Search PubMed⌕ Search

Biomedical subjects

G Parker

Publications and source records attributed to G Parker.

At least 181 records · Page 10Linked to original sources

Effect of exogenous hyaluronan and hyaluronan oligosaccharides on hyaluronan and aggrecan synthesis and catabolism in adult articular cartilage explants.

The addition of hyaluronan to the culture medium of explant cultures of articular cartilage was shown to suppress the synthesis of hyaluronan and aggrecan, the major proteoglycan present in cartilage, and resulted in a greater proportion of the newly synthesized aggrecan and hyaluronan appearing in the culture medium. This effect of exogenous hyaluronan on aggrecan and hyaluronan synthesis was concentration-dependent and reversible on removal of the glycosaminoglycan from the culture medium. The addition of tetra- and hexasaccharides derived from Streptomyces sp. hyaluronidase digestion of hyaluronan to explant cultures of articular cartilage did not change the rate of synthesis of aggrecan or hyaluronan or their ultimate distribution between tissue and medium. However, the addition of tetra- and hexasaccharides of hyaluronan resulted in a decrease in the rate of loss of hyaluronan from the tissue but not that of aggrecan, which remained the same as in control cultures. This suppression of the rate of loss of hyaluronan was eliminated on removal of the hyaluronan oligosaccharides from the culture medium. Analysis of the hydrodynamic size of the newly synthesized hyaluronan indicated that the presence of hyaluronan tetra- and hexasaccharides brought about an accumulation of hyaluronan of intermediate molecular mass. Since no radiolabeled hyaluronan was detected in the culture medium, it was concluded that the tetra- and hexasaccharides inhibited the internalization and intracellular catabolism of hyaluronan by the cartilage explant cultures. Regardless of whether hyaluronan or tetra- and hexasaccharides of hyaluronan were added to the culture medium, newly synthesized hyaluronan underwent depolymerization at a rate consistent with a mechanism involving oxygen-derived radicals.

Adult↗

The role of the continence adviser in England and Wales.

Continence advice in England and Wales is a relatively new specialism within nursing and, over the past 20 years, the number of continence advisers has grown substantially. There are, however, no formal qualifications for the role and the service has grown up in a piecemeal fashion. A study carried out by the Social Policy Research Unit of the University of York sought to answer basic quantitative questions about: (1) the number of continence advisers in post, their professional backgrounds and so on; (2) the structures within which continence advisers work; and (3) the nature of their current practice; as well as more attitudinal and developmental questions about the history and future development of continence advisers' work.

England↗

Antagonism of botulinum toxin-induced muscle weakness by 3,4-diaminopyridine in rat phrenic nerve-hemidiaphragm preparations.

The effects of the potassium channel inhibitor and putative botulinum toxin antagonist 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile properties of rat diaphragm muscle. In the presence of 100 pM botulinum neurotoxin A (BoNT/A), twitches elicited by supramaximal nerve stimulation (0.1 Hz) were reduced to approximately 10% of control in 3 hr at 37 degrees C. Addition of 3,4-DAP led to a rapid reversal of the BoNT/A-induced depression of twitch tension. In the presence of 100 microM 3,4-DAP, antagonism of the BoNT/A-induced blockade began within 30-40 sec and reached 82% of control with a half-time of 6.7 min. The beneficial effect of 3,4-DAP was well maintained and underwent little or no decrement relative to control for at least 8 hr after addition. Application of 1 microM neostigmine 1 hr after 3,4-DAP led to a further potentiation of twitch tension, but this action lasted for < 20 min. Moreover, neostigmine caused tetanic fade during repetitive stimulation. In contrast to the efficacy of the parent compound, the quaternary derivative of 3,4-DAP, 3,4-diamino-1-methyl pyridinium produced little or no twitch potentiation up to a concentration of 1 mM. The potassium channel blocker, tetraethylammonium, generated a transient potentiation followed by a sustained depression of twitch tensions. It is concluded that 3,4-DAP is of benefit in antagonizing the muscle paralysis following exposure to BoNT/A. Co-application of neostigmine or tetraethylammonium with 3,4-DAP, however, appears to confer no additional benefit.

Aminopyridines↗

The capacity of a measure of disability (the LSP) to predict hospital readmission in those with schizophrenia.

