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Biomedical subjects

C Parkes

Publications and source records attributed to C Parkes.

14 recordsLinked to original sources
PubMed2006

Working across boundaries: clinical outcomes for an integrated mental health service for people with intellectual disabilities.

BACKGROUND: The Mental Health Service for People with Learning Disabilities (MHSPLD) is a service development in keeping with UK government policy that promotes cross agency working and access to mainstream mental health services for people with intellectual disabilities. We aimed to show whether the service model brought about improvements in people's mental state and level of functioning. METHODS: Community and inpatient groups were compared across three time points using a range of clinical outcome measures that assessed psychiatric symptoms, risk, needs and level of functioning. RESULTS: Inpatients and community groups had similar mental health problems, but inpatients had higher unmet needs and lower functioning, and were at greater risk. There were significant improvements across the range of outcome measures in both groups. CONCLUSIONS: Working with mainstream mental health services and across health and social service boundaries delivers effective mental health care for people with intellectual disabilities.

Activities of Daily Living↗
PubMed2005

Systems failure in hospitals--using Reason's model to predict problems in a prescribing information system.

Both hospitals and hospital patients are bearing a massive cost as a result of the occurrence of medication prescribing errors in the public health system (Bates, D., et al. J. Am. Med. Inform. Assoc. 8(4):299-308, 2001; Lombardi, T. Medscape Pharm. Online J. 02(1), 2001; Roberts, M., and Stokes, J. eMed. J. Aust. 168:317-318, 1998). Consequently, it is important to examine and address the possible causes of this problem. In this paper we suggest that poor information systems may be a contributing factor in the occurrence of these errors. We research this issue in an HIV ward of a large public hospital through interviews and a survey instrument. We find that in a significant number of instances prescribing errors are linked to situations where information is unavailable or inaccessible. This link, between problems in information delivery and prescribing errors, is a link whose extent has not been measured previously. It is, however, a link which exposes all stakeholders in the hospital system, the patient, the clinicians, the hospital, and governments funding prescription medications, to possible loss and damage and indicates a need for the implementation of more effective systems in this area. We use Reason's model for predicting systems error (Vincent, C. BMJ 316:1154-1157, 1998) as a tool to suggest that prescribing errors have an increased likelihood of occurring if one or more of the types of failure identified in the model are present in the existing prescribing information delivery process in the hospital. While Reason's model has been applied in a medical context, it has not been previously applied to errors which result from information systems failure. We feel that applying it in this way may shed some light on the causes of prescribing error.

HIV Infections↗
PubMed1995

Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer.

OBJECTIVE: To evaluate measurement of serum prostate specific antigen as a potential screening test for future clinical prostate cancer among healthy men. DESIGN: Nested case-control study with stored serum samples collected from 49,261 men with follow up using national death and cancer registration systems. SUBJECTS: 265 asymptomatic men who subsequently developed clinical prostate cancer and 1055 controls matched for age, study centre, and duration of storage of samples. MAIN OUTCOME MEASURES: Distribution of concentrations of the antigen in men who developed prostate cancer and in controls. RESULTS: Prostate specific antigen concentrations were significantly higher in men who subsequently developed prostate cancer than in controls. In the first three years after blood collection the median concentration was 23 times greater in cases than in controls of the same age at the same centre (that is, 23 multiples of the median). A smaller difference persisted thereafter; 4.0 multiples of the median 3-6 years after blood collection, 3.6 6-10 years, and 1.8 after 10 years. In the first three years the proportion of men who developed prostate cancer and had raised levels of the antigen (> or = 12 multiples of the median) (detection rate or sensitivity) was 81% (95% confidence interval 54% to 96%). The proportion of men who did not develop prostate cancer but had levels this high (false positive rate) was only 0.5%. CONCLUSION: Prostate specific antigen measurement is a highly discriminatory screening test for prostate cancer among healthy men. In the general population, 60-74 year old men who had > or = 12 times the normal median level would have about a 50% chance of developing clinical prostate cancer in the next three years. Measurement of this antigen is a good enough screening test to justify a randomised controlled trial to determine any reduction in mortality from prostate cancer.

Aged↗
PubMed1995

UKCCCR multicentre randomised controlled trial of one and two view mammography in breast cancer screening.

