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At least 163 records · Page 9Linked to original sources
PubMed2000

Functional interaction of general transcription initiation factor TFIIE with general chromatin factor SPT16/CDC68.

BACKGROUND: Transcriptional initiation of class II genes is one of the major targets for the regulation of gene expression and is carried out by RNA polymerase II and many auxiliary factors, which include general transcription initiation factors (GTFs). TFIIE, one of the GTFs, functions at the later stage of transcription initiation. As recent studies indicated the possibility that TFIIE may have a role in chromatin transcriptional regulation, we isolated TFIIE-interacting factors which have chromatin-related functions. RESULTS: Using the yeast two-hybrid screening system, we isolated the C-terminal part of the human homologue of Saccharomyces cerevisiae (y) Spt16p/Cdc68p, a general chromatin factor. The C-terminal part of human SPT16/CDC68 directly interacts with TFIIE, and ySpt16p/Cdc68p also interacts with yTFIIE (Tfa1p/Tfa2p), thus indicating the existence of an evolutionarily conserved interaction between TFIIE and SPT16/CDC68. Functional interaction of yTFIIE and ySpt16p/Cdc68p was examined using a conditional yTFIIE-alpha mutant strain. Over-expression of ySpt16p/Cdc68p suppressed the phenotype of cold sensitivity of the yTFIIE-alpha-cs mutant strain, and in vitro binding assays revealed that yTFIIE-alpha-cs mutant protein showed diminished binding affinity to ySpt16p/Cdc68p. CONCLUSIONS: These observations indicate that general transcription initiation factor TFIIE functionally interacts with general chromatin factor SPT16/CDC68, a finding which provides new insight into the involvement of TFIIE in chromatin transcription. This may well lead to a breakthrough in relationships between the transcription initiation process and structural changes in chromatin.

Amino Acid Sequence↗
PubMed2002

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 1st communication: effects on general behavior and central nervous system.

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on general behavior and the central nervous system were investigated in mice, rats and cats. 1. General behavior: When SNI-2011 was administered orally to mice at 100 mg/kg, mydriasis, a decrease of spontaneous motor activity, tremor, convulsions, salivation, abnormal posture, abnormal gait, reduced grip strength and reduced response against external stimulating were observed, and 2 out of 6 animals died. At 10 mg/kg or lower, no particular sign was observed except mydriasis, which appeared to be caused via the peripheral muscarinic acetylcholine receptors. 2. Central nervous system: SNI-2011 had no effect on the motor coordination in mice. Hypothermia was observed in rats and reduced spontaneous motor activity, analgesia and enhanced maximum electroshock-induced convulsions were observed in mice after oral administration of 30 mg/kg SNI-2011. Slight increase in the rate of theta-wave band in the hippocampal EEG of rats and spinal multisynaptic reflexes in cats were observed after intravenous injection of 10 mg/kg SNI-2011. At an oral dose of 10 mg/kg, prolongation of thiopental-induced sleeping time in mice was observed. The prolongation of sleeping time was inhibited by a peripheral muscarinic antagonist. These results suggest that SNI-2011 has muscarinic effects on general behavior and the central nervous system at the doses approximately 10-fold higher than the effective doses needed for saliva secretion.

Anesthetics, Intravenous↗
PubMed2004

Positive self-assessed general health in patients with medical problems. A qualitative study from general practice.

BACKGROUND: Patient and doctor do not always agree on the status of the patient's health. By underestimating the patient's strong sides, the doctor may be contributing to disempowerment and bypassing knowledge needed for adequate medical diagnosis and management. OBJECTIVE: To understand how our patients with medical problems assess their general health as good. DESIGN AND SETTING: Qualitative observational study based on audiotaped material from general practice consultations in authors' practices (Norway and Denmark). The patients were asked to rate their current state of health on a scale ranging from zero to 100, and then to explain their score. SUBJECTS: From 41 consecutive consultations we compiled a purposeful sample of 12 patients who reported positive self-assessed general health although medical problems were present. The 7 women and 5 men were aged between 43 and 96 years, and had been diagnosed with musculoskeletal disorders, heart disease, cancer, depression, headache or severe menopausal symptoms. MAIN OUTCOME MEASURES: Salutogenesis, represented by the authors' Health Resource/Risk Balance Model, and Antonovsky's Sense of Coherence (SOC) concept comprised the theoretical framework. Transcripts from audiotaped consultations were used for qualitative text condensation analysis, inspired by Giorgi's phenomenological method. Analysis was theory-driven, applying comprehensibility, manageability and meaningfulness as entries to elaborate patients' accounts of positive health. RESULTS: Patients' answers demonstrated how a feeling of logical reasoning related to symptom perception could provide comfort and sometimes lead to advantageous coping strategies. Personal and social resources were mentioned as essential means for tolerating and managing the burden of disease. Even fairly extensive endeavours could be experienced as worthwhile when sometimes providing relief, even only temporarily. CONCLUSIONS: Patients' accounts of general health can challenge the traditional medical views on assessment of health and disease.

