Thermodynamic integration methods, infinite swapping, and the calculation of generalized averages.

In the present paper we examine the risk-sensitive and sampling issues associated with the problem of calculating generalized averages. By combining thermodynamic integration, stationary phase Monte Carlo, and infinite swapping techniques, we develop an approach for such problems and explore its utility for a prototypical class of applications.

Reirradiation: A complex situation.

Reirradiation of a tumor recurrence or second cancer in a previously irradiated area is challenging due to lack of high-quality physical, radiobiological, clinical data and inherent substantial risks of toxicity with cumulative dose and uncertain tissue recovery. Yet, major advances have been made in radiotherapy techniques, that have the potential to achieve cure while limiting severe toxicity rates, but still much research is necessary to better appraise the therapeutic index in such a complex situation.

Mid-position treatment strategy for locally advanced lung cancer: a dosimetric study.

OBJECTIVE: The internal target volume (ITV) strategy generates larger planning target volumes (PTVs) in locally advanced non-small cell lung cancer (LA-NSCLC) than the Mid-position (Mid-p) strategy. We investigated the benefit of the Mid-p strategy regarding PTV reduction and dose to the organs at risk (OARs). METHODS: 44 patients with LA-NSCLC were included in a randomized clinical study to compare ITV and Mid-p strategies. GTV were delineated by a physician on maximum intensity projection images and on Mid-p images from four-dimensional CTs. CTVs were obtained by adding 6 mm uniform margin for microscopic extension. CTV to PTV margins were calculated using the van Herk's recipe for setup and delineation errors. For the Mid-p strategy, the mean target motion amplitude was added as a random error. For both strategies, three-dimensional conformal plans delivering 60-66 Gy to PTV were performed. PTVs, dose-volume parameters for OARs (lung, esophagus, heart, spinal cord) were reported and compared. RESULTS: With the Mid-p strategy, the median of volume reduction was 23.5 cm3 (p = 0.012) and 8.8 cm3 (p = 0.0083) for PTVT and PTVN respectively; the median mean lung dose reduction was 0.51 Gy (p = 0.0057). For 37.1% of the patients, delineation errors led to smaller PTV with the ITV strategy than with the Mid-p strategy. CONCLUSION: PTV and mean lung dose were significantly reduced using the Mid-p strategy. Delineation uncertainty can unfavorably impact the advantage. ADVANCES IN KNOWLEDGE: To the best of our knowledge, this is the first dosimetric comparison study between ITV and Mid-p strategies for LA-NSCLC.

[Gadolinium-enhanced thoracic CTA: retrospective analysis of image quality and tolerability in 45 patients evaluated prior to the description of nephrogenic systemic fibrosis]. / Angioscanographie thoracique au gadolinium en TDM multicoupe du thorax: analyse rétrospective de la qualité image et de la tolérance chez 45 patients évalués antérieurement à la description de la fibrose systémique néphrogénique.

