[Practice review on the use of proton pump inhibitors]. / Utilisation des inhibiteurs de la pompe à protons en pratique.

Proton pump inhibitors (PPI), these antacid drugs that have revolutionized the treatment of peptic disease, have become, in the daily practice of primary care physicians as well as hospital practitioners, an inescapable treatment since their introduction on the market in 1989, and even the 4th most prescribed drug class in Switzerland. Therefore, multiple studies as well as numerous recommendations and expert opinions on their effectiveness and use have been -published. This article will present their proper use, by reviewing the knowledge available to date on these essential drugs in our -therapeutic arsenal.

Les inhibiteurs de la pompe à protons (IPP), ces médicaments antiacides ayant révolutionné le traitement de la maladie peptique, sont devenus, dans la pratique quotidienne du médecin de premier recours tout comme du praticien hospitalier, un traitement incontournable depuis leur mise sur le marché en 1989, et sont même la 4e classe médicamenteuse la plus prescrite en Suisse. Par conséquent, de multiples études ainsi que de nombreux ­avis d'experts et recommandations sur leur efficacité et leur ­utilisation ont été publiés. L'objectif de cet article est de ­présenter leur bon usage et de passer en revue les connaissances actuel­lement disponibles sur ces médicaments essentiels de notre ­arsenal thérapeutique.

Simultaneous determination of melatonin and 6-hydroxymelatonin in human overnight urine by LC-MS/MS.

For the quantification of the pineal hormone melatonin and its metabolite, 6-hydroxymelatonin, in human overnight urine, a single accurate method by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed. Urine samples were deconjugated using ß-glucuronidase/arylsulfatase from Helix pomatia before solid phase extraction (SPE) purification. Chromatographic separation was performed using a reverse phase C18 column with a 7-minute gradient elution. Water was used as matrix to prepare the calibration standards, and deuterated analogues of melatonin and 6-hydroxymelatonin were used as internal standards. This newly developed method was validated in terms of linearity, accuracy, repeatability, intermediate precision, recovery, matrix effect, and stability according to the guidelines of the European Medicines Agency. The method was successfully applied to the analysis of overnight urine samples from 12 healthy volunteers, showing significant correlations of urinary melatonin and 6-hydroxymelatonin excretion rates with age. The urinary 6-hydroxymelatonin to melatonin ratio was also established and will be assessed in further studies as a potential endogenous metric of CYP1A2 activity.

Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs.

AIM: Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin-Resistant dogs with increase plasma triglycerides. METHODS: HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured. RESULTS: NA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very-low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification. CONCLUSION: NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile.

Integrating the therapeutic into the developmental in treating disturbed adolescents.

This clinical study is organized around the treatment of a late adolescent who feared suiciding impulsively during an immobilizing depression and who proceeded to develop other severe symptoms. Yet he steadfastly refused to take medication and objected to seeing a therapist as well. His reason was an overriding wish to deal with his difficulties himself, a feature of his normal developmental imperative to emancipate to a young-adult level of psychological autonomy. Thus, the therapeutic task was to simultaneously hold him in treatment while supporting that normal developmental requisite. Elaborating upon this integration of the psychodynamic and the developmental is the major purpose of this study.

Myristic acid increases dihydroceramide Δ4-desaturase 1 (DES1) activity in cultured rat hepatocytes.

