Objective.This randomized, controlled trial was designed to determine the efficacy of inhaled fluticasone propionate on oxygen therapy weaning in a population of preterm infants who were born at <32 weeks of gestation and experienced moderate bronchopulmonary dysplasia (BPD). Methods.Thirty-two infants who were ≤32 weeks of gestation, had moderate BPD that required supplemental oxygen (fraction of inspired oxygen ≥0.25), and were aged between 28 and 60 days were randomized. Fluticasone propionate 125 μg twice daily for 3 weeks and once daily for a fourth week was delivered to infants who weighed between 500 and 1200 g. The dosage was doubled for infants who weighed ≥1200 g. Results.Compared with placebo, treatment had no effect on either duration of supplemental O2 therapy or ventilatory support as assessed by survival analysis. At 28 days, a trend toward a lower cortisol/creatinine ratio in the treatment group was noted compared with placebo (25.1 ± 18.9 vs 43 ± 14.4). In the fluticasone group at 28 days, the systolic arterial pressure (78 ± 3 vs 68 ± 3 mm Hg) and diastolic arterial pressure (43 ± 3.4 mm Hg vs 38 ± 2.0 mm Hg) were higher compared with baseline fluticasone values. The chest radiograph score was lower than baseline (2.8 ± 1.4 vs 3.7 ± 2.2) in the fluticasone group at 28 days. This study has a statistical power of 1.0 to detect a significant difference in the duration of oxygen supplementation of >21 days between the study groups. Conclusion.We conclude that fluticasone propionate reduces neither supplemental O2 use nor the need for ventilatory support in this patient population. However, fluticasone does have a positive radiologic effect in lowering chest radiograph scores. In addition, our data point to a possible association among inhaled fluticasone treatment and higher arterial blood pressure. Thus, the results of this investigation do not support the use of inhaled corticosteroids in the treatment of oxygen-dependent infants who have established moderate BPD.

BACKGROUND:The impact on family life and social relations that may result from symptoms associated with exposure to neurotoxic substances has never been addressed. This exploratory study assessed the associations between exposure to neurotoxic agents in the workplace, mental health, and marital difficulties.METHODS:Fifty-five (55) male workers and their spouses completed standardized measures of mental health and marital difficulties. Workers' exposure to neurotoxic substances was evaluated by questionnaire and interview, using a semiquantitative classification system.RESULTS:A positive relation was observed between exposure level and measures of workers' psychological symptoms and marital stress; no relation was observed between workers' exposure level and wives' psychological symptoms. More severe exposure to neurotoxic substances was associated with wives' reports of more severe marital conflicts, and this association was mediated by husbands' psychological symptoms. As compared to low exposure husbands, high exposure husbands reported higher degrees of stress surrounding marital discussions, more consistent incidence of minor physical assaults by wives, and stronger associations between their levels of stress, the verbal aggressions of wives, and the number of marital conflicts.CONCLUSIONS:The results of this study confirm that neurotoxic exposure is a risk factor for mental health and suggest how this may influence marital relations. Because of the importance of these findings for the well-being of workers and their families, these associations should be further studied.