PURPOSE: To assess the accuracy and torerability of gadolinium-enhanced thoracic CTA using a 64 MDCT compared to a 16 MDCT. Because this study was started prior to the description of NSF, particular attention was paid to long-term follow-up of the patient population. MATERIALS AND METHODS: The study protocol was approved by the ethics committee of our institution and informed consent was obtained from all patients. Fourteen patients (Group 1) (9 males and 5 females; mean age: 64.3 years) with contraindication to the administration of iodinated contrast material underwent thoracic CTA (collimation: 32 x 2 x 0.6 mm; pitch: 1.2) with gadolinium administration (0.5 mml/ml) at 0.4 mmol/kg injected at 6 ml/sec with evaluation of clinical and biological tolerability of the gadolinium based contrast agent. Results from this patient population were compared to results from a population of 31 patients (21 males; 10 females; mean age: 63.2 years) (Group 2) imaged on a 16 MDCT. All patients were folloowed-up for a mean time of 22.6 months. RESULTS: Using a mean contrast volume (standard deviation) that was not significantly different (Group 1: 54.8+/-11 ml; Group 2: 53.4+/-6.9 ml) (p=0.94), patients in Group 1 underwent complete thoracic CTA whereas patients in Group 2 underwent CTA of only the middle third of the thoracic region. All CTA examinations were diagnostic for Group 1 and Group 2 patients; however, evaluation of subsegmental vessels was possible in a significantly larger proportion of patients in Group 1 (10/14; 72%) compared to Group 2 (6/31; 19%) (p=0.003). Mean attenuation values within pulmonary arterial branches were similar for Groups 1 and 2 (central arteries: 194.5+/-51.3 HU vs 180.6+/-53.8 HU; p=0.38) (lobar arteries: 208.5+/-52.5 HU vs 189.9+/-60.1 HU; p=0.33) (segmental arteries: 220.4+/-50.4 HU vs 201.5+/-54.7 HU; p=0.42). Transient alteration of renal function was recorded in one patient from Group 1 with severe pre-existing chronic renal failure. No change in renal function was observed for Group 2 patients. No case of NSF was reported in patients with pre-existing renal failure at the time of enrollment. CONCLUSION: The use of gadolinium-based contrast agent for thoracic CTA using a 64 MDCT provides diagnostic quality examinations in all patients with improved image quality compared to a 16 MDCT. No complication other than transient alteration of renal function was observed. Because the likelihood of developing NSF may vary with the type of gadolinium-based contrast agent used, the least toxic agent should be used.

Do all the linear accelerators comply with the ICRU 91's constraints for stereotactic body radiation therapy treatments?

Recent technological developments in linear accelerators (linacs) and their imaging systems have made it possible to routinely perform stereotactic radiotherapy (SRT) treatments. To ensure the security and quality of the treatments, national and international recommendations have been written. This review focuses on the recommendations of the report 91 of the International Commission on Radiation Units (ICRU) on stereotactic treatments with small photon beams and proposes to answer the question of the eligibility of the commercially available accelerators for the treatment of extra-cranial SRT (SBRT). The ICRU 91 report outlines important features needed to respect the constraints, which are high intensity photon beam, integrated image-guidance, high mechanical accuracy of the linac, multileaf collimator with reduced leaf width, bundled motion management and bundled 6 Dimensional "robotic" couch tabletop. Most of the contemporary linacs meet these recommendations, in particular, stereotactic dedicated linacs, or modern gantry-based linacs equipped with 3 dimensional cone-beam CT imaging and 2D-stereoscopic planar imaging. Commercially available ring-based linacs have some limitations: they offer only coplanar treatments, and couch movements are limited to translations and, some have limited imaging equipment and no ability to manage intrafraction motion. However, for performing SBRT, non-coplanar irradiations are not mandatory, contrarily to intracranial stereotactic irradiations. Furthermore, patients' rotations can be corrected, thanks to real-time adaptive radiotherapy available on MRI-linacs. Finally, significant improvements are expected in the short term to compensate the weaknesses of the current devices.

Volumetric and dosimetric comparison of two delineation guidelines for the radiation treatment of laryngeal squamous cell carcinoma.

PURPOSE: Three methods have been recently proposed for the delineation of the primary tumor clinical target volume (CTV-P) in Head and Neck Cancers: the anatomic method popularized in the French literature by Lapeyre et al. the geometric methods proposed by the DAHANCA group, and more recently the international guidelines promoted by Grégoire et al. integrating the latter two. The aim of this study was to perform a volumetric and dosimetric comparison of the French and the International consensus methods in laryngeal SCC. PATIENTS AND METHODS: Two radiation oncologists independently delineated the high dose and low dose primary tumor CTV in four patients with T2 or T3 N0-M0 laryngeal SCC following either the so-called French guidelines or the International guidelines. For the 4 cases, the GTV was delineated by a single radiation oncologist. Nodal CTVs were delineated by one radiation oncologist for the 4 cases using International guidelines. Dose optimization was then performed with VMAT (MONACO version 5.11) using 6 MeV photons. Differences in target volumes and dose distributions in OARs and PTVs were then evaluated with various metrics such as the DICE Similarity Coefficient and the homogeneity index. RESULTS: Major differences were observed in the CTV delineation between the 2 delineation methods for the low dose volumes and to a lower extend for the high dose volumes. These differences translated into variations in dose distribution favoring the International guidelines for decreasing dose to various OARs. Such differences toned down when dose distribution on the primary tumors PTVs and nodal PTVs were combined. CONCLUSION: This study demonstrated large differences in CTV delineation between the 2 delineation guidelines. Such differences translated into differences in dose distribution.

Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils.

Leukotriene A4 hydrolase was rapidly and extensively purified from rat neutrophils using anion exchange and gel filtration high-pressure liquid chromatography. The enzyme which converts the allylic epoxide leukotriene A4 to the 5,12-dihydroxyeicosatetraenoic acid leukotriene B4 was localized in the cytosolic fraction and exhibited an optimum activity at pH 7.8 and an apparent Km for leukotriene A4 between 2 X 10(-5) and 3 X 10(-5) M. The purified leukotriene A4 hydrolase was shown to have a molecular weight of 68 000 on sodium dodecylsulfate polyacrylamide gel electrophoresis and of 50 000 by gel filtration. The molecular weight and monomeric native form of this enzyme are unique characteristics which distinguish leukotriene A4 hydrolase from previously purified epoxide hydrolases.

Expression of a ciliate gene in Escherichia coli using a suppressor tRNA to read the UAA and UAG glutamine codons.

Most ciliates use a particular genetic code where the standard stop codons UAA and UAG encode glutamine. Ciliate genes cannot therefore be expressed in heterologous systems such as Escherichia coli. To overcome this problem, we worked out a system of inducible suppression to permit efficient readthrough of UAAs and UAGs: a strong UAA tRNA suppressor that inserts glutamic acid was cloned downstream from a tac promoter whose efficiency was reduced by a transcription terminator. This system proved to be operational (1) to suppress UAG mutations by wobble pairing in an E. coli lacI-lacZ gene fusion and (2) to read through at least eight UAA glutamine codons in a Paramecium alpha-tubulin gene, as detected by Western blotting and colony hybridization. This work opens the way for cloning Ciliate genes from expression libraries and for expressing particular sequences without extended in vitro mutagenesis. A similar approach can be envisaged for expression of genes from Mycoplasma, mitochondria or other genomes that use non-standard genetic codes.

Selective induction of peripheral and mucosal endothelial cell addressins with peripheral lymph nodes and Peyer's patch cell-conditioned media.

Vascular endothelial cell addressins play an important role in lymphocyte homing in secondary lymphoid organs and in chronic inflammatory areas. A SV40 large T antigen-immortalized cell line from peripheral lymph nodes, HECa1O [Bizouarne et al., 1993a], was used to characterize the location of addressins with regard to environmental factors and cytokines. For this purpose, two monoclonal antibodies, MECA 79 and MECA 367, specific for peripheral lymph node vascular addressin and for mucosal addressin (Peyer's patches), respectively, were bound to unstimulated HECa1O cells. Both mucosal and peripheral addressins were detected inside the cells and in cellular extracts of the resting cells. On the cell surface, both addressins could be evidenced on the same cells at a moderate level of expression. They partly mediate the EL4/EL4IL2 lymphoma cells' adhesion to HECa1O cells. Supernatants of cultured peripheral lymph node or Peyers' patch cells induced expression of MECA 79 or MECA 367 antigens, respectively, on the surface of HECa1O cells. Interleukins, IL-7, IL-3, and IL-8, induced the cell-surface appearance of MECA 79 but not of MECA 367 antigen. Therefore, the same cell type synthesizes both antigens, but the expression of these antigens on the cell surface is independently regulated, thus uncovering a characteristic tissue type-specific as well as environment-sensitive properties of microvascular endothelial cells.

New human microvascular endothelial cell lines with specific adhesion molecules phenotypes.

