Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials.

Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

Monitoring of Dermanyssus gallinae in free-range poultry farms.

Various methods for monitoring Dermanyssus gallinae infestations within free-range egg production units were compared. The study was carried out in five egg-producing free-range poultry buildings infested with D. gallinae. Each farm was divided into six zones (each zone including nest boxes, perches and duckboard) for placing two types of traps (corrugated cardboard and thick card traps) or examining dried droppings for presence of mites. Traps were removed 24 h later, placed into bags and mites were counted at the laboratory using binocular magnification. Droppings were also inspected by eye and mite numbers were estimated. All the methods used allowed us to detect mites although their efficacy differed. The number of mites collected was independent of the type of trap used. Examination of the droppings did not differentiate between buildings with differing mite populations. Placing traps in the nest boxes is a less reliable indicator than placing them on the perches. It appears that the most coherent method for evaluating the D. gallinae population within a free-range flock is to place thick card traps throughout the building, on perches favoured by birds.

[Comparison of IPSS and ICS male SF in the initial assessment of urinary disorders]. / Comparaison de l'IPSS et de l'ICS male SF dans le bilan initial des troubles urinaires.

UNLABELLED: The IPSS is considered to be the standard questionnaire for evaluation of lower urinary tract voiding disorders in men with benign prostatic hyperplasia (BPH). However, the absence of questions concerning urinary incontinence can be considered to be a weakness of this tool in view of the symptom profile of these patients. The ICS male SF, which comprises a supplementary domain of urinary incontinence, was compared to the IPSS in the context of the initial assessment of men with BPH. METHODS: One hundred and fifty-eight patients with voiding disorders associated with BPH completed the two questionnaires on two occasions at an interval of two weeks. RESULTS: The prevalence of urinary incontinence symptoms was very low (3.7%) and these symptoms were not independent of the symptoms of the urinary frequency domain. CONCLUSION: Despite the addition of a urinary incontinence domain, the ICS male SF does not provide any decisive advantage compared to the IPSS for the initial assessment of urinary disorders related to BPH.

Significant dose reduction using synchrotron radiation computed tomography: first clinical case and application to high resolution CT exams.

Since the invention of Computed Tomography (CT), many technological advances emerged to improve the image sensitivity and resolution. However, no new source types were developed for clinical use. In this study, for the first time, coherent monochromatic X-rays from a synchrotron radiation source were used to acquire 3D CTs on patients. The aim of this work was to evaluate the clinical potential of the images acquired using Synchrotron Radiation CT (SRCT). SRCTs were acquired using monochromatic X-rays tuned at 80 keV (0.350 × 0.350 × 2 mm3 voxel size). A quantitative image quality comparison study was carried out on phantoms between a state of the art clinical CT and SRCT images. Dedicated iterative algorithms were developed to optimize the image quality and further reduce the delivered dose by a factor of 12 while keeping a better image quality than the one obtained with a clinical CT scanner. We finally show in this paper the very first SRCT results of one patient who received Synchrotron Radiotherapy in an ongoing clinical trial. This demonstrates the potential of the technique in terms of image quality improvement at a reduced radiation dose for inner ear visualization.

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas.

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 µm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial.

PURPOSE: The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown. The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery. PATIENTS AND METHODS: Patients with rectal carcinoma accessible to rectal digital examination, staged T2 to T3, NX, M0, were randomized before radiotherapy (39 Gy in 13 fractions) into two groups: in the short interval (SI) group, surgery had to be performed within 2 weeks after completion of radiation therapy, compared with 6 to 8 weeks in the long interval (LI) group. Between 1991 and 1995, 201 patients were enrolled onto the study. RESULTS: A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response (53. 1% in the SI group v 71.7% in the LI group, P =.007) and pathologic downstaging (10.3% in the SI group v 26% in the LI group, P =.005). At a median follow-up of 33 months, there were no differences in morbidity, local relapse, and short-term survival between the two groups. Sphincter-preserving surgery was performed in 76% of cases in the LI group versus 68% in the SI group (P = 0.27). CONCLUSION: A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results. When sphincter preservation is questionable, a long interval may increase the chance of a successful sphincter-saving surgery.

