Are eye movement abnormalities indicators of genetic vulnerability to schizophrenia?

UNLABELLED: Fifty to eighty-five percent of schizophrenic patients are impaired on ocular pursuit paradigms. However, results regarding the relatives are more discordant. The aim of this study was to investigate whether eye movement disorders could be a vulnerability marker of schizophrenia. METHOD: Twenty-one schizophrenic patients (DSM-IV), 31 first-degree relatives of those patients without schizophrenic spectrum disorders, and two groups of healthy controls matched by age and sex were included. Three oculomotor tasks (smooth pursuit, reflexive saccades and antisaccades) were used. RESULTS: Patients had a lower averaged gain (P= 0.035) during smooth pursuit than controls, made less correct visually guided saccades (P< 0.001) and more antisaccades errors (P= 0.002) than controls. In contrast, none of the comparison between the relatives and their controls was significant. CONCLUSION: Schizophrenic patients were impaired on smooth pursuit and antisaccade paradigms. None of these impairments was, however, observed in their first-degree relatives. Our results suggest that the eye movement parameters tested could not be considered as vulnerability markers for schizophrenia.

Inhibitory effect of almitrine on dopaminergic activity of rat carotid body.

Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.

Studies on the central or peripheral origin of free and sulfated 3,4-dihydroxyphenylacetic acid in rat plasma.

The concentrations of free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma to investigate their potential central or peripheral origin. Stimulation of central dopamine (DA) metabolism by a long-acting neuroleptic, pipotiazine (PPZ) selectively increased plasma levels of DOPAC sulfate whereas peripheral inhibition of monoamine oxidase by debrisoquin sulfate decreased free DOPAC levels only. These data suggest that the two forms of plasma DOPAC (free and sulfate) may have independent topographic origins. Peripheral DA pools seem to be the most likely sources for plasma free DOPAC whereas central dopaminergic neurons mainly contribute to plasma sulfated DOPAC. Our findings thus demonstrate that plasma DOPAC sulfate may be a useful indicator for central DA function in rat. Although further experiments are necessary to extrapolate our findings from rat to man, arguments are given indicating that measurements of plasma DOPAC sulfate might be of interest in human pathological and pharmacological investigations.

Striatal and mesolimbic dopaminergic contribution to 3,4-dihydroxyphenylacetic acid sulfate in rat plasma.

Free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma after bilateral 6-hydroxydopamine lesions of striatum or mesolimbic tissue (nucleus accumbens + olfactory tubercle). Both lesions selectively reduced plasma DOPAC sulfate levels without altering free DOPAC or catecholamine levels in plasma, sympathetic ganglia or adrenal medulla. The present work confirms our previous findings and suggests that DOPAC sulfate functional state of striatal and mesolimbic dopaminergic neurons.

Personal exposure assessment studies may suffer from exposure-relevant selection bias.

We evaluated exposure-relevant selection bias within the framework of a study on personal air pollution exposure, using traffic data as exposure proxy. Based on random samples of 3000 (Basel) and 2532 (Helsinki) persons, 50 and 250 subjects, respectively, were recruited for direct monitoring and 250 (Basel, Helsinki) for indirect monitoring. In Basel, participants of direct monitoring as compared to non-participants were more likely to live at streets with low traffic volume (49% below 1st quartile vs. 27%). Adjusted for sex, age and nationality, an increase of 100 cars per hour was associated with 14% less participation (odds ratio (OR): 0.861; 95% CI: 0.731, 1.007). Although in Helsinki, traffic volume was neither significantly related to participation in direct nor indirect monitoring, the point estimates indicate a tendency to decreased participation with increasing traffic intensity at home. We conclude that selection bias regarding exposure-relevant characteristics is likely to occur when recruiting participants for studies including demanding personal exposure assessment. Correction for factors routinely collected may not fully account for exposure-relevant bias. This is of particular importance when using exposure data for modelling population exposure distributions, whereas in epidemiological studies, a reduced range of exposure must not a priori distort the exposure-response relationship.

Personal exposure to atmospheric polycyclic aromatic hydrocarbons in a general adult population and lung cancer risk assessment.