Dihydroceramide Δ4-desaturase 1 (DES1) catalyzes the last step of the de novo ceramide biosynthesis, which consists of the introduction of a trans Δ4-double bond in the carbon chain of the dihydroceramide. It was previously observed that myristic acid binds DES1 through N-myristoylation. This N-terminal modification significantly increased the activity of the recombinant DES1 in COS-7 cells and targeted part of the enzyme initially present in the endoplasmic reticulum to the mitochondrial outer membrane, leading to an increase in ceramide levels. Since these results were obtained in a recombinant COS-7 cell model with high expression of rat DES1, the purpose of the present study was to investigate if the native DES1 enzyme was really upregulated by its N-myristoylation in cultured rat hepatocytes. We first showed that DES1 was the main dihydroceramide desaturase isoform expressed in rat hepatocytes. In this model, the wild-type myristoylable recombinant form of rat DES1 was found in both the endoplasmic reticulum and the mitochondria whereas the mutated non-myristoylable recombinant form (N-terminal glycine replaced by an alanine) was almost exclusively localized in the endoplasmic reticulum, which evidenced the importance of the myristoylation. Then, we showed that compared to other fatty acids, myristic acid was the only one to increase native DES1 activity, in both total cell lysates and mitochondrial fractions. The myristic acid-associated increase in DES1 activity was not linked to elevated mRNA or protein expression but more likely to its N-terminal myristoylation. Finally, the myristic acid-associated increase in DES1 activity slightly enhanced the number of apoptotic cells.

[The EU drinking water recommendations: objectives and perspectives]. / Die EU Trinkwasserrichtlinie: Zielsetzung und Weiterentwicklung.

Protection of our drinking water resources and provision of safe drinking water are key requirements of modern water management and health policy. Microbiological and chemical quality standards have been established in the EU water policy since 1980, and are now complemented by a comprehensive protection of water as a resource. This contribution reflects a presentation at the scientific conference of the Federal Associations of Physicians and Dentists within the Public Health Service in May 2011 and provides an overview on objectives and challenges for drinking water protection at the European level.

Effect of citrus polyphenol- and curcumin-supplemented diet on inflammatory state in obese cats.

Among obesity-associated disorders, low-grade inflammation has been described. The putative therapeutic properties of citrus and curcumin polyphenols could be associated with their anti-inflammatory properties. Two diets supplemented either with hesperidin (0.05 %) and naringin (0.1 %) from citrus extract or with highly bioavailable curcumin from Curcuma longa extract (0.09 %) were fed to eight obese cats for two 8-week periods (cross-over study design) while maintaining animals in an obese state. Plasma acute-phase protein (APP; α1-acid glycoprotein (AGP), serum amyloid A and haptoglobin) levels were assessed before and at the end of each test period. TNF-α, IL-1ß, IL-2, IL-4, IL-5, IL-10, IL-12, IL-18, transforming growth factor-ß, interferon (IFN)-γ mRNA levels were determined in peripheral blood mononuclear cells (PBMC) by real-time PCR. Compared with pre-study values, supplementation with citrus polyphenols resulted in lower plasma AGP and haptoglobin concentrations, while that with curcumin resulted in lower plasma AGP concentration. There were no differences between the supplementations. TNF-α, IL-1ß, IL-4, IL-5, IL-10, IL-12, IL-18, transforming growth factor-ß, mRNA levels remained unaffected by either dietary supplementation. In contrast, IFN-γ and IL-2 mRNA levels were lower at the end of the citrus and the curcumin supplementation, respectively. There were no differences between the supplementations. The present study results show a slight effect of citrus and curcumin supplementation on inflammatory markers expressed by PBMC, and a decreased concentration of APP, which are mainly expressed by the liver. This would confirm that hesperidin and naringin or highly bioavailable curcumin extract have beneficial effects, targeted in the liver and could improve the obesity-related inflammatory state.

Lipid profile and insulin sensitivity in rats fed with high-fat or high-fructose diets.

