and 10.8 at the final extension visit. There was a statistically significant reduction of 2.1 MADRS units from entry into the extension phase to the final extension visit. At extension entry, 36.7% patients were in remission, as defined by a MADRS score of less than 12, whereas at the final extension visit, this had increased to 49%. Improvement in Clinical Global Impressions Scale scores (both patient and physician ratings) was maintained throughout the extension period, with 88% of patients reporting some improvement (75% with "very much" or "much") and 92% of doctors noting some improvement in patients (79% with "very much" or "much") at the last extension visit. The safety profile during the extension phase of the study was similar to that found in the initial phase and in other studies. The most common study events were somnolence (21%), headache (18%), insomnia (16%), sweating (16%), constipation (14%), dry mouth (11%), nausea (10%), and dizziness (10%). Patients with resistant depression that was treated with venlafaxine maintained their response for up to 10 months after an 8-week phase of treatment and showed some evidence of further improvement.

Adult↗
PubMed2001

Detection of subarachnoid haemorrhage with magnetic resonance imaging.

OBJECTIVES: To measure the sensitivity and specificity of five MRI sequences to subarachnoid haemorrhage. METHODS: Forty one patients presenting with histories suspicious of subarachnoid haemorrhage (SAH) were investigated with MRI using T1 weighted, T2 weighted, single shot fast spin echo (express), fluid attenuation inversion recovery (FLAIR), and gradient echo T2* sequences, and also by CT. Lumbar puncture was performed in cases where CT was negative for SAH. Cases were divided into acute (scanned within 4 days of the haemorrhage) and subacute (scanned after 4 days) groups. RESULTS: The gradient echo T2* was the most sensitive sequence, with sensitivities of 94% in the acute phase and 100% in the subacute phase. Next most sensitive was FLAIR with values of 81% and 87% for the acute and subacute phases respectively. Other sequences were considerably less sensitive. CONCLUSIONS: MRI can be used to detect subacute and acute subarachnoid haemorrhage and has significant advantages over CT in the detection of subacute subarachnoid haemorrhage. The most sensitive sequence was the gradient echo T2*.

Adult↗
PubMed2001

Cognitive deficits in depression: possible implications for functional neuropathology.

BACKGROUND: While depression is known to involve a disturbance of mood, movement and cognition, its associated cognitive deficits are frequently viewed as simple epiphenomena of the disorder. AIMS: To review the status of cognitive deficits in depression and their putative neurobiological underpinnings. METHOD: Selective computerised review of the literature examining cognitive deficits in depression and their brain correlates. RESULTS: Recent studies report both mnemonic deficits and the presence of executive impairment--possibly selective for set-shifting tasks--in depression. Many studies suggest that these occur independent of age, depression severity and subtype, task 'difficulty', motivation and response bias: some persist upon clinical 'recovery'. CONCLUSIONS: Mnemonic and executive deficits do no appear to be epiphenomena of depressive disorder. A focus on the interactions between motivation, affect and cognitive function may allow greater understanding of the interplay between key aspects of the dorsal and ventral aspects of the prefrontal cortex in depression.

Aging↗
PubMed2001

Diabetes and risk of fracture: The Blue Mountains Eye Study.

OBJECTIVE: To examine associations between measures of diabetes and risk of fracture in a population-based sample of older Australians. RESEARCH DESIGN AND METHODS: This was a prospective study of 3,654 subjects aged 49 years and older who were residents in the Blue Mountains, west of Sydney, Australia. At baseline, subjects were asked questions about history and treatment of diabetes, and fasting blood samples were taken. Photographs were taken of the retina and lens to grade retinopathy and cataract. Details of fractures (excluding rib and vertebral fractures) were collected by a combination of self-report and medical record searches; all fractures were radiologically confirmed. RESULTS: After 2 years of follow-up, we found that several diabetes-related factors were significantly associated (in multivariate models) with increased risk of all fractures combined, including presence of diabetic retinopathy (adjusted RR 5.4, 95% CI 2.7-10.8), diabetes duration > or = 10 years (3.3, 1.3-8.2), cortical cataract involving > or = 25% of the lens area (2.5, 1.3-4.7), and insulin treatment (5.9, 2.6-13.5). The proximal humerus was the only individual fracture site associated with diabetes. Diabetic retinopathy (10.3, 2.2-48.0), diabetes duration (for > or = 10 years duration; 11.4, 2.4-54.2), and insulin treatment (18.8, 4.0-88.7) were all associated with proximal humerus fracture. CONCLUSIONS: These data suggest a significantly increased risk of fracture associated with diabetic retinopathy, advanced cortical cataract, longer diabetes duration, and insulin treatment. However, there are some shortcomings in this study that may limit these findings.