Exposure data and bioindicators were obtained for a study whose objective was detection of early manifestations of manganese (Mn) neurotoxicity in a population with potential environmental exposure. The study included persons with no history of neurotoxic workplace exposure in Southwest Quebec, drawn from seven postal code regions, defining a set of geographically contiguous zones. Blood samples were analyzed for total Mn (MnB), lead (PbB), total mercury (HgT) and serum iron (FeS). Drinking water samples from participants' residences were analyzed for manganese (MnW). At 4 sites, limited 24-hour high volume air samples for total particulates (TP) and PM10, were analyzed for Mn and Pb. Sociodemographic and dietary information was obtained by self-administered questionnaire. The geometric mean (GM) for MnB values (n = 297) was 7.14 micrograms/L. Levels of MnB in women (n = 156; GM 7.50 micrograms/L) were significantly higher than in men (n = 141; GM 6.75 micrograms/L). No relationship was found between MnB and PbB or HgT. FeS was significantly higher in men (GM 18.38 mumol/L) than women (GM 15.0 mumol/L). For women, MnB was correlated to FeS, with a tendency to decrease with increasing age. For men, no relationship was found between MnB levels and either FeS or age, although FeS showed a strong inverse relationship with age. The 24-hour mean levels of MnTP at the 4 sites varied between 0.009 microgram/m3 and 0.035 microgram/m3; intersite differences were not significant. For Mn in PM10 (MnPM10), mean values ranged from 0.007 microgram/m3 to 0.019 microgram/m3; intersite differences were significant. A total of 278 MnW samples were obtained, 16 from residences served by wells. The GM for MnW was 4.11 micrograms/L (range: 0.50-71.1 micrograms/L, excluding wells; MnW for wells ranged from non-detectable to 158.9 micrograms/L. Individually, there was no relation between MnW and MnB. Geographic analysis of the MnB and MnW data by an algorithm grouping contiguous postal code zones, combined with air data, lead to definition of a geographic parameter, distinguishing two regions relative to a former manganese alloy plant, which contributed significantly to MnB. A multiple regression model was developed, explaining 6.7% of the variability in MnB (F = 5.12; p < 0.001); when controlling for gender, geographic region with higher levels of airborne manganese and the frequency of consumption of cereals and leaf vegetables contributed positively to MnB levels, while serum iron was negatively related.

The toxicity of interferon (IFN) alfa-2b therapy was prospectively evaluated in 53 children treated from 1991 to 1996 in 2 successive studies of IFN alfa therapy for severe hemangiomas at Sainte-Justine Hospital. Toxicity was generally mild and transient, with grade 1 toxicity occurring in 100% of patients, grade 2 toxicity in 89%, grade 3 toxicity in 58%, and grade 4 toxicity in 17%. Ten of 43 patients available for evaluation had an abnormal neurologic examination. Severe neurotoxicity in the form of spastic diplegia occurred in one patient. In conclusion, IFN alfa therapy is generally well tolerated in children. However, it may rarely be associated with severe toxicity and must be used with caution. (J Pediatr 1999;135:782-5)

Excessive manganese (Mn) has been associated with neurobehavioral deficits and neurological and/or neuropsychiatric illness, but the level at which this metal can cause adverse neurotoxic effects, particularly with long-term exposure, is still unknown. The objective of the present study was to assess nervous system functions in residents exposed to manganese from a variety of environmental sources. A random stratified sampling procedure was used to select participants; persons with a history of workplace exposure to Mn and other neurotoxic substances were excluded. A self-administered questionnaire provided data on socio-demographic variables. Blood samples were analyzed for total manganese (MnB), lead, mercury and serum iron. Nervous system assessment included computer and hand-administered neurobehavioral tests, computerized neuromotor tests, sensory evaluation and a neurological examination. The present analyses include 273 persons (151 women and 122 men); MnB range: 2.5 micrograms/L-15.9 micrograms/L (median: 7.3 micrograms/L). Multivariate analyses were used and neuro-outcomes were examined with respect to MnB, taking into account potential confounders and covariables. Results were grouped according to neurofunctional areas and MANOVA analyses revealed that higher MnB (7.5 micrograms/L) was significantly associated with changes in coordinated upper limb movements (Wilks' lambda = 0.92; p = 0.04) and poorer learning and recall (men: Wilks' lambda = 0.77; p = 0.002; women: Wilks' lambda = 0.86; p = 0.04). Further analyses revealed that with increasing log MnB (Simple regression: p < 0.05) performance on a pointing task was poorer, frequency dispersion of hand-arm tremor decreased, while harmonic index increased, and the velocity of a pronation/supination arm movement was slower. An Mn-age interaction was observed for certain motor tasks, with the poorest performance observed among those _50 y and in the higher MnB category. Differences between genders suggest that men may be at greater risk than women, although effects were also observed in women. These findings are consistent with the hypothesis that Mn neurotoxicity can be viewed on a continuum of dysfunction, with early, subtle changes at lower exposure levels.

