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Biomedical subjects

M Knapp

Publications and source records attributed to M Knapp.

At least 91 records · Page 5Linked to original sources
PubMed1999

Evaluating mental health policy in England. Care Programme Approach and supervision registers.

BACKGROUND: The Care Programme Approach (CPA) and supervision register policies in England are intended to prioritize patients to receive specialist mental health care. AIMS: To describe and evaluate the practical application of the policies. METHOD: A questionnaire survey of key informants in mental health provider trusts and an analysis of aggregated data collected by health authorities using the Mental Illness Needs Index as a measure of population need. RESULTS: On average, 1175 per 100,000 total population are subject to the CPA (95% CI = 1055-1309) and 8.6 per 100,000 (95% CI = 7.5-9.9) are on supervision registers. Wide local variations in the number of people subject to the CPA and supervision registers are not explained by variations in population need. CONCLUSIONS: Prioritization to receive specialist mental health services is carried out inconsistently, and inequitable use of resources may result.

Community Mental Health Services↗
PubMed1999

The EPSILON study of schizophrenia in five European countries. Design and methodology for standardising outcome measures and comparing patterns of care and service costs.

BACKGROUND: There is a lack of cross-national research on care for people with schizophrenia. AIMS: To produce standardised European versions of five instruments in key areas of mental health service research in five languages, and to compare data from five European countries regarding patients with schizophrenia and mental health care provision and costs. METHOD: Five centres, in Amsterdam, Copenhagen, London, Santander and Verona, participated. Instruments assessing needs, service use, informal career involvement, quality of life, and service satisfaction were subjected to a conversion procedure including translation, back-translation, focus group discussion and reliability assessment. Patients of local mental health services with a Schedules for Clinical Assessment in Neuropsychiatry diagnosis of schizophrenia were interviewed. RESULTS: Service provision varied between sites; 404 patients were studied. Instrument reliability was found to be good. CONCLUSIONS: The instruments developed were reliable across the range of countries, and will facilitate future comparative health service research.

Adolescent↗
PubMed1999

hSKCa3: no association of the polymorphic CAG repeat with bipolar affective disorder and schizophrenia.

hSKCa3 is a neuronal small conductance calcium-activated potassium channel, which contains a polyglutamine tract, encoded by a polymorphic CAG repeat in the gene. Since an association between longer alleles of this CAG repeat and bipolar disorder or schizophrenia has been reported, we genotyped the polymorphic CAG repeat in 91 German family trios of patients with bipolar disorder I and used the transmission disequilibrium test (TDT) to test for association. Applying a dichotomized model (< or = 19 or > 19 CAG triplets), we found no evidence for an association of longer alleles with bipolar disorder (TDT = 0.75, P = 0.386). Regarding the whole range of alleles, there was no preference in transmitting the larger of the two observed alleles from parents to the affected offspring. In parallel we performed an independent case-control study on German patients with bipolar disorder and schizophrenia. Again we did not detect an overrepresentation of longer CAG repeats in patients. Thus, our data do not support the hypothesis that longer CAG repeats in the hSkCa3 gene contribute to the susceptibility for bipolar disorder and schizophrenia.

Adult↗
PubMed1998

Short CAG repeats within the hSKCa3 gene associated with schizophrenia: results of a family-based study.

In a family-based association study we investigated transmission of a multiallelic CAG repeat in a novel neuronal potassium channel gene, hSKCa3, in 59 parent/ offspring trios. In contrast to recent reports of an association of moderately large repeats with schizophrenia in case-control studies, our findings indicate that short CAG repeats (< or=19 repeats) are transmitted at an increased frequency to schizophrenic offspring (p=0.014), particularly among familial cases (p=0.007). No evidence for a parent-of-origin effect was found. Multiallelic TDT procedure showed no association of individual CAG repeats to schizophrenia. Further studies using family-based designs should clarify whether hSKCa3 is a susceptibility factor to schizophrenia or co-segregates with a major disease gene in tight linkage.

Adolescent↗
PubMed1998

The 0.78 A structure of a serine protease: Bacillus lentus subtilisin.

