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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 379 records · Page 21Linked to original sources

Patient assessment of a combined medical and nursing preparation to cytotoxic chemotherapy.

At Auckland hospital there is a combined medical and nursing preparation for patients receiving cytotoxic chemotherapy. The aim of the current study was to assess whether patients felt that this combined approach had prepared them adequately for chemotherapy. Patients were asked to complete three questionnaires anonymously at different times in their treatment programme: immediately prior to chemotherapy, after three cycles of chemotherapy and 2 months after completion of chemotherapy. A high level of satisfaction with the programme was demonstrated: 68% of patients thought the orientation programme had prepared them "very well", 32% "adequately" and none "poorly" for their chemotherapy. Separate interviews with medical and nursing staff were thought a "good idea" by 86% of patients and only 1 of 100 medical and 100 nursing interviews was assessed as "not worthwhile". This study suggests that a combined medical and nursing preparation is a worthwhile practice in preparing patients for cytotoxic chemotherapy.

Adult↗

The colour cognition of children.

It is well known that young children have great difficulty in stating the appropriate colour name when presented with a colour stimulus, even though they may be effective at matching one colour stimulus with another and possess a good vocabulary of colour terms. The present studies demonstrate a further, but distinct, impairment in dealing with coloured stimuli. Three- to four-year-old children were given the task of distinguishing an appropriately coloured option from one with an inappropriate colour. Despite displaying a preference for the appropriate colour over the inappropriate one, children found the task very difficult. In contrast, they succeeded on the task more frequently when the alternatives were presented verbally, rather than in terms of two pictures. We discuss the results within a theoretical framework which distinguishes the access to object-colour knowledge from colour naming. The model makes divisions within the mental templates required for object matching. In particular, colour detail is functionally separated from shape detail and appears to be represented in more than one code.

Child, Preschool↗

Inter-rater reliability of a refined index of melancholia: the CORE system.

We report an inter-rater reliability study of the modified 18-item, sign-based CORE index of melancholia, undertaken on 205 ratings of 35 patients by five clinical research psychiatrists. Inter-rater agreement about the presence or absence of individual items was slight to moderate when examined by the kappa coefficient, but moderate to high when examined by the intraclass correlation statistic. For total CORE scores, perhaps the most important application of the index of melancholia, high levels of intraclass correlation coefficients (ranging 0.79 to 0.90 across the varying rater dyads) were established. When a single cut-off score (of 7/8) was used to allocate patients to either a 'melancholic' or 'non-melancholic' class, only moderate agreement was established between raters in such 'class' assignments--a limitation which can be redressed by imposing a 'probable/possible melancholia' band of scores.

Depressive Disorder↗

Exclusion of close linkage of bipolar disorder to the dopamine D3 receptor gene in nine Australian pedigrees.

The recently cloned dopamine D3 receptor (DRD3) gene is of potential relevance to the aetiology of bipolar disorder because of an almost exclusive expression in limbic tissue, the region of the brain putatively responsible for control of emotion. We therefore aimed to determine whether bipolar disorder in nine pedigrees (with 171 members) was linked to this receptor gene, which has been mapped to chromosomal region 3q 13.3. Linkage of bipolar disorder and recurrent depression to the DRD3 gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness (ranging from bipolar I alone to all affective disorders). Close linkage to the DRD3 gene was strongly excluded using each model and definition, and these conclusions persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis.

Adolescent↗

Psychomotor disturbance in depression: defining the constructs.

Four hundred and thirteen depressed patients were rated on eighteen signs of psychomotor disturbance, and the data examined by factor analyses. A three-factor solution was favoured. In addition to 'retardation' and 'agitation' dimensions (whose derived factor scores suggested independence of those two dimensions), a third 'non-interactive' dimension was evident--with derived factor scores correlating significantly with both the retardation and agitation dimensions. Thus, a 'trunk and branch' analogy was suggested for construing psychomotor disturbance, with a truncal 'psychic' component arborising into retardation and agitation 'motoric' expressions. Higher scores on all three factors were significantly linked with features weighted more to the melancholic 'type' of depression.

Adjustment Disorders↗

Specificity of interpersonal sensitivity to non-melancholic depression.

Scores of 69 remitted depressed patients were compared to control subjects on the Interpersonal Sensitivity Measure (IPSM). The patients were categorised into melancholic and non-melancholic sub-groups according to DSM-III criteria. Differences between the depressives and controls were detected but were principally the result of high IPSM scores being returned by the non-melancholic depressives. Melancholic depressives did not differ from the controls in their IPSM scores, supporting the proposition that this depressive sub-type is not associated with a vulnerable personality style.

Adult↗

Phenoxyethanol is effective topical therapy of gram-negative cellulitis in neutropenic patients.

