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The adaptation of the European directive 2001/20/CE on clinical drug trials was the opportunity for a profound reform of the legislative framework on biomedical research in France. Within the main innovations, the distinction between the three broad research categories was retained: biomedical research, research on standard care, and non-interventional research. These changes have rendered the legislative arsenal of research more complex, and therefore these changes should be reviewed. This article presents how the 2007 French healthcare research regulations can be applied. Briefly, four questions should be asked before research is undertaken: (1) does the study require a specific procedure on a person (intervention or investigation)? (2) Does it use material from the human body that will be preserved or discarded? (3) Does it require processing personal patient data? (4) Does it include genetic data? Researchers are expecting a simplification of procedures with the new regulations. This objective has been partially met, but a certain number of questions remain unanswered, particularly in the field of epidemiology.

The expectations of patients with osteoarthritis are essential for health care provision and may be used to improve the patient-doctor relationship.A total of 96 osteoarthritis patients aged 42-89 years (mean=65; 81% female) were recruited among customers of 10 pharmacies in 10 towns in 10 regions (selected at random from the 22 French regions). Ten focus groups were organized looking at three categories of expectation: 1) Information about and understanding of osteoarthritis; its impact on lifestyle, and its treatment, consequences, and outlook; 2) Communication skills, attitudes of practitioners and communication between health professionals; 3) Support available from doctors, family circle and society.The patient-practitioner relationship begins with a dialogue, the quality of which, the participants could be improved by: developing greater trust: patients expect communication skills and expressions of sympathy that practitioners seem ill-prepared to provide. Strengthening involvement: general practitioners in particular should act as mediators and facilitators to improve recognition and understanding of osteoarthritis by employers and public decision-makers.The present study enabled patients to express their expectations. Meeting those expectations could markedly improve the therapeutic process, but the question arises of whether practitioners are ready to agree that there is a need to reconsider and modify the care they provide for their patients.

Population ageing and longer duration of the working career could increase the prevalence of impairments and disabilities whereas there have been few data to help prevention and care. This study aimed at describing the prevalence of various types of impairments and assessing their social inequalities in the Lorraine population (north-eastern France).The sample included 6.214 subjects aged 15 or more from 8.000 households randomly selected in the Lorraine population. A mailed questionnaire including socio-demographical characteristics, job, and various types of impairments was used. The data were analysed with the chi2 independence test, the adjusted odds ratio (OR) and the Mantel-Haenszel test.The prevalence of at least one impairment was 30% in both sexes. It varied from about 20% for subjects aged less than 40 years to about 60% for the subjects aged 70 years or more. It was higher in men than in women among the individuals aged more than 50 years (OR adjusted on age: 1.22, 95% CI: 1.04-1.44). The impairments were generally multiple for the subjects aged over 50. The prevalence of at least one impairment was higher for workmen (OR adjusted on age: 2.11, 95% CI: 1.68-2.66), farmers, craftsmen, traders and heads of firms (OR adjusted on age: 1.60, 95% CI: 1.17-2.18) and for employees (OR adjusted on age: 1.62, 95% CI: 1.29-2.03) in comparison with executives, intellectual professionals and teachers. For workmen a higher prevalence was observed for all types of impairments: intellectual and psychological functions, language, hearing, vision, visceral functions, and skeleton and posture. Farmers, craftsmen, traders, heads of firms and employees showed an excess for most types of impairments. Social inequalities were significant for various age groups during their period of occupational activity, but not after retirement. Unemployed people also had an excess of impairments.The prevalence of impairments strongly increased with advancing age. Marked inequalities were observed between various socio-occupational categories. Men were more affected than the women over 50 years of age. Impairments represent a health index which is useful for prevention to reduce their causes and consequences.

Patients with spinal dysraphism may have severe constipation and faecal incontinence. The impact of antegrade colonic enema (ACE) in the management of patients with spina bifida (SB) is analysed. In a multicentre cross-sectional study, constipation, faecal incontinence and faecal management were described. Cases surgically treated were identified. Data were collected from 423 patients, of whom 230 did not use any manoeuvre or laxatives to assist evacuation. Conventional treatment was used in 193 patients, including digital extraction in 39%, retrograde enema in 21% and oral laxatives in 52%. For intractable constipation and overflow of faecal incontinence, 47 patients were treated with ACE, of whom 41 used the method at a mean time of interview of 4.1 +/- 1.9 years after ACE operation; six abandoned ACE for conventional management. With ACE, faecal continence was significantly improved compared with conventional management, and neither retrograde rectal enema nor digital extraction were required. The conduit was fashioned to the right colon in 32 cases and to the left colon in nine cases. This study provides information on a multicentre experience in bowel management in SB patients. Whatever the technique used, ACE has improved faecal status compared with conventional therapy.

Summary Objective To develop and validate a new health related quality of life (HRQOL) questionnaire specific to obesity and its management. Methods This study was in two parts. The first (Study 1) consisted of the creation of a new tool derived from the American "Impact of Weight on Quality of Life Questionnaire" (IWQOL, 74 items) by adding to it a 17 items specific complementary module. This initial questionnaire (91 items) was reduced so as to obtain a questionnaire adapted to socio-cultural factors of obesity and dietary weight management in France. The objective of the second (Study 2) was to validate this final questionnaire by evaluating its psychometric properties: construction validity, internal reliability, concurrent validity in relation to a generic questionnaire, the SF-12, clinical validity by studying the effects of age, gender and body mass index (BMI), and reproducibility. Results The results of Study 1, obtained in 128 obese patients (mean age: 42.5 12.1, BMI: 34.5 2.8 kg/m 2 , women: 83.6%) enabled reduction of the 91 questionnaire items to 36, grouped into 5 dimensions: physical impact, psycho-social impact, sex life, comfort with food and diet experience. Two hundred and twelve patients (mean age: 43.3 12.2, BMI: 35.8 7.4 kg/m 2 , women: 77.7%) were included in Study 2, among whom 75 filled out the questionnaire twice at a one week interval. Analyses enabled verification of the construction validity and internal reliability (Cronbach alpha > 0.7) of the questionnaire as well as its concurrent validity in relation to summarized SF-12 scores and its clinical validity. The "physical impact" dimension was significantly influenced by BMI and age, the dimensions "sex life" and "diet experience" by the factors gender and BMI, while "psycho-social impact" was influenced by the 3 factors cited. Its reproducibility was also deemed satisfactory (intra-class correlation coefficient > 0.8). Conclusion This new questionnaire, called the "Echelle Qualite de Vie, Obesite et Dietetique (EQVOD)"/"Quality of Life, Obesity and Dietetics (QOLOD)" rating scale is sufficiently reliable and reproducible to be used in clinical practice. It is a simple tool adapted to socio-cultural factors of obesity in France, enabling taking into account of the effects of dietary management on the HRQOL of obese people.

