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M Knapp

Publications and source records attributed to M Knapp.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1998

Evaluation of a restricted likelihood ratio test for mapping quantitative trait loci with extreme discordant sib pairs.

Risch and Zhang recently proposed to use extreme discordant sib pairs for mapping quantitative trait loci. Here, it is shown that the set of genetically possible distributions of the number of marker alleles in such sib-pairs is described by two inequalities. Thus, a likelihood ratio test analogous to Holmans's possible triangle test for affected sib pairs can be defined. The performance of this test is compared to the mean test considered by Risch and Zhang. For most of the genetic models considered, the mean test is slightly more powerful than the restricted likelihood ratio test. However, for models with a rare recessive gene (or equivalently a common dominant gene), the restricted likelihood ratio test is much more powerful.

Alleles↗
PubMed1998

[The costs of schizophrenia].

Schizophrenia is regarded as the most expensive mental illness because of its specific symptoms and characteristics (e.g. early onset, often chronic course, high rates of readmission to hospital treatment, high rate of disabilities and extensive rehabilitative interventions), which prove to be extremely costly. Despite this, studies on the financial aspects of schizophrenia or the provision of care for schizophrenic patients has become an issue of psychiatric research only since the beginning of the reform of mental healthcare. Early cost studies had been conducted in the United States (US) during the fifties. Since then, they have grown in number not only in the US and in Great Britain, but also on the Continent of Europe. On an international level, comprehensive literature concerning methodology has attempted to establish cost studies as an integral part of mental health services research. Germany, however, is far behind international developments. Although the fundamental lack of empirical data on costs both in psychiatry as a whole and in schizophrenia had already been ascertained in a large national survey called "Psychiatrie-Enquête" in the mid-seventies, little has changed since then. One reason for these possibly great methodological problems is associated with the assessment of cost data in fragmented community mental health care networks, which in Germany include the additional obstacle--unlike abroad--of non-availability of access to data from case registers. Psychiatric case registers are not permitted in Germany because of very strict data protection laws. Despite the problems in methodology, there is an urgent need in Germany to remedy the lack of cost data for schizophrenic-patient care. The pressure of curbing costs in health care will probably force the German mental health care services to provide detailed cost data with regular reports in the future.

Humans↗
PubMed1998

A gene for universal congenital alopecia maps to chromosome 8p21-22.

Complete or partial congenital absence of hair (congenital alopecia) may occur either in isolation or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal-recessive mode of inheritance (MIM 203655). As yet, no gene has been linked to isolated congenital alopecia, nor has linkage been established to a specific region of the genome. In an attempt to map the gene for the autosomal recessive form of the disorder, we have performed genetic linkage analysis on a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia). We have analyzed individuals of this family, using >175 microsatellite polymorphic markers of the human genome. A maximum LOD score of 7.90 at a recombination fraction of 0 has been obtained with locus D8S258. Haplotype analysis of recombination events localized the disease to a 15-cM region between marker loci D8S261 and D8S1771. We have thus mapped the gene for this hereditary form of isolated congenital alopecia to a locus on chromosome 8p21-22 (ALUNC [alopecia universalis congenitalis]). This will aid future identification of the responsible gene, which will be extremely useful for the understanding of the biochemistry of hair development.

Alopecia↗
PubMed1998

Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.

The action of antipsychotic drugs on dopamine receptors suggests that dopaminergic signal transmission may play a role in the development of schizophrenia. We tested eight candidate genes (coding for dopamine receptors, the dopamine transporter, and G-proteins) in 59 families from Germany and Israel, for association. A P value of .00055 (.0044 when corrected for the no. of markers tested) was obtained for the intronic CA-repeat marker G-olfalpha on chromosome 18p. The value decreased to .000088 (.0007) when nine sibs with recurrent unipolar depressive disorder were included. Linkage analysis using SSLP markers densely spaced around G-olfalpha yielded a maximum two-point LOD score of 3.1 for a marker 0.5 cM distal to G-olfalpha. Multipoint analysis under the assumption of heterogeneity supported this linkage-whether the affected pheotype was defined narrowly or broadly-as did nonparametric linkage (NPL). In 12 families with exclusively maternal transmission of the disease, the NPL value also supported linkage to this marker. In order to test for association/linkage disequilibrium in the presence of linkage, the sample was restricted to independent offspring. When this sample was combined with 65 additional simplex families (each of them comprising one schizophrenic offspring and his or her parents), the 124-bp allele of G-olfalpha was transmitted 47 times and was not transmitted 21 times (P=.009). These results suggest the existence, on chromosome 18p, of a potential susceptibility locus for functional psychoses.

