PMID- 17364224 TI - The localization of ribosomal DNA in Sciaridae (Diptera: Nematocera) reassessed. AB - The chromosomal localization of ribosomal DNA (rDNA) was studied in polytene and diploid tissues of four sciarid species, Trichosia pubescens, Rhynchosciara americana, R. milleri and Schwenkfeldina sp. While hybridization to mitotic chromosomes showed the existence of a single rDNA locus, ribosomal probes hybridized to more than one polytene chromosome region in all the species analyzed as a result of micronucleolar attachment to specific chromosome sites. Micronucleoli are small, round bodies containing transcriptionally active, probably extrachromosomal rDNA. In T. pubescens the rDNA is predominantly localized in chromosome sections X-10 and X-8. In R. americana the rDNA is frequently found associated with centromeric heterochromatin of the chromosomes X, C, B and A, and also with sections X-1 and B-13. Ribosomal probes in R. milleri hybridized with high frequency to pericentric and telomeric regions of its polytene complement. Schwfenkfeldina sp. displays a remarkably unusual distribution of rDNA in polytene nuclei, characterized by the attachment of micronucleoli to many chromosome regions. The results showed that micronucleoli preferentially associate with intercalary or terminal heterochromatin of all sciarid flies analyzed and, depending on the species, are attached to a few (Trichosia), moderate (Rhynchosciara) or a large (Schwenkfeldina sp.) number of polytene chromosome sites. PMID- 17364225 TI - Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). AB - OBJECTIVE: Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer. METHODS: Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors. RESULTS: During 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35-75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01-1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate. CONCLUSION: This large European study supports previous findings that recent alcohol intake increases the risk of breast cancer. PMID- 17364226 TI - Evaluation of a summer research institute in behavioral health for undergraduate students. AB - Because of the need for additional researchers in the interdisciplinary field of behavioral health services research, the Florida Mental Health Institute at the University of South Florida developed and pilot tested a summer research institute for undergraduate students. Participants completed a 6-week program in which they developed a research project with a mentor and participated in a research seminar. The long-term objectives of the program were to attract promising students to the field and encourage them to pursue careers in behavioral health services research; short-term goals of the program were to strengthen participants' research skills and knowledge, provide an intensive and enjoyable learning experience, and positively impact participants' intentions to pursue graduate education in behavioral health. These goals were evaluated using a pre-post design with 6-month follow-up. Findings suggested that short-term goals were met. Suggestions for future improvements and implementation at other research settings are discussed. PMID- 17364227 TI - The influence of diabetes on cardiac beta-adrenoceptor subtypes. AB - Despite the significant developments in the treatment of diabetes mellitus, diabetic patients still continue to suffer from cardiac complications. The increase of cardiac adrenergic drive may ultimately contribute to the development and progression of diabetic cardiomyopathy. beta-Adrenoceptors play an important role in the regulation of heart function. However, responsiveness of diabetic heart to beta-adrenoceptor agonist stimulation is diminished. The chronotropic responses mediated by beta(1)-subtype, which is mainly responsible for cardiac effects of catecholamines are decreased in the atria of diabetic rats. The expression of cardiac beta(1)-subtype is significantly decreased in diabetic rats as well. beta(2)-Adrenoceptors also increase cardiac function. Although the expression of this subtype is slightly decreased in diabetic rat hearts, beta(2) mediated chronotropic responses are preserved. On the other hand, functional beta(3)-adrenoceptor subtype was characterized in human heart. Interestingly, stimulation of cardiac beta(3)-adrenoceptors, on the contrary of beta(1)- and beta(2)-subtypes, mediates negative inotropic effect in human ventricular muscle. Cardiac beta(3)-adrenoceptors are upregulated in experimental diabetes as well as in human heart failure. These findings suggest that each beta-adrenoceptor subtype may play an important role in the pathophysiology of diabetes-induced heart disease. However, it is still not known whether the changes in the expression and/or responsiveness of beta-adrenoceptors are adaptive or maladaptive. Therefore, this review outlines the potential roles of these receptor subtypes in cardiac pathologies of diabetes. PMID- 17364228 TI - Molecular identification of a novel G1 VP7 gene carried by a human rotavirus with a super-short RNA pattern. AB - AU19 is a human rotavirus strain carrying a G1P2C[6] specificity and a super short RNA pattern. Neutralization assay revealed an asymmetric cross neutralization between AU19 and Wa, a representative G1 rotavirus strain, and it is noteworthy that AU19 was neutralized poorly by anti-Wa hyper-immune serum. In the phylogenetic tree the VP7 gene of AU19 formed a lineage different from the established lineages of known human G1 rotaviruses. A signature code MFTKLLTAA was noted for AU19 lineage. These results provide evidences that the VP7 gene of AU19 represents a novel G1 lineage. PMID- 17364230 TI - Effects of alcohol intoxication and instructional set on women's sexual arousal vary based on sexual abuse history. AB - The influence of alcohol intoxication and arousal instructional set on psychophysiological measures of sexual responding was examined in a non-clinical sample of sexually abused (SA) and non-sexually abused (NSA) women. Participants (n=42) were randomly assigned to consume alcoholic (target blood alcohol level = .08%) or non-alcoholic drinks and to receive instructions to maximize or suppress their sexual response to erotic films. Measures included vaginal pulse amplitude (VPA), self-reported sexual arousal, and mood. SA classification interacted with instruction condition such that NSA women's VPA scores were higher under maximize than suppress instructions, but this did not occur for SA women. SA classification interacted with alcohol such that, compared to their sober counterparts, intoxicated NSA women reported less sexual arousal, whereas intoxicated SA women reported more sexual arousal than their sober counterparts. Moreover, positive mood ratings were highest among intoxicated SA women. Findings indicate that alcohol may affect women differently based on SA history and imply that SA history may be associated with differences in response to subsequent sexual situations. PMID- 17364231 TI - Brief report: 25-year follow-up of a high-functioning autistic child. AB - The following case report based on a 25-year experience with a high-functioning autistic child is offered (1) to provide some historical perspective on our approaches to ASD over the past 25 years, and (2) to illuminate some areas of continuing need for improvement. PMID- 17364233 TI - Electrophysiological evidence of different interpretative strategies in irony comprehension. AB - We explore the hypothesis that induction of holistic or analytic strategies influences comprehension and processing of highly contextualized expressions of ordinary language, such as irony. Twenty undergraduate students were asked to categorize as coherent or incoherent a group of sentences. Each sentence completed a previous story, so that they could be ironical, literal or nonsensical endings. Participants were asked to evaluate whether each sentence was coherent or incoherent. Half of them were initially instructed to consider whether the sentences made sense (holistic condition); the other half were instructed to consider whether the sentences were congruent or incongruent (analytic condition). Behavioral responses and Event Related Potentials were registered during the experiment. Both behavioral and electrophysiological results allow clearly distinguishing between the holistic and the analytic strategies. The fact that the same set of stimuli elicits different ERP waveforms, depending on the strategy with which they are analyzed, suggests that different cognitive processes and different areas of the brain are operating in each case. PMID- 17364232 TI - Host innate immune response to Mycobacterium tuberculosis. AB - This review focuses on recent progress in our understanding of Mycobacterium tuberculosis survival in macrophages, the interaction of M. tuberculosis with Toll-like receptors (TLRs) and the establishment of the link between innate and adaptive immunity, and TLRs and interferon-gamma-mediated antimicrobial pathways in macrophages. We also propose a paradigm that TLR2 signaling regulates the magnitude of the host Th1 response leading to either M. tuberculosis persistence and latent infection or replication and disease. PMID- 17364234 TI - A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers. AB - The prognosis of advanced biliary tract carcinoma is poor with chemotherapy limited to a palliative role. This randomised study was designed to evaluate the effectiveness of a new liposomal thymidylate synthase inhibitor (TSI), OSI-7904L, in parallel with a modified de Gramont regimen of 5-FU/LV in patients with advanced biliary cancer. Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI 7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5 FU/LV (intravenous l-LV 200 mg/m2, bolus 5-FU 400 mg/m2 and a 46-h infusion of 5 FU 2,400 mg/m2) every 14 days. Twenty-two patients were randomised, 11 to each group. No patients responded in the OSI-7904L arm, while one patient achieved a partial response in the 5-FU/LV arm. The rates of disease stabilisation were 4/11 (OSI-7904L) and 10/11 (5-FU/LV). Both treatment arms were generally well tolerated. These results show that the activity of OSI-7904L is below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilisation. A simplified de Gramont schedule appears to have marginally more activity. Both treatments were well tolerated. PMID- 17364235 TI - A phase I trial of BMS-247550 (NSC# 710428) and gemcitabine in patients with advanced solid tumors. AB - The purpose of this study is to establish the maximum tolerated dose and define the dose-limiting toxicity of the investigational epothilone BMS-247550 in combination with fixed dose-rate gemcitabine. Patients with advanced, recurrent solid tumors who had received or=7 days occurred in one of six patients. Two of three patients in cohort 2 (gemcitabine 900 mg/m2 plus BMS-247550 30 mg/m2) had dose-limiting toxicities of grade 4 neutropenia. An additional three patients were treated at dose level 1 with no additional dose-limiting toxicities observed. At an intermediate dose level (gemcitabine 750 mg/m2 plus BMS-247550 30 mg/m2), two of six patients experienced a dose-limiting toxicity (febrile neutropenia and grade 3 hypophosphatemia in 1, grade 3 hypophosphatemia and grade 3 hyponatremia in (1), and five of six patients experienced dose delays. In the final cohort (gemcitabine 750 mg/m2 plus BMS-247550 25 mg/m2), two of two patients experienced a dose-limiting toxicity. Treatment-related toxicities included neutropenia, thrombocytopenia, neutropenic fever, hypophosphatemia, and hyponatremia. Nine of 14 patients evaluable for response had stable disease. The maximum tolerated dose for this schedule is gemcitabine 900 mg/m2 over 90 min days 1 and 8 plus BMS 247550 20 mg/m2 on day 8. Attempts to increase the dose of BMS-247550 by decreasing the gemcitabine dose did not sufficiently ameliorate myelosuppression. Stable disease was observed in some patients with prior taxane exposure. PMID- 17364236 TI - Biothermal modeling of post-cryoplasty atherosclerosis in restenotic patients. AB - Atherosclerosis is a leading cause of heart diseases and mortality around the world. Recently, cryoplasty has emerged as a potential alternative method to treat arterial atherosclerosis. Finite element heat transfer and mass transfer models are developed using ANSYS in this study. The model analyzes the heat transfer within the atherosclerotic plaque and arterial wall during the cryoplasty procedure. The model is useful in predicting the transient temperature through the diseased wall tissues. The results may be used to decide required treatment procedure to effectively freeze the plaque with minimal damage to the healthy arterial tissues. Finally, the model investigates the parameters that may effect temperature distribution within the tissues during the ablative procedure. PMID- 17364237 TI - Malathion, carbofuran and paraquat inhibit Bungarus sindanus (krait) venom acetylcholinesterase and human serum butyrylcholinesterase in vitro. AB - Carbofuran and malathion, well known pesticides, and paraquat, a world widely used herbicide, were tested on acetylcholinesterase (AChE) from Bungarus sindanus venom and butyrylcholinesterase (BChE) from human serum. The calculated IC(50 )values for inhibition of venom enzyme by malathion, carbofuran and paraquat were 2.5, 0.14, and 0.16 microM, respectively. The values for inhibition of serum butyrylcholinesterase (BChE) were 3.5, 0.09 and 0.18 microM, respectively. Analysis of kinetic data indicated that the inhibition caused by malathion, carbofuran and paraquat was mixed for venom AChE. For BChE from human serum, the inhibition caused by malathion and paraquat was mixed and for carbofuran it was uncompetitive. The present results suggest a commercial paraquat preparation (a popular herbicide) inhibits cholinesterases with similar or higher potency than classical pesticide inhibitors. Furthermore, this inhibition was observed both in human serum and snake venom, a newly studied source of AChE. PMID- 17364238 TI - Flow cytometric analysis of red-eared slider turtles (Trachemys scripta) from Tar Creek Superfund Site. AB - Tar Creek Superfund Site (TCSFS) was heavily mined from the 1890s to 1970 and currently is contaminated with lead, zinc, and cadmium. Flow cytometry (FCM) was used to measure variation in nuclear DNA content of red blood cells collected from Trachemys scripta living within TCSFS and reference sites, Lake Carl Blackwell (LCB) and Sequoyah National Wildlife Refuge (SNWR). We also used atomic absorption spectrometry to measure Pb in blood and carapace and Cd in blood samples of turtles from TCSFS and SNWR. Mean coefficients of variation around the G(1) peak ranged from 5.33 to 5.48 and showed no significant difference between contaminated and reference populations; however, there was a significantly higher frequency of aneuploidy at TCSFS when compared with both reference populations. Blood Pb levels were not significantly different between TCSFS and SNWR populations. Pb levels in carapace samples did not differ significantly between sites; however, Pb levels were higher in carapace than blood for both populations. Blood Cd was significantly higher in animals at TCSFS than SNWR. PMID- 17364239 TI - Trace element residues in eggshells of grey heron (Ardea cinerea) and black crowned night heron (Nycticorax nycticorax) from Nallihan Bird Paradise, Ankara Turkey. AB - Concentrations of four trace elements (Cd, Ni, Cu and Pb) were determined in eggshells of grey heron (Ardea cinerea) and black-crowned night herons (Nycticorax nycticorax) from Nallihan Bird Paradise, which is located in the northern part of Sariyar Dam Reservoir, Turkey. Results indicated that, within the same area, these ardeid species differed in the levels of Cd, Cu and Pb in their eggshells (generally grey heron > night heron), possibly because females may have foraged in different habitats and regions. Geometric means found for Cd, Ni, Cu and Pb in eggshells were 0.931 mg/kg, 0.405 mg/kg, 6.755 mg/kg and 4.567 mg/kg, respectively, for grey heron; and 0.230 mg/kg, 0.220 mg/kg, 1.369 mg/kg and 1.108 mg/kg, respectively, for night heron. High bioaccumulation from sediments to eggshells occured for Cu and Pb, while Cd and Ni exhibited low accumulation. Bioaccumulation ratios were calculated as 19.63 (Cu) and 22.9 (Pb) in eggshells of grey herons. In conclusion, eggshells of grey herons appeared to be good bioindicators for monitoring of Cu and Pb in Nallihan Bird Paradise. PMID- 17364240 TI - Mercury and methylmercury accumulation and excretion in prairie voles (Microtus ochrogaster) receiving chronic doses of methylmercury. AB - Methylmercury cation (MeHg) and divalent mercury (Hg++) accumulation in liver, kidney, and brain were quantified in prairie voles (Microtus ochrogaster) at 0, 3, 6, and 12 weeks during chronic exposure to aqueous MeHg. Dose groups received deionized water or aqueous solutions containing 9, 103, or 920 ng MeHg/ml. Our study presents temporal patterns of Hg++ and MeHg concentrations in organ tissues and makes inter-tissue comparisons at each time point to illustrate the accumulation and distribution of Hg species during the study. MeHg was accumulated in tissues for 3 weeks and then concentrations plateaued. Mercury accumulated in brain, liver, and kidney to average concentrations of 510 ng/g, 180 ng/g, and 3400 ng/g, respectively. MeHg and Hg++ concentrations were roughly equivalent in liver, kidney, and urine. MeHg concentrations in brain tissue were 2 to 20 times the concentrations of Hg++. Regression analysis was also used to demonstrate the utility of urinalysis as an indicator of Hg++ and MeHg concentrations in organ tissue (p < 0.001). PMID- 17364241 TI - Preliminary study of the use of terrestrial moss (Pleurozium schreberi) for biomonitoring traffic-related Pt and Rh deposition. AB - The use of Pt and Rh as active components in automobile catalytic converters has led to increasing concentrations of these elements in several natural matrices. Because of this, the suitability of the use of a terrestrial moss (Pleurozium schreberi) for the passive biomonitoring of traffic-related Pt and Rh deposition was studied. The moss samples collected from Finland in and around areas with heavy traffic had increased Pt and Rh concentrations, with maximum values of 12.2 and 4.5 ng g(-1), respectively. In addition, the concentrations of commonly used catalytic converter additives (Al, Ce, La, Y, and Zr) and some elements related to traffic or mineral dust (Cd, Cu, Fe, Hf, Pb, and Zn) were also measured to obtain more information about the sources of Pt and Rh. Multivariate principal component analysis and cluster analysis were applied for identification of the emission sources of the elements. The results indicated a common traffic-related source of Pt and Rh. However, the results also showed that Pt and Rh concentrations in mosses are increased only in areas located close to traffic lanes. PMID- 17364242 TI - Moving towards shared decision making in prostate cancer screening. PMID- 17364243 TI - Hypertensive patients' race, health beliefs, process of care, and medication adherence. AB - BACKGROUND: African Americans have higher rates of hypertension and worse blood pressure (BP) control than Whites, and poorer medication adherence may contribute to this phenomenon. We explored associations among patients' race, self-reported experiences with clinicians, attitudes and beliefs about hypertension, and ultimately, medication adherence, among a sample with no racial disparities in BP control, to determine what lessons we could learn from patients and providers in this setting. METHODS: We recruited 793 White and African-American (58%) patients previously diagnosed with hypertension from 3 VA medical centers to participate in survey assessments of each of the above dimensions, subsequent to a primary care clinic visit. RESULTS: African-American patients' providers were significantly more active in advising and counseling about hypertension care and medication adherence. African-American patients indicated greater knowledge or heightened awareness of the importance of controlling their BP, but there were no race differences on a summary adherence measure. In multivariate models modeling medication adherence, race was not significant, but having been told to split one's pills, believing one's BP continues to be high, and having one's provider discuss things to do to make it easier to take BP medications were each significantly associated with worse adherence, whereas having more confidence in one's ability to take BP medications as prescribed was associated with better adherence (all p's < or = .02). CONCLUSION: When both physicians and patients take BP management seriously, disparities in BP adherence and control may be reduced. PMID- 17364244 TI - Effect of sublethal exposure to chlordecone on life history characteristics of freshwater rotifer Brachionus calyciflorus pallas. PMID- 17364245 TI - Presence of Wolbachia in insect eggs containing antimicrobially active anthraquinones. AB - Wolbachia are obligatory, cytoplasmatically inherited alpha-proteobacteria, which are common endosymbionts in arthropods where they may cause reproductive abnormalities. Many insects are well known to protect themselves from deleterious microorganisms by antibiotic components. In this study, we addressed the question whether Wolbachia are able to infect insects containing antimicrobial anthraquinones and anthrones, and if so, whether these genotypes of Wolbachia comprise a monophyletic cluster within one of the known supergroups. Leaf beetles of the taxon Galerucini (Galerucinae) are known to contain 1,8-dihydroxylated anthraquinones and anthrones. Also, the scale insect Dactylopius contains an anthraquinone glycoside, carminic acid. Our analyses revealed that a representative of the Galerucini, Galeruca tanaceti and Dactylopius, are indeed infected by endosymbiotic Wolbachia bacteria. Phylogenetic analysis of the wsp and ftsZ genes of these bacteria revealed that strains in G. tanaceti cluster in supergroup A, whereas those present in Dactylopius are distinctive from each other and from those of G. tanaceti. They are clustering in supergroups A and B. Wolbachia strains present in close, but anthraquinone-free relatives of G. tanaceti were shown to belong also to supergroup A. From these results, we can conclude (1) a double infection in Dactylopius, (2) that the presence of antimicrobial compounds such as anthraquinones does not necessarily protect insects from infection by Wolbachia, and (3) that genotypes of Wolbachia infecting anthraquinone-containing insects most likely do not comprise a unique genotype. These results show that Wolbachia bacteria might be adapted to cope even with conditions usually detrimental to other bacteria and that these adaptations are widespread among Wolbachia supergroups. PMID- 17364246 TI - Bacterial diversity and distribution in the holocene sediments of a northern temperate lake. AB - Sediments contain an abundance of microorganisms. However, the diversity and distribution of microorganisms associated with sediments are poorly understood, particularly in lacustrine environments. We used banding patterns from denaturing gradient gel electrophoresis (DGGE) and 16S rDNA sequences to assess the structure of bacterial communities in the Holocene sediments of a meromictic lake in Minnesota. Cluster analysis of the DGGE banding patterns indicates that the early- and middle-Holocene samples group separately from the late-Holocene samples. About 79% of the recovered bacterial sequences cluster with the alpha-, beta-, delta-, epsilon-, and gamma- Proteobacteriaceae and Firmicutes. The remaining approximately 21% lack cultured representatives. The taxonomic lineages of bacteria differ statistically among the early-, middle-, and late-Holocene samples, although the difference is smallest between early- and middle-Holocene samples. Early- and middle-Holocene samples are dominated by epsilon Proteobacteriaceae, and late-Holocene samples are dominated by sequences from uncultured subphyla. We only recovered delta-Proteobacteriaceae in late-Holocene sediments and alpha- and gamma- Proteobacteriaceae in late- and middle-Holocene sediments. Diversity estimates derived from early-, middle-, and late-Holocene clone libraries indicate that the youngest (late-Holocene) samples had significantly greater bacterial diversity than the oldest (early-Holocene) samples, and the middle-Holocene samples contained intermediate levels of diversity. The observed patterns of diversity may be caused by increased bacterial niche-partitioning in younger sediments that contain a greater abundance of labile organic matter than older sediments. PMID- 17364247 TI - Mineralogy influences structure and diversity of bacterial communities associated with geological substrata in a pristine aquifer. AB - Our understanding of mineralogical influences on subsurface microbial community structure and diversity has been difficult to assess due to difficulties in isolating this variable from others in the subsurface environment. In this study, biofilm coupons were used to isolate specific geological substrata from the surrounding geological matrix during colonization by microorganisms suspended in the surrounding groundwater for an 8-week period. Upon retrieval, the structure and diversity of the microbial community associated with each type of substratum was evaluated using 16S rDNA-based terminal-restriction fragment length polymorphism (T-RFLP). Phylogenetic affiliations of the populations associated with each type of substratum were established based on sequence analysis of near full-length 16S rDNA obtained through construction of a clone library. Hematite, quartz, and saprolite each harbored a community dominated by members of the division Proteobacteria (>67% of community). However, the different substrata selected for different subdivisions of bacteria within the Proteobacteria. After accounting for the influence exerted by substratum type on recovery of DNA from the attached populations, both phylogenetic data and Jaccard and Bray-Curtis similarity indices derived from terminal-restriction fragment (T-RF) profiles suggested a strong mineralogical influence on the structure and composition of the solid phase-associated community. The results suggest that mineralogical heterogeneity influences microbial community structure and diversity in pristine aquifers. PMID- 17364248 TI - Influence of ozone on litter quality and its subsequent effects on the initial structure of colonizing microbial communities. AB - Ozone is considered as the main factor in air pollution related to a decline of forest in North America and Europe. In the present study, the effect of changed litter quality, due to ozone stress to trees, on the microbial communities colonizing the subsequent litter was investigated. Litter bag technique using beech and spruce litter from ozone-stressed and control trees, was combined with 16S and 18S rRNA-based fingerprinting methods and cloning to characterize phylogenetic diversity. Litter bags were incubated for 2 and 8 weeks in a beech spruce mixed forest. Differences between the structure of microbial communities colonizing control and ozone-exposed litter were evident by fingerprints of 16S and 18S rRNA RT-PCR products. RT-PCR products, from litter degraded for 8 weeks, were cloned to identify the bacterial and fungal groups. Clones similar to members of Actinobacteria dominated the bacterial libraries, whereas effects of changed litter quality were mainly observed for the Proteobacteria. Fungal libraries were dominated by clones similar to Ascomycota members. Reduced proportion of clones similar to Basidiomycota and Zygomycota in library from ozone-stressed spruce trees and Chytridiomycota from ozone-stressed beech trees was observed when compared to their control counterparts. As hypothesized, changed litter quality due to elevated O3 did influence the structure of litter colonizing microbial communities. However, these differences were not as pronounced as those between the two plant species. PMID- 17364249 TI - Sponge-specific bacterial associations of the Mediterranean sponge Chondrilla nucula (Demospongiae, Tetractinomorpha). AB - A stable and specific bacterial community was shown to be associated with the Mediterranean sponge Chondrilla nucula. The associated bacterial communities were demonstrated to be highly similar for all studied specimens regardless of sampling time and geographical region. In addition, analysis of 16S rDNA clone libraries revealed three constantly C. nucula-associated bacterial phylotypes belonging to the Acidobacteria, the Gamma- and Deltaproteobacteria present in sponge specimens from two Mediterranean regions with distinct water masses (Ligurian Sea and Adriatic Sea). For the first time, candidate division TM7 bacteria were found in marine sponges. A major part (79%) of the C. nucula derived 16S rDNA sequences were closely related to other sponge-associated bacteria. Phylogenetic analysis identified 14 16S rRNA gene sequence clusters, seven of which consisted of exclusively sponge-derived sequences, whereas the other seven clusters contained additional environmental sequences. This study adds to a growing database on the stability and variability of microbial consortia associated with marine sponges. PMID- 17364250 TI - [Shifting to subcutaneous infusion of apomorphine in advanced Parkinson's disease patients on an out-patient basis: experience and recommendations]. AB - INTRODUCTION: Shifting from oral medication to continuous subcutaneous infusion of apomorphine (CSIA) in Parkinson's disease (PD) may be complicated. It is unclear whether hospitalization is necessary. OBJECTIVE: To observe efficacy and side effects in advanced PD patients shifting to CSIA managed as out-patients with hospital-based support. MATERIAL AND METHODS: CSIA was started on 7 PD patients with uncontrollable on-off fluctuations on a waiting list for surgery. Two patients were initially admitted to hospital, all others being managed as out patients. Awake off time was assessed with daily charts and motor function with UPDRS subscale and a scale for dyskinesias severity. Appropriate scales were applied for mood changes, neuropsychiatric complications and quality of life measures. Apomorphine dosage and oral antiparkinsonian medication were adjusted daily (mean: 6.1 days) according to motor responses. Follow-up visits were scheduled at 3 and 6 months. Patients were offered phone calls, unprogrammed visits, and 24 hours neurological care if required. RESULTS: All patients required phone calls (mean, 4.4), but unprogrammed visits were rare (1.5). Off time was reduced in the overall group by a 68.1 %. Co-medication with levodopa was necessary in all patients, but all other antiparkinsonian medications could be discontinued. CONCLUSION: Shifting from oral dopaminergic therapy to CSIA is safe and effective in advanced PD managed on an out-patient basis in a hospital based setting providing that daily in-person evaluation is available during the first week and follow-up by phone calls thereafter. PMID- 17364251 TI - [Prevalence of vascular risk factors among Spanish populations aged 70 years and over, as reported in door-to-door studies on neurological diseases]. AB - INTRODUCTION: The aim of this study was to re-analyze door-to-door studies on neurological diseases among the elderly, in which vascular risk factors (VRF) were studied, describing methodological characteristics and prevalence of VRF. METHODS: The surveys were identified in two phases. They were aimed at ascertaining prevalence of stroke, dementias or Parkinsonisms and, at the time of individual screening, had collected data on at least three of the following VRF: arterial hypertension (AHT), smoking habit, diabetes mellitus and hypercholesterolemia. A questionnaire was drawn up to collect the data reported in each study, and a database was constructed. VRF prevalences were quantified and analyzed using logistic regression. RESULTS: The total of the re-analyzed population was 12,510 persons aged 70 years and over, residents in seven geographic areas during the period 1994-2002. Information available on VRF was essentially self-reported. The prevalence of self-reported AHT was 25.7 % in men and 44.2 % in women, and that of measured AHT was 61 % and 71.9 %, respectively. Populations with arterial pressure obtained by direct measurement registered 138 higher risks (OR: 1.74; 95 % CI: 1.51-2.01, and OR: 1.48; 95% CI: 1.33-1.64). Reported prevalence of diabetes, hypercholesterolemia and smoking habit were 14.3 %, 23.3% and 8.5 %, respectively. CONCLUSIONS: There was a high prevalence of VRF among the Spanish elderly population. However, its relationship with dementia, Parkinsonisms and cerebrovascular disease could not be studied due to the poor quality of the VRF data. The differences between measured and self-reported arterial pressure suggest the existence of undetected AHT and wide scope for prevention. PMID- 17364252 TI - [Adaptation and validation of a naming test for Spanish speakers: reliability and discrimination of patients with dementia and unilateral brain lessions]. AB - INTRODUCTION: Psychometric studies with this confrontation- naming test have not been reported in Spanish speakers. OBJECTIVES: To study the internal consistency (N = 304), test-retest (N = 33) and inter-scorer (N = 37) reliability on healthy subjects. To study the concurrent validity (preliminary data) in 46 patients with unilateral brain lesions (left: 18, right: 28) including healthy subjects (N = 101), and in 28 patients referred for suspected dementia. METHODS: MATERIAL: the test was based initially on the nouns used by Oldfield and Wingfield in English. Data were obtained from consecutive patients and healthy volunteers. Lateral lesions were confirmed by neuroimages and surgery. The three groups of the validity study with lateral lesions were matched by gender, age, education and manual preference. Both groups of the dementia validity study were matched by gender, age, education and presence of vascular lesion. Patients who scored < 24 points in the mini- mental test and>9 points in the Blessed behavioral rating scale were operationally defined as patients with dementia (N=15). STATISTICAL ANALYSIS: For reliability studies: Cronbach's alpha, Pearson and intraclass correlation coefficients were used. Differences between scorers and between tests were analyzed by dependent sample Student's t tests. For the validity study with lateral lesions, ANOVA was employed. For the dementia validity study: independent sample Student's t test was used. RESULTS: All reliability coefficients were > 0.82 without differences in the t tests between scorers and tests. Validity was verified by the significant differences obtained between all the pairs of groups analyzed. DISCUSSION: The test demonstrated a suitable validity and reliability. PMID- 17364253 TI - [Reliability assessment of the EUROTEST]. AB - INTRODUCTION: The EUROTEST is a valid and useful instrument for detecting cognitive impairment and dementia. Our aim was to assess the test-retest reliability (TRTR) and the inter-rater reliability (IRR) of this instrument. METHODS: We assessed the TRTR by means of a cross-sectional repeated measures design in 30 subjects with no cognitive impairment. The IRR was determined through the blind assessment of 10 test administrations by 20 independent observers. In both instances we calculated the intra-class correlation coefficient and we compared those coefficients with the ones of the semantic Verbal Fluency Test (sVFT) obtained with the same samples and procedures. RESULTS: There were not significant differences concerning the characteristics of the subjects included in this study and those of previous studies on the EUROTEST. The EUROTEST showed a significantly higher TRTR (0.94 [95% CI: 0.87 0.97]) than the sVFT (0.51 [95% CI: 0.17- 0.74]), but there was not significant difference in IRR between the EUROTEST (0.91 [95% CI: 0.82-0.97]) and the sVFT (0.96 [95% CI: 0.91-0.99]). CONCLUSIONS: The EUROTEST shows high TRTR and IRR; therefore, this instrument is appropriate for the longitudinal assessment of subjects with dementia and their response to treatment. PMID- 17364254 TI - [Glioma therapy up-date]. AB - The prognosis for patients with malignant brain tumors has always been poor and until recently chemotherapy had not shown to be very effective. Temozolomide is a novel second-generation alkylating agent that has shown efficacy for the treatment of high-grade gliomas. Temozolomide is well-tolerated by most patients and has favorable pharmacodynamic and pharmacokinetic properties. In patients with newly diagnosed glioblastoma multiforme, radiation therapy with concurrent and adjuvant temozolomide significantly improves overall survival compared to treatment with only radiation. The benefit of temozolomide is greatest in patients with tumors that have a methylated 06-methyl-guanine DNA methyl transferase gene promoter that results in decreased repair of temozolomide induced DNA damage. This chapter will briefly review the diagnosis and treatment of patients with malignant brain tumors and then will focus on the role of temozolomide in glioma therapy. PMID- 17364255 TI - [Application of proteomics to neurological diseases]. AB - Proteomic is a set of tools that allows the separation and identification of proteins expressed by a cell, tissue or organism. Two-dimensional electrophoresis is the central tool that allows qualitative and quantitative comparisons of protein patterns between samples. Differential analysis of protein expression patterns in different neurological diseases (stroke, Alzheimer, Parkinson, amyotrophic lateral sclerosis, Hungtington, epilepsy) allows the identification of diagnostic and/or prognostic biomarkers. Subsequently, validation of these markers may help to identify new diagnostic and therapeutic targets. PMID- 17364256 TI - [Change of blood-brain barrier permeability after cerebral ischemia]. PMID- 17364257 TI - [Hyperdense posterior cerebral artery sign]. PMID- 17364258 TI - [Sign of hyperdense and hyperintense anterior cerebral artery]. AB - INTRODUCTION: The sign of a hyperdense middle cerebral artery (MCA) in computed tomography (CT) scan, or hyperintense MCA in magnetic resonance imaging (MRI) has been associated with recent acute occlusion of the vessel. Hyperdense or hyperintense signs in the basilar and cerebral posterior arteries in association with acute infarct have also been reported. These signs may help to clarify localization and provide prognostic information, especially when the clinical findings are not clear or conclusive. We hereby report on a case of acute infarct in the anterior cerebral artery (ACA) territory with hyperdensity and hyperintensity of the affected vessel. CASE REPORT: This is a case report of a 74 year old male patient with vascular risk factors who had the acute onset of speech impairment and left side hemiparesis, evolving over the next several hours to include depression of the level of consciousness, mutism, and right leg paresis. The A2 segment of the right ACA was found to be hyperdense in CT scan without contrast, and hyperintense in the FLAIR-MRI respectively. MR-angiography showed occlusion of the probably dominant right ACA at the A2 segment shortly after its onset. CONCLUSIONS: The finding of a hyperdense and hyperintense ACA may be useful for diagnosis of acute stroke in the ACA territory, particularly in clinically ambiguous cases. To our knowledge, this is the first reported case of hyperdense and hyperintense ACA as an early sign of acute stroke. Its prognostic value in the ACA is thus far unknown. PMID- 17364259 TI - [Extravasation of contrast medium after carotid stent with brain infarction symptoms]. AB - Angioplasty, with or without stent placement, as a carotid revascularisation technique, has become an alternative treatment for carotid stenosis, it being considered under certain circumstances the treatment of choice. The main concern about