In neutropenic patients cellulitis caused by Gram-negative organisms may prove difficult to control and cause considerable tissue damage. Phenoxyethanol has activity against a range of bacteria, including Pseudomonas aeruginosa, and is absorbed by intact skin. Three severely neutropenic patients are described in whom cellulitis failed to respond to appropriate intravenous antibiotics. However the topical application of phenoxyethanol solution gave prompt local control. This cheap and nontoxic agent may give dramatic improvement in this difficult clinical situation.

Administration, Topical↗

Lessons from a mood disorders unit.

Specialist treatment centres, such as the Mood Disorders Unit (MDU) at Prince Henry Hospital, Sydney, have developed in response to the high prevalence of mood disorders and their frequent persistence and treatment resistance. The MDU's assessment and treatment of patients from a state-wide catchment area and its teaching and research effectiveness are reviewed. Of 479 patients assessed between 1985 and 1989, there were 304 with primary depressive disorders, of whom 154 were followed up by clinical assessment at 52 weeks and 231 by telephone interview at 3 1/2 years. At intake, 59% were tertiary referral patients and 88% were from outside the local area. Two-thirds were recovered 3 1/2 years later, despite the disorders having been generally severe and protracted. Treatment modality was associated primarily with diagnosis, but also with age and somewhat with the patient's personality and consultant psychiatrists' preferences. No consistent predictors of outcome were discerned. Specialist tertiary referral centres, such as the MDU, contribute significantly to treatment success, especially of difficult cases, and enrich teaching and research.

Adjustment Disorders↗

Clustering of modified nucleotides at the functional center of bacterial ribosomal RNA.

An aryl trifluoromethyl diazirine photoreactive derivative was attached to the 2-thiocytidine residue at position 32 of tRNA(IArg) and this derivatized tRNA was bound to Escherichia coli 70S ribosomes. After irradiation at 350 nm the site of cross-linking to the 16S RNA was analyzed by our standard procedures and found to lie within the secondary structural element comprising bases 956-983; this region contains two modified nucleotides at positions 966 and 967. Similarly, an aryl azido photoreactive derivative was attached to the phenylalanine residue of Phe-tRNA(Phe), and the derivatized aminoacyl tRNA was bound to the ribosome either at the A- or the P-site. In both cases, after irradiation at 250 nm, the cross-link site was localized to position 2439 of the 23S RNA; in the secondary structure of the latter the neighboring nucleotide 2442 is base-paired to a modified nucleotide at position 2069. Taken together with other cross-linking data, these results now directly implicate a total of 27 out of the 29 modified nucleotides in E. coli 16S and 23S RNA as lying within or close to the functional center of the ribosome.

Azirines↗

Prognosis of depression in the elderly. A comparison with younger patients.

The prognosis of depression in the elderly was investigated in a mixed-age sample of 242 consecutive referrals, with DSM-III defined unipolar major depressive episode, to a specialist unit for mood disorders. Subjects were followed up at about 1 and 3.8 years. There was no significant difference in outcome between younger (under 40 years), middle aged (40-59 years) and older (60 years or more) depressed patients. For the 61 elderly subjects with depression, prognosis improved with time, with 25% having a lasting recovery at the first and 41% at the second follow-up. Early onset, recurrence, and poor premorbid personality were associated with a worse prognosis. Three (5%) elderly depressives had committed suicide and seven (11%) had died from natural causes by the second follow-up. Despite some methodological limitations, our findings suggest a more optimistic outlook and the need for longer, more assertive treatment for elderly, depressed patients.

Adolescent↗

Chlorpromazine turns forty.

It is difficult for the contemporary psychiatrist to comprehend the impact that the introduction of chlorpromazine had on psychiatric practice in the early 1950s. With potent psychotropic medications largely taken for granted, our awareness of the limitations of these agents blinds us to the therapeutic revolution which they introduced.

Chlorpromazine↗

The genetics of bipolar disorder.

Growing interest in the application of molecular biological techniques to psychiatric disorders has reinvigorated interest in the genetics of the psychoses. It is therefore timely to review the current state of knowledge of the genetics of bipolar disorder. Family, twin and adoption studies are all consistent in confirming the strongly heritable nature of this condition. As segregation analyses have been unable to determine the mode of transmission of bipolar disorder, ongoing linkage analyses using DNA markers will be crucial in determining whether this condition is due to a single major gene, a small number of genes, or multifactorial polygenic inheritance.

Adoption↗

Methylation sites in Escherichia coli ribosomal RNA: localization and identification of four new sites of methylation in 23S rRNA.