This work shows the development of a tool useful in the characterization of intestinal noises (INN), this with the aim to identify certain pathologies of the digestive system in the nearby future. The proposed system has 8 audio transducers (7 for reception from INN and 1 for environmental noises (ENN). Signals are detected through a circuit that conditions them and then they are digitalized, filtered (eliminating ENN), compacted and finally stored for its further analysis.

Multicellular spheroids are three-dimensional structures that are used to mimic small tumors. Cellular organization of spheroids allows the formation of in vivo tumors much better than two-dimensional in vitro models. Spontaneous spheroid generation is presently performed in T-flask, on agarose layer to prevent cell attachment at the bottom of the flasks and spheroids can then be expanded in agitated systems such as spinner flasks. The aim of the current research is to develop a novel spheroid model based on tumour cells cultivated in polymer microcapsules, which could mimic in vivo tumors. We mainly focused on the effect of the operating conditions on the capsule size and stability, with the objective to reach small size spheroids with a narrow distribution.

Health related quality of life is becoming of greater importance in the medical field. Nevertheless, methodological problems persist, and particularly when it comes to processing missing data on quality of life questionnaires. In fact, this leads to three difficulties: (i) loss of power; (ii) bias; (iii) choice of the most adequate method for treating missing data. Prevention is the best recommendation in order to avoid unanswered questions. Unfortunately, this does not guarantee the absence of missing data. Therefore, the treatment of missing data depends on: i) identification of the missing data mechanism and ii) choice of the most appropriate method to correct the data. The main objective of this article is to illustrate the identification of non-response items as described in the SF-36 questionnaire items in the SU.VI.MAX study.A logistic regression on the characteristics of the subjects was used to distinguish between two missing data mechanisms: missing completely at random (MCAR) and missing at random (MAR). Two global Chi-2 tests on MCAR mechanism were proposed. The missing data not at random (MNAR) mechanism was also analysed considering the questionnaire features.The percentage of non-responses was small (1.7%), with a maximum equal to 3% for four questions of the General Health dimension (GH2 to GH5). Both global Chi-2 tests rejected the hypothesis that all SF-36 non-responses were MCAR. As to the 32 items with less than 2.3% of non-responses, the mechanisms were: MCAR for 29 items, MAR for 2 items, and probably MNAR for 1 item. The logistic regression indicates that the factors related to non-responses were gender (female), age (or =50 years), attention problem, and number of children (or =3). The hierarchical feature of item PF5 (climb one flight of stairs) in relation to PF4 (climb several flights of stairs) would be a generator MNAR non-responses. The "I don't know" response modality of bloc GH2 to GH5 would also be generator of non-responses of the MNAR type.The identification of missing data mechanisms through statistical analysis and through further reflection on the questionnaire's features is a necessary preliminary in the treatment of non-responses.

Radiofrequency (RF) is a method of in situ destruction of liver tumor. Biliary complications are bile ducts stenosis or biliary abcess. The aim of this work was to study consequences of liver RF on bile ducts.A porcine model of biliary lesions was created using radiofrequency ablation liver. Twenty-two pigs were used for the study. The RF RITA 1500 generator (RITA Medical Systems, Mountain View, Calif., USA) was used for all experiments. The needle was positioned under sonographic control in liver parenchyma beside bile ducts. Two lesions were performed in left liver. Four groups of 5 pigs were treated. The pigs were sacrificed 1 or 3 weeks after the procedure. Pringle maneuver was utilized in half of the RF procedures. An ex vivo cholangiogram was obtained by direct injection into the main bile duct. Samples of RF lesions of liver parenchyma near and at a distance from the RF lesions were taken for pathological studies.Radiological lesions were biliary stenosis, with or without upstream bile duct dilatation, or complete interruption of the bile duct, or extravasation of the radiological contrast agent. Histological lesions of bile ducts were observed near RF lesions and at distance of the RF lesions when a Pringle maneuver was used or when the liver was removed after 3 weeks.RF ablation in contact of the intrahepatic bile duct induced biliary lesions. Therefore, it is required to stay away from the bile duct or to protect it when performing RF ablation.

To determine the value of known computed tomographic (CT) criteria to differentiate non-complicated from complicated (strangulation, necrosis) small bowel obstruction.43 patients with a definitive diagnosis of small bowel obstruction based on clinical, sonographic, CT, surgical and pathological findings were included. All patients had small bowel obstruction caused by adhesions confirmed at surgery. The obstruction was non-complicated in 28 patients and complicated in 15 patients. The CT examinations from all patients were retrospectively reviewed by three experienced radiologists using a set of pre-defined criteria. Attention was focused on the following signs: reduced enhancement of the small bowel wall, mural thickening, congestion of small mesenteric veins, and ascites. Results were correlated with surgical and/or pathological data.For the diagnosis of complicated obstruction, reduced bowel wall enhancement had a sensitivity of 57% and a specificity of 100%, a bowel wall thickness greater than 3 mm had a sensitivity of 35% and a specificity of 100% and a bowel wall thickness less than 1 mm had a sensitivity of 35% and a specificity of 93%. Ascites and congestion of small mesenteric veins were not significant. The multivariate analysis showed that the association of bowel-wall thickening and reduced enhancement of the small bowel wall was significant (sensitivity of 71%, specificity 100%, and accuracy 90%).Among the CT criteria used to diagnose complications from small-bowel obstruction that were evaluated in this study, only three were significant with a high specificity but low sensitivity.

