Structural and functional characterization of an egg-laying hormone signaling system in a lophotrochozoan - The pacific oyster (Crassostrea gigas).

The egg-laying hormones (ELHs) of gastropod mollusks were characterized more than forty years ago. Yet, they have remained little explored in other mollusks. To gain insights into the functionality of the ELH signaling system in a bivalve mollusk - the oyster Crassostrea gigas, this study investigates the processing of its ELH precursor (Cragi-ELH) by mass spectrometry. Some of the ELH mature peptides identified in this study were subsequently investigated by nuclear magnetic resonance and shown to adopt an extended alpha-helix structure in a micellar medium mimicking the plasma membrane. To further characterize the ELH signaling system in C. gigas, a G protein-coupled receptor phylogenetically related to ecdysozoan diuretic hormone DH44 and corticotropin-releasing hormone (CRH) receptors named Cragi-ELHR was also characterized functionally and shown to be specifically activated by the two predicted mature ELH peptides and their N-terminal fragments. Both Cragi-ELH and Cragi-ELHR encoding genes were mostly expressed in the visceral ganglia (VG). Cragi-ELH expression was significantly increased in the VG of both fully mature male and female oysters at the spawning stage. When the oysters were submitted to a nutritional or hyposaline stress, no change in the expression of the ligand or receptor genes was recorded, except for Cragi-ELHR only during a mild acclimation episode to brackish water. These results suggest a role of Cragi-ELH signaling in the regulation of reproduction but not in mediating the stress response in our experimental conditions.

Gonadotropin-inhibitory hormone in teleosts: New insights from a basal representative, the eel.

Since its discovery in birds, gonadotropin-inhibitory hormone (GnIH) has triggered investigation in the other groups of vertebrates. In the present study, we have identified a single gnih gene in the European eel (Anguilla anguilla), a representative species of a basal group of teleosts (Elopomorphs). We have also retrieved a single gnih gene in Osteoglossomorphs, as well as in more recently emerged teleosts, Clupeocephala. Phylogeny and synteny analyses allowed us to infer that one of the two gnih paralogs emerged from the teleost-specific whole genome duplication (TWGD or 3R), would have been lost shortly after the 3R, before the emergence of the basal groups of teleosts. This led to the presence of a single gnih in extant teleosts as in other vertebrates. Two gnih paralogs were still found in some teleost species, such as in salmonids, but resulting from the additional whole genome duplication that specifically occurred in this lineage (4R). Eel gnih was mostly expressed in the diencephalon part of the brain, as analyzed by quantitative real-time PCR. Cloning of eel gnih cDNA confirmed that the sequence of the GnIH precursor encoded three putative mature GnIH peptides (aaGnIH-1, aaGnIH-2 and aaGnIH-3), which were synthesized and tested for their direct effects on eel pituitary cells in vitro. Eel GnIH peptides inhibited the expression of gonadotropin subunits (lhß, fshß, and common a-subunit) as well as of GnRH receptor (gnrh-r2), with no effect on tshß and gh expression. The inhibitory effect of GnIH peptides on gonadotropic function in a basal teleost is in agreement with an ancestral inhibitory role of GnIH in the neuroendocrine control of reproduction in vertebrates.

Ulnar neuropathy at the elbow: Reappraisal of the wrist-upper arm latency difference between ulnar and median nerves.

OBJECTIVES: To evaluate the sensitivity and specificity of the latency difference (DLat) between ulnar and median nerves of the arm after stimulation at the wrist; one of the easiest techniques proposed for recognizing ulnar neuropathy at the elbow (UNE). As latency difference is not a standardized technique, we set up a multicenter study to recruit large numbers of normal subjects and patients with UNE or generalized neuropathy. METHODS: Six centers participated in the study with data obtained from three groups of participants, controls (CTRLs), patients with UNE and patients with generalized neuropathy (GNP). We first verified the anatomical superposition of the ulnar and median nerves in cadaver examination. The optimal recording site for these two nerves was found to be 10 cm above the medial epicondyle. We then standardized the position of the arm with full extension of the elbow and stimulated first the median and then the ulnar nerves at the wrist. CTRLs were examined on both arms at two consecutive visits. RESULTS: We recorded 32 idiopathic UNE cases, 44 GNP patients and 62 controls. We demonstrated that a DLat cut-off value of 0.69 ms brings a sensitivity of 0.86 and specificity of 0.89 to discriminate CTRLs from UNE. We also validated that intra-examiner reproducibility was good. CONCLUSION: We report a lower normal value for DLat than reported in several non-standardized studies and CTRL and UNE groups have clearly separated DLat values. SIGNIFICANCE: Due to its high sensitivity, our standardized technique could be used as a first-line diagnostic tool when UNE is suspected.