this technique is the distal embolisation during the procedure, while other, less frequent, complications have also been described such as dissection, vasospasm or even arterial rupture. Some of the infrequent complications include the hyperperfusion syndrome, and, more exceptionally, cases of extravasation of the contrast medium. We present the case of a patient who was subjected to angioplasty and stent insertion due to carotid stenosis with signs of calcification who suffered a stroke-like disorder in her right medial brain artery as a consequence of the extravasation of contrast medium after the rupture of the angioplasty balloon, a situation which has never been described in the literature before. PMID- 17364260 TI - [Hepatomioneuropathy secondary to mitochondrial DNA depletion]. AB - INTRODUCTION: Mitochondrial DNA depletion (mtDNA) is an highly heterogeneous condition characterized by a decreased number of mtDNA copies. CASE REPORT: The patient is a 22-month-old girl with generalized hypotonia, marked weakness, respiratory failure, arterial hypertension, hyperlactacidemia, hepatosplenomegaly and mild hypertransaminasemia without hepatic failure neither hypoketotic hypoglycemia. Electromyographic findings were consistent with neuromyopathy and muscle biopsy suggested a neurogenic atrophy. Electron microscopy revealed lipid droplets, subsarcolemmal accumulation of mitochondrias and glycogen granules. Respiratory chain enzime activities were normal. Genetic study in muscle showed mtDNA depletion, and the diagnosis of spinal muscular atrophy caused by survival motoneuron gene deletion was excluded. CONCLUSIONS: This case might be a novel phenotype of mtDNA depletion which could be named hepatomioneuropatyc form. A normal result of respiratory chain enzimes in muscle doesn't excluded mtDNA depletion. PMID- 17364261 TI - [Horner's syndrome secondary to epidural anesthesia]. AB - INTRODUCTION: The Horner's syndrome in association with the anesthetic techniques is produced by a blockade of the stellate ganglion sympathetic fibers. This complication is produced by the local anesthetic non-expected migration when it is administered either in the epidural space while performing an epidural block or inside the aponeurosis vascular elements during the performance of a brachial plexus block. Its evolution is quick, with benign incident that disappears in a few hours, without leaving any sequels. It can occur in patients without any previous clinical condition. CLINICAL CASE: We described the case of 28 years old pregnant woman, with a body mass index of 40.6, without any previous neurological background, who was admitted into hospital for labour. She had epidural analgesia and needed a caesarean section 2 hours later. Twenty minutes after the administration of an epidural dose of local anesthetic, the patient developed a completed left side Horner's Syndrome, as well as ipsi-lateral brachial paresis, that lasted for three hours, with complete recovery. CONCLUSIONS: Several etiopathologenic options were considered at the time, such as a possible subdural or paravertebral migration of the local anesthetic, the influence of the patient's position (decubitus) and the possible existence of fibrotic compartments in the epidurals space. PMID- 17364263 TI - [The impact of socioeconomic and sociodemographic factors on the criminal behavior of patients with a psychotic disorder]. AB - INTRODUCTION: The impact of socioeconomic and demographic factors on the criminal behavior of patients with a psychotic disorder was evaluated. METHOD: The study included 70 psychotic men hospitalized in the forensic psychiatry unit of the Bakirkoy State Hospital for Psychiatric and Neurological Diseases for compulsory treatment who were compared to 70 psychotic disorder cases with no criminal history hospitalized in the acute wards in the same hospital. Socioeconomic and sociodemographic data were collected and statistical evaluations were made. RESULTS: The vast majority of all the patients (90.7%) in both groups were diagnosed with schizophrenia. The forensic group was significantly less educated than the control group (7.99+/-3.81 years vs. 9.37+/-3.62 years, P<0.05). More than 50% of the cases in both groups were never married ; when considering divorced and widowed patients together with these unmarried patients, the percentage rose to 83%. Fewer forensic cases lived in urban areas than did control cases (50% vs. 84.3%). Logistic regression analysis highlighted a relationship between unemployment and the lack of social insurance to the criminal behaviour of the forensic group. Of those in the forensic group, 48.6% had no social insurance, whereas only 15.7% of the control group had none. CONCLUSION: The data suggested that unemployment and the lack of social insurance are 2 independent variables that may contribute to the probability that patients with a psychotic disorder will engage in criminal behavior. PMID- 17364264 TI - [General Health Questionnaire-12 for the detection of depression]. AB - OBJECTIVE: The aim of this study was to assess the validity and the possible cut off points of the General Health Questionnaire-12 (GHQ-12) in detecting depression in university students. METHODS: The study included 170 students (115 females and 55 males) that consecutively applied to a university student health center psychiatric clinic and who were asked to complete a sociodemographic data form and the GHQ-12 before their visit with the psychiatrist. DSM-IV psychiatric diagnoses were established using the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I). RESULTS: Depression was the most prevalent DSM-IV diagnosis (49%) and 35% of the students did not have any psychiatric diagnosis. Mean GHQ-12 score was 7.5+/-3.7 (8.0+/-3.6 for females and 6.4+/-3.7 for males, p<0.05). Sensitivity and specificity for depressive disorder were 83% and 65% (for the cut-off point 7/8), 75% and 77% (for the cut-off point 8/9), and 62% and 88% (for the cut-off point 9/10), respectively. The internal consistency (Cronbach's alpha 0.88) was good. Kappa coefficient for agreement between DSM diagnosis for depression and GHQ (cut-off 8/9) was 0.52. Item 9, which inquired about pleasure, produced the highest odds ratio for the diagnosis of depression (OR(CI)=11.84 (4.66-30.08)). CONCLUSION: The results of this study revealed that GHQ-12 is a useful screening instrument for the detection of depression with a high cut-off point (8/9). The students' tendency to report more psychological symptoms and the administration of the instrument in a student psychiatric clinic could be the reasons for the high GHQ-12 cut-off points. We propose the use of high cut-off points for students who applied to a psychiatric clinic for more accurate detection of depression. PMID- 17364265 TI - [The relationship between psychological factors and health care-seeking behavior in fibromyalgia patients]. AB - OBJECTIVE: The aim of this study was to examine whether cognitive factors, such as attributions, expectations, and anger management style, contribute to the decision to seek medical care for fibromyalgia syndrome (FMS). METHOD: We recruited 3 groups of subjects; patients from a FMS tertiary care setting, community residents with FMS who had not sought medical care for their FMS symptoms (nonpatients), and healthy controls. In all, 38 FMS nonpatients were compared to 37 FMS patients and 41 healthy controls on measures of anxiety, depression, anger, locus of control (LOC), attributions, pain intensity, and disability, as well as demographic characteristics. RESULTS: The prevalence of FMS non-patients was 2%. There was a significant difference between the 3 groups on the measures of anxiety, depression, LOC, and somatic and normalizing subscale scores of the symptom interpretation questionnaire (SIQ). FMS nonpatients, relative to FMS patients and healthy controls, were characterized by a significantly higher measure of both LOC and normalizing subscale score on the SIQ. There were no differences between the 2 FMS groups in demographical percentage and other psychometric measures. A hierarchical logistic regression model showed that the number of tender points, normalizing attribution style, and depression were independent predictors of help-seeking behavior. CONCLUSION: The rate of psychiatric and medical history is not related to the FMS syndrome. Expectations and a normalizing attribution style may contribute to help-seeking behavior for FMS. PMID- 17364266 TI - [The prevalence of depression and its associated factors among resident doctors working in a training hospital in Istanbul]. AB - OBJECTIVES: The objectives of this study were to determine the prevalence of depression and to evaluate the association of sociodemographic factors, as well as aspects of the work environment, with depression among resident doctors working in a training hospital in Istanbul. METHODS: This cross-sectional study was conducted in a teaching hospital which has 332 residents in Istanbul. The required sample size was determined to be 207. The study population was stratified proportionally according to hospital departments and a random sampling method was used. Data were collected with a questionnaire consisting of sociodemographic variables, the Beck Depression Inventory (BDI), and the Minnesota Job Satisfaction Questionnaire (MJSQ). The associations were studied through univariate and multivariate analyses. FINDINGS: The study included 156 residents who agreed to participate (response rate: 75.3%). The prevalence rate of probable depression was 16.0% (95% CI: 10.7-22.7). In the multivariate analysis, the rate of depression was significantly higher among women compared to men (OR: 5.16, 95% CI: 1.51-17.68, p<0.01). Age, marital status, hospital department, duration of residency, number of night shifts, and duration of exposure to daylight in the work environment were not associated with depression. Among the participants, 90.4% did not want to get a feedback concerning their BDI scores. A negative correlation was determined between depression and job satisfaction scores. CONCLUSION: Among resident doctors, women in particular should be evaluated as an important at-risk group for depression. Prevention and control programs that also include components for reducing stigma should be implemented. PMID- 17364267 TI - [Patients' explanation models for their illness and help-seeking behavior]. AB - OBJECTIVE: The aim of this study was to investigate some variables that affect patients' explanation models for their illness and help-seeking behavior. METHODS: Sampling was done between 2002 and 2003 among psychiatric patients who were admitted to university hospital in Malatya. Diagnoses of schizophrenia and schizoaffective disorder were made according to DSM-IV criteria. A semi structured interview based on a short questionnaire was conducted for collecting patient demographic data, and patient explanatory model for illness and help seeking behavior. RESULTS: The 88 patients that were evaluated included 50 males and 38 females. The mean age of the patients was 31.22+/-9.29 years (range: 16-57 years). In explaining their disease, 46.6% of the patients cited family trouble, 42% their inner problems, 19.3% economic difficulties, and 10.2% cited the consequences of supernatural forces. Among the patients, help-seeking behavior included visiting traditional and religious healers (51.1%), presenting to medical doctors (19.3%), and visiting a psychiatrist (65.9%). CONCLUSION: The study revealed that patients with low-level education were more prone to seek religious solutions and those with high-level education tended to visit a psychiatrist. It has been suggested that psycho-educational programs for patients and families will be very useful in ameliorating the problems created by the disease. PMID- 17364268 TI - [Validation of the Turkish versions of the short-form Conners' teacher and parent rating scales]. AB - OBJECTIVES: To investigate factorial and criterion validity as well as reliability of the Turkish translations of the 28-item Conners' Teacher Rating Scale (CTRS) and 48-item Conners' Parent Rating Scale (CPRS), which both measure attention deficit, hyperactivity, and conduct problems in children, through a series of studies conducted with either normal or clinical samples. METHOD: Normal sample data for the teacher and parent rating scales were collected at several elementary schools in Ankara through 2 different studies. The teacher rating scale sample consisted of 1539 pupils rated by their teachers, and the parent scale sample consisted of 954 pupils rated by their parents. The clinical sample consisted of 270 children diagnosed with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ADD), and/or conduct disorder (CD), who were rated by a child psychiatrist on a DSM-IV criteria form, as well as by their parents and teachers on the respective Conners' rating scales (CRS). The patients' clinical criteria scores related to these diagnostic categories were used to evaluate, and if necessary, to modify item content of the corresponding subscales. RESULTS: Turkish versions of the CTRS and CPRS demonstrated good internal consistency as indicated by Cronbach's alpha coefficients of .95 and .90, respectively. Factor analytical data from the normal sample studies supported the construct validity of both Turkish CRS despite non differentiation of the conduct factor from the hyperactivity factor on the teacher scale. The clinical criteria scores suggested the necessity of adapting the item content of all the subscales, except the hyperactivity subscale. CONCLUSION: The adapted and original subscales of the CRS Turkish forms demonstrated such psychometric properties that they could be employed in assessing attention deficit and disruptive behavior disorders in Turkish children. PMID- 17364269 TI - [Comorbid anxiety disorders in bipolar disorder patients: a review]. AB - In recent years, a growing number of clinical and epidemiological studies have reported high rates of comorbid anxiety disorder in patients with bipolar disorder. These studies have stated that comorbid anxiety disorder in bipolar patients is the rule rather than the exception. Lifetime anxiety disorder comorbidity rates among bipolar disorder patients are estimated to be between 24% and 93%, based on several different clinical and epidemiological studies. Bipolar patients usually are diagnosed with comorbid multiple anxiety disorders rather than a single one. Anxiety disorder comorbidity is associated with greater psychopathology, decreased treatment response, poor outcome, and increased suicidality. Current prevalent treatment approaches almost always give priority to the symptomatic treatment of bipolar episodes, which inevitably influences the provision of adequate attention and care to the diagnosis and treatment of a comorbid anxiety disorder. This approach has important therapeutic and clinical implications, such as delays in treatment leading to resistance to drugs and severe functional losses. Therefore, the treating psychiatrist needs to carefully evaluate, diagnose, and treat comorbid anxiety disorders in the early stages to avoid any unpleasant consequences and to improve the quality of life of patients. In this paper, an overview of comorbid anxiety disorder in bipolar disorders is presented, with a special emphasis on its prevalence, its relationship to sociodemographic and clinical variables, and possible therapeutic approaches. PMID- 17364270 TI - [Transference and countertransference in medically ill patients]. AB - Transference and countertransference feelings/reactions are a valuable source of information about a patient's inner world. A consultation liaison psychiatrist has to help the entire treatment team to understand the patient as well as treat the patient. Studies about transference and countertransference in medical settings are insufficient. An idealized transference often develops, usually at the beginning of the treatment, whereas negative transference occurs rarely. At other times a displaced transference, with anger, directed toward the medical team or one of its members may develop. Acute intense transference and countertransference feelings/reactions may be indicators of serious character pathology, such as Cluster B personality disorders. Patients with terminal illness are in need of perceiving the physician as an ideal and omnipotent figure; therefore, encouragement of a regressive relationship is recommended. There is always a risk of either avoidance or over involvement with the patient, especially in cases of catastrophic illness or injury. Not infrequently, interaction with the patient may evoke a traumatic experience in the therapist that has not been worked through sufficiently, and may hinder the therapist's ability to relate to his patient. Therapist countertransference feelings may be informative about the entire medical treatment process of the patient. Collaborative meetings with the medical team may help a therapists to understand their patients' inner worlds and to correct his/her dysfunctional attitudes, which in turn might positively affect treatment compliance and improve prognosis. Herein, the literature regarding transference and countertransference in medical patients is reviewed with case examples. PMID- 17364271 TI - [Case report: kleptomania and other psychiatric symptoms after carbon monoxide intoxication]. AB - Carbon monoxide (CO) intoxication is usually a serious condition, which can result in neurological disturbances or death. In some patients with CO intoxication, but not usually, a biphasic pattern can be seen. In this condition, after antitoxic treatment, patients may completely recover and after a short recovery period, neurological and/or psychiatric symptoms appear again. This condition is known as delayed encephalopathy and its occurrence rate is between 0.06% and 11.8%. Herein, we report a case with delayed encephalopathy after CO intoxication, which began with neurological symptoms and continued with obsessive compulsive disorder, depression, kleptomania, and psychotic disorder. The 41-year old female patient had no psychiatric or neurological symptoms or disorders prior to CO intoxication. Increased signal intensity changes in the basal region of the left temporal lobe (including the cortex and subcortical white matter), globus pallidus (bilateral), and cerebellar cortical and subcortical white matter (bilaterally symmetrical) was detected on axial T2-weighted magnetic resonance imaging (MRI). In addition, there were atrophic changes in both cerebellar hemispheres. To the best of our knowledge, this is the first case of kleptomania described after CO intoxication in the literature. We discuss the organic etiology of kleptomania and the other psychiatric symptoms of this patient in the light of recent research. We concluded that the kleptomania seen in this patient was related to concurrent lesions in the temporal lobe and globus pallidus; in other words, her kleptomania may have been related to dysfunction simultaneously seen in both the temporolimbic and frontal-subcortical circuits. PMID- 17364272 TI - [Case report: comorbid anorexia nervosa and schizophrenia in a male patient]. AB - Anorexia nervosa is a rare psychiatric disorder and epidemiological studies have shown a female to male ratio of 10:1, suggesting it is a disorder predominantly seen among females. The prevalence of anorexia nervosa comorbid with other psychiatric disorders has been reported to be quite high. Whereas depression and anxiety disorders are the most common comorbid diagnoses in anorexic patients, the dual-diagnosis of anorexia and schizophrenia is a relatively rare condition. Based generally on the observations from single case reports or case series, several explanations have been made about the co-occurrence of anorexia and schizophrenia. Herein, we present a male patient who developed schizophrenia after an anorexic period of 4 years that began when he was 14 years old with the decision to lose weight, which then progressed to a pattern of disordered eating and body image. This case is rare because the patient is male and has a comorbid diagnosis of anorexia nervosa and schizophrenia. To the best of our knowledge, there is only one previous case report in the literature describing a male anorexic patient with comorbid schizophrenia. In this case presentation, the diagnosis of anorexia nervosa in males is addressed, the definition and significance of sub-threshold cases are discussed, and the comorbidity of anorexia nervosa and schizophrenia are reviewed in light of the literature. PMID- 17364273 TI - Lifestyle during pregnancy and evidence based information. PMID- 17364274 TI - Total or subtotal hysterectomy for benign uterine diseases? A meta-analysis. AB - BACKGROUND: Total and subtotal abdominal hysterectomy for benign indications have been compared in randomized clinical trials and observational studies. A meta analysis is performed to summarize the evidence. METHODS: Thirty-four randomized clinical trials and observational studies comparing total and subtotal abdominal hysterectomy for benign indications were included. Endpoints were self-reported urinary incontinence, postoperative complications, operation time, quality of life, constipation, prolapse, sexual functioning, pelvic pain, and cervical stump problems after subtotal hysterectomy. Odds ratios and tests for heterogeneity and overall effect were calculated. RESULTS: Urinary incontinence and prolapse showed a significant difference favoring the total hysterectomy. Some of the women having a subtotal hysterectomy had cervical stump problems (bleeding and abnormal smear). Operation time and peroperative bleeding are postoperative complications were significantly in favor of the subtotal hysterectomy. Lower urinary tract symptoms other than incontinence, quality of life, constipation, pelvic pain, and sexual life were not in favor of either of the hysterectomy methods. CONCLUSION: Less women suffered from urinary incontinence and prolapse and cervical stump problems after total than after subtotal hysterectomy. However, subtotal hysterectomy is faster to perform, has less peroperative bleeding, and seems to have less intra- and postoperative complications. PMID- 17364275 TI - Homocysteine levels are unaffected by metformin treatment in both nonpregnant and pregnant women with polycystic ovary syndrome. AB - BACKGROUND: Women with polycystic ovary syndrome have elevated homocysteine levels. Elevated homocysteine levels associate with pregnancy complications. Women with polycystic ovary syndrome are often treated with metformin, a drug that may increase homocysteine levels. Hence, we investigated the effect of metformin treatment on homocysteine levels in nonpregnant and pregnant women with polycystic ovary syndrome. METHODS: Two prospective randomized placebo-controlled studies included women with polycystic ovary syndrome in a university hospital setting. Sixty-three infertile women were treated with metformin 1,000 mg bid or placebo for 16 weeks and 38 pregnant women with metformin 850 mg bid or placebo from the first trimester and throughout pregnancy. All the women had polycystic ovary syndrome and all participants received diet and lifestyle advice, and oral folate and vitamin B12 substitution, and a daily oral multivitamin tablet. The main outcome measures were serum levels of homocysteine, folate, and vitamin B12. RESULTS: Serum homocysteine levels were unaffected by metformin treatment both in nonpregnant and pregnant women with polycystic ovary syndrome. However, in nonpregnant women both serum folate and vitamin B12 levels decreased with treatment. At inclusion in nonpregnant women, serum homocysteine levels associated negatively with serum levels of folate and methyl malonic acid and positively with free testosterone index. No such associations were seen in pregnant women. CONCLUSIONS: Metformin treatment in women with polycystic ovary does not increase serum homocysteine levels in the nonpregnant or the pregnant state. PMID- 17364276 TI - Cervical phIGFBP-1 in the evaluation of the risk of preterm delivery. AB - BACKGROUND: To evaluate the accuracy of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions to predict premature delivery in symptomatic and asymptomatic pregnant women. METHODS: The study included 332 pregnant women: 109 symptomatic patients (study group) and 223 asymptomatic women (control group). For all women, qualitative and quantitative assessment of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions was carried out, but the quantitative assay was finally performed in 282 of 332. Student's test, the chi2 test, and Fisher's exact test were used as appropriate. RESULTS: The phosphorylated insulin-like growth factor binding protein-1 qualitative test was positive in 35 of 301 women (11.6%) and 11 (31.4%) of them delivered before 37 weeks; in the remaining 266 women with a negative test, there were 11 (4.7%) premature deliveries (relative risk = 5.8; 95% CI = 3.3-10.3). The mean values of quantitative phosphorylated isoform of insulin-like growth factor binding protein 1 were 56.9 microg/l (95% CI = 40.7-73.1) in cases of a positive qualitative test and 6.1 microg/l (95% CI = 4.0-8.3; p = 0.0001) in women with a negative result. The sensitivity, specificity, positive predictive value, and negative predictive value for phosphorylated isoform of insulin-like growth factor binding protein-1 test in symptomatic patients were 69.2%, 90.5%, 50%, and 95.6% respectively, while in the asymptomatic patients they were 22.2%, 91.8%, 11.8%, and 96% respectively. CONCLUSIONS: The phosphorylated isoform of insulin-like growth factor binding protein-1 in cervical secretions is a potential specific marker for preterm delivery occurring before 37 weeks. This test may have an important role in the management of women presenting with symptoms suggestive of preterm labour. PMID- 17364277 TI - Maternal smoking does not affect fetal size as measured in the mid-second trimester. AB - BACKGROUND: Cigarette smoking during pregnancy is causally related to birthweight, but we do not know whether fetal growth restriction is a continuous process or, if not, at what stage of pregnancy it affects weight gain. MATERIAL AND METHODS: A random sample of para 1 and 2 mothers, drawn from the population of pregnant women in Bergen and Trondheim, Norway, and Uppsala, Sweden, were examined by a detailed questionnaire concerning smoking habits, menstrual history and pregnancy dating, and subjected to morphometric sonography of their fetuses in or around week 17. Of the 547 study participants, 31.9% were smokers. Gestational age was primarily determined by the last menstrual period [LMP], except in those with irregular cycles, and in 30 cases (6.6% of those with regular cycles) in whom the biparietal diameter [BPD]-determined age deviated >14 days from the LMP-based date. RESULTS: The analysis did not reveal any statistically significant differences between the fetuses of non-smokers, light smokers (0-9 cigarettes per day) and heavy (10+ cigarettes per day) smokers, regarding BPD, mean abdominal diameter [MAD] femur length [FL], and a 'body contour index': [BPD+FL]/MAD. CONCLUSION: Tobacco-induced fetal growth restriction probably begins after gestational week 17. PMID- 17364278 TI - Coffee consumption and the risk of gestational diabetes mellitus. AB - BACKGROUND: Coffee consumption has been associated with a decreased risk of type 2 diabetes mellitus. We examined the relationship between coffee consumption and the risk of gestational diabetes mellitus [GDM]. METHODS: In this prospective study, 1744 non-diabetic pregnant women were questioned during early gestation about their coffee consumption. We studied the association of coffee consumption before and during pregnancy, and the subsequent risk of GDM. Generalised, linear models were fitted to estimate risk ratios and 95% confidence intervals. RESULTS: Women who reported moderate pre-pregnancy caffeinated coffee intake had a significantly reduced risk of GDM (adjusted RR 0.50; 95% CI 0.29-0.85) compared with non-consumers. No risk reduction was associated with decaffeinated coffee intake. CONCLUSIONS: Moderate pre-pregnancy caffeinated coffee consumption may have a protective association with GDM. Prospective studies, including a wider range of consumption habits, are necessary. PMID- 17364279 TI - Routine assessment of amniotic fluid alpha-Fetoprotein in early second-trimester amniocentesis is no longer justified. AB - BACKGROUND: Open fetal neural tube defects are often followed by an increase in alpha-Fetoprotein concentration in amniotic fluid. For over 25 years there has been a routine to measure amniotic fluid alpha-Fetoprotein in conjunction with early genetic amniocentesis. The efficacy of such a screening test in a low-risk population has been questioned but never evaluated in a Swedish population. METHODS: Data were reviewed retrospectively from all consecutive early second trimester genetic amniocenteses from two hospitals during the years 1993-2003. Indications for the genetic amniocenteses were maternal age > or = 35 years, maternal anxiety or a history of fetal aneuploidy. A questionnaire was sent to all obstetric clinics in Sweden regarding current common policy and experience of routine amniotic fluid alpha-Fetoprotein measurements, in the detection of open fetal neural tube defects. RESULTS: A total of 1,813 samples were included. In eight cases (0.4%) the amniotic fluid alpha-Fetoprotein concentrations were > or = 3 multiples of median, but five of them were false positive (63%). Out of the three true positive cases, one had clinical relevance. In the other two cases the detection of open fetal neural tube defects was of subordinate importance. In Sweden, during 2004, 91% of the obstetric clinics performed routine assessment of amniotic fluid alpha-Fetoprotein at second-trimester genetic amniocentesis, but only 9% regarded the analysis useful in clinical practice. CONCLUSIONS: According to our results, routine measurement of amniotic fluid alpha-Fetoprotein in early second-trimester genetic amniocentesis, to rule out a risk of open fetal neural tube defects, does not seem justified. The clinical usefulness seems to be limited. PMID- 17364280 TI - Pregnancy outcome in patients with previous uterine rupture. AB - BACKGROUND: To review the outcome of subsequent pregnancies in conservatively managed cases of uterine rupture. METHODS: Charts of patients with full thickness uterine rupture in the past 25 years were reviewed and information on subsequent pregnancies was extracted from maternal and neonatal charts. RESULTS: Thirty seven patients with uterine rupture were identified; the uterus was scarred in 62.2%. Ruptures were repaired in 26 (70.3%). Twelve patients subsequently conceived (24 pregnancies), with recurrence in 8/24 (33.3%) pregnancies or 5/12 (41.7%) patients. Patients with recurrence had a shorter median interval from previous rupture (2 versus 5 years), a higher incidence of previous longitudinal ruptures (60.0% versus 0.0%), and the median gestational age at the preceding rupture was lower without reaching statistical significance (34 versus 38 weeks; p = 0.209). CONCLUSIONS: Longitudinal ruptures and short intervals between rupture and subsequent pregnancy predispose to recurrence of uterine rupture. PMID- 17364281 TI - A prospective study on buprenorphine use during pregnancy: effects on maternal and neonatal outcome. AB - BACKGROUND: Exposure to illicit drugs in utero is associated with low birth weight and premature birth. Therefore, maintenance therapy for opioid dependence during pregnancy has been recommended to help withdrawal from street drugs, in order to improve maternal health and decrease risks to the fetus. METHODS: In 2002-2005, 67 pregnancies of 66 buprenorphine users were followed prospectively in an outpatient multidisciplinary antenatal setting by an obstetrician, a midwife, a psychiatric nurse and a social worker. Decreasing doses or even abstinence from buprenorphine was encouraged. Outcome measures were daily buprenorphine dose, fetal growth, gestational age at birth, mode of delivery, birth weight, Apgar scores, umbilical pH values, and occurrence of neonatal abstinence syndrome [NAS]. National statistics were used as reference values. RESULTS: The daily dose of buprenorphine decreased by 2.3 mg (median, range increase of 8 mg to decrease of 24 mg). There were no more incidences of premature birth, cesarean section, low Apgar scores (< or = 6) or umbilical artery pH <7.05 at birth than in the national register, despite the lower birth weight. A total of 91% of the infants needed treatment in a neonatal care unit, 76% had NAS, and 57% needed morphine replacement therapy. Seven infants were taken into care directly from the maternity hospital. Two sudden infant deaths occurred later. CONCLUSIONS: The pregnancies and deliveries of buprenorphine using women were uneventful, but severe NAS and need for morphine replacement therapy was seen in 57% of the buprenorphine-exposed newborns. A high number of sudden infant deaths occurred. PMID- 17364282 TI - Impact of subclinical chorioamnionitis on maternal and neonatal outcomes. AB - BACKGROUND: Chorioamnionitis is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The controversy about the benefits/risks of delaying labor is a critical issue concerning the management of chorioamnionitis. METHODS: The database between July 2001 and March 2006 was reviewed for women with singleton pregnancies between 22 and 28 weeks of gestation and with chorioamnionitis diagnosed on admission by amniotic fluid neutrophil elastase level. Women were classified according to the severity of chorioamnionitis (group A, amniotic fluid neutrophil elastase level of 0.15-1 microg/ml; B, 1-10 microg/ml; and C, > or = 10 microg/ml). During expectant management, serum C-reactive protein levels monitored the remission and aggravation of chorioamnionitis. Following deliveries, placentas were examined for histologic chorioamnionitis. RESULTS: One hundred women were enrolled (group A, 38; B, 34; C, 28). The latency period until delivery was significantly longer in group A than in groups B and C. C-reactive protein levels just before delivery were higher than those on admission in 61% of the overall cases. Histologic chorioamnionitis and funisitis were manifested in 90.4% and 65.5%, respectively. Intrauterine fetal demise (4 cases) and neonatal and postneonatal deaths during admission (10 cases) were observed. Bronchopulmonary dysplasia was the most common major morbidity noted in groups B and C. CONCLUSION: Chorioamnionitis could be controlled but is hard to cure. Higher levels of amniotic fluid neutrophil elastase are associated with a shorter interval from admission to delivery in women with subclinical chorioamnionitis. PMID- 17364283 TI - Obstetric brachial plexus palsy: a prospective study on risk factors related to manual assistance during the second stage of labor. AB - BACKGROUND: To evaluate the association between obstetric brachial plexus palsy and obstetrical maneuvers during the second stage of delivery. METHODS: Prospective population-based case control study. Cases of obstetric brachial plexus palsy were compared with a randomly selected control group with regard to obstetric management. RESULTS: Five or more obstetrical maneuvers were used to deliver the infants in 82% in the obstetric brachial plexus palsy group versus 1.8% in the controls. Risk factors independently associated with obstetric brachial plexus palsy were force applied when downward traction was imposed on the fetal head (odds ratio 15.2; 95% confidence interval 8.4-27.7). The incidence of obstetric brachial plexus palsy in the infants in the population was 3.3 per thousand. At 18 months of age 16.1% (incidence of 0.05%) of children had residual functional deficits and downward traction with substantial force was applied in all these cases. CONCLUSIONS: Forceful downward traction applied to the head after the fetal third rotation represents an important risk factor of obstetric brachial plexus palsy in vaginal deliveries in cephalic presentation. PMID- 17364284 TI - A validation of the diagnosis of obstetric sphincter tears in two Norwegian databases, the Medical Birth Registry and the Patient Administration System. AB - BACKGROUND: The purpose of the present study was to validate the registration of obstetric sphincter tears in 2 registers, the Medical Birth Registry of Norway [MBRN] and Patient Administration System [PAS]. METHODS: A retrospective cohort study of all obstetric sphincter tears that occurred in our department in 1990 1992 and 2000-2002 was performed. The case records of all patients registered either in MBRN, PAS or the birth logs were compared with the information in the medical records, which constituted the 'golden standard'. RESULTS: The incidence of obstetric sphincter tears in 1990-1992 was 5.8% (774/13381), 5.6% (745/13381) had a perineal tear of third degree and 0.2% (29/13381) of fourth degree. In 2000 2002, the total incidence was 6.6% (813/12380), 5.9% (731/12380) was a third degree perineal tear and 0.7% (82/12380) fourth degree, respectively. The sensitivity and specificity of the MBRN database to detect obstetric sphincter tears was 85.3 and 99.5% in 1990-1992, and 91.8 and 99.7% in 2000-2002, respectively. The positive and negative predictive values of a MBRN-registered diagnosis of obstetric sphincter tears in 1990-1992 were 91.4 and 99.1%, while the corresponding percentages in 2000-2002 were 95.4 and 99.4%, respectively. The sensitivity and specificity of the PAS database was correspondingly 52.1 and 99.0% in 1990-1992, and 84.6 and 98.5% in 2000-2002. The positive and negative predictive values of a PAS-diagnosis of obstetric sphincter tears were 75.8 and 97.1% in 1990-1992. In 2000-2002, they were 92.7 and 98.9%, respectively. CONCLUSION: The validity of a diagnosis of obstetric sphincter tears, based on the MBRN, is sufficiently high to justify future large-scale epidemiologic studies based on this database, while the validity of a PAS diagnosis is lower, but improves. PMID- 17364285 TI - Postpartum ultrasound in women with postpartum endometritis, after cesarean section and after manual evacuation of the placenta. AB - OBJECTIVES: To measure anteroposterior (AP) diameters, and to describe qualitative findings of the uterus and the uterine cavity in women with postpartum endometritis, after caesarean section (CS) and after manual evacuation of the placenta, and to compare these women with those in a normal puerperium. METHODS: A prospective, descriptive, observational study of 103 postpartum women was conducted. Fifty-five women had clinical symptoms of postpartum endometritis, 28 had undergone CS, and 20 had manual placental evacuation. Ultrasound examinations were scheduled for days 1, 3, 7, 14, 28 and 56 postpartum. Women with endometritis underwent their first examination on the day they presented with clinical symptoms. RESULTS: The AP diameters of the uterus and uterine cavity in all three groups overlapped considerably with the reference values. On day 56 postpartum, the uterus had achieved the same dimensions as found in our reference population. Compared with the reference group, during early puerperium, an empty cavity was less common among women with the three study conditions, and gas was present more often after CS and after manual evacuation of the placenta. An anteverted position of the uterus was less common among women with endometritis on day 14 and 28 postpartum, and among women delivered by CS on days 7, 14 and 28 postpartum. The incision site in the lower uterine segment was visible after CS. CONCLUSION: The ultrasonic findings in women with postpartum endometritis, after CS and after manual evacuation of the placenta, do not differ substantially from those during an uncomplicated puerperium. A delayed uterine involution process might explain the slight morphological differences observed. PMID- 17364286 TI - N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. AB - OBJECTIVE: To compare clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome. DESIGN: Prospective cross-over trial. SETTING: University teaching hospital and a private practice setting. PATIENTS: Five hundred and seventy-three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N-acetyl cysteine for another cycle. All women suffered from polycystic ovary syndrome. INTERVENTIONS: Patients had clomiphene citrate 50-mg tablets twice daily alone or with N-acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle. OUTCOME MEASURES: Primary outcomes were number of mature follicles, serum E2, serum progesterone, and endometrial thickness. Secondary outcome was the occurrence of pregnancy. RESULTS: Ovulation rate improved significantly after the addition of N acetyl cysteine (17.9% versus 52.1%). Although the number of mature follicles was more in the N-acetyl cysteine group (2.1+/-0.88 versus 3.2+/-0.93), the difference was not statistically significant. The mean E2 levels (pg/ml) at the time of human chorionic gonadotropine injection, serum progesterone levels (ng/ml) on days 21-23 of the cycle, and the endometrial thickness were significantly improved in the N-acetyl cysteine group. The overall pregnancy rate was 11.5% in the N-acetyl cysteine group. Insulin resistance occurred in 260 patients (55.4%). There was no significant difference between the insulin resistance group (n = 260) and non-insulin resistance group (n = 210) as regards ovulation rate, number of follicles, serum E2 (pg/ml), serum progesterone (ng/ml), endometrial thickness (mm), or pregnancy rate. CONCLUSION: N-Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients. PMID- 17364287 TI - Emergency obstetric hysterectomy. AB - BACKGROUND: All cases of obstetric hysterectomies that were performed in our hospital during a seven-year study period were reviewed in order to evaluate the incidence, indications, risk factors, and complications associated with emergency obstetric hysterectomy. METHODS: Medical records of 45 patients who had undergone emergency hysterectomy were scrutinized and evaluated retrospectively. Maternal age, parity, gestational age, indication for hysterectomy, the type of operation performed, estimated blood loss, amount of blood transfused, complications, and hospitalization period were noted and evaluated. The main outcome measures were the factors associated with obstetric hysterectomy as well as the indications for the procedure. RESULTS: During the study period there were 32,338 deliveries and 9,601 of them (29.7%) were by cesarean section. In this period, 45 emergency hysterectomies were performed, with an incidence of 1 in 2,526 vaginal deliveries and 1 in 267 cesarean sections. All of them were due to massive postpartum hemorrhage. The most common underlying pathologies was placenta accreta (51.1%) and placenta previa (26.7%). There was no maternal mortality. CONCLUSIONS: Obstetric hysterectomy is a necessary life-saving procedure. Abnormal placentation is the leading cause of emergency hysterectomy when obstetric practice is characterized by a high cesarean section rate. Therefore, every attempt should be made to reduce the cesarean section rate by performing this procedure only for valid clinical indications. PMID- 17364288 TI - Lower uterine blood supply: extrauterine anastomotic system and its application in surgical devascularization techniques. AB - BACKGROUND: To establish the arterial components that determine lower uterine blood supply, varieties and anastomoses that result in complications during selective devascularization procedures. METHODS: Thirty-nine female cadaveric pelvises with latex repletion in pelvic arteries were used. All the material was studied through direct dissection, and dissection enlarged with a 90-diopter magnifying glass, establishing origin, course, and anastomoses of the genital arteries. Axial calibers of the uterine and the main vaginal arteries were compared. An anatomical and a historical compilation of the uterine artery was made, with special reference to anastomotic areas in the lower sector. RESULTS: Three main pedicles were determined in the lower uterine blood supply: a cephalic one constituted by the uterine artery, a medial one made up by the cervical artery, and a distal one formed by the vaginal arteries. Different types of anastomoses were distinguished among the upper, middle, and lower pedicles. All types of anastomoses displayed similar features and were interconnected along the isthmic-vaginal borders, or as an intramural anastomotic network. In many cases, a transmedial interuterine anastomosis of axial caliber equivalent to the uterine artery itself could be observed. The bibliography consulted provided neither detailed descriptions of the cervical-segmental arterial system nor of the vaginal system or its anastomoses. In two cases, images were found in books that show this anastomotic system without further explanation. CONCLUSION: A not very well known anastomotic system was described between uterine and vaginal arteries. This system explains some reported failures, complications, and hemodynamic changes after uterine devascularization procedures. PMID- 17364289 TI - Where is the aorta? Is it worth palpating the aorta prior to laparoscopy? AB - BACKGROUND: Injury to major retroperitoneal vessels is the most catastrophic complication of laparoscopy. Knowledge of the site of the aortic bifurcation prior to inserting the umbilical port would be expected to reduce the risk of this type of injury. The aim of the study is to determine the feasibility of identifying the aortic bifurcation by palpation prior to the operation. METHODS: We studied 100 patients undergoing laparoscopic surgery or laparotomy. After prepping and draping, the operating surgeon felt for the aortic bifurcation to determine its position in relation to the umbilicus. We then related our findings to the height, weight, and body mass index of the patient. RESULTS: The aorta could not be palpated in 15% of cases, including almost 2/3 of women who were obese (body mass index >30). In the remaining 85% cases, where the aorta was palpable, the bifurcation was above the level of the umbilicus in 30 (35%) cases, at the umbilicus in 45 (53%) cases, and below in 10 (12%) cases. We did not find any significant effect of body mass index, height, or weight on the level of the aortic bifurcation by palpation. No vascular injury occurred in the laparoscopic cases during the study. CONCLUSIONS: The aortic bifurcation is palpable in the majority of women undergoing surgery, including 93% of those with a low or normal body mass index who are at higher risk of vascular injury. We recommend the routine palpation for the aortic bifurcation as a simple means to reduce the risk of injury to a major retroperitoneal vessel. PMID- 17364290 TI - Maternal deaths after elective cesarean section for breech presentation in the Netherlands. AB - BACKGROUND AND METHODS: The cesarean section rate for term singleton breech babies in the Netherlands rose from 57 to 81% after the Term Breech Trial in 2000. The Dutch Maternal Mortality Committee registered and evaluated maternal mortality due to elective cesarean section for breech. RESULTS: Four maternal deaths after elective cesarean section for breech presentation, from 2000 to 2002 inclusive, were registered, 7% of total direct maternal mortality in that period. Two women died due to massive pulmonary embolism, both were obese, and thromboprophylaxis was not adjusted to their weight. The other two women died from sepsis, one had not receive perioperative prophylactic antibiotics. The case fatality rate for elective cesarean section for breech presentation was 0.47/1,000 operations. No death after emergency cesarean section for breech presentation was registered at the committee. CONCLUSIONS: Elective cesarean section does not guarantee the improved outcome of the child, but may increase risks for the mother, compared to vaginal delivery. PMID- 17364291 TI - Fragile X syndrome: relation to premature ovarian failure and infertility treatment. PMID- 17364292 TI - Congenital hypodysfibrinogenemia and abruptio placentae in a woman with history of cerebral thrombosis. PMID- 17364293 TI - Congenital cytomegalovirus infection presenting with echogenic bowel and oligohydramnios. PMID- 17364294 TI - Synechia vulvae -- an unusual cause of urinary symptoms in a 15-year-old girl. PMID- 17364295 TI - Shoulder dystocia and nuchal cord. PMID- 17364298 TI - Peritoneal fluid as an unrecognised vector between female reproductive tissues. AB - This essay discusses the potential contribution of peritoneal fluid to the regulation of reproductive processes in female mammals. After noting the relatively high concentrations of diverse hormones in peritoneal fluid, and accepting that it bathes the surface of all the internal reproductive organs, peritoneal fluid is then proposed as a means of communication between the two ovaries. It could act to influence both the hierarchy of Graafian follicles and the rate and extent of development of a newly-formed corpus luteum. Cytokines in peritoneal fluid are considered in this context, as are the differing populations of leukocytes. Circumstantial evidence is offered for entry of peritoneal fluid into the Fallopian tubes, especially close to the time of ovulation, with the suggestion that such entry could modify the nature of endosalpingeal secretion and transudation. Thereafter, the spectrum of gonadal hormones in peritoneal fluid could be influencing uterine tissues in a local manner. Finally, reference is made to regional differences in the concentration of steroid hormones in the peritoneal fluid of women, likewise to regional differences in domestic animals. PMID- 17364299 TI - Severe life events and impaired fetal growth: a nation-wide study with complete follow-up. AB - BACKGROUND: To estimate the association between severe maternal life events and infants small for gestational age at different gestational ages at birth. METHODS: From 1980 to 1992 all women exposed to severe life events such as death or first hospitalization for cancer or acute myocardial infarction in partners or children during pregnancy or up to 485 days before were identified through national registers. We included all 3,402 exposed pregnancies and 19,551 unexposed pregnancies randomly selected to the control cohort and performed adjusted stratified Cox proportional hazards regression analyses with time dependent covariates. RESULTS: These life events were not associated with SGA in general, but exposed infants born before 32 weeks of gestation had twice the risk for being born with a birth weightor=7.0 mmol/l (127.8 mg/dl). Data was analysed according to glucose levels at diagnosis, ie, mild or severe GDM. RESULTS: GDM was diagnosed in 2.28% of the women who were older and had higher Body Mass Index [BMI]. A high proportion was of non-Nordic origin (44.5%); they had severe GDM more often (49.1%) than the Nordic group (33.1%). The GDM-mild group had less complications and abnormalities, compared to the GDM-severe group, although both groups differed from the control group in this respect. Delivery was spontaneous in 70.2% of GDM-mild, 65.7% of GDM-severe and 81.0% of the control group. LGA (+2 SD) was found in 4.8, 10.5 and 3.2%, respectively. CONCLUSION: Early non-fasting random universal screening and multidisciplinary antenatal teamwork intervention seems to be favourable, with low rates of excessive fetal growth, instrumental vaginal delivery and caesarean section. PMID- 17364302 TI - Factors associated with depressive symptoms among postnatal women in Nepal. AB - BACKGROUND: Depression after childbirth affects both the mother and her infant. In South-Asia, maternal depression might also contribute to poor infant growth. Knowledge of risk factors could improve the health workers' recognition of depression. AIM: To examine possible risk factors for depression in the postnatal period among women in one clinical, one urban and one rural population in Lalitpur district, Nepal. METHOD: A total of 426 postnatal women were included in a cross-sectional structured interview study, 5-10 weeks after delivery. Depressive symptoms were measured by the Edinburgh Postnatal Depression Scale [EPDS]. RESULTS: Multivariate analysis showed that depression (EPDS>12) was strongly associated with husband's alcoholism, polygamy and previous depression. Other significant factors were stressful life events, multiparity, smoking and depression during pregnancy. There was a non-significant trend of lower depressive scores among women living in arranged marriages, and among women practicing the tradition of staying in their maternal home after delivery. CONCLUSIONS: In addition to previously documented risk factors, traditional family structures may influence the risk of depression among postnatal women in Nepal. PMID- 17364303 TI - Childbearing or induced abortion: the impact of education and ethnic background. Population study of Norwegian and Pakistani women in Oslo, Norway. AB - OBJECTIVE: To study patterns of induced abortion versus childbirth related to education among Norwegian and Pakistani women. DESIGN AND SETTING: Population based study in Oslo, Norway. POPULATION: All women 15-50 years of age of Norwegian (n=94,428) or Pakistani (n=5,390) descent living in Oslo. MAIN OUTCOME MEASURES: Induced abortion or child delivery. RESULTS: In Norwegian women with a university education, 15.3% delivered a child and 2.9% had an induced abortion between 2000 and 2002. In women with less than high school education, the figures were 5.3% and 4.3%. Pregnant women with less than high school education were twice as likely to have an induced abortion as women with a university education (odds ratio, 2.0; 95% confidence interval, 1.7-2.5), after adjustment for age, parity, marital status, and residential area. Among Pakistani women with a university education, 23.0% gave birth and 2.9% had an induced abortion. In Pakistani women with less than high school education, the figures were 20.8% and 2.8%. Among pregnant Pakistani women, those with less than high school education were less likely to have an induced abortion compared to women with a university education (odds ratio, 0.5; 95% confidence interval, 0.2-1.1). CONCLUSIONS: Childbirth was substantially more common in Pakistani than in Norwegian women living in Oslo. In Norwegian women, low education was associated with lower frequency of child delivery but higher frequency of induced abortion. In Pakistani women, child delivery was not related to education, but induced abortion tended to be more frequent in those with a university education. PMID- 17364304 TI - The effect of smoking and hypertensive disorders on abruptio placentae in Norway 1999-2002. AB - OBJECTIVE: To assess the effects of smoking and hypertension on abruptio placentae and whether the effect of hypertension is modified by smoking and vice versa. To quantify the proportion of abruptio placentae cases attributable to hypertension and smoking. DESIGN: Registry based national cohort study. MATERIALS AND METHODS: 814 cases of abruptio placentae among a total of 211,868 births in Norway during the period 1999-2002. Logistic regression analysis was used to assess whether the risk of abruptio placentae is influenced by maternal smoking habits and hypertensive disorders and to evaluate interactions in the effects on abruptio placentae of smoking and hypertension. RESULTS: In occasionally and daily smokers at the onset of pregnancy, abruptio placentae occurred in 5.4 and 5.7 per 1000, respectively, against 3.4 per 1000 in non-smokers (adjusted odds ratios (ORs) for maternal age and birth order 1.6-1.7). No significant dose response effect was found. Adjusted ORs for abruptio placentae in women with pre eclampsia superimposed on chronic hypertension, transient hypertension, mild and severe pre-eclampsia, and pre-eclampsia with onset before 34th weeks of gestation were significantly increased (ORs 1.6-4.1). The combined effects of smoking and hypertensive disorder were additive. Hypertension explained 3.3% of abruptio placentae, while smoking explained 6.9% of abruptio placentae cases. CONCLUSIONS: The effects on abruptio placentae of hypertensive pregnancy disorders and smoking are independent and additive, indicating that smoking and hypertension have their effects though separate mechanisms. If smoking were eliminated in pregnant women, the number of abruptio placentae cases would be reduced by 7%. PMID- 17364305 TI - A comparison of high- versus low-intensity, high-frequency transcutaneous electric nerve stimulation for painful postpartum uterine contractions. AB - BACKGROUND: Breast-feeding in the postpartum period is known to induce intense uterine contractions with pain in the lower abdomen. AIMS: The primary aim of this study was to compare the effects of high and low intensity, high frequency Transcutaneous Electric Nerve Stimulation (TENS) on pain and discomfort of postpartum uterine contractions. The secondary aim was to evaluate discomfort experienced from the stimulation itself. METHODS: Twenty-one newly delivered women participated in this single-blind trial, 12 women received high intensity, high-frequency TENS (HI TENS) and 9 women received low intensity, high-frequency TENS (LI TENS). The electrodes were placed abdominally on each side of the uterus. Stimulation was done during one minute. Visual analogue scales were used to evaluate the intensity of the pain before and after stimulation. A verbal scale was used to estimate sensation of discomfort before, during and after stimulation. RESULTS: The median decrease in pain ratings before and after treatment by VAS was larger in the HI TENS group -49 mm (95% CI -66.5--33.2) than in the LI TENS group -21 mm (95% CI -39.0--20.0). The reduction of pain was most pronounced in the HI TENS group (median difference 28 (95% CI was 14.0-53.0). Furthermore, the HI TENS group experienced significantly less discomfort of the uterine contractions after stimulation (p<0.01) but they also experienced more discomfort of the stimulation than women in the LI TENS group (p<0.01). CONCLUSION: The women treated with HI TENS, experienced significantly less postpartum pain and discomfort to those treated with LI TENS even though the discomfort from the stimulation with HI TENS was greater. PMID- 17364306 TI - Analysis of malpractice claims with a focus on oxytocin use in labour. AB - BACKGROUND: The objective of this study was to analyse the motives behind disciplinary action in obstetric malpractice cases concerning delivery, and to evaluate the frequency of inappropriate oxytocin use in these cases. METHODS: An analysis of all malpractice claims resulting in disciplinary action against physicians and midwives during the period 1996-2003. Investigations and decisions made by the Board of Medical Responsibility were reviewed with special focus on the use of oxytocin. RESULTS: Of 77 cases, 60 regarded patients in labour. In the majority, there had been a normal pregnancy and spontaneous start of labour (78%). At the beginning of labour, 87% showed a normal fetal heart rate (FHR) pattern, indicating fetal well-being. In 70%, there was adverse fetal outcome with brain damage or death. The most common reason for disciplinary action was improper interpretation of fetal monitor tracings and corresponding failure to recognise fetal distress (76%). Injudicious use of oxytocin was common (68.5%), and was the primary reason for disciplinary action in 33% of the cases. CONCLUSION: In a Swedish setting, a few common clinical problems pervade; interpretation of FHR patterns and the use of oxytocin account for the majority of rulings of negligence in malpractice cases regarding delivery. Analysis of the cases suggests that the adverse fetal outcomes could possibly have been prevented. PMID- 17364307 TI - Maternal-neonatal 8-hydroxy-deoxyguanosine serum concentrations as an index of DNA oxidation in association with the mode of labour and delivery. AB - AIM: To investigate the effect of the mode of labour and delivery on the total antioxidant status (TAS), and the biomarker of DNA oxidation, 8-hydroxy deoxyguanosine (8-OHdG) serum levels, in mothers and their newborns. SUBJECTS AND METHODS: Some 106 women with normal pregnancy and normal blood biochemical parameters were divided into 4 groups: Group A (n=28) with normal labour and vaginal delivery (VG), Group B (n=25) with scheduled cesarean section (CS), Group C (n=26) with 'emergency' CS, and Group D (n=27) with prolonged labour+VG. Blood was obtained from the mothers at the beginning of labour, and immediately after delivery (pre- and post-delivery), as well as from the umbilical cord (CB). TAS, 8-OHdG and creatine kinase (CK) were measured in the sera with appropriate methodology. RESULTS: TAS levels were almost similar in all the groups pre delivery, and in CB irrespective of the mode of labour and delivery, and remarkably decreased in Groups C and D post-delivery. 8-OHdG levels in Group C (0.94+/-0.08 ng/ml) and Group D (0.98+/-0.08 ng/ml) were significantly higher than those in Group A (0.26+/-0.01 ng/ml, p<0.001) and Group B (0.28+/-0.07 ng/ml, p<0.001) post-delivery. 8-OHdG levels were low in CB, independent of the mode of labour. CK positively correlated with 8-OHdG (r=0.48, p<0.001), the latter negatively correlated with TAS (r=-0.53, p<0.01). CONCLUSIONS: The lowest TAS and the highest 8-OHdG levels were found in Groups C and D post-delivery, probably due to the long-term participation of the mothers' skeletal and uterus muscles, whereas 8-OHdG levels were low in CB irrespective of the mode of delivery, possibly as a consequence of the antioxidant action of the placenta and/or the low lipid levels in the serum of the umbilical cord. PMID- 17364308 TI - Attitudes among sperm donors in 1992 and 2002: a Danish questionnaire survey. AB - BACKGROUND: Sweden prohibited anonymous sperm donation in 1985 and Norway in 2005. In recent years the question of continued use of sperm from anonymous sperm donors for insemination in couples and the question of insemination of single and lesbian women have been vividly debated in Denmark. This survey examines the sperm donors' attitude towards these questions and describes any changes in attitude between 1992 and 2002. The objective is to investigate the likely consequences of abolishing anonymous sperm donation in Denmark. METHODS: A questionnaire survey carried out among donors at a private Danish sperm bank, Cryos-International Sperm Bank Ltd. Over a period of 9 weeks in 2002 an anonymous questionnaire was handed out to all donors who were in contact with the sperm bank. The results were compared to a questionnaire survey carried out in 1992 at the same sperm bank. RESULTS: In 2002, 25% (19% approved; 35% non-approved) of the donors stated that they would continue as donors if anonymity was abolished, whereas in 1992 the number was 32%. But when donors were asked whether they would accept that the children could contact them, only 22% agreed in 1992 and 13% (15% approved; 10% non-approved) in 2002. Altruistic as well as financial motives were the main factors for becoming a donor in both 1992 and 2002. Approximately 50% would accept sperm donation to lesbians in both surveys. In 2002 approximately one third was positive towards donation to single women. CONCLUSION: Maintaining anonymity is still important for the vast majority of the donors. PMID- 17364309 TI - Ten-year follow-up of endometrial ablation. AB - BACKGROUND: This paper presents a ten-year follow-up of a randomized, controlled trial which gives the long-term hysterectomy rate and patient satisfaction rate of transcervical hysteroscopic endometrial ablation in the treatment of heavy dysfunctional bleeding. METHODS: There were 120 women enrolled in the study, from June 10, 1993 to August 31, 1995, all requiring endometrial ablation for the treatment of heavy dysfunctional bleeding. All patients were offered a clinical examination two years postoperatively. Long-term outcome was assessed by completion of a questionnaire five and ten years after initial treatment. Any new symptomatology and need for further treatment or a hysterectomy was registered. A bleeding index and the patients' satisfaction rate and acceptability of the treatment method were stated. RESULTS: Sixty-one patients were treated by endometrial coagulation, and 59 by endometrial resection. No significant difference in the number of hysterectomies or satisfaction rate between the two groups was observed. At a ten-year follow-up, 63% of patients only had one ablation, 11% were treated twice, and 22% had a hysterectomy. Only 3% were lost to follow-up. For the group of patients above 40 years of age, only 17% had a hysterectomy. Since the two-year follow-up only six patients with one hysteroscopic treatment have had further intervention. Ninety-four percent of the women would recommend the treatment to their best female friend. CONCLUSION: The long-term results show that an ablation for heavy dysfunctional bleeding is an excellent treatment. Overall 22% of patients had a hysterectomy. If the patient had no further intervention at the two-year clinical control, there was only a 6% risk of hysterectomy after a period of at least ten years. PMID- 17364310 TI - Treatment of vulvovaginal erosive and stenosing lichen planus by surgical dilatation and methotrexate. AB - We treated five patients with stenosing lichen planus [LP] of the vulvovaginal region with methotrexate supplemented with ultrapotent corticosteroid cream and tacrolimus, in combination with surgical dilatation. All patients experienced long-term symptom relief, and there was only minimal or moderate re-stenosing of the vagina on follow-up for 2-41 months. PMID- 17364311 TI - Outpatient cervical ripening before first-trimester surgical abortion: a comparison between misoprostol and isosorbide mononitrate. AB - BACKGROUND: Vaginal administration of prostaglandin analogues as well as nitric oxide donors before first-trimester surgical abortion has been shown to induce effective cervical ripening. In addition, nitric oxide donors, such as isosorbide mononitrate and nitroglycerin, have been associated with a patient-friendly side effect profile when administered 3 h before the surgical procedure. We wanted to compare the cervical ripening effect and possible side effects of isosorbide mononitrate and the prostaglandin analogue misoprostol when self-administered at bedtime the evening before surgical abortion. METHODS: One hundred and twenty nulliparous women scheduled for suction termination of pregnancy in the first trimester were randomly assigned to receive per vaginam either 40 mg of isosorbide mononitrate or 200 microg of misoprostol. Sixty of the women were included for assessment of cervical ripening as well as evaluation of side effects. The other 60 women were recruited for assessment of side effects only. Cervical ripening was evaluated by measuring baseline cervical dilation and the cumulative force to dilate the cervix to 9 mm by means of a cervical tonometer. For assessment of side effects, the women were asked to complete a symptom questionnaire. RESULTS: Cervical resistance was significantly higher in women treated with isosorbide mononitrate compared to misoprostol (median cumulative force 73 versus 15 N). Common side effects of misoprostol were abdominal pain (69%), nausea (44%), and vaginal bleeding (66%), while in the isosorbide mononitrate group headache was frequently experienced (79%). In both treatment groups, the frequency and intensity of side effects gradually increased during the treatment interval. CONCLUSIONS: Misoprostol induced a more pronounced cervical ripening than isosorbide mononitrate, but both regimens were associated with a high frequency of side effects. PMID- 17364312 TI - Patients' experiences of abuse in health care: a Nordic study on prevalence and associated factors in gynecological patients. AB - BACKGROUND: In an earlier Swedish study conducted with The NorVold Abuse Questionnaire, we found that one-third of female patients who had experienced adult abuse in health care (AAHC) had a background of childhood emotional, physical and/or sexual abuse (EPSA) ('revictimised'). But since the majority of women with AAHC were 'new victims' without such a background, there might be other factors associated with AAHC. The present study aimed to map prevalence of abuse in health care (AHC), and associated variables among new victims and revictimised patients. METHODS: We carried out a cross-sectional questionnaire study at 5 Nordic gynecological clinics. Associations between AAHC and other variables were tested in a multivariate model in 4 groups of women with adult EPSA, childhood EPSA, childhood and adult EPSA, and no EPSA. RESULTS: The response rate was 77% (n=3,641). The overall prevalence of any lifetime experience of AHC was 13-28%. High educational level, physical complaints, post traumatic stress symptoms, and sleeping problems were associated with AAHC in women without EPSA (new victims). Poor self-rated health was strongly associated with AAHC in the 3 groups of women with EPSA. CONCLUSION: AHC is commonly reported by gynecological patients in the Nordic countries, but not yet properly explored or understood. The most important factors associated with AAHC were high educational level and poor self-rated health. PMID- 17364313 TI - Treatment of prolonged voiding dysfunction after tension-free vaginal tape procedure. AB - BACKGROUND: No consensus on the proper treatment of prolonged voiding dysfunction after incontinence operations exists. We, therefore, evaluated the treatment of this problem. METHODS: We reviewed all 143 patients who underwent a tension-free vaginal tape procedure (TVT) between April 1998 and June 2005. Prolonged voiding dysfunction was defined as the need to perform intermittent catheterisation for more than 1-2 weeks, and a subjective feeling of incomplete emptying. RESULTS: Ten patients (7%) with prolonged voiding difficulties were encountered. In 5 patients (50%) the tape was pulled down. This was performed after 1 week (1 patient), 2 weeks (2 patients) and 3 weeks (2 patients). All these patients were cured of their voiding dysfunction and remained dry. In 2 patients, the tape was cut after 5 and 7 months. Both patients were cured of their voiding difficulties, but had recurrent stress incontinence. Three patients performed clean intermittent catheterisation for a period of 5 weeks, 7 months and 9 months, and some degree of prolonged voiding and/or urgency persisted in all three patients. CONCLUSION: The patients with voiding difficulties after TVT should be followed closely for the first 1-2 weeks, and pulling the tape down should be carried out if the voiding dysfunction persists. PMID- 17364314 TI - Evaluation of density of Langerhans cells in human cervical intraepithelial neoplasia. AB - OBJECTIVE: To compare the number of Langerhans cells in areas of CIN 3 and in areas without histopathological alteration adjacent to CIN 3 with those found in histologically normal control cases. MATERIAL AND METHODS: Specimens were obtained from 46 normal cervixes from women undergoing hysterectomies due to uterine leiomyomata and 71 from conization specimens for CIN 3. The identification of the Langerhans cells was performed by immunohistochemical analysis, using antibodies to S-100 protein. The number of intraepithelial Langerhans cells was counted at a 400x magnification under light microscope and a 10 field count was performed in areas of epithelium of the normal cervix (group A), areas of CIN 3 in the conization specimens (group B), and areas of epithelium without histopathologic alteration adjacent to CIN 3 (group C). Results were expressed as number of cells per square millimeter of epithelium. RESULTS: Comparing groups A and B, we observed that the number of Langerhans cells was significantly higher in the latter group; between groups A and C, the number of cells was significantly lower in the second group. The number of Langerhans cells was also compared between groups B and C and it was significantly lower in the latter, independent of smoking habits. CONCLUSIONS: We theorize that the increase in the population of Langerhans cells in areas of CIN 3 could be explained by migration of these cells from adjacent areas without histopathologic alterations in order to act in the restraint of the development of neoplasia; cigarette smoking did not influence this migration. PMID- 17364315 TI - HPV DNA testing as an adjunct in the management of patients with low grade cytological lesions in Finland. AB - BACKGROUND: Patients with recurrent low grade cytological abnormalities are at increased risk for high grade lesions. We wanted to see whether these patients could be identified by HPV DNA and pap tests. METHODS: A prospective study of 663 patients referred for a colposcopy on the basis of ASC-US or LSIL cytology. High risk HPV DNA positivity and cytology were compared with histology. RESULTS: In total 65.6% samples were positive for HC2, and the overall proportion of CIN2+ lesions was 14.6%. No CIN2+lesions were found in patients testing HC2-, pap-. There were 5/97 (5.2%) high grade lesions, which were HC2-negative but pap positive, including 1 cervical adenocarcinoma in situ. The corresponding histological sections were all positive for p16INK in immunostaining. In further analysis by PCR, 3 samples were positive for HPV DNA. High-risk HPV type 67, which is not included in the HC2 probe cocktail, was found in 1 case, and 2 cases were HPV positive but could not be typed. One CIN3 and one AIS remained HPV negative. In these 5 cases, the concomitant pap smear showed ASC-USx1, LSILx1, HSILx2 and AGCx1. During 6-month follow-up, a relatively high number of CIN2+(28/557, 5.0%) emerged from the non-CIN-CIN1 group. CONCLUSIONS: The HC2 test or pap test alone were not sensitive enough to detect all CIN2+lesions. A relatively high number of CIN2+cases emerged from the non-CIN-CIN1 group after 6 months. Adequate follow-up of patients with mild cytological abnormalities, including a repeat pap smear taken during colposcopy and control at 6 months is underscored. Combination of hrHPV DNA and pap test should be considered, since it had high negative predictive value. PMID- 17364316 TI - Women's experiences of giving birth in Northwest Russia in 2000 and 2002 and in Northern Norway 2000. PMID- 17364317 TI - Second trimester cervical ectopic pregnancy treated by conservative surgery. PMID- 17364318 TI - Cavernous lymphangioma of the vulva. PMID- 17364319 TI - Spontaneous uterine rupture during pregnancy, related to a horse fall 8 weeks earlier. PMID- 17364320 TI - Successful treatment of a heterotopic cervical pregnancy and twin gestation by sonographically guided instillation of hyperosmolar glucose. PMID- 17364321 TI - Hemilaryngeal flap for hypopharyngeal reconstruction in pyriform sinus carcinoma. AB - CONCLUSION: The hemilaryngeal flap is a technique for hypopharyngeal reconstruction with the use of adjacent uninvolved tissue. The technique's advantages are that it is technically simpler than other surgical techniques for hypopharyngeal reconstruction, and involves no donor site morbidity. Its disadvantages are that it only can be employed in tumors which are confined to one side of the hemilarynx, and also there is always potential for skip lesions and incomplete resection. OBJECTIVE: To determine the indications, oncologic considerations, complication rate and survival of the surgical technique. MATERIALS AND METHODS: A meta-analysis of the available literature using the Medline database. RESULTS: There are 86 reported cases. The surgical technique was used only when one side of the hypopharynx was spared. Pharyngocutaneous fistulae developed in 16 patients (19%) and 2 patients developed pharyngeal stenosis. The technique was employed with advanced squamous cell carcinoma of the hypopharynx and the survival rates are similar to those reported when other reconstruction techniques are used. PMID- 17364322 TI - Subunits of voltage-gated calcium channels in murine spiral ganglion cells. AB - CONCLUSION: The results show that alpha1D, alpha1E, alpha2/delta, beta1, and beta3 subunits are expressed in spiral ganglion cells (SGCs), and the coexpression of alpha1D and alpha1E suggests the presence of L-type and R-type calcium channels in mammalian SGCs. OBJECTIVE: To investigate the types of subunits of voltage-gated calcium channels in SGCs of the mouse. MATERIALS AND METHODS: SGCs were isolated from cochleae of neonatal mice and cultured for 24 h. Total RNA was extracted from cultured cells. After reverse transcription, the resulting cDNA was amplified by PCR with primers targeted to nucleotide sequences corresponding to seven different calcium channel subunits. The types of calcium channel subunits were identified by PCR analysis and nucleotide sequencing. RESULTS: RT-PCR showed the strong and consistent amplification of alpha1D, alpha1E, alpha2/delta, beta1, and beta3 subunits from the mRNA of SGCs, and nucleotide sequencing confirmed the identity of mouse cochlear subunit cDNAs. PMID- 17364324 TI - Hearing results after ossiculoplasty using Polycel prosthesis. AB - CONCLUSIONS: Polycel is an effective material to use in ossiculoplasty. Good prognostic factors for hearing improvement after ossiculoplasty were healthy middle ear mucosa and the presence of stapes superstructure. OBJECTIVE: During the last decade, the surgical use of alloplasts has become increasingly widespread among otologists. This study aimed to evaluate the hearing results after ossiculoplasty using Polycel prosthesis. MATERIALS AND METHODS: We retrospectively reviewed 188 patients who underwent ossicular chain reconstruction using Polycel prosthesis and were followed up postoperatively for more than 12 months at Severance Eye-ENT Hospital from 1998 to 2002. Postoperative hearing results were assessed by measuring the postoperative air bone gap (ABG) and closure of the ABG. Successful postoperative ABG criteria were defined as the following three measurements: ABG of 1 (n=19) (p=0.0138). PMID- 17364334 TI - High mobility group HMGI(Y) protein expression in head and neck squamous cell carcinoma. AB - CONCLUSION: We conclude that increased expression level of the high mobility group I (HMGI(Y)) is closely associated with malignant transformation in head and neck squamous cell carcinomas (HNSCCs), and the measurement of HMGI(Y) levels in HNSCCs may be useful as a prognostic marker. OBJECTIVES: To investigate whether HMGI overexpression is observed in HNSCCs, and its value as a prognostic marker in HNSCCs. MATERIALS AND METHODS: HMGI(Y) expression was determined at the protein level by immunohistochemisty using a HMGI(Y)-specific antibody and RT-PCR in 10 surgically resected specimens of non-neoplastic tissue (normal palatal tissue) and 40 HNSCCs. We also evaluated the association of HMGI(Y) overexpression within clinicopathologic parameters, i.e. clinical stage, pathologic grade, status of cervical lymph node metastasis, recurrence rate. RESULTS: Expression of HMGI(Y) by immunohistochemical staining was observed in 35 of 40 (87.5%) HNSCC samples, whereas normal mucosa and/or the mucosa adjacent to the tumor tissue showed negative or weakly positive staining (p<0.05). Semi quantification of HMGI(Y) by RT-PCR was 2.98+/-2.24 in cancer and 0.47+/-0.25 in normal tissue (p<0.001). High expression of HMGI(Y) was observed in recurrent cases, compared with non-recurrent cases (p<0.05). However, no significant correlation was observed between the levels of HMGI(Y) expression and other clinical factors such as clinical stage, pathologic grade, and status of cervical lymph node metastasis. PMID- 17364335 TI - Quality assessment of a multidisciplinary tumour meeting for patients with head and neck cancer. AB - Head and neck oncology MDT meetings are held in our region to establish a correct diagnosis and an appropriate treatment plan for each reviewed patient. The quality of these MDT meetings was assessed based on the following factors: How often can a diagnosis, a TNM-classification and a treatment plan be successfully established