[Psychophysiological factors in high intellectual potential: comparative study in children aged from 8 to 11 years old]. / Les facteurs psychophysiologiques de la précocité intellectuelle: résultats d'une enquête comparative chez l'enfant entre 8 et 11 ans.

UNLABELLED: Factors of intellectual talent as well as physiological and psychological characteristics are little known. However, giftedness is now a social problem and the knowledge of precocity hallmarks should permit the diagnosis in order to undertake the adequate educational orientation of these children. From questionnaires given anonymously to parents, this work showed comparative results between a population of gifted children and a control one. OBJECTIVES: The aim of this study was to present precocity hallmarks in the gifted population, following factorial analysis of socio-economic and familial parameters, as well as medical and psycho-physiological variables linked with the children's post-natal life. POPULATION: Four hundred and twelve children aged eight to 11 years, from Lyon, have been used in the survey: 217 children (control group) were included after a random selection in schools, and 195 children (gifted group, IQ >130, Wechsler test) were enrolled after clinician's diagnoses in four medical departments. RESULTS: Regression analysis allowed to draw relation between several factors and giftedness: abnormal pregnancy (CR =3.205, P =0.009), perinatal stress (CR =2.166, P =0.003), and presence of migraine (CR =3.169, P =0.001). Parents living together (married or not) (CR =2.100, P =0.080) with a good and superior level of learning (CR =5.464, P =0.0002) were also linked with giftedness. CONCLUSION: Our results indicate that precocity hallmarks are multifactorial. These data confirm some socio-economic and medical physiological features correlated with giftedness, and suggest that psychological factors may bear on the etiology of intellectual talent. We focus on the hypothesis than early stress may play a role on central nervous system maturation in these children.

Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment.

Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.

Lack of cell death enhancement after irradiation with monochromatic synchrotron X rays at the K-shell edge of platinum incorporated in living SQ20B human cells as cis-diamminedichloroplatinum (II).

In this paper we describe the results of experiments using synchrotron radiation to trigger the Auger effect in living human cancer cells treated with a widely used chemotherapy drug: cis-diamminedichloroplatinum (II) (cisplatin). The experiments were carried out at the ID17 beamline of the European Synchrotron Radiation Facility, which produces a high-fluence monochromatic beam that is adjustable from 20 to 80 keV. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). Cell survival curves were comparable with those obtained for the same cells under conventional irradiation conditions. At a low dose of cisplatin (0.1 microM, 48 h), no difference was seen in survival when the cells were irradiated above and below the K-shell edge of platinum. Higher cisplatin concentrations were investigated to enhance the cellular platinum content. The results with 1 microM cisplatin for 12 h showed no difference when the cells were irradiated with beams above or below the platinum K-shell edge with the exception of the higher cell death resulting from drug toxicity. The intracellular content of platinum was significant, as measured macroscopically by inductively coupled plasma mass spectrometry. Its subcellular localization and particularly its presence in the cell nucleus were verified by microscopic synchrotron X-ray fluorescence. This was the first known attempt at K-shell edge photon activation of stable platinum in living cells with a platinum complex used for chemotherapy. Its evident toxicity in these cells leads us to put forth the hypothesis that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation above the K-shell edge. However, K-shell edge photon activation of stable elements provides a powerful technique for the understanding of the biological effects of Auger processes. Further avenues of development are discussed.

Effect of tidal volume on distribution of ventilation assessed by synchrotron radiation CT in rabbit.

A respiration-gated synchrotron radiation computed tomography (SRCT) technique, which allows visualization and direct quantification of inhaled stable xenon gas, was used to study the effect of tidal volume (Vt) on regional lung ventilation. High-resolution maps (pixel size 0.35 x 0.35 mm) of local washin time constants (tau) and regional specific ventilation were obtained in five anesthetized, paralyzed, and mechanically ventilated rabbits in upright body position at the fourth, sixth, and eighth dorsal vertebral levels with a Vt from 4.9 +/- 0.3 to 7.9 +/- 0.4 ml/kg (means +/- SE). Increasing Vt without an increase in minute ventilation resulted in a proportional increase of mean specific ventilation up to 65% in all studied lung levels and reduced the scattering of washin tau values. The tau values had log-normal distributions. The results indicate that an increase in Vt decreases nonuniformity of intraregional ventilatory gas exchange. The findings suggest that (SRCT) provides a new quantitative tool with high spatial discrimination ability for assessment of changes in peripheral pulmonary gas distribution during mechanical ventilation.