The occurrence and severity of obesity- and insulin resistance-related disorders vary according to the diet. The aim of the present longitudinal study was to examine the effects of a high-fat or a high-fructose diet on body weight (BW), body fat mass, insulin sensitivity (IS) and lipid profiles in a rat model of dietary-induced obesity and low IS. A total of eighteen, 12-week-old male Wistar rats were divided into three groups, and were fed with a control, a high-fat (65 % lipid energy) or a high-fructose diet (65 % fructose energy) for 10 weeks. BW, body fat mass ((2)H2O dilution method), IS (euglycaemic-hyperinsulinaemic clamp technique), plasma glucose, insulin, NEFA, TAG and total cholesterol were assessed before and at the end of 10-week period. Cholesterol was measured in plasma lipoproteins separated from pooled samples of each group and each time period by using fast-protein liquid chromatography. All rats had similar BW at the end of the 10-week period. Body fat mass was higher in the high-fat group compared to the control group. There was no change in basal glycaemia and insulinaemia. The IS was lower in the high-fat group and was unchanged in the high-fructose group, compared to the control group. Plasma TAG concentration and cholesterol distribution in lipoproteins did not change over time in any group. Plasma NEFA concentration decreased, whereas plasma TAG concentration increased over time, regardless of the diet in both cases. The 10-week high-fat diet led to obesity and low IS, whereas rats fed with the high-fructose diet exhibited no change in IS and lipidaemia. The high-fat diet had more deleterious response than high-fructose diet to induce obesity and low IS in rats.

Nicotinic acid decreases apolipoprotein B100-containing lipoprotein levels by reducing hepatic very low density lipoprotein secretion through a possible diacylglycerol acyltransferase 2 inhibition in obese dogs.

Apolipoprotein B100 (apoB100) is an essential component of very low density lipoprotein (VLDL) and low-density lipoprotein (LDL), both independent markers of cardiovascular risk. Nicotinic acid (NA) is an efficacious drug for decreasing VLDL and LDL, but the underlying mechanisms are unclear. For this purpose, six obese insulin-resistant dogs were given 350 mg/day of NA for 1 week and then 500 mg/day for 3 weeks. Turnover of apoB100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was used to derive kinetic parameters before and at the end of NA treatment. Hepatic diacylglycerol acyltransferase 2 (DGAT2), microsomal triglyceride transfer protein (MTP), hepatic lipase (HL), and adipose lipoprotein lipase (LPL) mRNA expression was also determined. NA treatment decreased plasma triglyceride (TG) (p < 0.001), VLDL-TG (p < 0.05), total cholesterol (p < 0.0001), and LDL cholesterol (p < 0.05), whereas plasma nonesterified fatty acids were unchanged. The decrease in VLDL-apoB100 concentration (p < 0.001) was the result of a lower absolute production rate (APR) (p < 0.001), despite a moderate decrease (p < 0.05) in fractional catabolic rate (FCR). LDL-apoB100 concentration was reduced (p < 0.05), an effect related to a decrease in LDL APR (p < 0.05) and no change in FCR. NA treatment reduced DGAT2 expression (p < 0.05), whereas MTP, HL, and LPL expression was unchanged. Our results suggest that NA treatment reduced VLDL and LDL concentration as a consequence of a decrease in VLDL production.

Hypertriglyceridaemic insulin-resistant obese dog model: effects of high-fat diet depending on age.

In humans, obesity is closely associated with insulin resistance (IR) and dyslipidaemia. The purpose of this study was to explore the effect of age on metabolic disturbances related to obesity in dogs (n = 25). Three age-groups of dogs (puppies, young adults and mature adults) were overfed to induce obesity, and body composition, insulin sensitivity index (I(IS)) (euglycaemic-hyperinsulinaemic glucose clamp) and plasma lipids were measured. Fat mass was similar in the three obese groups (30 +/- 1% in puppies, 34 +/- 1% in young adults and 39 +/- 1% in mature adults). In mature adults, body weight (BW) increased (+45%, p < 0.001) and I(IS) decreased (-60%, p < 0.001) over 22 weeks. In young adults, BW gain was similar but slower (60 weeks) and I(IS) decreased to a lesser extent (-49%, p < 0.001). Overfed puppies weighed 30% more (p < 0.01) than normally-fed control puppies, but there was no change in I(IS). Unlike young and mature adults, obese puppies did not exhibit significant changes in triglycerides (TG) and free fatty acid concentrations. In conclusion, as in humans, obese dogs develop IR that is associated with high TG levels; however, younger animals may be better able to balance energy needs with energy consumption.

