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PubMed2005

A novel theory: biological processes mostly involve two types of mediators, namely general and specific mediators Endogenous small radicals such as superoxide and nitric oxide may play a role of general mediator in biological processes.

A great number of papers have shown that free radicals as well as bioactive molecules can play a role of mediator in a wide spectrum of biological processes, but the biological actions and chemical reactivity of the free radicals are quite different from that of the bioactive molecules, and that a wide variety of bioactive molecules can be easily modified by free radicals due to having functional groups sensitive to redox, and the significance of the interaction between the free radicals and the bioactive molecules in biological processes has been confirmed by the results of some in vitro and in vivo studies. Based on these evidence, this article presented a novel theory about the mediators of biological processes. The essentials of the theory are: (a) mediators of biological processes can be classified into general and specific mediators; the general mediators include two types of free radicals, namely superoxide and nitric oxide; the specific mediators include a wide variety of bioactive molecules, such as specific enzymes, transcription factors, cytokines and eicosanoids; (b) a general mediator can modify almost any class of the biomolecules, and thus play a role of mediator in nearly every biological process via diverse mechanisms; a specific mediator always acts selectively on certain classes of the biomolecules, and may play a role of mediator in different biological processes via a same mechanism; (c) biological processes are mostly controlled by networks of their mediators, so the free radicals can regulate the last consequence of a biological process by modifying some types of the bioactive molecules, or in cooperation with these bioactive molecules; the biological actions of superoxide and nitric oxide may be synergistic or antagonistic. According to this theory, keeping the integrity of these networks and the balance between the free radicals and the bioactive molecules as well as the balance between the free radicals and the free radical scavengers would be of vital importance for physiological processes, and disturbance of these networks and balances would be a critical factor of pathological processes. Therefore, the investigators who want to get a deep and full understanding of the mechanism of a biological process should pay attention to the roles of both free radical and bioactive molecule species, and the free radical scavengers, which are used for health protection, such a vitamin E and carotenoid, should be taken in a suitable dosage.

Models, Biological↗
PubMed2000

General base and general acid catalyzed intramolecular aminolysis of esters. Cyclization of esters of 2-aminomethylbenzoic acid to phthalimidine.

Plots of log k(0) vs pH for the cyclization of trifluoroethyl and phenyl 2-aminomethylbenzoate to phthalimidine at 30 degrees C in H(2)O are linear with slopes of 1.0 at pH >3. The values of the second-order rate constants k(OH) for apparent OH(-) catalysis in the cyclization reactions are 1.7 x 10(5) and 5.7 x 10(7) M(-)(1) s(-)(1), respectively. These rate constants are 10(5)- and 10(7)-fold greater than for alkaline hydrolysis of trifluoroethyl and phenyl benzoate. The k(OH) for cyclization of the methyl ester is 7.2 x 10(3) M(-)(1) s(-)(1). Bimolecular general base catalysis occurs in the intramolecular nucleophilic reactions of the neutral species. The value of the Bronsted coefficient beta for the trifluoroethyl ester is 0.7. The rate-limiting step in the general base catalyzed reaction involves proton transfer in concert with leaving group departure. The mechanism involving rate-determining proton transfer exemplified by the methyl ester in this series (beta = 1.0) can then be considered a limiting case of the concerted mechanism. General acid catalysis of the neutral species reaction or a kinetic equivalent also occurs when the leaving group is good (pK(a) </= 12.4). That the mechanism and/or rate-determining step of the intramolecular aminolysis reactions is different than in bimolecular reactions or the intramolecular reactions of other esters is attributed to the excellent steric fit of the nucleophile to the reaction center of the 2-aminomethylbenzoate esters.

Buffers↗
PubMed2001

Validation of general practitioner-diagnosed COPD in the UK General Practice Research Database.

