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Biomedical subjects

C Shaw

Publications and source records attributed to C Shaw.

At least 37 records · Page 2Linked to original sources

Psychological stress and burnout in medical students: a five-year prospective longitudinal study.

The aim of this study was to assess psychological morbidity and symptoms of burnout in medical students during their undergraduate training, and to identify baseline factors that predict psychological morbidity in students in the final year of the course. It was a 5-year prospective longitudinal cohort study. Students were assessed in years 1, 4 and 5 of their medical undergraduate training by means of the GHQ-12 and the Maslach Burnout Inventory. 172 (84.3%), 157 (77.0%) and 155 (75.9%) students out of an original group of 204 completed assessments in years 1, 4 and 5, respectively. 18 students were above threshold on the GHQ-12 on all three occasions, 25 on two occasions and 43 on one occasion; 69 students were never a 'case'. Students who were cases on two or more occasions were more likely to find the medical course stressful during the first year, but not subsequent years. There was no significant difference between the percentages of men and women who scored as cases on the GHQ-12 in any of the years. The best predictor of psychological morbidity in the final year of the course was the GHQ-12 score in year 1. This study suggests that a small group of students repeatedly experience psychological distress during their medical training.

Alcohol Drinking

Hospital accreditation in Europe.

Health service accreditation systems have explicit standards for organisation against which the participating hospital assesses itself before a structured visit by outside "surveyors". They submit a written report back to the hospital with commendations and recommendations for development prior to a follow-up survey. Accreditation may be awarded for a fixed term or may be with held by an independent assessment Board if the hospital does not meet a defined threshold of standards. In Europe, some government and medical organisations initially distanced themselves from the pilot hospital wide programmes, arguing that they would cost too much and undermine management, or that they were irrelevant to clinical practice. But gradually it became obvious that accreditation worked for hospitals; purchasers and insurers saw its potential for quality and resource management; and professional bodies recognised the links between clinical training, practice and outcome and the environment in which health care is provided. If nothing else, it offered a multi-professional bridge between the existing numerous fragmented systems such as inspecting (statutory safety), visiting (professional training), and monitoring (service contracts). The introduction of accreditation appears to benefit hospitals in many different countries and health systems and provides a vehicle for integrated quality management which is visible to funding agencies, government and the public. Interest is growing within Europe.

Accreditation

1996-based national population projections for the United Kingdom and constituent countries.

The 1996-based national population projections, carried out by the Government Actuary in consultation with the Registrars General, show the population of the United Kingdom rising from 58.8 million in 1996 to over 62 million by 2021. The population will become gradually older with the mean age expected to rise from 38.4 years in 1996 to nearly 42 years by 2021. The number of children aged under 16 is projected to fall by 1.0 million (9 per cent) by 2021, while the number aged 65 and over is projected to increase by 2.7 million (29 per cent). Longer-term projections suggest the population will peak around 2031 and then gradually start to fall.

Actuarial Analysis

APEASPFIRFamide, a novel FMRFamide-related decapeptide from Caenorhabditis elegans: structure and myoactivity.

To date, 9 FMRFamide-related peptides (FaRPs) have been identified in Caenorhabditis elegans. Eight of these peptides are encoded on the flp-1 gene. However, AF2 (KHEYLRFamide) which was not co-encoded was the most abundant FaRP identified in ethanolic extracts. Further radioimmunometrical screening of acidified ethanol extracts of C. elegans has revealed the presence of other novel FaRPs, which are not encoded on the flp-1 gene. One of these peptides has been isolated by sequential rpHPLC and subjected to Edman degradation analysis and gas-phase sequencing and the unequivocal primary structure of the decapeptide Ala-Pro-Glu-Ala-Ser-Pro-Phe-Ile-Arg-Phe-NH2 was determined following a single gas-phase sequencing run. The molecular mass of the peptide was found to be 1133.7 Da, determined using a time-of-flight mass spectrometer. Synthetic replicates of this peptide were found to induce a profound relaxation of both dorsal and ventral somatic muscle-strip preparations of Ascaris suum with a threshold for activity of 10 nM. The inhibitory response was not dependent on the presence of nerve cords, indicating a post-synaptic site-of-action. The relaxation was Ca(+2)- and Cl(-)-independent but was abolished in high-K+ medium and could be distinguished from those of other inhibitory nematode FaRPs, including PF1 (SDPNFLRFamide) and PF4 (KPNFIRFamide).