One hundred and eighteen subjects with an admission diagnosis of schizophrenia were reassessed after 12 months to establish whether hospital readmission had occurred. All subjects were rated at baseline and after 12 months on the Life Skills Profile (LSP), a 39-item measure of disability, with scores demonstrating moderate stability. The baseline LSP score was a significant predictor of readmission, both in univariate and multivariate analyses. By contrast, several univariate variables (e.g. unemployment and non-compliance with medication over the review period) did not maintain their predictive capacity in multivariate analyses, suggesting that they were manifestations or consequences of significant disability, rather than independent contributors to poor outcome.

Activities of Daily Living↗

Sub-typing depression, I. Is psychomotor disturbance necessary and sufficient to the definition of melancholia?

Melancholia is most commonly distinguished from non-melancholic depression by the presence of psychomotor disturbance (PMD) and a set of 'endogeneity' symptoms. We examine the capacity of an operationalized clinician-rated measure of PMD (the CORE system) to predict diagnostic assignment to 'melancholic/endogenous' classes by the DSM-III-R and Newcastle systems. Examining a pre-established CORE cut-off score (> or = 8) against independent diagnostic assignment, PMD was present in 51% of those assigned as melancholic by DSM-III-R, and 85% of those assigned as endogenous by the Newcastle system, quantifying the extent to which it is 'necessary' to the two definitions of 'melancholia'. Additionally, multivariate analyses established that the addition of a refined set of historically suggested endogeneity symptoms added only slightly to overall discrimination of melancholic and non-melancholic depressives. While only few endogeneity symptoms independent of psychomotor disturbance were suggested, their specific relevance varied against system definition of melancholia (appetite/weight loss and terminal insomnia being identified for DSM-III-R; anhedonia for Newcastle; and diurnal variation in mood and energy for both systems). Results allow consideration of the relative importance of two domains (psychomotor disturbance and 'endogeneity' symptoms) to clinical definition of melancholia, and have the potential to assist both classification and pursuit of neurobiological determinants. We interpret findings as suggesting a 'core and mantle' model for conceptualizing the clinical features of melancholia, with psychomotor disturbance as the core and with independent endogeneity symptoms as only a thin mantle.

Adult↗

Sub-typing depression, II. Clinical distinction of psychotic depression and non-psychotic melancholia.

We have attempted to clarify clinical differentiating features of psychotic depression. Forty-six depressed subjects meeting DSM-III-R criteria for major depression with psychotic features were compared with (i) DSM-defined melancholic, (ii) Newcastle-defined endogenous, and (iii) a residual DSM-defined major depressive episode group. Additionally, a 'bottom up' latent class analysis (LCA) suggested a larger sample of 82 'psychotic depressive' subjects, and multivariate analyses contrasted these subjects with both LCA-identified melancholic and all residual depressed subjects. Analyses suggested that, in addition to two features with absolute specificity (delusions and hallucinations), both the DSM-defined and LCA-defined 'psychotic depressive' subjects were significantly more likely to demonstrate marked psychomotor disturbance, to report two morbid cognitions (feeling sinful and guilty; feeling deserving of punishment), as well as be more likely to report constipation, terminal insomnia, appetite/weight loss and (variable across the defined 'psychotic depressive' groups) loss of interest and pleasure. The study identifies a wider set of potentially discriminating clinical variables than previous studies, as well as both indicating the existence and assisting identification of 'true' psychotic depression in the absence of formal psychotic features being acknowledged or elicited.

Adult↗

Sub-typing depression, III. Development of a clinical algorithm for melancholia and comparison with other diagnostic measures.

We describe the development of a clinical algorithm to differentiate melancholic from non-melancholic depression, using refined sets of 'endogeneity' symptoms together with clinician-rated CORE scores assessing psychomotor disturbance. Assignment by the empirically developed algorithm is contrasted with assignment by DSM-III-R and with several other melancholia sub-typing indices. Both the numbers of 'melancholics' assigned by the several systems and their capacity to distinguish 'melancholics' on clinical, demographic and a biological index test (the DST) varied across the systems with the algorithm being as 'successful' as several systems that include inter-episode and treatment response variables. Analyses provide information on the criteria set developed for DSM-IV definition of 'melancholia'.

Adult↗

Can the chronic fatigue syndrome be defined by distinct clinical features?