Vascular endothelial cells recognize blood-borne circulating cells and allow them to extravasate in a tissue-specific manner. Because this property determines the selectivity of lymphocyte homing, it is fundamental in physiological as well as pathological processes (inflammation, autoimmune diseases, metastasis). As a tool to assess the molecular basis of endothelium selectivity, microvascular endothelial cell lines of distinct tissue origin were established. Endothelial cells, isolated from lymphoid tissues (lymph nodes and appendix) and from nonlymphoid immune sites--intestine, lung, and skin--were immortalized in vitro. Their general endothelial characteristics, such as the presence of von Willebrand factor (wWf), angiotensin-converting enzyme (ACE), VE-cadherin, and the intracellular E-selectin, were preserved. This article shows that these cell lines display phenotypic characteristics related to their tissue origin. Hence, endothelial cells from lymph nodes expressed peripheral lymph node addressins (PNAds). Endothelial cells from nonlymphoid tissues were ICAM-1 (intercellular adhesion molecule-1) and CD49e positive, whereas P-selectin was not equally distributed among the cell lines. Endothelial cells from mucosal sites reacted with antibody against human MAdCAM-1 (mucosal addressin cell adhesion molecule). In the adhesion test, lymphoid and myeloid cells adhere to endothelial cell lines in a distinct manner. These lines could be useful to study molecular mechanisms involved in tissue-specific cell-cell interaction.

Hormonal regulation of glucose transport in contracting skeletal muscle from normal and diabetic rats.

Using the hindlimb perfusion system, we have studied glycogenolysis and glucose transport in resting and contracting skeletal muscle from normal and diabetic rats. Glucose transport was measured using the glucose analogue 2-deoxyglucose. The muscles were treated for 15 minutes with either saline solution, insulin (1 mU/mL) or epinephrine (10(-7) mol/L) at rest and during electrical stimulation. In the resting muscle, basal glycogen was lower in diabetic rats (25 v 40 mumol/g), was not affected by insulin in either group, and was decreased by epinephrine in normal rats (to 26 mumol/g) but not in diabetic rats. Basal glucose transport was identical in the two groups (7.5 mumol/100 g/minute), was stimulated by insulin to a greater extent in diabetics (fivefold) than in normal rats (threefold), but was unaffected by epinephrine in either group. In contracting muscle, glycogen was decreased by 10 mumol/g in normal and diabetic rats independently of hormonal treatment. Basal glucose transport was not affected by muscle contraction with or without epinephrine, whereas the stimulatory effect of insulin on this process was blunted by such contraction (result, 10 mumoles/100 g/minute). We conclude that in normal and diabetic rats, muscle contraction stimulates glycogen breakdown independently of hormonal treatment; muscle contraction per se does not increase glucose transport; and finally, contracting muscle uses glycogen rather than circulating glucose as energy substrate.

Radiologic diagnosis of degenerative lumbar spinal instability.

A lumbar motion segment is considered to be unstable when it exhibits abnormal movement. This movement can be abnormal in quality (abnormal coupling patterns) or in quantity (abnormal increased motion). This instability can be symptomatic or asymptomatic, depending on the demands made on the motion segment. Pain is a signal of impending or actual tissue damage, and when present it indicates that a certain mechanical threshold has been reached or transgressed. Repeated transgressions will damage the stabilizing structures beyond physiologic repair, thus putting abnormal demands on secondary restraints. Radiographic study with dynamic views obtained in the frontal and lateral planes identify unstable states in the clinical environment.

Secondary expansion of a totally replanted scalp for aesthetic adjustment.

Total scalp avulsion is an uncommon and dramatic accident. Replantation is the only way for acceptable aesthetic final results. However, partial loss of tissue can result, and secondary procedures can be required. A total avulsion of a scalp involving the upper part of the right ear and both eyebrows was replanted after a long delay in our department. As a result, loss of a third of the hair-bearing area occurred. Secondary expansion of the replanted scalp achieved complete reconstruction.

Mug shot exposure prior to lineup identification: interference, transference, and commitment effects.