Adult↗
PubMed1953

Studies on the generalized Shwartzman reaction. IV. Prevention of the local and generalized Shwartzman reactions with heparin.

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.

Animals↗
PubMed2005

Monitoring health inequalities through general practice: the Second Dutch National Survey of General Practice.

BACKGROUND: For the second time a plan to monitor public health and health inequalities in the Netherlands through general practice was put into action: the Second National Survey of General Practice (DNSGP-2, 2001). The first aim of this paper is to describe the general design of DNSGP-2. Secondly, to describe self assessed health inequalities in the Netherlands. Thirdly, to present differences in prevalence of chronic conditions by educational attainment using both self-assessed health and medical records of GPs. Finally, inequalities in 1987 (DNSGP-1) and 2001 will be compared. METHODS: Data were collected from 96 (1987) and 104 (2001) general practices. The data include background information on patients collected via a census, approximately 12,000 health interview surveys per time point and more than one million recorded contacts of patients with their GPs in both years. The method of statistical analysis is logistic regression. RESULTS: The analyses shows that the lower educated have significantly higher odds of feeling unhealthy and having chronic conditions in 2001. Diabetes and myocardial infarction (GP data) showed the largest difference in prevalence between educational groups (OR 2.5 and 2.4, self-reported data). The way the data is collected (self-assessment versus GP registration) hardly affects the magnitude of the educational differences in the prevalence of chronic conditions. The pattern of health inequalities across chronic conditions in 1987 and 2001 hardly differs. Diabetes doubled in prevalence and health inequalities were not significant in 1987, but compared to the other conditions were largest in 2001 (OR 1.1 versus 2.5). CONCLUSION: Health inequalities were shown to be substantial in 2001 and persistent over time. Socio-economic differences were shown to be similar using self-assessed health data and GP data. Hence, a person's educational attainment did not appear to play a part in presenting health problems to the GP.

Adult↗
PubMed2003

Use of rules of thumb in the consultation in general practice--an act of balance between the individual and the general perspective.

BACKGROUND: Rules of thumb used by GPs could be considered as empirical evidence of intuition and a link between science and practice in general practice. OBJECTIVE: The purpose of the present study was to analyse the description of the application of rules of thumb with regard to different situations in general practice. METHODS: An explorative and descriptive study was started with focus group interviews. Four groups with 23 GPs were interviewed. The interviews were transcribed and analysed, and the rules and their application were classified by an editing analysis. RESULTS: A specific set of rules of thumb was used for rapid assessment, when emergency and psychosocial problems were identified. When the main focus of the problems was identified as somatic or psychosocial, the GPs did not disregard the other aspects but described the use of rules in a simultaneous individualizing and generalizing process. The rules contained probability reasoning and risk assessment. CONCLUSION: Rules of thumb seemed to serve as a link between theoretical knowledge and practical experience and were used by the GPs in an act of balance between the individual and the general perspective.

Family Practice↗
PubMed2004

Generalized chromosome genetic algorithm for generalized traveling salesman problems and its applications for machining.

Traveling salesman problems (TSP) and generalized traveling salesman problems (GTSP) are two kinds of well known and challenging combinatorial optimization problems with much diversified application fields. Between the two application problems the GTSP is more complex than TSP. Many researchers have studied TSP extensively, but relatively fewer studies pay attention to GTSP, and also its solution using genetic algorithm (GA). In this paper, the structure of conventional chromosome is generalized to be a chromosome termed as a generalized chromosome (GC). A genetic scheme named as generalized-chromosome-based genetic algorithm (GCGA) is also presented. The proposed GCGA enables GTSP and TSP to be solved under a uniform algorithm mode. Forty one benchmark test problems have been solved with the known optimal solutions using the proposed algorithm to verify its validity. The test results show that GCGA can directly solve GTSP without the need of intermediate transformation to TSP.