Ultrahigh-resolution X-ray diffraction data from cryo-cooled, B. lentus subtilisin crystals has been collected to a resolution of 0.78 A. The refined model coordinates have a rms deviation of 0.22 A relative to the same structure determined at room temperature and 2.0 A resolution. Several regions of main-chain and side-chain disorder have been identified for 21 out of 269 residues in one polypeptide chain. Hydrogen atoms appear as significant peaks in the Fo - Fc difference electron density map, and carbon, nitrogen, and oxygen atoms can be differentiated. The estimated standard deviation (ESD) for all main-chain non-hydrogen bond lengths is 0.009 A and 0.5 degrees for bond angles based on an unrestrained full-matrix least-squares refinement. Hydrogen bonds are resolved in the serine protease catalytic triad (Ser-His-Asp). Electron density is observed for an unusual, short hydrogen bond between aspartic acid and histidine in the catalytic triad. The hydrogen atom, identified by NMR in numerous serine proteases, appears to be shared by the heteroatoms in the bond. This represents the first reported correlation between detailed chemical features identified by NMR and those in a cryo-cooled crystallographic structure determination at ultrahigh resolution. The short hydrogen bond, designated "catalytic hydrogen bond", occurs as part of an elaborate hydrogen bond network, involving Asp of the catalytic triad. While unusual, these features appear to have conserved analogues in other serine protease families although specific details differ from family to family.

Aspartic Acid↗
PubMed1998

Promoter-independent regulation of cell-specific dopamine receptor expression.

Here we describe the construction of recombinant adenoviruses expressing dopamine D2 and D4 receptors, and their ability to mediate high levels of heterologous expression in a variety of cell types in vitro and in vivo for at least 7 days post infection. These experiments demonstrated that maximum receptor expression is achieved generally within 24 h and remains constant thereafter. Maximum expression levels were highly variable between cell lines and dependent on infection efficiency and promoter strength. Correction for these two variables revealed differences in relative expression levels between cell lines varying by two orders of magnitude. Our results indicate that in addition to gene transcription, post-transcriptional mechanisms play a dominant role in determining dopamine receptor levels in this system.

Animals↗
PubMed1998

The impact on general practitioners of the changing balance of care for elderly people living in institutions.

OBJECTIVES: To describe utilisation of general practitioners by elderly people resident in communal establishments; to examine variations in general practitioner utilisation and estimate the likely impact of the "downsizing" of long stay provision in NHS hospitals. DESIGN: Secondary analyses of the survey of disability among adults in communal establishments conducted by the Office of Population Censuses and Surveys in 1986, and projection to present day. SETTING: Nationally representative sample of communal establishments in Great Britain. SUBJECTS: Disabled residents aged 65 or more without mental handicap. RESULTS: Residents with higher levels of disability, disorders of the digestive system, resident in smaller local authority homes or larger voluntary residential homes were more likely to consult a general practitioner. For those who consulted, higher levels of disability and morbidity and residence in a private nursing home or a larger private residential home were all associated with greater general practitioner utilisation. Overall, when residents' characteristics and size of home was controlled for, residents in nursing homes had greater predicted utilisation than those in residential care homes. People who would previously have been cared for in NHS hospitals and are now cared for in nursing homes have high predicted utilisation due to their greater morbidity and disability. CONCLUSION: The "downsizing" of NHS provision for elderly people has increased demand on general practitioners by 160 whole time equivalents per year in Britain.

Aged↗
PubMed1998

High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene.

Central serotonergic neurotransmission has been implicated in the aetiology of ethanol tolerance and dependence. Cellular expression of the serotonin transporter and serotonin reuptake is modulated via a polymorphic, repetitive element in the 5'-flanking regulatory region of the serotonin transporter gene (5-HTTLPR). We report the association of the low-activity, short variant of the 5-HTTLPR with high ethanol tolerance among young adults in a case-control association study (n = 713). The low-activity 5-HTTLPR showed a significantly increased allele frequency (chi2 = 7.30; df = 2; P = 0.007) and genotype frequency among young adults (< or =26 years) with high ethanol tolerance homozygous for the short allele (chi2 = 7.58; df = 1; P = 0.02). The estimated odds ratio for the homozygous short variant compared to the homozygous long variant was 2.82 (95% CI 1.30-6.11). This indicates that the low-activity 5-HTTLPR may be involved in the neuronal mechanisms responsible for ethanol tolerance and dependence.

Adult↗
PubMed1998

Fine mapping of the autosomal recessive polycystic kidney disease locus (PKHD1) and the genes MUT, RDS, CSNK2 beta, and GSTA1 at 6p21.1-p12.