First human transvenous coronary angiography at the European Synchrotron Radiation Facility.

The first operation of the European Synchrotron Radiation Facility (ESRF) medical beamline is reported in this paper. The goal of the angiography project is to develop a reduced risk imaging technique, which can be used to follow up patients after coronary intervention. After the intravenous injection of a contrast agent (iodine) two images are produced with monochromatic beams, bracketing the iodine K-edge. The logarithmic subtraction of the two measurements results in an iodine enhanced image, which can be precisely quantified. A research protocol has been designed to evaluate the performances of this method in comparison with the conventional technique. Patients included in the protocol have previously undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both at the ESRF and at the hospital with the conventional technique, within the next few days. This paper reports the results obtained with the first patients. To date, eight patients have been imaged and excellent image quality was obtained.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent.

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.

Rheumatoid metatarsus. The original evolution of the first metatarsal.

Three hundred and eight unselected rheumatoid feet underwent a weight-bearing X-ray examination. If the malformations of the forefoot studied here present a statistical association, the primus metatarsus adductus is closely connected with tarsal arthritis and flattened foot but does not depend on the duration of the disease. The spread forefoot is indeed related to the duration of the disease and the presence of a metatarsal erosion at the foot level, but is not affected by the lesions of the midfoot. It appears then that an early orthopaedic treatment should be prescribed, once the first signs of involvement of the first ray or pronounced pronation of the hindfoot are noticed; it must affect the hindfoot, the midfoot and the first ray which progress together.

A graphical and statistical method for investigation of time series in chronobiology according to the cosinor procedure.

The mathematical and statistical analysis of biological time series is complex. In view of the necessity to deal with non equidistant data to analyse biological variables, preference is often given to the "cosinor procedure". We propose here a graphical and statistical assistance program for single or multiple cosinor procedure applicable to time series in chronobiology. This program investigates whether a cosine function or a mixture of cosine functions describe the experimental data adequately. The computer program is illustrated on data which have been published in a preceding paper.

[Drug prescription in the postinfarction period; results of the EPPI II (Study of Postinfarct Prescription). A French cooperative study]. / La prescription médicamenteuse dans le postinfarctus; résultats de l'EPPI II (étude de prescription postinfarctus).Etude coopérative française.

An enquiry into drug prescription of patients discharged from hospital after myocardial infarction was carried out in 27 French hospital departments and included 430 patients. Each patient was prescribed an average of 3.9 drugs. Aspirin was the most widely prescribed drug (79.3%); this was followed by the betablockers (67.4%), long acting nitrate derivatives (42.3%) and calcium antagonists (35.1%). These results, though an improvement compared with those of an enquiry carried out 3 years ago, suggest that much prescription in the post-infarction period is not consistent with our present knowledge.

[Drug prescription in myocardial postinfarction: results of the EPPI (étude de prescription postinfarctus). A French cooperative study]. / La prescription médicamenteuse dans le postinfarctus: résultats de l'EPPI (étude de prescription postinfarctus). Etude coopérative française.

An enquiry into the prescribing behaviour in patients discharged from hospital after myocardial infarction was performed in 36 hospital departments in France and included 528 patients. Each patient was prescribed an average of 3.6 drugs. The most commonly prescribed drug was Aspirin (63.3%) followed by the calcium antagonists (61.7%) long acting nitrate derivatives (49.5%) and betablockers (41.5%). These results suggest that many post-infarction prescriptions disregard recently acquired scientific knowledge.

[Idiopathic dilated cardiomyopathies in children. Development and prognostic factors]. / Les myocardiopathies dilatées idiopathiques de l'enfant. Evolution et facteurs pronostiques.