The effects of viewing mug shots on subsequent identification performance are as yet unclear. Two experiments used a live staged-crime paradigm to determine if interpolated eyewitness exposure to mug shots caused interference, unconscious transference, or commitment effects influencing subsequent lineup accuracy. Experiment 1 (N = 104) tested interference effects. Similar correct decision rates were obtained for the mug shot and no mug shot groups from both perpetrator-present and absent lineups. Experiment 2 (N = 132) tested for commitment and transference effects. Results showed that the commitment group made significantly more incorrect identifications than either the control or the transference group, which had similar false-identification rates. Commitment effects present a serious threat to identification accuracy from lineups following mug shot searches.

[A simplified terminology for abnormalities of the lumbar disks]. / Une terminologie simplifiée des anomalies des disques lombaires.

The terminology for abnormalities of the lumbar disk has always been a source of confusion. Recent advances in pathological studies have inspired the authors to propose a simple classification of common disk anomalies suitable not only for diagnostic radiologists but also for referring clinicians. Although the diagnosis of a few pathological entities will only be possible with specific imaging techniques, the proposed classification is appropriate for reporting observations from plain films, conventional tomograms, myelograms, discograms, computed tomography scans and magnetic resonance images. All lumbar disks can thus be classified into one or more of the following categories: normal, aging, scarred, ruptured and herniated. A disk herniation is defined as a localized exit of disk material beyond the limits of the original intervertebral space.

[The changes in acid base balance of the fetus at term in the second stage of labour typed according to the CTG patterns (author's transl)]. / Modification de l'équilibre acido-basique du foetus à terme en phase expulsive en fonction du type CTG d'expulsion.

This work studies the changes in the acid base balance from the beginning to the end of expulsive stage of 73 labours (52 primiparas and 21 multiparas). These are typed according to the CTG patterns proposed by Melchior. All the pregnancies were normal and at or near term. The variation in pH measured is not the same in the primiparas as in the multiparas. For the multiparas the short stage of expulsion results in little change in the acid base balance, and with little correlation to the CTG type. Conversely for the primiparas the lowering of the pH measured corresponds well to the CTG type. For the type 0 it is 0.04 units of pH for the entire expulsive stage. This corresponds to a fall of -0.004 units of pH for each contraction. For the type 2 the fall is -0.12 units of pH or -0.02 per contraction. For the type 1 (the most frequent pattern seen, 71%) the fall is 0.1 units of pH, or -0.01 per contraction. For this last type of CTG pattern characterized by decelerations synchronous with the contractions, and considered for a long time as innocuous, these figures should alert the obstetrician to not permit the expulsive stage of labour to become unduly long. Finally the use of epidural anesthesia did not modify the fall of pH in this last group.

[Epidemic of viral gastroenteritis in an elderly community]. / Epidémie de gastro-entérite virale dans une collectivité de sujets âgés.

Rotaviruses and adenoviruses are the main aetiologic pathogens of gastroenteritis in infants. Adults may also be concerned with usually mild clinical symptoms. An epidemic of viral gastroenteritis occurred in a long-term hospitalization ward from July 25 to August 21, 1991: 101 patients. This study involved 26 females and 6 males with a mean age of 86 years (range 70-101 years), presenting clinical symptoms of gastroenteritis. The clinical attack rate was 27.7%. Outcome was favourable for the majority of patients who recovered in 4-5 days. The main clinical signs were diarrhoea (90.6%), hyperthermia (18.8%) and vomiting (18.8%). Virology investigations gave the diagnosis of 8 rotavirus infections, 6 adenovirus infections and 2 rotavirus and adenovirus mixed infections. Among staff members, 3 rotavirus and one adenovirus infections were diagnosed. The precise origin of the epidemic could not be determined from rotavirus electropherotypes obtained from stools of elderly and paediatric patients hospitalized during the same period. This outbreak recalls the viral involvement in diarrhoeal episodes of elderly people. These episodes of viral gastroenteritis are responsible for high morbidity in the elderly and may upset a precarious physiological state.