Amino Acid Sequence

Immunocytochemical evidence for the involvement of an FMRFamide-related peptide in egg production in the flatworm parasite Polystoma nearcticum.

The monogenean flatworm Polystoma nearcticum exhibits reproductive synchrony with its treefrog host, Hyla versicolor, and becomes reproductively active only during the short period of host sexual activity at spawning. In this way, it provides a useful model system for exploring factors that may influence egg production in flatworm parasites. One such factor is the peptidergic innervation of the egg chamber or ootype. By using immunocytochemical techniques, the occurrence and distribution of GYIRFamide-like immunoreactivity, an authentic flatworm FMRFamide-related peptide (FaRP), have been monitored in the cells and fibres innervating the reproductive apparatus of worms collected at different stages of host sexual activity. Serotonin (5-HT) immunoreactivity in the worm was mapped for comparison. Extensive immunostaining for the FaRP and 5-HT was obtained throughout both the central and the peripheral nervous systems of worms, which were recovered from reproductively active frogs. In contrast, the innervation of the ootype of worms that were determined to be sexually inactive, including those recovered from frogs postspawning, showed little or no immunoreactivity for the FaRP; immunostaining for 5-HT in the ootype was unaffected by the reproductive state of the worm. These results indicate that FaRP expression in the neurons of the ootype innervation of P. nearcticum coincides with the parasite's brief period of egg production and, thus, provides evidence that regulatory peptides may be involved in the egg-assembly mechanism in flatworm parasites.

Animals

Cholinergic, serotoninergic and peptidergic components of the nervous system of Haematoloechus medioplexus (Trematoda, Digenea), characterised by cytochemistry.

Cholinergic, serotoninergic and peptidergic neuronal pathways have been demonstrated in whole-mount preparations of the frog-lung digenean trematode, Haematoloechus medioplexus, using enzyme cytochemical methodologies and indirect immunocytochemical techniques in conjunction with confocal scanning laser microscopy. All 3 classes of neuroactive substance were found throughout both central and peripheral elements of a well-developed orthogonal nervous system. Peptidergic immunoreactivity was particularly strong, using antisera directed to native flatworm neuropeptides, neuropeptide F, and FMRF amide-related peptides (FaRPs), and there was significant overlap in the staining with that for cholinergic components. The serotoninergic system appeared quite separate, with the staining localised to a different set of neurons.

Animals

Structure-activity relationships of FMRFamide-related peptides contracting Schistosoma mansoni muscle.

This study reports the potent myoactivity of flatworm FMRFamide-related peptides (FaRPs) on isolated muscle fibers of the human blood fluke, Schistosoma mansoni. The turbellarian peptides YIRFamide (EC50 4 eta M), GYIRFamide (EC50 1 eta M), and RYIRFamide (EC50 7 eta M), all induced muscle contraction more potently than the cestode FaRP GNFFRFamide (EC50 500 eta M). Using a series of synthetic analogs of the flatworm peptides YIRFamide, GYIRFamide and RYIRFamide, the structure-activity relationships of the muscle FaRP receptor were examined. With a few exceptions, each residue in YIRFamide is important in the maintenance of its myoactivity. Alanine scans resulted in peptides that were inactive (Ala1, Ala2, Ala3 and Ala4 YIRFamide; Ala4 and Ala5 RYIRFamide) or had much reduced potencies (Ala1, Ala2 and Ala3 RYIRFamide). Substitution of the N-terminal (Tyr1) residue of YIRFamide with the non-aromatic residues Thr or Arg produced analogs with greatly reduced potency. Replacement of the N-terminal Tyr with aromatic amino acids resulted in myoactive peptides (FIRFamide, EC50 100 eta M; WIRFamide, EC50 0.5 eta M). The activity of YIRFamide analogs which possessed a Leu2, Phe2 or Met2 residue (EC50's 10, 1 and 3 eta M, respectively) instead of Ile2 was not significantly altered, whereas, YVRFamide had a greatly reduced (EC50 200 eta M) activity. Replacement of the Phe4 with a Tyr4 (YIRYamide) also greatly lowered potency. Truncated analogs were either inactive (FRFamide, YRFamide, HRFamide, RFamide, Famide) or had very low potency (IRFamide and MRFamide), with the exception of nLRFamide (EC50 20 eta M). YIRF free acid was inactive. In summary, these data show the general structural requirements of this schistosome muscle FaRP receptor to be similar, but not identical, to those of previously characterized molluscan FaRP receptors.

