Neurology 2006 May 23; 66(10): 1495-9 (Read article online)

Pressler RM, Binnie CD, Coleshill SG, Chorley GA, Robinson RO

BACKGROUND: Lamotrigine does not affect cognition in healthy adult volunteers or adult patients with epilepsy, but its effect on cognition in children is uncertain. OBJECTIVE: To compare the effect of lamotrigine and placebo on cognition in children with well-controlled or mild epilepsy. METHOD: In a double-blind, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Each treatment phase was 9 weeks, the crossover period 5 weeks. A neuropsychological test battery was performed during EEG monitoring at baseline and at the end of placebo and drug phases. The paired Student' t test was used for statistical analysis for neuropsychological data (two tailed) with a p value of 0.01 considered significant. Carryover and period effect were analyzed with generalized linear modeling (SPSS 10). RESULTS: Forty-eight children completed the study. Seizure frequency was similar during both treatment phases. No significant difference was found in continuous performance, binary choice reaction time, verbal and nonverbal recognition, computerized visual searching task, verbal and spatial delayed recognition, and verbal and nonverbal working memory between placebo and lamotrigine treatment phase. There was no significant carryover and period effect when corrected for randomization. CONCLUSION: Lamotrigine exhibits no clinically significant cognitive effects in adjunctive therapy for children with epilepsy.

Fertil Steril 2006 May 20; (Read article online)

Bedaiwy MA, Casper RF

This pilot study examined the effect of a low-dose E and pulsed progestogen hormone therapy (HT) regimen for add-back during long-term GnRH-agonist therapy on bone mineral density (BMD) in five patients with stage IV endometriosis. Bone mineral density was stable after initiation of HT for the entire follow-up period (up to 10 years). One patient stopped her treatment on two occasions to conceive and was successful each time with delivery of a normal baby. No patient had return of pelvic pain after HT add-back.

No To Hattatsu 2006 May; 38(3): 177-81 (Read article online)

Adachi T, Hirabayashi S, Shiota M, Suzuki S, Wakamiya E, Kitayama S, Kono M, Maeoka Y, Koeda T

The purpose of this study is to clear up the difference between Asperger's disorder (AS) and high functioning autism (HFA) with a newly developed test, the metaphor and sarcasm scenario test (MSST) can be used to distinguish pervasive developmental disorder (PDD) from attention deficit/hyperactivity disorders (AD/HD). So 66 AS children, 20 HFA children and 37 AD/HD children were selected, compared the profiles of score on the MSST. The results showed that the inability to understand sarcastic situation was specific to group with AS, both group with HFA and AD/HD were differ little to understand between metaphor and sarcasm. In this study suggest differences in situational recognition among the PDD subtypes, the clinical symptoms of PDD reflects characteristics of AS.

J Chromatogr B Analyt Technol Biomed Life Sci 2006 May 19; (Read article online)

Martins LF, Yegles M, Chung H, Wennig R

A novel chiral derivatisation agent, (2S,4R)-N-heptafluorobutyryl-4-heptafluorobutoyloxy-prolyl chloride, was used for the indirect resolution of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) enantiomers using gas chromatography coupled to mass spectrometry operating in the negative-ion chemical ionization mode (GC/MS-NICI). This new chiral derivatisation reagent was readily obtained in optically pure form after a simple two-step synthesis. Optimal derivatisation was accomplished in 15min at room temperature in a carbonate buffer and the resulting diastereoisomers were base line separated by GC in 12min only. No racemization was observed during the derivatisation. The method was applied and fully validated for the enantiomeric quantification of amphetamines and methylenedioxylated amphetamines in hair. The analyses of 24 hair specimens from suspected ATS abusers showed that 24 cases were positive for MA and/or AM enantiomers and that in most cases the concentrations of (R)-MA and (R)-AM exceeded those of the corresponding (S)-enantiomers. One hair specimen was tested positive for both enantiomers of MDMA and MDA.