A total of 33 polymorphic markers were analyzed to generate a high-resolution genetic linkage map of the locus PKHD1 (polycystic kidney and hepatic disease 1) for the autosomal recessive polycystic kidney disease (ARPKD), using a combination of recombination mapping and linkage analysis in 164 families. Recombinants narrowed the PKHD1 region from 3.8 cM to a 1-cM interval flanked by the markers D6S1024 and D6S1714. Linkage disequilibrium analysis in 13 Finnish ARPKD families identified two different highly conserved haplotypes with four distal flanking markers, suggesting the existence of at least two major mutations of Finnish origin. The genes MUT (methylmalonyl coenzyme A-mutase), RDS (retinal degeneration, slow), CSNK2 beta (casein kinase II, beta subunit), and GSTA1 (glutathione S-transferase alpha, type 1) were excluded as PKHD1 genes using both established and novel intragenic polymorphisms in families with key recombinants. These genetic data, combined with our YAC-based physical map of the 6p21-p12 region, will facilitate efforts to positionally clone the PKHD1 gene.

Casein Kinase II↗
PubMed1998

Adenosine A1 receptor and bipolar affective disorder: systematic screening of the gene and association studies.

In the present study we sought to identify genetic variation in the adenosine A1 receptor (A1AR) gene on chromosome 1q31-32.1, which through alteration of protein function or level of expression might contribute to the genetic predisposition to bipolar affective disorder. We performed a systematic mutation scan of the whole coding sequence as well as 5' and 3' untranslated regions by means of single-strand conformation analysis. The region upstream to the coding sequence we investigated contains two functional promoters. Screening 42 patients with bipolar affective disorder, we detected 11 DNA sequence variants (48T/A, 267 + 275C/T, 805T/G, 1777C/A, 1827C/T, 1904C/T, 2126G/T, 2294insT, 2776C/T, 2777del36, 2819T/G). Determining the frequency of these variants in 42 anonymous blood donors, we observed a non-significant (P < 0.06) trend towards an underrepresentation of the 2126T variant in patients when compared to controls. On the other hand, the 2777del36 and the 2819G variant were not found among the controls. These findings were followed up in a large independent replication sample. However, we were not able to confirm the initial findings in the second sample. Our data suggest that genetically determined variation of the A1AR and its two promoters do not play a major role in the development of bipolar affective disorder.

Base Sequence↗
PubMed1998

The economic consequences of Alzheimer's disease in the context of new drug developments.

The first national symptomatic treatment for Alzheimer's disease has received a very mixed and perhaps ageist reception from purchasers of health care in the UK. This is largely because detailed information on the long-term effects of this class of drugs is scarce. However, by looking at the published evidence on the economic burden of Alzheimer's disease, some observations and assumptions can be made as to the influence of the new drug treatments. The drug therapies available and those most likely to become licensed are reviewed and the potential economic impact is discussed. Long-term outcome studies would properly address this, but as these drugs have now demonstrated efficacy, particularly in non-cognitive behaviours, it will be ethically more difficult to maintain patients on placebo for long periods. Some assumptions therefore have to be made from long-term open-label studies. Those drugs currently available, and those in development, may offer effective treatment for some of the core symptoms of Alzheimer's disease, slowing the rate of cognitive decline and preserving competence in activities of daily living for longer. If handled correctly, these treatments have the potential to offer cost savings for many patients, and cost-effectiveness improvements look probable.

Aged↗
PubMed1998

Does a hostel's managing agency determine the access to psychiatric services of its residents?

This study examines the effect of managing agency (local authority, private or voluntary) on the use of other health and social care services by residents in mental health hostels and group homes with different levels of staffing in England and Wales. The sample comprised 1323 residents in 275 facilities in eight districts. The measures of service use were number of days in hospital and number of other service contacts. There were highly significant differences between facilities with similar levels of staffing managed by different agencies. Residents in the voluntary sector used fewer community services overall; residents in low-staffed local authority facilities used more services than those in similar facilities managed by other agencies. These differences were not easily explained by differences in the social or clinical characteristics of residents. This suggests that there may be organisational factors, e.g. hostel staff, knowledge of services, which influence access to and use of community services.

Adult↗
PubMed1998

Susceptibility for schizophrenia is not influenced by a functional insertion/deletion variant in the promoter of the serotonin transporter gene.

