Multi-frequency detection of a dielectric object using flexible contactless RF sensors for tissue diagnosis.

The aim of this paper is to experimentally assess the capacity of radio-frequency flexible sensors to localize a dielectric object inside a fluid, which could be used as a non contact sensor detected to the detection or the monitoring a local modification of a tissue, such as a tumor or a lesion. The used sensor is an MRI-like antenna, which consists in a flat, flexible and low cost multi-turn split resonator (MTLR), which features a geometrically pre-determined resonance frequency. The MTLR is used here as a transmit and receive sensor monitored by a distant loop coil. The complex impedance changes observed at the ends of the monitoring coil is known to be linked to the dielectric properties of the resonator environment. If a dielectric object is placed close to the resonator, the complex impedance is altered. In this work, an experimental set up is used to assess the relevance of such a measurement scheme to detect the presence of a dielectric inclusion embedded in another dielectric medium. The setup includes a spherical object of 1.5 cm diameter filled with various NaCl solutions moved vertically inside a tank filled with deionized water by means of a three axis robotic arm, to create an electrical conductivity contrast between the inclusion and the media, and three 2 cm diameter MTLR sensors featuring 30, 47 and 70 MHz resonance frequencies, respectively. The sensors are operated through the use of monitoring coils connected to a network analyzer, and measurements are carried out at each position of the spherical object. The resulting sensor responses are plotted and used for the assessment of sensor performances. In addition, a method to combine the multi-frequency data provided by the three different sensors is proposed. Two different metrics regarding the spatial resolution (SR) and the peak signal to noise ratio (PSNR) are computed to characterize the single sensor performances, as well as the enhancement provided by the proposed multi-frequency approach.

Imaging of a dielectric inclusion using a contactless radio-frequency inductive probe for tissue diagnosis.

In this paper, a contactless radio-frequency (RF) inductive probe is used to spatially localize and characterize a complex dielectric organic inclusion in a fluid. The effect of dielectric properties (DP) of this organic material is investigated experimentally and by numerical computations.The used RF probe is a 135 MHz 3 cm diameter and 10 cm long, cylindrical bracelet resonator, placed close to a water tank filled with deionized water which includes a 1.5 cm diameter inclusion filled of air or NaCl solutions and placed in arbitrary positions. The water tank and the inclusion are used to model an organic material including a tumor. The RF probe is used as a transmit and receive sensor. It induces a magnetic field inside the water tank, which, by reciprocity, conveys information about the DP of the investigated material. The impedance changes at the end of the RF probe are directly related to the modifications of the magnetic field, and are measured by means of a network analyzer. A complex fit of the impedance frequency response around the resonance frequency gives access to two quantities proportional to the electrical conductivity and dielectric constant of the inclusion. The inclusion is moved into the water tank along the three axes by means of a robotic arm, so that two three dimensional maps of the equivalent dielectric quantities in function of the inclusion position are sensed by the probe. Then, the inclusion is filled with different conductive NaCl solutions from 0.1 to 1.1 S/m in order to test the ability of the probe to sense the modifications of the dielectric properties of the inclusion. Experimental as well as computation results obtained using the Distributed Point Source Method (DPSM) validate the ability of the proposed probe to localize the inclusion as deep as 1 cm into the water, and the ability of the probe to sense the dielectric property changes of the inclusion.

[Affectivity and alexithymia: two dimensions explicative of the relationship between anxiety and depressive symptoms]. / Affectivité et alexithymie : deux dimensions explicatives des relations entre symptômes dépressifs et anxieux.