Personal exposure to nine particulate-phase atmospheric polycyclic aromatic hydrocarbons (PAHs) was assessed among adult non-smoking volunteers in the Grenoble, France, metropolitan area. Using Toxic Equivalency Factors, the associated total atmospheric PAHs lifelong cancer risk was estimated. For 48 hours continuously, 38 subjects without specific occupational exposure to combustion sources carried a PM2.5 particles personal exposure monitor while at home, at work, commuting, or involved in other activities. One phase of the study took place in summer; a second in winter. The monitor set was composed of a pump with an airflow of 4 L.mn-1, a 2.5-micron cyclone, and Teflon filters. The PAH concentrations were determined on seven PM2.5 filters by using high performance liquid chromatography with fluorimetric detection. The predominant PAHs are fluoranthene and indeno pyrene. According to the compound, the personal exposure estimates ranged from 0.13 to 1.67 ng/m3 (yearly means). The average benzo(a) pyrene value is 0.67 ng/m3 (95% confidence interval = 0 to 2.1 ng/m3). Winter exposures were 3 to 25 times greater than summer exposures. The total PAHs lung cancer lifelong risk is 7.8 10(-5) and is driven by exposure to benzo(a) pyrene. Although these risk estimates are 2 to 3 orders of magnitude lower than those associated with specific occupational exposures in the coal or smelter industries, they are of public health concern because they are spread over large urban populations. Further personal exposure studies in adult or children populations are needed.

Health effects costs of particulate air pollution.

We conducted a cross-sectional study in December 1994 in three metropolitan areas of the Rhone-Alpes region in France (Lyon, Grenoble, and Chambéry; total number of inhabitants = 970,000) to assess the medical costs resulting from exposure to particulate air pollution. Probability samples of the general population (508 families, 1265 subjects) and of the physicians (395) and 13 hospital respiratory care and emergency units in the study area provided data on the prevalence of respiratory disorders and on medical care usage. Measurements from air-quality monitoring networks were used to ascribe a fraction of the respiratory morbidity to the ambient air particle concentrations present during the study period, on the basis of attributable risk estimates drawn from recent meta-analyses. The medical care usage and absenteeism related to respiratory disorders were converted into direct and indirect medical and social costs by use of a "cost of illness" approach. These costs were extrapolated to annual costs of disease attributable to particulate pollution in 1994, using daily values of air pollution. The average particulate concentrations during the study period were moderate (39, 41, and 10 micrograms/m3 in the three cities), yielding attributable fractions that ranged between 0.6% and 13.8% according to the health condition and to the city. Three hundred ninety-five subjects reported respiratory symptoms (prevalence, 31.2%) during the study period; 1182 patients visited a doctor and 158 used hospital services. The extrapolated annual estimates of the attributable cost of respiratory diseases for a population of 1 million range between 79 and 135 million French francs (FF) (20th and 80th percentiles of the cost distribution, after a Monte Carlo simulation, respectively; 50th percentile, 107 x 10(6) FF [16.3 x 10(6) Euros]). Over-the counter drug consumption represents the largest cost item (approximately 44% of total costs), followed by wage losses (38%). Hospital expenditures amount to a low percentage of total costs (about 5%) because most respiratory disorders do not require hospital care. Mortality was not considered in this study. Most of these costs occur at relatively low levels of air pollution (67% of the total annual costs are incurred during days with particle concentrations lower than 50 micrograms/m3). Such substantial figures are useful for assessing the social impacts of air pollution and for evaluating the cost efficiency of abatement policies.

Can one use ambient air concentration data to estimate personal and population exposures to particles? An approach within the European EXPOLIS study.