Journal Article↗
PubMed1999

A general maximum likelihood analysis of variance components in generalized linear models.

This paper describes an EM algorithm for nonparametric maximum likelihood (ML) estimation in generalized linear models with variance component structure. The algorithm provides an alternative analysis to approximate MQL and PQL analyses (McGilchrist and Aisbett, 1991, Biometrical Journal 33, 131-141; Breslow and Clayton, 1993; Journal of the American Statistical Association 88, 9-25; McGilchrist, 1994, Journal of the Royal Statistical Society, Series B 56, 61-69; Goldstein, 1995, Multilevel Statistical Models) and to GEE analyses (Liang and Zeger, 1986, Biometrika 73, 13-22). The algorithm, first given by Hinde and Wood (1987, in Longitudinal Data Analysis, 110-126), is a generalization of that for random effect models for overdispersion in generalized linear models, described in Aitkin (1996, Statistics and Computing 6, 251-262). The algorithm is initially derived as a form of Gaussian quadrature assuming a normal mixing distribution, but with only slight variation it can be used for a completely unknown mixing distribution, giving a straightforward method for the fully nonparametric ML estimation of this distribution. This is of value because the ML estimates of the GLM parameters can be sensitive to the specification of a parametric form for the mixing distribution. The nonparametric analysis can be extended straightforwardly to general random parameter models, with full NPML estimation of the joint distribution of the random parameters. This can produce substantial computational saving compared with full numerical integration over a specified parametric distribution for the random parameters. A simple method is described for obtaining correct standard errors for parameter estimates when using the EM algorithm. Several examples are discussed involving simple variance component and longitudinal models, and small-area estimation.

Adrenergic beta-Antagonists↗
PubMed2005

The development of a screening tool to identify carers in a general practice by a large-scale mailed survey: the experience in one Scottish general practice.

AIMS AND OBJECTIVES: To determine the feasibility of a screening tool to identify carers in a general practice. BACKGROUND: The need to support informal carers is well established in policy and practice, but many carers continue to lack the support they need. Identifying carers is a fundamental precondition to providing them with support. Studies often recruit carers who are members of carers' organizations or via the care recipient in receipt of services. However, as nearly 60% of carers receive no support from the statutory services, this group of carers may not be representative of the majority of carers. This paper describes the results of a study undertaken to identify a broader group of carers in a general practice in a large Scottish city. DESIGN AND METHODS: A quantitative research design was employed using a mailed screening survey to identify carers within a general practice. Carers were systematically identified, independent of the care recipient, using a screening tool developed by the researcher which was sent to all adult patients registered with the practice. RESULTS: The response rate was 69%. Overall, 11% of the surgery population identified themselves as carers with a mean age of 55 years. The carers were involved in a range of caring activities of varying levels and duration. CONCLUSION: The screening exercise was time consuming and costly. However, it would be feasible and useful to identify carers in smaller groups. RELEVANCE TO PRACTICE: This study tackles issues that are pertinent to health policy and practice. Carers were systematically identified from a general practice population and included those at an early stage of the caring role, prior to being involved with service providers, as well as those established in their role. If carers are identified early in their caring career the primary health care team is more able to support them proactively.

Adolescent↗
PubMed1992

Management of somatic presentations of psychiatric illness in general medical settings: evaluation of a new training course for general practitioners.

An improved teaching package is described which aims to help general practice trainees manage somatized presentations of psychological distress. The package comprises a training videotape in which a reattribution model is demonstrated, with material for role-play of new skills and small-group video feedback of consultations. Eighteen general practice trainees attending an 8-week course in psychiatry participated fully in the somatization management teaching programme. The teaching package was evaluated by blind rating of general interview skills and model specific skills demonstrated by trainees during 10 to 15-minute clinical interviews with professional role-players. Ratings were made on pre-training and post-training videotaped interviews. A significant improvement was demonstrated in general interview skills. Improvements were also noted in specific reattribution skills post-training. The evaluation revealed that skills in the model can be effectively learned, and that improvements in the package have resulted in its improved efficacy.

Clinical Competence↗
PubMed1994

Assessing the competence of general practitioners in diagnosing generalized anxiety disorder using standardized patients.