OBJECTIVE: To compare one view (oblique) and two view (oblique and craniocaudal) mammography in breast cancer screening. DESIGN: Randomised controlled trial. SETTING: Nine breast screening centres in England. SUBJECTS: 40,163 women aged 50-64 attending their first breast screening examination. INTERVENTIONS: Women were randomised to have one view mammography, two view mammography, or two view mammography in which one view was read by one reader and both views were read by another. MAIN OUTCOME MEASURES: Prevalence of cancer detected, recall rates, cost per cancer detected, and marginal cost per extra cancer detected. RESULTS: Two view mammography detected 24% more women with breast cancer (95% confidence interval 16% to 31%) than one view mammography. Prevalence of detected cancer was 6.84 with two view mammography and 5.52 per 1000 women with one view. The proportion of women recalled for assessment was 15% lower (95% confidence interval 6% to 23%) with two view (6.97%) than with one view (8.16%) mammography. The cost of two view screening was higher (26.46 pounds compared with 22.00 pounds per examination) but the average cost per cancer detected was similar (5330 pounds compared with 5310 pounds) and the marginal cost per extra cancer detected with two views was similar to the average cost (5400 pounds). CONCLUSION: Two view mammography is medically more effective than one view; it detects more cancers and reduces recall rates; it is also similarly cost effective financially.

Breast Neoplasms↗
PubMed1986

Human low-Mr kininogen contains three copies of a cystatin sequence that are divergent in structure and in inhibitory activity for cysteine proteinases.

We point out that human low-Mr kininogen contains three cystatin-like sequences, rather than two, as had previously been thought. The protein was purified by affinity chromatography on carboxymethyl-papain-Sepharose, and subjected to limited proteolysis by trypsin and chymotrypsin. Fragments were isolated, and three corresponding to the individual cystatin-like domains were identified. By comparison with the known amino acid sequence of the protein they were numbered 1 to 3 from the N-terminus. Domain 1 was not found to have any inhibitory activity for cysteine proteinases, which is consistent with the absence of residues that are highly conserved in inhibitors of the cystatin superfamily, and have previously been suggested to be essential for activity. Domain 2 was a good inhibitor of chicken calpain, and also papain and cathepsin L. Domain 3 showed negligible inhibition of calpain, but inhibited papain and cathepsin L strongly. The probable arrangement of disulphide bonds in the heavy chain of low-Mr kininogen is deduced from the homology with the cystatins and other evidence contained in the present paper.

Amino Acid Sequence↗
PubMed1985

Calpain inhibition by peptide epoxides.

A Ca2+-activated cysteine proteinase (calpain II) was purified from chicken gizzard smooth muscle by use of isoelectric precipitation, (NH4)2SO4 fractionation, chromatography on DEAE-Sepharose CL-6B, Reactive-Red 120-agarose and Mono Q. The apparent second-order rate constants for the inactivation of calpain by a series of structural analogues of L-3-carboxy-trans-2, 3-epoxypropionyl-leucylamido-(4-guanidino)butane (E-64) were determined. The fastest rate of inactivation was observed with L-3-carboxy-trans-2, 3-epoxypropionyl-leucylamido-(4-benzyloxy-carbonylamino)buta ne. It was possible to determine the active-site molarity of solutions of calpain by titration with E-64. When incubated with Ca2+, calpain underwent several steps of intermolecular limited proteolysis, via multiple pathways, followed by a slower loss of enzymic activity. The proteolytic steps preceding the loss of activity did not affect the rates of reaction of calpain with E-64 analogues.

Animals↗
PubMed1984

Studies on the mechanism of action of methoxatin-requiring methanol dehydrogenase: reaction of enzyme with electron-acceptor dye.

Bacterial methoxatin-dependent methanol dehydrogenase requires an electron acceptor, e.g., phenazine methosulfate (PMS), for activity. Oxidation of methanol shows a deuterium isotope effect of 4.3 in the presence of high concentrations of PMS; the effect is reduced at low PMS concentrations. This suggests that the catalytic reaction comprises at least two steps, one involving substrate and the other PMS. The UV-visible spectrum of methanol dehydrogenase undergoes a series of characteristic changes when PMS is added to the enzyme. It is proposed that these changes correspond to the formation of an enzyme intermediate, resulting from the reaction of PMS with the enzyme, which can subsequently react with substrate. Preincubation of the enzyme with PMS followed by dilution into a solution containing [14C]methanol results in an additional enzyme turnover compared to the control performed without preincubation with PMS. This confirms the proposal that the enzyme reacts with PMS before reacting with substrate. The reaction between the enzyme and PMS is not a redox reaction since no oxygen is consumed during the reaction nor is the PMS reduced. Methanol dehydrogenase is inactivated by cyclopropanol in the presence of PMS. The intermediate formed by reaction of the enzyme with PMS is also an intermediate in the cyclopropanol inactivation reaction. Preincubation of the enzyme with PMS gives an increase in the rate of inactivation by cyclopropanol. Cyclopropanol stoichiometrically equivalent to 13% of the enzyme is sufficient to completely inactivate the enzyme. The inactivation reaction shows neither a deuterium nor a tritium isotope effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Oxidoreductases↗
PubMed1984

The effects of iodine and thiol-blocking reagents on complement component C2 and on the assembly of the classical-pathway C3 convertase.