OBJECTIVES: The main objective of this study was to support the existence of emotional dimensions common to anxiety and depressive symptomatology, and confirm the common elements of emotional vulnerability, characterized by negative affectivity and alexithymia. The second objective of this study was the identification of characteristics specific to each disorder. We made three assumptions: there is a significant relationship between anxiety and depressive symptoms, exists on community processes between these two entities, objectified by the sub dimensions of negative affectivity and the difficulty in identifying emotions certain dimensions are specific to each disorder. METHOD: The study participants were students from 1st to 4th year of the University of Provence. The sample consisted of 317 subjects (77% female and 23% male; mean age=20, 61 ± 1.55 years), who gave written informed consent and completed questionnaires collectively. We administered a protocol to the subjects consisting of three self-assessment scales to assess emotional dimensions and anxiety and depressive symptomatology. The dimensions of affectivity were assessed by the EPN-31. It consists of 31 items grouped into three factors: positive emotions, negative emotions and feelings of surprise. The emotional functioning was assessed by the scale of the Twenty-item Toronto Alexithymia Scale (TAS-20). It allows an overall assessment of the level of alexithymia, as well as three dimensions as represented by specific sub scales: difficulty identifying emotions (DIE), difficulty differentiating emotions (DDE), and externally oriented thinking (EOT). This scale is most used in the assessment of alexithymia. The anxiety and depressive symptoms were assessed by the subscale of anxiety and depression of the SCL90-R. This scale is widely used in screening for psychiatric symptoms, and has been validated internationally. STATISTICAL ANALYSIS: we performed descriptive analysis, correlational analysis (Bravais-Pearson's correlation) and hierarchical multiple regression using SPSS 15 software. RESULTS: The results validate our assumptions, showing that women are more anxious (M=6.68 ± 6.20 ; P=0.02) and more depressed (M=10.61 ± 8.73 ; P=0.01) than men (mean-anxiety=4.77 ± 4.97 ; mean-depression-6=7.75 ; 53). They also have more "difficulty" identifying feelings (M=17.92 ± 5.95, P=0.01) than men (m=15.65 ± 6.00). The analysis of relationships between the different variables shows the existence of several significant connections. Among them we find a strong positive correlation (r>.50 ; P=0.01) between anxiety and depression. Moreover, these two symptoms maintain strong relationships (r>.50; P=0.01) with negative affectivity, moderate and negative with positive affectivity (r>.30; P=0.01), and moderate and low with emotional activation (r>.10; P=0.01). There are also significant relationships between affective symptoms and emotional dimensions of alexithymia: difficulty identifying feelings (r>.40; P=0.01) and difficulty describing emotions (r>.20; P=0.01). Finally, the regression analysis shows, for the anxiety factor, which only contribute significantly following dimensions: gender, negative affectivity, emotional activation and the two sub dimensions of alexithymia "difficulty identifying feelings" and "externally oriented thoughts", which explain 43% of the variance in scores (R(2)=.43, P=0.0001). Depression shares with the following dimensions: gender, negative affectivity, difficulty in identifying emotions, and includes a specific dimension, positive affectivity. This model explains 51% of the variance (R(2)=. 51, P=0.0001). However, the lack of contribution of emotional activation and "externally oriented thoughts" must be emphasized. DISCUSSION: Our study reveals the existence of a "common nucleus of vulnerability" characterized by negative affectivity associated with difficulty identifying emotions. Specific dimensions nevertheless appear to exist, and depression is strongly explained by low positive affect (anhedonia dimension); anxiety associated specifically to emotional activation and finally thought outward, marking the size limitation. The imaginary life in alexithymia, appears to operate in depression, perhaps as a mechanism of emotional repression. The involvement of alexithymia in the functioning of the affective disorder is confirmed, this helps to clarify the modalities of therapeutic care that we offer.

[Comparative study of the subjective emotional experience among adolescents showing depressive symptoms associated or not with risk-taking behavior]. / Étude comparative de l'expérience émotionnelle subjective chez des adolescents présentant une symptomatologie dépressive associée ou non à des conduites à risques.