The human body sends signals that reveal the condition (state of health) of its internal systems. These signals sometimes are very difficult to detect or quantify because special equipment designed for this purpose is required. Intestinal noises (IN) are such signals and give useful information that may be used in the prevention and treatment of intestinal diseases. To alleviate this problem, the design of a system for detecting, storing and analyzing IN is presented. It is shown that long time records are possible due to the use of a data compression algorithm and a noise canceller filter.

With the ATM block transfer with a delayed transmission (ABT/DT) capability, the amount of bandwidth allocated to the different cell flows of a connection (namely the CLP=0+1 and possibly the OAM cell flows) is constant over an ATM block and is referred to as the block cell rate (BCR). Successive BCR values are dynamically negotiated between the user and the network via the exchange of resource management cells. The BCR negotiation for a given ATM block may be initiated either by the source or the destination. As a basic principle, before transmitting an ATM block the source should receive an explicit authorization from the network. This paper gives the existence proof of a protocol for supporting the ABT/DT capability as specified in the May 1996 version of lTU-T Recommendation I.371.

The cingulate gyrus (CG) is often involved during partial epileptic seizures. The purpose of the study was to analyse the CG morphology and to measure the CG volume in epileptic patients, in order to detect subtle MRI abnormalities such as atrophy, which could be indicative of its implication in the epileptogenic area. The population consisted of 20 epileptic patients (31.2 +/- 9.4 years) and 20 normal volunteers (31.8 +/- 7.7 years). The epileptic patients underwent intracerebral recordings, and were sub-divided into five patients presenting with seizures involving the CG (CG 1), seven patients in whom the CG was only secondarily involved (CG 2) and eight patients in whom the CG was not invoved at all (CG 3). All subjects were investigated by MRI (1.5 tesla Gyroscan Philips): axial T1w 3D Gradient Echo acquisitions, thickness 1.5 mm, reconstructions in all planes. At first, we described the sulcal limits of the CG, trying to define a "normalised CG". In a second step, we segmented the CG intrasulcal grey matter using the "Surgiscope Scopeplan" (Elekta). We compared (Mann and Whitney U test [alpha=0.05]), the CG volumes of CG 1 to CG 2 + 3, and the volume of CG 1 and of CG 1 + 2 + 3 to that of normal volunteers. There was no significant difference between CG 1 and CG 2 + 3 (P= 0.89), between CG 1 and normal volunteers (P= 0.75) or between CG1 + 2 + 3 and normal volunteers (P = 0.83). The volumetric analysis showed no atrophy of the CG in epileptic patients and did not distinguish the group in whom seizures involved the CG, from the other groups.

Developing countries exhibit the highest adolescent fertility rate in the world. Undesirable outcome frequency during adolescents' pregnancy and delivery is debated. The aim of this study is to determine the incidence of these events and the factors predicting their occurrence among pregnant Senegalese adolescents and their newborn. The study was conducted between August 1st, 1999 and July 31st, 2000 in a national sample of 435 women attending prenatal clinics after a 20-week gestation. The data were collected by interviews: sociodemographic characteristics, obstetrical antecedents, current pregnancy history before inclusion in the study; the clinical characteristics were determined at inclusion. Then pregnancy and delivery complication occurrences were observed for mothers and their newborn during follow-up. Logistic regression analyses were performed to determine the factors associated with each complication, controlling the effects of other sociodemographic and clinical factors. The most frequent pregnancy complications were pregnancy-induced hypertension and toxaemia (17.5%). Anemia occurred in 25% of the women. At delivery, at least one of dystocia, eclampsia, or placenta haemorrhage complications occurred in 46% of women. The caesarian rate was 20% and the mortality rate was 71%. When planned, caesarian interventions lowered mortality. Forty percent of the newborns presented a neonatal distress while 17.9% of them weighed less than 2,500 g. The pregnancy-induced hypertension and toxaemia incidence rates were higher when the weight at onset of pregnancy was unknown (OR = 3.7 [1.9-7.5] for hypertension and 3.1 [1.3-7.6] for toxaemia). When a woman with a narrow pelvis was less than 1.50 m tall, the delivery was more frequently assisted by forceps and extracting action in breech delivery. Dystocia, eclampsia, placenta haemorrhage and premature delivery were associated with high mortality. Overall, complications were not more frequent in the youngest (16 years and below), as suggested in previous studies. Those results suggest that undesirable events occur frequently during adolescents' pregnancy and delivery, and in their newborn, while attendance in prenatal clinics is adequate. The prognostic factors of these complications are identified. These complications can be avoided by improving ante- and perinatal care quality.

Experimental results and clinical trials showed that bladder tumours Tis and pT1a can be diagnosed by photodynamic diagnosis and treated by photodynamic therapy. These photochemical methods are based on a selective photosensitizer uptake in the tumour tissue. After subsequent irradiation, these tissues emit a fluorescence (diagnosis) or can be destroyed by chemically induced oxidative compounds (treatment). Hematoporphyrin derivative and its oligomeric part have been the light-sensitizing drugs the most commonly studied. Interest has now shifted to 5-aminolevulinic acid, or its hexylester form, inducing protoporphyrin IX which shows better tumour localising properties and could avoid side effects. While photodynamic treatment is still an experimental modality, photodynamic diagnosis could achieve a more accurate detection of occult dysplasia compared to white light cystoscopy.

OBJECTIVE: To determine the prevalence rates of morbidity in the general population through bibliographic research. METHODS: Articles relating to impairment, disability, handicap, quality of life and their prevalence in the general population, published between January 1990 and March 1998, were selected on the MEDLINE database. FINDINGS: The 20 articles retained out of 433 used 41 different indicators. Indicators of impairment, disability, handicap and low quality of life showed prevalence rates of 0.1-92%, 3.6-66%, 0.6-56% and 1.8-26% respectively, depending on age and the accuracy of indicators. The heterogeneity of the conceptual framework and insufficient recognition of the importance of indicator accuracy, the age factor and the socioeconomic characteristics of the studied populations impede reliable international comparison. CONCLUSION: Further standardization of indicators is therefore required. The revision of the International Classification of Impairments, Disabilities and Handicaps may make it possible to resolve some of the difficulties encountered.