from the workup presented at the patient's first MDT meeting? And what are the reasons for failure? Further, how often are the TNM-classification altered at treatment start? All patients (n=329) presented at MDT meetings during one year were included prospectively and data were collected in a protocol. As telemedicine recently was introduced to reduce travel, any eventual impact on quality on decisions with regard to telemedicine were also studied. A diagnosis and a treatment plan could be established for 236 (73%) of 324 patients at the first MDT meeting. TNM classification was revised in four patients (1.4%) before treatment. In conclusion, the validity of decisions made at the MDT meeting is satisfactory, but improvements regarding the quality of workups are possible. The mode of presentation of patients at the MDT meeting was not decisive for the quality of decisions regarding diagnosis and treatment plans. PMID- 17364336 TI - An effective management regimen for laryngeal granuloma caused by gastro esophageal reflux: combination therapy with suggestions for lifestyle modifications. AB - According to our previous study, lifestyle modification in combination with drug therapy is much more effective than drug therapy alone in cases of laryngopharyngeal reflux (LPR). Most patients with LPR will have chronic gastro esophageal reflux diseases (GERD) and require long-term medical therapy for control, resulting in high total expenditure on pharmacologic agents. We combined pharmacologic management with lifestyle modifications for the management of GERD with successful outcomes in patients with GERD-related laryngeal granulomas. Although further studies are needed, guidance concerning lifestyle modifications in combination with PPI therapy may be not only a clinically effective but also a cost-effective method for the management of laryngeal granulomas caused by gastro esophageal reflux. PMID- 17364337 TI - Mastoiditis complicated with Gradenigo syndrome and a hypertrophic pachymeningitis with consequent communicating hydrocephalus. AB - We present the clinical, radiological and pathological features of a case of a cranial hypertrophic pachymeningitis that developed in the course of mastoiditis and petrous apex inflammation and responded to immunosuppressive therapy only. Documented by the development of clinical findings, magnetic resonance imaging, cerebrospinal fluid changes, histopathology findings, by otosurgical intervention and finally by the insertion of a ventriculo-peritoneal shunt, the case illustrates a gradual development of pachymeningitis with consequent hydrocephalus and intracranial hypertension. We consider this disease development an example of immune-induced proliferative fibrotic changes in meninges. PMID- 17364338 TI - Phenotypic consequences in a Japanese family having branchio-oto-renal syndrome with a novel frameshift mutation in the gene EYA1. AB - Branchio-oto-renal (BOR) syndrome is an autosomal dominant inherited disorder characterized by malformations of the ear associated with hearing impairment, branchial fistulae or cysts, and renal malformations. Mutations in the gene EYA1 have been found to be responsible for BOR syndrome in approximately 40% of the subjects. Here we report a Japanese family with BOR syndrome associated with a frameshift mutation in EYA1. This mutation, 1667-1668insT, has not been previously reported and is also the first frameshift mutation in exon 16 of this gene. We describe the detailed clinical features and medical highlights of the family members, and based on their clinical histories we propose that genetic testing for EYA1 mutations would contribute to the diagnosis of BOR syndrome, facilitate genetic counseling for recurrence, give precautions regarding possible renal disorders later in life, and impact the consideration of surgical intervention for middle ear anomalies. PMID- 17364339 TI - Spindle cell carcinoma of the external auditory meatus with intracranial extension: histological, immunohistochemical and electron microscopic evaluation. AB - We present a case of squamous spindle cell carcinoma of the external auditory meatus in a 38-year-old man. The tumour was extended to the inner ear, the temporal bone, the middle cranial fossa and the meningo-cerebral tissue. The surgical intervention of temporo-occipital craniotomy removed most of the neoplasia. At pathologic examination, the tumour showed an undifferentiated spindle cell pattern. Immunohistochemistry with a large antibody panel found a weak positivity only to EMA. The diagnosis was made when the electron microscopy showed rare junctional structures and tonofilaments. PMID- 17364340 TI - Synchronous benign and malignant tumors in the ipsilateral parotid gland. AB - Synchronous benign and malignant tumors in the ipsilateral salivary glands are extremely rare. We report a unique case of synchronous unilateral parotid tumors in a 71-year-old man. The main parotid lesion was preoperatively suggested to be adenocarcinoma by fine needle aspiration cytology. A coexisting Warthin's tumor was also diagnosed on microscopic examination of total parotidectomy specimens. We describe this case of rare synchronous salivary gland tumors exhibiting both benign and malignant components with a review of the literature. PMID- 17364341 TI - Pattern of cochlear damage caused by short-term kanamycin application using the round window microcatheter method. AB - CONCLUSION: Short-term local application of kanamycin by the microcatheter method can control the region and severity of drug effect on the cochlea by changing the concentration and administration time. OBJECTIVES: To investigate the effect of short-term round window administration of kanamycin by the microcatheter method on cochlear stereociliary bundle loss in a guinea pig model. MATERIALS AND METHODS: Two concentrations and two time periods were used for drug administration to the inner ear. In groups of six animals, a total dose of 172.5 mg/ml or 345 mg/ml of kanamycin was instilled at the rate of 0.1 ml/h into the round window niche over either a 1 h or 2 h period by the microcatheter method. One group of six animals received a saline infusion as a control. The animals were sacrificed after 4 days and stereociliary bundle loss was observed by SEM. Functional changes were evaluated by auditory brainstem response. RESULTS: With regard to the severity of the damage, higher drug concentrations were associated with more severe effects. The severity of damage was the same when the same total dose was used; however, it was found that when the dose was administered over a longer period, the damage region was wider. The functional changes also corresponded with the morphological changes. PMID- 17364342 TI - Atraumatic surgical approach to the cochlea with a micromanipulator. AB - CONCLUSIONS: Our design and preliminary results show that the the micromanipulator could be a great help to the surgeon in the atraumatic surgical approach to the lateral wall of the cochlea at the promontory. OBJECTIVES: Hearing preservation in cochlear implant opens new frontiers in the treatment of sensorineural hearing loss. To preserve the membranous labyrinth intact, new surgical tools are needed, either for cochlear implantation or for other applications. The objectives of this study were to design and test a micromanipulator coupled to a drilling tool for the atraumatic exposure of the spiral ligament. The micromanipulator is designed to increase precision when drilling the otic capsule bone. MATERIALS AND METHODS: A group from the University of Navarra worked on the device design -- based on a compliant mechanism -- and in vitro test. The components and functioning of the micromanipulator are described. It was tested in 10 formalinized temporal bones after a mastoidectomy, a posterior tympanotomy, and a transcanal tympanotomy were performed. The micromanipulator was placed over the cranial surface, and used to expose the endostium, anteriorly to the round window niche. RESULTS: A combined approach through the external auditory canal was feasible, together with a posterior tympanotomy to visually control the work and make complementary manoeuvres. Drilling was easy, and visual control through the posterior tympanotomy was excellent. A high degree of drilling precision was achieved. A little disruption of the membranous labyrinth was found only in the first bone of the series. PMID- 17364343 TI - Tissular changes induced by Pseudomonas aeruginosa in an otitis media rat model with tubal obstruction. AB - CONCLUSIONS: This is a suitable model for the study of different features of middle ear inflammation. This model allows manipulations inside the middle ear while preserving relevant structures such as the tympanic membrane, and provides a useful model for the study of interactions between bacterial infection and eustachian tube dysfunction. OBJECTIVES: Analysis of early and late histological features in an experimental model of Pseudomonas aeruginosa middle ear inoculation in the rat designed for the study of middle ear procedures. MATERIALS AND METHODS: Thirty Wistar rats were inoculated with Pseudomonas aeruginosa in the tympanic bulla followed by the cauterization of the eustachian tube. Culturing of middle ear effusion was carried out at 7 days follow-up and at sacrifice. Processing of the temporal bones for light microscopy was performed at 7, 14, 30 and 60 days. RESULTS: Early cultures were positive in most cases, thus proving that middle ear inflammation was due to the presence of inoculated Pseudomona aeruginosa. Mucoperiosteal inflammatory changes similar to those observed in human middle ear infection were seen. Acute inflammatory cell infiltration was seen at 7 and 14 days, gradually decreasing to chronic inflammatory changes with fibroplasia at 60 days. Bone resorption was observed at 7 and 14 days, changing to a bony deposition at 30 and 60 days. PMID- 17364344 TI - The localization of matrix metalloproteinases-8 and -13 in cholesteatoma, deep meatal and post-auricular skin: a comparative analysis. AB - CONCLUSION: The presence of matrix metalloproteinase (MMP)-8 and MMP-13 was found to be significantly higher in cholesteatoma compared with post-auricular skin. The results show that the control group used has implications for further studies. OBJECTIVES: To compare the presence of MMP-8 and MMP-13 in cholesteatoma, deep meatal and post-auricular skin. Our null hypothesis was that there was no difference in expressions of MMP-8 and MMP-13 in the three groups. MATERIALS AND METHODS: The study was carried out in a secondary care specialist centre and used prospective retrieval of specimens for immunohistological localization of MMP-8 and MMP-13. Eleven patients undergoing cholesteatoma surgery were recruited for the study. Eleven cholesteatoma specimens, 10 deep meatal skin specimens and 10 post-auricular skin specimens were analysed. Specimens were analysed by immunohistochemistry using monoclonal antibodies to MMP-8 and MMP-13. Two observers scored the slides independently in a blind fashion. RESULTS: The presence of MMP-8 and MMP-13 was found to be significantly higher in cholesteatoma compared to post-auricular skin (p=0.02, p=0.03, respectively). There were no significant differences in expression of MMP-8 and MMP-13 between cholesteatoma and deep meatal skin (p=0.08, p=0.09, respectively). There were no significant differences in the control groups. PMID- 17364345 TI - General anesthesia changes gap-evoked auditory responses in guinea pigs. AB - CONCLUSION: General anesthesia induced by sodium pentobarbital reduces temporal resolution as represented by an increase in the threshold of gap-evoked auditory responses in guinea pigs. OBJECTIVES: To explore the potential impact of general anesthesia by sodium pentobarbital (PB), a common anesthetic used in animal research, on gap-evoked responses. MATERIALS AND METHODS: The evoked potentials in response to gaps formed by bursts of broadband noise were recorded from electrodes implanted in the inferior colliculus (IC) and the auditory cortex (AC) of guinea pigs. The gap responses were compared in three conditions: unanesthetized and anesthetized with two doses of sodium pentobarbital (40 mg/kg and 20 mg/kg). RESULTS: PB increased the gap response thresholds, especially when applied at the higher dose. The threshold shift induced by PB was greater in the AC than in the IC. In addition, the higher dose of PB significantly increased the gap response latency in both IC and AC, and decreased response amplitude in IC only. PMID- 17364346 TI - Hearing in women at menopause. Prevalence of hearing loss, audiometric configuration and relation to hormone replacement therapy. AB - CONCLUSION: Hormone replacement therapy (HRT) may have a protective effect on hearing impairment in postmenopausal women. New guidelines for classification of audiometric configuration in age-related hearing loss are suggested. OBJECTIVES: To describe prevalence of hearing loss and audiometric configuration in a group of middle-aged women with respect to menopausal stage and HRT. SUBJECTS AND METHODS: A total of 143 women around menopause were sampled through the Swedish population register. The mean hearing threshold levels were compared according to menopausal status. The audiograms in the 57 women with hearing loss were classified according to audiometric configuration. RESULTS: In all, 57 women (40%) had any kind of hearing loss; 42 had very minute hearing loss; 15 had a 4FA (average of thresholds at 0.5, 1, 2, and 4 kHz) of at least 20-39 dB HL in at least one ear. Two of these had a 4FA of 40-69 dB HL in at least one ear. The most common configurations were: gently sloping (47%), steeply sloping (14%), and high-frequency U-shaped (14%). The postmenopausal women who were not on HRT had poorer hearing mainly at 2 and 3 kHz, compared with pre- and perimenopausal women, and postmenopausal women on HRT. PMID- 17364347 TI - Diplopia in orbital fractures: a simple method to evaluate eye motility. AB - CONCLUSION: This study on eye motility demonstrates a new application of electro oculography which proved to have a high potential for establishing and diagnosing the cause of diplopia in orbital floor fractures. Electro-oculography is objective and easy to perform even when the restricted eye is covered. The 'uninjured' eye can be used as the reference. Any motility difference between the left and the right eye was easily detected. OBJECTIVE: It is essential in orbital floor fractures to distinguish entrapment from other causes of diplopia. We investigated whether vertical eye motility and restricted elevation can be detected and characterized by means of electro-oculography. MATERIALS AND METHODS: Electronystagmography equipment used for vestibular testing in daily ENT practice was used in a different context. Unilateral mechanical restriction was generated in the test subjects through fixation of one eye bulb. The velocity and range of eye motility of both eyes were measured and compared in 12 healthy test subjects and 7 patients with long-term vertical diplopia after orbital floor fractures. RESULTS: Simulated entrapment was easily detected as a distinct difference between right and left eye motility recordings (p<0.001). Recordings of patients with diplopia differed significantly from those of healthy test subjects with respect to velocity (p<0.05) and range of motility (p<0.05). PMID- 17364348 TI - Clinical experience with patients with olfactory complaints, and their quality of life. AB - CONCLUSION: A special consulting team for patients with olfactory disorders would be able to verify, describe, and explain the characteristics of the disorders, also in cases where a patient experiences a disorder, but has a normal sense of smell. OBJECTIVES: The general purpose of this paper was to present our experience with patients seeking medical attention for olfactory disorders, and to describe how quantitative and qualitative olfactory disorders are diagnosed, what the etiologies are, and how quality of life is compromised in patients with olfactory disorders. SUBJECTS AND METHODS: This investigation was performed prospectively over a 10-year period by one physician responsible for the consulting team for patients with olfactory disorders. Based on a standardized clinical examination, a structured interview, and assessment of olfactory function, its aim was to diagnose quantitative and qualitative disorders in 303 consecutive patients. Health-related quality of life was assessed with the Nottingham Health Profile (NHP) in about one-third of patients. RESULTS: In the majority of patients, a reduced sense of smell was found after testing. Often, but not always, this was combined with qualitative disorders. Dominating etiologies were infections, nasal polyposis, head trauma, and aging. Patients complaining of olfactory disorders experience a significantly reduced quality of life regarding the impact of their health problem on paid employment, household work, and social and family life. PMID- 17364349 TI - The role of flexible autofluorescence laryngoscopy in the diagnosis of malignant lesions of the larynx. AB - CONCLUSION: Autofluorescent endoscopy (AFE) combined with microlaryngoscopy (MLS) gives a more accurate diagnosis of laryngeal pathology and can be further refined to minimize the need for MLS under general anaesthesia. OBJECTIVE: The aim of the present study was to evaluate the diagnostic potential and limitations of autofluorescent flexible laryngoscopy in comparison to MLS. PATIENTS AND METHODS: We examined 40 patients using the Pentax SAFE 1000 system. All patients then underwent direct MLS and biopsy under general anaesthesia. Biopsies were taken from areas that were visually suspicious and then from areas that showed disturbed autofluorescent signals. RESULTS: The overall sensitivity of AFE for various pathologies was 90.625%, while the sensitivity of MLS was 75%. Combining the findings of AFL and MLS we had a 100% diagnostic yield. PMID- 17364350 TI - Clinical features of head and neck cancer patients with methicillin-resistant Staphylococcus aureus. AB - CONCLUSIONS: The risk factors for methicillin-resistant Staphylococcus aureus (MRSA) detection in head and neck cancer patients are the duration of hospitalization, intravenous hyperalimentation, prior antibiotic use, and the coexistence of other pathogens. OBJECTIVES: To shed light on the clinical characteristics of MRSA-positive inpatients with head and neck cancers. The secondary goal was to evaluate risk factors for MRSA detection in comparison with methicillin-sensitive S. aureus (MSSA). PATIENTS AND METHODS: Sixty-one consecutive inpatients with head and neck cancers with S. aureus detection were analyzed based on their medical records. The antimicrobial susceptibility of isolated S. aureus was tested by the broth microdilution method. RESULTS: MRSA and MSSA were detected in 46 (75.4%) and 15 (24.6%) of the 61 patients, respectively. There was no significant difference in the male/female ratio, age, primary site, comorbidity, cancer stage, cancer treatment, or 5-year survival rate between the MRSA and MSSA groups. Compared with the MSSA group, the MRSA group had significantly longer hospitalization periods and intervals between admission and MRSA detection, as well as significantly greater likelihood of intravenous hyperalimentation, prior antibiotic use, and co-isolation of other pathogens. Isolated strains of MRSA were thoroughly sensitive to vancomycin and arbekacin and moderately sensitive to minocycline. PMID- 17364351 TI - Clinical impact of positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) in head and neck tumours. AB - CONCLUSION: PET plays an important role in staging, on suspicion of recurrence and for detection of occult primary tumours in the head and neck. OBJECTIVE: Since 1998 we have used positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) to assess selected patients. This procedure has often helped in making decisions on staging and treatment. PATIENTS AND METHODS: The case records of the first 80 patients (104 PET examinations) were studied retrospectively. RESULTS: A total of 39 examinations were performed for staging. PET detected all primary tumours except two (stage T1), and staging was adjusted after 13%. In all, 33 PET examinations were performed on suspicion of recurrent tumour. In 52% of these PET determined further treatments; in 21% PET had a direct impact on the surgical planning. In 18 patients with metastases from an occult primary tumour, PET detected 39% of those tumours; in 22% it was the sole modality to do so. No recurrences or second primary tumours were detected when PET was used for follow-up of clinically cured patients. Results were similar when squamous cell carcinomas (SCCs) were considered alone as compared to the complete material. The mean standardized uptake value (SUV) was higher for cases deemed tumour-positive than in negative cases. PMID- 17364352 TI - Osteomyelitis in the head and neck. AB - CONCLUSION: All bones of the facial skeleton and spine are susceptible to osteomyelitis due to various predisposing conditions. Current radiological tools are sufficient to provide adequate diagnosis. Treatment can be conservative resection of the diseased bone with adequate clearance in all cases except in cases of osteomyelitis due to osteoradionecrosis (ORN) where resection has to be more radical. OBJECTIVE: In today's antibiotic era, osteomyelitis in the head and neck is a rare occurrence. Dealing with osteomyelitis in head and neck bones is not the same as in other bones of the body due to the nature of the bones, complex anatomy of the region, and esthetics. Our purpose was to analyze the behavior of osteomyelitis in the head and neck bones and its management. MATERIALS AND METHODS: A total of 84 cases of osteomyelitis in head and neck were reviewed in a 10-year period. Pus for culture, antibiotic sensitivity, and radiology were the main investigations. A medical line of treatment was effective in acute cases. Surgery was opted for in chronic cases. RESULTS: Mandible, frontal bone, cervical spine, maxilla, temporal bones, and nasal bones were involved, in descending order of frequency, i.e. the mandible was the most common bone affected. Nine patients were diagnosed as having acute osteomyelitis (11%); 75 were diagnosed as having chronic osteomyelitis (89%). Radiation-induced ORN leading to osteomyelitis was the most common cause of osteomyelitis of the mandible (13 of the 32 cases; 41%). Odontogenic infections and chronic sinusitis each gave rise to osteomyelitis in 3 of 10 cases (30%) of the patients with osteomyelitis of the maxilla. Chronic sinusitis was the main cause of frontal bone osteomyelitis in all 20 cases (100%). Tuberculosis (10 of 15 cases; 67%) and malignancy (5 of 15 cases; 33%) were the main predisposing factors in cervical spine osteomyelitis. Malignant external otitis (MEO) with diabetes mellitus was an underlying factor in all four cases of osteomyelitis of the temporal bone. Of the 18 patients with a diagnosis of ORN, the mandible was found to be the most susceptible bone (13 cases; 72%), followed by the maxilla (four cases; 22%) and cervical spine (1 case). Acute osteomyelitis responded to antibiotics. Sequestrectomy was carried out in all chronic cases but in cases of ORN more radical surgery was performed. PMID- 17364353 TI - Small cell carcinoma of the nasopharynx. AB - Small cell carcinoma is predominantly found in the lung and only about 5% of small cell carcinoma cases have been noted to be extrapulmonary; these are commonly found in the esophagus, pancreas, skin, uterus, and breast. A head and neck origin for small cell carcinoma is extremely rare. Both pulmonary and extrapulmonary small cell carcinomas usually have a good response to chemotherapy initially, but a poor prognosis finally. We report here a case of small cell carcinoma of the nasopharynx. The patient underwent chemotherapy and irradiation for the disease, but died of lung metastasis 38 months later. PMID- 17364354 TI - Synchronous double primary cancers of the unilateral parotid gland. AB - Synchronous parotid neoplasms, especially synchronous neoplasms of two separate and histologically different types, are extremely uncommon. A review of the literature revealed that most reported cases were either a combination of two distinct benign neoplasms or a benign neoplasm and another malignant tumor. To the best of our knowledge, there has been no report of synchronous unilateral double primary carcinomas of the parotid gland. Here we report a 39-year-old woman who exhibited basal cell adenocarcinoma and mucoepidermoid carcinoma simultaneously in the left parotid gland. PMID- 17364355 TI - Ambiguus motoneurons innervating laryngeal and esophageal muscles are malpositioned in the Reelin-deficient mutant rat, Shaking Rat Kawasaki. AB - CONCLUSIONS: The present study confirmed that ambiguus motoneurons innervating intrinsic laryngeal and esophageal muscles are radially malpositioned in the brainstem of the Shaking Rat Kawasaki (SRK), a reelin-deficient mutant rat. OBJECTIVES: Ambiguus motoneurons innervating the striated muscles of the larynx and esophagus take a long migration from their original birth plate in the floor of the fourth ventricle to their final settlement in the ventral margin of the medulla oblongata. To examine whether the migration of ambiguus nucleus neurons is affected in SRK, we studied localization of ambiguus motoneurons of postnatal day 21 (P21) normal and SRK rats. MATERIALS AND METHODS: To label ambiguus motoneurons retrogradely, horseradish peroxidase (HRP) was injected into some laryngeal muscles including cricothyroid, thyroarytenoid and posterior cricoarytenoid muscles, and the cervical and abdominal esophageal muscles of the SRK and normal controls 2 days before sacrifice. RESULTS: In the P21 normal rat, HRP-positive laryngeal and esophageal motoneurons were found in the nucleus ambiguus, whereas in the P21 SRK, they were scattered from the base of the fourth ventricle to the ventro-lateral margin of the medulla, suggesting that radial migration of ambiguus motoneurons from their birthplace to their final settlement is guided by Reelin protein. PMID- 17364356 TI - Disregard of cholesteatoma in congenital aural stenosis. AB - Congenital aural stenosis (CAS) is one type of congenital aural atresia (CAA) and is assumed to be a relatively mild type. Although CAS may be associated with cholesteatoma in the external ear canal, little attention has been paid to this association. We present two cases of CAS with middle ear infection due to destructive cholesteatoma. Both had been followed for microtia by a plastic surgeon. These patients had already exhibited cholesteatoma on CT examination, although it had been missed before the emergence of ear symptoms, otorrhea, and otalgia. We present our cases with successive changes in CT findings over time and discuss the problems of CAS with cholesteatoma. PMID- 17364357 TI - Induction of localized cochlear hypothermia. AB - CONCLUSIONS: Localized cochlear hypothermia was induced in a rat model, demonstrating the feasibility of modulating cochlear temperature without affecting core body temperature. OBJECTIVES: Systemic hypothermia has been demonstrated to protect the rat cochlea against electrode insertion trauma induced hearing loss. Due to potential adverse effects of systemic hypothermia, we set out to demonstrate the feasibility of inducing localized cochlear hypothermia and compared the efficacy of three cooling techniques. MATERIALS AND METHODS: Twenty-four ears were prepared by sealing a temperature micro-probe into the basal turn of the cochlea. Cochleae were then cooled by cold saline irrigation of the external auditory canal (EAC) or bulla or by direct application of ice over the bulla. Cochlear temperature measurements were recorded every 30 s during the cooling period until stable. Rectal temperature was monitored continuously and maintained at 36 degrees C. RESULTS: All techniques resulted in cochlear hypothermia without a concomitant change in rectal temperature. EAC irrigation (14 degrees C and 11 degrees C) decreased cochlear temperature on average by 1.1 degrees C and 1.6 degrees C, respectively. Bulla irrigation (14 degrees C and 11 degrees C) decreased cochlear temperature on average by 3.3 degrees C and 4.1 degrees C, respectively. The ice produced an average cochlear temperature decrease of 4.1 degrees C. In all cases, a cochlear temperature nadir was reached in 5-6 min with no significant differences between groups with respect to time. PMID- 17364358 TI - The role of deferoxamine in the prevention of gentamicin ototoxicity: a histological and audiological study in guinea pigs. AB - CONCLUSION: The addition of deferoxamine to gentamicin seems to confer partial functional and histological protection to the cochlea. OBJECTIVE: Aminoglycosides are known ototoxic agents. The toxicity occurs via an activation process involving the formation of an iron-gentamicin complex with free radical production. Iron chelation will supposedly limit this toxic effect. This study aimed to determine the possible cochleoprotective role of deferoxamine on the ototoxic effect of gentamicin. MATERIALS AND METHODS: Sixty healthy active guinea pigs, weighing 400-600 g, with an average age of 6 months were used. They were divided into three groups. Group 1 received intramuscular gentamicin 8 mg/kg/day, group 2 received gentamicin 8 mg/kg/day and deferoxamine 150 mg/kg twice daily for 19 days and group 3 served as a control. All animals had a baseline measurement of distortion product oto-acoustic emissions. At the end of 33 days they were submitted to another measurement and then the animals were sacrificed and their cochleas were examined histologically by light and transmission electron microscopy. RESULTS: In group 1 the mean amplitude post-injection ranged from 5.83 dB at 1001 Hz to 22.33 dB at 6348 Hz. In the deferoxamine + gentamicin group the mean amplitude post-injection ranged from 5.10 dB at 1001 Hz, to 24.45 dB at 6348 Hz. This was statistically significant. At 4004, 5042 and 6348 Hz group 2 showed less histological damage than group 1. PMID- 17364359 TI - Ventral approach to rat inner ear preserves cochlear function. AB - CONCLUSION: This technique enabled us to visualize the cochlea without causing damage. OBJECTIVE: The mammalian inner ear is difficult to approach surgically. This is particularly true in the cases of the rat and mouse, which both have small cochleae. Rat and mouse research is particularly important because their genomes are well characterized, and significantly similar to that of the human. The aim of the present study was to develop a method of accessing the rat cochlea without affecting its function. MATERIALS AND METHODS: In the ventral approach, a small hole was made for access to the scala tympani. Cochlear function was assessed through auditory brainstem response (ABR) threshold measurements. RESULTS: The ventral approach enabled the direct visualization of the tympanic bulla. Thus, the tympanic bulla could be easily opened in a manner that was benign to cochlear function. There was no significant difference in ABR threshold before and after surgery. PMID- 17364360 TI - Cochlear pathology of the circling mouse: a new mouse model of DFNB6. AB - CONCLUSION: The circling mouse (cir/cir) has phenotypes which follow the pattern of neuroepithelial defects of deafness from 10 days after birth. The cir mouse is defective in Tmie gene, the function of which should be further elucidated. OBJECTIVES: We previously reported a recessive mutation of deafness called circling mice (cir/cir). The present study focused on investigating phenotypes and histological findings of the cochlea in circling mice with respect to age. MATERIALS AND METHODS: In order to analyze cochlear pathology over time, five different age groups of circling mice were examined (10, 18, 21, 35, and 90 days old). The organs of Corti and spiral ganglion neurons in basal and middle turns were evaluated. RESULTS: The pathology of the organ of Corti followed the pattern of neuroepithelial defects. Hair cells in organs of Corti had degenerated in circling mice at 10 days old, in a time-dependent manner. Scanning electron microscopy (SEM) showed that stereociliary bundles were irregular in size and had shortened at 10 days, and that this degeneration was complete at 21 days. The number of spiral ganglion neurons significantly reduced with age. RT-PCR analysis indicated that the transmembrane inner ear gene (Tmie) was absent in various organs in circling mice. PMID- 17364361 TI - Audiological performance after cochlear implantation: a 2-year follow-up in children with inner ear malformations. AB - CONCLUSIONS: Open-set speech perception in children with an inner ear malformation is equal to that of other congenitally deaf children after an average of 2 years follow-up. OBJECTIVE: To analyze audiological performance after cochlear implantation in a sample of children with radiographically detectable malformations of the inner ear compared to performance in prelingually deafened children at large. MATERIALS AND METHODS: Nine children with osseous inner ear malformations were compared to 22 congenitally deaf children, all of whom underwent cochlear implantation. All subjects were tested on their electrical evoked compound action potential. Speech perception tests were performed using the monosyllabic trochee polysyllabic test without visual support and the open-set monosyllabic wordlist. RESULTS: In all, 20% of the congenitally deaf children in our center study have inner ear abnormalities. Inner ear malformations were limited to incomplete partition of the cochlea; none of the subjects had common cavity malformations. Electrical compound action potentials were successfully recorded in both groups intraoperatively. Speech perception tests on open-set speech yielded an average of 48.8% (SD 21.2%) in the group of children with inner ear malformations vs 54.5% (SD 21.1%) in congenitally deaf children. In four of nine cases with an inner ear malformation we encountered a minor CSF leak. PMID- 17364362 TI - How to reliably evaluate middle ear diseases? Comparison of different methods of post-processing based on multislice computed tomography examination. AB - CONCLUSIONS: Multislice computed tomography (MSCT) virtual endoscopy was useful in evaluating mainly post-traumatic and postoperative cases. In other pathological conditions axial images and MPR reformations were most useful. OBJECTIVES: Evaluation of cross-sectional images, multiplanar 2-D reformations, 3 D reconstructions and virtual endoscopy (VE) in assessment of the middle ear in inflammatory diseases, trauma, otosclerosis and tumours. Comparison of each method and correlation with surgical findings. MATERIALS AND METHODS: Investigations were carried out in 80 patients with middle ear pathology. In each case MSCT of the petrous bone was performed. In addition to cross-sectional native scans, frontal and sagittal images were achieved using MPR reconstructions. 