INTRODUCTION: Relationships between risk-taking behavior and depressive disorders in young people are considered as a complex psychopathological problem. Previous findings showed strong correlations between substance abuse, risk-taking behavior and depressive symptoms. Nevertheless, questions remain concerning potential common factors of depression and risk-taking behavior. Besides research focusing on personality dimensions, some others highlight the role played by emotions and their pathological aspects. In these studies, pathological emotional processing such as alexithymia or specific deficit in emotional intensity was linked to both risk-taking behavior and depressive disorders. The aim of this study was to investigate potential specific emotional profiles of adolescents engaged in pathological risk-taking or depressive symptomatology, versus adolescents presenting an association of both. METHOD: Four hundred and eigty-eight adolescents (m(age)=14,93, SD=1,44), with 257 boys (m(age)=15, SD=1,51) and 231 girls (m(age)=14,52, SD=1,23), were spread into four groups: adolescents engaged in high level risk-taking, adolescents showing both high risk-taking and high depressive symptoms, depressed adolescents, and a control group without any pathological aspects. The four groups completed a set of three assessments: Youth Risk Behavior Surveillance Scale (YRBSS), Level of Emotional Awareness Scale (LEAS) and Differential Emotional Scale (DES). RESULTS: Adolescents engaged in risk-taking have the lowest level of emotional awareness and subjective emotional intensity, while adolescents of the second group (depression with risk-taking behavior) have a higher level on both measures. Depressed adolescents present the highest score of emotional awareness within the pathological groups, lower than controls. Paradoxically, their ability to represent themselves others' emotions were higher than the control group, just as the intensity of their subjective emotional experience in case of negative emotions. DISCUSSION: The results may be explained by a specific developmental hypothesis, in which emotional awareness growth from the early period of life to late childhood, allowing children to gradually experiment more and more complex subjective emotional experiences. However, early exposure to traumatic experiences or inadequate environment may lead to developmental arrests, in which emotional awareness is weak. In this case, a lack of emotional information caused by low emotional awareness may have pathological issues, in terms of depression and risk-taking behavior. Clinical implications of this interpretation are discussed.

[Exploratory study of relations between emotional awareness, social sharing of emotions, anxious and depression states]. / Etude exploratoire des relations entre conscience émotionnelle, partage social des émotions, états anxieux et états dépressifs.

BACKGROUND: The anxious and depressive states are increasingly common. Their respective current prevalence is estimated of around 12%. AIM OF THE STUDY: This research aims to study how the emotional specific individuals may submit each type of condition (anxiety and/or depression). Our objective is to analyse the relationships that might exist between these states, the level of emotional awareness (capacity for the identification and differentiation of one's own emotions and those of others) and the social sharing of emotions process (mechanism interpersonal emotional regulation). DESIGN: The sample is composed of 107 volunteers from general medical practice on the one hand and population-run second. The average age of all subjects is of 43.21 years (+/-12.76) with a ratio of 13 men for 94 women. Two groups of subjects were formed on the basis of their levels of anxiety and depression assessed by the Hospital Anxiety and Depression Scale (HAD); [Acta Psychiatr Scand 67 (1983) 361-70]. The "AD" group consisted of anxious and anxiety-depression subjects (N=60). The "NAD" group consisted of subjects not anxious and not depressive (N=47). Scales of self-evaluation made up our protocol: the assessment of levels of emotional awareness (LEAS); [Am J Psych 144 (1990) 133-43] and the assessment of social sharing emotions (Rimé, 1989) used on the basis of the recall of a significant negative event. RESULTS: Correlation analysis showed the presence of a negative relationship between the level of emotional awareness and dimension of anxiety (r=-0.26, p=0.04), but positive between the level of awareness and depression (r=0.37; p=0.003). In addition, anxious individuals demonstrated a trend of social inhibition in sharing emotions (r=-0.26; p=0.05), in order not to reactivate the negative emotional experience, whereas in the case of depression, it was the inhibition of certain aspects of emotional experiences (r=0.33; p=0.01) that the individual does not wish to submit to the view of others. CONCLUSION: The results show interesting data in a "sub-clinical" population (anxiety-depressive subjects cared for in general medicine). Their scope is limited by the size of the sample, which could be expanded to continue our investigations. This study helps to deepen knowledge on the capabilities of identification and regulation of emotions of people showing symptoms of anxiety and/or depression.

Aldosterone and anti-aldosterone effects in cardiovascular diseases and diabetic nephropathy.