Liver lipid metabolism.

The liver plays a key role in lipid metabolism. Depending on species it is, more or less, the hub of fatty acid synthesis and lipid circulation through lipoprotein synthesis. Eventually the accumulation of lipid droplets into the hepatocytes results in hepatic steatosis, which may develop as a consequence of multiple dysfunctions such as alterations in beta-oxidation, very low density lipoprotein secretion, and pathways involved in the synthesis of fatty acids. In addition an increased circulating pool of non-esterified fatty acid may also to be a major determinant in the pathogenesis fatty liver disease. This review also focuses on transcription factors such as sterol-regulatory-element-binding protein-1c and peroxisome proliferator-activated receptor alpha, which promote either hepatic fatty acid synthesis or oxidation.

Substitution of dietary oleic acid for myristic acid increases the tissue storage of α-linolenic acid and the concentration of docosahexaenoic acid in the brain, red blood cells and plasma in the rat.

Various strategies have been developed to increase the cellular level of (n-3) polyunsaturated fatty acids in animals and humans. In the present study, we investigated the effect of dietary myristic acid, which represents 9% to 12% of fatty acids in milk fat, on the storage of α-linolenic acid and its conversion to highly unsaturated (n-3) fatty acid derivatives. Five isocaloric diets were designed, containing equal amounts of α-linolenic acid (1.3% of dietary fatty acids, i.e. 0.3% of dietary energy) and linoleic acid (7.0% of fatty acids, i.e. 1.5% of energy). Myristic acid was supplied from traces to high levels (0%, 5%, 10%, 20% and 30% of fatty acids, i.e. 0% to 6.6% of energy). To keep the intake of total fat and other saturated fatty acids constant, substitution was made with decreasing levels of oleic acid (76.1% to 35.5% of fatty acids, i.e. 16.7% to 7.8% of energy) that is considered to be neutral in lipid metabolism. After 8 weeks, results on physiological parameters showed that total cholesterol and low-density lipoprotein-cholesterol did not differ in the diets containing 0%, 5% and 10% myristic acid, but were significantly higher in the diet containing 30% myristic acid. In all the tissues, a significant increasing effect of the substitution of oleic acid for myristic acid was shown on the level of both α-linolenic and linoleic acids. Compared with the rats fed the diet containing no myristic acid, docosahexaenoic acid significantly increased in the brain and red blood cells of the rats fed the diet with 30% myristic acid and in the plasma of the rats fed the diet with 20% myristic acid. Arachidonic acid also increased in the brain of the rats fed the diet with 30% myristic acid. By measuring Δ6-desaturase activity, we found a significant increase in the liver of the rats fed the diet containing 10% of myristic acid but no effect at higher levels of myristic acid. These results suggest that an increase in dietary myristic acid may contribute in increasing significantly the tissue storage of α-linolenic acid and the overall bioavailability of (n-3) polyunsaturated fatty acids in the brain, red blood cells and plasma, and that mechanisms other than the single Δ6-desaturase activity are involved in this effect.

Swiss psychiatrists beliefs and attitudes about cannabis risks in psychiatric patients: ideologically determined or evidence-based?

The objective of this survey was to assess the beliefs of Swiss psychiatrists about the risks associated with cannabis, and to assess their prohibitive attitudes toward their patients. Eighty-two doctors agreed to fill-up the questionnaire. Cluster analysis retained a 3-cluster solution. Cluster 1: "Prohibitionists" believed that cannabis could induce and trigger all forms of psychiatric disorder, and showed a highly prohibitive attitude. Cluster 2: "Causalists" believed that schizophrenia, but not other psychiatric disorders, could be induced and triggered. Cluster 3: "Prudent liberals" did not believe that psychiatric disorders could be induced by cannabis, and were generally less prohibitive.

Myristic acid increases the activity of dihydroceramide Delta4-desaturase 1 through its N-terminal myristoylation.