Amino Acid Sequence

Comparative analysis of the distribution of bradykinin-, GYIRFamide- and neuropeptide F-like immunoreactivities in the monogenean, Diclidophora merlangi.

An indirect immunocytochemical technique combined with confocal scanning laser microscopy has been used to demonstrate immunoreactivities to the nonapeptide, RPPGFSPFR (bradykinin, BK) and the endogenous flatworm regulatory peptide, GYIRFamide in the nervous system of the monogenean, Diclidophora merlangi. In addition, a simultaneous double-labelling technique was employed to examine possible co-localization of GYIRFamide- and neuropeptide F (NPF) immunoreactivities, using antisera to the C-terminal nonapeptide-amide of NPF (Moniezia expansa, FAIIGRPRF. NH2). BK immunostaining was restricted to a small population of nerve cells and associated fibres within the ventral nerve cords and to 2 pairs of nerve cells innervating the cirrus and the pharynx, respectively. No immunopositive nerve cells and fibres were identified within the brain or in association with the female reproductive apparatus. In contrast, GYIRFamide staining was abundant throughout the central and peripheral nervous systems, and appeared similar to the staining pattern revealed using an FMRFamide antiserum. GYIRFamide immunoreactivity was localized to nerve cells and fibres within the paired cerebral ganglia and the longitudinal ventral, dorsal and lateral nerve cords and their numerous interconnecting transverse commissures. The plexuses of the buccal suckers, pharynx and clamps of the haptor were strongly immunopositive for GYIRFamide, as were nerve cells innervating the ootype, the oviduct and the vitelline reservoir of the reproductive apparatus. Double-labelling experiments indicated an apparent co-localization of GYIRFamide and NPF immunoreactivities.

Animals

Physiological effects of platyhelminth FMRF amide-related peptides (FaRPs) on the motility of the monogenean Diclidophora merlangi.

The actions of known platyhelminth FaRPs on the contractility of whole-worm preparations of the monogenean, Diclidophora merlangi have been examined in vitro for the first time. All of the peptides tested had excitatory effects on the motor activity of the worm. The order of potency for the peptides tested was: YIRFamide > GYIRFamide = RYIRFamide > GNFFRFamide = FLRFamide. However, although YIRFamide was more potent than GYIRFamide, the latter was the most efficacious on each of the motility parameters (tension, contraction amplitude and contraction frequency) examined at concentrations > or = 0.1 microM. Serotonin, which stimulates contractility in the worm was used as a positive control. The excitatory activity of turbellarian and cestode neuropeptides on a monogenean indicates at least some structural similarities in the neuropeptide receptors of these classes of flatworm.

Animals

The effect of the neutral endopeptidase inhibitor drug, candoxatril, on circulating levels of two of the most potent vasoactive peptides.

AIMS: Candoxatril is a specific neutral endopeptidase (NEP) 24.11 inhibitor, and previous work has documented the effect of NEP inhibition on atrial and brain natriuretic peptides (ANP, BNP). The aim of the present study was to ascertain the effect of NEP inhibition on circulating levels of vasoactive peptides. METHODS: We studied seven patients with chronic heart failure who were randomized to receive candoxatril, candoxatril/captopril, captopril and placebo in a four way cross over, double-blind pattern. RESULTS: The mean circulating level of endothelin (ET) was increased 2 h after placebo (10 to 20 pg ml-1) and also calcitonin gene-related peptide (CGRP) (27 to 51 pg ml-1), but ANP levels changed little during this time (73 to 75 pg ml-1). Following candoxatril, however, ET (10 to 39 pg ml-1, P < 0.05), CGRP (34 to 99 pg ml-1, P < 0.05) and ANP (72 to 108 pg ml-1, P < 0.05) increased further. A similar result was observed following combined treatment with candoxatril and captopril. CONCLUSIONS: We conclude that neutral endopeptidase inhibition increases circulating plasma levels of ET and CGRP in addition to the natriuretic peptides.

