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M Knapp

Publications and source records attributed to M Knapp.

At least 73 records · Page 4Linked to original sources
PubMed2000

Aims, outcome measures, study sites and patient sample. EPSILON Study 1. European Psychiatric Services: Inputs Linked to Outcome Domains and Needs.

BACKGROUND: Cross-national research into the care of people with severe mental illnesses is hampered by a lack of standardised measures. The European Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) Study is a European Union funded project within the BIOMED-2 programme. The project aims to develop standardised instruments to facilitate future cross-national research. AIMS: To describe the aims, outcome measures, study sites and patient samples of the EPSILON Study. METHOD, RESULTS, CONCLUSIONS: See companion papers in this supplement.

Adolescent↗
PubMed2000

Quality and costs of community-based residential supports, village communities, and residential campuses in the United Kingdom.

The costs, nature, and benefits of residential supports were examined for 86 adults with mental retardation living in village communities, 133 adults living in newly built residential campuses, and 281 adults living in dispersed housing schemes (small community-based group homes and supported living). Results indicated that (a) the adjusted comprehensive costs of provision in dispersed housing schemes were 15% higher than in residential campuses and 20% higher than in village communities; (b) dispersed housing schemes and village communities offered a significantly greater quality of care than did residential campuses; and (c) there appeared to be distinct patterns of quality of life benefits associated with dispersed housing schemes and village communities, with both approaches offering a greater quality of life than did residential campuses.

Adult↗
PubMed2000

Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans.

Vitamin D has been shown to exert manifold immunomodulatory effects. Because type 1 diabetes is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse, we investigated the role of the vitamin D receptor (VDR) gene as a candidate for type 1 diabetes susceptibility. A total of 152 Caucasian families with at least one affected offspring were genotyped for four VDR restriction-site polymorphisms (FokI, BsmI, ApaI, and TaqI). Whereas the BsmI, ApaI, and TaqI polymorphisms are in strong linkage disequilibrium with each other, no significant linkage disequilibrium with the FokI site was observed. Extended transmission disequilibrium testing (ETDT) was used to detect preferential transmission of allelic combinations to affected offspring. We found significant haplotype-wise ETDT results for the BsmI/ApaI/TaqI (chi2 = 18.886, df = 7, P = 0.0086), the BsmI/TaqI (chi2 = 8.373, df = 3, P = 0.0389), and theApaI/TaqI (chi2 = 17.182, df = 3, P = 0.0006) haplotypes. The "At" and "Bt" alleles confer an increased risk, whereas "AT" and "at" are protective. The combination with the strongest susceptibility was the "BAt" haplotype (64% transmitted, P = 0.0106). Analysis of the FokI site does not provide more information on susceptibility (FokI/BsmI/ApaI/TaqI [chi2 = 24.702, df = 15, P = 0.0541]). These findings suggest a linkage of VDR itself or a nearby gene with type 1 diabetes susceptibility in Germans, confirming respective observations previously made in Indian Asians.

Adolescent↗
PubMed2000

Same-day transfer of patients to the cardiac telemetry unit after surgery: the Rapid after Bypass Back into Telemetry (RABBIT) program.

Early data from this project suggest that the RABBIT program fulfilled the process improvement goals of decreasing costs of cardiac surgery and maintaining high quality. Decreased cost was achieved by decreasing time to extubation and decreasing length of stay in the ICU and the total length of stay in the hospital. The cost savings were achieved without compromising the quality of care, which was assessed by measuring rates of readmission to the ICU and to the hospital and by surveying patients about their level of satisfaction. The success of the RABBIT program can be attributed to several factors. First, members of the cardiac surgery quality improvement team worked well together to solve problems and overcome obstacles, particularly after the pilot program. Second, naming the program helped to motivate staff, physicians, and patients. Outcome data was shared with the staff quarterly, and successes were celebrated. Finally, the use of a facilitator early in the process to establish the process with the surgeons and the staff was invaluable. Opportunities for continued improvement include resolving operational difficulties related to availability of beds and staffing, continuing work with physicians in changing practice patterns, increasing efficiency in scheduling operating rooms, and adjusting the preoperative education provided to patients and their families about the length of stay to expect. Quarterly outcome analysis continues, with reports to the cardiac surgery quality improvement team. The team continues to explore creative solutions to the aforementioned issues, as the goal of having 25% of patients who undergo cardiac surgery be transferred to the CTU on the day of surgery has remained elusive.