A cluster-randomized trial to reduce major perinatal morbidity among women with one prior cesarean delivery in Québec (PRISMA trial): study protocol for a randomized controlled trial.

BACKGROUND: Rates of cesarean delivery are continuously increasing in industrialized countries, with repeated cesarean accounting for about a third of all cesareans. Women who have undergone a first cesarean are facing a difficult choice for their next pregnancy, i.e.: (1) to plan for a second cesarean delivery, associated with higher risk of maternal complications than vaginal delivery; or (b) to have a trial of labor (TOL) with the aim to achieve a vaginal birth after cesarean (VBAC) and to accept a significant, but rare, risk of uterine rupture and its related maternal and neonatal complications. The objective of this trial is to assess whether a multifaceted intervention would reduce the rate of major perinatal morbidity among women with one prior cesarean. METHODS/DESIGN: The study is a stratified, non-blinded, cluster-randomized, parallel-group trial of a multifaceted intervention. Hospitals in Quebec are the units of randomization and women are the units of analysis. As depicted in Figure 1, the study includes a 1-year pre-intervention period (baseline), a 5-month implementation period, and a 2-year intervention period. At the end of the baseline period, 20 hospitals will be allocated to the intervention group and 20 to the control group, using a randomization stratified by level of care. Medical records will be used to collect data before and during the intervention period. Primary outcome is the rate of a composite of major perinatal morbidities measured during the intervention period. Secondary outcomes include major and minor maternal morbidity; minor perinatal morbidity; and TOL and VBAC rate. The effect of the intervention will be assessed using the multivariable generalized-estimating-equations extension of logistic regression. The evaluation will include subgroup analyses for preterm and term birth, and a cost-effectiveness analysis. DISCUSSION: The intervention is designed to facilitate: (1) women's decision-making process, using a decision analysis tool (DAT), (2) an estimate of uterine rupture risk during TOL using ultrasound evaluation of low-uterine segment thickness, (3) an estimate of chance of TOL success, using a validated prediction tool, and (4) the implementation of best practices for intrapartum management. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN15346559 . Registered on 20 August 2015.

A Model for Transfer of P-Glycoproteins in MCF-7 Breast Cancer Cell Line with Multiple Transfer Rules.

In this paper, we consider a direct protein transfer process between cells in co-culture. Assuming that cells continually encounter each other, and from some hypotheses on cell-to-cell rules of transfer, we derive discrete and continuous Boltzmann-like integro-differential equations. The novelty of this model is to take into account multiple transfer rules. This new transfer model is used to fit the experimental data of cell-to-cell protein transfer in breast cancer.

The assessment and management of risks associated with exposures to short-range Auger- and beta-emitting radionuclides. State of the art and proposals for lines of research.

The assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk.Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly.The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides.

First evidence for a direct inhibitory effect of kisspeptins on LH expression in the eel, Anguilla anguilla.