The competence of general practitioners (GPs) in diagnosing anxiety neurosis was assessed using standardized patients (SPs) unknown to the doctors. Out of a computer-generated random sample of 100 general practitioners in Kuala Lumpur, 42 volunteered to participate in the study. The results showed that the GPs can be divided into three groups: group A made the correct diagnosis and informed the SPs about their condition (11.9%); group B prescribed tranquillizers and did not inform the SPs of the actual diagnosis but instead said that they were either normal or were suffering from some stress (28.6%); and group C made various diagnoses of physical disorder or did not detect any abnormality at all (59.5%). Thus about 40% of the doctors considered an emotion-related disorder and only 12% of the doctors were confident enough to make and inform the patient of the actual diagnosis. Group A significantly (P < 0.001) asked higher numbers of relevant questions in the signs and symptoms section of the history than the other two groups. No differences between the three groups were observed in the other two sections of history-taking (personality, family, social and precipitating factors), in the general and specific physical examination and interpersonal skills. Generally, with the exception of the interpersonal skills section, the doctors performed less than 40% of the expected tasks in every section. The study highlighted the lack of competence in making a definite diagnosis of anxiety disorder. Among those who apparently made the diagnosis (group B) or made the diagnosis with certainty (group A), there was no demonstration of appropriate treatment behaviour with respect to pharmacological intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Anxiety Disorders↗
PubMed1989

General practitioners' referrals to specialist outpatient clinics. I. Why general practitioners refer patients to specialist outpatient clinics.

There has been much concern about the wide variations in general practitioners' referral rates and the consequent implications for cost and quality of care. This has led to a call to evaluate the appropriateness and effectiveness of referrals. A collaborative audit of referrals to outpatient clinics was conducted by 127 general practitioners in 33 practices in the Oxford region. Records were kept of 18,754 referrals, which included data on diagnoses and reasons for referral. Overall, 6553 (35.4%) of the referrals were for particular treatments or operations and a further 6475 (34.9%) were for specific investigation or diagnosis. Advice on management was the main reason for referral in 2656 (14.3%) cases, and in 1719 (9.3%) cases the general practitioners wanted the consultants to take over managing their patients. Reassurance of either the general practitioner or the patient was recorded as the main reason in only 762 (4.1%) referrals. There seems to be scope for rationalising the referral process. A programme with three stages for evaluating referrals to outpatient clinics is recommended.

England↗
PubMed1991

Study of general practice consultations and menopausal problems. Oxford General Practitioners Menopause Study Group.

OBJECTIVE: To investigate the nature of work related to the menopause in general practice. DESIGN: Questionnaire study over six months among general practitioners after each consultation with a woman aged 40-69 at which issues related to the climacteric had been discussed. SETTING: 9 General practices in the Oxford area. SUBJECTS: 416 Women who had 572 consultations. MAIN OUTCOME MEASURES: Age, menopausal state, and first or subsequent consultation. Symptoms were classified together with the treatment and the outcome of the consultation. RESULTS: The consultation rate varied greatly between practices, the overall rate being 4.4%. There were many premenopausal women and women in their 60s presenting; women with hysterectomies presented more often--36% (37/103) of women with hysterectomies had more than one consultation compared with 26% (38/144) for premenopausal women and 24% (38/155) for postmenopausal women. 409 women had symptoms and 218 were prescribed oestrogen treatment. 156 of the consultations involved discussion and advice only. Only four women were referred to a local specialist clinic. CONCLUSION: There is a low overall use of hormone replacement therapy in the general postmenopausal population despite the recent media coverage of its benefits in the prevention of osteoporosis and subsequent fractures.

Adult↗
PubMed1992

Medical audit in general practice. I: Effects on doctors' clinical behaviour for common childhood conditions. North of England Study of Standards and Performance in General Practice.