Aged

The epidermal nerve fibre network: characterization of nerve fibres in human skin by confocal microscopy and assessment of racial variations.

As a first line of defence, the skin is equipped with a complex and interactive nerve fibre system to detect irritants and maintain homeostasis. The dermal component of this fibre network has been well characterized and fibres are known to extend throughout the viable epidermis as free nerve endings. To date, this epidermal component remains poorly characterized. We have visualized human volar forearm epidermal nerve fibres by laser-scanning confocal microscopy using the pan-neuronal marker, protein gene-product 9.5 and specific antibodies to substance P. calcitonin gene-related peptide and nerve growth factor. In addition to the varicose free nerve endings, there is a 3-D fibre network in normal human epidermis, with frequent branching of fibres. Branching can be seen to converge on a central trunk apparently extending to the dermis. Thin unmyelinated fibres can be seen in all layers of the viable epidermis. Substance P staining is rarely observed and is much less intense than the protein gene-product 9.5 staining. Calcitonin gene-related peptide and nerve growth factor were not detected in volar forearm epidermis by this method. Pretreatment of the skin in vivo with the neuropharmacological agent, capsaicin, resulted in loss of epidermal fibre staining indicating that these are sensory fibres of the primary C-afferent type. Epidermal innervation in racial and ethnic skin types was also assessed. No apparent difference in innervation was observed between European caucasian and Japanese/Chinese skin at the architectural or biochemical level, i.e. the presence, properties and biochemical content of fibres was similar in all cases tested.

Asian People

Responses of atrial natriuretic peptide and brain natriuretic peptide to exercise in patients with chronic heart failure and normal control subjects.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.

Adult

Glial lineages and myelination in the central nervous system.

Oligodendrocytes, derived from stem cell precursors which arise in subventricular zones of the developing central nervous system, have as their specialist role the synthesis and maintenance of myelin. Astrocytes contribute to the cellular architecture of the central nervous system and act as a source of growth factors and cytokines; microglia are bone-marrow derived macrophages which function as primary immunocompetent cells in the central nervous system. Myelination depends on the establishment of stable relationships between each differentiated oligodendrocyte and short segments of several neighbouring axons. There is growing evidence, especially from studies of glial cell implantation, that oligodendrocyte precursors persist in the adult nervous system and provide a limited capacity for the restoration of structure and function in myelinated pathways damaged by injury or disease.

Adult

Substance P and neurokinin A in gingival crevicular fluid in periodontal health and disease.

The aims of the present study were to investigate whether the tachykinins substance P and neurokinin A were present in gingival crevicular fluid in both periodontal health and disease and to study the relationship with periodontal inflammation. Gingival crevicular fluid (GCF) was collected from a healthy, a gingivitis and a periodontitis site in 20 subjects with periodontitis and from a healthy site in 20 subjects without periodontitis. The volume of GCF was measured and each sample subsequently analysed for substance P and neurokinin A by radioimmunoassay. There were significantly increased levels of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) in gingivitis and periodontitis sites compared with healthy sites. Both tachykinins were significantly elevated in periodontitis affected subjects, with significantly more tachykinin-like immunoreactivity at healthy sites in periodontitis affected compared with periodontally-healthy subjects. Despite the considerable individual variation in the levels of SP-LI and NKA-LI, both tachykinins were present at levels at which they could have biological activity. It is concluded that substance P and neurokinin A may have a rôle in the pathogenesis of periodontal disease and that further investigations could prove useful in clarifying the mechanisms through which neuropeptides could modulate periodontal health and disease.

Adult