Dihydroceramide Delta4-desaturase (DES) catalyzes the desaturation of dihydroceramide into ceramide. In mammals, two gene isoforms named DES1 and DES2 have recently been identified. The regulation of these enzymes is still poorly understood. This study was designed to examine the possible N-myristoylation of DES1 and DES2 and the effect of this co-translational modification on dihydroceramide Delta4-desaturase activity. N-MyristoylTransferases (NMT) catalyze indeed the formation of a covalent linkage between myristoyl-CoA and the N-terminal glycine of candidate proteins, as found in the sequence of DES proteins. The expression of both rat DES in COS-7 cells evidenced first that DES1 but not DES2 was associated with an increased dihydroceramide Delta4-desaturase activity. Then, we showed that recombinant DES1 was myristoylated in vivo when expressed in COS-7 cells. In addition, in vitro myristoylation assay with a peptide substrate corresponding to the N-terminal sequence of the protein confirmed that NMT1 has a high affinity for DES1 myristoylation motif (apparent K(m)=3.92 microM). Compared to an unmyristoylable mutant form of DES1 (Gly replaced by an Ala), the dihydroceramide Delta4-desaturase activity of the myristoylable DES1-Gly was reproducibly and significantly higher. Finally, the activity of wild-type DES1 was also linearly increased in the presence of increased concentrations of myristic acid incubated with the cells. These results demonstrate that DES1 is a newly discovered myristoylated protein. This N-terminal modification has a great impact on dihydroceramide Delta4-desaturase activity. These results suggest therefore that myristic acid may play an important role in the biosynthesis of ceramide and in sphingolipid metabolism.

Efficacy and tolerability of quetiapine in cluster B personality disorder: an open-label study.

Objective. The aim of this open-label 8-week study was to assess the effectiveness of quetiapine on aggressive behaviour and social dysfunctions in patients suffering from a cluster B personality disorder (DSM-IV). Methods. The visits were performed at baseline and at days 14, 28 and 56. After a standard titration schedule, the patients received a dose augmented or reduced dose, within a range from 50 to 400 mg/day during the visits, depending on efficacy and tolerance. Assessment of efficacy was based on the French version of the Social Disability and Aggression Scale SDAS (SDAS-21). Response was defined as a decrease of ≥50% reduction of the total scores compared to baseline. Tolerability was assessed with the CGI, UKU, EPS-scales. Results and conclusion. Eight of the 12 patients included received 200 mg/day quetiapine after titration (all patients: 50-400 mg/day). At week 8, five out of 12 patients were responders based on the SDAS-21 scores for the average expression of the symptoms, and six out of 12 on the basis of SDAS-21 scores for the peak expression. There was a significant correlation between weight change and total SDAS variation (Kendall's τb= -0.644; p=0.02). These findings should be reexamined in further studies.

Routine therapeutic drug monitoring in patients treated with 10-360 mg/day citalopram.