Ann Readapt Med Phys 2006 Apr 25; (Read article online)

Belmont A, Agar N, Hugeron C, Gallais B, Azouvi P

Fatigue is frequent and disabling in patients with traumatic brain injury (TBI). Its mechanisms are complex and multifactorial. We performed a literature review of reports of the condition using the following key words: brain injury, depression, neuroendocrine dysfunction, and treatment. Five scales have been used to evaluate fatigue in TBI patients: the Fatigue Severity Scale, the visual analog scale (VAS) for fatigue, the Fatigue Impact Scale, the Barrow Neurological Institute (BNI) Fatigue Scale and the Cause of Fatigue (COF) Questionnaire. The BNI Fatigue Scale and the COF Questionnaire have been designed specifically for brain-injured patients. Fatigue is present in 43-73% of patients and is one of the first symptoms for 7% of them. Fatigue does not seem to be significantly related to injury severity not to time since injury. It can be related to mental effort necessary to overcome attention deficit and slowed processing ("coping hypothesis"). It can also be related to sleeping disorders and depression, although the relation between fatigue and depression are debated. Finally, fatigue can also be related to infraclinical pituitary insufficiency (growth hormone insufficiency, hypocorticism). To date, no published study of treatment of fatigue after TBI exists.

Immunity 2006 May; 24(5): 591-600 (Read article online)

Czopik AK, Bynoe MS, Palm N, Raine CS, Medzhitov R

Semaphorins play an essential role in axonal guidance, and emerging evidence points to diverse functions of several Semaphorin family members in the immune system. Semaphorin 7A (Sema7A) promotes axonal growth in the central nervous system. Here, we show that Sema7A also plays a critical role in negative regulation of T cell activation and function. T cells deficient in Sema7A exhibit enhanced homeostatic and antigen-induced proliferative response. Moreover, autoreactive Sema7A-deficient T cells mediate aggressive autoimmune disease. The deficiency in Sema7A leads to defective TCR downmodulation and T cell hyperresponsiveness. These results demonstrate an important role of Sema7A in limiting autoimmune responses and add to growing evidence of shared signaling pathways used by the immune and nervous systems.

Water Res 2006 May 19; (Read article online)

Crosa G, Froebrich J, Nikolayenko V, Stefani F, Galli P, Calamari D

Although the use of the water resources in Uzbekistan is strongly limited by their quality, it has to be noted that there is a lack of information and data within the international scientific literature with regard to the water chemical characteristics of the Amu Darya River, one of the main water resources in Central Asia. To add to such knowledge, this paper examines the spatial and temporal variation of the water quality of the Amu Darya River in order to assess its degree of degradation and the main causal factors. The functional relationships of the pollutants with respect to the flow regime are investigated. Finally an "opportune temporal window" for water withdrawal for filling the reservoirs, in relation to human consumption, will be indicated. The high salinization levels of the waters are mainly due to the presence of sulphates and chlorine. At the up-stream site salinity, although presenting elevated concentrations, does not exceed palatability levels; after the 450km point the opportune temporal window for water withdrawal with acceptable salinity values is reduced to the period from May to September. Two main driving forces govern the temporal variation of the salinity of the Amu Darya water: a low drainage density of the area which limits the salt loads induced by the natural runoff processes, and snow and glacier melting in the upper catchment area which promotes dilution of the dissolved salts during the high-flow period. During low-flow periods salinity is strongly influenced by the return of waters used for land washing and irrigation.