Chromosomes, Human, Pair 18↗
PubMed1998

Collaborating for improvement in health professions education.

Continual improvement efforts have been slower in health professions education than in health care delivery. This article identifies the lessons learned by teams working in an Interdisciplinary Professional Education Collaborative in overcoming barriers to carrying out continual improvement efforts in these educational organizations.

Competency-Based Education↗
PubMed1998

Public, private and voluntary residential mental health care: is there a cost difference?

OBJECTIVES: To determine how public (NHS or local government), private (for-profit) and voluntary (non-profit) providers of residential mental health care compare. Do they support different clienteles? And do their services cost different amounts? METHODS: Based on a cross-sectional survey of residential care facilities and their residents in eight English and Welsh localities, the characteristics and costs of care in the different sectors (NHS, local government, private, voluntary) were compared. Variations in cost were examined in relation to residents' characteristics using multiple regression analyses, which also allowed standardisation of results before making inter-sectoral comparisons. RESULTS: Private and voluntary providers of residential care support different clienteles from the public sector. The patterns of inter-sectoral cost differences vary between London and non-London localities. In London, voluntary sector facilities may be more cost-efficient than the other sectors, but local government/private sector comparisons show no consistent difference. Outside London, the results suggest clear cost advantages for the private and voluntary sectors over the local government sector. CONCLUSIONS: Private and voluntary providers may have some economic advantages over their public counterparts. However, outcomes for residents were not studied, leaving unanswered the question of comparative cost-effectiveness.

Community Mental Health Services↗
PubMed1998

Cost-effectiveness evaluation of compliance therapy for people with psychosis.

BACKGROUND: Non-compliance rates with antipsychotic medication can be high, and the personal and societal costs are considerable. A new psychological intervention, compliance therapy seeks to improve compliance and patient outcomes and reduce treatment costs. METHOD: A randomised controlled study examined the cost-effectiveness of compliance therapy compared to non-specific counselling over 18 months for 74 people with psychosis admitted as inpatients at the Maudsley Hospital. Bivariate and multivariate analyses were conducted to test for differences and to explore inter-patient cost variations. RESULTS: Compliance therapy is more effective and is no more expensive. Consequently, compliance therapy is more cost-effective than non-specific counselling at six, 12 and 18 months. CONCLUSIONS: There are compliance, outcome and cost-effectiveness arguments in favour of compliance therapy in preference to non-specific counselling.

Adult↗
PubMed1998

Home-based versus hospital-based care for serious mental illness. Controlled cost-effectiveness study over four years.

BACKGROUND: The Daily Living Programme (DLP) offered intensive home-based care with problem-centred case management for seriously mentally ill people facing crisis admission to the Maudsley Hospital, London. The cost-effectiveness of the DLP was examined over four years. METHOD: A randomised controlled study examined cost-effectiveness of DLP versus standard in/out-patient hospital care over 20 months, followed by a randomised controlled withdrawal of half the DLP patients into standard care. Three patient groups were compared over 45 months: DLP throughout the period, DLP for 20 months followed by standard care, and standard care throughout. Bivariate and multivariate analyses were conducted (the latter to standardise for possible inter-sample differences stemming from sample attrition and to explore sources of within-sample variation). RESULTS: The DLP was more cost-effective than control care over months 1-20, and also over the full 45-month period, but the difference between groups may have disappeared by the end of month 45. CONCLUSIONS: The reduction of the cost-effectiveness advantage for home-based care was perhaps partly due to the attenuation of DLP care, although sample attrition left some comparisons under-powered.

Adolescent↗
PubMed1998

Economic burden of drug dependency. Social costs incurred by drug users at intake to the National Treatment Outcome Research Study.

BACKGROUND: The use of illegal drugs is seen as a major social problem. The social costs can be high. METHODS: Self-report data from interviews at intake to the National Treatment Outcome Research Study (NTORS) for 1075 drug users and cost data from various sources were used to estimate criminal behaviour and health and addiction service costs for a 12-month period. Multivariate statistical analysis was used to analyse cost variations. RESULTS: Total costs for one year for the drug users amounted to over 12 million Pounds, the majority attributable to self-reported criminal behaviour. Social costs were positively related to a variety of factors including instability in living circumstances, amount of heroin used and whether or not drugs were taken intravenously. CONCLUSIONS: The study clearly demonstrates the economic and social burden associated with heavy drug users and highlights the need for further investigations into the costs and benefits of policies that can reduce these social costs.

Age Factors↗