Cells in the cortical collecting duct of distal nephron have been considered for a long time as the unique cellular targets of aldosterone. However, it is now clear that other cell types in non-epithelial tissues are also potential targets for aldosterone. The functions that this hormone controls in non-epithelial tissues are still a matter of debate. Clinical and experimental studies have established that aldosterone plays a major role in the pathophysiology of cardiovascular and renal diseases. The aldosterone receptor antagonists spironolactone and eplerenone have demonstrated specific effects not related to their hypotensive properties in hypertension or cardiac diseases. It appears that a key action of these molecules is related to prevention or treatment of end-organ damage. The latter fact, and the recognition of aldosterone escape on long-term treatment of heart failure, diabetic nephropathy and some forms of hypertension with ACE inhibitors, justify the clinical use of aldosterone receptor antagonists provided that kaliemia is controlled. Experimental studies have allowed to draw a still incomplete but comprehensive scheme of aldosterone cardiovascular actions in pathological conditions. When elevated, aldosterone has deleterious effects in blood vessels, in the heart and in kidney, which are secondary to the induction of inflammatory and oxidative processes and necrosis, that induce the increased synthesis of extracellular matrix proteins.

[Study and evaluation of patients with obliterating arteriopathy of the lower limbs: use of isokinetics to analyze muscular strength and fatigue]. / Evaluation par isocinétisme de la force et de la fatigabilité musculaire chez les patients porteurs d'artériopathie oblitérante des membres inférieurs.

OBJECTIVES: The aim of the study was to evaluate strength of the dorsal and plantar flexors in patients with obliterating arteriopathy of the lower limbs (stage 2) and to evaluate fatigue. POPULATION AND METHODS: The comparison was based on two groups of ten patients: one with obliterating arteriopathy, and the second with healthy limbs as a control group. Each group of patients underwent bilateral plantar flexion and dorsiflexion of the ankle on an isokinetic machine, with the following movements: three series of five movements at 120 degrees/s, then three series of three movements at 30 degrees/s in a concentric mode to evaluate strength. The exercise was repeated 20 times at 180 degrees/s to evaluate fatigue. The isokinetic parameters selected were the couple peak and ratio of workload to total weight of the patient. Tests controlled for cardiac frequency, as measured by electrocardiography, and blood pressure. RESULTS: Patients with obliterating arteriopathy of the lower limbs were generally weaker in global strength of plantar and dorsal flexors and had greater muscular fatigue than the control group (P < 0.05). CONCLUSION: Decreased performance in the leg muscles in patients with obliterating arteriopathy of the lower limbs is likely due to arterial deficit. Muscular metabolism anomalies such dysfunction of the terminal stages of the oxidative phosphorylation could also affect strength. Use of isokinetics represents an interesting possibility for treatment of patients with multiple cardiovascular abnormalities.

Protein (lysine) restriction in primiparous lactating sows: effects on metabolic state, somatotropic axis, and reproductive performance after weaning.

Low protein intake during lactation has been demonstrated to increase the loss of body protein and to reduce the reproductive performance of female pigs. The objectives of the current experiment were 1) to determine whether protein (lysine) restriction alters levels of somatotropic hormones, insulin, follicle-stimulating hormone, and leptin around weaning, and 2) to evaluate the relationships between these eventual alterations and postweaning reproductive performance. One day after farrowing, crossbred primiparous sows were randomly allocated to one of two diets containing 20% crude protein and 1.08% lysine (C, n = 12) or 10% crude protein and 0.50% lysine (L, n = 14) during a 28-d lactation. Diets provided similar amounts of metabolizable energy (3.1 Mcal/kg). Feed allowance was restricted to 4.2 kg/d throughout lactation, and litter size was standardized to 10 per sow within 5 d after farrowing. Catheters were fitted in the jugular vein of 21 sows around d 22 of lactation. Serial blood samples were collected 1 d before (day W - 1) and 1 d after (day W + 1) weaning, and single blood samples were collected daily from weaning until d 6 postweaning (day W + 6). Sows were monitored for estrus and inseminated. They were slaughtered at d 30 of gestation. During lactation, litter weight gain was similar among treatment groups. Reduced protein intake increased (P < 0.001) sow weight loss (-30 vs -19 kg) and estimated protein mobilization throughout lactation (-4.1 vs -2.0 kg). On day W - 1, L sows had higher (P < 0.02) plasma glutamine and alanine concentrations, but lower (P < 0.05) plasma tryptophan and urea than C sows. Mean and basal plasma GH were higher (P < 0.001), whereas plasma IGF-I and mean insulin were lower in L than in C sows on day W - 1. Preprandial leptin did not differ between treatments on day W - 1, but was higher (P < 0.01) in L sows than in C sows on day W + 1. Mean FSH concentrations were similar in both treatments on day W - 1 (1.3 ng/mL), but L sows had greater (P < 0.001) mean FSH on day W + 1 than C sows (1.6 vs 1.2 ng/mL). The weaning-to-estrus interval (5 +/- 1 d) was similar in both groups. Ovulation rate was lower in L than in C sows (20.0 +/- 1 vs 23.4 +/- 1, P < 0.05). No obvious relationships between reproductive traits and metabolic hormone data were observed. In conclusion, these results provide evidence that protein (lysine) restriction throughout lactation alters circulating concentrations of somatotropic hormones and insulin at the end of lactation and has a negative impact on postweaning ovulation rate.