BACKGROUND: Information in large, automated databases can be useful to study the natural history of respiratory diseases in the community, but the validity of definitions needs to be demonstrated. AIM: To compare a simple computer algorithm that identifies patients diagnosed with chronic obstructive pulmonary disease (COPD) and severity of COPD in the UK General Practice Research Database (GPRD) with general practitioner (GP) clinical records, to evaluate the utility of this algorithm for identifying COPD patients and for distinguishing COPD from asthma. METHODS: Using a computer algorithm identifying patients by diagnostic codes and allotting three grades of severity by drug use, a sample of 225 patients in the GPRD with a diagnosis of COPD and an age-sex matched group of 75 patients with asthma were randomly selected. Questionnaires were posted to the GPs of the 300 selected patients who were asked to state diagnosis and to grade severity based on the individual's medical record. Agreement was quantified with the kappa index, an estimator that accounts for agreement that occurs by chance. RESULTS: Response rate was 85.7%. The concordance between COPD diagnosis by the GPRD algorithm with that of the GP was quantified as a kappa of 0.52, and the concordance between COPD severity by the GPRD algorithm with that of the GP was quantified as a kappa of 0.54. The kappa index for COPD diagnosis increased with increasing severity of COPD (0.46, 0.59, and 0.68 for mild, moderate and severe COPD, respectively), but similar good agreement was observed in a stratified analysis by sex, age, smoking status and number of comorbidities. CONCLUSIONS: It is concluded that the GPRD algorithms used for diagnosis and severity of COPD are a good screening tool for COPD in the UK general population, and satisfactorily differentiate COPD from asthma patients, particularly when disease is moderate or severe.

Aged↗
PubMed1998

The development of general practice standards in Australia. Royal Australian College of General Practitioners.

The Royal Australian College of General Practitioners has spent 4 years developing a set of entry standards which define the minimum features of general practices expected for the mid-1990s. The project design followed a slow, iterative process, with several opportunities for wide consultation with professional, consumer and Government groups. The draft standards were piloted in 25 volunteer practices, modified and then field-tested in 200 randomly selected practices representing urban and rural practices. Results of this field testing showed that the standards had content validity and that reliable measures were possible using triangulation from several data sources. The current version of the standards has been distributed widely for voluntary application in Australian general practices from early 1997.

Australia↗
PubMed2001

A national general practice census: characteristics of rural general practices.

OBJECTIVES: The aim of the present study was to describe, using a national census, the characteristics of rural general practices and compare these with city and town general practices. METHODS: A previously piloted, anonymous but linked, questionnaire was issued to all GPs in Ireland. A liaison network covering the country was developed to increase the response rate. Respondents were asked to designate the location of their main surgery as being city (>20 000 population), town (>5000) or rural (<5000). Each responding practice was asked to nominate one partner to complete a specific section on practice information. RESULTS: Completed individual questionnaires were returned from 2093 GPs (86% response rate). Information on 1429 practice centres was provided; 488 (34%) of these were designated as city, 405 (28%) as town and 536 (38%) as rural. Rural practices reported fewer private patients (P < 0.001) and more socio-economically deprived patients (P < 0.001) than those in towns or cities. The mean number (SD) of total scheduled hours per average week per GP was 77.95 (37.0) for city practices, 80.6 (35.9) for town and 103.6 (39.0) for rural (P < 0.001). Rural practices are more likely, in comparison with those in cities and towns, to have attached staff working from purpose-built premises which are publicly owned. Rural practices also have more contacts with members of the primary care team such as Public Health Nurses, and the quality of these contacts is described more positively. The range of available services is broadly similar, with emergency medical equipment being available more frequently in rural practices. CONCLUSION: This study suggests that rural practitioners and their practices differ from their urban counterparts in many important aspects. Consideration should be given to the development of formal under- and postgraduate rural general practice programmes to prepare new, and continue to enthuse present, rural GPs.

Censuses↗
PubMed1988

Recognition of dementia in general practice: comparison of general practitioners' opinions with assessments using the mini-mental state examination and the Blessed dementia rating scale.

In a study of 226 elderly residents in a retirement village in Sydney, Australia, general practitioners' opinions about dementia status had high positive and negative predictive values and high specificity, but low sensitivity when evaluated against the mini-mental state examination and the Blessed dementia rating scale. General practitioners were found to disagree with these two measures more often when patients were in advanced old age, and when they considered the patients to be depressed. We conclude that the general practitioner can increase his or her sensitivity to dementia in the elderly by use of either measure.

