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Biomedical subjects

C Jones

Publications and source records attributed to C Jones.

At least 217 records · Page 12Linked to original sources
PubMed1998

A randomised controlled trial of postal versus interviewer administration of a questionnaire measuring satisfaction with, and use of, services received in the year before death.

STUDY OBJECTIVES: To develop a short form of an interview schedule used successfully in previous national surveys of care for the dying, and to investigate the effect of administering it by post on response rate, response bias and on the nature of responses to questions. DESIGN: Randomised controlled trial. SETTING: An inner London health authority. PARTICIPANTS: Informants (person registering death) of random sample of cancer deaths between June 1995 and July 1996. MAIN RESULTS: The shortened questionnaire (VOICES) has 158 questions. Response rate did not differ significantly between postal and interview groups (interview; 56% (69 of 123), postal: 52% (161 of 308). Responders in the two groups did not differ in terms of their sociodemographic characteristics. Postal questionnaires had significantly more missing data, particularly on questions about service provision and satisfaction with services. Responses to questions differed between the groups on 11 of 158 questions. Interview group respondents were more likely to give top ranking responses to questions on service satisfaction and symptom control. CONCLUSIONS: Postal questionnaires are an acceptable alternative to interviews in retrospective post-bereavement surveys of care for the dying, at least in terms of response rate and response bias. However, the increased costs of interview surveys need to be balanced against the fact that postal questionnaires result in more missing data, and possibly less reliable answers to some questions. Caution is needed in combining results from the two data collection methods as interview respondents gave more positive answers to some questions.

Adult↗
PubMed1998

5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation.

OBJECTIVE: Olanzapine is a new atypical antipsychotic recently introduced for the treatment of schizophrenia. The purpose of this study was to investigate olanzapine's binding to the serotonin 5-HT2 and dopamine D2 receptors in schizophrenic patients being treated with clinically relevant doses. METHOD: Twelve patients with schizophrenia were randomly assigned to 5, 10, 15, or 20 mg/day of olanzapine in a prospective fashion. Three other subjects taking 30-40 mg/day were also included. Once steady-state plasma levels were achieved, dopamine D2 and serotonin 5-HT2 receptors were assessed by using [11C]raclopride and [18F]setoperone positron emission tomography imaging, respectively. Ratings of clinical status, extrapyramidal side effects, and prolactin levels were also obtained. RESULTS: Olanzapine induced near saturation of the 5-HT2 receptors, even at 5 mg/day. Its D2 occupancy increased with dose: patients taking 5-20 mg/day showed 43%-80% D2 occupancy, while patients taking 30-40 mg/day showed 83%-88%. CONCLUSIONS: Olanzapine is a potent 5-HT2 blocker and shows a higher 5-HT2 than D2 occupancy at all doses. However, its D2 occupancy is higher than that of clozapine and similar to that of risperidone. In the usual clinical dose range of 10-20 mg/day, its occupancy varies from 71% to 80%, and this restricted range may explain its freedom from extrapyramidal side effects and prolactin elevation. However, doses of 30 mg/day and higher are associated with more than 80% D2 occupancy and may have a higher likelihood of prolactin elevation and extrapyramidal side effects.

Adult↗
PubMed1998

Suppressibility of plasma adrenocorticotropin by hydrocortisone: potential usefulness in the diagnosis of Cushing's disease.

Repeatedly normal cortisol suppressibility by dexamethasone in 2 patients with Cushing's disease led to the present study of the prevalence of this phenomenon in 58 patients with otherwise incontrovertible evidence of Cushing's disease. Because as many as 23% of these patients manifested this phenomenon, we investigated the suppressibility of plasma ACTH: 1) during i.v. infusion of hydrocortisone, after a priming dose (7 mg), at 3 mg/h in 8 patients and 8 normal controls; and 2) for 2 h, after oral hydrocortisone, 0.25 mg/kg, in 13 patients and 16 controls. The data showed invariable suppression of plasma ACTH to < or = 10 pg/mL (< or = 2.2 pmol/L) after 120 min of the infusion or at 90 min after oral hydrocortisone in 16 fasting normal subjects given oral hydrocortisone between 0800 and 0830 h. Plasma ACTH exceeded 10 pg/mL (2.2 pmol/L) at the same times in 14/14 patients with active Cushing's disease, including 3 patients whose cortisol suppressibility by dexamethasone had been misleadingly normal and in 4/7 patients with intermittent hypercortisolism. Occasional variations in plasma cortisol elevations after the oral dose require that plasma cortisol concentration be monitored at 60 min after the oral hydrocortisone dose, because the present evidence supports the validity of the conclusion that a plasma ACTH concentration below 10 pg/mL excludes Cushing's disease only when plasma cortisol concentration at 60 min lies between 16 and 38 microg/dL. Further evaluation of ACTH suppressibility by cortisol would be worthwhile, to confirm its potential value in facilitating positive diagnosis of Cushing's disease when dexamethasone suppressibility seems misleading.