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

Many measurement instruments, particularly measures of hand functional ability, frequently comprise a large number of items. Reduced versions of these instruments can facilitate their use. This work proposes a new method for shortening an instrument.The method proposed was based on a scale of item difficulty calculated using the Rasch model. It was applied on a hand functional measure comprising 67 tests. The sample included 194 patients with hand lesions. The shortened instrument obtained was compared with those provided by classic methods used in the literature, with item random choice, and with shortened versions proposed by four independent experts, two rehabilitation physicians and two occupational therapists, who are clinicians familiar with the tool. All the statistical analyses were carried out on a random sub-group of two-thirds of the sample. A cross validation was then carried out on the remaining third.The reduction obtained had score non significantly different from that of the original instrument. In addition, the intra-class correlation coefficient and the Cronbach alpha coefficient were high. Among the different degrees of reduction investigated, the 12-item version seemed to be appropriate. Our method appeared to provide better results in terms of discriminant validity and internal validity than the choices of the four experts. The reductions produced were also better than those obtained by classic methods based on principal component analysis and multiple linear regression, as well as those obtained by random choices of items.The method presented is pertinent and useful. The reduction obtained appeared to be better than the choices of experts and the reductions provided by classic methods. The method could be used in other fields.

To examine the links between the quality of life (QOL) and season and weather conditions in ankylosing spondylitis (AS) patients.A cohort of 146 AS patients (67% males), with a mean age of 47.3 years and a mean disease duration of 12.8 years, answered a self-administered questionnaire, the AS-AIMS2 validated for AS, 4 times over a period of one year in a postal survey. Clinical measures were assessed in a subsample of the cohort. Meterological data including daily temperature, hygrometry, wind speed and atmospheric pressure were collected over the same period.In this cohort, 106 patients completed the follow-up. A higher lumbar spine flexibility (Schober index) was associated with a higher climatic temperature and lower wind speed. Physical QOL improved in the summer, as did Social Interaction in the summer and fall, while Role QOL decreased in winter. A lower perceived QOL was significantly associated with a higher temperature and wind speed over the past 4 weeks, and with a higher hygrometry and atmospheric pressure over the past 2 days prior to completion of the questionnaire.This study provides some support to the popular belief and frequent patient complaints of a link between health status and perceived quality of life, as assessed by a specific questionnaire, with season and weather conditions.

Rheumatoid arthritis (RA) is a chronic disease with severity and consequences varying from one patient to another, and potential impact on individual, family and society over the long term. The impact can be defined as the various outcomes beyond the patho-physiological disease process. The components of the impact of RA comprise of joint damage, functional disability, impairment of quality of life in several dimensions and socio-economic consequences, like work disability, social participation restriction, and economic costs. These consequences should be analysed in the frame of the recent revision of the international classification of impairment, disability and handicap (ICIDH-2). This model will help understand the mechanisms of resistance to and limitation of the impact of the disease. The measurement of such outcomes has largely benefited of research focused on this particular disease in the past two decades. A reliable measure is necessary to assess the impact, and to document the progression of impact over time. Outcome measures should be sensitive to natural changes or therapy effects over the disease progression. - Radiographic lesions are now well documented by increasingly accurate and standardised assessment scoring methods of joint damage. - Self-assessment questionnaire of functional disability has now its standard, the HAQ, with some variants, primarily developed and documented in RA. - Health-related quality of life measures have been an exploding area of methodology and research development in the recent years, making generic and RA specific instruments like the AIMS2, or the AIMS2 Short Form valid and easily accessible in clinical practice. - Socio-economic consequences are less documented. Several studies have examined and quantified the amount of work disability the frequency of which varies by country. Recent analysis of the EURIDISS cohort study has examined the social network changes and the influence of social support provided to patients. The direct and indirect costs of RA have been well documented in some country and appear substantial. The prediction of outcome by a simple equation modelling outcome as a function of measurable predictors would be ideal for monitoring patient therapy from the very start of the disease. Unfortunately, despite extensive studies looking at large numbers of patients, a part of individual variation and the irregular progression over time still challenges the search for an accurate group of predictors. It is readily possible to obtain a reasonable probability estimate of outcomes from a consensual set of determinants that will be reviewed. But it is not yet possible to monitor individual patient with sufficient accuracy, with the exception of a few outcomes using mathematical models demanding intensive data collection. In an epidemiological perspective, longitudinal observational studies are the standard to determine such predictors. They can be conducted retrospectively, with the risk of selection and measurement bias, or prospectively, at the cost of study duration and loss to follow-up. The identified determinants of radiographic damage and of functional disability will be reviewed, while the prognostic factors of quality of life have been less frequently documented over time. Determinants of health care resources utilisation and of cost of illness are being investigated. A better knowledge of predictors of RA impact, if modifiable by a medical or a social intervention, helps decrease the severity of the condition, decrease the frequency of deleterious consequences, increase patients quality of life and reduce costs to society. An investigation of societal and economic aspects of the disease impact is still needed over the long term. Condition for impact prediction may well change with the RA condition recently entering a new therapeutic era.

To appreciate the evolution of serum angiogenic and/or adhesion molecules levels during a long term follow-up of rheumatoid arthritis (RA) patients.Serum levels of 5 soluble adhesion/angiogenesis glycoproteins (VEGF, CD31, CD54, CD62E, CD106) were measured in Elisa in samples collected over 6 years in a cohort of 43 RA patients with monitored clinical parameters of disease activity and severity.RA patients had significantly higher levels (p0.0001) of sCD106 (VCAM-1) than control subjects. Conversely, the levels of soluble VEGF, CD31, CD54 and CD62E were normal or lower than normal. No statistically significant time effect was noted. No effect either was noted as related to the therapeutic agents taken by the patients.The sustained elevated serum levels of sCD106 observed here imply that this molecule might be related to the chronicity and progression of RA.