Aged↗
PubMed1993

The stochastic general epidemic model revisited and a generalization.

While the mathematical theory of epidemics has its origins with Ross (1911), it was not until Kryscio (1975) that explicit expressions for the state probabilities of the classical general epidemic model established by Bartlett (1949) were found. However, these formulae were of limited practical use when the population size was of even moderate size. By shifting the focus from the bivariate pair representing the number of susceptibles and infectives to that for the number of infectives and removals, one is able to obtain solutions that are considerably simpler and easier to manage than those previously derived and which are not restricted by the size of the population. The results are obtained for a generalized general epidemic process in which transition probabilities are arbitrary functions of the state space, and then applied to the classical model. An extension to time-dependent transition rates is also considered.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Magnification, blur, and ray state at the retina for the general eye with and without a general optical instrument in front of it: 1. Distant objects.

PURPOSE: To derive general equations that characterize rays, magnification, and blur at the retina in the case of distant object points for a naked eye and for an eye looking through an arbitrary optical instrument. The eye and optical instrument may be astigmatic and noncoaxial. METHOD: The derivation is based on linear optics and makes use of the concept of the augmented ray transference of an optical system. Because the transference completely characterizes the linear optics, the analysis can claim completeness. RESULTS: Equations are presented for position and direction of rays at the retina from distant object points. They lead naturally to the definition of six properties that characterize blur, shape, size, orientation, and position of images of distant objects viewed by the naked eye and by the eye looking through an instrument. By way of example, the general equations are applied to the simple examples of a thin contact lens and a thin spectacle lens in particular. CONCLUSION: The analysis provides a framework, complete as far as linear optics is concerned, for the analysis of light arriving at the retina through any instrument from a distant point. In so doing, it unifies and generalizes concepts like blur and spectacle magnification, which, in the past, have been treated separately.

Contact Lenses↗
PubMed2001

Magnification, blur, and ray state at the retina for the general eye with and without a general optical instrument in front of it: 2. Near objects.

PURPOSE: To derive general equations that characterize rays, magnification, and blur at the retina in the case of near object points for the naked eye and for the eye in combination with a general optical instrument. METHOD: The paper draws on results obtained via linear optics in an accompanying paper. RESULTS: Equations are presented that completely characterize the state of rays at the retina from objects at any distance. They allow quantification of blur, size, shape, orientation, and magnification at the retina. CONCLUSION: The analysis provides a framework, complete in linear optics, for the analysis of light arriving at the retina of a general eye through any instrument from any object point.

Contact Lenses↗
PubMed1982

The psychiatric contribution to general medical education. Some problems of generalization.

Little difference was found in the extent to which psychosocial data were recorded in two samples of general hospital case-notes written 10 years apart, in spite of a significant increase of apparently relevant material in the undergraduate medical curriculum. Although the house physicians responsible acknowledge the importance of the data, their estimate of recording frequency was much higher than was actually the case. Impediments to such recording were identified. The apparent lack of generalization of learning is presented as an important problem relevant to psychiatrists who have a major responsibility for teaching in these areas. Suggestions are made of ways in which generalization might be facilitated.

Behavioral Sciences↗
PubMed1994

Asthma at the interface: bridging the gap between general practice and a district general hospital.

A clinic supervised by a nurse, using principles originally developed in general practice, was established in the paediatric department of a district general hospital. A randomised controlled study was conducted comparing children admitted with asthma or attending outpatients who were given a patient education programme and self management plan (intervention group) with a control group. The study comprised 91 patients aged 3-14 years admitted for asthma or attending a hospital outpatient department from November 1989 to November 1990. Seventy seven patients completed the study and kept diaries for a median of 283 days. Patients in the intervention group had significantly less restriction of activity (95% confidence interval (CI) -0.27 to -0.01) and fewer episodes of peak flow below 30% of best (95% CI 0.03 to 1.17). Patients in the intervention group were more likely to make the correct response to an acute exacerbation of their asthma than the control group (71% v 47%, 95% CI 9.51 to 39.1). The intervention group had fewer school absences and fewer home visits by a general practitioner. There was an increase in the readmission rate for the intervention group. A subgroup of patients who self managed by doubling their use of inhaled steroids during an exacerbation performed better than those patients who only increased their bronchodilator or were managed on salbutamol or sodium cromoglycate alone. Improvements in patient follow up and the structure of the self management plans used, particularly changing the peak flow level at which inhaled steroids are doubled, may further improve the outcome of patients attending the asthma clinic.