The purpose of the study is to determine the effect of intradialytic parenteral nutrition (IDPN) and its components on delivered Kt/V (Kt/Vd ). Nineteen patients undergoing routine outpatient hemodialysis and receiving IDPN were enrolled onto this prospective, crossover study. To reduce the confounding of time, assigned treatment in the first week was random, with patient crossover in the fourth week. Patients served as their own controls. In the successive 6 weeks, patients received IDPN solutions differing in whether amino acids (AAs), dextrose, or lipids were included or excluded. The primary end point was Kt/Vd , measured with a single-pool, variable-volume urea kinetic model. Other factors with the potential to impact on Kt/Vd were controlled and/or monitored. The administration of IDPN with all three components resulted in a significantly reduced mean Kt/Vd . When patients received AA-containing solutions, mean Kt/Vd was significantly less than when IDPN was withheld. Administration of solutions without AA resulted in a mean Kt/Vd not significantly different from mean Kt/Vd when IDPN was withheld. The mean prescribed Kt/V did not differ from mean Kt/Vd when IDPN was withheld. Simulation analyses of increased urea generation (Gu ) showed an increase in patient urea volume and decreased Kt/V similar to the study findings. AA-containing IDPN solutions resulted in a significant reduction in Kt/Vd , possibly mediated by increased Gu . Administration of IDPN solutions may have important clinical and economic consequences that warrant further investigation.

An important component of the pathophysiologic response to hyperoxia (O2) is pulmonary inflammation, although the roles of specific inflammatory mediators during pulmonary O2 toxicity are not completely known. Interleukin-1 (IL-1) is an early inflammatory mediator and is sufficient to elicit many of the responses associated with acute injury. The IL-1 family comprises two bioactive proteins, IL-1alpha and IL-1beta, and their natural antagonist IL-1ra. Here we report studies of IL-1 regulation during hyperoxic lung injury in the adult mouse. When assayed by Northern blot, increases in IL-1beta mRNA were seen after 2 days of hyperoxia. In contrast, IL-1alpha mRNA was barely detectable before 4 days of hyperoxia. To further understand the cellular origin of IL-1beta expression in lungs, in situ hybridization and immunohistochemical analyses were performed. IL-1beta mRNA or protein was not detected in the lungs of unexposed animals. At 3 days, we observed the accumulation of IL-1beta transcripts in pulmonary interstitial macrophages and in a subset of neutrophils, and immunodetectable IL-1beta protein was co-localized in adjacent sections. At 4 days of exposure, IL-1beta transcripts were widespread in lung tissue, but many areas rich in IL-1beta mRNA were devoid of immunodetectable IL-1beta. However, it is not known whether increased synthesis of IL-1beta or the uncoupling of IL-1beta protein and mRNA accumulation has a role in pathophysiology of pulmonary O2 toxicity.

Purpose: Vigabatrin (VGB) and lamotrigine (LTG) are two new antiepileptic drugs (AEDs) with different mechanisms of action for treatment of refractory epilepsies. Previous reports have indicated efficacy of both drugs in a number of epileptic syndromes.Methods: We compared these new AEDs drugs to determine their respective efficacy against-different types of epileptic syndrome and to develop a rational approach to their use. We reviewed the charts of 105 children, with partial and generalized epilepsies.Results: VGB was to be significantly more effective in children with partial epilepsies, and LTG was more effective in those with generalized epilepsies.Conclusions: VGB and LTG have different therapeutic profiles. Combination treatment with the two drugs may represent rational polytherapy for patients with epilepsy resistant to treatment with either drug alone or as add-on to other AED treatment.