Synapse 2006 May 19; 60(2): 172-183 (Read article online)

Galineau L, Wilson AA, Garcia A, Houle S, Kapur S, Ginovart N

This study reports on the binding kinetics and pharmacological characterization of [(11)C]-(+)-PHNO ((+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol), a promising agonist radiotracer for in vivo evaluation of the D2-receptor. Its in vivo kinetics were monitored in rat striatum and cerebellum using a beta-sensitive Microprobe system. Control studies showed that [(11)C]-(+)-PHNO binding was reversible and reached a peak time equilibrium of specific binding in striatum 30 min after radiotracer injection. The binding potential (BP) calculated by the simplified reference tissue model was 3-fold higher than that measured with [(11)C]-(-)-NPA (2.14 +/- 0.50 vs. 0.66 +/- 0.01, respectively). In contrast, the methyl analog of (+)-PHNO, [(11)C]-(+)-MHNO, which displayed promising D2-agonist properties in vitro, showed no specific binding in the striatum in vivo. [(11)C]-(+)-PHNO binding was totally blocked by raclopride (1 mg/kg; i.v.) and 97% displaced by NPA (2 mg/kg; i.v.) suggesting that [(11)C]-(+)-PHNO was specific for the high affinity states of D2/D3-receptors. However, (+)-PHNO (1 mg/kg; i.v.) totally blocked and displaced [(11)C]-raclopride binding in striatum. Thus, (+)-PHNO at high concentrations might be able to bind to the low affinity states of D2/D3-receptors. After an amphetamine pretreatment (2 mg/kg; i.v.), a 69% decrease in BP value (P < 0.05) was observed for [(11)C]-(+)-PHNO indicating that its binding was highly sensitive to variations of endogenous DA. These results substantiate the use of [(11)C]-(+)-PHNO as an agonist radiotracer for D2-imaging. The sensitivity of its binding to competition with endogenous DA suggests an association with the subset of high affinity state D2-receptors. Synapse 60:172-183, 2006. (c) 2006 Wiley-Liss, Inc.

J Food Prot 2006 May; 69(5): 1134-8 (Read article online)

Visciano P, Perugini M, Amorena M, Ianieri A

The occurrence of polycyclic aromatic hydrocarbons (PAHs) in smoked fish as a consequence of cold smoking was studied. Raw fillets of Salmo salar from Norway or the Irish Sea were sampled in a modern smokehouse and examined for PAH content. The same fillets, labeled with an identification number, were sampled immediately after the smoking process and analyzed. Among the investigated compounds, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, and benzo[ghi]perylene were detected in both raw and smoked fillets. No significant difference (P < 0.01) was observed between raw and smoked samples in the concentrations of six PAHs, but significant differences were found for fluorene, anthracene, fluoranthene, benz[a]anthracene, and benzo[ghi]perylene. Results confirm that PAHs concentrations in smoked fish are the product of both sea pollution and the smoking process. A modern smoking plant with an external smoke generator and a mild treatment as described here will not add significantly to the concentration of PAHs, except for some compounds.

Toxicol Sci 2006 May 19; (Read article online)

Lewis NA, Williams TD, Chipman JK

Cytochrome P450 1A (CYP 1A) is a member of a multigene family of xenobiotic metabolizing enzymes. CYP 1A is highly inducible by numerous environmental contaminants including polycyclic aromatic hydrocarbons (PAHs), and is widely used in bio-monitoring studies. Therefore understanding the regulation of this gene is important for accurate interpretation of biomarker data. We describe here the functional role of a metal response element in the European flounder CYP 1A promoter region. To help elucidate the potential role of this MRE, reporter gene constructs with or without site-directed mutagenesis, were used in conjunction with a dual luciferase assay. The electrophoretic mobility shift assay (EMSA) was also used to investigate potential protein binding at this MRE site. Treatment with the prototypical PAH 3-methylcholanthrene (3MC) (1.0 microM) produced a dose-dependent response at the CYP 1A promoter, whereas treatment with cadmium (0 - 1.0 microM) produced little transcriptional activity at either the wild-type or mutated promoter. Co-treatment with cadmium (1.0 microM) and 3MC (1.0 microM) reduced induction at this promoter to 1.83 fold compared to 3MC treatment alone (4.0-fold induction). Mutation of the MRE site resulted in abolishment of this cadmium-related loss of 3MC-dependent activity. Furthermore, a retarded band was observed in the EMSA when the MRE was used as a probe and incubated with liver nuclear protein from flounder treated with cadmium. The results not only add to knowledge of the diversity in vertebrate CYP 1A regulation, but raise the complexity of interpretation of CYP 1A induction in monitoring studies that involve mixtures of PAH and metals.