Coronary Artery Bypass↗
PubMed1999

Human delta-opioid receptor gene and susceptibility to heroin and alcohol dependence.

In the present study, we tested the hypothesis that addictive behavior may be influenced by genetic variation in the human delta-opioid receptor gene. We investigated the contribution of a silent T to C change in the coding region to the development of heroin and alcohol dependence using large case-control and family-based association samples. Presence of the C allele was previously reported to significantly increase the risk for heroin dependence. In the present study, however, we did not find statistically significant differences between patients and controls nor did we find preferential transmission of the C allele from parents to affected offspring. Our results, therefore, do not support an association between genetic variation of the delta-opioid receptor and addictive behavior in man.

Adult↗
PubMed1999

Engineered Bacillus lentus subtilisins having altered flexibility.

The three-dimensional structures of engineered variants of Bacillus lentus subtilisin having increased enzymatic activity, K27R/N87S/V104Y/N123S/T274A (RSYSA) and N76D/N87S/S103A/V104I (DSAI), were determined by X-ray crystallography. In addition to identifying changes in atomic position we report a method that identifies protein segments having altered flexibility. The method utilizes a statistical analysis of variance to delineate main-chain temperature factors that represent significant departures from the overall variance between equivalent regions seen throughout the structure. This method reveals changes in main-chain mobility in both variants. Residues 125-127 have increased mobility in the RSYSA variant while residues 100-104 have decreased mobility in the DSAI variant. These segments are located at the substrate-binding site and changes in their mobility are believed to relate to the observed changes in proteolytic activity. The effect of altered crystal lattice contacts on segment flexibility becomes apparent when identical variants, determined in two crystal forms, are compared with the native enzyme.

Bacillus↗
PubMed1999

Functional PAX-6 gene-linked polymorphic region: potential association with paranoid schizophrenia.

BACKGROUND: Early differentiation of the nervous system and adult CNS neuroplasticity is modulated by PAX-6. We have shown previously that a highly polymorphic, functional AC/AG repeat in the 5' regulatory region of the gene showed significantly increased promoter activity, if containing > or = 29 repeats, and that the heterozygous genotype (< or = 28/> or = 29) revealed increased mRNA PAX-6 levels in human brain tissue compared to the homozygous short variant. METHODS: In a case-control study of 655 unrelated individuals, allele frequencies and genotype distributions of the functional PAX-6 promoter polymorphism were investigated comprising patients with DSM-IV schizophrenia, patients with affective disorders, and population controls. RESULTS: No allelic or genotypic association of the PAX-6 promoter polymorphism to affective disorder or to schizophrenia as one disease entity was observed. After subtyping schizophrenia into paranoid and nonparanoid forms, potential evidence was found for a genotypic association of the high-activity variant with the paranoid subtype of schizophrenia (p = .02). The estimated odds ratio was 1.7 (95% CI .98 to 2.95) for those heterozygous and 1.4 (95% CI .82 to 2.42) for those heterozygous or homozygous for the high-activity variant compared to the homozygous low-activity variant. CONCLUSIONS: Our finding indicates that early developmental genes may be involved in the etiopathogenesis of schizophrenia subtypes via variable transcriptional regulation in the developing and adult human brain.

Adult↗
PubMed1999

DAT1 gene polymorphism in alcoholism: a family-based association study.

BACKGROUND: The present study tests the hypothesis that the 9-repeat allele of the dopamine transporter gene (DAT1; SLC6A3) is more frequent in alcohol-dependent probands--and in particular those with severe withdrawal symptoms (seizures and/or delirium)--compared to nonalcoholics. METHODS: To avoid stratification effects, the family-based association approach of Falk and Rubinstein was used in our sample of 87 alcohol-dependent probands and their biological parents. RESULTS: By applying a family-based association approach, we were not able to detect significant association between allele 9 at DAT1 (SLC6A3) and alcoholism as well as between patients with or without severe withdrawal symptoms. CONCLUSIONS: Based on our data, the impact of the 9-repeat allele of the dopamine transporter gene in alcoholism and the severity of alcohol withdrawal symptoms is putatively not substantial.