Pollution of hydrographic basins has affected the flora and fauna that thrive in these aquatic ecosystems, and fish, which constitute an important food resource, often contain a plethora of potentially toxic chemicals. In a major research project on early neurotoxic effects of environmental exposure to manganese among residents in Southwest Quebec, fish consumption from 2 lakes of the Upper St. Lawrence River System, was surveyed as a potential confounding factor. Participants were selected using a random, stratified sampling strategy from lists of the Quebec Health Plan. Following exclusions, 273 men and women between 20-69 years were retained for the present analysis. A total of 103 (37.7%) reported eating fish from the Upper St. Lawrence. Although fisheaters and non-fisheaters were similar for most socio-demographic variables, significantly more fisheaters (65.2%) reported consuming alcoholic beverages as compared to non-fisheaters (42.4%) (Chi Sq. <0.01). To eliminate this possible bias, fisheaters were matched to non-fisheaters for the variables sex, alcohol consumption (never or occasionally vs. regularly), age (+/-5y) and education (+/-2y). A total of 63 matched pairs were thus created. Paired analyses (t-test or Signed Rank) showed that fisheaters had higher levels of blood organic mercury and lead. Analysis of nervous system functions revealed that both groups performed similarly on tests of sensory function, visual memory and recognition, fine motor performance and some motor tests, but fisheaters performed significantly more poorly (p<0.05) on tests requiring cognitive flexibility, word naming, auditory recall, and more complex motor tasks. The profile of deficits is consistent with diminished capacity for information processing. These observations were made within a study that was not specifically designed to examine the effects of fish eating from these two lakes, and the characterization of fish dietary habits has many limitations. Nevertheless, the findings are sufficiently compelling to warrant further studies, since fish from the Upper St. Lawrence Lakes are known to contain multiple neurotoxic substances.

Fifty-five (55) workers and their spouses took part in assessments of the effect of exposure to nerve agents in the work place on mental health and marriage. Standardized measurements were used to assess exposure level, mental health problems and marital discord. Results show that a) significant levels of exposure are related to a high incidence of psychological symptoms, b) workers' psychological symptoms mediate the impact of exposure on spouses' perceptions of marital discord and c) exposure regulates the relationship between mental health and marital discord. Exposure therefore poses a risk to marital stability.

In vitro, bilirubin is a strong antioxidant, but in vivo its capacity to act as a scavenger of toxic oxygen radicals remains poorly documented. The aim of this study was to evaluate of bilirubin had antioxidant properties in jaundiced infants. The antioxidant capacity of neonatal plasma was measured in Trolox equivalents (TEAC, mmol/l) and correlated in vitro with plasma bilirubin concentrations (r2 = 0.99). Plasma TEAC was compared before and after exchange transfusions for neonatal hyperbilirubinemia (250-435 mumol/l). The antioxidant properties of the paired blood samples before and after exchange transfusions (TEAC: 1.67 +/- 0.12 vs. 1.37 +/- 0.09 mmol/l, n = 11) varied in proportion to the serum bilirubin levels. The changes in other antioxidants were not large enough to account for the magnitude of change in antioxidant capacity. Therefore, in vivo, the plasma antioxidant capacity of jaundiced newborn infants is related to the level of bilirubin.