The aim of this study was to examine the quality of life (QoL) profiles of patients with early rheumatoid arthritis (RA) and to relate these to disease and impairment variables as indicated, respectively, by erythrocyte sedimentation rate (ESR) and by tender joint count (Ritchie Articular Index), fatigue, and pain.The present study uses part of the European Research on Incapacitating Disease and Social Support data of 573 patients with recently diagnosed RA (268 from the Netherlands, 216 from Norway, and 89 from France). A series of clinical and psychosocial data were collected on 4 (the Netherlands, France) and 3 (Norway) occasions, with 1-year intervals separating the waves of data collection.Of the disease activity (ESR) and impairment variables (tender joint count, fatigue, pain), fatigue was identified as the consequence of disease that differentiated best on a series of QoL aspects such as disability, psychological well-being, social support, and "overall evaluation of health." Next came pain and tender joint count, and ESR showed by far the least differentiating ability. A principal-component analysis on the QoL measures used in this study yielded one general factor measuring "overall QoL." After rotation, two separate factors were encountered, one referring to the physical domain and the other to the psychological and social domains of QoL. Again, the QoL of RA patients experiencing much fatigue appeared to decline the most.Because of the highly variable nature of RA, impairments, activities of daily living (ADL) and instrumental ADL restrictions, and psychosocial distress can vary erratically. In particular, "fatigue" as measured over a period of 2 to 3 years distinguished best among RA patients as shown by their QoL profiles. Although the physical domain was most affected, the significant effect of RA on the psychosocial domain should not be underestimated.

The organization of the management of pain and other symptoms all along the cancer disease, of psychological support and palliative care is a complex question that does not correspond to any perfectly established model, both in France and abroad. Different structures are implied in there care and coexist with an insufficient coordination: cancerology structures, structures of chronic pain management, structures of psycho-oncology, structures of palliative care. Some other assistances are more or less isolated inside the hospital: nutritional support, social assistance, action against tobacco and other addictions, volunteer work. Because of the evolution of practices and mentalities over the last ten years, the highlights of evident interfaces and complementary activities, the notions of "continuous care" and "integrated care" inside conventional departments, the budgetary and organizational restraints, it is now possible to propose a model of hospital structure adapted to the problem of supportive care. The creation is proposed from preexisting structures, consultations, units, departments of supportive oncological care according to the size of the institution. The structure should comply with some specifications, sometimes regulations, and to coordinate at best different competencies in the interest of the patients and medical teams : pain and symptoms management (of which palliative care is an important part), psycho-oncology, rehabilitation (functional rehabilitation, nutrition, social work, fights against addictions). A pooling of technology settings is one of its interest. The model can be applied in other domains than cancerology and in most health institutions.

We report the influence of fluence rate on the photobleaching and cell survival in Colo 26 multicell spheroids photosensitized by meta-tetra-(hydroxyphenyl)chlorin (mTHPC). Photosensitizer degradation and therapeutic efficacy increased dramatically and progressively when the fluence rate was reduced over the range from 90 to 5 mW cm-2. These experimental results were compared to a mathematical model of photobleaching based on self-sensitized singlet oxygen reactions with the photosensitizer ground state. This model incorporates photophysical parameters obtained from microelectrode measurements of oxygen depletion at the surface of mTHPC-sensitized spheroids and was refined by including the inhomogeneous distribution of mTHPC in spheroids and oxygen depletion in the bulk medium. Since the model is consistent with the experimental data we conclude that the fluence rate dependence of the cell survival and of mTHPC photobleaching is due to photochemical oxygen consumption and a predominantly singlet oxygen-mediated mechanism of mTHPC photobleaching. The threshold dose of reacting singlet oxygen was calculated to be 7.9 +/- 2.2 mM in this system.

Concepts and methods in professional practices evaluation are often confused. After a description of the classical conceptual framework, we present these methods in an approach in which practice is the principal result to be measured. Thus it makes it possible to apply the traditional epidemiological concepts to the evaluation of the professional practices with their three traditional fields: 1) In the descriptive approach, cross-sectional practice studies allow an observation and description of the usual behaviors, possibly compared to references. The methodological constraints are the same as which of descriptive epidemiological studies; 2) In the analytical approach, factors associated with practice - simple or conformed to criteria - are evidenced on a representative sample; 3) In the evaluative approach of practices improvement, the objectives are the assessment of formative, organizational or structural interventions, aiming at modifying practices. Three types of studies are to be used: quasi experimental in which clinical audit is the reference method in the field of medical care. The six main steps of clinical audit are described; experimental, based on the community randomized trial scheme, which have the advantage to provide results that can be immediately generalized; observational in which no control on the implementation of intervention is done. "Here and else" and "before and after" studies are used. To be effective for evaluation of professional practice, theses methods must come within the scope of a favorable institutional context.

3-D optical fluorescence microscopy becomes now an efficient tool for volumic investigation of living biological samples. However, acquired raw data suffer from different distortions. In order to carry out biological analysis, restoration of raw data by deconvolution is mandatory. The system identification is useful to obtain the knowledge of the actual system and to quantify the influence of experimental parameters. High order centered moments are used as PSF descriptors. Oil immersion index, numerical aperture and specimen thickness are critical parameters for data quality. Furthermore, PSF identification is helpful to precise the experimental protocol. Application to 3-D anthracycline distribution in breast cancer cells is presented.

Photodynamic therapy (PDT) using meta-tetrahydroxyphenylchlorin (mTHPC) performed on HT29 human colon adenocarcinoma xenografts in nude mice was shown to be enhanced by Trolox, a water-soluble vitamin E analogue. Trolox, injected i.p. at 250 mg/kg body weight 90 min before PDT, delayed tumor doubling time from 13 (PDT only) to 19 days. Enhancement of the tumoricidal effect of PDT by Trolox required the presence of the drug at the photochemical stage since its injection after irradiation is ineffective. HPLC measurements indicated that 1 hr after injection the Trolox concentration in plasma was as high as 0.8 mM. In vivo measurements of mTHPC fluorescence in mice treated by PDT with or without Trolox injection showed that Trolox did not protect mTHPC from photodegradation. Laser flash photolysis studies performed in solution demonstrated that Trolox reduces triplet mTHPC efficiently (reaction rate constant 2 x 10(7) M(-1) * sec(-1)) leading to the formation of radical products. Kinetic considerations suggest that the Trolox-mediated radical pathway can work in relay with singlet oxygen in hypoxic conditions, providing a possible explanation for the observed enhancement of mTHPC-sensitized PDT by Trolox.