Adolescent↗
PubMed1998

Paediatric dental general anaesthesia rates and dental caries regionally and in districts in the former north western region.

OBJECTIVE: To chart paediatric dental general anaesthesia activity following implementation of the Poswillo Report recommendations and to characterise the relationship between dmft/DMFT and rates of paediatric dental general anaesthesia. DESIGN: An ecological study, using results of the NHS dental epidemiological surveys and routine NHS activity data. SETTING: The general, community and hospital dental services. SUBJECTS: Former regional and district health authorities' residents. OUTCOME MEASURES: Correlations between the regional and district rates of dental general anaesthesia and dmft/DMFT from the NHS dental epidemiology surveys. RESULTS: About half of all paediatric dental general anaesthetics are carried out in the General Dental Service. There were significant correlations between regional mean dmft/DMFT and under 18 combined dental general anaesthesia rates in 1991/2 and 1992/3. In the North West Region there were significant correlations between 0-4-year-old district dental general anaesthesia rates and dmft of 5-year-old children in 1989/90 (r = 0.45, P < 0.05) and 0-17-year-old district dental general anaesthesia rates and 12-year-old DMFT (r = 0.49, P < 0.05) in 1992/3. CONCLUSIONS: The number of paediatric dental general anaesthetics provided since the Poswillo Report was implemented (1991) has increased in the last two years (1993/4 and 1994/5). District rates of dental general anaesthesia bore little relation to dental need as measured by dmft/DMFT, except in 1989/90 for 5-year-old children and in 1992/3 for 12-year-old children. This suggests dental general anaesthesia is not provided in response to dental needs at a district health authority level.

Adolescent↗
PubMed1998

Malignant melanoma of the head and neck.

Malignant melanoma is rapidly increasing in incidence. The primary lesion is frequently seen in the head and neck and general dental practitioners thus have the opportunity to identify suspicious lesions at an early stage. This article gives an overview of the pathology and clinical features of melanoma.

Head and Neck Neoplasms↗
PubMed1997

Residues at the carboxy terminus of T4 DNA polymerase are important determinants for interaction with the polymerase accessory proteins.

Three T4 DNA polymerase accessory proteins (44P/62P and 45P) stimulate the polymerase (pol) activity and the 3'-5' exonuclease (exo) activity of T4 DNA polymerase (43P) on long, double-stranded DNA substrates. The 44P/62P "clamp loader" facilitates the binding of 45P, the "sliding clamp", to DNA that is primed for replication. Using a series of truncated 43P mutants, we identified a region at the extreme carboxy terminus of the DNA polymerase that is required for its interaction with accessory proteins. Truncation mutants of 43P lacking the carboxy-terminal 3, 6, or 11 residues retained full pol and exo activity on short synthetic primer-templates. However, the ability of the accessory proteins to enhance these activities on long double-stranded DNA templates was drastically reduced, and the extent of the reduction in activity was greater as more residues were deleted. One of the truncation mutants (N881), which had 17 residues removed from the carboxy terminus, showed reduced binding affinity and diminished pol activity but enhanced exo activity upon incubation with a small primer-template. The exo activity of the N881 mutant, on short, single-stranded DNA was unchanged, however, compared to the wild-type enzyme. These results are consistent with inferences drawn from the crystal structure of a DNA polymerase from a related T-even phage, RB69, where the carboxy-terminal 12 residues (equivalent to the 11 residues of 43P from phage T4) protrude from the thumb domain and are free to interact with complementary surfaces of the accessory proteins. The structural integrity of the thumb region in the N881 mutant is probably perturbed and could account for its reduced binding affinity and pol activity when incubated with short, double-stranded DNA substrates.

Amino Acid Sequence↗
PubMed1997

Comparison of the diphtheria mutant toxin, CRM197, with a Haemophilus influenzae type-b polysaccharide-CRM197 conjugate by optical spectroscopy.