In a pilot study, serum dopamine beta-hydroxylase (DBH), platelets monoamine oxidase type B (MAO B) activities and basal plasma prolactin (PRL) were measured, among 10 workers occupationally exposed to toluene and 10 control subjects, preceding and immediately following vacation. Six exposed subjects were employed in an adhesive tape making industry and 4 in a paint making industry. Their median basal levels of urinary hippuric acid were 0.44 mmole/mmole creatinine (cr) (range 0.23-1.97) and 0.18 mmole/mmole cr (range 0.15-0.19) respectively, the second to last morning of the work week, preceding vacation. The level of basal urinary hippuric acid among the control group was 0.26 mmole/mmole cr (range 0.03-0.38). The workers from the adhesive tape plant reported a significantly higher number of symptoms experienced frequently (Kruskal, Wallis, p < 0.05). On a group basis, serum DBH was lowest among the workers from the adhesive tape plant, who had the highest levels of basal urinary hippuric acid. In addition, a negative relation was observed between hippuric acid and serum DBH, preceding and following vacation (Rho = -0.46, p = 0.05; Rho = -0.51, p = 0.03). The observed changes in serum DBH activity are consistent with its decrease in human, following long-term exposure to styrene, another aromatic hydrocarbon. The findings of this pilot study, on a limited number of individuals suggest that DBH may be a sensitive peripheral bioindicator. Further studies of larger groups should be done to confirm the decrease in serum DBH activity with toluene exposure and explore whether this alteration is related to the neurotoxic impairments associated with exposure.

AIMS: To determine if decreasing arterial blood saturation from 95% to 90% could cause vasoconstriction of the pulmonary vasculature and dilatation of a patent ductus arteriosus in preterm newborn infants with respiratory distress syndrome (RDS). METHODS: Doppler echocardiographic studies were compared at 95% and 90% pulse oxygen saturation (SpO2) in 13 preterm infants aged 61.7 (4.3) hours with RDS and Doppler echocardiographic evidence of tricuspid regurgitation. RESULTS: The mean (SD)Doppler echocardiographic indices determined at 95% were heart rate (146 (3.60) beats per minute), acceleration time of the velocity wave forms of the pulmonary artery (PAAT) (51.8 (2.5) milliseconds), ratio of PAAT to right ventricular ejection time (ET) (0.26 (0.02)), diameter of the ductus arteriosus (2.6 (0.6) mm), pulmonary blood flow (0.33 (0.03) l/minute) and the left ventricular shortening fraction (SF)(0.4 (0.02)%). The ascending aorta flow velocity wave form was used for the calculation of pulmonary blood flow. The right ventricular to right atrial systolic pressure gradient calculated using the peak velocity of the tricuspid regurgitation jet was 26.7 (7.4) mm Hg. CONCLUSIONS: A decrease from 95% to 90% SpO2 did not have any effect on the pulmonary circulatory haemodynamics nor the ductus arteriosus.

Surveillance of early neurotoxic alterations was undertaken in 3 reinforced plastics plants, with a view to preventive intervention. Using a longitudinal study design, exposure parameters (environmental styrene in the respiratory zone of each worker and end-shift mandelic acid (MA)) and neurobehavioral performance (Neurobehavioral Core Test Battery and Field Assessment: Sensory Tests), were assessed at time zero (T0); recommendations were made to reduce exposure at jobsites with the highest risk. Reassessment was made two years later (T2). Complete exposure data was available for 118 workers at T0; 75 were still employed at T2; of these, 57 (76%) returned for testing. Those who returned had more seniority (p < 0.001) and higher MA (p < 0.01) and styrene (p < 0.05) levels at T0 than the others. Analyses, performed on the T0-T2 differences, showed improvement in exposure parameters in Plant 3, where lower levels were observed at T2 for styrene (p < 0.05) and MA (p < 0.001). workers in Plant 3 (n = 29) performed better (p < 0.05) at T2 for short term memory, perceptuo-motor speed, motor precision and manual dexterity; they reported more vigor (p < 0.05) and less anger (p = 0.07). This was not the case for the workers from the other plants. Generally, the T0-T2 difference in MA was associated (Spearman's Rho) with differences in color vision (p < 0.001), simple reaction time (mean and standard deviation), digit span forward, tension, fatigue and the number of symptoms (p < 0.05); aiming precision showed a similar tendency (p < 0.10). These findings suggest that group surveillance of early nervous system changes for jobs with exposure to neurotoxins, using a sensitive neurofunctional test battery, may be useful for preventive intervention.