The objective of this paper is to devise a way to facilitate the use of fixed air monitors data in order to assess population exposure. A weighting scheme that uses the data from different monitoring sites and takes into account the time-activity patterns of the study population is proposed. PM2.5 personal monitoring data were obtained within the European EXPOLIS study, in Grenoble, France (40 adult non-smoking volunteers, winter 1997). Volunteers carried PM2.5 personal monitors during 48 h and filled in time-activity diaries. Workplaces and places of residence were classified into two categories using a Geographic Information System (GIS): some volunteers' life environments are seen as best represented by PM10 ambient air monitors located in urban background sites; others by monitors situated close to high traffic density sites (proximity sites). Measurements from the Grenoble fixed monitoring network using a TEOM PM10 sampler were available across the same period for these two types of sites (PM10block and PM10prox). These data were used to compute a translator parameter deltai that forces the measured PM2.5 personal exposures (PM2.5persoi) to equate the average PM10 urban ambient air concentrations ([PM10back + PM10prox]/2) measured the same days. Average deltai was 4.2 microg/m3 (CI95%[-3.4; 11.9]), with true average PM2.5 personal exposure being 36.2 microg/m3 (28.2; 44.1). PM10 ambient levels at the proximity site and at the background site were respectively PM10prox = 43.8 microg/m3 (37.1; 50.6) and PM10back = 37.0 microg/m3 (31.8; 42.3). In order to assess the consistency of this approach, six scenarios of 'proximity' and 'background' environments were accommodated, according to traffic intensity and road distance. Deltai was estimated for the entire EXPOLIS population and for subgroups, using terciles based on the percentage of time spent in proximity by each subject. Other similar studies need to be conducted in different urban settings, and with other pollutants, in order to assess the generalizability of this simple approach to estimate population exposures from air quality surveillance data.

[Personal exposure to fine particles (PM 2.5) in the Grenoble population: European EXPOLIS study]. / Exposition personnelle aux particules fines (PM 2.5) de la population grenobloise: l'étude européenne EXPOLIS.

BACKGROUND: The aim of this article is to describe PM(2.5) personal exposures within the Grenoble population and to identify the implications of such measurements on epidemiological or risk assessment studies of air quality. METHODS: Non smoking adult volunteers, selected in summer 1996 (n=40), in winter 1997 (n=40) and in summer 1998 (n=20), carried a case containing 2 PM(2.5) personal monitors. One of the monitors was running continuously for 48h. (cumulative exposures), the other one was running only while indoors (indoor exposure). PM(2.5) masses were determined by reflectometry (black smoke method) and by deionised weighting (Mettler MT5 micro-balance; gravimetric method). RESULTS: Cumulative PM(2.5) personal exposures ranged on average from 21.9 in summer to 36.7 microgram/m(3) in winter (arithmetic mean), using the gravimetric results; the dispersion of these personal exposures was greatest in winter (s.d.=23.1 microgram/m(3)) than in summer (s.d.=10.4 microgram/m(3)). There was a good correlation (R=0.7) between the reflectometry and weighting results in winter, but not in summer. Outdoor personal exposures, determined by difference between the cumulated and indoor masses, were slightly higher than the cumulative personal exposures: the geometric means was 49.6 microgram/m(3) (geometric standard deviation=2.7 microgram/m(3)) in summer and 55.1 microgram/m(3) (3.7 microgram/m(3)) in winter (gravimetric results). Due to these greater outdoor concentrations, the fraction of outdoor exposure was high (25%) relative to the small amount of time spent outdoors (less than 10%). CONCLUSION: These descriptive data, consistent with the literature, show the importance of "expology" studies aiming at characterizing PM(2.5) personal measurements across the year. This would lead, in the future, to optimizing the use of "ecological" estimates of exposures from ambient air concentrations provided by the ambient air quality networks, for the characterization of exposure in epidemiological or risk assessment studies.

[Conjugation of catecholamines: basic and physiopathological aspects]. / La conjugaison des catécholamines: aspects fondamentaux et physiopathologiques.

In man, the major portion of plasmatic and urinary catecholamines is found in a conjugated/sulfate form. The biological characteristics of the conjugates (formation sites, kinetics of appearance and disappearance from the plasma, genetic regulation, influence of biological factors) are different from those of the free forms. Physiopathological data show that the dosage conjugated catecholamines together with that of free amines, provides interesting informations on the integrative level of sympathetic activity and on the regulation of the catecholamines plasma concentrations by conjugation. In these two objectives, the dosage of DA sulfate proves very important.

[Eye tracking disorders in schizophrenic patients and their parents]. / La poursuite oculaire lente chez les patients schizophrènes et leurs parents.