Functional disability and quality of life in rheumatoid arthritis (RA) are key outcomes that determine patients' demand for care, and influence their compliance and satisfaction with treatment. In the past decade, there has been a shift from physician-focused assessment toward methods based on the postulate that patients can better report their perceptions of health impairment. There are several disease-specific and generic instruments available that have proven valuable in outcome testing in RA. While there are several obvious advantages to patient self-assessment, clinicians may be reluctant to adopt these measurements. Functional assessment testing will be easier to implement if physicians have access to computer resources for quantitation of disease outcomes and if normative data can be provided to make interpretation clear. Despite current limited access to computer resources and normative data, functional disability and quality of life assessment of RA should be encouraged in clinical practice because it fosters better patient-physician relations and provides much needed long-term outcome information on drug therapy beyond clinical trials.

The development of quality of life (QOL) instruments has made it possible to obtain an objective assessment of the impact of surgical procedures taking into consideration the physical, psychological and social aspects of the patient's everyday activities. The aim of this work was to evaluate the short-term and long-term course of QOL after total hip arthroplasty (THA) and total knee arthroplasty (TKA).This study included a prospective multicentric cohort of patients with a first intention indication for degenerative bone and joint disease. Clinical assessment was obtained preoperatively and 6 weeks, 6 months and 12 months postoperatively. The Merle d'Aubigné and Harris scores were determined for THA and the Hospital Special Surgery score for TKA. Clinical data (pain, walking distance), and QOL scores [French version of the Nottingham Health Profile (NHP) and the French version of the Arthritis Impact Measurement Scale 2 (AIMS2)] were also obtained.One hundred twenty-three patients had a THA (mean age 62 years) and 60 had a TKA (mean age 68 years). Preoperative clinical features were those commonly found in these populations. For THA, the 6-week, 6-month and 1-year assessments showed an improvement (2.7 and 2.8 points on the 0 to 10 NHP). For TKA, improvement came later and was less significant with 0.8, 1.8 and 1.5 point improvements. The AIMS 2 did not appear to be perfectly adapted to measure this dimension. Improvement in pain came earlier and was greater for THA than for TKA on all measurement scales. For THA, psychological capacity improved by 0.7, 1.4 and 1.5 points on the 0 to 10 AIMS 2 at 6 weeks, 6 months and 12 months respectively. For TKA, improvement was to the same order with 1.1 and 1.2 point improvements at 6 weeks and 6 months respectively.These findings confirm the clear improvement in QOL after THA and TKA, mainly due to physical and psychological dimensions. The QOL measurements allow comparisons with other surgical procedures in other fields. They provide supplementary information, notably concerning pain and are particularly useful in orthopedic surgery. The questionnaires are generally well accepted by the patients, particularly short self-administered questionnaires. They provide useful information on the efficacy of THA and TKA in terms of human and social costs and open new perspectives for analysis of prognostic factors for optimal QOL of operated patients.

To delineate compliance with drug therapy in rheumatoid arthritis patients, determine specific characteristics of compliant and noncompliant patients, and look for changes in compliance over time.A prospective European cohort study (EURIDISS) recruited 556 patients in four countries over three years. Compliance with drug dosages and dosing times was evaluated yearly using a questionnaire.Of the 556 patients, 429 (77.2%) were on drug therapy at all three evaluation time points. Use of steroids, nonsteroidal anti-inflammatory drugs, and second-line drugs varied significantly across countries. The compliance behavior was stable over time in 59.5% of them (35.7% of patients were consistently compliant and 23.8% consistently noncompliant); it was independent of disease duration and from the clinical features of the disease. Older patients and women were more likely to be compliant (odds ratios, 2.5 and 2, respectively).Compliance with drug therapy can be measured using two simple questions. Compliance is more closely dependent on individual behavior than on responses to specific features of rheumatoid arthritis.

To describe the costs of medical imaging practices in the diagnosis management of acute abdominal pain (AAP).Medical imaging techniques until decision for treatment were prospectively recorded in patients presenting with AAP. Direct costs used hospital analytic accountability. Time of human resources involved was also surveyed prospectively.In 122 adult patients (2.3 examinations on average) before treatment decision making, the more frequent practices were: initial plain abdomen x-ray followed by tomodensitometry (36.8%), by echography or endoscopy (17.2%), plain abdomen solely (19.6%) or initial abdominal tomodensitometry (12.3%). Direct costs ranged from 977 to 1073 FF for practices with initial plain abdomen x-ray, and from 996 to 1150 FF with initial tomodensitometry. It ranged from 808 to 880 FF when the treatment decision was surgery, and 300 FF higher when it was medical.Differences in costs assessed for practices were very narrow. Such information should be taken into account to determine cost-effective strategies, and to built up reference guidelines.

Quality-of-life (QoL) outcomes have become increasingly important in the evaluation of health interventions. The objective of the present study was to determine which of three generic QoL instruments was most suitable for use in an 8-year nutritional primary prevention trial. We compared the Duke Health Profile, the Nottingham Health Profile, and the Short Form Health Survey Questionnaire (SF36). We conducted the comparison in two stages: (1) a statistical analysis of data from a pilot study (n = 963) comparing the psychometric properties of the three instruments; and (2) an assessment of the practicality of the tools. With regard to psychometric properties, convergent validity was comparable for the three scales, and the correlation with Global Health Assessment ranged from 0.24 to 0.72. Discriminant validity was best for the SF36, with a difference between scores in healthy subjects and those with chronic disease in the range of 4.4 to 15.8 (scores could range from 0 to 100, where 100 indicates perfect health). Reproducibility was good for all three instruments, with a test-retest intraclass correlation coefficient of over 0.60 for most dimensions. DHP and SF36 performed best in terms of responsiveness. We judged the practicality of the three tools as satisfactory. We chose the SF36 for its high responsiveness. We also selected the Duke Health Profile for its practicality and favorable psychometric properties.