Alcoholism↗
PubMed1999

Genetic analysis of a complex disease in the presence of an environmental risk factor.

The role of a gene in a disease may be hidden by the presence of another risk factor such as an environmental factor. In that case, stratifying the data according to this factor strengthens power to detect linkage or association. We followed this strategy on the simulated data provided by GAW11. The transmission/disequilibrium test (TDT) and the maximum likelihood score (MLS) were performed on the first replicate of 100 sib pairs from the population in which the disease risk was significantly influenced by an environmental factor (E1). However, only the TDT was powerful enough to detect one of the four loci involved in the genetic determination of the disease. The MLS showed no evidence for linkage after taking into account the fact that multiple tests were performed. Even when stratifying the sample according to the presence of E1, no additional loci could be detected. Given the simulated models, 100 sib pairs are too low a sample size for a systematic screening of the genome, which in this case was an analysis of 300 markers.

Environment↗
PubMed1999

Carboxyl-terminal domain of human apolipoprotein E: expression, purification, and crystallization.

Thioredoxin fusion expression vectors for two carboxyl-terminal fragments of human apolipoprotein (apo) E (residues 223-272 and 223-299) were generated from an apoE cDNA with the objective of obtaining structural information on this functionally important region of apoE by X-ray crystallography. A thrombin cleavage recognition site was positioned at the fusion junction to release the apoE fragments from the fusion protein. The fusion proteins were expressed in Escherichia coli, isolated from cell lysates by nickel-affinity column chromatography, and cleaved with thrombin. After gel filtration and ion exchange chromatography, yields of each fragment were approximately 14 mg/L. Both fragments bind to the phospholipid dimyristoylphosphatidylcholine in a manner similar to that of the 216-299 fragment of apoE isolated from plasma, which represents the major lipid-binding region of the protein. Orthorhombic crystals of the apoE 223-272 fragment that diffracted to 1.8 A were obtained in a mixture of 0.1 M imidazole (pH 6.0) and 0.4 M NaOAc (pH 7.0-7.5), containing 30% glycerol. The space group is C222 with cell dimensions of a = 35.17 A, b = 38.95 A, and c = 133.27 A.

Amino Acid Motifs↗
PubMed1999

Extraction of rutin from buckwheat (Fagopyrum esculentumMoench) seeds and determination by capillary electrophoresis.

The content of the flavonoid rutin was determined in different milling fractions of buckwheat seeds and in buckwheat stems, leaves, and flowers. The extraction was performed by using a solvent containing 60% of ethanol and 5% of ammonia in water. The extracts were analyzed by capillary electrophoresis (running buffer of 50 mM borate (pH 9.3), 100 mM sodium dodecyl sulfate; determination at 380 nm). In bran fractions the concentration of rutin was 131-476 ppm, and in flour fractions 19-168 ppm. On average, about 300, 1000, and 46000 ppm of rutin were found in leaves, stems, and flowers, respectively. The results indicate that buckwheat could be an important nutritional source of flavonoids, especially in countries with a low mean daily flavonoid intake.

Electrophoresis, Capillary↗
PubMed1999

Association between hSKCa3 and schizophrenia not confirmed by transmission disequilibrium test in 193 offspring/parents trios.

A possible association between the small conductance calcium-regulated potassium channel gene, hSKCa3, and schizophrenia has recently been described by Chandy et al using a case-control design with patients with schizophrenia (n=141) and matched controls (n = 158). The gene may be considered as an excellent candidate gene for psychiatric disorders, since it plays a role in modulating neuronal firing patterns by regulating the slow component of after hyperpolarisation. In addition, the gene contains a highly polymorphic trinucleotide sequence (CAG) within exon 1, which encodes a polyglutamine stretch. The possible contribution of unstable trinucleotide repeats to the development of psychiatric disorders has previously been discussed. Chandy et al reported an over-representation of alleles with higher repeat number in schizophrenics as compared to controls (P = 0.0035). In an attempt to replicate these findings, we have performed a family-based study with 193 offspring/parent combinations using a sample of 49 multiplex families (two or more affected siblings with parents) and a second sample of 83 simplex families (one affected offspring with parents). No evidence for the association of longer repeats with schizophrenia was obtained when each sample was tested separately or when both samples were combined and tested for transmission disequilibrium.