Neurology 2006 May 23; 66(10 Suppl 4): S2-9 (Read article online)

Poewe W

Slowing of disease progression remains a major unmet need in the treatment of Parkinson's disease (PD). Multiple factors are responsible for progression of disability in this disorder including worsening of cardinal motor features due to progressive nigral pathology, the evolution of poorly levodopa-responsive symptoms like freezing, postural instability and falls as well as motor complications of sustained treatment with levodopa. In addition, non-motor symptoms including cognitive decline, autonomic failure, sleep disorders and pain become increasingly prevalent with advancing disease and add to the overall burden of this disease. So far no treatment has been shown to significantly retard the progression of overall disability, and neuroprotective trials have been limited by design issues and a narrow focus on rates of decline of motor scores or imaging markers of nigrostriatal dysfunction only. Current evidence suggests that it may soon be possible to define populations at increased risk to develop PD and thus to target the "preclinical" phase of PD for neuroprotection. Such future trials will test intervention for their ability to prevent or retard the development of clinically overt PD in at-risk individuals.

Clin Nucl Med 2006 Jun; 31(6): 335-7 (Read article online)

Rubino V, Kirkwood ID, Bellon M, Chatterton BE

A 39-year-old man presented to the emergency department with an ischemic left hand after inadvertent injection of amphetamine into the left radial artery 4 days before presentation. Examination revealed a gangrenous left thumb and index finger without clear demarcation and a weak radial pulse. Brachial angiography demonstrated absent blood flow to the digital arteries of the distal left thumb and entire left index finger. A 3-phase Tc-99m MDP (methylene diphosphonate) bone scan was performed 6 days later, which demonstrated nonviability of the distal phalanx of the left thumb and left index finger, distal to the midportion of the proximal phalange. The patient subsequently underwent amputation of the left thumb and index finger at these levels with the bone scan accurately reflecting the operative findings. The 3-phase bone scan was useful in determining the need for and extent of amputation in this case.

Nat Mater 2006 May 21; (Read article online)

Clouet E, Laé L, Epicier T, Lefebvre W, Nastar M, Deschamps A

One usual way to strengthen a metal is to add alloying elements and to control the size and the density of the precipitates obtained. However, precipitation in multicomponent alloys can take complex pathways depending on the relative diffusivity of solute atoms and on the relative driving forces involved. In Al-Zr-Sc alloys, atomic simulations based on first-principle calculations combined with various complementary experimental approaches working at different scales reveal a strongly inhomogeneous structure of the precipitates: owing to the much faster diffusivity of Sc compared with Zr in the solid solution, and to the absence of Zr and Sc diffusion inside the precipitates, the precipitate core is mostly Sc-rich, whereas the external shell is Zr-rich. This explains previous observations of an enhanced nucleation rate in Al-Zr-Sc alloys compared with binary Al-Sc alloys, along with much higher resistance to Ostwald ripening, two features of the utmost importance in the field of light high-strength materials.