To determine whether patients diagnosed as having chronic fatigue syndrome (CFS) constitute a clinically homogeneous class, multivariate statistical analyses were used to derive symptom patterns and potential patient subclasses in 565 patients. The notion that patients currently diagnosed as having CFS constitute a single homogeneous class was rejected. An alternative set of clinical subgroups was derived. The validity of these subgroups was assessed by sociodemographic, psychiatric, immunological and illness behaviour variables. A two-class statistical solution was considered most coherent, with patients from the smaller class (27% of the sample) having clinical characteristics suggestive of somatoform disorders. The larger class (73% of sample) presented a more limited combination of fatigue and neuropsychological symptoms, and only moderate disability but remained heterogeneous clinically. The two patient groups differed with regard to duration of illness, spontaneous recovery, severity of current psychological morbidity, utilization of medical services and CD8 T cell subset counts. The distribution of symptoms among patients was not unimodal, supporting the notion that differences between the proposed subclasses were not due simply to differences in symptom severity. This study demonstrated clinical heterogeneity among patients currently diagnosed as CFS, suggesting aetiological heterogeneity. In the absence of discriminative clinical features, current consensus criteria do not necessarily reduce the heterogeneity of patients recruited to CFS research studies.

Fatigue Syndrome, Chronic↗

Trends in voice rehabilitation in the United Kingdom.

Three main basic forms of vocal rehabilitation are available for post-laryngectomy patients in this country: oesophageal, mechanical vibrator and valved speech. In Sheffield, we advocate the use of valved speech, and insertion of the prosthesis preferably at the time of laryngectomy. We studied current vocal rehabilitation trends in the United Kingdom by a random survey of 100 consultant otolaryngologists and present our findings here. While all forms of vocal rehabilitation are provided in the majority of centres, 20% of units involved in head and neck surgery do not have optimum levels of speech therapy involvement.

Humans↗

How do research psychiatrists rate? Views of neuroscientists.

OBJECTIVE: The aim of the paper is to define views of neuroscientists about research psychiatrists that might be restricting collaborative research. METHOD: A questionnaire was distributed to all members of the Australian Neuroscience Society. Forty-nine questionnaires were returned, and both quantitative and qualitative analyses undertaken. RESULTS: Neuroscientists rated research psychiatrists as "poor scientists" in having limited scientific training, being loose methodologists and in tending to cut corners, but also viewed research psychiatrists as addressing domains that generate harder research questions. Several factors inhibiting and promoting collaboration between neuroscientists and research psychiatrists were elicited. CONCLUSIONS: If collaborative links involving neuroscientists and research psychiatrists are to be enhanced, research psychiatrists will need to address and redress views about perceived limitations of their scientific competence.

Attitude of Health Personnel↗

Practice visits: a pilot study.

OBJECTIVE: The aim of the paper is to report a pilot study of practice visits. METHOD: The study involved 35 psychiatrists as hosts and/or visitors, as well as four non-psychiatrist visitors, with the model and subsequent design changes described. RESULTS: The Quality Assurance Committee's rationale for practice visits is detailed, together with several focal concerns raised by committee members and other Fellows of the College. CONCLUSIONS: Feedback was highly positive, with visitors being generally more positive and enthusiastic than hosts. A follow-up questionnaire indicated ongoing enthusiasm for such an activity and provided evidence of participants making changes to their practices. Identified concerns and some suggested modifications to the pilot study design are noted.

Attitude of Health Personnel↗

A clinical perspective on SPECT.

The potential clinical utility of SPECT (Single Photon Emission Computed Tomography) brain imaging to clarifying certain diagnostic dilemmas faced by clinical psychiatrists is considered generally and is illustrated by several case vignettes. Three case histories consider dementia vs depressive pseudodementia, two the possibility of a cerebral vasculitis in patients with auto-immune conditions, and two whether the patient had a "type" of depression likely to benefit from a course of ECT. Published studies reviewing the utility of SPECT in dementia, depression, depressive "pseudodementia" and cerebral lupus are considered. It is suggested that SPECT is an important investigatory technique providing additional information that may assist some diagnostic decisions, while its utility in assisting other clinical decisions awaits clarification.

Adult↗

A brief self-report depression measure assessing mood state and social impairment.

Many measures of depression severity appear confounded by including depressive sub-typing features. We report the design of a brief (11 item) self-report scale of depression severity (the AUSSI), assessing both mood state and social impairment domains, and designed to be independent of sub-typing features. Mood severity and functional impairment scores demonstrated some independence in a sample of 360 patients. Patients with a 'melancholic' depressive type (categorised by four differing systems) differed from residual 'non-melancholic' depressed patients by having higher impairment scores, but the assigned groups did not differ, in the main, by mood severity scores. Advantages of the measure are summarised.