The kisspeptin system has emerged as one of the main puberty gatekeepers among vertebrates. The European eel (Anguilla anguilla) is a remarkable model due to its phylogenetical position at the basis of teleosts, and its unique life cycle with a blockade of puberty before reproductive migration. We cloned the full-length coding sequence of a kisspeptin receptor (Kissr) in the eel. Comparison of Kissr sequences assigned the eel Kissr to a basal position in a clade including most of the known teleost Kissr, in agreement with the eel phylogenetical position. Eel Kissr tissue distribution was analyzed by quantitative real-time PCR. Eel Kissr was highly expressed in the brain, especially in the telencephalon and di-/mes-encephalon, while a very low or undetectable expression was observed in various peripheral organs. A high expression of Kissr was also found in the pituitary indicating a possible direct pituitary role of kisspeptin. Primary cultures of eel pituitary cells were performed to investigate the direct effects of kisspeptin on pituitary hormone expression. Human/lamprey kisspeptin exerted a time- and dose-dependent inhibitory effect on LHß expression. All other tested kisspeptins had a similar inhibitory effect on LHß expression. The inhibitory effect of kisspeptins was exerted specifically on LHß as no change was induced on the expression of other glycoprotein hormone subunits (GPα, FSHß and TSHß) nor of growth hormone. These data provide the first evidence for the existence, in the European eel, of a kisspeptin system, which may play a direct inhibitory role on pituitary LHß expression.

[Complications and monitoring of the latency period after a preterm premature rupture of the fetal membranes: literature review]. / Les complications et la surveillance pendant la période de latence après une rupture prématurée des membranes avant terme : mise au point.

Preterm premature rupture of the membranes (PPROM) begins a high-risk period for both mother and fetus. This literature review updates the knowledge on latency-period complications and proposed monitoring strategies. Four latency-period complications are described: spontaneous onset of labor, infection (chorioamnionitis), abruptio placentae, and fetal, distress which can be linked to umbilical cord prolapse. Admittedly, the infection/inflammation process plays a key role during the latency period. Conservative management of PPROM is recommended and is associated with significant pregnancy prolongation. This strategy allows a gain in fetal maturity, but increases the risk of complications. The prediction of infection seems to be essential; classical markers, such as blood count and reactive C protein are not very effective. New markers have been tested, with IL-6 appearing to be one of the best infection markers. Fetal pulmonary maturity can be evaluated with a rapid screening test and can yield arguments for the management strategy.

[Fetal membranes: embryological development, structure and the physiopathology of the preterm premature rupture of membranes]. / Les membranes foetales : développement embryologique, structure et physiopathologie de la rupture prématurée avant terme.

Fetal membranes development is a complex process. The amniotic and exo-celomic cavities are appearing first. The rapid growth of the amniotic cavity is leading to the disappearance of the exo-celomic cavity and the chorion is merging with the decidua. Fetal membranes consist of three layers: the amnion and the chorion, issued from fetal tissues and the decidua issued from maternal tissue. A balance between the synthesis and the degradation of membranes components is physiologic throughout the gestation. Two main mechanisms are involved in the degradation process: apoptosis in the cellular compartment and matrix metalloproteinase (MMP) in the extracellular matrix. Regulation of MMP is depending on factors increasing their expression (cytokines) and factors decreasing their activity tissue inhibitor of metalloproteinases (TIMPS). Particular conditions can induce an unbalance between synthesis and degradation leading to the weakening of the membranes. Different factors can be associated to induce this unbalance: infection, hormonal factors, default in membranes fusion, oxidative stress and mechanic factors. In fine, the spontaneous rupture of the membranes is always occurring in regard of the uterine cervix after a process started several weeks before.

Preliminary investigation into the use of Autonomous Fall Detectors.

A study was realized in France to meet the requirements of an autonomous fall sensor worn on the body. It consisted of a written questionnaire of which 149 were returned completed, which reveals that users are favorable to the use of a portable fall detector, worn like a watch, all through their daily activities, with a special wish for an audio feed back of the correct activity and, moreover, are ready to pay for the service on a monthly rate basis.

[Uterine electromyogram: principle and interest in the diagnosis of preterm labour]. / L'électromyogramme utérin: principes et intérêt pour le diagnostic de travail prématuré.