To document the prevalence of rheumatoid arthritis (RA) and spondyloarthropathy (SpA) in Brittany, France.(1) Members of rheumatism self-help groups screened cases using questionnaires. (2) Rheumatologists in our unit contacted persons who had possible inflammatory rheumatic diseases and persons who refused the first interview. (3) When diagnosis remained unknown or discordant with the questionnaire, the general practitioner or the rheumatologist of these patients was interviewed. (4) Patients without diagnosis and who had not had a rheumatological examination were examined without charge by a rheumatologist.An overall prevalence rate of 0.62% (0.33-0.91) and 0.47% (0.22-0.72) was found for RA and for SpA, respectively. The prevalence of RA and SpA was 0.86 (0.39-1.33) and 0.53 (0.16-0.9) in women and 0.32 (0.01-0.63) and 0.41 (0.05-0.77) in men. The minimum prevalence of RA and SpA calculated on the estimated initial group (3189 persons) was 0.53 (0.28-0.78) and 0.41 (0.18-0.63), respectively.Our telephone survey revealed that the prevalences of RA and SpA are nearly similar among our population and that SpA is as common in women as in men.

Patient compliance is considered necessary for the success of drug treatment in chronic diseases. We document compliance with drug treatment and the factors affecting it in a cohort of patients with rheumatoid arthritis (RA).A prospective cohort study of 556 patients with RA followed for 3 years in 4 counties: Oslo, Norway; Groningen, The Netherlands; and Nancy and Reims, France. Compliance to treatment was assessed annually by interview in terms of adherence to the dose and timing of the prescribed drug regimen.Of the 556 subjects, 429 (77.2%) were taking medication for RA throughout the observation period. Consistent behavior was recorded in 59.5% of cases: 35.7% were consistently compliant, and 23.8% consistently noncompliant. Factors significantly associated with good compliance were older age (p = 0.00), female sex (p = 0.03), decreased disability (p = 0.04), very satisfactory contacts with health care professionals (p = 0.03), and more personal knowledge about the disease and its treatment (p = 0.03).This longitudinal study identified compliance behavior as consistent over time in 60% of patients, determined by quality of contact with professionals and the amount of patient information available.

The photodynamic properties of a second-generation photodynamic sensitizer, meta-tetra(hydroxyphenyl)chlorin (mTHPC) were studied by dye-sensitized photoinactivation (650 nm) of HT29 human adenocarcinoma cells in culture. The photocytotoxicity of mTHPC in vitro depended on the presence of molecular oxygen. A strong inhibition of the photocytotoxicity of mTHPC was observed upon addition of sodium azide, a known singlet oxygen quencher. Photocytotoxicity was not inhibited by scavengers of superoxide anion radical, hydrogen peroxide and hydroxyl radicals. We suggest that mTHPC photosensitizes cell killing predominantly by type II, singlet oxygen-mediated photodynamic reactions. Illumination of cells preloaded with mTHPC induced peroxidation of membrane lipids. Inhibition of photoperoxidation by alpha-tocopherol (0.1 mM) present during illumination did not result in any decrease in toxicity, suggesting that reactions of lipid peroxidation play only a minor role in the overall photocytotoxic effect of mTHPC.

Histamine has been incriminated as having a responsibility for intolerance reaction to wines. We have made a study by double blind oral provocation test to find the effect of ingestion of a histamine-rich (22.8 mg.l-1) and a histamine free wine in eight healthy subjects. Blood samples were taken at 0, 10, 30 and 45 minutes after ingestion of the wine for measurement of plasma histamine and methylhistamine. Urines were collected 5 hours before and 5 hours after ingestion for measurement of urinary methylhistamine. No subject presented a reaction of intolerance after ingestion of wine rich or poor in histamine. No change in plasma histamine and plasma and urinary methylhistamine was seen. This study shows that the amount of histamine in wine has no clinical or biological effect in healthy subjects, and this emphasized the efficiency in man of the systems for degradation of histamine that is absorbed by the alimentary tract.

This paper aims to clarify the concepts and terminology of clinical research, evaluation, and quality. Clinical research or clinical epidemiology aims to demonstrate the efficacy of medical care. The optimal methodology is a randomized, double-blind trial that allows a causal inference in respect of efficacy. This should be the first stage before generalization of all medical practice. Evaluation of quality of care aims to verify the effectiveness of medical care by comparing practice with references. The optimal methodology is clinical audit that allows fine-tuned diagnosis of the existence of deviant practices. The analysis of causes and correction of the care process are an integral part of the evaluation work. Thus quality assurance and quality management concepts and methods have been developed which tend to ensure solutions for better care and to maintain the level of quality of care to achieve patient satisfaction. Evaluation, clinical research and management quality could in fact be seen as the complementary facets of a comprehensive approach to quality of care.

Photochemotherapy (PCT) consists in administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study is to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After first studying the biodistribution of hematoporphyrin derivative (HpD) in vivo in the rat bladder, two and four hours after intravesical administration, by fluorescence microscopy, we compared two different methods for the induction of superficial bladder tumors in rats with AY-27 tumor cell line in order to perform the same study on bladder tumors. The best results for the penetration depth of HpD in the normal bladder wall were obtained two hours after the bladder instillation where the photosensitizer was detected only in the bladder surface (urothelium and small part of the chorion). That's why we must choose the most appropriate bladder tumor model in order to obtain superficial bladder tumors that mimic the clinical behavior of superficial bladder cancer in man. Both techniques used in this study gave a high tumor take rate in a short time (90%). But we really obtained superficial bladder tumors directly attached to the bladder surface with one of the two methods of tumor induction consisting in the abrasion of the bladder surface prior to the administration of the tumoral cells in the bladder cavity.