Absenteeism↗
PubMed1987

Screening for cervical cancer: a new scope for general practitioners? Results of the first year of colposcopy in general practice.

A survey was carried out over one year of all the women who attended a colposcopy clinic in a general practice. During the year 1254 women underwent cytological screening in the practice and 197 of these underwent colposcopy. Of 79 women with abnormal smears that suggested cervical intraepithelial neoplasia, 62 (79%) were confirmed by biopsy to have cervical premalignancy. In addition, the remaining 118 women with normal or inflammatory smears underwent colposcopy either because of their history or because they requested the investigation. A general underestimate of cervical intraepithelial neoplasia when cytology alone was used was discovered. Seven out of 28 women with inflammatory smears were found to have important cervical premalignancy. Mildly dyskaryotic smears led to a falsely reassuring estimate of the degree of severity of cervical lesions. Seven out of 13 patients who underwent colposcopy because they were thought to be at high risk of neoplasia because of a history of genital warts, unexplained recurrent cystitis, heroin abuse, or immunosuppression had cervical intraepithelial neoplasia proved at biopsy. This report shows that both in screening for and in the follow up of known cervical disease a normal smear cannot guarantee normal pathology. Diagnostic colposcopy is a valuable complementary investigation that could be carried out in a general practice.

Adult↗
PubMed1997

Evaluation of specialists' outreach clinics in general practice in England: process and acceptability to patients, specialists, and general practitioners.

OBJECTIVES: The wider study aimed to evaluate specialists' outreach clinics in relation to their costs, processes, and effectiveness, including patients' and professionals' attitudes. The data on processes and attitudes are presented here. DESIGN: Self administered questionnaires were drawn up for patients, their general practitioners (GPs) and specialists, and managers in the practice. Information was sought from hospital trusts. The study formed a pilot phase prior to a wider evaluation. SETTING: Nine outreach clinics in general practices in England, each with a hospital outpatient department as a control clinic were studied. SUBJECTS: The specialties included were ear, nose, and throat surgery; rheumatology; and gynaecology. The subjects were the patients who attended either the outreach clinics or hospital outpatients clinics during the study period, the outreach patients' GPs, the outreach patients' and outpatients' specialists, the managers in the practices, and the NHS trusts which employed the specialists. MAIN OUTCOME MEASURES: Process items included waiting lists, waiting times in clinics, number of follow up visits, investigations and procedures performed, treatment, health status, patients' and specialists' travelling times, and patients' and doctors' attitudes to, and satisfaction with, the clinic. RESULTS: There was no difference in the health status of patients in relation to the clinic site (ie, outreach and hospital outpatients' clinics) at baseline, and all but one of the specialists said there were no differences in casemix between their outreach and outpatients' clinics. Patients preferred, and were more satisfied with, care in specialists' outreach clinics in general practice, in comparison with outpatients' clinics. The outreach clinics were rated as more convenient than outpatients' clinics in relation to journey times; those outreach patients in work lost less time away from work than outpatients' clinic patients due to the clinic attendance. Length of time on the waiting list was significantly reduced for gynaecology patients; waiting times in clinics were lower for outreach patients than outpatients across all specialties. In addition, outreach patients were more likely to be first rather than follow up attenders; rheumatology outreach patients were more likely than hospital outpatients to receive therapy. GPs' referrals to hospital outpatients' clinics were greatly reduced by the availability of outreach clinics. Both specialists and GPs saw the main advantages of outreach clinics in relation to the greater convenience and better access to care for patients. Few of the specialists and GPs in the outreach practices held formal training and education sessions in the outreach clinic, although over half of the GPs felt that their skills/expertise had broadened as a result of the outreach clinic. CONCLUSIONS: The processes of care (waiting times, patient satisfaction, convenience to patients, follow up attendances) were better in outreach than in outpatients' clinics. However, waiting lists were only significantly reduced for gynaecology patients, despite both GPs and consultants reporting reduced waiting lists for patients as one of the main advantages of outreach. Whether these improvements merit the increased cost to the specialists (in terms of their increased travelling times and time spent away from their hospital base) and whether the development of what is, in effect, two standards of care between practices with and without outreach can be stemmed and the standard of care raised in all practices (eg, by sharing outreach clinics between GPs in an area) remain the subject of debate. As the data were based on the pilot study, the results should be viewed with some caution, although statistical power was adequate for comparisons of sites if not specialties.