Feed restriction in cyclic gilts: gonadotrophin-independent effects on follicular growth.

Our objective was to determine whether changes in metabolic hormones, induced by feed restriction, can alter follicle distribution in swine ovaries through effects independent of LH pulsatility. In a factorial arrangement, 24 gilts were fed a high or a low level of dietary energy (240 or 80% of maintenance requirements) and given an antagonist of GnRH or saline between days 3 and 12 of the oestrous cycle. Serial blood samples were collected on day 12 and ovaries on day 13. Antagonist treatment, that blocked LH pulsatility, decreased the number of follicles larger than 2 mm and increased the number of follicles smaller than 1 mm. The feed restriction did not alter gonadotrophin secretion, decreased the number of follicles smaller than 1 mm and increased the number of 1 - to 1.9-mm follicles. These findings indicate that feed restriction can alter the growth of small follicles independently of gonadotrophin levels.

Influence of insulin treatment and feed restriction on follicular development in cyclic gilts.

Crossbred gilts were used to investigate whether exogenous insulin can restore normal follicular growth in feed-restricted gilts. After an 18-day altrenogest treatment, the first day of oestrous behaviour was designed as day 0. From day 0 to 13, all gilts received the same amount of feed, calculated to meet 200% of the energy requirements for maintenance. On day 14, luteolysis was induced by injection of an analogue of prostaglandin F2alpha. All gilts were slaughtered on day 19 and their ovaries removed. In Experiment 1, gilts received a high (240% of maintenance) or low (80%) level of feeding (n=10/group) from day 14 to 18. The number of large follicles (> or = 5 mm) on day 19 was reduced in feed-restricted gilts (16.9 versus 20.6, P<0.05). The same protocol of feed restriction was used in Experiment 2 (240% versus 80% of maintenance from day 14 to 18), and some gilts received daily injections of insulin (0.6 IU live weight kg(-1)). The three experimental groups were H: 240% and no insulin (n=8); H-I: 240%+insulin (n=8) and L-I: 80%+insulin (n=7). On day 18, 4 h after insulin injection, plasma insulin was higher in insulin-treated than in untreated gilts and glucose concentrations were reduced more dramatically in L-I than in H-I gilts (P<0.05). Concentrations of IGF-I were lower in L-I than in other gilts (P<0.05) and plasma IGFBPs were not significantly affected by treatments. On day 19, the number of large follicles (> or = 5 mm) was not significantly influenced by treatments (19.4, 17.6 and 15.3 for H, H-I and L-I gilts, respectively). Insulin, IGF-I and IGFBP-2 levels in follicular fluids from large follicles did not differ between females whereas IGFBP-3 levels were lower in L-I than in H gilts (P<0.05) and intermediate in H-I gilts. Intrafollicular levels of glucose were higher in feed-restricted than in well-fed gilts (P<0.05). These results suggest that exogenous insulin does not restore final follicular growth impaired by acute undernutrition.

Influence of feed restriction in primiparous lactating sows on body condition and metabolic parameters.