Expert Rev Cardiovasc Ther 2006 May; 4(3): 353-359 (Read article online)

Gaddam KK, Pratt-Ubunama MN, Calhoun DA

Resistant hypertension is defined as blood pressure that remains above target levels despite treatment with three different antihypertensive agents. Cross-sectional analyses and hypertension outcome studies indicate that it is a common clinical problem, which will undoubtedly become increasingly prevelant with an aging and increasingly overwight population. Secondary causes of hypertension are common in patients with resistant hypertension, particularly hyperaldosteronism, with a prevalence of approximately 15-20%. This, however, is likely to be an underestimation of the role excess aldosterone plays in causing resistance to treatment. In subjects with resistant hypertension, suppressed renin levels are common, exceeding 60% in studies conducted by the authors and from centers elsewhere in the world, suggesting occurrence of excess aldosterone beyond cases of true primary aldosteronism. Recent clinical studies indicate that aldosterone antagonists provide significant additional blood pressure reduction when added to treatment regimens of patients with resistant hypertension independent of aldosterone levels. These agents are generally well tolerated. Hyperkalemia is an uncommon complication of aldosterone antagonists, but it can occur. Therefore, biochemical monitoring is necessary, particularly in high-risk patients.

Synapse 2006 May 19; 60(2): 141-151 (Read article online)

Ko F, Tallerico T, Seeman P

To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia. Synapse 60:141-151, 2006. (c) 2006 Wiley-Liss, Inc.

Support Care Cancer 2006 May 23; (Read article online)

McGrath C, Montgomery K, White K, Kerridge IH

GOALS OF WORK: The purpose of this study was to explore the experience of autologous stem cell transplant recipients (ASCT) and those who care for them. MATERIALS AND METHODS: This was a qualitative prospective, longitudinal study. Ten patients who were about to have ASCT and nine carers were recruited to the study. Interviews were to be conducted at regular intervals six times over 2 years. The narratives of two widowed carers were analysed using Grounded Theory and read for themes on positive thinking and death. MAIN RESULTS: Positive thinking has a range of meanings, and its use can have a range of consequences. It can either be a useful coping strategy or can interfere with important conversations and planning about the end of life, and subsequently add to the distress of a grieving partner. CONCLUSIONS: It is important for patients, their partners and their health professionals to be able to discuss potential adverse consequences of illness, including death, without being hindered by the obligation to be positive or optimistic.

Ecol Appl 2006 Feb; 16(1): 33-50 (Read article online)

Latimer AM, Wu S, Gelfand AE, Silander JA

Models of the geographic distributions of species have wide application in ecology. But the nonspatial, single-level, regression models that ecologists have often employed do not deal with problems of irregular sampling intensity or spatial dependence, and do not adequately quantify uncertainty. We show here how to build statistical models that can handle these features of spatial prediction and provide richer, more powerful inference about species niche relations, distributions, and the effects of human disturbance. We begin with a familiar generalized linear model and build in additional features, including spatial random effects and hierarchical levels. Since these models are fully specified statistical models, we show that it is possible to add complexity without sacrificing interpretability. This step-by-step approach, together with attached code that implements a simple, spatially explicit, regression model, is structured to facilitate self-teaching. All models are developed in a Bayesian framework. We assess the performance of the models by using them to predict the distributions of two plant species (Proteaceae) from South Africa's Cape Floristic Region. We demonstrate that making distribution models spatially explicit can be essential for accurately characterizing the environmental response of species, predicting their probability of occurrence, and assessing uncertainty in the model results. Adding hierarchical levels to the models has further advantages in allowing human transformation of the landscape to be taken into account, as well as additional features of the sampling process.

Behav Genet 2006 May 19; (Read article online)

Torkamanzehi A, Boksa P, Ayoubi M, Fortier ME, Ng Ying Kin NM, Skamene E, Rouleau G, Joober R