3-D volume rendering (VR) and VE images were also generated. The value of native scans information, 2-D, 3-D reconstructions and VE of the tympanic cavity structures was assessed in comparison to intraoperative findings. RESULTS: MPR reconstructions were most useful in the assessment of skull base trauma, skull base tumours and in cases of chronic middle ear inflammation. Highly vascularized tumours, disruption of ossicular chain and stapes prosthesis were best evaluated on 3-D reconstructions. Axial images proved to be the best for otosclerosis interpretation. PMID- 17364363 TI - The effect of the sympathetic and sensory nervous system on active eustachian tube function in the rat. AB - CONCLUSION: We propose that simultaneous activation of the sensory and sympathetic nervous system may adversely affect eustachian tube function, which may have a role in the genesis of Meniere's disease. OBJECTIVE: We have determined the distribution of sympathetic and nociceptive sensory axons in the mucosa of the rat eustachian tube and investigated whether sympathetic or nociceptive neurons influence the function of the eustachian tube. MATERIALS AND METHODS: We tested whether the ability of a rat to equalize air pressure in the middle ear during evoked swallowing was altered by activation or blockade of the local sympathetic nervous system, or by stimulation of nociceptive neurons with capsaicin. RESULTS: Sympathetic axons were sparse, but CGRP-immunoreactive, nociceptive axons formed a dense subepithelial plexus beneath the eustachian tube epithelium. Neither the adrenergic blocking drug, bretylium, nor electrical stimulation of the superior cervical ganglion significantly altered eustachian tube function. Capsaicin alone did not affect eustachian tube function but capsaicin applied with an alpha adrenoceptor agonist impaired the function of the eustachian tube. Capsaicin applied to the bulla also increased spontaneous swallowing in anaesthetized rats and this effect was enhanced by addition of an alpha adrenoceptor agonist and by stimulation of the superior cervical ganglion. PMID- 17364364 TI - Cross-coupling in a body-translating reaction: interaural optokinetic stimulation reflects a gravitational cue. AB - CONCLUSION: The velocity storage integrator does not play a dominant role in the postural response to vertical visual cues; more likely, retinal slip provides the main driving force. By contrast, sideways eye movement can drive the velocity storage integrator and preserve a gravitational cue, which would be observed as a cross-coupling effect on the postural response. OBJECTIVES: To investigate the mechanism by which optokinetic stimulation causes the body to translate and to determine whether the optokinetic information is accompanied by a gravitational cue, which would appear as a cross-coupling effect. MATERIALS AND METHODS: Directionally diverse optokinetic stimuli were presented to seven healthy subjects, with and without a fixation target, and the body-translation of the subjects was recorded. RESULTS: Horizontal optokinetic stimulation with a fixation target caused the body to translate in the same direction as the optic flow. Upward or downward vertical optokinetic stimulation caused the body to translate backward or forward, respectively, only when a fixation target was present. When the subject's interaural axis was parallel to the optokinetic flow, diagonal optokinetic stimulation in the absence of a fixation target elicited responses in the pitch plane similar to those elicited by vertical stimulation in the presence of a fixation target. PMID- 17364365 TI - Mucoepidermoid carcinoma of the external auditory canal (EAC). AB - We present the third case of mucoepidermoid carcinoma of the external auditory canal (EAC) in the English literature, and discuss the management of this lesion. The patient underwent a wide local resection, superficial parotidectomy, and selective neck dissection. Although intraoperative frozen section margins were negative, permanent histopathologic examination demonstrated tumor in the medial margin, and the tumor was upgraded to a high-grade mucoepidermoid carcinoma. The patient returned to the operating room for a wider local resection, and EAC reconstruction with a temporoparietal pedicled flap and split thickness skin graft. All margins were negative on final histopathologic examination. Radiotherapy was deferred in the event of a recurrence. The patient is currently disease-free 29 months after the final excision. Most authors advocate an aggressive surgical approach, which includes a form of a temporal bone resection, for the treatment of EAC carcinoma. Although this may be warranted in cases of squamous cell carcinoma, mucoepidermoid carcinoma of the EAC may be amenable to a conservative step-by-step approach for local control with less postoperative morbidity. Given the difficulty in detecting mucoepidermoid carcinoma in surgical margins by frozen section analysis, patients should be informed of the possibility of further surgery (re-resection) when a conservative approach is used. PMID- 17364366 TI - Lipopolysaccharide-induced down-regulation of uteroglobin in the human nose. AB - CONCLUSION: Lipopolysaccharide (LPS) challenge of the human nose has the capacity to reduce the amount of natural anti-inflammatory proteins, such as uteroglobin. OBJECTIVES: Nasal challenge with LPS, an activator of innate immunity, has been shown to increase the amount of pro-inflammatory mediators in nasal lavage fluid. Uteroglobin is a newly described anti-inflammatory mediator that is secreted in the nose. This study examined the effect of nasal LPS application on the level of uteroglobin in nasal lavage fluid as well as on the expression of uteroglobin in nasal mucosa. MATERIALS AND METHODS: Thirty-eight volunteers were challenged nasally with either 50 microg LPS or vehicle; 6 h later, nasal lavage fluid was collected and a nasal biopsy was obtained. Levels of uteroglobin, albumin and the pro-inflammatory mediators interleukin (IL)-6 and IL-8 were analysed in the lavage fluids using enzyme-linked immunosorbent assays (ELISAs). Biopsies were used for either quantification of uteroglobin mRNA by real-time PCR or for localization of the corresponding protein with immunohistochemistry. RESULTS: The uteroglobin level decreased in nasal lavage fluid following LPS challenge, whereas the levels of IL-6 and albumin increased. Uteroglobin was mainly seen in the respiratory epithelium and its mRNA expression decreased as a consequence of the LPS challenge. PMID- 17364367 TI - Juvenile nasopharyngeal angiofibromas in Denmark 1981-2003: diagnosis, incidence, and treatment. AB - CONCLUSIONS: Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor in young males, with a non-negligible potential for recurrence. Preoperative embolization is a safe procedure that diminishes the peroperative blood loss and the need for blood transfusion. The endoscopic approach was used with good results in JNA stage I and II (Chandler). OBJECTIVES: To estimate the incidence rate of JNA in the Danish population and to describe symptoms and treatment. PATIENTS AND METHODS: This was a national retrospective cohort study. All cases of JNA diagnosed in Denmark from 1981 to 2003 were identified. Data were extracted from medical records. RESULTS: Forty-five male (no female) JNA cases were identified. In 43 cases, clinical data were recovered. Median age was 15 years. The incidence rate in Denmark was 0.4 cases per million inhabitants per year and 3.7 cases per million males (aged 10-24) per year. All patients underwent surgery, and the endoscopic approach was increasingly being used. The embolization procedure proved to be safe and decreased the intraoperative blood loss statistically to 650 ml in the embolized group from an average of 1200 ml in the non-embolized group (p<0.05). Similarly, the need for peroperative blood transfusion was reduced (p<0.005). The primary recurrence rate was 23% and no patients died. PMID- 17364368 TI - A completed audit cycle on post-tonsillectomy haemorrhage rate: coblation versus standard tonsillectomy. AB - CONCLUSION: A significant reduction in post-tonsillectomy secondary haemorrhage rate was observed after coblation tonsillectomy was abandoned in our department. OBJECTIVE: Comparison of the postoperative haemorrhage rate following coblation tonsillectomy and routine dissection tonsillectomy. PATIENTS AND METHODS: This was a retrospective study. In the first audit period, 441 sequential tonsillectomies between January and September 2002 were reviewed. Coblation was compared with cold steel and diathermy dissection with either ties and/or diathermy used for haemostasis. Coblation tonsillectomy was subsequently abandoned in our unit and, in the second audit period, all tonsillectomies (n=416) between July 2003 and August 2004 were included. Statistical analysis was performed using the chi2 test. RESULTS: The overall primary haemorrhage rate in the first audit cycle was 1.8% (8/441). In the second cycle with no coblation procedures, 1.4% of patients (6/416) suffered from primary haemorrhage (c.f. 8/441 (1.8%) in the first cycle, p=0.666). Secondary haemorrhage, was seen among 15.4% of patients (68/441) in the first audit cycle. In the second cycle, after coblation was discontinued, the secondary haemorrhage rate fell significantly (p<0.001) to 5.8% (24/416). A breakdown of the results of cold steel/diathermy and coblation techniques in both adults and children is also presented. PMID- 17364369 TI - Thymidine phosphorylase mRNA level predicts survival of patients with advanced oropharyngeal cancer. AB - CONCLUSION: The present study suggested that a high level of thymidine phosphorylase (TP) gene expression is significantly associated with favorable prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. Further studies consisting of large series should be performed to confirm our present results. BACKGROUND: Expression levels of the thymidylate synthase (TS) and 5-FU metabolic enzymes including dihydropyrimidine dehydrogenase (DPD), TP, and orotate phosphoribosyl transferase (OPRT), are reported to be associated with sensitivity to 5-FU-based chemotherapy in several cancers. PATIENTS AND METHODS: Intratumoral mRNA expression levels of TS, DPD, TP, and OPRT in pretreatment biopsy specimens were quantified in 27 patients with advanced oropharyngeal squamous cell carcinomas. Association of these expression levels with response to platinum and 5-FU-based chemotherapy and survival were analyzed statistically. RESULTS: By Spearman's correlation analysis, significant correlation was observed between TS and TP (gamma=0.51, p=0.018). While no correlation was observed between the tumor regression and expression of any of the genes investigated, significant association was observed between prognosis and mRNA expression levels of TS and TP. Multivariate Cox regression analysis revealed that TP mRNA expression level is a significant factor predicting prognosis (hazard ratio (HR) = - 0.204, p=0.043). PMID- 17364370 TI - The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas: are autoantibodies of influence? AB - CONCLUSIONS: The incidence rate of hypothyroidism after treatment for laryngeal and hypopharyngeal cancer is high, especially after combination treatment. An association between hypothyroidism and autoantibodies was found. OBJECTIVES: The incidences of hypothyroidism and autoantibodies were assessed retrospectively in 156 patients with laryngeal and hypopharyngeal carcinoma who were treated with surgery and/or radiotherapy between 1977 and 2002. PATIENTS AND METHODS: Patients treated for T2-T4 carcinoma or a recurrence after T1 who visited the outpatient clinic for their regular follow-up visit were included. All patients were evaluated for the development of hypothyroidism, defined as increased thyroid stimulating hormone level (>4.5 mU/L) and the presence of autoantibodies. A questionnaire regarding symptoms was administered. RESULTS: The prevalence of undiagnosed hypothyroidism following treatment of laryngeal carcinoma was 28.2%: 18.6% subclinical hypothyroidism and 9.6% clinical hypothyroidism. The prevalence of circulating antithyroid antibodies (anti-thyreoperoxidase and/or anti thyreoglobulin) was 10.5%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, ipsilateral neck dissection and autoantibodies had a higher risk of hypothyroidism. The combination of surgery and radiotherapy increased the risk. Symptoms such as weight gain and cold intolerance were significantly associated with hypothyroidism. Multivariate analysis showed hemithyroidectomy, autoantibodies, weight gain and cold intolerance to be prognostic factors for the development of hypothyroidism. PMID- 17364371 TI - Updated definition of level VI lymph node classification in the neck. AB - CONCLUSION: This update will enable us to precisely address the involvement pattern of level VI and to standardize treatment procedures in order to refine their indications and eventually improve their results and avoid treatment morbidity. BACKGROUND: The neck level classification is being used worldwide to describe the lymph nodes status of the neck. It provides standardized data to properly evaluate and then improve our protocols for the management of neck metastasis in an evidence-based medical manner. Although level VI treatment is challenging in cancer of the larynx, pharynx, trachea, esophagus, and thyroid, our knowledge about its involvement relies on few non-standardized data, due to the inadequate definition of this region. METHOD: We propose an updated radiological and surgical definition of level VI, with the introduction of two sublevels which fulfill surgical, radiotherapy, radiological, and pathological concerns. RESULTS: Level VIa encompasses prelaryngeal, intercricothyroidal, pretracheal, and perithyroidal nodes. Level VIb encompasses inferior laryngeal nodes. Within the traditional limits of level VI, all lymph nodes lying between the inferior border of the hyoid bone and the inferior border of the cricoid cartilage belong to level VIa. Between the inferior border of the cricoid cartilage and the top of the suprasternal notch, lymph nodes lying in front of the posterior face of the thyroid gland belong to level VIa; those lying behind this boundary belong to level VIb. We also discuss the definition of the superior mediastinal lymph nodes, which should not be mistaken for level VI. PMID- 17364372 TI - Diagnosis of the pathological exposure of the mastoid portion of the facial nerve by CT scanning. AB - CONCLUSIONS: High resolution CT imaging can provide useful information about the pathological exposure of the mastoid portion of the facial nerve before mastoid surgery and can assess the injury site of the facial nerve after operation. OBJECTIVES: To evaluate the diagnostic value of high resolution CT scanning of pathological exposure of the mastoid portion of facial nerve and provide valuable information for otologic surgery, and to analyse the cause of facial nerve paralysis after operation. MATERIALS AND METHODS: Routine CT scanning was used to examine patients with chronic suppurative otitis media and external auditory canal cholesteatoma preoperatively by axial-transverse and coronal views. If there was any pathological exposure of the mastoid portion of the facial nerve on CT imaging, then this was compared with intraoperative findings. In addition, one patient who had suffered postoperative facial nerve paralysis was also examined by CT scanning to determine whether any pre-existing pathological exposure of facial nerve could be found. RESULTS: Through routine CT scanning six patients with chronic suppurative otitis media and three patients with external auditory canal cholesteatoma were found to have pathological exposure of the mastoid portion of the facial nerve. Coronal views could more clearly show the size and the position of the exposure; the corresponding surgical findings (pathological exposure) for the facial nerve could be confirmed in all nine patients. CT imaging could also show that the patient who had suffered postoperative facial nerve paralysis did indeed have pre-existing pathological exposure of the mastoid portion of the facial nerve. PMID- 17364373 TI - A new procedure of arytenoid adduction combined with type I thyroplasty under general anesthesia using a laryngeal mask. AB - Laryngeal framework surgery is usually performed under local anesthesia. However, some patients are unable to tolerate extended surgery. A case of an 82-year-old woman who underwent medialization thyroplasty and arytenoid adduction of direct lateral cricoarytenoid (LCA) muscle pulling at the same time under general anesthesia using a laryngeal mask is reported. Endoscopic observation through the laryngeal mask allows direct visual control of the vocal cord. The LCA pulling method does not touch the posterior border of the thyroid cartilage so that the laryngeal mask does not disturb the arytenoid adducts. PMID- 17364374 TI - Non-recurrent inferior laryngeal nerve with multiple arterial abnormalities. AB - Non-recurrent inferior laryngeal nerve (NRILN) is a rare embryologic anomaly that can increase the risk of injury during thyroid surgery. Although the association between the NRILN and an aberrant right subclavian artery has been reported, to date there have been no reports describing cases of NRILN with multiple vascular abnormalities. A 60-year-old man with papillary thyroid carcinoma and a history of right internal carotid artery occlusion by thrombosis was examined with magnetic resonance angiography (MRA). The right NRILN was found during a total thyroidectomy with surrounding lymph node dissection. MRA revealed an aberrant right subclavian artery and aplasia of the bilateral posterior communicating arteries composing the circle of Willis. This is the first clinical report demonstrating NRILN with multiple vascular abnormalities. Patients with NRILN must be examined for vascular anomalies and associated lesions such as aneurysms and thromboembolism. PMID- 17364375 TI - Age-related differences in the use of background layout in visual search. AB - The effect of background layout on visual search performance, and more specifically on the tendency to refixate previously inspected locations and objects, was investigated. Older and younger adults performed a search task in which a background layout or landmark was present or absent in a gaze contingent visual search paradigm. Regardless of age, participants demonstrated fewer refixations when landmarks were present, with older adults showing a larger landmark advantage. This visual search advantage did not come at the cost of saccadic latency. Furthermore, the visual search performance advantage obtained in the presence of a background layout or landmark was observed both for individuals with small and large memory spans. PMID- 17364376 TI - Effects of noise on identification and serial recall of nonsense syllables in older and younger adults. AB - The present experiment investigated the hypothesis that age-related declines in cognitive functioning are partly due to a decrease in peripheral sensory functioning. In particular, it was suggested that some of the decline in serial recall for verbal material might be due to even small amounts of degradation due to noise or hearing loss. Older and younger individuals identified and recalled nonsense syllables in order at a number of different speech-to-noise ratios. Performance on the identification task was significantly correlated with performance on a subsequent serial recall task. However, this was restricted to the case in which the stimuli were presented in a substantial amount of noise. These data show that even small changes in sensory processing can lead to real and measurable declines in cognitive functioning as measured by a serial recall task. PMID- 17364377 TI - Factor structure of patient and caregiver ratings on the dementia quality of life instrument. AB - Preliminary evidence suggests that quality of life reports from patients diagnosed with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) are as reliable and valid as data provided by caregivers. To date, no studies compared the factor structure of data provided by caregivers and patients. Factor analyses are important to conduct because they are an indicator of validity. This study compared the factor structure of patient and caregiver reports on the Dementia Quality of Life scale (DQoL). Participants (N=67) were patients diagnosed with amnestic MCI or mild AD and their caregivers. Principal axis factor analyses were run separately on patient and caregiver report data. The three-factor solutions for patient and caregiver data were nearly identical. Three factors corresponding to positive affect, negative affect, and aesthetics emerged reliably from analyses. Thus, data from patients demonstrated a factor structure that was highly consistent with caregiver report data and conformed to meaningful psychological constructs. PMID- 17364378 TI - Age differences in Stroop interference: contributions of general slowing and task specific deficits. AB - This study examined the contributions of general slowing and task-specific deficits to age-related changes in Stroop interference. Nine hundred thirty-eight participants aged 20 to 89 years completed an abbreviated Stroop color-naming task and a subset of 281 participants also completed card-sorting, simple reaction time, and choice reaction time tasks. Age-related increases in incongruent color-naming latency and card-sorting perseverative errors were observed. Hierarchical regression analyses showed that the processing speed measures accounted for significant variance on both dependent measures, but that there was also a significant residual effect of age. An additional regression analysis showed that some of the variance in incongruent color-naming, after controlling for processing speed, was shared with the variance in perseverative errors. Overall, findings suggest that the age difference in Stroop interference is partially attributable to general slowing, but is also attributable to age related changes in task-specific processes such as inhibitory control. PMID- 17364379 TI - Comparing older and younger adults in an event-based prospective memory paradigm containing an output monitoring component. AB - Two experiments with younger and older adults were conducted to investigate the output-monitoring component of event-based prospective memory. In the standard form of the task, participants must remember to press a key when a certain class of items is encountered. To evaluate output monitoring, event-based cues were repeated and participants were asked to press a different key if they could remember that an earlier response was made to a particular cue. Younger adults forgot fewer of their successful responses, but displayed a distinct bias to claim that they had responded earlier when actually they had forgotten to respond. By contrast, older adults displayed this bias much less frequently. Elaborated responding to cues had the effect of improving the performance of younger, but not older adults. The results are discussed in terms of natural repetitions and omission errors that might be made in everyday prospective memory tasks. PMID- 17364380 TI - Reading comprehension in aging: the role of working memory and metacomprehension. AB - This study examines age-related differences in reading comprehension analyzing the role of working memory and metacomprehension components in a sample of young (18-30 years), young-old (65-74 years), and old-old (75-85 years) participants. Text comprehension abilities were measured by a standardized test, including two texts: a narrative and an expository text. The elderly's reading comprehension performance, when compared to the norm, emerged to be adequate. More specifically, the young-old showed an equivalent level of comprehension as the young adults for the narrative text. However, a clear age-related decline was found in the case of the expository text. Hierarchical regression analyses showed that working memory capacity, as well as different metacomprehension components but not age, are the key aspects in explaining the different patterns of changes in the comprehension of narrative and expository texts. PMID- 17364382 TI - Exploring equity and inclusion in the responses to AIDS. AB - The HIV and AIDS epidemic feeds on, and worsens, unacceptable situations of poverty, gender inequity, social insecurity, limited access to healthcare and education, war, debt and macroeconomic and social instability. The number of people living with HIV and AIDS continues to increase in several regions, most markedly in sub-Saharan Africa, the Pacific, Eastern Europe and Central Asia. The persistent nature of the epidemic and its increasing incidence in less powerful, more economically marginalised communities signals a need for a critical review of past policy and practice, particularly where this has left unchanged or worsened the risk environments that lead to new infection. Available evidence suggests that the caring and consumption burdens of AIDS have largely been met by households, limiting the capacities for future caring and mitigation of impact. Social cohesion or the collective networking, action, trust and solidarity of society, plays a positive role in reducing risk and dealing with vulnerability but is itself negatively affected by AIDS. This paper introduces the programme of work reported in this supplement of AIDS Care with an analysis of background evidence of community responses to HIV and AIDS. It explores how interventions from state institutions and non-governmental organizations (NGOs) support and interact with these household, family and community responses. How far is risk prevention reliant on individuals' limited resources and power to act, while risk environments are left unchanged? How far are the impacts of AIDS borne by households and extended families, with weak solidarity support? Where are the examples of wider social responses that challenge the conditions that influence risk and that support household recovery? Through review of literature, this background paper sets out the questions that the studies reported in this supplement have, in various settings, sought to explore more deeply. PMID- 17364383 TI - Autonomy and susceptibility to HIV/AIDS among young women living in a slum in Belo Horizonte, Brazil. AB - In Brazil in the last decade there has been an increase in the susceptibility of young women to HIV. This study explored the link between autonomy, or control over major domains of economic, social and sexual life, and susceptibility to HIV infection among poor young women living in an urban slum area of Brazil. A cross sectional survey was carried out on a random sample of 356 young women between 15 and 24 years old. The study found that indicators of autonomy that relate to sexuality, mobility and freedom from threat by partners were significantly correlated with practices linked to HIV prevention and with access to health services promoting prevention, especially among adolescents. Young women who talked to their partner about condom use before first intercourse and co-decided with them on condom use were more likely to use condoms. In contrast, those who had ever been victim of physical violence by a partner or whose partners restricted their mobility were less likely to use condoms. The study found that young women were more likely to have accessed health services for gynaecological examinations, family planning services and HIV testing if they had ever been pregnant. The findings indicate that structural gender inequalities translate into unequal relationships and reduced autonomy, increasing young women's susceptibility to HIV. A bias in HIV testing and reproductive health services towards pregnant women leaves many susceptible youth without early access. The study suggests the development of a reproductive health policy that ensures that young women access services before they get pregnant and that also reaches young males. PMID- 17364384 TI - Effectiveness of small scale income generating activities in reducing risk of HIV in youth in the Republic of Congo. AB - This short report examines the outcomes from income generating HIV prevention activities initiated in 2002 for youth in Ewo, Republic of Congo. Four years later, a follow up inquiry found that the organised schemes had collapsed, and only 24.2% of the youth were involved in income generating activities. The follow up visit explored practices associated with risk of HIV in young people. The findings suggest that for the youth in Ewo, income generating activities bring revenue, autonomy and new skills that contribute to reduced susceptibility to HIV. PMID- 17364385 TI - Putting on a brave face: the experiences of women living with HIV and AIDS in informal settlements of Nairobi, Kenya. AB - This paper examines two key dimensions of HIV and AIDS in sub-Saharan Africa, namely poverty and gender, within the particular context of informal settlements. The study, conducted in five informal settlements of Nairobi, Kenya explored the challenges facing women living with HIV and AIDS (WLWA) in informal settlements in Nairobi in terms of the specific risk environments of informal settlements, the support they receive and their perceptions of their future. The data were gathered through an interviewer-based questionnaire administered to 390 WLWA and 20 key informant interviews with Kenya Network of Women with AIDS (KENWA) project personnel. The results show that for WLWA in informal settlements, poverty and poor living conditions combine to increase the risk environment for HIV infection and other opportunistic infections and that the WLWA then face HIV- and AIDS related problems that are exacerbated by poverty and by the poor living environments. In response, the WLWA had devised coping strategies that were largely centred on survival, including commercial sex work and the sale of illicit liquor, thus increasing their susceptibility to re-infections. Insecurity in informal settlements curtailed their participation in income generating activities (IGAs) and increased their risk of rape and HIV re-infection. Recognising the disadvantaged position of communities in informal settlements, the non-governmental organizations (NGOs), community-based organizations (CBOs) and faith-based organizations (FBOs) provide a range of services including HIV and AIDS information and therapy. Paradoxically, living in urban informal settlements was found to increase WLWA's access to HIV and AIDS prevention and treatment services through NGOs and social networks that are not found in more established residential areas. The sustainability of these services is, however, questioned, given the lack of local resources, weak state support and high donor dependency. We suggest that the economic and tenure insecurity found among WLWA demands in response consistent support through comprehensive, sustainable HIV and AIDS services complemented by social networks and community sensitisation against stigma and discrimination. Fundamentally, the upgrading of informal settlements would address the wider risk environments that exacerbate the poor health of the WLWA who line in them. PMID- 17364386 TI - Contextualising AIDS and human development: Long-term illness and death among adults in labouring low-caste groups in India. AB - This study compared evidence from two low caste labouring communities in India: a relatively modernized urban group and a rural group in a backward region. It explored their levels of ill health, their capacities to respond to adult illness and the support they received. In each region, a baseline survey of approximately 1,000 households provided background quantitative evidence with qualitative evidence was collected from about 55 families. HIV infection and AIDS deaths were found to occur in the 'less poor' segments of the study group in both regions. In keeping with the official data, they formed a small proportion of the overall mortality and morbidity in this group. Stigma and discrimination were found to be low but fear of stigma was high, generated by the medical response to AIDS and used opportunistically for personal gains. The study provides insights into the structural determinants of health and coping mechanisms in these communities. The best conditions for a healthy life were found in the group that had a rooted community setting, collective political power, migrant economic support and improved working conditions--the less poor rural group. While improved economic status was associated with better health status, this relationship was stronger when combined with the presence of improved working conditions, with social cohesion at family and community levels and with political power as indicated by levels of organized collective representation and identity formation in workplace, local- and state-level politics. However, the traditional forms of social cohesion are under stress and new forms, moderated by commercial relations, are proving inadequate to meet major household shocks, like adult mortality. PMID- 17364387 TI - Expanding community through ARV provision in Thailand. AB - Anti-retrovirals (ARVs) have altered the complexion of HIV/AIDS management in Thailand. In 2005, ARVs were included within a subsidised health scheme making provision widespread. Increased access has been brought about through the legal and political advocacy of the Thai Network for People Living with HIV/AIDS (TNP+) who now play a central role in expanded ARV provision. HIV-infected volunteers help the state deliver comprehensive services and assist with follow-up and adherence programs. Alongside improvements in drug provision, a focus on pharmaceutical treatment has left other issues, such as community support of orphans and the social responses to living with HIV, less central within community responses. As they take on new responsibilities, people living with HIV/AIDS (PLHA) groups move from activities focused on reversing local stigma to constitute a new social movement that is increasingly prominent in Thai civil society. Networks of PLHA confront new social and political challenges as they also seek to broaden access to marginalised groups who remain excluded from these services. Many ethnic minority groups without full Thai citizenship have been denied access to subsidised health services including ARVs. As part of a broadening advocacy profile, the PLHA movement is now engaging in a politics of difference defined not simply by presence or absence of HIV but also by wider issues of national identity and belonging. PMID- 17364388 TI - Under the radar: community safety nets for AIDS-affected households in sub Saharan Africa. AB - Safety nets are mechanisms to mitigate the effects of poverty on vulnerable households during times of stress. In sub-Saharan Africa, extended families, together with communities, are the most effective responses enabling access to support for households facing crises. This paper reviews literature on informal social security systems in sub-Saharan Africa, analyses changes taking place in their functioning as a result of HIV/AIDS and describes community safety net components including economic associations, cooperatives, loan providers, philanthropic groups and HIV/AIDS initiatives. Community safety nets target households in greatest need, respond rapidly to crises, are cost efficient, based on local needs and available resources, involve the specialized knowledge of community members and provide financial and psycho-social support. Their main limitations are lack of material resources and reliance on unpaid labour of women. Changes have taken place in safety net mechanisms because of HIV/AIDS, suggesting the resilience of communities rather than their impending collapse. Studies are lacking that assess the value of informal community-level transfers, describe how safety nets assist the poor or analyse modifications in response to HIV/AIDS. The role of community safety nets remains largely invisible under the radar of governments, non-governmental organizations and international bodies. External support can strengthen this system of informal social security that provides poor HIV/AIDS-affected households with significant support. PMID- 17364389 TI - Gender differentiation in community responses to AIDS in rural Uganda. AB - AIDS has been reported in Africa to push households into poverty and chronic food insecurity. At the same time there are reports of significant household resilience to AIDS. This study explored how a mature epidemic in rural Uganda has affected rural farming households. It focused on gender differences in the experience of AIDS and, in particular, household capabilities to sustain livelihoods. The study compared the vulnerability of male- and female-headed households in relation to their ability to mitigate human resource losses, as well as their access to natural and physical resources, to social networks and to finance capital for production. The findings suggest that when rural households are affected by AIDS, depleting productive resources and directing resources towards immediate needs, there are gender differences in responses to, and in impacts of, the epidemic due to the different resources available to male- and female- headed households. Female-headed households were found to be more vulnerable to AIDS than male-headed counterparts. Women's remarriage opportunities were lower than men's, they faced greater risk of losing control over land and livestock and they accessed less state and private sector support. Women-headed households were more dependent on livelihood support from non governmental organizations, which were found to provide both welfare and credit support to female-headed households affected by AIDS. Women were found to play an important role in social networks and resources at community level but themselves received little support from many formal community networks and services. PMID- 17364390 TI - Community health workers as a cornerstone for integrating HIV and primary healthcare. AB - Haiti is the poorest and most heavily HIV-burdened country in the Western hemisphere, with even less health infrastructure than many countries of sub Saharan Africa. Since the early 1980s the HIV epidemic has affected the poorest communities in Haiti, who lack access to even basic healthcare. Large-scale HIV treatment requires that basic healthcare services be built and scaled up simultaneously with HIV-prevention and -care programmes. Such improvement in access to general healthcare will require substantial investments in health infrastructure, service delivery and human development. This study describes the contribution of the non-governmental organization, Zanmi Lasante (ZL) to the HIV prevention and treatment scale-up and to the ongoing efforts to improve primary healthcare (PHC) services in the public health system in Haiti. The model depends on community health workers (CHWs) who supervise antiretroviral therapy (ART) and provide community outreach, including active case finding and outreach to marginalized populations. Zanmi Lasante has recruited, trained and financed a large cadre of CHWs to provide such linkages between communities and health centres in rural Haiti. The study analysed key components of their work--their self-perception, their role in enhancing community uptake of services and their role in targeting vulnerable groups. We found that most patients at risk were properly identified at a community level. The CHWs are facilitating the uptake of PHC services, including by the most vulnerable households. The general training of CHWs has created a positive self-definition in these cadres of their medical, patient support and health service roles; although with some variability across different groups. The results of this study will be used to emphasize, standardized and strengthen the biosocial training of CHWs. PMID- 17364391 TI - Learning from diverse contexts: equity and inclusion in the responses to AIDS. AB - This paper situates the findings of the diverse studies reported in this journal supplement in a global context that both fuels the epidemic through inequality and poverty and also provides new opportunities for global commitments, solidarity and resources. The studies in this issue signal that, while information and awareness about HIV and AIDS is now high, there is still poor access to services for people to know their own risk and a deeper need to address the asymmetries of power and access to resources that influence the control people have over their sexual relationships and lives. The studies in this supplement describe, in very different contexts, responses to the impact of AIDS that are grounded within the actions of individuals, households and extended families, against a background of existing disadvantage in assets, endowment and access to state and private sector resources. Community networks reduce social isolation and provide solidarity to households struggling to respond to AIDS. The extra work involved is often done by women, particularly where the weakening of the state has left communities disadvantaged. The paper argues that connections across communities to support survival need vertical links to national and global resources, services and markets to support, sustain and transform lives. The studies demonstrate the positive effect of this through primary healthcare systems, non-government organisation support and the social movements of people living with HIV and AIDS. If the first wave of the global response to AIDS built awareness and an emergency response to prevention, treatment and care, there is now need for a 'second wave' that provides strong measures to connect communities to social, national and global resources. Elements of this 'second wave' include people's--especially women and young people's--access to services to know their individual risk, measures that enhance their autonomy and the need for a massive increase in investment in and access to decent work. PMID- 17364392 TI - Assessment of the patient flow at the infectious diseases institute out-patient clinic, Kampala, Uganda. AB - In order to cope with the increasing patient load, a study was performed to identify bottlenecks in patient flow at the Infectious Diseases out-patient clinic in Kampala, Uganda on 10 January 2005. On a standardised questionnaire we recorded for all patients: the time they presented at reception, waiting times for different services and in- and out times for nursing, counselling and doctor visits. 