Female↗
PubMed1999

The transmission/disequilibrium test and parental-genotype reconstruction: the reconstruction-combined transmission/ disequilibrium test.

Spielman and Ewens recently proposed a method for testing a marker for linkage with a disease, which combines data from families with and without information on parental genotypes. For some families without parental-genotype information, it may be possible to reconstruct missing parental genotypes from the genotypes of their offspring. The treatment of such a reconstructed family as if parental genotypes have been typed, however, can introduce bias. In the present study, a new method is presented that employs parental-genotype reconstruction and corrects for the biases resulting from reconstruction. The results of an application of this method to a real data set and of a simulation study suggest that this approach may increase the power to detect linkage.

Genetic Linkage↗
PubMed1999

A note on power approximations for the transmission/disequilibrium test.

The transmission/disequilibrium test (TDT) is a popular method for detection of the genetic basis of a disease. Investigators planning such studies require computation of sample size and power, allowing for a general genetic model. Here, a rigorous method is presented for obtaining the power approximations of the TDT for samples consisting of families with either a single affected child or affected sib pairs. Power calculations based on simulation show that these approximations are quite precise. By this method, it is also shown that a previously published power approximation of the TDT is erroneous.

Alleles↗
PubMed1999

Costs and disability among stroke patients.

BACKGROUND: The high costs of health and social care support for stroke survivors, and the development of new service arrangements, have concentrated growing attention on economic issues. However, there are few data on costs and their association with levels of disability. METHODS: Secondary analyses of data from the OPCS (Office of Population Censuses and Surveys) Surveys of Disability conducted in the mid-1980s were used to examine service utilization and costs for more than 1000 people who have had a stroke. Costs were estimated for all health and social care services. Regression analyses examined the cost-disability association in the context of other covariates for people living in private households. RESULTS: Disability problems were common among stroke survivors, particularly in relation to locomotion, self-care and holding. Among people living alone, the major contributors to costs were in-patient care (Pound Sterling 27 per week) and home help (Pound Sterling 30 per week). Among people living with others, in-patient hospital care was also a major cost (Pound Sterling 28 per week). Other services costing more than Pound Sterling 5 per week were general practitioner consultations, hospital out-patient care and day centre attendances. Resource use patterns varied considerably. Costs were associated with severity of disability, time since stroke and whether the person was living alone. Looking at the overall balance of care, a greater proportion of stroke survivors with severe disability were resident in communal establishments. CONCLUSION: The analyses provide a baseline from which more recent local studies and evaluations can be compared. Key issues for economic studies of stroke are the inclusion of a broad range of services, a reasonable duration of follow-up and consideration of the impact of the substitution of informal for formal services.

Adult↗
PubMed1999

Cognitive disability and direct care costs for elderly people.

BACKGROUND: Population ageing and the high costs of care support for elderly people have concentrated attention on economic issues. Is there an association between costs and cognitive disability? AIMS: To compare service utilisation and direct costs for elderly people with different degrees of cognitive disability, and between people living in households and in communal establishments. METHOD: Secondary analysis of Office of Population Censuses and Surveys (OPCS) Disability Surveys data compared service utilisation and costs for 8736 elderly people with cognitive disability. Cost estimates were constructed for all health and social care services. RESULTS: A much greater proportion of people at higher levels of cognitive disability lived in communal establishments, where their (direct) costs were much higher than when supported in households. Service utilisation patterns and costs varied with cognitive disability. CONCLUSIONS: It is important to look at the full range of living arrangements and support services when examining costs. The potential cost implications of pharmacotherapies, other treatments or new care arrangements cannot be appreciated without such a broad perspective.

Aged↗