The aim of the study was to evaluate mammography rates and indications (diagnosis or screening) among women from 35 to 50 of age, and to search the main factors associated to mammographic screening.The data were collected from 6409 women through a specific questionnaire completed by a nurse.Among women from 35 to 50 years of age, 61% have undergone at least one mammography during their life; 25.6% had undergone a screening mammogram within the last three years. Whatever women's age or indications, the gynecologist was the first physician to prescribe mammography. Logistic regression model adjusting for multiple variables was used to examine factors associated with women who underwent a screening mammography within the last three years. Women more likely to be screened were 45 to 50 years of age (vs 35-40 years of age: adjusted OR 8.9, 95% CI: 7.2 to 11.2), had higher educational level (adjusted OR 1.3, 95% CI: 1.1 to 1.5), had family history of breast cancer (adjusted OR 2.7, 95% CI: 2.1 to 3.4), and used routine gynecologic care (adjusted OR 1.9, 95% CI: 1.6 to 2.4).Individual screening by mammography very often occurs after 40 years, Such behaviors may lead public health professionals to question current recommendations for breast cancer mass screening in women 50 years of age and older.

A tamoxifen-resistant cell line (MCF7TAM) was established from tamoxifen-sensitive MCF-7 human breast cancer cells expressing estrogen receptors. Though the resistant cell line grows in the presence of tamoxifen, estrogen receptors continue to be expressed at similar levels as in the parental cell line. However, estrogen receptors appeared to be altered in the resistant cell line since important discrepancies are observed between results obtained with ligand binding assays and immunoenzymatic assays, tending to show modifications of estrogen receptor ligand binding capacity. The intracellular distribution of tamoxifen in sensitive and resistant cell lines was investigated using fluorescence of eosin-tamoxifen ionic association. Fluorescence emission spectra of eosin, tamoxifen and eosin-tamoxifen complex (lambda(ex)=480 nm) were analyzed and the maximal fluorescence intensity found for the complex (lambda(em)=540 nm) was four times higher than that of eosin alone, while tamoxifen alone did not emit any fluorescence in this spectral range. In MCF-7 cells, tamoxifen was found to be mainly located surrounding the nucleus, although nuclear fluorescence intensity was significantly lower. No highly fluorescent granules were observed in the resistant cell lines as opposed to sensitive cells. Improvement of this fluorescence microscopy methodology could appear of interest, taking into account the complexity of tamoxifen resistance molecular pathways.

Gastric cancer has experienced a marked change in prevalence during the last decades. Although in some countries, as in the Far East, gastric cancer continues to be a national health problem, the incidence in most Western countries is decreasing. Most importantly, whereas the overall incidence of gastric cancer has decreased in Europe and the United States, there has been an increase in the relative percentage of proximal gastric adenocarcinomas and adenocarcinomas arising in the gastroesophageal junction. With the exception of Japan, where mass screening programs have increased the number of patients diagnosed of early gastric cancer, diagnosis at an advanced stage is the rule. Approximately 50–75% of the patients who have gastric resection for cancer have serosal invasion and/or lymph node involvement. This helps to explain why cure rates have remained unchanged for decades in spite of improvements in oncologic therapy. Investigators should consider that both accrual and design of future trials in gastric cancer will probably be affected by these epidemiological trends.

Language disorders in children are frequent and may sometimes severely affect their development. ERTL4 (screening test for language disorders of children aged 4) is the first test for screening language disorders to be used by doctors. It has not yet been evaluated.The objective of this study is to assess and optimize the diagnostic value of the ERTL4 test and to evaluate its potential interest as a screening test.A sample of 370 children was randomly constituted among children aged between 3 years 9 months and 4 years 6 months from schools in Nancy, France and surrounding areas. These children undertook both the ERTL4 test and a standardized examination of language and speech as a reference.Among the 325 children included in the analysis, 34.1% presented with disorders requiring speech and language therapy. ERTL4 sensitivity and specificity were 88.6% and 66.8%, respectively. Varying thresholds for disorder diagnoses and proposals for a modified test led to a sensitivity of 72.9% and a specificity of 91.0%. The proportion of well-classified subjects improved from 73.8% to 85.3% (P10(-3)). The positive predictive value was 78.7% and the negative predictive value was 88.1% (with the observed frequency in the sample).ERTL4 is a good test for doctors to screening of children's language disorders and their management.

To compare helical CT with MR angiography in pre-operative assessment of abdominal aortic aneurysm (AAA).Twenty patients with AAA underwent helical-CT, MR-angiography and digital angiography. All exams were interpreted independently by two groups of observers. Kappa and rho were calculated to assess correlations. Sensitivity and specificity were calculated to compare each method with the "gold standard" digital angiography.Inter-observer correlation was excellent. There was a very good agreement between both methods in the assessment of the maximal diameter and the proximal neck of the aneurysm. There was no significant difference in the assessment of stenoses of the visceral and iliac arteries, the number of renal arteries, and iliac extension.Helical CT and MR angiography are equivalent in pre-operative assessment of AAA.

From 1975 to 1996, 98 patients with infiltrative vesical carcinomas were treated at the Centre Alexis Vautrin by conservative surgery and interstitial brachytherapy (192lr). The mean follow-up was about eight years. From this retrospective non randomized study, we tried to determine the tolerance to this treatment.There were 86 men and 12 women. The mean age was 63 years. We found three pTis tumors, 28 stage pT1 tumors, 38 stage pT2 tumors, 24 stage pT3A tumors, four stage pT3B tumors and one stage Tx tumors. The therapeutic scheme consisted of pelvic radiation therapy (3 fractions of 3,5 Gy) immediately followed by lymphadenectomy (for stage pT3 tumors) and by cystotomy or partial cystectomy during which we inserted brachytherapy plastic tubes. The delivered dose was 50 Gy for superficially infiltrative tumors and 30 Gy for deeply infiltrative tumors; at the lowest dose, the treatment ended with external beam irradiation.At 5 years the control rate was 72%, the specific survival 80% and the global survival 71%. Twenty-nine patients had a local recurrence. Of these, seven underwent total cystectomy. Thirty-seven patients developed 43 complications; 35 were intravesical, 10 (28%) were estimated to be higher than grade 2 because of technical problems that led us to modify the technique.It is essential to develop close collaboration between surgeons and brachytherapists, to select patients and to use a rigorous technique. Interstitial brachytherapy for infiltrative vesical carcinomas thus yields both high local control and satisfying results in regard to patient's well-being.