Aged↗
PubMed2001

Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study.

BACKGROUND: Although efficacy studies suggest equal potency among antidepressant treatments, their effectiveness in clinical practice appears more variable, particularly in that the newer antidepressants may be less effective in either more severe depression or the melancholic subtype of depression. We pursue some factors that may impact the effectiveness of antidepressant treatments in a clinical sample. METHOD: A sample of 182 patients with DSM-IV major depressive disorder was assessed at baseline and 12 months later to establish treatments provided, identify patients who had recovered from the index episode, and quantify likely treatment determinants. Four systems for distinguishing patients with melancholic and non-melancholic depression were examined to assess for differential effects of the antidepressant strategies across those subtypes. RESULTS: Multimodal therapy (commonly, psychotherapy combined with an antidepressant drug) and patients' frequent attribution of recovery to spontaneous improvement made for difficulty in disentangling recovery determinants. After excluding a spontaneous improvement component, electroconvulsive therapy (ECT) and the irreversible monoamine oxidase inhibitors (MAOIs) appeared to be the most effective therapies across the sample, while the reversible inhibitor of monoamine oxidase-A (RIMA) appeared to be the least effective. The distinct gradient of suggested effectiveness of various strategies appeared to be contributed to principally by the varied effectiveness of alternate treatments across the melancholic subtype, whereby ECT, tricyclic antidepressants, and MAOIs were the most effective, and the selective serotonin reuptake inhibitors (SSRIs), RIMAs, and antipsychotic drugs were much less effective. For the nonmelancholic disorders, the effectiveness of SSRIs appeared to be comparable with that of older antidepressants. CONCLUSION: Although most patients received a physical treatment, they commonly judged psychotherapy and spontaneous improvement to be influential in their recovery. Reasons for such attributions are worthy of clarifying studies. Despite patients' concerns about the side effects and stigma of ECT as well as the side effects associated with the older antidepressants, these therapies were rated as more helpful by patients-and were more strongly associated with recovery-than the newer antidepressant drugs. Such overall results are compatible with an earlier study undertaken by us involving an independent sample and retrospective data. The overall gradient is clarified by studying depressive subtypes, allowing an important conclusion. Although the newer and older antidepressant drugs may be of similar effectiveness in nonmelancholic depression, the newer agents appear comparatively inferior for the treatment of melancholia, findings that have clinical implications and perhaps inform us about the pathogenesis of melancholia.

Adult↗
PubMed2001

Susceptibility to illusions and performance on visuospatial tasks in individuals with autism.

The current study follows a recent paper reporting that individuals with autism were just as susceptible to visual illusions as those without autism (Ropar & Mitchell, 1999). The possibility that individual differences may account for the failure to replicate Happe's (1996) findings is explored by presenting a battery of visuospatial tasks thought to measure weak central coherence (embedded figures, block design, Rey complex figure test). Participants with autism were distinguished by relatively good performance on visuospatial tasks, though there was no superiority effect in those with Asperger's syndrome. Performance on the visuospatial battery did not significantly predict susceptibility to illusions in various participant groups, including those with autism and Asperger's syndrome. This suggests that perception of illusions and performance on visuospatial tasks may rely on different mechaisms. The implications for the theory of weak central coherence are discussed.

Autistic Disorder↗
PubMed2001

Cystadenomas of the liver: a spectrum of disease.