A Haemophilus influenzae type-b capsular polysaccharide-CRM197 protein conjugate vaccine was compared with unconjugated CRM197 and diphtheria toxin, its parent molecule. Using CD and fluorescence spectroscopy, it has been possible to observe differences in structure and stability to pH and temperature due to the G52-->E mutation in CRM197 and the 'glycosylation' of CRM197 in the conjugate. CRM197 resembles the 'open' conformation of diphtheria toxin [Blewitt, M. G., Chung, L. A. & London, E. (1985) Biochemistry 24, 5458-5464] and the attachment of poly(ribosyl-ribitol phosphate) carbohydrate chains results in a still 'more open' state, although only a small decrease in the amount of ordered structure was observed. Fluorescence spectra of gel-filtration column fractions of the conjugate suggest that material of higher apparent molecular size is in the 'more open' conformation. Conjugated CRM197 begins unfolding at slightly lower temperatures (25-35 degrees C) than native material (> 35 degrees C). In the conjugate, tryptophan residues are more accessible to the non-ionic fluorescence quencher acrylamide at 35 degrees C. The conformational change observed at pH4-6 for diphtheria toxin is also observed for CRM197, but in the conjugate begins at higher pH. This may result from the presence of charged oligosaccharide residues on the surface or the conjugation methods used. The consequences of these changes in conformation and solution behaviour of the carrier protein in terms of its ability to induce a protective, T-cell-dependent response to H. influenzae polysaccharide remain to be determined.

Bacterial Proteins↗
PubMed1997

In vivo imaging of fatty acid incorporation into brain to examine signal transduction and neuroplasticity involving phospholipids.

An in vivo method is presented that allows quantification and imaging of fatty acid incorporation into different brain phospholipids in relation to membrane synthesis, neuroplasticity, and signal transduction. The method can be used with positron emission tomography, and may help to evaluate brain phospholipid metabolism in humans with brain tumors, neurodegenerative disease, cerebral ischemia or trauma, or neurotoxic effects of drugs or other agents.

Animals↗
PubMed1997

Structure of the repeating oligosaccharide from the lipopolysaccharide of the nitrogen-fixing bacterium Acetobacter diazotrophicus strain PAL 5.

Acetobacter diazotrophicus is an acid-tolerant nitrogen-fixing bacterium found in roots, rhizosphere, stems, and leaves of sugar cane (Saccharum officinarum) cultivated in Brazil. The O-polysaccharide from the lipopolysaccharide of the root isolate strain PAL 5 has been determined by a combination of methylation analysis and two-dimensional high field NMR spectroscopy. The pentasaccharide repeat has the structure: [formula: see text] Minor resonances in the NMR spectra are consistent with the presence of a proportion of repeating units which lack the beta-D-Glc side-chain.

Acetobacter↗
PubMed1997

Frontal interhemispheric asymmetry: self regulation and individual differences in humans.

Sixteen subjects naive to biofeedback learned lateralised interhemispheric control of slow cortical potentials (SCPs) across electrode sites F3-F4 during three sessions of visual electroencephalograph (EEG) biofeedback. Subjects were required to generate slow negativity shifts either towards the left or the right hemisphere in sixty pseudorandomly ordered trials per session. Group 1 (n = 8) were told to use emotional strategies in the task (positive emotions for left hemisphere activation, negative emotion for right hemisphere activation), group 2 received no guidance. Both groups received feedback in the form of an on-screen rocket-ship, initially centrally placed, which rose to indicate an increase in left hemisphere negativity (relative to the right hemisphere) and fell to indicate an increase in right hemisphere negativity (relative to the left hemisphere). A 2 x 3 x 3 x 2 ANOVA (group x session x block x trial) showed no performance differences between the strategy and no strategy groups. Both groups learned to produce correct direction shifts in the final third of each session during both trial types (P < 0.001). The no strategy group showed a particularly strong within session learning effect (P < 0.0037) with poor performance in the early part of the sessions, and strong shifts at the end. Subjects high on withdrawal showed stronger rightward shifts in keeping with right hemisphere involvement in behavioural withdrawal. This is the first demonstration of self regulation of interhemispheric frontal asymmetry.

Adult↗
PubMed1997

Biomonitoring study of a group of workers potentially exposed to traffic fumes.

Risk assessment of environmental pollutants is concerned with the identification of compounds in the environment that might be hazardous to human health: measuring exposure levels, measuring cellular damage and then estimating the probability of harm occurring. The feasibility of such a comprehensive approach has been explored in this study of two groups of workers, one of which may be occupationally exposed to exhaust fumes. No statistically significant difference in cellular damage, as measured by the lymphocyte micronucleus assay, was found between these two groups of workers, although clear differences in exposure levels to volatile organic compounds were detected. A number of other factors identified in the study did show clear effects on micronucleus frequency.