Preterm labour diagnosis rely on clinical arguments exhibiting low positive predictive values. Discrimination between uterine contractions leading to preterm delivery and physiologic uterine activity increase throughout pregnancy and remains difficult. Uterine electrical activity can be recorded non-invasively from the abdominal wall and could help in the diagnosis of preterm labour. Electrical signal characteristics are reflecting myometrial cells electrical properties which are varying throughout pregnancy and labour. During pregnancy, uterine electrical activity is very low. During term and preterm labour, uterine electrical activity increases as well as mechanical activity. Bursts become regular with high amplitude. Spectral analysis demonstrates an increase in the frequency content, as represented by the shift of the burst power density spectrum peak frequency from low to high frequencies. Consequently, the electromyogram signal reflects myometrial excitability and allows differentiating powerful uterine contractions leading to delivery from uterine physiologic activity. Moreover, electromyogram signal modifications occur before any increase in mechanical activity in the pregnant rats, allowing identification of preterm labour earlier than uterine mechanical activity measured by intrauterine pressure. Two studies performed in women present with preterm contractions are supporting the potential interest of the uterine electromyogram recording to help in the diagnosis of preterm labour; but further investigations are necessary.

Steady-state expression of self-regulated genes.

MOTIVATION: Regulatory gene networks contain generic modules such as feedback loops that are essential for the regulation of many biological functions. The study of the stochastic mechanisms of gene regulation is instrumental for the understanding of how cells maintain their expression at levels commensurate with their biological role, as well as to engineer gene expression switches of appropriate behavior. The lack of precise knowledge on the steady-state distribution of gene expression requires the use of Gillespie algorithms and Monte-Carlo approximations. METHODOLOGY: In this study, we provide new exact formulas and efficient numerical algorithms for computing/modeling the steady-state of a class of self-regulated genes, and we use it to model/compute the stochastic expression of a gene of interest in an engineered network introduced in mammalian cells. The behavior of the genetic network is then analyzed experimentally in living cells. RESULTS: Stochastic models often reveal counter-intuitive experimental behaviors, and we find that this genetic architecture displays a unimodal behavior in mammalian cells, which was unexpected given its known bimodal response in unicellular organisms. We provide a molecular rationale for this behavior, and we implement it in the mathematical picture to explain the experimental results obtained from this network.

Effects of residential distance to hospitals with neonatal surgery care on prenatal management and outcome of pregnancies with severe fetal malformations.

OBJECTIVES: To examine the effect of maternal origin and distance between maternal residence and the nearest maternity ward with a neonatal surgical center in the same hospital, on prenatal diagnosis, elective termination of pregnancy, delivery in an adequate place and neonatal mortality for pregnancies with severe malformations requiring neonatal surgery, and to examine the effect of the place of delivery on neonatal mortality. METHODS: This was a retrospective study, through the France Central-East malformation registry, of 706 fetuses with omphalocele (n = 123), gastroschisis (n = 99), diaphragmatic hernia (n = 222), or spina bifida (n = 262), but without chromosomal anomalies. Maternal origin was classified as Western European and non-Western European. Adequate place for delivery was defined as birth in a Level-III maternity ward with a neonatal surgical center in the same hospital. RESULTS: The prenatal diagnosis rate was 67.7% in 1990-1995 and 80.2% in 1996-2001 (odds ratio (OR), 2.07 (95% CI, 1.24-3.45)). On multivariate analysis, the rate was significantly lower for women living 11-50 km (adjusted OR, 0.49 (95% CI, 0.25-0.94)), or > 50 km (adjusted OR, 0.39 (0.20-0.74)) from the closest adequate place of delivery, compared with those living < 11 km from it, but there was no difference for maternal origin. Non-Western European women had fewer elective terminations of pregnancy (adjusted OR, 0.34 (95% CI, 0.14-0.81)) and fewer deliveries in an adequate place (adjusted OR, 0.40 (95% CI, 0.18-0.89)). Neonatal mortality was lower in the case of delivery in an adequate place (adjusted OR, 0.22 (95% CI, 0.07-0.72)) and was not associated with maternal origin and distance from nearest maternity ward with a neonatal surgical center. CONCLUSION: Rate of prenatal diagnosis decreases with increasing distance between parental residence and referral center. Non-Western European women are diagnosed prenatally as often as are Western Europeans, but terminate their pregnancy less often, perhaps for cultural reasons. Non-Western European women with malformed fetuses deliver in adequate centers less often, probably because of the way the perinatal care system is run.