I2 can react with complement component C2 in a two-stage process. In the first stage, a form of C2 with enhanced haemolytic activity is produced. This form of C2 is cleaved to C2a and C2b by C1s at the same rate as native C2. The enhanced C2 haemolytic activity correlates with the ability to form a stable fluid-phase C3 convertase on addition of the C2 to C4b and C1s. It reflects an increased affinity for C4b of C2a formed from I2-treated C2, although the affinity for C4b of I2-treated C2 itself is not markedly increased. The specific activity of C3 convertase formed from I2-treated C2 is the same as that formed from native C2. The second stage of the reaction with I2, which is favoured at high pH or in the presence of excess I2, inactivates C2 on production of a species that cannot be cleaved by C1s. The presence of a single free thiol group in C2, which is the site of modification by I2, was confirmed by titration with p-chloromercuribenzoate, iodoacetamide and 5,5'-dithiobis-(2-nitrobenzoic acid). A single thiol group is also present in Factor B, and the cysteine residue, like that in C2, requires denaturation of the protein before reaction with iodoacetamide and 5,5'-dithiobis-(2-nitrobenzoic acid) but not p-chloro- mercuribenzoate .

Chloromercuribenzoates↗
PubMed1983

The reaction of iodine and thiol-blocking reagents with human complement components C2 and factor B. Purification and N-terminal amino acid sequence of a peptide from C2a containing a free thiol group.

Human complement components C2 and Factor B each contain one free thiol group/molecule. Reaction with p-chloromercuribenzoate destroyed the haemolytic activity of C2 but had no effect on Factor B. Reaction of C2 with I2 gave a 16-fold enhancement of its haemolytic activity. The pH optimum for the reaction was 7.0. The I2 reacted at the thiol group in C2 with a stoicheiometry of 1 mol of I2/mol of C2. The product of the reaction was unaffected by millimolar concentrations of dithiothreitol; however, azide and cyanide were inhibitory. Reaction with azide did not result in re-expression of the thiol group. Mild oxidation of the thiol group with m-chloroperbenzoic acid did not enhance the haemolytic activity. The results suggest that reaction with I2 causes intramolecular covalent, but not disulphide, bond formation. I2 reacted with Factor B at the free thiol group without affecting the haemolytic activity. A CNBr-cleavage peptide from C2a (obtained by cleavage of C2 by subcomponent C1s) containing the free thiol group was isolated. Automated Edman degradation of the peptide showed that it was the N-terminal peptide of C2a. The free thiol group was identified at position 18.

Amino Acid Sequence↗
PubMed1981

The separation of functionally distinct forms of the third component of human complement (C3).

Complement component C3 prepared by the method of Tack & Prahl [(1976) Biochemistry 15, 4513-4521] was found to contain the following trace contaminants: C3b, haemolytically inactive C3 with intact alpha- and beta-chains (C3u) and degraded C3 (apparent mol.wt. 140000) with an intact beta-chain but with a fragmented alpha-chain. The proportion of C3u in the C3 is increased on standing and by freezing and thawing. These contaminants could be separated from each other and from native C3 by chromatography on sulphated Sepharose. They have been characterized by their susceptibility to C3b inactivator in the presence of beta 1H, their ability to be cleaved by C3 convertase and their ability to form alternative-pathway C3 convertase in solution. Incubation of C3b or C3u with beta 1H and C3b inactivator resulted in cleavage of the C3 species; the alpha'-chain of C3b was cleaved to fragments of apparent mol.wts. 67000 and 43000, the alpha-chain of C3u was cleaved to fragments of apparent mol.wt. 75000 and 43000. Native C3 and degraded C3 were unaffected by incubation with beta 1H and C3b inactivator. C3u, unlike C3, was not cleaved to C3b by the classical- or alternative-pathway C3 convertase in solution. When C3b or C3 was incubated with factors B and D, forming C3 convertase, the initial rate of factor-B cleavage was several order of magnitude lower in the presence of C3 than in the presence of C3b. The slow rate observed for C3 could be decreased by preincubation with beta 1H and C3b inactivator or by rechromatography of the C3. The degraded C3 did not support factor-B cleavage by factor D.

Chromatography, Affinity↗
PubMed1972

Mannitol sensitivity.

The addition of mannitol to cultures of Salmonella typhimurium mutants missing mannitol-1-phosphate dehydrogenase causes stasis or lysis. Mannitol-1-phosphate accumulates intracellularly to concentrations of 20 mm. The incorporation of acetate into lipid is inhibited before cell wall, protein, or nucleic acid synthesis.

Acetates↗