Adult↗
PubMed1997

The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study.

The purpose of this study was to determine the relationship between dopamine D2 receptor occupancy and plasma haloperidol. Twelve patients treated with 1-5 mg/day of haloperidol had their D2 occupancy measured using [11C]-raclopride and positron emission tomography and haloperidol plasma levels measured using gas chromatograph mass spectrophotometer. The patients exhibited haloperidol plasma levels ranging from 0.5 to 5.8 ng/ml and D2 occupancy from 53 to 88%. The D2 occupancy was related to the plasma level as a saturating rectangular hyperbola relationship (r2 = 0.84) and it showed that, on average, 50% D2 occupancy was achieved with 0.51 ng/ml and 80% D2 occupancy with 2.0 ng/ml. Our findings demonstrate that 2-5 mg/day of haloperidol, which usually leads to plasma levels of 1-2 ng/ml, would be expected to induce 60-80% dopamine D2 receptor occupancy. If, as has been claimed, 70% D2 occupancy is adequate for typical neuroleptic response, then the conventional use of > 10 mg/day may have been too high, since 70% occupancy can be achieved in most patients by 2-5 mg/day. On the other hand, if as others have suggested, 8-12 ng/ml of haloperidol is the correct therapeutic window for plasma levels, then the required therapeutic D2 occupancy is closer to 90%, not 70%. The implications of the D2 occupancy findings for the optimal dosing of neuroleptics are discussed.

Administration, Oral↗
PubMed1997

Metallothionein overexpression in human brain tumours.

Metallothioneins (MTs) are metal binding proteins overexpressed in various human neoplasms which are associated with resistance to cytotoxic drugs. A series of 156 archival human brain tumours were investigated immunohistochemically for expression of MTs; these included 10 low-grade gliomas, 44 high-grade gliomas, 98 meningeal tumours (19 classical, 30 atypical, 38 anaplastic meningiomas, and 11 haemangiopericytomas or papillary meningiomas), and 4 other tumours. Low-grade gliomas showed heterogeneous MT expression; 32 high-grade gliomas (72.7%) showed MT expression of more than 25% of tumour cells without statistically significant differences between first operations and recurrent tumours. In 2 glioblastomas, the presence of MT was confirmed by Western blotting. The extent of MT immunoexpression showed a statistically significant inverse relationship to the degree of p53 immunoreactivity. In meningiomas, a tendency to a higher percentage of MT-expressing cells was observed from classical over atypical to anaplastic meningiomas, but these differences were not statistically significant. In conclusion, MT expression is present in a significant portion of, especially malignant, brain tumours and might be involved in their poor response to antineoplastic drugs.

Adult↗
PubMed1997

Changes in the mechanical properties of human and amphibian muscle after eccentric exercise.

Following a series of eccentric contractions, that is stretching of the muscle while generating active tension, the length-tension relationship of isolated amphibian muscle has been shown to shift towards longer muscle length (Katz 1939; Wood et al. 1993). Here we report observations of electrically stimulated ankle extensor muscles of nine human subjects, demonstrating a similar shift in optimum angle for torque generation [3.9 (1.5) degrees] following exercise on an inclined treadmill that involved eccentric contractions in one leg. (All values are means with the SEMs in parentheses). The shift in the unexercised, control leg was significantly less [mean 0.4 (0.7) degree P < 0.05]. Correlated with this shift was a drop in torque [25.1 (5.6)% for the experimental leg; 1.6 (0.7)% for the control leg, P < 0.002]. Optimum angles returned to pre-exercise values by 2 days post-exercise, while torque took a week to recover. A similar shift in optimum length [12 (1.3)% of rest length] was obtained for five toad (Bufo marinus) sartorius muscles subjected to 25 eccentric contractions. Isometrically contracted control muscles showed a smaller shift [3.5 (1.6)%, n = 5]. Accompanying the shift was a drop in tension of 46 (3)% after the eccentric contractions [control isometric, 23 (6)%, P < 0.0001]. By 5 h after the eccentric contractions the shift had returned to control values, while tension had not recovered. When viewed with an electron microscope, sartorius muscles fixed immediately after the eccentric contractions exhibited many small, and a few larger, regions of myofilament disruption. In muscles fixed 5 h after the contractions, no small regions of disruption were visible, and the number of large regions was no greater than in those muscles fixed immediately after the eccentric contractions. These disruptions are interpreted as the cause of the shift in length-tension relationship.

Adult↗