OBJECTIVE: To estimate the effects of medical audit, particularly setting clinical standards, on general practitioners' clinical behaviour. DESIGN: Before and after study strengthened by a replicated Latin square. SETTING: 62 training general practices in the north of England. SUBJECTS: 92 general practitioner trainers, 84 (91%) of whom completed the study; random sample of 3500 children consulting one of these trainers for any of five conditions--acute cough, acute vomiting, bedwetting, itchy rash, and recurrent wheezy chest--stratified by doctor consulted, condition, and age. INTERVENTIONS: Clinical standard set by each of 10 small groups of general practitioner trainers for one randomly selected childhood condition. Each group also experienced a different type of medical audit, randomly selected, for each of the four other study conditions (receiving a clinical standard set by another trainer group, tabulated data comparing clinical performance with that of all other groups, tabulated data from only their own group, and nothing ("control" condition)). MAIN MEASURES: Content of initial consultation divided into: history, examination, investigation, diagnosis, and management (abstracted from medical records and "enhancement forms" completed by doctors). RESULTS: There was increased prescribing of bronchodilators for acute cough, oral rehydration fluids for acute vomiting, antibiotics for itchy rash, and bronchodilators and oral steroids for recurrent wheezy chest and reduced prescribing of antibiotics for acute cough and recurrent wheezy chest and tricyclic antidepressants for bedwetting. Fewer children were "discharged." Each change was consistent with the standard and either limited to doctors who set a standard for that condition or significantly greater for them than all other doctors. CONCLUSION: Setting clinical standards improved prescribing and follow up.

Acute Disease↗
PubMed1999

Influence on general practitioners of teaching undergraduates: qualitative study of London general practitioner teachers.

OBJECTIVE: To examine the perceived effect of teaching clinical skills and associated teacher training programmes on general practitioners' morale and clinical practice. DESIGN: Qualitative semistructured interview study. SETTING: General practices throughout north London. SUBJECTS: 30 general practitioners who taught clinical skills were asked about the effect of teaching and teacher training on their morale, confidence in clinical and teaching skills, and clinical practice. RESULTS: The main theme was a positive effect on morale. Within teacher training this was attributed to developing peer and professional support; improved teaching skills; and revision of clinical knowledge and skills. Within teaching this was attributed to a broadening of horizons; contact with enthusiastic students; increased time with patients; improved clinical practice; improved teaching skills; and an improved image of the practice. Problems with teaching were due to external factors such as lack of time and space and anxieties about adequacy of clinical cover while teaching. CONCLUSION: Teaching clinical skills can have a positive effect on the morale of general practitioner teachers as a result of contact with students and peers, as long as logistic and funding issues are adequately dealt with.

Anxiety↗
PubMed1975

Access by general practitioners to physiotherapy department of a district general hospital.

There has been much opposition, voiced most notably in the Tunbridge Report, to general-practitioner access to hospital rehabilitation services. Co-operation between general practitioners, physiotherapists, and the consultant with responsibility for the physiotherapy department at a general district hospital has provided an efficient open-access service. This service has been welcomed by the general practitioners because it supplies prompt treatment for their patients and by the physiotherapists because it enables them to minimise disability by treating musculoskeletal problems at an early stage.

Family Practice↗
PubMed1989

The role of the general practitioner in the care of mentally disturbed subjects in the general population--results of the Upper Bavarian Study.

The role of the general practitioner in the care of mentally disturbed non-institutionalised persons aged 20 years and older was examined. Data were based on the representative community sample of the Upper Bavarian Field Study with a sample size of 1495 interviewees--aged 20 years and older. The 5-year prevalence of mental illness according to the definition used was 32.8%. 38.5% of all persons, identified as cases, consulted their general practitioner because of psychiatric or emotional problems. Females and the elderly were most likely to have received treatment by their general practitioner. The majority of treated persons were neurotic and psychosomatic patients. The general practitioner provided care for more psychiatric patients than the psychiatrist and for 25% of all "cases", without additional psychiatric consultation.

Adult↗
PubMed2000

High demand, low control, and impaired general health: working conditions in a sample of Swedish general practitioners.

This cross-sectional survey of 1,004 Swedish general practitioners (GPs) aged 32 64 years analyses the extent to which low control, high work demand, and other work-related conditions are associated with self-rated impaired general health and impaired quality of life among Swedish GPs. The first part of the questionnaire contained "SF-36 Health Survey", from which we chose five psychosocial multi-item scales as dependent variables. The second part of the questionnaire had questions about working conditions from "The Swedish Survey of Living Conditions". Unconditional logistic regression was used. Female and male GPs with high job strain, i.e. low control and high work demand, exhibited a more than threefold increased risk of impaired general health compared with those with medium job strain. Low job strain among male GPs was associated with a low risk of impaired health. The finding of significant associations between psychosocial working conditions and impaired general health and impaired, quality of life in GPs in 1996 highlights the need to improve working conditions in Swedish primary healthcare, for example, by reducing number of inhabitants per full-time GP to 1,500.

Adult↗