Emotional instability which might be an early symptom of more severe disorders, is one of the first manifestations of chronic exposure to organic solvents. The present study measures the association between exposure to styrene and mood states of active workers. A total of 128 workers (85% of the total population) from 3 factories where styrene is used, participated on a voluntary basis. They filled out the following self-administered questionnaires Profile of Mood States (POMS), Psychiatric Symptom Index and Well-being Index. The results indicate a significant relationship between post work-shift urinary mandelic acid (biological indicator of styrene exposure) and the scores obtained on the POMS scales of tension-anxiety (Spearman's rank correlation rho = 0.30; p<0.01), anger-hostility (rho = 0.29; p<0.01), fatigue-inertie (rho = 0.34; p<0.01), and confusion-bewilderment (rho = 0.23; p = 0.04), as well as the Psychological Distress Index (rho = 0.30; p<0.01). All scores were adjusted for the effects of 4 potentially confounding variables : age, schooling, alcohol and cigarette consumption. These indicators of mood states do not constitute a diagnosis of mental disease but reveal progressive deterioration of well being associated with neurotoxic exposure in the workplace.

OBJECTIVES:The present study was undertaken to examine the relation between visual functions and occupational exposure to styrene.METHODS:A total of 128 workers (85% of the total population), from three glass-reinforced plastics plants in Canada, agreed to participate in the study. Environmental and biological measures were made on the day(s) prior to the assessment of near visual acuity (National Optical Visual Chart), chromatic discrimination (Lanthony D-15 desaturated panel), and near contrast sensitivity (Vistech 6000). The analyses were performed on 81 workers with near visual acuity of at least 1 min of arc at 0.5 m.RESULTS:The subjects were relatively young [29 (SD 8) years], with little seniority [5 (SD 4) years]. Styrene exposure for 8 h ranged from 6 to 937 (first quartile 21 mg.m-3, third quartile 303 mg.m-3), depending on the job site. The end-shift concentrations of urinary mandelic acid ranged from nondetectable to 1.90 mmol.mmol creatinine-1. Significant positive relations were found between the internal and external styrene exposure measurements and color vision loss adjusted for age, alcohol consumption, and seniority in a multiple regression analysis. The multiple regression analysis is also showed that the end-shift concentration of urinary mandelic acid was inversely related to contrast sensitivity at 6 and 12 cycles.degree-1. Logistic multiple regression models indicated that the end-shift concentration of urinary mandelic acid was related to the prevalences of blurred vision, tearing, and eye irritation.CONCLUSIONS:These findings suggest that there is a positive relation between styrene exposure and early color and contrast vision dysfunction.

The relationship between organic solvent exposure and central nervous disorders make early detection of neurophysiologic et neuropsychologic alterations in organic solvent exposed workers a priority. Moreover the variability in the frequency of exposure and the numerous organic solvents encountered in scientific laboratories render the environmental and biological measurements used in medical surveys almost impossible. The present study was undertaken to appreciate the potential neurotoxic effects of organic solvents handling in laboratory employees. Neurophysiological and neuropsychological tests batteries were used with each worker and data were adjusted for potential confounding factors (age and education level), A Principal Components Analysis was performed to reduce the information and the first five factors corresponded to mood states, speed coding, contrast vision in high frequencies, manual dexterity and contrast vision in low frequencies. These five factors were compared between the daily manipulators of at least one solvent (n=75) and the non or occasional solvent users (n=35). The results from this study showed that subjects directly in contact with solvents had a poorer mood state than those who were not or rarely exposed (p<0.01) and that independently of the "work activity". Mood state impairment in chronic solvent exposed workers has been shown by many authors, with or without psychomotor alteration, and may reflect possible over-exposure. Detection of this instability may lead to early neurophysiologic alteration in exposed workers and permit health services to intervene before the development of irreversible effects.