From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications. Dose-corrected CIT plasma concentrations (C/D ratio) were 2.51 +/- 2.25 ng mL-1 mg-1 (n = 258; mean +/- SD). Patients >65 years had significantly higher dose-corrected CIT plasma concentrations (n = 56; 3.08 +/- 1.35 ng mL-1 mg-1) than younger patients (n = 195; 2.35 +/- 2.46 ng mL-1 mg-1) (P = 0.03). CIT plasma concentrations in the generally recommended dose range were [mean +/- SD, (median)]: 57 +/- 64 (45) ng/mL (10-20 mg/d; n = 64), 117 +/- 95 (91) ng/mL (21-60 mg/d; n = 96). At higher than usual doses, the following concentrations of CIT were measured: 61-120 mg/d CIT, 211 +/- 103 (190) ng/mL (n = 93); 121-200 mg/d: 339 +/- 143 (322) ng/mL (n = 70); 201-280 mg/d: 700 +/- 408 (565) ng/mL (n = 18); 281-360 mg/d: 888 +/- 620 (616) ng/mL (n = 4). When only one sample per patient (at the highest daily dose if repeated dosages) is considered, there is a linear and significant correlation (n = 48, r = 0.730; P < 0.001) between daily dose (10-200 mg/d) and CIT plasma concentrations. In experiments with dogs, DDCIT was reported to affect the QT interval when present at concentrations >300 ng/mL. In this study, DDCIT concentration reached 100 ng/mL in a patient treated with 280 mg/d CIT. Twelve other patients treated with 140-320 mg/d CIT had plasma concentrations of DDCIT within the range 52-73 ng/mL. In a subgroup comprised of patients treated with > or =160 mg/d CIT and with CIT plasma concentrations < or =300 ng/mL, and patients treated with < or =200 mg/d CIT and CIT plasma concentrations > or = 600 ng/mL, the enantiomers of CIT and DCIT were also analyzed. The highest S-CIT concentration measured in this subgroup was 327 ng/mL in a patient treated with 140 mg/d CIT, but the highest S-CIT concentration (632 ng/mL) was measured in patient treated with 360 mg/d CIT. In conclusion, there is a highly linear correlation between CIT plasma concentrations and CIT doses, well above the usual dose range.

EU policy on nutrients emissions: legislation and implementation.

After 25 years of EU water legislation the European Union has just thoroughly restructured its water policy. The European Parliament and the Council, following a tough conciliation procedure between the two legislators, have in summer 2000 agreed a proposal by the European Commission for a Water Framework Directive. This legislation will have the following main objectives: integrated river basin management across borders, with coordinated programmes of measures protection of all waters, surface waters and groundwater, in quality and quantity with a proper ecological dimension emissions and discharges controlled by a "combined approach" of emission limit values and quality standards, plus the phasing out of particularly hazardous substances introducing water pricing policies strengthening public participation This new Water Framework Directive adopted in September 2000 will complement existing EU water legislation on nutrients reduction--the 1991 Directive on nitrates pollution from agricultural sources and the 1991 Directive on urban waste water treatment. These Directives will remain main pillars of EU water policy whilst at the same time being integrated into the river basin management in a coherent way.

Identification of barley and rye varieties using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry with neural networks.

Cereal varieties are normally identified using time-consuming methods such as visual examination of either the intact grain or one-dimensional electrophoretic patterns of the grain storage proteins. A fast method for identification of wheat (Triticum aestivum L.) varieties has previously been developed, which combines analysis of alcohol-soluble wheat proteins (gliadins) using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry with neural networks. Here we have applied the same method for the identification of both barley (Hordeum vulgare L.) and rye (Secale cereale L.) varieties. For barley, 95% of the mass spectra were correctly classified. This is an encouraging result, since in earlier experiments only a grouping into subsets of varieties was possible. However, the method was not useful in the classification of rye, due to the strong similarity between mass spectra of different varieties.

What is the target?

Reconciling the differential perspective with the Piagetian perspective is a very difficult task. The Piagetian perspective admits the existence of interindividual differences but interprets them as noise masking the universal logical succession of structures, whereas the differential perspective views development as consisting of "vicarious processes." As a matter of historical fact, the main aim of the "procedural studies" carried out in Geneva was to introduce concrete microgenesis into the macrogenetic Piagetian model.

Ocular motility and visuo-spatial attention in children with periventricular leukomalacia.

Periventricular leukomalacia (PVL) is known to cause visual, motor, and cognitive impairments varying in their severity. Most studies focused on impairment at early ages. Little is known about the PVL's later outcome. Effects of neural plasticity are for instance insufficiently known to prognose precisely their behavioral outcome. It is even hard to determine the consequence of one defect on global development over time. Because of the established neural link between eye motion and space perception, 5-to-9 year-old PVL's were tested in visual detection, postural control, and space attention tasks. In this paper, discussion will focus on behavioral asymmetry, developmental outcome, and brain injury.