A possible dysregulation of serotonergic neurotransmission has been implicated in the aetiology of schizophrenic psychoses. In the present study we analysed allelic and genotypic variations of a recently described functional polymorphic region in the promoter of the human serotonin transporter gene (5-HTTLPR) and a variable tandem repeat (VNTR) in intron 2 of the 5-HTT gene. We investigated 413 unrelated individuals, 180 schizophrenic patients and 233 blood donors as controls. With regard to the 5-HTTLPR, both the schizophrenic and the control group did not significantly differ between genotype frequencies (chi2, p = 0.920) and allele frequencies (chi2, p = 0.836). The odds ratio for subjects with schizophrenia who were homozygous for the short allele was 1.04 (95% CI 0.59-1.84). No evidence of allelic association to specific schizophrenia subtypes was found. The 5-HTT associated VNTR also showed no significant differences between either the allelic or the genotypic distributions. Haplotype analysis revealed a significant overall linkage disequilibrium at a level of p = 0.00004. Our findings indicate that both polymorphisms are unlikely to play a substantial role in the genetic predisposition to schizophrenic disorders.

Adolescent↗
PubMed1998

Insertion/deletion variant (-141C Ins/Del) in the 5' regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder. Short communication.

A possible dysregulation of dopaminergic neurotransmission has been implicated in the aetiology of schizophrenic psychoses, in particular of paranoid-hallucinatory states, and of the manic episodes of bipolar affective disorder. In the present study we analysed allelic and genotypic variations of a recently described functional deletion/insertion variant (-141C Ins/Del) in the 5' flanking region of the human dopamine D2 receptor gene. We investigated a total of 620 unrelated individuals, comprising 260 schizophrenic patients, 70 patients with bipolar affective disorder, and 290 population controls. Analysis of the -141C Ins/Del variant revealed that the schizophrenic, bipolar affective and control groups did not differ significantly regarding genotype frequencies and allele frequencies. No evidence of an allelic association with either a family history of schizophrenic psychosis or a diagnosis of schizophrenia of the paranoid type (according to ICD 10) was found. Our findings indicate that the -141C Del variant in the 5' flanking region of the human dopamine D2 receptor gene is unlikely to play a substantial role in genetic predisposition to major psychiatric disorders in Caucasians.

Adult↗
PubMed1998

The costs of community-based psychiatric care for first-ever patients. A case register study.

BACKGROUND: Analysing costs measures in conjunction with psychiatric case register (PCR) data can provide important epidemiologically-based information on resource utilization. Costing the service use patterns of first-ever patients can indicate the shape and likely resource consequences for mental health services operating within a community-based system of care. METHODS: Yearly costs were calculated for the 299 first-ever patients and 768 longer-term patients who contacted the South-Verona Psychiatric Case Register between 1 January 1992 and 31 December 1993. Bivariate and multivariate analyses were used to compare costs between these groups and to test the associations between costs and the sociodemographic and diagnostic data recorded on the PCR. RESULTS: For all diagnostic groups identified, first-ever patients were found to be less costly to support than longer-term patients, even after adjustment for various factors, including whether patients were single consulters. When multivariate analyses were employed, between 20% and 69% of the cost variation for first-ever patients could be explained by patient and other characteristics, and the effect of the contact (first or subsequent) variable was reduced. CONCLUSION: This study considered only the costs to the specialist psychiatric services but the methodology allows the likely annual resource implications of supporting new patients to be predicted from data collected at first contact. Such information can help ensure that services are adequately funded and that the resources are deployed appropriately between client groups.

Adolescent↗
PubMed1998

Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease.

Several lines of evidence suggest a contribution of adenosinergic neurotransmission to the development of panic disorder. We therefore hypothesized that variation in the A1 and A2a adenosine receptor (AR) genes modifies genetic susceptibility to panic disorder. To test this hypothesis, we screened 38 patients with panic disorder for mutations in the coding sequence of the A1AR and A2aAR genes. An association study between the identified DNA sequence variants and panic disorder was performed in an extended sample of 89 patients and matched controls. One silent mutation (716T/G) in the A1AR gene and two silent mutations (432C/T and 1083C/T) in the A2aAR gene were detected. The association sample shows a significant association between the 1083T allele (P=0.01) and 1083T/T genotype (P=0.024) of the A2AR gene and panic disorder. Our findings thus lend further support to the hypothesis that the A2aAR gene, or a locus in linkage disequilibrium with it, confers susceptibility to panic disorder. Replication studies in independent samples with nuclear families applying the transmission disequilibrium test (TDT) are warranted.

DNA Primers↗