Prenatal diagnosis of Aicardi-Goutières syndrome.

OBJECTIVES: Aicardi-Goutières syndrome is an autosomal recessive neurodegenerative disorder inducing cerebral atrophy, intracerebral calcification and developmental arrest. Diagnosis requires the presence of progressive encephalopathy with clinical onset shortly after birth, typical neuroimaging features associated with a raised blood and cerebrospinal fluid interferon-alpha level.A case of prenatal diagnosis of Aicardi-Goutières syndrome is reported. METHODS: An MRI performed at 26 gestational weeks showed bilateral calcifications and white matter abnormalities, cerebral anomalies typically described in this disease. The fetal blood analysis revealed an increase in interferon-alpha. RESULTS: Therefore, the prenatal diagnosis of Aicardi-Goutières syndrome in this fetus was based on the following facts: the familial background with the affected first child and consanguineous parents, a normal pregnancy and normal fetal growth, cerebral anomalies diagnosed on prenatal ultrasound and cerebral MRI, raised interferon-alpha in the fetal serum and no evidence of any infectious etiology. The autopsy performed postdelivery at 28 1/2 weeks' gestation confirmed the diagnosis of Aicardi-Goutières syndrome. CONCLUSION: To the best of our knowledge, this is the first prenatal diagnosis of this syndrome. Such a diagnosis may prove useful for families at risk as long as genetic screening is not available.

Suburethral tape via the obturator route: is the TOT a simplification of the TVT?

Suburethral meshes can be implanted via the classic retropubic route (TVT) or by a new insertion technique that passes the tape into the obturator foramen (TOT). In a retrospective study we compared one 18-month period of 94 TOT (tension-free obturator tape) and one 18-month period of 99 TVT (tension-free vaginal tape), which preceded the change in the approach route. All operations were performed by the same surgeon using the same Prolene mesh and with no other surgical procedure associated. These two series were similar in terms of patient age, previous surgical history, degree of incontinence and preoperative urethral closure pressure. The analysis shows more hemorrhagic complications in the TVT group (10%) than in the TOT group (2%), but the difference was not significant. Bladder injuries were more frequent in the TVT group (10%) than in the TOT group (0%), but there was one urethral injury in the TOT group. The mean follow-up was 29.5 months in the TVT group and 12.8 months in the TOT group. The urinary results were the same, with 90% and 95% cured, respectively. In conclusion, the obturator approach shows identical urinary results to the classic retropubic approach. Because of the nature of the procedure, major hemorrhage and bowel perforation are excluded in the TOT procedure. Thus simplicity, safety and continence result mean that the obturator approach represents the best method of suburethral tape insertion for the treatment of urinary stress incontinence.

[Value of single photon emission computed tomography in the characterization of fronto-temporal dementia subtypes]. / Intérêt de la tomographie d'emission monophotonique dans l'identification de sous-types de démences fronto-temporales.

DFT (fronto-temporal dementia) was diagnosed in 33 patients (17 males and 16 females), mean age 74.9 years, using the criteria from Neary et al. (1998). The severity of the disease was evaluated based on the presence or absence of 4 clinical groups of signs (behavioral, affective, neurological signs and language) allowing the calculation of a global clinical ratio on 20. A CT-scan and a Single Photon Emission Computed Tomography (SPECT) scan using Tc99m-ECD with quantification of brain perfusion were then performed. This study confirmed the classical clinical forms of DFT: a psycho-affective form (21%), where negative symptoms are predominant, and a behavioral disinhibited form (9%). Most of our cases (40%) corresponded to a global form. Finally we also identified a fourth clinical form: cognitive form because of predominance of language disturbances (30%). Concerning SPECT, we found 4 topographic forms: frontal global (46%), frontal superior (24%), frontal inferior (15%) and frontal unilateral (12%). In the frontal inferior form, behavioral disturbances were correlated to the intensity of frontal inferior hypoperfusion, corresponding to an orbito-frontal dysfunction. In the frontal superior form, psycho-affective disturbances (apathy) were correlated with frontal superior hypoperfusion (anterior cingulum and superior dorso-lateral cortex). Finally, in global and frontal inferior SPECT forms, language disturbances were correlated with a frontal inferior hypoperfusion (prefrontal and inferior left frontal cortex).