Amphetamine (AMPH)-induced locomotor activity is a rodent behavioral trait that reflects mesolimbic dopaminergic activity. To identify potential quantitative trait loci (QTL) associated with this behavior, we used 34 recombinant congenic strains (RCSs) of mice derived from A/J (A strains) and C57BL/6J (B strains) and measured AMPH-induced total distance traveled (AMPH-TDIST). Two strains in the A panel (A52 and A63) showed significantly elevated AMPH-TDIST compared to the parental A/J strain and behaved similarly to C57BL/6J. Simple sequence length polymorphism (SSLP) markers on chromosomes 1, 2, 3, 5, 6, 8, 9, 10 and 20 were significantly associated with AMPH-TDIST in the A strains. Within the B panel, two strains (B81 and B74) had significantly higher and two strains (B69 and B75) had significantly lower AMPH-TDIST than C57BL/6J. Markers associated with AMPH-TDIST in the B strains appeared on chromosomes 5, 17 and 20. Combining data from this approach and other genetic (mapping data in humans) and functional (cDNA expression) sources may help to identify suitable candidate genes relevant to human disorders where mesolimbic dopamine dysregulation has been postulated.

Int J Environ Res Public Health 2005 Aug; 2(2): 245-50 (Read article online)

Al-Rawi SM

This paper presents an overall view of major sources that may lead to the pollution of the Tigris within Mosul city. A stretch exceeding 20kms in length is selected that represents the "sick" path of the river. Many sites along the studied stretch are likely to affect the river quality in some way or another. Samples from 40 sources sites are taken for quality analyses These sources--as huge as 400000 m3 a day--are characterized as (medium - strong) in composition. Such wastewaters with the pollutants they carry alter the river water quality rendering it unsuitable for beneficial uses. Such alterations--do leave--many negative consequences concerning human beings and aquatic life. It is found that domestic discharges are among the most important sources of pollution. Sanitary wastes are often discharged--untreated--into the Tigris. Other illegal practices such as in-house slaughtering add to the pollution as well. Industrial, tourist and institutional wastes put an additional burden on pollution of the river water quality. These wastes contain lead, chrome, and other heavy metals that may pose health risks. Wastewater treatment plants that exist in some sectors do not perform as they are expected. They need proper evaluation and rehabilitation. Eutrophication--a characteristic problem in lakes--finds an access to occur into the Tigris. This problem results from intensive use of detergents rich in nutrients (P&N compounds). In general, pollutants of different sources heavily affect the river water. Recovery and self purification of the river is estimated to occur at 40 km far from reference point. The paper concludes with the necessity of construction of a central treatment plant(s) or tackling the pollutants at their origin. The paper also stresses on importance of environmental education and awareness in order to combat pollution problems.

Altern Ther Health Med 2006 May-Jun; 12(3): 34-9 (Read article online)

Chou SC, Chen KW, Hwang JS, Lu WT, Chu YY, Lin JD, Chang HJ, See LC

CONTEXT: Other than weight reduction by dieting or physical activity, there are no well-documented medical treatments for fatty liver disease. OBJECTIVE: To evaluate the efficacy of the add-on Gynostemma pentaphyllum (GP) in research subjects with nonalcoholic fatty liver disease. DESIGN: A randomized, single-blind, controlled clinical trial. SETTING: Hospital-based clinic. PATIENTS: Fifty-six research subjects who were diagnosed with nonalcoholic fatty liver by abdominal ultrasound scanning. INTERVENTIONS: The treatment group and the control group followed a controlled diet for 2 months. After 2 months, the treatment group continued to diet and received 80 mL GP extraction for 4 months; the control group continued to diet and received a placebo capsule for 4 months. MAIN OUTCOME MEASURES: Body mass index (BMI), biochemistry data, and fatty liver score were measured at baseline, at 2 months, and at 6 months. RESULTS: After 2 months of dieting, BMI and most biochemistry data decreased in both study groups. There were no significant differences in BMI or biochemistry data at month 2 between the 2 study groups. At month 6, BMI, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, insulin (ALP), insulin resistance index (HOMA-IR), and fatty liver score were reduced in both groups. The treatment group saw significant reductions in BMI, AST, ALP, insulin, and HOMA-IR, however. Changes in uric acid levels in the 2 groups from month 2 to month 6 were statistically significant (P = .028) CONCLUSION: GP is an effective adjunct treatment to diet therapy for patients with nonalcoholic fatty liver disease.