OBJECTIVES: To describe the wide variation in presentation of cystadenomas of the liver and to delineate useful tests for diagnosis and effective surgical treatment. DESIGN: A case series. SETTING: A university-affiliated hospital. PATIENTS: Four patients (3 women, 1 man) having cystadenoma of the liver, 2 of whom had associated mesenchymal stroma. MAIN OUTCOME MEASURES: Serum and cyst fluid carcinoembryonic antigen (CEA) and CA19-9 levels, type of surgery, morbidity and recurrence rates. RESULTS: Cyst fluid CEA and CA19-9 levels were elevated. One patient had resection, 2 had complete enucleation and 1 had partial enucleation. There were no deaths. Morbidity included 1 wound infection; there were no biliary fistulas. The patient with partial enucleation had a radiologically confirmed recurrence. CONCLUSIONS: Analysis of cyst fluid CEA and CA19-9 is useful for diagnosis; besides hepatic resection, complete enucleation should be considered as a reasonable treatment for patients with this disease.

Adult↗
PubMed2001

Multimodality MR imaging depiction of hemodynamic changes and cerebral ischemia in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a common and serious neurologic emergent condition. We tested the hypothesis that multimodality MR imaging depicts changes in cerebral blood flow SAH, before any surgical or endovascular intervention, and that the frequency of these changes increases with time after ictus. METHODS: We prospectively examined 37 patients with suspected SAH and three with symptoms of acute stroke but who subsequently had SAH. Routine CT and multimodality MR imaging were performed within 18 h of presentation. Standard MR imaging, diffusion-weighted MR imaging, time-of-flight MR angiography, and dynamic first-pass gadolinium-enhanced MR perfusion imaging were performed. Images were reviewed for abnormalities in cerebral blood flow, ischemia, and infarction. Nine patients did not have SAH at CT and CSF investigations. Of 31 patients with proved SAH, 13 were examined during the acute stage (within 4 d of ictus) and 18, during the subacute stage (4-14 d after ictus). RESULTS: MR imaging showed alteration in cerebral blood flow parameters in 16 of 31 patients before surgery or endovascular treatment. The frequency of blood flow changes and associated complications increased with worsening clinical grade and increasing time after ictus. CONCLUSION: Multimodality MR imaging provides information not available from CT in patients with SAH. MR imaging shows oligemic and ischemic areas in SAH before surgery or endovascular treatment. MR imaging is a simple noninvasive method of assessing cerebral blood flow and its complications in SAH. It can be performed in a clinical environment.

Adult↗
PubMed2000

Effect of apomorphine on motor and cognitive function in melancholic patients: a preliminary report.

Given the many clinical parallels between melancholia and disorders associated with impaired dopaminergic function such as Parkinson's Disease (PD), it has been hypothesised that major depressive disorder, and in particular the psychomotor features of melancholic depression, may also be associated with a hypodopaminergic state. If this is the case, then the use of a dopamine agonist might lead to reversal of both the cognitive and motor impairments seen in these patients. A double-blind, placebo-controlled cross-over design was used to test the effect of apomorphine on motor and cognitive function in seven melancholic subjects (as defined by the CORE instrument) and five control subjects. The testing battery included the following items: finger tapping, rapid alternating movements, verbal fluency, Rey Auditory Verbal Learning Task, digit symbol substitution task and simple and complex reaction times. The independent t-test, after covarying for age, revealed significant impairment in melancholic subjects for the walking task and digit symbol substitution at baseline. Results of the ANCOVA revealed no impact of time or drug condition, either alone or in combination, upon task performance in either group whether assessed separately or jointly. Results of a MANCOVA revealed that apomorphine impaired performance on some cognitive tasks, and that this was seen to a lesser extent in melancholics than control subjects. There was no evidence that the dopamine agonist apomorphine improved cognitive or motor function in subjects with strictly defined melancholia, suggesting that psychomotor retardation is not associated with a hypodopaminergic state. Our conclusions, however, were limited by small sample size; minimal baseline task impairment in depressed compared to control subjects; mild sedation in many subjects during task performance; and lack of serum apomorphine levels.

Aged↗
PubMed2000

Degradation of ribosomal RNA precursors by the exosome.