250 patients visited the clinic the study day: 36 (20 per cent) were asymptomatic; 133 (75 per cent) symptomatic but not critically ill and 8 (4.5 per cent) severely ill; 63 (37.5 per cent) were on antiretroviral treatment. The median time spend at the clinic was 157 minutes (range 22-426). The median time from reception to the triage/vital-signs measuring unit was 34 minutes (range 3 92), from triage nurse to doctor 51 minutes (range 1-205), from doctor to pharmacy 24 minutes (range 5-292). The median waiting time at the pharmacy was 30 minutes (range 10-175). Based on these results, organisational changes were proposed. A similar methodology could be used to evaluate and compare health service delivery systems for persons with HIV infection in Africa in order to identify the most efficient models of care. PMID- 17364393 TI - Formal and informal sector health providers in southern India: role in the prevention and care of sexually transmitted infections, including HIV/AIDS. AB - Healthcare providers (HCPs) play a central role in the provision of prevention and care services for people with sexually transmitted infections (STIs), including HIV/AIDS. However, the degree of readiness for this role through appropriate training and experience is not clear. In the case of both the urban and rural areas of the state of Karnataka, India, primary and secondary healthcare is provided by practitioners who can be categorised into three major groups: qualified allopathic physicians, qualified non-allopathic doctors (homeopathic and Ayurvedic) and registered medical practitioners. In 2002, the India-Canada Collaborative HIV/AIDS Project conducted a study in an urban area and a rural district of the state of Karnataka, collecting information from 998 care providers regarding attitudes, knowledge and practices related to STI care and HIV/AIDS care in particular. This paper analyses and compares the three different types of HCPs with respect to these parameters and discusses implications for STI/HIV/AIDS prevention and care programs. PMID- 17364394 TI - The acceptability of a directly-administered antiretroviral therapy (DAART) intervention among patients in public HIV clinics in Los Angeles, California. AB - Directly administered antiretroviral therapy (DAART) is an intensive adherence support strategy for highly active antiretroviral therapy (HAART) that requires patient acceptance to be effective. In one arm of a randomized adherence study, community workers (CW) delivered and observed ingestion of one HAART dose to participants five days a week for six months. We evaluated acceptability by study participation, retention, attendance and a satisfaction survey. Chi-square and nonparametric tests were used to examine differences between participants who did and did not complete DAART. Between November 2001 and March 2004, 416 eligible participants were identified; 250 were enrolled and 166 refused to participate (22 of these (13%) because of DAART specifically). Of the 82 randomized to DAART (70% Latino, 20% African American, 27% female and 69% foreign-born), 65 (79%) completed six months of DAART. Participants attended 6,953/7,390 (94%) appointments. Latinos were more likely to complete DAART compared to African Americans (OR=4.76, 95%CI=1.38, 16.44, p=0.01). In addition, foreign-born participants were more likely to complete DAART than US-born participants (OR=3.38, 95%CI=1.11-10.22, p=0.03). Participants completing DAART reported high rates of satisfaction. Retention, attendance and participant satisfaction suggest that DAART is an acceptable adherence support strategy in this public clinic population, particularly among Latino and foreign-born participants. PMID- 17364395 TI - Late HIV diagnosis of people from culturally and linguistically diverse backgrounds in Sydney: the role of culture and community. AB - In Australia more than 85% of newly diagnosed HIV infections in 1999-2003 were homosexually acquired. In contrast, among people from culturally and linguistically diverse backgrounds, there is a much higher proportion of heterosexual exposure and many of the heterosexually acquired infections are diagnosed 'late', with people sometimes presenting with symptoms of AIDS. This paper reports on circumstances of late HIV diagnosis, meaning of an HIV-positive diagnosis and perceptions of risk among HIV-positive people from a variety of cultural and ethnic backgrounds in Sydney. The focus was on commonalities across cultures and ethnicities. Data were collected through semi-structured in-depth interviews with clients of the Multicultural HIV/AIDS and Hepatitis C Service and a sexual health clinic. Regular HIV tests were the exception in this group. Testing was usually motivated by a serious health crisis. Participants interpreted their diagnosis in the context of their knowledge and experiences with HIV/AIDS in their country of birth and the perceptions of HIV/AIDS in their ethnic communities in Australia. Many were not aware of the relationship between HIV and AIDS. Risk was perceived in terms of 'risk group' membership not in terms of practices and behaviours. Late diagnosis cannot be explained solely by association with country of birth, race or ethnicity. Rather, it is located within complex sets of social and cultural relations: the values attributed to HIV/AIDS and those infected and the social and cultural relations of ethnic communities in Australia and the dominant culture. These are enacted in healthcare seeking behaviour, perceptions of people with HIV and perceptions of being 'at risk'. PMID- 17364396 TI - Symptom management and self-care for peripheral neuropathy in HIV/AIDS. AB - Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, sociodemographic and disease-related correlates and self-care strategies. A convenience sample of 1,217 respondents was recruited from data collection sites in several US cities, Puerto Rico, Colombia and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified 20 self-care behaviors including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Ratings of frequency and effectiveness were also included. An activities checklist summarized into five categories of self-care behaviors including activities/thoughts, exercise, medications, complementary therapies and substance was used to determine self-care behaviors. Taking a hot bath was the most frequent strategy used by those with peripheral neuropathy (n=292) and received the highest overall rating of effectiveness of any self-management strategies included in this study at 8.1 (scale 1-10). Other self-care strategies to manage this symptom included: staying off the feet (n=258), rubbing the feet with cream (n=177), elevating the feet (n=236), walking (n=262), prescribed anti epileptic agent (n=80), prescribed analgesics (n=84), over-the-counter medications (n=123), vitamin B (n=122), calcium supplements (n=72), magnesium (n=48), massage (n=156), acupuncture (n=43), reflexology (n=23) and meditation (n=80). Several behaviors that are often deemed unhealthy were included among the strategies reported to alleviate peripheral neuropathy including use of marijuana (n=67), cigarette smoking (n=139), drinking alcohol (n=81) and street drugs (n=30). PMID- 17364397 TI - Late entry into HIV/AIDS medical care: the importance of past relationships with medical providers. AB - Data are presented from a qualitative study that explored the impact of relationships with medical providers on late entry into HIV/AIDS medical care. In depth interviews were conducted with ten males living on the US-Mexico border who entered medical care late in the progression of HIV. The findings focus on past relationships with medical providers and the perception of risk on both the part of the medical provider and the study participant. Current policy and programmatic trends and recommendations are discussed. PMID- 17364398 TI - Factors associated with use of HIV primary care among persons recently diagnosed with HIV: examination of variables from the behavioural model of health-care utilization. AB - The delay between testing positive for human immunodeficiency virus (HIV) and entering medical care can be better understood by identifying variables associated with use of HIV primary care among persons recently diagnosed with the virus. We report findings from 270 HIV-positive persons enrolled in the Antiretroviral Treatment Access Study (ARTAS). 74% had not seen an HIV care provider before enrollment; 26% had one prior visit only. Based on Andersen's behavioural model of health care utilization, several variables reflecting demographic, healthcare, illness, behavioural, and psychosocial dimensions were assessed and used to predict the likelihood that participants had seen an HIV care provider six months after enrollment. Overall, 69% had seen an HIV care provider by six months. In multivariate analysis, the likelihood of seeing a provider was significantly (p<.05) higher among men, Hispanics (vs. non-Hispanic Blacks), those with higher education, those who did not use injection drugs, those with three or more HIV-related symptoms, those with public health insurance (vs. no insurance), and those who received short-term case management (vs. passive referral). The findings support several conceptual categories of Andersen's behavioural model of health services utilization as applied to the use of HIV medical care among persons recently diagnosed with HIV. PMID- 17364399 TI - Relationship quality among HIV patients and their caregivers. AB - Despite the increasing attention to caregivers of HIV patients, no previous study has systematically investigated the effects of the relationship quality between an HIV patient and their caregiver. The present study assessed 176 dyads consisting of an HIV-infected patient and their self-identified 'caregiver'. Relationship quality was measured by the Family Assessment Device (FAD). Dependent measures included the Beck Depression Inventory, SF-36 Physical Functioning Scale, Caregiver Strain Index and 4-day HIV treatment adherence. A substantial proportion of HIV patient-caregiver dyads reported difficulties in their relationships (17-66% depending upon FAD scale). The level of relationship difficulties was not strongly related to the type of patient-caregiver relationship. However, the quality of the HIV patient-caregiver relationship was significantly associated (p<0.05) with caregiver depression and burden as well as HIV patient depression, physical functioning and HIV medication adherence, even when the potential effects of length of HIV infection and social support were controlled. These results suggest that relationship quality is impaired in many patient-caregiver dyads and is uniquely associated with levels of depression, caregiver burden and treatment adherence. PMID- 17364400 TI - Recognizing HIV/AIDS volunteers' stressors and desire for support. AB - Little research has focused on experiences of volunteers for people living with HIV/AIDS but other research on caregivers for this population illustrates the stress often experienced. This study identifies stressors experienced by volunteers for people with HIV/AIDS, and determines the types of social support needed to help volunteers cope with the stressors identified. Six volunteers were interviewed at a small non-profit organization in Appalachia providing such services. Participants indicated that providing services for people with HIV/AIDS is a rewarding experience; however, stress and frustration played a large role in their experiences with the organization. Further, the results of this study indicate that emotional and informational social support may help volunteers cope with stressors associated with providing services for people with HIV/AIDS. PMID- 17364401 TI - Perceived stress is associated with CD4+ cell decline in men and women living with HIV/AIDS in Spain. AB - This study assessed whether perceived stress as measured by the Perceived Stress Scale (PSS) was associated with a decline in CD4+ cell counts over a six-month period in 59 men and 41 women living with HIV-1. Participants underwent psychological and medical assessment at the study entry (baseline) and again at six months post-baseline. In a hierarchical regression model controlling for sociodemographic (e.g. age, gender, education, income) and disease-related variables (e.g. duration of antiretroviral treatment, antiretroviral treatment and adherence, CD4+ cell count and viral load), perceived stress was associated with the decline in CD4+ cell count over the six-month period. These findings suggest perceived psychosocial stress is associated with CD4+ cell count decline independent of sociodemographic factors and disease status among men and women on antiretroviral medication for HIV/AIDS. PMID- 17364402 TI - Psychiatric co-morbidity in vulnerable populations receiving primary care for HIV/AIDS. AB - Considerable evidence suggests that people with HIV disease are significantly more distressed than the general population, yet psychiatric disorders are commonly under-detected in HIV care settings. This study examines the prevalence of three stress-related psychiatric diagnoses--depression, posttraumatic stress disorder (PTSD), and acute stress disorder (ASD), among a vulnerable population of HIV-infected patients. Among approximately 350 patients attending two county based HIV primary care clinics, 210 participants were screened for diagnostic symptom criteria for depression, PTSD, and ASD. Standardized screening measures used to assess for these disorders included the Beck Depression Inventory, the Posttraumatic Stress Checklist, and the Stanford Acute Stress Questionnaire. High percentages of HIV-infected patients met screening criteria for depression (38 per cent), PTSD (34 per cent), and ASD (43 per cent). Thirty eight percent screened positively for two or more disorders. Women were more likely to meet symptom criteria for ASD than men (55 per cent vs. 38 per cent, OR=1.94, CI95 per cent=1.1-3.5). ASD was detected more commonly among African-American and white participants (51 per cent and 50 per cent respectively), compared with other ethnic groups. Latinos were least likely to express symptoms of ASD (OR=0.52, CI95 per cent=0.29-0.96). Of the 118 patients with at least one of these disorders, 51 (43 per cent) reported receiving no concurrent mental health treatment. Patients with HIV/AIDS who receive public healthcare are likely to have high rates of acute and posttraumatic stress disorders and depression. These data suggest that current clinical practices could be improved with the use of appropriate tools and procedures to screen and diagnose mental health disorders in populations with HIV/AIDS. PMID- 17364403 TI - HIV status, trust in health care providers, and distrust in the health care system among Bronx women. AB - Trust in health care providers and the health care system are essential. This study examined factors associated with trust in providers and distrust in the health care system among minority HIV-positive and -negative women. Interviews were conducted and laboratory tests performed with 102 women from the Women's Interagency HIV Study Bronx site. Interviews collected information about trust in providers, distrust in the system, substance use, mental health symptoms and medications, and sociodemographic characteristics. Many reported distrust of the health care system related to HIV, and most reported trust in their providers. On linear regression analyses, characteristics associated with distrust in the health care system included depressive symptoms (beta=0.48, p<0.05). Characteristics associated with trust in providers included HIV-positive status (beta=0.35, p<0.05), taking mental health medications (beta=0.39, p<0.05), and having a white provider (beta=0.36, p<0.05). Despite distrust in the health care system related to HIV, most reported high trust in their providers, with HIV positive women trusting their providers more than HIV-negative women. Studies are needed to understand how trust in providers and the health care system is achieved and maintained, and how trust is correlated with HIV-related health outcomes. PMID- 17364404 TI - Body image in older men with or at-risk for HIV infection. AB - We performed a cross-sectional analysis of factors associated with negative body image among 550 older men with or at-risk for HIV infection, including demographics, depression, illicit drug use, and antiretroviral therapy adherence. Overall, 31 per cent of participants reported negative body image, which was independently associated with increased BMI, self-rated fair/poor health, depression, and erectile dysfunction, but not HIV status. Screening for and treating depression, sexual dysfunction, and obesity in older men should be considered. PMID- 17364405 TI - Examining HIV/AIDS provider stigma: assessing regional concerns in the islands of the Eastern Caribbean. AB - HIV/AIDS provider stigma has been understudied in the context of prevention, testing, and treatment. Results of a survey of persons associated with HIV/AIDS education, health care, and social service delivery in the Eastern Caribbean are described. Reliable constructs were observed for warmth towards PLHA, comfort in association with them, tendencies to distance from or condemn them, beliefs in viral transmission myths, and perceived capacity to counsel effectively. Most discrimination was directed towards MSM and IDUs. Providers whose roles were likely to involve touch felt less comfortable around PLHA and more likely to distance from and condemn them than providers whose roles were not. Implications for improved measurement and incorporation of mindfulness techniques in stigma intervention are discussed. PMID- 17364406 TI - Ancillary services and retention of youth in HIV care. AB - The purpose of this prospective study was to test the relationship between receipt of ancillary services (case management, advocacy, counseling) over six months and retention of youth in HIV care in the subsequent six months. Medical records of 75 youth (ages 16-25) enrolled in a comprehensive HIV care program at a university-affiliated medical center in Detroit, Michigan were reviewed for receipt of services in a 12-month period. The youth program offered medical and ancillary services in a one-stop-shopping model. The expectation for medical care for youth was at least quarterly medical appointments. A three-point scale was constructed with a score of '0' indicating no gaps (at least one medical care appointment every three months in a six-month period), a score of '1' indicating one gap (no appointment in one of the two quarters) and a score of '2' indicating two gaps (no appointments in six months). Increased receipt of ancillary services in the first six months predicted lower gap scores in the second six months, even controlling for gap scores in the first six months. Counseling appointments were the strongest predictor. Preliminary results suggest the continued need for resources allocated to ancillary services to support retention in care. PMID- 17364407 TI - Adverse quality of life consequences of antiretroviral medications. AB - To identify the effects of antiretroviral therapy on quality of life, we performed a qualitative content analysis of the Medical Outcomes Study-Human Immunodeficiency Virus (MOS-HIV) Health Survey. We used focus groups to elicit views about antiretroviral effects on quality of life from a purposive sample of treatment-experienced participants. Data were analysed using a grounded theory approach. We appraised the content of the MOS-HIV against the themes identified from our analysis. Participants also completed the MOS-HIV survey and were asked whether the survey captured all important medication-related aspects of quality of life. Participants (n=38) viewed the use of antiretrovirals as a trade-off between poorer quality of life and being alive. The net effect was increased longevity but without hope and future. Features of quality of life included the downstream consequences of side effects and toxicities, tensions with health care providers and loss of independent decision-making, dilemmas regarding drugs and career, burdens of medication-taking responsibilities, and the stress of living life under a pretense and hiding an HIV diagnosis. The MOS-HIV missed or under emphasised these features. Quality of life concerns of people living with HIV, particularly those related to medication use, are not well captured by the MOS HIV. A broad concept of quality of life is needed to encompass all dimensions important to people living with HIV. PMID- 17364408 TI - Stigmatization and shame: consequences of caring for HIV/AIDS patients in China. AB - Using a representative sample of 478 doctors, nurses, and lab technicians working with people living with HIV/AIDS (PLWHA), a cross-sectional study was conducted to assess the impact of the AIDS epidemic on medical care systems and service providers in China. Correlation analyses showed significant association between internalized shame reported by service providers and their perception of being stigmatized due to working with PLWHA. Multivariate analyses revealed that the perceived level of institutional support for AIDS care was significantly related to the stigmatization and shame reported by the service providers. The study findings suggest that improved institutional support for AIDS care at the facility level and HIV-related stigma reduction intervention are crucial to maintain a high quality performance by the workforce in the health care system. PMID- 17364409 TI - AIDS-defining opportunistic illnesses in the HAART era in New York City. AB - Despite widespread availability of HAART, opportunistic illnesses (OIs) still occur and result in an increased risk of mortality among persons with AIDS. We estimated the incidence of OIs among all new adult AIDS cases in New York City in 2000 overall and in demographic and clinical subgroups and identified factors associated with occurrence of an AIDS-defining OI versus AIDS diagnosis based on low CD4+ values only. In 2000, 5,451 new AIDS cases were reported to the New York City Department of Health and Mental Hygiene. Of these 27.4% (95% CI: 22.8-32.6) had at least one OI, most frequent being Pneumocystis jiroveci pneumonia (12.2%) and M. tuberculosis (5.3%); 47.1% (41.7-52.5) had a late HIV diagnosis (i.e.< or =6 months before AIDS diagnosis). Persons with a late HIV diagnosis not in recent care had a 3.5-fold increased odds (1.29-9.63) of an OI, compared to non-late testers in care. Other predictors of an OI were injection drug use and older age. We conclude that OIs remain prevalent in the HAART era and late testers not in care are especially likely to develop an OI. Our results support comprehensive HIV programs promoting early HIV testing and linkage to care to prevent OI related morbidity and mortality. PMID- 17364410 TI - Appropriateness of antiretroviral therapy in clients of an HIV/AIDS case management organization. AB - We sought to assess appropriateness of antiretroviral therapy (ART) reported by clients of an HIV/AIDS case management organization and identify variables associated with appropriate ART receipt. A total of 295 such clients were mailed a survey asking them to identify antiretroviral medications they were taking. Of them 220 (75%) returned surveys; 201 (93%) were taking antiretrovirals. Of these, 159 were on appropriate and 36 on inappropriate ART, as determined by guidelines created by the CDC, the International AIDS Society (USA Panel), and the Panel on Clinical Practices for Treatment of HIV Infection. In unadjusted analyses, age, sex, race, sexual orientation, history of injection drug use, history of sexual risk, and HIV knowledge were associated (p< or =0.10) with appropriate ART and entered into one of two logistic regression models. The first model indicated that women (p=0.003) and heterosexuals (p=0.001) were less likely to receive appropriate ART than men and gay/bisexuals (and variables interacted, p=0.001). HIV knowledge--a proxy indicator determined by self-report of a CD4 cell count and viral load--was added to variables retained in first model to create a second model. Only sexual orientation was retained in this second model (p=0.02, in the same direction as in the first model), and those with less versus more HIV knowledge (p=0.04) were found to be less likely to receive appropriate ART (and variables interacted, p=0.04). Findings suggest that heterosexual men are less likely than women who, in turn, are less likely than gay/bisexual men to receive appropriate ART. HIV-related knowledge appears to increase likelihood of receiving appropriate ART and it attenuates the effect of sex. PMID- 17364411 TI - Migration, behaviour change and HIV/STD risks in China. AB - This paper examines if and how temporary migration increases the risk for HIV/STDs in China. Results suggest that temporary migrants had significantly higher prevalence of HIV-risk sexual and drug using behaviours but no significant differences were found between migrants and non-migrants in prevalence of HIV/STDs. Employing logistic regression analysis, we examined three mechanisms- lax social control, social isolation and migrant selectivity--by which the process of migration may lead to behaviour changes that increase migrants' HIV/STD risks. Results indicate that post-migration lax social control was the most significant mediating factor between migration and HIV risk behaviours. Temporary migrants are at high risk of HIV/STDs. Prevention interventions need to pay particular attention to migrants' post-migration lax social control. PMID- 17364412 TI - Profiling of HIV clinic patients to determine the prevalence and characteristics of recent infections. AB - Patients newly attending the government HIV clinic in Hong Kong were studied for the prevalence and characteristics of recent HIV infection, which was defined as having a negative HIV antibody test and/or seroconversion illness within one year of a first positive antibody result. Fifty-nine (12.0%) of 492 HIV-positive patients first seen from 2001 to 2004 were determined to be recently infected. This likely represented the lower bound of the real situation. Compared with non recent infections on univariate analysis, recent cases were more likely to be men who have sex with men (OR 2.23; 95%CI, 1.23-4.05), never married (OR 1.96; 95%CI, 1.03-3.89), had tertiary or above education (OR 3.93; 95%CI, 1.65-10.09) and with a baseline CD4>=500 cells/ul (OR 3.65; 95%CI, 1.87-6.93). Upon multivariate analysis, tertiary or above education (adjusted OR 4.23; 95%CI, 1.76-10.16) and CD4>=500 cells/ul at diagnosis (adjusted OR 3.58; 95%CI, 1.88-6.84) remained independent variables. HIV clinics are feasible settings for collecting epidemiological information of on-going infection. Differences in the profile between recent and non-recent cases may shed light on targeting efforts to prevent new HIV infections. PMID- 17364413 TI - Marijuana as therapy for people living with HIV/AIDS: social and health aspects. AB - Therapeutic use of marijuana has emerged as an important issue for people living with cancer, HIV/AIDS and multiple sclerosis. This paper examines therapeutic use of marijuana in the Positive Health cohort study, a longitudinal cohort study of men and women living with HIV/AIDS in NSW and Victoria, Australia. Factors that distinguish therapeutic use of marijuana from recreational use were assessed by comparisons on a range of social and health-related variables. The results show that among 408 participants, 59.8% reported some use of marijuana in the past six months. Of those participants (n=244), 55.7% reported recreational use only of marijuana and 44.3% report mixed use of marijuana for therapeutic and recreational purposes. Multivariate logistic regression analysis showed that participants who used marijuana for therapeutic purposes were significantly more likely than recreational-only users to have used other complementary or alternative therapies, experienced HIV/AIDS-related illness or other illnesses in the past 12 months, had higher CD4/T-cell counts, had lower incomes, be younger in age and less likely to have had a casual partner in the six months prior to interview. These results show that a substantial proportion of people living with HIV/AIDS (PLWHA) use marijuana for therapeutic purposes, despite considerable legal barriers, suggesting marijuana represents another option in their health management. Rather than solely using marijuana in response to illness, the experience of illness may influence a person's understanding of their marijuana use, so that they come to understand it as therapeutic. Further research might consider possible interactions between cannabinoids and antiretroviral treatments, potential use of oral THC and the difficulties faced by clinicians and PLWHA in discussing marijuana in the current legal context. PMID- 17364415 TI - Gambling and substance use disorders: current status and future directions. AB - This paper briefly reviews the clinical presentation of pathological gambling and presents data related to the co-occurrence of pathological gambling and substance use disorders. Both epidemiological and treatment data are reviewed. The putative physiological substrates underlying pathological gambling are described, along with the limited genetics data. Types of treatments applied to gamblers are described, including data on efficacy and overlap of issues that relate to both gambling and substance use disorders. Finally, areas for future research are suggested to advance our understanding of pathological gambling and its relationship to substance use disorders. PMID- 17364416 TI - Criminal behavior in antisocial substance abusers between five and fifteen years follow-up. AB - Antisocial personality disorder (ASPD) is one of the most common co-occurring disorders in substance abusers, characterized among other things by a high propensity for criminal actions. A cohort of 125 substance abusers were followed in a longitudinal design. Patients were diagnosed with ASPD at an index treatment episode, interviewed at five-year follow-up, and followed-up through the Swedish criminal justice register by 2005 for the years 1995-2003. ASPD and non-ASPD subjects were compared using Mann Whitney U test for ordinal variables (number of offenses and months in prison) and chi-square tests for categorical variables. A total of 107 were alive by 1995, when the period of observation began. ASPD diagnosed at baseline was related to criminal offenses and incarceration during the follow-up from 5 to 15 years. For most categories, ASPD diagnosis was associated with higher frequency of offense. An ASPD diagnosis based on SCID-II interview made at five-year follow-up was related to the number of offenses but unrelated to incarceration. In a sample of drug abusers, ASPD was associated with high levels of criminal behavior, even years after the diagnosis was given. A diagnosis based on clinical observation during treatment was at least as predictive of criminal behavior as a diagnosis based on a SCID-II interview. PMID- 17364417 TI - Socially sanctioned coercion mechanisms for addiction treatment. AB - Coercion as a strategy for treatment of addiction is an effective but often negatively perceived approach. The authors review current policies for involuntary commitments and explore coercive dimensions of treating alcohol and drug dependence in the workplace, sports, and through professional licensure. Gender-specific issues in coercion are considered, including evidence for improved treatment retention among pregnant and parenting women coerced via the criminal justice system. Social security disability benefits represent an area where an opportunity for constructive coercion was missed in the treatment of primary or comorbid substance use disorders. The availability of third-party funding for the voluntary treatment of individuals with substance use disorders has decreased. This unmet need, coupled with the evidence for positive clinical outcomes, highlights the call for implementing socially sanctioned mechanisms of coercion. PMID- 17364418 TI - A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV). AB - This pilot study evaluated the efficacy of a twelve-session cognitive behavioral group therapy for alcohol-dependent males with co-occurring interpersonal violence (IPV). Participants were 85 alcohol-dependent males who were arrested for domestic violence within the past year. Seventy-eight male adults were randomized to either a cognitive behavioral Substance Abuse Domestic Violence (SADV) group (N = 40) or a Twelve-Step Facilitation (TSF) Group (N = 38). There was no significant difference between SADV versus TSF in the number of sessions attended. Regarding substance use, the group assigned to SADV reported using alcohol significantly fewer days (eg, 90 days of abstinence across the 12 weeks of treatment) as compared to the TSF group. Regarding physical violence, there was a trend for participants in the SADV condition to achieve a greater reduction in the frequency of violent episodes across time compared to individuals in the TSF group. These data suggest the promise of the SADV group therapy approach for alcohol-dependent males with a history of IPV who present for substance abuse treatment. PMID- 17364419 TI - Cigarette smoking and long-term alcohol and drug treatment outcomes: a telephone follow-up at five years. AB - This prospective study examined the relationship between cigarette smoking and five-year substance abuse treatment outcomes. Of 749 individuals who began private outpatient treatment, 598 (80%) were re-interviewed by telephone at five years. At five-year follow-up, 53% reported smoking cigarettes in the prior 30 days. Smokers were less likely to be abstinent from alcohol and drugs in the prior 30 days (48.3% vs. 64.0%), and had higher Addiction Severity Index (ASI) scores in employment, alcohol, drug, psychiatric, and family/social problems; worse self-reported health; and greater self-reported depression. Findings inform understanding of long-term substance abuse treatment outcomes and potential service needs of smokers. PMID- 17364420 TI - Individual and social network factors that predict entry to drug treatment. AB - Prospective data were analyzed to examine individual and social network characteristics that predict entry into drug treatment among a sample of 557 heroin and cocaine users. Entering treatment was associated with being HIV positive [AOR: 2.25, 95% CI: 1.33-3.81] and a history of drug treatment [AOR: 3.41, 95% CI: 2.19-5.31]. Individuals with a greater number of social network members who were in drug treatment [AOR: 1.29, 95% CI: 1.07-1.56] and fewer network members who smoked crack [AOR: 0.86, 95% CI: 0.75-0.99] were more likely to enter treatment. Social network-based interventions that promote successful outcomes in drug treatment are needed. PMID- 17364421 TI - Influence of attention-deficit/hyperactivity disorder symptoms on methadone treatment outcome. AB - A review of 687 consecutive admissions to a Midwestern methadone maintenance program was undertaken to establish the prevalence of ADHD symptoms and their association with treatment outcome. Of the 687 admissions, 396 (58%) patients self-reported experiencing one or more ADHD symptoms during the two weeks prior to admission, and 131 (19%) patients reported ADHD symptoms that significantly interfered with functioning in daily activities. At nine months post-admission, the patients who reported significant symptoms of ADHD were able to reduce their drug use but were less likely to have achieved abstinence than those who did not report significant symptoms (p < or = 0.001). The authors discuss the importance of screening for ADHD symptoms in methadone treatment programs and propose interventions believed helpful in improving management of ADHD symptoms and improving outcome. PMID- 17364422 TI - Friends, family, and alcohol abuse: an examination of general and alcohol specific social support. AB - Social support may be considered from several different dimensions. While general social support promotes well-being, specific social support is tied to particular functions, such as alcohol use. Not only may the form of social support vary, but also the source (ie, friends vs. family). This study investigated the impact of general and specific support for alcohol use from family versus friends on alcohol use among 897 U.S. residents of abstinent communal-living settings (Oxford Houses). Results indicated that general support from friends and length of stay in Oxford House significantly predicted less alcohol use. Implications for alcohol recovery are discussed. PMID- 17364423 TI - A retrospective case control study of alcohol relapse and spiritual growth. AB - In the context of an NIAAA/Fetzer Institute-funded study designed to look at the impact of spirituality in an inpatient alcohol treatment, this retrospective case control study investigated whether spiritual growth occurred during an inpatient phase of treatment for alcohol dependence, the degree to which spiritual gains (if noted) would be maintained at follow-up, and whether spiritual growth would be associated with follow-up sobriety. To accomplish this goal, thirty-six individuals who reported relapsing to alcohol at three-month follow-up were compared with thirty-six matched controls who reported abstinence at follow-up. Spiritual development and change was assessed via a set of six measures. Paired t tests revealed that spiritual growth occurred across all measures during the treatment phase. Repeated measures analysis of variance (ANOVA) indicated that this growth was maintained at three-month follow-up. Two-way repeated measures ANOVA revealed that while non-relapsers maintained spiritual growth over the course of four weeks of treatment and in the three-month period following treatment, renewed alcohol use was associated with decreased spirituality. PMID- 17364424 TI - Adolescents with conduct disorder: early smoking and treatment requests. AB - This study explored the relationship of a diagnosis of conduct disorder (CD) with the developmental smoking trajectory among 117 adolescent volunteers. Logistic regression analyses revealed that adolescents with CD smoked their first whole cigarette earlier (p = 0.03) and sought cessation treatment earlier (p = .01) compared to non-CD adolescents. Additionally, adolescents who smoked their first whole cigarette before the age of nine were eight times more likely to have CD. These findings suggest that in addition to addressing disruptive behaviors, early prevention and access to interventions for tobacco use are needed for youths with CD. PMID- 17364425 TI - Tramadol dependence: treatment with buprenorphine/naloxone. PMID- 17364426 TI - Treating inhalant abuse with buspirone. PMID- 17364428 TI - A prospective study to evaluate the impact of 31P-MRS to determinate mitochondrial dysfunction in skeletal muscle of ALS patients. AB - Impaired mitochondrial energy production probably plays a role in motor neuron death in amyotrophic lateral sclerosis (ALS) and has been found not only in motor neurons but also in skeletal muscle of patients with ALS. 31P magnetic resonance spectroscopy (31P-MRS) has the potential to reflect the energy metabolism of skeletal muscle in vivo. We sought to determine whether an altered mitochondrial energy metabolism of the muscle cell in patients with SALS can be detected by 31P MRS, and to this end we recorded 31P-MR spectra of the gastrocnemius muscle of patients with ALS under a standardized isometric muscle exercise protocol. In a prospective setting we compared ten patients with sporadic ALS and 38 age-matched controls. The patients were characterized by a disease duration of approximate 18 months and classified as having probable to definite ALS by means of the revised El Escorial criteria. The time constant of oxidative PCr recovery after aerobic (tau1) and ischaemic muscle contraction (tau2) was used to determine the capacity of mitochondrial ATP formation. We found that mitochondrial impairment in skeletal muscle of patients with ALS could not be confirmed by 31P-MRS and therefore cannot be used as a surrogate factor of the disease. PMID- 17364429 TI - Brain perfusion imaging in amyotrophic lateral sclerosis: extent of cortical changes according to the severity and topography of motor impairment. AB - In amyotrophic lateral sclerosis (ALS), attempts have been made to correlate the extent of cortical lesions with the intensity of motor dysfunction in ALS patients. Our aim was to compare the cerebral perfusion as measured by SPECT with the topography and severity of motor impairment as measured by ALSFRS. Fifty-five patients with sporadic ALS were included. 