Twenty-four primiparous sows were allocated at farrowing to a high (H: 5.5-6 kg feed/day) or a low (L: 2.5-3 kg/day) level of feeding. Litters (8-10 piglets) were weaned at 28+/-2 days. Serial blood samples were collected 1 day before weaning (W-1), in the hours following weaning (W) and 1 day after (W + 1). L sows lost significantly more weight (38 versus 15 kg) and backfat (5.3 versus 2.3 mm) during lactation than H sows. On day W-1, L sows had higher mean concentrations of NEFA (P < 0.01) and GH (P < 0.1 ) and lower concentrations of insulin and IGF-I (P < 0.05) than H sows. Mean concentrations of glucose and cortisol did not differ between groups of sows. On day W + 1, these parameters were not different between treatments, except IGF-I concentrations which remained lower in L than in H sows (P < 0.05). We conclude that lactating primiparous sows alter secretion of metabolic hormones to favour mobilization of body reserves to support milk production. Low insulin and IGF-I may be involved in reduced ovarian activity at and after weaning, through LH-dependent and independent pathways.

Influence of feed restriction during lactation on gonadotropic hormones and ovarian development in primiparous sows.

Effects of nutritional deficit during lactation on secretion of gonadotropic hormones and ovarian follicular populations around weaning were investigated in 24 primiparous crossbred sows. Sows were allocated to receive close to ad libitum intakes (H) or approximately 50% of this amount (L) during a 28-d lactation. Serial blood samples were collected 1 d before weaning (W-1), in the hours following weaning (W), and 1 d after (W+1). Their ovaries were removed on the day of weaning or 2 d later (W+2) and subjected to macroscopic and histological observations. Mean and basal LH concentrations were not influenced by the level of feeding. Frequency of LH pulses was reduced in L sows (.17, .5, and .5 vs 1.50, 1.17, and .83 pulses/6 h at d W-1, W, and W+1 respectively; P < .05). Mean and basal concentrations of LH were influenced by the day of sampling, being significantly increased within hours following weaning. Mean FSH concentrations were influenced neither by the level of feeding nor by the day of sampling. At weaning, the ovaries from L sows were lighter and had smaller follicles and fewer follicles > or = 4 mm (P < .05). Values of these macroscopic characteristics increased after weaning ( P < .05). At weaning, the percentage of healthy follicles was higher in the first class (< 1 mm) and lower in the second class (1 to 2.99 mm) in L compared to H sows (P < .05). Whatever the day of sampling, IGF-I concentrations in follicular fluid tended to be lower in L than in H sows. These results indicate that feed restriction during lactation inhibits LH pulsatility and ovarian activity.

Subacute and chronic myelomonocytic leukemia in children (juvenile CML). Clinical and hematologic observations, and identification of prognostic factors.

The clinical and hematologic characteristics of 38 children with subacute and chronic myelomonocytic leukemia (S & CMMOL) are described, and the prognostic significance of these characteristics as recorded at diagnosis is reported. The common and distinctive feature of these children was the excessive proliferation of cells of neutrophilic and monocytic series. The disease predominated in younger children, 95% were younger than 4 years, and boys were more affected than girls (22/16). The onset of the disease was heralded most often by acute or subacute symptoms. Splenomegaly was the most common physical finding at diagnosis. Leukocytosis was usually under 100 X 10(9)/l. Monocytosis and granulocytosis were often associated with normoblastosis, and, in some cases, with moderate blastosis (less than or equal to 30%). Severe anemia and marked thrombocytopenia were found in about one third of patients, increased fetal hemoglobin levels in 53%, and increased gamma-globulin levels in 50% of cases. The Philadelphia chromosome was absent in all blood and marrow cell karyotypes. Thirty-three of 38 patients were treated with moderate or intensive chemotherapy, and in all cases treatment never resulted in a complete remission. Terminal acute leukemia occurred in 11 cases. Of the 38 patients, 29 have died (median survival time, 16 months). Initial characteristics predicting a short survival (log-rank test) included: older age (greater than or equal to 2 years) (P less than 0.001), hepatomegaly (P less than 0.05), bleeding (P less than 0.001), thrombocytopenia (P less than 0.01), high counts of blasts and normoblasts in peripheral blood (P less than 0.01, P less than 0.01). Sex, infections, cutaneous manifestations, lymphadenopathy, degree of splenomegaly, hemoglobin levels, fetal hemoglobin, leukocyte counts, percent of blasts in bone marrow, and serum gamma-globulin levels were of no prognostic value. When survival was plotted on a semilogarithmic scale, a change in death rate was evident at the second year of survival suggesting that there may be two subgroups of patients with myelomonocytic picture, one with very rapid, and another with a slower rate of mortality. A stepwise discriminant-function analysis was performed in an attempt to distinguish between those children who lived less than or equal to 2 years and those who lived longer. A linear combination of variables which best discriminated between these two subgroups was found. Nearly all patients could be classified as a short-survivor or long-survivor on the basis of age and platelet, blast, and normoblast counts in peripheral blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Philadelphia chromosome-positive chronic myelocytic leukemia in children. Survival and prognostic factors.