Attitude of Health Personnel↗
PubMed1997

Emergency admission of patients to general surgical beds: attitudes of general practitioners, surgical trainees, and consultants in Liverpool, UK.

OBJECTIVES: To determine (a) whether doctors involved in the process of emergency surgical admission could agree about which patients should be admitted, (b) whether there were consistent differences between doctors in different specialty groups, and (c) whether these opinions were greatly influenced by non-clinical factors. DESIGN: Independent assessment of summarised case histories by three "expert" clinicians (two consultant surgeons and one general practitioner (GP)), by a group of 10 GPs, and by a group of 10 junior and senior surgeons. Experts, but not other observers, scored admissions both independently and as a consensus group. Observers indicated for each patient whether they would admit, would not admit, or were unsure. SETTING: An urban general hospital with teaching status. SUBJECTS: Fifty consecutive patients admitted to the general surgical unit as emergencies during 1995. MAIN OUTCOME MEASURES: Proportion of admissions considered unnecessary or uncertain: agreement between observers on these proportions: effect of social and procedural factors on the admission decision. RESULTS: Between 8 and 34% of admissions were considered unnecessary and 20-38% of unclear necessity. Agreement between the groups of clinicians was not good. GPs and consultant surgeons showed the poorest agreement (kappa = 0.08 to 0.25, 4 comparisons), and the GPs scored a higher percentage of admissions as unnecessary (34 v 8-12%). After discussion, the consensus group achieved good to very good agreement (kappa 0.61-0.84). CONCLUSIONS: Different groups of doctors vary widely in their views about the need for emergency surgical admission. Good agreement can be reached by consensus discussion. GPs are less likely than surgeons to consider emergency surgical admission necessary.

Attitude of Health Personnel↗
PubMed1995

Chronic symmetric symptomatic polyneuropathy in the elderly: a field screening investigation in two Italian regions. I. Prevalence and general characteristics of the sample. Italian General Practitioner Study Group (IGPSG).

The prevalence and general characteristics of chronic symmetric symptomatic polyneuropathy were assessed in two elderly populations living in Varese, northern Italy, and San Giovanni Rotondo, southern Italy. We interviewed 4,191 subjects (3,027 in Varese and 1,164 in San Giovanni Rotondo), 55 years and older, seen in office consultations by 27 general practitioners. A neurologist examined 734 patients who had two or more symptoms of polyneuropathy. A diagnosis of possible polyneuropathy (screening neuropathic symptoms and one of the following findings: bilateral impairment of strength; bilateral impairment of sensation; bilateral impairment of deep tendon reflexes) was made in 213 patients (7.0%) in Varese and 94 (8.1%) in San Giovanni Rotondo. Probable polyneuropathy (screening symptoms and at least two of the physical findings) was present in 111 Varese patients (3.7%) and 40 San Giovanni Rotondo patients (3.4%). The age- and sex-adjusted prevalence rate of probable polyneuropathy was 3.6 per 100 in Varese and 3.3 per 100 in San Giovanni Rotondo. The disease was more prevalent in women in Varese and in men in San Giovanni Rotondo and was significantly correlated with age in Varese. Diabetes was found in association with probable polyneuropathy in 43.7% of patients. Muscle cramps and distal paresthesia were the main symptoms. In general, polyneuropathy was mild to moderate, impairment of deep tendon reflexes and sensation being the most common findings.