[Secondary recurrent hepatitis in ventricular arrhythmia]. / Hépatite récurrente secondaire à une arythmie ventriculaire.

INTRODUCTION: A major episode of hepatic cytolysis, rapidly regressive and occasionally recurrent, evokes a bilary or toxic pathology. We report an exceptional case in which several episodes of cytolysis were secondary to a paroxystic cardiac rhythm disorder. OBSERVATION: A 44 year-old woman was hospitalized 3 times during 4 months for episodes of asthenia and rapidly regressive cytolysis. Lithiasic, viral, metabolic, autoimmune and toxic causes were eliminated. A cardiac rhythm disorder was revealed during the last two episodes and diagnosis was made of intermittent and asymptomatic ventricular tachycardia, secondary to arryhthmogenic right ventricular dysplasia, and was confirmed on the electrocardiogram, cardiac scan and magnetic resonance imaging. Treatment of the cardiac rhythm led to the absence of further relapse. COMMENTS: In our patient, the clinical and chronological imputability appeared highly probable. The responsibility of perturbed cardiac rhythm in the genesis of an ischemic hepatopathy is classical, but little documented. Our observation confirms that severe unexplained cytolysis requires systematic search for a cardiac rhythm disorder, even in the absence of a known or symptomatic cardiopathy.

Hodgkin's disease: prognostic role of gallium scintigraphy after chemotherapy.

Evaluation of the response to therapy is important for optimal selection of treatment strategy in patients with Hodgkin's disease (HD). Refractory disease requires intensive high-dose chemotherapy, whereas unnecessary treatment should be avoided in patients in complete remission. The purpose of this study was to evaluate the contribution of gallium-67 scintigraphy in predicting the clinical outcome in patients with HD and mediastinal involvement on the basis of scan results at the end of chemotherapy. Seventy-four patients with HD and mediastinal involvement were retrospectively investigated with 67Ga scintigraphy 72 h after injection of 220 MBq 67Ga citrate (planar and single-photon emission tomographic studies) following the completion of chemotherapy. At the same time, they all underwent computed tomography (CT). Patients were followed up for an average of 63 months (range 28-124 months). The disease status was newly diagnosed disease in 64 of the patients and relapse in 10. Systemic symptoms were absent (A) in 34 cases and present (B) in 40 cases. Forty-one patients had stage I or II disease and 33 patients had stage III or IV disease. Twenty-two patients had bulky disease on initial diagnosis. At the end of chemotherapy, all 74 patients showed regression of the mass by more than 50% (50%-100%) on CT. Patients were divided into two groups according to the positivity or negativity of the gallium scan after chemotherapy: 61 patients had negative and 13 patients had positive gallium scans. In the gallium-negative group, 19.7% of the patients relapsed and 91.8% were alive at the end of the follow-up. Relapse occurred in 20% of the patients with residual mass and in 19.6% of the patients without residual mass. In the gallium-positive group, 84.6% of the patients had recurrent disease and 61.5% were alive after intensive chemotherapy. There was a statistically significant difference in overall survival between patients with positive and patients with negative gallium results (P=0.0034). Disease-free survival differed significantly between patients with positive and patients with negative gallium scans at the end of chemotherapy (P<0.0001). The relative risk of death was 5.2 and the relative risk of relapse was 11.3 for patients with positive gallium scans, in comparison to those with negative gallium scans. The positive and negative predictive values for predicting relapse were 85% and 87%, respectively. It is concluded that even if gallium scan is performed at the end of chemotherapy, it can predict outcome. Alternative therapy may be required on the basis of gallium scan results obtained after treatment.