99mTc-ECD brain perfusion tomographic studies were performed and reconstructed slices analysed with a voxel-based statistical method (Statistical Parametric Mapping). Correlations between ALSFRS total score and sub-scores were calculated. We observed a positive correlation between the degree of involvement of the motor functions as measured by the ALSFRS score and the perfusion decrease of the cerebral cortex. Analysis of the ALSFRS sub-scores revealed that the cortical involvement was important for lower limbs score, moderate for bulbar score and below the level of statistical significance for the respiratory and upper limb scores. The decrease of perfusion was asymmetrical (right hemisphere) and observed mainly in the lateral premotor cortex, the insula and the cingulate cortex. Our study confirms that in ALS the cortical involvement is asymmetrical and predominant in the premotor region and the insula. PMID- 17364430 TI - Measuring the cortical silent period can increase diagnostic confidence for amyotrophic lateral sclerosis. AB - We evaluated a modified measurement of the cortical silent period (CSP) as a simple procedure to add further confidence in the diagnostic work-up for ALS. Thirty-seven consecutive patients with a suspicion of having ALS were included together with 25 healthy volunteers, and followed until a final diagnosis (ALS versus 'ALS mimic') was reached. Using a CSP cut-off value of 200 ms for males and 150 ms for females, the following test characteristics were obtained for ALS versus ALS mimics together with controls: sensitivity for excluding ALS 0.83, specificity 0.56 (males) and sensitivity 0.81, specificity 0.82 (females). A CSP longer than the mentioned cut-off values should alarm the clinician for the presence of a disorder other than ALS. PMID- 17364431 TI - Sexual dimorphism in disease onset and progression of a rat model of ALS. AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing the progressive loss of brain and spinal cord motor neurons. The exact etiology of ALS is still uncertain, but males have consistently been shown to be at a higher risk for the disease than females. Recently, transgenic rats overexpressing mutant forms of the human SOD1 (hSOD1) gene have been established as a valuable disease model of ALS. Here we show that sexual dimorphism in disease onset is also observed in hSOD1G93A transgenic rats. Disease onset was consistently earlier in male than in female hSOD1G93A rats. We also found that hSOD1G93A male rats lost weight more rapidly following disease onset compared to hSOD1G93A females. Furthermore, we tested locomotor function using the Basso Beattie-Bresnahan (BBB) rating scale and a beam walking test. We found that motor dysfunction started earlier in males than in females but progressed similarly in the two sexes. These results have important implications for future experimentation and therapeutic development using the rat model of ALS. PMID- 17364432 TI - Are enteroviral receptors different in sporadic motor neuron disease? AB - Enteroviruses have been suspected to play a part in the pathogenesis of sporadic motor neuron disease (SMND). Intercellular adhesion molecule type-1 (ICAM1) and coxsackie and adenovirus receptor (CAR) act as receptors for a number of enteroviruses. We therefore examined the viral binding domains of ICAM1 and CAR to see if any changes could be found that might predispose to enteroviral infections. Single nucleotide polymorphisms in the ICAM1 viral binding domain, the adjacent intron and a region implicated in other neurological disorders, as well as the CAR viral binding regions in exons 2-5, were compared in 139 SMND patients and 139 matched controls. The distribution of the polymorphisms was similar in both groups. Therefore, based on linkage disequilibrium and genotype it is unlikely that either ICAM1 or CAR is implicated in SMND. PMID- 17364433 TI - Erythropoietin does not preserve motor neurons in a mouse model of familial ALS. AB - Recombinant human EPO (r-Hu-EPO) protects cultured motor neurons from kainate- and serum deprivation-induced toxicity and readily enters the CNS after systemic injection. We examined the effect of rHuEPO in transgenic mice expressing the human Cu/Zn dependent-superoxide dismutase with G93A mutation (SOD1G93A), a model of familial amyotrophic lateral sclerosis. rHuEPO (4 unit/g BW s.c. three times/week), increased the haematocrit and induced a slight delay in impairment of motor function as measured by the rotating bar test. However, it did not prolong life span or reduce motor neuron loss in lumbar spinal cord. The effect on motor function may be due to the improvement of skeletal muscle oxygenation induced by chronic EPO administration. PMID- 17364434 TI - Respiratory systems abnormalities and clinical milestones for patients with amyotrophic lateral sclerosis with emphasis upon survival. AB - Respiratory system complications and abnormalities are common in patients with amyotrophic lateral sclerosis (ALS) and respiratory failure remains the most common cause of death. Extensive epidemiological longitudinal data have documented the extent, magnitude, and clinical course of these abnormalities, but few studies have provided objective information that can have prognostic significance for individual patients. In this study, the reported data represent results from a retrospective review of the medical records of 153 patients with ALS cared for at a single institution (The Penn State Milton S. Hershey Medical Center) over a 50-month period. Medical information in relation to respiratory system abnormalities and complications including pulmonary function measurements was extracted for data analyses. The intent of this review of longitudinal data from a relatively large cohort of patients with ALS was to identify clinically relevant easily-identifiable objective information and clinical milestones that could have potential prognostic significance when applied to individual patients. Demographic data including gender, survival outcome, respiratory symptoms, age of disease onset, and age at death were similar to previously published epidemiological studies: mean age at ALS disease onset was 58.9+/-12.7 years, and mean age at death was 66.7+/-10.8 years. For 151 patients with available data, the incidence of study defined respiratory complications included infectious pneumonia 13 (9%), venothromboembolism 9 (6%), and tracheostomy and mechanical ventilation 6 (4%). For 139 patients with serial measurements of forced vital capacity (FVC), median values for calculated rate of decline in FVC was 97 ml/30 days (2.4% predicted/30 days); 25% of patients had FVC rates of decline less than 52 ml/30 days (1.4% predicted/30 days) and 25% had rates of decline greater than 170 ml/30 days (4.4% predicted/30 days). Stratifying patients into two distinct clinical subgroups based upon rates of decline in FVC less than or greater than the median value of 97 ml/30 days identified an apparent two-fold increase in survival duration for ALS patients with slower rates of pulmonary physiology deterioration when referenced to either date of dyspnea onset or time from bi level positive airway pressure (BiPAP) initiation (2.0+/-1.4 vs. 1.0+/-0.8 years; 1.9+/-1.5 vs. 1.0+/-0.9 years, respectively). We concluded that the correlation between clinically defined milestones, most importantly onset of dyspnea, and the calculated rate of decline in FVC represent obtainable and objective measurements that predict the natural course of respiratory muscle dysfunction in patients with ALS and provide important prognostic information in relation to individual patient survival duration. PMID- 17364435 TI - Excellent inter-rater, intra-rater, and telephone-administered reliability of the ALSFRS-R in a multicenter clinical trial. AB - We wished to determine whether the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) is reliable when used as primary outcome measure in a multicenter clinical trial. To establish inter-rater reliability, we randomly assigned 19 primary raters and 11 back-up raters to score nine amyotrophic lateral sclerosis (ALS) patients using the ALSFRS-R. To assess intra rater reliability and reliability of telephone administration, we randomly assigned consecutive participants of the Clinical Trial of High Dose Coenzyme Q10 in ALS (QALS) to have in-person ALSFRS-R interviews at both screening and baseline visits (n=41 patients) or to have the ALSFRS-R interview by telephone at screening and in person at the baseline visit (n=27). An intraclass correlation coefficient (ICC) of reliability was calculated using a one-way random effects analysis of variance model. In the inter-rater reliability assessment, the primary raters performed 54 ratings on nine patients with ICC=0.93 (95% CI 0.84 0.98). For back-up raters, 32 ratings on nine patients resulted in ICC=0.93 (95% CI 0.82-0.98). The intra-rater reliability for in-person interviews was ICC = 0.95 (95% CI 0.92-0.98). The reliability of telephone administration compared to in-person interviews was ICC=0.97 (95% CI 0.93-0.98). We conclude that the ALSFRS R shows excellent inter- and intra-rater reliability, and reliability of telephone administration when used as primary outcome measure in a multicenter ALS trial. PMID- 17364436 TI - Maximum voluntary isometric contraction: reference values and clinical application. AB - Maximum voluntary isometric contraction (MVIC) is a standardized method for measurement of muscle strength in patients with neuromuscular disease. Values obtained from MVIC testing are difficult to interpret at present as normative data are limited. The objective of this study was to generate reference values for MVIC. A convenience sample of 494 healthy men and women aged 20-76 years was recruited. MVIC testing was performed on nine muscle groups bilaterally: neck flexors, shoulder abductors, shoulder adductors, elbow and knee flexors and extensors, and hip and ankle flexors. MVIC was performed using the Quantitative Muscle Assessment system. Age and sex related reference values were calculated for each muscle group using quantile regression. A clinical reporting system was developed to facilitate interpretation of patient values with reference to normal percentiles. Reference values generated from this study can be used to determine the presence and extent of muscle weakness in a given population and to evaluate the effectiveness of treatment interventions. PMID- 17364437 TI - Detecting neurobehavioral changes in amyotrophic lateral sclerosis. AB - Cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) is well documented, but behavioral abnormalities are not well defined. The Frontal Systems Behavior Scale (FrSBe) was used to assess changes in apathy, disinhibition, and executive dysfunction in 45 patients with ALS. Results suggest a high incidence of behavioral change, most notably in apathy associated with the onset of the disease and independent of mood. Apathy and verbal fluency were correlated, lending further support to the hypothesis that an underlying continuum exists between ALS and frontotemporal dementia (FTD), which is characterized predominantly by behavioral disturbance. The FrsBe is useful for detecting behavioral change and abnormalities in patients with ALS. PMID- 17364438 TI - Elevated creatine kinase and transaminases in asymptomatic SBMA. AB - X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease) has a variable prognosis. Most male carriers are affected by their fourth or fifth decade of life, while some remain asymptomatic lifelong. Elevations of serum creatine kinase are well known to occur in clinically manifesting SBMA patients. Elevations prior to the onset of the clinical syndrome have not been reported. Here we report two cases of SBMA presenting with 'idiopathic' elevations of serum transaminases and creatine kinase a decade in advance of their symptomatic onset. These cases emphasize the need to consider SBMA and genetic testing for the androgen receptor trinucleotide CAG expansion in males otherwise healthy with 'idiopathic' elevated creatinine kinase. PMID- 17364439 TI - Construct synthetic gene encoding artificial spider dragline silk protein and its expression in milk of transgenic mice. AB - Based on the known partial cDNA sequence of dragline silk protein an artificial gene monomer, a 360 bp sequence, was designed and polymerized to encode an analog of dragline silk protein. Six tandem copies of monomer were cloned into pBC1 vector and microinjected into the pronuclei of fertilized Kunming White eggs. Transgenic mice were screened by Polymerase Chain Reaction (PCR) and Southern blot which revealed that 10 mice (5 male, 5 female) among 58 mice were transgenic positive. Milk of five F0 mice and eight F1 mice was analyzed by Western blot, and two F0 mice and seven F1 mice expressed recombinant dragline silk protein. In transgenic mice milk a maximum of concentration of recombinant dragline silk protein was 11.7 mg/L by radioimmunoassay. PMID- 17364440 TI - Effect of in-straw thawing on in vitro- and in vivo-development of vitrified mouse morulae. AB - For the purpose of ascertaining parameters to embryo transfer on some domestic animals, mouse morulae were used as a model to investigate the effect of in-straw thawing on in vitro and in vivo-development of vitrified embryos. Embryos were vitrified in 0.25 ml straws preloaded with dilution solution (0.5 M Sucrose) and thawed in the straw by mixing the vitrification solution (Ethylene glycol + Ficoll 70 + Sucrose) and the dilution solution at 25 degrees C. The embryos were randomly divided into six groups and expelled from the straws after they had been suspended in the in-straw mixture for 3 min, 5 min, 8 min, 12 min, 16 min, and 20 min, respectively, and then they were collected under a microscope for in vitro culture or direct transfer. The in vitro developmental rates of the embryos were 92.3% to 98.4% and hatching rates were 64.1% to 75.6% for the groups of 3 min to 16 min, showing no significant differences with those of nonfrozen controls (100%, 76.2%; P > 0.05). While embryos were suspended in the straw for 20 min, the developmental rate (86.6%) and hatching rate (52.4%) were significant lower than those of the control (100%, 76.2%; P < 0.01). When the 168 frozen-thawed embryos (in-straw thawing for 5 min) and 168 fresh embryos were transferred, respectively, the proportion of live fetuses in the pregnant recipients between them (58.7% vs. 54.5%) showed no significant difference (P > 0.05). The data indicate that vitrification with EFS30 and suspension in the in-straw mixture for 3 min to 16 min, when thawing, did not affect the in vitro developmental rate and hatching rate. Moreover, the in vivo developmental rate between vitrified embryos and fresh embryos did not differ significantly. It can be concluded that this method is fit for nonsurgical embryo transfer in some domestic animals with a suggestion that the operation of embryo transfer should be accomplished within 16 min. PMID- 17364441 TI - Characterization and physical mapping of the porcine CDS1 and CDS2 genes. AB - CDP-diacylglycerol synthase (CDS) catalyzes the conversion of phosphatidic acid to CDP-diacylglycerol, an important precursor for the synthesis of phosphatidylinositol, phosphatidylglycerol, and cardiolipin. We amplified and sequenced 2,053 bp of the pig CDS1 mRNA. The structure of the pig CDS1 gene was determined, being very similar to that of the human, rat, and mouse genes with respect size and organization of the 13 exons. In addition, we identified three polymorphic positions in exons 10 and 11. One of them, the A/C1006, was genotyped in samples belonging to Iberian, Landrace, Large White, Pietrain, and Meishan pig breeds. Expression of this gene was also analyzed by real-time polymerase chain reaction (PCR) in different tissues showing a high CDS1 expression in testis. Moreover, a 1240-bp fragment of the pig CDS2 mRNA was amplified and sequenced. Finally, the CDS1 and CDS2 genes were physically mapped to porcine chromosomes 8 and 17, respectively, by using the INRA, University of Minnesota porcine Radiation Hybrid panel (IMpRH). PMID- 17364442 TI - Association of a new SNP in promoter region of the porcine FABP3 gene with fatness traits in a polish synthetic line. AB - Associations between FABP3 (alternatively named H-FABP) gene polymorphisms and fatness traits were tested in two pig breeds (Polish Large White and Polish Landrace) and one synthetic line - 990. Three known single nucleotide polymorphisms, detected by HinfI, MspI and HaeIII restriction enzymes, were analyzed. Moreover, three new polymorphisms in the 5' regulatory region were identified: C(-221)T, C(-160)G and T(-158)G, but only the third one was widely distributed and correlated with backfat thickness in line 990. The obtained results suggest that the FABP3 gene is linked with an unknown gene directly affecting backfat thickness, but the analyzed polymorphisms do not influence fatness traits. PMID- 17364443 TI - Open-pulled straw (OPS) vitrification of mouse hatched blastocysts. AB - This study was first employed to investigate the developmental potential of mouse hatched blastocyts (HBs) vitrified by a two-step open-pulled straw (OPS) method. HBs were obtained by culture of morulae in vitro. First, the embryos were placed in four cryprotectant solutions - that is, 10% ethylene glycol (EG), 10%E + 10%D (10% EG and 10% dimethyl sulphoxide (DMSO) in mPBS), EFS30 (30% EG, Ficoll, and sucrose) and EDFS30 (15% EG, 15% DMSO, Ficoll, and sucrose)--at 25 degrees C for 0.5 to 10 min, respectively, to determine their optimal survival after rapid dilution in 0.5 M sucrose. Secondly, based on the above best survival, the embryos were plunged into liquid nitrogen after first pretreatment in 10%E for 0.5 min and then 0.5 min equilibration in EFS30 (Group 1), or 10%E + 10%D and EDFS30 for 0.5 min, respectively (Group 2). When warming, three methods were used to dilute the cryoprotectants from the vitrified embryos. The embryos were assessed by the re-expansion of the blastocoel or development to term. The result showed that all the vitrified-warmed HBs got high in vitro survival rates (83.7% to 98.9%). The highest in vitro survival rates (87.8% in Group 1, 98.9% in Group 2) were obtained when the vitrified embryos were diluted first in 0.3 M sucrose for 5 min, then in 0.15 M sucrose for 2 min (method C). When the vitrified embryos diluted with method C were transferred, their survival rate in vivo (35.5% to 42.2% of the total) were similar to (P > 0.05) that of control (45.7%). These results demonstrate OPS method was highly efficient for the cryopreservation of mouse HBs. PMID- 17364444 TI - Somatic cell hybrid mapping of expressed sequence tags for genes showing early embryonic death-associated changes of expression patterns in the fetal placenta of the cow carrying somatic nuclear-derived cloned embryo. AB - We previously detected 368 expressed sequence tags showing early embryonic death associated changes of expression patterns in the fetal placenta of the cow carrying somatic nuclear-derived cloned embryo. In the present study 7 (presumed expressed sequence tags for HYPC, SPTBN1 and TNNC2, and four expressed sequence tags for unknown novel genes) out of the 368 expressed sequence tags were mapped to bovine chromosomes by analyzing deoxyribonucleic acids of bovine/murine somatic cell hybrid panel with polymerase chain reaction using primers specific for those bovine genes. PMID- 17364445 TI - Characterization of the porcine carboxypeptidase E cDNA: comparative analysis and investigation of a non-synonymous SNP. AB - Carboxypeptidase E (CPE) is an important enzyme responsible for the proteolytic processing of prohormone intermediates. A naturally occurring point mutation, leading to an accumulation of many neuroendocrine peptides has been characterized within exon 5 of the CPE gene in mice. In the present study the sequence of the cDNA for the porcine CPE gene including all the coding region and the 3'-UTR region was generated. Comparisons with bovine, human, mouse, and rat CPE cDNA sequences showed that the coding regions of the gene are highly conserved both at the nucleotide and at the amino acid level. A very low nonsynonymous/synonymous substitution ratios between the proteins was found indicating that purifying selection is acting on the CPE gene. A nonsynonymous SNP identified at position 1272 in the transcript resulting in a codon change from TCA (Serine) to TTA (Leucine) was genotyped in the Danish pig populations. However, the mutated allele was only identified in one particular family. Exon 5 was sequenced in 45 unrelated pigs. No evidence of variation was found in this region. In accordance with previous results and in accordance with comparative mapping information the gene was accurately mapped to porcine chromosome 8 using the ImpRH panel. PMID- 17364446 TI - Prolactin receptor as a candidate gene for prolificacy of small tail han sheep. AB - DNA polymorphism of the ovine prolactin receptor gene (PRLR) was investigated and used to study its effect on litter size in sheep. By means of PRLR gene sequence homology between sheep and human, three primer pairs were designed for polymerase chain reaction (PCR) amplification within intron 1 and exon 10 of the PRLR gene in sheep. In these parts of the gene the single nucleotide polymorphisms were detected by PCR-single strand conformation polymorphism (SSCP) in 314 Small Tail Han ewes. These poly-morphisms were used to study the associations with litter size. The results indicated that there were three genotypes (AA, AB and BB) detected by three primer pairs. For three primer pairs the frequency of allele A was 0.96, 0.79, 0.68; and the frequency of allele B was 0.04, 0.21, 0.32, respectively. The frequency of genotype AA was 0.93, 0.62, 0.51; the frequency of genotype AB was 0.06, 0.34, 0.34; the frequency of genotype BB was 0.01, 0.04, 0.15, respectively. The Small Tail Han ewes with genotype BB or AB had 0.64-0.76 or 0.44-0.54 more lambs than those with genotype AA, respectively. These results preliminarily showed that the prolactin receptor locus is either a major gene that influences the prolificacy in Small Tail Han sheep or is in close linkage with such a gene. PMID- 17364447 TI - The utility of levosimendan in the treatment of heart failure. AB - Calcium sensitizers are a new group of inotropic drugs. Levosimendan is the only calcium sensitizer in clinical use in Europe. Its mechanism of action includes both calcium sensitization of contractile proteins and the opening of adenosine triphosphate (ATP)-dependent potassium channels as mechanism of vasodilation. The combination of K-channel opening with positive inotropy offers potential benefits in comparison to currently available intravenous inotropes, since K-channel opening protects myocardium during ischemia. Due to the calcium-dependent binding of levosimendan to troponin C, the drug increases contractility without negative lusitropic effects. In patients with heart failure levosimendan dose-dependently increases cardiac output and reduces pulmonary capillary wedge pressure. Since levosimendan has an active metabolite OR-1896 with a half-life of some 80 hours, the duration of the hemodynamic effects significantly exceeds the 1-hour half life of the parent compound. The hemodynamic effects of the levosimendan support its use in acute and postoperative heart failure. Several moderate-size trials (LIDO, RUSSLAN, CASINO) have previously suggested that the drug might even improve the prognosis of patients with decompensated heart failure. These trials were carried out in patients with high filling pressures. Recently two larger trials (SURVIVE and REVIVE) in patients who were hospitalized because of worsening heart failure have been finalized. These trials did not require filling pressures to be measured. The two trials showed that levosimendan improves the symptoms of heart failure, but does not improve survival. The results raise the question whether a 24-hour levosimendan infusion can be used without invasive hemodynamic monitoring. PMID- 17364448 TI - Cardiovascular risk of cyclooxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs. AB - Since selective cyclooxygenase-2 inhibitors (coxibs) entered the market, there has been concern about the cardiovascular safety of coxibs. In addition, recent data suggest that classical non-steroidal anti-inflammatory drugs (NSAIDs) have a similar cardiovascular risk. Importantly, all of the clinical trials with NSAIDs and coxibs so far were not purpose-designed to specifically and prospectively address cardiovascular safety and were clearly underpowered to detect any meaningful differences. In this current uncertainty about safety of NSAIDs and coxibs, the definitive answer as to the net effect of coxibs and NSAIDs on cardiovascular events can only be provided by well designed adequately powered, long-term clinical trials, which is now under way. PMID- 17364449 TI - Breast response to menopausal hormone therapy--aspects on proliferation, apoptosis and mammographic density. AB - Breast cancer is the major malignancy among women in the Western world. The breast is clearly a target organ for sex steroid hormones and hormonal treatments have been associated with an increased risk of breast cancer. The balance between proliferation and apoptosis is important for breast cell homeostasis. Mammographic breast density has been identified as a strong and independent risk factor for breast cancer. It seems clear that there is a difference between various hormonal treatments with regard to their effects on breast density and cell proliferation. Also, not all women respond similarly to the same treatment. Combined estrogen and progestogen therapy generally will enhance density and proliferation more than treatment with estrogen alone. Certain constitutional and hormonal factors appear to be predictive of breast reactivity. Older women with a low body mass index respond more strongly to treatment. Estrogen levels have a positive and androgens a negative association to increase in density and proliferation. A combination of increased proliferation and decreased apoptosis could be one mechanism to explain the excess risk of breast cancer during combined estrogen/progestogen treatment. Tibolone seems to have less impact on breast response than conventional hormone therapy. Efforts should be made to identify those women with an adverse response to treatment as well as therapeutic principles with the least possible influence on the breast. PMID- 17364450 TI - Update on pathophysiology of scleroderma with special reference to immunoinflammatory events. AB - Scleroderma or systemic sclerosis (SSc) is a complex disease in which the vasculopathy and the activation of the immune system with production of inflammatory mediators lead to dysregulated fibroblast activation. The resulting excessive deposition of collagens and other extracellular matrix proteins ends in fibrosis and organ dysfunction. The cause is unknown, but environmental factors are thought to play a role by triggering abnormal responses in genetically susceptible hosts. The recent past has witnessed important advances in the definition of mechanisms that underlie the persistent activation in fibroblasts of genes involved in uncontrolled fibrosis, a hallmark of SSc. These include the preferential production of type 2 T cell cytokines in target organs, the presence of autoantibodies with fibroblast-activating capacities, the production of vasoconstrictive mediators that impact on fibroblast biosynthetic properties, the transforming growth factor-beta-related metabolic signature, and the presence of altered signaling pathways in fibroblasts. Furthermore, while no animal models recapitulate all the features of SSc, they have been instrumental for assessing the relevance of specific processes to the development of fibrosis. More importantly, some of the research findings are leading to therapies that target altered processes with the potential of changing the prognosis of some dismal aspects of the disease. PMID- 17364451 TI - Novel spectral indexes of heart rate variability as predictors of sudden and non sudden cardiac death after an acute myocardial infarction. AB - BACKGROUND: Various indexes of 24-hour heart rate variability (HRV) have been able to predict all-cause mortality after an acute myocardial infarction (AMI), but their value in predicting specific modes of cardiac death has been limited. AIM: The aim of this study was to assess the role of two novel spectral indexes of HRV as predictors of either sudden (SCD) or non-sudden cardiac death after an AMI. Method. We used two novel methods of spectral analysis of HRV: 1) the high frequency (HF) spectral component, V(index), calculated as an average HF power from the most linear portion of HF power versus the R-R interval regression curve, and 2) the prevalent low-frequency oscillation of heart rate (PLF). V(index), conventional HRV measures, and PLF were analyzed from 24-hour Holter recordings of 590 patients with a recent AMI. RESULTS: During the mean follow-up of 39+/-14 months, SCD occurred in 3% (n = 17) and non-sudden cardiac death in 5% (n = 28) of the patients. In univariate analysis, V(index) was the most potent predictor of SCD (RR: 6.0, 95% CI: 1.7-20.7, P<0.01), also remaining the most powerful predictor of SCD after adjustment for clinical variables and ejection fraction (RR: 4.2, 95% CI: 1.2-15.2, P<0.05). PLF was a potent predictor of non sudden cardiac death (RR: 13.9, 95% CI: 5.9-32.5, P<0.001), but it did not predict SCD. CONCLUSIONS: Novel spectral HRV analysis methods, V(index) and PLF, provide significant information of the risk of the specific mode of death after an AMI. PMID- 17364452 TI - Mortality of patients with acute coronary syndromes still remains high: a follow up study of 1188 consecutive patients admitted to a university hospital. AB - BACKGROUND: Based on randomized clinical trials, mortality of acute coronary syndrome (ACS) has been considered to be relatively low. The prognosis of clinical presentations of ACS in real-life patient cohorts has not been well documented. AIM: The aim of this study was to evaluate actual clinical outcome across the whole spectrum of ACS in a series of unselected prospectively collected consecutive patients from a defined geographical region, all admitted to one university hospital. METHODS: A total of 1188 patients with ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI) or unstable angina pectoris (UA) were included. Results. In-hospital mortality was 9.6%, 13% and 2.6% (P<0.001) and mortality at a median follow-up of 10 months 19%, 27% and 12% (P<0.001), for the three ACS categories, respectively. In multivariate Cox regression analysis age, diabetes mellitus type 1, diuretic use at admission, creatinine level, lower systolic blood pressure, STEMI and NSTEMI ACS category were associated with higher mortality during follow-up. CONCLUSIONS: In an unselected patient cohort, short-term mortality of MI patients, especially those classified as NSTEMI, still was high despite increasing use of proven treatment modalities. PMID- 17364453 TI - Assessment of platelet activation indices using the ADVIATM 120 amongst 'high risk' patients with hypertension. AB - BACKGROUND: Platelet activation is involved in the pathogenesis of the thrombotic complications of hypertension. Novel surrogate markers of platelet activation (mean platelet volume (MPV), mean platelet component (MPC, measure of platelet density), platelet component distribution width (PCDW, a marker of platelet shape change) and the number of platelet clumps) have been related to cardiovascular risk. We hypothesized a stepwise increase in these platelet activation indices between healthy controls (HC, n = 60), 'high-risk' essential hypertensive subjects (HBP, n = 45) and treated, previously diagnosed patients with malignant phase hypertension (MHT, n = 45). METHODS: In a cross-sectional study, we measured comparative platelet counts and indices of platelet activation (MPV, MPC, PCDW and the number of platelet clumps) using the Bayer ADVIATM haematology system, in our three study groups. RESULTS: There was a stepwise increase in MPV (P = 0.0002) and MPM (P = 0.03), and a stepwise decrease in the MPC (P = 0.03) and PCDW (P = 0.001) across the three study groups, despite similarities in platelet count. These differences were only significantly different (on post-hoc analysis) between the healthy controls and the MHT group. On multivariate analysis, there was a significant relationship (R2 = 66.5%; P<0.0001) between the MPV and the PCDW (P<0.0001), systolic blood pressure (P = 0.008) and platelet count (P<0.0001). CONCLUSION: There is a stepwise increase in platelet activation indices, despite similar platelet counts, with increasing severity of hypertensive disease. This may contribute to the pathogenesis of thrombosis related complications in hypertension. PMID- 17364455 TI - A successful pregnancy outcome using testicular sperm from an infertile male pretreated with HCG. AB - A very rare case of successful pregnancy was reported using testicular sperm from a severely infertile man given the treatment of hCG in advance. Prior to treatment, no sperm were present in the ejaculate and testicle. hCG was administrated to the patient for spermatogenesis. After a period of hCG treatment, a few immature sperm were observed in the minced testicular specimen. A successful pregnancy was established by ICSI using the sperm. Treatment by administration of hCG to generate sperm followed by ICSI for the azoospermia patients was effective and practicable. PMID- 17364456 TI - Evaluation of sperm chromatin quality and screening of Y chromosome microdeletions in Greek males with severe oligozoospermia. AB - Normal (n = 20) and abnormal (n = 21) semen samples were explored for possible relationships between conventional semen parameters, chromatin status, and microdeletions in the Y chromosome. DNA fragmentation was detected by the terminal deoxynucleotidyl trasferase-mediated dUTP-nick end labelling (TUNEL) assay, chromatin condensation, and DNA packaging quality were assessed by chromomycin A3 (CMA(3)) staining. All men were investigated for Y chromosome microdeletions using polymerase chain reaction (PCR). No deletions were detected in 21 severely oligozoospermic men for the three screened regions (AZFa, AZFb, and AZFc). Men with normal semen parameters showed better chromatin condensation. Spermatozoa with low motility were more likely to contain loosely packaged chromatin. In the abnormal semen group, DNA fragmentation (TUNEL) correlated significantly with sperm motility, concentration, and chromatin packaging assessed by chromomycin A3. However sperm morphology did not correlate significantly with TUNEL and CMA(3) staining. PMID- 17364457 TI - Severe hypospadias with micropenis, case of confused sex, psychosocial changes and treatment. AB - Disorders such as severe hypospadias presenting as ambiguous genitalia have serious and potentially life-long consequences for affected individuals and, depending on the underlying cause, are likely to entail surgery in childhood and in later life, psychosocial and psychosexual support, and possible fertility treatment including assisted conception. Genetic males with severe hypospadias who were wrongly brought up as females formed the study group. They were reassigned as males and underwent surgery for correction of hypospadias. Three children with severe hypospadias were reassigned to male gender. Psychosocial changes were made and psychosexual counseling was done. All three have adjusted to their new environment and gender. It is preferable to reassign these children who are genetic males but wrongly assigned as females at birth. Repair of hypospadias, psychosocial changes, and psychosexual counseling will help these children to reorient themselves. PMID- 17364458 TI - Relationships between levels of estradiol and testosterone in seminal plasma and GSTM1 polymorphism in infertile men. AB - Glutathione S-transferase M1 (GSTM1) enzyme serves as a steroid-binding protein by its ability to bind to testosterone and estradiol. The levels of total estradiol and testosterone were measured by using an electrochemiluminescence immunoassay in serum and seminal plasma from 103 subjects including 62 subfertile patients. GSTM1 polymorphism was examined using polymerase chain reaction. The estradiol and testosterone levels in seminal plasma were not different in control and subfertile subjects. No role for GSTM1 enzyme as a steroid-binding protein seemed likely as there was also no significant difference in seminal plasma estradiol and testosterone levels according to GSTM1 genotype. Significant positive correlations were found between seminal estradiol and serum estradiol in infertile males, and between seminal testosterone and serum testosterone in fertile males, independent of GSTM1 genotype. GSTM1 polymorphism is not a genetic risk factor of seminal estradiol and testosterone levels in infertile males although further studies are warranted. PMID- 17364459 TI - Finasteride to evaluate the efficacy of dutasteride in the management of patients with lower urinary tract symptoms and enlarged prostate. AB - Patients with lower urinary tract symptoms and enlarged prostate were randomized to receive, in a double blind fashion, either Finasteride 5 mg/day or Dutasteride 0.5 mg/day for a period of 12 weeks. IPSS score, Qmax, and Quality of Life were assessed at the end of 0 and 12 week periods. Dutasteride significantly improved Qmax, reduced IPSS score, and improved Quality of Life as compared to Finasteride at the end of the 12-week period. Dutasteride with its inhibitory effects on type 1 and 2 5alpha-reductase, produces significantly better results than Finasteride. PMID- 17364460 TI - Correlation of seminal parameters with serum lipid profile and sex hormones. AB - The phospholipids and fatty acid composition of sperm are altered under the influence of serum lipids on impaired seminal parameters in infertile men. We studied the correlation of the serum lipid profile and sex hormone results of a group of infertile men with sperm characteristics of 18 infertile men. Semen samples were collected and analyzed. Serum fasted and post-meal glucose levels, insulin, total cholesterol, HDL, LDL, VLDL, triglyceride, FSH, LH, and testosterone measurements were performed. The increased serum VLDL, total triglyceride, and testosterone values were significantly correlated with decreased sperm motility. Serum FSH values were also inversely correlated with normal sperm morphology. The increased VLDL impaired seminal parameters; additionally, increased triglycerides may have deleterious effects on spermatogenesis. Deterioration is related with increased serum VLDL and triglyceride levels. PMID- 17364461 TI - Combination of hypoosmotic swelling/eosin Y test for sperm membrane integrity evaluation: correlations with other sperm parameters to predict ICSI cycles. AB - The objective of our study was to evaluate the accuracy of the combination of hypoosmotic swelling (HOS) and eosin Y (Ey) exclusion tests to predict the ICSI cycles' outcome and its correlations with other sperm parameters. The functional and structural integrity of sperm membrane was evaluated with the combined HOS/Ey test in 95 ICSI cycles and the results were correlated with other sperm parameters, including concentration, motility, strict morphology, and total motile sperm count. The combined HOS/Ey test was evaluated for the prediction of the ICSI cycles' outcome parameters including fertilization, cleavage, and pregnancy rates. The HOS/Ey test presented significant relationships with concentration, motility, and strict morphology (p < 0,0001) but it couldn't predict the fertilization, cleavage, and pregnancy outcomes of ICSI cycles. The combined HOS/Ey test has strong correlations with motility and strict morphology parameters of sperm samples but is not sufficiently sensitive to estimate the outcome of ICSI cycles. PMID- 17364462 TI - Sperm survival: relationship to age-related sperm DNA integrity in infertile men. AB - The purpose of our study was to evaluate the effect of age and sperm DNA integrity on sperm survival. Semen samples from fifty six unselected patients undergoing infertility evaluation were assessed in terms of standard semen parameters, DNA integrity, and sperm survival after 6-24 h of incubation. Prolonged incubation of density gradient selected sperm adversely effects sperm survival in older patients and patients with extensive sperm DNA damage. Immediate preparation of such samples prior to use for assisted reproductive technology (ART) may overcome the negative effect of extended incubation. PMID- 17364463 TI - Testicular sperm retrieval method: histological effects of location of incision. AB - This research was conducted to evaluate the effects of a transverse vs. longitudinal incision for testicular sperm retrieval. Rats were divided into 4 groups: I: control, II: sham operation, III: longitudinal incision TSRM, IV: transverse incision TSRM. Group II (sham operation) had a dissection of left testis/spermatic cord, then closure of wound. Group III underwent dissection of left testis, then a "longitudinal" incision (15 mm long) of testis, which was fully opened then closed again and sutured with 5-0 Vicryl sutures. Group IV underwent dissection of the left testis, opening of the testis with a "transverse" incision, then closure with 5-0 Vicryl. The seminiferous tubule diameter was 0.118-0.224 mm in all groups. Inflammation and abscess formation occurred in one testis each in the sham and longitudinal incision groups, and in two testes in the transverse incision group. There were no differences in histopathology or scoring between the longitudinal and the transverse incision. PMID- 17364464 TI - Increased total antioxidant capacity in seminal plasma of varicocele patients: a multivariate analysis. AB - To investigate seminal antioxidant systems and