Aged↗
PubMed1994

Cholesterol management in Dutch general practice. A comparison with national guidelines. Dutch College of General Practitioners.

OBJECTIVE: To examine cholesterol diagnosis and treatment by Dutch general practitioners (GPs) in the period before publication of national guidelines, in order to develop implementation strategies based on discrepancies found between daily practice and the guidelines. DESIGN: Data of the 'Dutch National Survey of General Practice', in which GPs were involved in extensive consultation registration, were used. Patients were included for analysis if serum cholesterol, or the ICPC-code lipid metabolism disorder, or cholesterol-lowering treatment was registered. SETTING: General practice. PARTICIPANTS: 161 GPs, 177 practice-nurses. OUTCOME MEASURES: Reasons for consultation, diagnoses, therapy, inter-doctor variation. RESULTS: The main discrepancies between daily practice and the guidelines concerned indications for cholesterol measurement, repeated measurements to diagnose hypercholesterolaemia, and attention for diet advice. A remarkable inter-doctor variation in diagnosis, and less so in treatment, was also found. CONCLUSION: The inter-doctor variation justifies the publication of the standard guidelines. Implementation strategies should aim at indications for cholesterol testing, repeating measurements for diagnosis, and advice on diet.

Adolescent↗
PubMed1995

Current and possible screening practices for diabetic retinopathy by general practitioners: new evidence from a pilot survey of Oxfordshire general practitioners.

AIM: To investigate the relationship between the number of general practitioners in a GP practice and screening for diabetic retinopathy in order to evaluate the viability of increased GP involvement in screening for blinding diabetic eye disease. METHOD: A ten point questionnaire was developed and sent to 50 randomly selected general practitioner practices throughout Oxfordshire. 41 (82%) of the general practitioner practices returned completed questionnaires. RESULTS: The mean number of GP's per GP practice was 4, with a standard deviation of 4 GP's while GP practice sizes ranged from 1 to 9 GP's per practice. Overall, 66% (n = 27) of GP practices indicated that they referred their diabetic patients for screening, even though 83% (n = 34) of GP practices performed funduscopy. 76% (n = 31) of GP practices ran diabetic clinics, and 66% (n = 27) of GP practices indicated that they wanted more training in the use of the ophthalmoscope and detecting diabetic retinopathy, despite the fact that 78% (n = 32) of this same group had received some form of postgraduate medical training in diabetes in the last five years. Lastly, only 27% (n = 11) of GP practices would alter their attitude to screening for diabetic retinopathy if they were paid substantially more to do so. CONCLUSIONS: Most GP practices referred their diabetic patients for screening, even though the majority of GP practices performed some form of funduscopy and that amongst the largest GP practice sizes all performed dilated funduscopy and did not refer for screening. Given sufficient remedial training in the use of the ophthalmoscope and practical sessions on detecting diabetic retinopathy, it is likely that smaller GP practice sizes would be encouraged to screen for sight-threatening diabetic retinopathy.

Data Collection↗
PubMed1993

Improving general practitioner involvement in urban hospitals. Departments or divisions of general practice.

OBJECTIVE: To discover what measures have been taken in urban Australian hospitals to involve general practitioners (GPs) in public hospital services. DESIGN: A descriptive study. Data were collected by postal survey. SETTING: Hospitals in urban areas. MAIN OUTCOME MEASURES: Appointment of GP affiliates or associates, existence of departments or divisions of general practice, appointed GP liaison positions and formal arrangements for GP shared care and discharge planning. RESULTS: Ninety-five of 102 hospitals (93%) responded to a postal survey. Sixty-five per cent of respondent hospitals had appointed GP affiliates or associates, 32% had a division or department of general practice and 41% had a designated GP liaison position. Forty per cent had formal GP shared care programs and 14% had formal GP involvement in discharge planning. CONCLUSION: There was a high level of adoption of measures to involve GPs in urban hospitals. However, only a minority of hospitals had comprehensive measures in place and sufficient support for this to occur.

Australia↗