The survival and the prognostic significance of the diagnostic characteristics of 39 children with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph1-positive CML), seen between 1963-1976 at the Hôpital Saint-Louis of Paris, have been analyzed. The disease predominated in children older than age 4 years (95%), with girls being more affected than boys (24 versus 15). The clinical and hematological picture at presentation was similar to that observed in adults with Ph1-positive CML. Most children of this series were treated with busulfan which, as in adults, led to reduction of leucocytosis and organomegaly but did not prevent the occurrence of blastic crisis. Well-documented blastic crisis was observed in 78% of cases. Of 39 children, 12 were still alive, all in the chronic phase. Twenty-seven have died, 21 of them after blastic crisis, 4-156 months after diagnosis (median survival, 53 months). The effect of each diagnostic characteristic on survival was evaluated using the log-rank test. Of the 14 characteristics studied, only the degree of blood and marrow blastosis was associated with a shorter survival. Age, sex, bleeding, lymphadenopathy, hepatomegaly, degree of splenomegaly, hemoglobin level, total leucocyte, immature granulocyte (promyelocytes + myelocytes + metamyelocytes), eosinophil, basophil, and platelet counts in the peripheral blood were of no prognostic significance. The failure to attain a level of statistical significance for some characteristics found to be of prognostic value for adults, could be due to the small sample size and/or to the disease homogeneity. The results of this study, however, stress the importance of the initial blastic infiltration in determining the duration of survival, which is ultimately determined by the occurrence of terminal acute leukemia. In conclusion, this study shows that the Ph1-positive CML of childhood exhibits the same course, incidence of blastic crisis, and survival as the disease of adults. It also indicates that treatment with moderate chemotherapy, such as busulfan, has no effect on the duration of survival. Therefore, new therapeutic approaches are urgently needed for the treatment of this disorder in children.

Long-term local and distal increases in tryptophan hydroxylase activity following intracerebral kainic acid injections in the rat.

The administration of kainic acid (1--2 micrograms) into the right striatum of adult rats resulted in a marked local increase in tryptophan hydroxylase activity (+ 54--106%). This change was significant as soon as on the second day after the treatment and persisted for at least 12 days. In addition, long-lasting elevations of tryptophan hydroxylase activity were also observed in the anterior raphe area, septum and ipsilateral hippocampus and cerebral cortex. In contrast, the intrahippocampal injection of kainic acid (1 microgram) induced a long-term increase in tryptophan hydroxylase activity only in the injected structure. In all cases, the changes in tryptophan hydroxylase activity were associated with significant increases in the Vmax of the enzyme with no alteration of its apparent affinities for tryptophan and the pterin cofactor. Studies of the sensitivity of tryptophan hydroxylase from control and from kainic acid-treated rats to in vitro activating conditions (Ca2+-dependent phosphorylation, partial trypsinization, exposure to sodium dodecyl sulfate) suggest that the intrastriatal injection of the neurotoxin induced a long-lasting activation of the enzyme. These findings indicate that intracerebral injections of kainic acid may be a valuable approach to explore further the mechanisms controlling tryptophan hydroxylase activity in vivo.