UNLABELLED: Several studies have confirmed the existence of genetic factors in schizophrenia. However, the genotype predisposing for the disease is not known yet. Nevertheless, those genetic factors in the families of schizophrenic patients urge us to search for genetic vulnerability markers of schizophrenia. Ocular pursuit disorders, in particular, could be one of those vulnerability markers. Eye movements have been often tested in schizophrenia. Most of the schizophrenic patients have eye-tracking disorders and their biological relatives demonstrate an increased prevalence of eye-tracking impairments. The aim of the study was to research if smooth pursuit eye movements could be a vulnerability marker of schizophrenia. In order to have an indication about this hypothesis, impairments of smooth pursuit eye movements were researched in both schizophrenics and their parents. METHODS: Fifteen DSM IV schizophrenic patients stabilized at the time of the inclusion and not treated with lithium, benzodiazepines, barbiturates, or chloral hydrate; 19 parents without history of schizophrenic spectrum disorders (SADSLA and IPDE), and 2 groups of healthy subjects matched in age and sex with probands and with the parents, were included in the study. Parents only were included (fathers or mothers) in order to have an homogeneous population for the genetic risk and age. The eye-tracking paradigm used was a smooth pursuit task. The stimulus was a sinusoidal wave form moving on a horizontal line, with a frequency of 0.4 Hz and an amplitude of 30 degrees. Different parameters were measured: gain (ratio between the eye velocity and the target velocity) and saccades frequencies (catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks). For each parameter, analysis of covariance (ANCOVA) with age as covariable was carried out. For the results reaching the significance of 0.05, the Bonferroni correction was applied (level of significance 0.016). The effect size of the parameter was calculated ((the mean of the subjects minus the mean of the matched controls) divided by standard deviation of the two groups). According to Cohen, 0.20 indicates a small effect size, 0.50 indicates a medium effect size and 0.80 indicates a large effect size. RESULTS: Comparison between patients and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between patients and their matched controls. The size effects are 0.31 for the global gain, 0.20 for the movements to the left and 0.41 for the movements to the right. The frequencies of total saccades, catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks did not differ significantly between patients and their controls. The size effects for those parameters were 0.09, 0.03, 0.00, 0.39 and 0.63 respectively. Comparison between parents and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between the two groups. The size effects for those parameters were 0.00, 0.05 and 0.17 respectively. The frequency of total saccades did not differ significantly between the groups whereas the size effect was 0.63. The frequency of catch-up saccades was significantly more important in parents than in controls (p = 0.006) and the size effect was 0.80. The other saccadic parameters did not differ significantly between groups, their size effects were 0.24 for the back-up saccades, 0.21 for the anticipatory saccades and 0.00 for the square-wave-jerks. Whereas the gain of the patients had a tendency to be lower than the gain of their controls, no significant difference was observed between patients and their controls. Only a size effect of 0.63 for the frequency of square-wave-jerks was obtained. This large effect size suggests that the difference between patients and controls might be significant in a larger sample. The catch-up saccades frequency between parents and controls was significant. The differences between our study and the previous studies could be due to several factors. The paradigms used were different between the studies and our sample was small (only 15 patients and 19 relatives). Moreover, some patients in the previous studies were treated by lithium, drug well known to modify ocular pursuit and, finally the relatives in the other studies were 10 years older than ours and age is known to alter ocular pursuit. Since an impairment of the smooth pursuit was observed in the relatives of schizophrenic patients but not in the probands, this study does not support the hypothesis that eye-tracking disorders could be considered as a marker of vulnerability of schizophrenia.

[Acute necrotizing retinitis. Apropos of 2 cases]. / La rétinite nécrosante aiguë. A propos de deux cas.

Two cases of acute retinal necrosis are reported, the etiology of this affection being priorly defined. The lesions were bilateral in the first case, and retinal detachment developed: the first eye was inoperable, and surgery was unsuccessful for the second eye in spite of a salvage vitrectomy after a classical operation. We therefore treated the second case with immediate and massive corticotherapy, and, mainly, preventive total vitrectomy as soon as the first signs of vitreous retraction appeared and before the occurrence of retinal detachment. This preventive vitrectomy, not previously described to our knowledge, seems to provide favorable results.