Four previously undetermined sites of methylation are mapped in Escherichia coli 23S rRNA employing a novel combination of methods. First, using a double-isotope approach, the total number of methyl groups in 23S rRNA was determined to be 14.9 +/- 1.6. Second, hybridization of methyl-labeled rRNA to complementary DNA restriction fragments and PAGE analysis were used to purify RNA-DNA heteroduplexes and to quantify methyl groups within specific 23S rRNA fragments. Third, the methylated nucleosides in these fragments were identified and quantified using HPLC, confirming the presence of 14 methylation sites in 23S rRNA, four more than had been previously identified. In contrast, a similar set of analyses conducted on 16S rRNA gave evidence for 10 sites of methylation, at all approximate locations consistent with published 16S methylated nucleoside identities and locations. Selected regions of the 23S rRNA molecule containing previously unidentified methylated nucleosides were released by site-directed cleavage with ribonuclease H and isolated by PAGE. Sites of methylation within the RNA fragments were determined by classical oligonucleotide analyses. The four newly identified methylation sites in 23S rRNA are m2G-1835, m5C-1962, m6A-2503, and m2G at one of positions 2445-2447. Together with previously described sites of modification, these new sites form a group that is clustered in a current model for the three-dimensional organization of the 23S rRNA in the 50S ribosomal subunit, at a locus congruent with nucleotides previously implicated in ribosomal function.

Base Sequence↗

Protonation states of the catalytic intermediates of cytochrome c oxidase.

Protonation changes accompanying conversion of oxidised (O state) cytochrome c oxidase to the 2-electron-reduced P state, and 3-electron-reduced F state at pH 8.0 have been measured. It was found that 2 and 3 protons, respectively, were taken up. The fourth proton required for the reduction of O2 to H2O must therefore be consumed in the remaining F----O portion of the catalytic cycle.

Animals↗

How are tRNAs and mRNA arranged in the ribosome? An attempt to correlate the stereochemistry of the tRNA-mRNA interaction with constraints imposed by the ribosomal topography.

Two tRNA molecules at the ribosomal A- and P-sites, with a relatively small angle between the planes of the L-shaped molecules, can be arranged in two mutually exclusive orientations. In one (the 'R'-configuration), the T-loop of the A-site tRNA faces the D-loop of the P-site tRNA, whereas in the other (the 'S'-configuration) the D-loop of the A-site tRNA faces the T-loop of the P-site tRNA. A number of stereochemical arguments, based on the crystal structure of 'free' tRNA, favour the R-configuration. In the ribosome, the CCA-ends of the tRNA molecules are 'fixed' at the base of the central protuberance (the peptidyl transferase centre) of the 50S subunit, and the anticodon loops lie in the neck region (the decoding site) of the 30S subunit. The translocation step is essentially a rotational movement of the tRNA from the A- to the P-site, and there is convincing evidence that the A-site must be located nearest to the L7/L12 protuberance of the 50S subunit. The mRNA in the two codon-anticodon duplexes lies on the 'inside' of the 'elbows' of the tRNA molecules (in both the S-type and R-type configurations), and runs up between the two molecules from the A- to the P-site in the 3' to 5'-direction. These considerations have the consequence that in the S-configuration the mRNA in the codon-anticodon duplexes is directed towards the 50S subunit, whereas in the R-configuration it is directed towards the 30S subunit. The results of site-directed cross-linking experiments, in particular cross-links to mRNA at positions within or very close to the codons interacting with A- or P-site tRNA, favour the latter situation. This conclusion is in direct contradiction to other current models for the arrangement of mRNA and tRNA on the ribosome.

Cross-Linking Reagents↗

Rates of cyanide binding to the catalytic intermediates of mammalian cytochrome c oxidase, and the effects of cytochrome c and poly(L-lysine).

Rate constants of cyanide binding to 'fast' oxidase have been measured in the fully-oxidised (O), peroxy (P) and ferryl (F) states at pH 8.0. Values of 2.2, 8 and 10 M-1 s-1, respectively, were obtained. Thus, none of these states appears to exhibit a rate that would identify it as the species responsible for the extremely rapid cyanide binding observed during turnover. On the other hand, with 'oxidised' enzyme as prepared, containing a very small fraction of one-electron-reduced (E state) oxidase, a corresponding fraction of enzyme exhibited spectral changes consistent with cyanide binding with a rate constant in excess of 10(4) M-1 s-1. Evidence is presented suggesting that mediation of electron transfer from one-electron-reduced, cyanide-liganded enzyme to free, ferric oxidase, rather than a global protein conformational change of the enzyme, is responsible for the greatly enhanced cyanide binding rates seen in the presence of cytochrome c or poly(L-lysine). Inter-oxidase electron exchange in 'oxidised' enzyme can result in a complicated dependence of the binding rate on cyanide concentration. We have demonstrated that this may give rise to a saturation of the rate of cyanide binding.

Animals↗