Affect↗

Sequence and expression of human hair keratin genes.

Normal hair growth and differentiation requires co-ordinate expression of many hair specific structural protein genes. It has been established that one of the 4 major groups of hair structural proteins, low-sulphur hair keratins, belongs to the intermediate filament (IF) multigene family. Hair keratin IF proteins differ from those of other epithelia as they contain cysteine-rich terminal domains allowing more extensive disulphide bonding to the high-sulphur hair matrix proteins. Until recently, little information concerning the primary sequence of hair keratins was available but cloning of some mouse hair and sheep wool keratins has now been reported. Using these sequences, we have polymerase chain reaction (PCR) amplified genomic fragments of human hair-specific keratin IF genes and isolated cosmid clones containing full length genes. We have sequenced part of these genes and studied their expression in human hair follicles. Hair specific keratin fragments were amplified from placental gDNA by PCR primed with synthetic oligonucleotides. Fragments were cloned and sequenced after ligation into pGEM-3Z and labelled riboprobes were generated for in situ hybridization on human skin sections. A human cosmid library was screened with PCR fragments and clones encoding human hair keratin genes were characterised by southern hybridization and sequencing. The type I human hair-specific keratin clones obtained (HaKA1-b2, 386 bp; hHaKA1-XH1, 1202 bp) encoded 2B helix, C-terminal and 3'nc regions and were 65% homologous to mouse sequences. The type II hair keratin clone (hHaKB2-1, 829 bp) also encoded 2B helix and C-terminal regions and was 95% homologous to mouse. In situ hybridization on human skin sections showed a specific reaction with precortical cells of the hair follicle. One human cosmid clone, isolated with the hHaKB2-1 probe, contained two type II hair keratin genes about 7 kb apart, each of which had 9 exons spanning approximately 6 kb. The coding sequences were homologous to mouse cDNA (77-88%). These human hair-specific keratin clones are useful molecular tools for studies of hair differentiation.

Amino Acid Sequence↗

Sex differences in lifetime depression rates: fact or artefact?

To isolate determinants of any female preponderance in depressive disorder, we earlier selected a sample of young adults, then similar in terms of several potential social determinants of depression and with equivalent rates of lifetime depression. We now report a 10-year review, which initially suggested a female preponderance in DIS-generated RDC and DSM-III lifetime depressive categories. The presence of sex differences in rates of lifetime depression was influenced by the definition of caseness used and the vantage point from which rates were determined. The longitudinal design and earlier corroborative witness reports established, however, clear evidence of instability in prevalence estimates, together with a sex effect on stability. Men were more likely to 'forget' episodes, while women were more likely to 'remember' episodes that had generally not previously reached 'case' criteria. When correction was made for such artefactual influences, a sex difference in lifetime depression rates was no longer evident. Such findings require review in general community samples, and suggest modifications to 'case' definition in epidemiological enquiries.

Adult↗

The role and self-perceived training needs of nurses employed in general practice: observations from a national census of practice nurses in England and Wales.

This paper outlines the results of a national census of practice nurses in England and Wales. It not only shows that the numbers of practice nurses have increased dramatically in recent years but also demonstrates how their role has evolved. Many practice nurses are now involved in health promotion, and home visiting, as well as advice and counselling. The findings also indicate that many practice nurses express a need for training. Continuing education for practice nurses is important in ensuring practice nurses are fully qualified and trained for the tasks they undertake. In addition, it also enables them to develop their role and work alongside other community health professionals.

Adult↗

Defining melancholia: properties of a refined sign-based measure.

We hypothesised that psychomotor disturbance is specific to the melancholic subtype of depression and capable of defining melancholia more precisely than symptom-based criteria sets. We studied 413 depressed patients, and examined the utility of a refined, operationally driven set of clinician-rated signs, principally against a set of historically accepted symptoms of endogeneity. We specified items defining psychomotor disturbance generally as well as those weighted either to agitation or to retardation. We demonstrated the system's capacity to differentiate 'melancholic' and 'non-melancholic' depression (and the comparable success of DSM-III-R and Newcastle criteria systems) by reference to several patient, illness and treatment response variables, to an independent measure of psychomotor disturbance (reaction time) and to a biological marker (the dexamethasone suppression test).

Adult↗