The yeast exosome is a complex of 3'-->5' exonucleases involved in RNA processing and degradation. All 11 known components of the exosome are required during 3' end processing of the 5.8S rRNA. Here we report that depletion of each of the individual components inhibits the early pre-rRNA cleavages at sites A(0), A(1), A(2)and A(3), reducing the levels of the 32S, 20S, 27SA(2)and 27SA(3)pre-rRNAs. The levels of the 27SB pre-rRNAs were also reduced. Consequently, both the 18S and 25S rRNAs were depleted. Since none of these processing steps involves 3'-->5' exonuclease activities, the requirement for the exosome is probably indirect. Correct assembly of trans -acting factors with the pre-ribosomes may be monitored by a quality control system that inhibits pre-rRNA processing. The exosome itself degrades aberrant pre-rRNAs that arise from such inhibition. Exosome mutants stabilize truncated versions of the 23S, 21S and A(2)-C(2)RNAs, none of which are observed in wild-type cells. The putative helicase Dob1p, which functions as a cofactor for the exosome in pre-rRNA processing, also functions in these pre-rRNA degradation activities.

Hydrolysis↗
PubMed2000

Posttransplant cataract: lessons from kidney-pancreas transplantation.

INTRODUCTION: Cataract is a major cause of visual disturbance after transplantation. Although corticosteroid therapy has been linked with posterior subcapsular cataract, its natural history in the cyclosporine era is not well understood. METHODS: Baseline and regular postoperative slit-lamp biomicroscopy and ophthalmic examinations (n=432) were performed in 108 eyes of simultaneous kidney/pancreas (SPK) recipients (n=54) for up to 10 years after transplantation. Triple therapy immunosuppression of cyclosporine, azathioprine, and prednisolone was used. RESULTS: Cataract was present in 40% of eyes at simultaneous kidney/pancreas associated with duration of diabetes, lower insulin dose, and the use of pretransplant hemodialysis (P<0.05-0.01). Cataract became increasing more common 2 years after simultaneous kidney/pancreas, and lens abnormalities were virtually universal at 6-10 years by slit lamp biomicrosopy. The instantaneous hazard rate for new cataract formation was highest within the first 2 years and remained abnormal for the study duration. Nuclear and posterior subcapsular cataract increased significantly after transplantation (P<0.05) and were the predominant types of cataract presenting late. Risk factors for posttransplant cataract formation included older age and high-dose pulse methylprednisolone dose. Visual acuity was reduced by severity of cataract grade, presence of combined nuclear and subcapsular cataract, retinal hemorrhage and underlying diabetic retinopathy (P<0.05-0.001). Cataract formation imposed significant additional impairment of visual acuity above that of diabetic retinopathy. Cataract surgery was undertaken in 14% of eyes, improving visual acuity from mean decimalized score of 0.28 to 0.43, P<0.01 but did not normalize it to the noncataract level of 0.72. CONCLUSION: Transplantation substantially increases all types of cataract, and is highly prevalent by slit lamp examination. High-risk patients are older and diabetic, and received hemodialysis and pulse corticosteroid therapy. In contrast to older studies using high-dose corticosteroid and azathioprine, the pattern of cataract in the cyclosporine era is different with broader cataract types, a weaker association with corticosteroids and a progressive course. Regular screening of visual acuity and appropriate surgery for posterior subcapsular or severe cataract are recommended.

Adult↗
PubMed2000

Dietary sodium intake and cataract: the Blue Mountains Eye Study.

A population-based cross-sectional study (n = 2,873) was conducted near Sydney, Australia, from January 1992 to January 1994 to assess the relation between dietary sodium intake and risk of cataract. Photographs of subjects' lenses were graded for cortical, nuclear, and posterior subcapsular cataracts. Dietary sodium intake was assessed with a food frequency questionnaire. The study found that higher sodium intakes were associated with greater risk of posterior subcapsular cataract (p for trend = 0.006). The adjusted relative risk was 2.0 (95% confidence interval: 1.2, 3.4) for subjects in the highest versus the lowest quintile of sodium intake. These findings suggest that a high-salt diet may increase the risk of posterior subcapsular cataract.

Aged↗