[Bilateral retinal arteritis with multiple aneurysmal dilatations]. / Artérite rétinienne bilatérale avec dilatations anévrysmales multiples.

Bilateral retinal arteritis with multiple aneurysmal dilatations was described for the first time by Kincaid and Schatz in 1983. We have reported a typical case of this disease which occurred in a 49-year-old woman: retinal abnormalities were followed up during two years by repeated fluorescein angiographies. The etiology of the disease and its connexions with periarteritis nodosa are discussed. While the patient was given steroid therapy per os during 16 months, new segmental inflammation of retinal arteries were observed. Inflammation affecting retinal arteries would result in weakening of the arterial wall and aneurysmal outpouchings.

[Ophthalmologists without borders in Northern Cameroon]. / Ophtalmo sans Frontières au nord Cameroun.

Ophthalmologist without Borders (OWB) is a non-governmental organization founded in 1987 that operates mainly through medical and surgical care centers located in northern Cameroon. The goal of OWB is advancement of the fight against blindness and low vision in the third world. To achieve this goal OWB has four activities. In less than 10 years OWB has dispensed more than 90,000 consultations not only to patients with cataracts, the first cause of curable blindness, but also to numerous patients with conjunctivitis. Surgical therapy is another major activity of the OWB which has performed over 15,000 procedures with cataracts accounting for 85% of indications. Results have been encouraging but have demonstrated the need for dauntless surgeons and the importance of postoperative follow-up. Prevention and screening are priorities that are being progressively implemented. Training is an essential part of the mission of OWB with the ultimate aim being to leave local physicians and nurses with adequate facilities.

Exposure assessment of phthalates in French pregnant women: results of the ELFE pilot study.

The ubiquitous use of phthalate esters in plastics, building material, medical devices, personal care products and food packaging materials results in a widespread exposure of general population. This study reports measurement of urinary concentration of phthalate metabolites in France and provides a first assessment of the exposure of French pregnant women to this chemical class. For the majority of the phthalate metabolites, concentrations measured in urine were similar to those reported in previous studies except for two phthalates that were characterized by high concentrations of metabolites if compared to previous European and American studies: DiNP (Di-iso-nonylphthalate) and DEHP (Di(2-ethylhexyl)phthalate). In a second part of the study, a pharmacokinetic model was used in order to gain understanding on exposure to DEHP. A high concentration of the primary metabolite of DEHP, MEHP (Mono(2-ethylhexyl)phthalate), was thus identified probably because of a very recent exposure to perfusion materials at the hospital. Pharmacokinetics modelling highlighted that gathering data on the time gap between exposure and biomonitoring is an essential information requirement for reconstructing the dose of non persistent pollutants. Information about exposure pathway is also crucial for conducting effective reverse dosimetry.

Comparative effect of tropolone and diosmin on venous COMT and sympathetic activity in rat.

The ability of diosmin to inhibit venous catechol-O-methyltransferase (COMT) activity was studied comparing it with tropolone in rat superior mesenteric vein (MV), inferior vena cava (IVC) and saphenous vein (SV). Diosmin inhibited COMT activity in the mesenteric vein after 200 and 400 mg/kg i.p., but only at 400 mg/kg in IVC. The COMT inhibitory effect of diosmin (400 mg/kg) was smaller than that of tropolone (50 mg/kg). Furthermore, diosmin, but not tropolone, increased urinary normetanephrine (NMN) excretion (+56%) at 400 mg/kg and that of 3-methoxy 4-hydroxyphenylglycol (MHPG) in a dose-dependent way, thus suggesting that diosmin may exert an activating effect on sympathetic activity. Both mechanism--local inhibition of COMT and enhanced sympathetic activity--may contribute to increase NE levels in the synaptic clefts of the vascular wall and explain the venoconstrictor effect of this drug.

[Familial agenesis of the lacrimal glands and ducts]. / Agénésie familiale des points et canalicules lacrymaux.

Authors report three cases of hereditary malformation of excretory lacrymal system, two children and their father. One of the two children have a lacrymal fistula. A surgical treatment was successful.