This review is a retrospective study of the cases of 103 patients under 20 years of age with idiopathic dilated cardiomyopathy and represents the whole experience of the Department of Paediatric Cardiology of the Hospital of Cardiovascular Disease, Lyon, between January 1970 and December 1988. The aetiological investigations were constantly negative: hypertrophic, restrictive and secondary cardiomyopathies were excluded. The clinical, radiological, electrocardiographic and echocardiographic data of each patient was noted at the time of admission and at the end of the clinical course. There were many more infants in this series. The onset of the disease was usually sudden. All patients were given medical treatment. The study period ranged over 19 years. Forty one patients (39.8%) died mainly of terminal cardiac failure. Sixty two patients are still alive, of whom 39 are completely cured, 2 have undergone cardiac transplantation, and 21 have a variable degree of chronic invalidity. The six months survival was 77.5%; the 1 year survival was 70% and the 5 year survival was 60%. Over one third of deaths (36.6%) occurred during the first month, 56% during the first 3 months and 70% during the first year. A statistical analysis comparing the initial criteria to death by the chi 2 test revealed the following prognostic factors: age at presentation (32.9% of deaths in patients under 2 years of age compared to 56.6% in the group over 2 years of age, p less than 0.025) and a family history of myocardial disease. The other clinical, radiological and echocardiographic parameters had no predictive value in this series and it was not possible to identify potential candidates for cardiac transplantation.

Education program for general practitioners on breast and cervical cancer screening: a randomized trial. PRE.SA.GF Collaborative Group.

This study was aimed at evaluating the effects of an education program for general practitioners on their prescribing behaviour for cervical and breast cancer screening tests, and assessing the feasibility of general practitioners participation in screening programs. All three cytology laboratories and 19 of the 20 radiologists in one administrative region ("Haute-Savoie") in France agreed to participate. The 278 general practices in this region were randomly assigned to either the intervention group (a one-day seminar on screening for breast cancer and cervical cancer) or the control group (n for both = 139). The prescriptions of tests for the following year were noted from the laboratories' and radiologists' records. No significant differences were observed between the intervention group and the control group for the number of mammographies prescribed with a mean of 19.3 and 15.2 per practice, respectively. However, significantly more mammographies were prescribed in women aged over 50 by the intervention group (p = 0.038). Inversely, fewer smear tests were prescribed in the intervention group (mean per practice: 40.5 and 46.1, respectively). A significantly higher number of practices in the intervention group did not prescribe any smear tests (p = 0.007). This study suggests that it is possible to influence general practitioners' participation in screening programs, but that the messages should be carefully presented, since negative effects are possible.

[The value of anesthesia consultation in relation to the single preanesthetic visit]. / Intérêt de la consultation d'anesthésie par rapport à la seule visite préanesthésique.

OBJECTIVE: In France, a preanaesthetic assessment (PAA) several days prior to hospital admission for a scheduled surgical or diagnostic procedure under anaesthesia, associated with a preanaesthetic visit (PAV) the day before, are compulsory. This study aimed at comparing the benefits of PAA with those of a PAV not preceded by a PAA. STUDY DESIGN: Prospective, controlled, randomized study. PATIENTS: The study included 296 patients undergoing either a urologic, or ophthalmologic, or ENT procedure, randomly allocated either to a PAA (followed by a PAV) group or a PAV (without previous PAA) group. METHODS: The main criterion of comparison was the duration of preanaesthetic hospital stay and the secondary criteria were the incidence of procedure postponements and patients' satisfaction respectively. RESULTS: In the PAA group, the preanaesthetic hospital stay was shorter by 0.4 days (P = 0.001). Out of the 19 postponed procedures (7%), the cause of postponement was a medical one in 15 patients: 13 in the PAV group and 2 in the PAA group respectively (P = 0.009). The PAA was not considered as a constraint by most patients. CONCLUSION: The PAA shortens the duration of preanaesthetic hospital stay and decreases the incidence of procedures postponed for a medical cause.

[Study by NMR of the modifications of brain lipid composition related to the tumor processes]. / Etude par RMN des modifications de la composition lipidique cérébrale liées aux processus tumoraux.

1H, 13C, 31P and 14N NMR spectroscopies were used to investigate the lipid composition of brain tumors (GL6 glioma) in rats, by comparison with controlateral hemispheres. Comparative indexes derived from NMR signal intensities were used to establish the statistical analysis. It was found that sterol metabolism and sphingolipid/glycerolipids ratio are significantly modified when a tumor is present.