their correlation with hormonal pattern in varicocele patients, we studied 33 varicocele (VAR) patients (12 oligozoospermic, 21 normozoospermic) and 34 non-VARs (10 idiopathic oligozoospermic, 24 normozoospermic). Non-enzymatic total antioxidant capacity (TAC) was measured using H(2)O(2)-metamyoglobin, which generates the radical form, spectroscopically detectable, of the chromogen 2,2',-azinobis-3 ethylbenzothiazoline-6-sulphonate (ABTS): time till appearance (Lag) of ABTS*(-) signifies antioxidant concentration. Lag was significantly longer in VARs than controls suggesting ineffective utilization of antioxidants. A significant direct correlation (r = 0.65, p < 0.01) of Lag with sperm count was observed in non VARs, while in VARs it was inverted, as well as with hematic FSH levels. A multivariate analysis including FSH, Lag, progressive spermatozoa, oligozoospermia and varicocele indicated a strong inverse correlation between FSH and motility (r(2) = 0.31, p > F = 0.0007), not modified by Lag (r(2) = 0.31, p > F = 0.002). Their inverse correlation with Lag may suggest that higher FSH levels, improving sperm antioxidant efficiency, counterbalance varicocele-induced dyspermia. PMID- 17364465 TI - Varicocele-induced testicular dysfunction may be associated with disruption of blood-testis barrier. AB - The objective of this study was to examine E-cadherin and alpha-catenin expression at the junctions between adjacent Sertoli cells in testicular specimens from patients with varicocele in order to determine the presence of a possible link between blood-testis barrier and pathophysiology of varicocele. A total of 51 testicular biopsies were obtained from 28 infertile men with unilateral or bilateral varicocele. Twenty-three patients had bilateral and 5 had unilateral varicocele, Grade I varicocele was detected in 30 (59%), grade II in 15 (29%) and grade III in 6 (12%) patients. Abnormal expression of E-cadherin and alpha-catenin at the junctions between adjacent Sertoli cells was demonstrated in 100% and 90% of the patients with varicocele, respectively. In those with grade I III varicocele, the mean E-cadherin and alpha-catenin expression were 7.6 +/- 11.4 and 39 +/- 36; 7.6 +/- 0.0 and 49 +/- 30; 8.3 +/- 9.3 and 58 +/- 33, respectively, but the difference was not significant. Reduced E-cadherin and alpha-catenin expression at the junctions between adjacent Sertoli cells may be associated with disruption of blood-testis barrier in varicocele. PMID- 17364466 TI - Characterization of poly(ethylene glycol)-modified bovine hemoglobin by capillary zone electrophoresis. AB - In this study capillary zone electrophoresis (CZE) was used to analyze the poly(ethylene glycol)-modified bovine hemoglobin(PEG-bHb). The results show that CZE separated the subunit of bovine hemoglobin based on the number of PEG conjugating to the protein surface, which makes it possible to evaluate the degree of modification of hemoglobin subunit; meanwhile, it also reflected the stability of PEG attaching to hemoglobin after incubating with hydroxylamine, which makes it successful to detect the distribution of attachment site and evaluate the stability of PEG on the surface of hemoglobin. As a simple, fast and accurate method, CZE is suitable to monitor the production procedures and quality control of the final products of the PEG-bHb. PMID- 17364467 TI - Development of zero-link polymers of hemoglobin, which do not extravasate and do not induce pressure increases upon infusion. AB - Intramolecular crosslink of hemoglobin tetramers solved the problem of urine elimination and short intravascular retention time of cell free hemoglobin infusion. It also produced a family of crosslinked hemoglobins with P50 between 18 and 30 mmHg. However, it did not solve the problem of MAP increases in infused animals. It was proven that extravasation of hemoglobin into interstitial fluid was responsible for MAP increases. Extravasation and the MAP increase was avoided using a hemoglobin polymer with average size near 25 MDa. In spite of a very high oxygen affinity, this polymer delivered oxygen to tissues, producing either vasodilation or vasoconstriction according to oxygen needs. It was also proven that cell free hemoglobins are more efficient than red cells in delivering oxygen to tissues. PMID- 17364468 TI - Molecular aspects of the high oxygen affinity of non-hypertensive hexa pegylated hemoglobin, [(SP-PEG5K)(6)-Hb]. AB - The development of hexaPEGylated Hb, (SP-PEG5K)(6)-Hb, using the newly designed thiolation-mediated maleimide chemistry based PEGylation, has validated the concept that engineering 'plasma volume expander' -like properties to Hb neutralizes its vasoactivity. The high O(2) affinity of hexaPEGylated Hb has been attributed to the two PEG-5K chains on its two Cys-93(beta) residues. In an attempt to map the influence of the additional four PEG-5K chains of HexaPEGylated Hb on the O(2) affinity, we have now investigated the influence of PEGylation of the surface amino groups alone on the subunit interface interactions and O(2) affinity of Hb using rHb(betaC93A). The molecular radius of PEGylated rHb(betaC93A) was slightly smaller than that of (SP-PEG5K)(6)-Hb, and the overall site-selectivity of PEGylation in the PEGylated rHb(betaC93A) at Lys residues was comparable to that of (SP-PEG5K)(6)-Hb. Proton NMR studies have shown that the conjugation of the protein with PEG-5K does not have any significant influence on its subunit interface interactions. Surprisingly, the influence of PEGylation on the O(2) affinity and Bohr effect of HbA and rHb(betaC93A) is also nearly the same. Apparently, conjugation of PEG-chains to Lys residues of Hb by the thiolation mediated PEGylation induces unique changes in the structure of the hydration shell of Hb (layer of tightly bound water molecules), which, in turn, induces constraints in its R to T conformational transition to favor the more hydrated R-state. PMID- 17364469 TI - Synthesis of a hemoglobin polymer containing antioxidant enzymes using complementary chemistry of maleimides and sulfhydryls. AB - To increase the overall size of hemoglobin (Hb), we developed a novel system of polymerization based on the complementary chemistry between sulfhydryls and maleimides. The maleimides were introduced onto the protein through N-( maleimidobutyryloxy) succinimide, while the sulfhydryls were added using 2 iminothiolane hydrochloride (Trauts reagent). Resulting polymers showed SDS-PAGE bands with molecular weights as high as 96 kDa. Size exclusion chromatography has demonstrated species with molecular weight > 700 kDa. The flexibility of the sulfhydryl-maleimide chemistry has also allowed insertion of two antioxidant enzymes, catalase (Cat) and superoxide dismutase (SOD), into the Hb polymer. Cat was incorporated into the heavier fractions of the polymer, while SOD was found throughout the molecular weight range. PMID- 17364471 TI - Acellular invertebrate hemoglobins as model therapeutic oxygen carriers: unique redox potentials. AB - Natural acellular polymeric hemoglobins (Hb) provide oxygen transport and delivery within many terrestrial and marine invertebrate organisms. It has been our premise that these natural acellular Hbs may serve as models of therapeutic hemoglobin-based oxygen carriers (HBOC). Our attention has focused on the acellular Hb from the terrestrial invertebrate, Lumbricus terrestris (Lt), which possesses a unique hierarchical structure and a unique ability to function extracellularly without oxidative damage. Lumbricus Hb and Arenicola Hb are resistant to autoxidation, chemical oxidation by potassium ferricyanide, and have little or no capacity to transfer electrons to Fe(+3)-complexes at 37 degrees C. An understanding of how these invertebrate acellular oxygen carriers maintain their structural integrity and redox stability in vivo is vital for the design of a safe and effective red cell substitute. We report here a positive redox potential for these giant hemoglobins that may lie at the basis for its resistance to oxidation. PMID- 17364470 TI - Recombinant hemoglobins as artificial oxygen carriers. AB - This paper describes the approaches we have taken to construct a) mutant hemoglobins with different oxygen affinities, and b) mutant hemoglobins and myoglobins that polymerize to high molecular weight aggregates in an effort to prevent extravasation and the associated vasoactivity. In vivo testing indicates that exchange transfusion of polymeric hemoglobins in mice does not result in vasoactivity and that polymeric hemoglobins are effective oxygen carriers to ischemic tissues irrespective of their oxygen affinity and cooperativity. PMID- 17364472 TI - Trapping hemoglobin in rigid matrices: fine tuning of oxygen binding properties by modulation of encapsulation protocols. AB - Encapsulation of hemoglobin in a biocompatible matrix is a potential strategy for obtaining blood substitutes. Such a system would retain most of the immunogenic and functional properties of the physiologically relevant oxygen carrier but would prevent protein extravasation and dimer/dimer dissociation. We applied this approach by entrapping hemoglobin in wet nanoporous silica gel, in the presence and absence of allosteric effectors. Silica gels, although not suitable for intravenous perfusion, are inert and optically transparent, thus allowing a full characterization of the functional and structural properties of encapsulated hemoglobin by spectroscopic techniques. Results indicate that hemoglobin molecules, entrapped using different protocols, exhibit an oxygen affinity that can be modulated between 12 and 140 torr. This tunability could be exploited to meet distinct clinical needs. PMID- 17364473 TI - One-year observation of Wistar rats after intravenous infusion of hemoglobin vesicles (artificial oxygen carriers). AB - Hemoglobin-vesicles (HbV) or liposome-encapsulated Hb are artificial oxygen carriers. Our previous studies of the bolus infusion of HbV into Wistar rats showed that HbV was captured by the reticuloendothelial system from the blood stream and degraded completely with no deteriorative effect for 2 weeks. However, one authority on artificial organs research suggested conducting a one-year observation because he experienced, with one lipid-emulsified perfluorocarbon (PFC), that rats died within one year from a pulmonary abnormality after receiving the PFC emulsion due to the unstable dispersion state (personal communication). We thought this would never happen for HbV because the dispersion state of HbV is stable with PEG-modification. To confirm this, we made one-year observations after HbV infusion as suggested. Five male Wistar rats intravenously received 20 ml/kg HbV suspended in saline ([Hb] = 10 g/dL). They were housed in separated cages and provided with food and water ad libitum. All rats survived one year, and were apparently healthy. Their body weights (821+/-75 g) reflected obesity from their confinement in small cages. No histopathological abnormality was found in the lung. Plasma biochemical analyses showed overall normal organ functions. In our previous report, plasma lipid levels increased transiently at 1 or 2 days; then they reverted to the control level at 7 days. One year later, the rats showed much higher plasma lipid levels, a symptom of hyperlipidemia that is attributable to obesity and aging. It seemed the transient increases at the early days had no impact compared with the levels of hyperlipemia of the old rats. PMID- 17364474 TI - Expectations and implications of blood sparing with hemoglobin based oxygen carriers. AB - To gain insight into the degree to which hemoglobin based oxygen carriers may replace the need for transfusion in surgical patients experiencing blood loss, a simple mathematical model was developed. This model predicts the amount of blood sparing resulting from a bolus infusion of different doses of hemoglobin solution as a function of circulating hemoglobin half-life and degree of erythropoesis enhancement subsequent to treatment. The results of this analysis are consistent with published clinical data and imply that blood sparing increases with increasing oxygen carrier dose and half-life, as well as increasing levels of erythropoesis enhancement. The analysis also predicts that the total circulating hemoglobin content in patients infused with HBOC solutions may reach a minimum value up to ten days after treatment. PMID- 17364475 TI - Thiolation mediated pegylation platform to generate functional universal red blood cells. AB - The PEGylation that adds an extension arm on protein amino groups with the conservation of their positive charge masks the A and D antigens of erythrocytes efficiently. In the present study, the efficiency of masking the antigens of RBC by PEGylation protocols that do not conserve the charge with and without adding extension arms is compared. The conjugation of PEG-5000 to RBCs through the addition of extension arms masked the D antigen more efficiently than the other protocol. A combination of PEG-5 K and PEG-20 K is needed to mask the A antigen, irrespective of the PEGylation approach. The oxygen affinity of the PEGylated RBCs increased by the extension arm facilitated PEGylation. The protocol involving the conjugation of PEG-chains without adding extension arm did not alter the oxygen affinity of RBCs. A combination of PEGylation protocols is an alternate strategy to generate universal red blood cells with good levels of oxygen affinity. PMID- 17364476 TI - Long lived microbubbles for oxygen delivery. AB - Exceptionally long lived microbubbles containing a fluorocarbon as part of their filling gas have been obtained by using a fluorinated phospholipid instead of a standard phospholipid as shell component. An unexpected, strong synergistic effect between the fluorocarbon gas and the fluorinated phospholipid has been discovered. Such bubbles could be used for in vivo oxygen delivery, ultrasound contrast imaging and drug delivery. PMID- 17364477 TI - Lyophilized platelets: fifty years in the making. AB - Starting with the work of Klein et al. in the early 1950s, there has been a concerted effort to apply the process of freeze-drying for the preservation of platelets in order to provide hemorrhagic patients with a stable infusible hemostatic agent to stop bleeding. The original attempts did not preserve platelet structural integrity and proved to be of little clinical benefit. However, it was known that fixation by various cross-linking agents rendered platelets able to withstand structurally intact the stresses of lyophilization but with (assumed) complete loss of functionality. Read and coworkers showed that fixed and freeze-dried platelets could respond to ristocetin-induced agglutination, and thus devised a widely accepted assay for von Willebrands factor that demonstrated that reconstituted platelets participated well in this in vitro model of an important interaction in primary hemostasis. This review chronicles the efforts of the authors to refine the fixation process so that the freeze-dried and reconstituted platelets retain fundamental hemostatic properties necessary to stop bleeding. The resultant product has demonstrated correction or reduction of the bleeding times in animal models with platelet deficits including the thrombocytopenic rabbit model of Blajchman and coworkers, a canine cardiopulmonary bypass model of open-heart surgery at East Carolina University (ECU), and a porcine trauma model at The University of North Carolina at Chapel Hill (UNC-CH) involving exsanguination and complete blood exchange with a hemoglobin-based oxygen carrier (HBOC). In addition, it has been shown that the fixation process kills viruses and bacteria spiked into the platelet suspension, indicating that the final material may indeed be the first truly sterile cellular transfusion product. The initial goal for clinical benefit is to prevent exsanguination and hypovolemic shock in combat casualties of armed services personnel, for whom platelet transfusions are most often unavailable. Commercial interests are being brought to bear by Entegrion Inc. (formerly known as Hemocellular Therapeutics Corporation) to transfer this technology to a scaleable manufacturing platform for the production of Stasix, a pharmaceutical preparation of fixed and freeze-dried platelets for intravenous or topical use in the arrest of active hemorrhage in a wide variety of patients with a platelet-related bleeding diathesis. It has taken fifty+ years from the first attempt at making a clinically useful freeze-dried platelet preparation to get to the rapidly approaching clinical trials of Stasix; stabilization of the platelets has been the key to realizing this advance. PMID- 17364478 TI - Synthetic oxygen carriers in cardiac tissue engineering. AB - The prominence of cardiovascular diseases has prompted investigations into alternative treatment options, including tissue engineering. Currently, the biggest limitation in cardiac tissue engineering lies in delivering oxygen to all cells within the construct. Synthetic oxygen carriers hold much promise in that they have high affinity for oxygen and can be supplemented to culture medium without adverse effect on the cells. This review highlights two complementary studies by our group that utilized oxygen carriers in cardiac tissue engineering. Experimental and modeling studies were performed to evaluate the effect of a perfluorocarbon (PFC)-based synthetic oxygen carrier, Oxygent, on oxygen supply within tissue engineered cardiac constructs. Porous biorubber scaffolds with an array of parallel channels mimicking the capillary network were seeded with cardiomyocytes and fibroblasts, and cultivated in medium supplemented with PFC. The presence of PFC enhanced the transport of oxygen, increased oxygen concentrations, and yielded constructs that displayed stronger cardiac-like phenotype. PMID- 17364479 TI - A controlled study of Hostile-Helpless states of mind among borderline and dysthymic women. AB - The aim of this study was to determine whether women with borderline personality disorder (BPD) are more likely than those with dysthymia to manifest contradictory Hostile-Helpless (HH) states of mind. A reliable rater blind to diagnosis evaluated features of such mental representations in transcripts of Adult Attachment Interviews from 12 women with BPD and 11 women with dysthymia of similar socioeconomic status (SES), all awaiting psychotherapy. In keeping with three hierarchical (non-independent) a priori predictions regarding the mental representations of women with BPD, the results were that (a) all those with BPD, compared with half the group with dysthymia, displayed HH states of mind; (b) those with BPD manifested a significantly higher frequency of globally devaluing representations; and (c) they exhibited a strong trend toward identifying with the devalued hostile caregiver (58% BPD vs. 18% dysthymic). In addition, significantly more BPD than dysthymic patients made reference to controlling behavior towards attachment figures in childhood. These findings offer fresh insights into the nature of BPD and extend previous evidence concerning affected individuals' patterns of thinking and feeling about childhood attachment figures. PMID- 17364480 TI - Parents-child role reversal in trilogue play: case studies of trajectories from pregnancy to toddlerhood. AB - Role reversal, whereby a child attempts to meet her parent's adult needs for parenting, intimacy, or companionship, has been identified as a risk factor for developmental disturbances. It has been defined from diverse perspectives as a child attachment strategy, a parent - toddler relational disturbance, and a boundary disturbance between parents and child. The recently discovered infant's triangular capacity, namely the sharing of her attention and affects with both parents, allows one to analyse the infant's contribution to early family dynamics. Role reversal was detected in 4 out of 45 father - mother - infant interactions observed in trilogue play from pregnancy to toddlerhood. The developmental trajectories towards role reversal are explored by means of case analyses. Results are compared with cases of problematic triangulation encountered in the same sample. In role reversal, family interactions are rigidly organized around a "two against one" coalition, whereby the normative hierarchy between parents and child is reversed. The child's triangular capacity is overactivated, controlling the tension between her parents by provocation - animation strategies. PMID- 17364481 TI - Mother-child attachment in later middle childhood: assessment approaches and associations with mood and emotion regulation. AB - This study examined the overlap and validity of several measures of mother - child attachment developed for preadolescents. Validity was assessed in part by examining how attachment is related to children's mood and emotion regulation. Mother - child attachment was assessed in a sample of 9 to 11 year-old children using a story stem interview technique and questionnaires. Positive and negative mood were scored from daily logs completed by children. Emotion regulation was assessed with mothers' reports of constructive coping and teacher reports of children's ability to tolerate frustration. Interview and questionnaire measures of attachment were not consistently related to one another, although both were related to mood and emotion regulation. As expected, secure attachment and maternal secure base support were related to higher levels of positive mood, more constructive coping, and better regulation of emotion in the classroom, with effects stronger for emotion regulation than for mood. Children classified Disorganized or Ambivalent displayed the most negative mood. All effects remained significant after controlling for child temperament. PMID- 17364482 TI - God is nowhere, God is now here: attachment activation, security of attachment, and God's perceived closeness among 5-7-year-old children from religious and non religious homes. AB - God's perceived closeness (GC) is greater when the attachment system is activated. This conclusion is based primarily on adult studies, but some findings suggest its validity also in childhood. Adult studies have shown GC to vary in relation to security of attachment, but child studies have been few and methodologically limited. In this study, we tested differences between securely and insecurely attached children on GC in attachment activating and neutral conditions, as well as whether parental religiousness acted as a moderator. Participants were forty 5-7-year-olds, from non-religious and Christian homes. The adapted Separation Anxiety Test was used to assess attachment. Participating children were told brief stories about visually represented children in different situations, and placed a God symbol on a felt board to represent GC to the fictional child. Results showed that GC was greater in attachment activating situations, particularly for secure children, supporting a hypothesis of internal working model correspondence between models of Self/Others and God. Although a religious type of home emerged as predictive of GC, no support was found for a moderating role of parental religiousness. PMID- 17364483 TI - Reliance on leaders and social institutions: an attachment perspective. AB - The ramifications of attachment processes in adulthood at the societal level are explored, specifically, why and under what circumstances followers form attachment relationships with a leader, and how the variability in these relationships can reflect the followers' internal working models of attachment. It is argued that in crisis situations, individuals tend to form affectional bonds with (mostly charismatic) leaders that function in many respects like an attachment relationship between a child and a parent. Relations between individuals and various social institutions, such as community or state, are likewise portrayed as involving attachment dynamics. The provision of security and protection (the safe haven and the secure base functions) by social structures, institutions, and leaders is seen as needed because of the inherent perceived imperfection and fallibility of "regular" attachment figures in adulthood (e.g., parents, friends, and romantic partners). This reliance on leaders and social institutions is seen as reflecting the normative diversification in attachment dynamics that takes place with development. Cultural and individual variations in these processes are also considered. PMID- 17364484 TI - Long-term outcomes for individuals who use augmentative and alternative communication: part II--communicative interaction. AB - This study evaluated the communicative interaction skills of seven young men (ages 19-23 years) who had used AAC systems for at least 15 years. Turn-taking patterns, use of communicative functions, and linguistic complexity were analyzed. Current performance was compared to the participants' skills when they were preschoolers and participated in another study of interaction skills (Light, 1985; Light, Collier, & Parnes, 1985a,b,c). Results indicated that the turn distribution between partners was more equitable than it had been when the participants were preschoolers; five of the participants approached reciprocity in turn taking during at least two of the interactions observed. During interactions with their caregivers, the participants fulfilled most of their obligatory turns and more than half of their non-obligatory turns. The communicative functions used most frequently by the participants were confirmations/denials and provisions of information. Three of the participants demonstrated the ability to use complete and complex syntax and committed few errors in grammar, while the other four participants demonstrated many syntactic errors. The results are discussed with implications for clinical practice and directions for future research. PMID- 17364485 TI - Analysis of spelling error patterns of individuals with complex communication needs and physical impairments. AB - The purpose of this study was to examine the relationships between patterns of spelling error and related linguistic abilities of four persons with complex communication needs and physical impairments, compared to younger individuals without disabilities matched by spelling age. All participants completed a variety of spelling and linguistic tasks to determine overall spelling age, patterns of spelling errors, and abilities across phonemic, orthographic, and morphological awareness. Performance of the spelling-age matched pairs was similar across most of the phonemic, orthographic, and morphological awareness tasks. Analysis of the participants' spelling errors, however, revealed different patterns of spelling errors for three of the spelling-age matched pairs. Within these three pairs, the participants with complex communication needs and physical impairments made most of their spelling errors due to phonemic awareness difficulties, while most of the errors on the part of the participants without disabilities were due to orthographic difficulties. The results of this study lend support to the findings of previous investigations that reported difficulties among individuals with complex communication needs and physical impairments evidence when applying phonemic knowledge to literacy tasks. PMID- 17364486 TI - The effect of aided AAC modeling on the expression of multi-symbol messages by preschoolers who use AAC. AB - A single subject, multiple probe design across participants was used to evaluate the impact of using aided AAC modeling to support multi-symbol message production. Five preschoolers (three who used voice output communication systems, two who used non-electronic communication boards) participated in the study. Aided AAC models were provided by pointing to two symbols on the child's aided AAC system and then providing a grammatically complete spoken model while engaging in play activities. Four of the five preschoolers learned to consistently produce multi-symbol messages; the fifth did not demonstrate consistent gains. The four preschoolers who met criterion all evidenced long-term use of symbol combinations and generalized use of symbol combinations to novel play routines. Results, clinical implications, and future research directions are discussed. PMID- 17364487 TI - The effect of color on the recognition and use of line drawings by children with severe intellectual disabilities. AB - Line drawings are commonly used as communication symbols for individuals with severe intellectual disabilities. This study investigated the effect of color on the recognition and use of line drawings by young children with severe intellectual disabilities and poor verbal comprehension who were beginning picture users. Drawings where the color of the picture matched the object and where the color of the drawing did not match the object were used, as well as black and white line drawings. Tentative findings suggest that some students with intellectual disabilities may find it more difficult to recognize and line drawings where the color does not match the object compared to line drawings where the color of the drawing does match the color of the object. PMID- 17364488 TI - The AAC Mentor Project: web-based instruction in sociorelational skills and collaborative problem solving for adults who use augmentative and alternative communication. AB - In this study, we investigated the effects of a self-paced instructional program, delivered via an accessible website, to teach sociorelational skills and collaborative problem-solving skills to adults with cerebral palsy who used augmentative and alternative communication (AAC). The instruction was designed to prepare participants to serve as mentors, in an Internet-based mentor program, for adolescents and young adults who also used AAC (Light & McNaughton, 2002). The effect of the training program was evaluated in two separate studies utilizing single-subject multiple probe designs: Study 1 investigated the effects of Lesson 1 of the web-based instructional program on the acquisition of sociorelational skills by six adults who used AAC; and, Study 2 focused on the effects of Lesson 2 on the acquisition of collaborative problem-solving skills by 15 adults who used AAC. All participants in Study 1 successfully acquired the target sociorelational skills to help them establish positive mentoring relationships with their proteges, and all participants in Study 2 acquired the collaborative problem-solving skills to support proteges in overcoming challenges in their lives and attaining goals. Results are discussed, along with implications for practice and directions for future research. PMID- 17364489 TI - Brevity and speed of message delivery trade-offs in augmentative and alternative communication. AB - This study is the third in a series of studies that have concentrated on utterance-based systems--which allow the relatively quick selection of full sentences--and investigated trade-offs faced by users of such systems when there is a pragmatic mismatch between the prestored sentence and the current discourse context. While the previous studies focused on trade-offs between speed of message delivery and either relevance or informativeness, this study investigated the effects of trade-offs between speed of message delivery and brevity on public attitudes. Participating were 96 sales clerks who viewed scripted, videotaped trade-off message conditions in the context of a bookstore interaction and completed a questionnaire designed to assess their attitudes toward customers who used utterance-based systems and his or her communication. Significantly higher mean ratings were found for the trade-off condition involving the quickly delivered message with repetition when compared to each of the slowly delivered, non-repetitive message conditions (i.e., with and without a preceding conversational floorholder). Implications regarding the model of conversational trade-off choices and its technological applications are discussed. PMID- 17364490 TI - Research priorities in augmentative and alternative communication as identified by people who use AAC and their facilitators. AB - Two focus groups comprised of adults who used AAC and two focus groups comprised of adult AAC facilitators in Ontario, Canada were asked to identify their own AAC research priorities and to state their levels of agreement with previously identified research priorities in AAC. Members of the focus group who used AAC had physical disabilities since birth except one participant who became disabled at age 2 years. Using focus group methodology and analysis, the participants were asked to generate their own AAC research priorities. A questionnaire and Likert type scale was used to determine their levels of agreement with six research priorities set a decade earlier by a group of AAC researchers sponsored by the United States-based National Institute of Deafness and other Communication Disorders (NIDCD). Focus group members stressed the importance of (a) preparing people who use AAC to succeed in situations such as maintaining friendships, dating, and finding jobs; (b) improving service delivery of their AAC devices; (c) improving technology in high tech and low tech devices; (d) increasing public awareness of people who use AAC; (e) improving methods of teaching reading skills to people who use AAC; and (f) improving AAC communications training for all healthcare professionals. PMID- 17364491 TI - Increased expression of STAT3 in SLE T cells contributes to enhanced chemokine mediated cell migration. AB - Exposure of T cells to inflammatory cytokines leads to phosphorylation-dependent activation of signal transducer and activator of transcription (STAT) 3. T cells from patients with systemic lupus erythematosus (SLE) display increased levels of total and phosphorylated STAT3 which resides primarily in the nucleus. Increased STAT3 is associated with increased expression of target genes. Silencing of STAT3 expression using a small interfering RNA approach resulted in decreased chemokine provoked SLE T cell migration. Our data suggest that inhibition of STAT3 expression may reverse the signaling aberrations involved in SLE T cell migration. PMID- 17364492 TI - Down-regulation of CD72 and increased surface IgG on B cells in patients with lupus nephritis. AB - The significance of both the acceleratory and inhibitory functions of the CD72 molecule was investigated among patients with systemic lupus erythematosus (SLE) during modification of B cell differentiation. Expression of the CD72 molecule and mRNA on B cells was decreased in SLE with lupus nephritis, while CD100 expression on both CD4+ T cells and CD8+ T cells was not significant in comparison with the controls. When the relationship between CD72 expression and other B cell markers was examined, decreased expression of CD72 was associated with differences in the stage of differentiation. In patients with decreased expression of CD72, switching to IgG was evident, and the disease stage was started to severe. In patients with lupus nephritis, the decreased expression of CD72 was related to class switching on B cells, suggesting that CD72 is a useful marker for determining class switching of B cells in lupus nephritis. PMID- 17364493 TI - Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis. AB - Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-beta-1a; Rebif 44 microg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance. We validated IL-10 up-regulation, which is in accordance with previous reports, and other novel changes that underscore the capacity of IFN-beta to impair antigen presentation and migration of inflammatory elements into the central nervous system (up-regulation of filamin B and down-regulation of IL-16 and rab7). Overall, gene expression changes became less pronounced after 3 months of therapy, suggesting a homeostatic response to IFN-beta. This may be of use for the design of new treatment schedules. PMID- 17364495 TI - The balance shift in Th1/Th2 related IL-12/IL-5 cytokines in Graves' disease during methimazole therapy. AB - Th1 and Th2-like cytokines are involved in the pathogenesis of Graves' disease. The shift in balance in IL-12/IL-5 cytokines was applied in judging the immunological events in 74 patients with Graves' disease (50 had ophthalmopathy) during methimazole therapy and in 15 controls. The serum levels of IL-12 and IL-5 were measured with enzyme-linked immunosorbent assay in all Graves' patients. Twelve cases for IL-5 and 20 cases for IL-12 were positive. In Graves' patients only those without ophthalmopathy had higher levels of IL-12 when compared to controls (192.66 +/- 29.19 vs. 85.09 +/- 8.95 pg/ml, P < 0.04). After 2 months of methimazole therapy in Graves' patients without ophthalmopathy an increase in the ratio of IL-12 to IL-5 was also observed as compared to those with eye symptoms (91.78 +/- 34.14 vs. 20.72 +/- 6.36, P < 0.015). Age-related difference in the serum level of IL-5 could be demonstrated between Graves' patients without and those with ophthalmopathy aged < or = 35 years (4.89 +/- 0.57 vs. 50.14 +/- 20.2 pg/ml, P < 0.002). No association was found among the serum levels of IL-5 or IL 12, thyroid hormones and TSH receptor antibodies. The results demonstrated a difference in the balance shift of IL-12/IL-5 between Graves' patients with and without ophthalmopathy. The increased ratio of IL-12 to IL-5 after methimazole therapy could be explained by the elevation of serum IL-12 due to methimazole therapy and the age-related decrease of serum IL-5. PMID- 17364494 TI - Expression of messenger RNA for transforming growth factor-beta1 and for transforming growth factor-beta receptors in peripheral blood of systemic lupus erythematosus patients treated with low doses of quinagolide. AB - The objective of this study was to determine the expression of transforming growth factor-beta1 messenger RNA (TGF-beta1 mRNA) and the expression of mRNA for TGF-beta receptors (TGF-beta Rs mRNA) in whole peripheral blood of consecutive (treated from several months to several years) systemic lupus erythematosus (SLE) patients (21 women). A further aim of this study was to evaluate the association between expression of the above mentioned parameters in relation to the form of applied therapy (9 patients treated with quinagolide and 12 with quinagolide plus prednisone, azathioprine or cyclosporine A). The control group consisted of 15 healthy women. Most of the patients had mild SLE with SLE disease activity index (SLEDAI) score < 10 at time when blood samples were collected. Laboratory measurements included real-time polymerase chain reaction (RT-QPCR). The expression levels of TGF-beta1 mRNA and mRNA for TGF-beta RII and RIII were significantly lower in patients whereas the expression level of TGF-beta RI was statistically significantly higher in SLE patients than in the controls. A very high positive correlation between TGF-beta1 mRNA expression and expression levels of TGF-beta Rs mRNA was found. In compared subgroups selected according to the form of the applied therapy no statistically significant differences were observed. We conclude that the TGF-beta signaling pathway can be altered in circulating leukocytes derived from treated patients with SLE and that the assumed forms of the applied therapy in the group of patients under consideration are accompanied by similarity in the expression level of transcripts for TGF beta1 and TGF-beta Rs determined in whole blood. In our investigations, we cannot exclude the influence of the disease itself on the obtained results. PMID- 17364496 TI - Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies. AB - Antibodies against the N-terminal (NT) but not the basic domain (BD), DNA binding regions of the largest subunit (S1) of RNA polymerase I (RNAPI) were detected in the sera of MRL-lpr/lpr lupus mice. Antibodies against both RNAPI(S1)-NT and -BD, as well as other systemic lupus erythematosus (SLE) autoantigens (La, ribosomal P proteins and Sm/RNP) were produced by rabbits immunized with anti-DNA antibodies that had been affinity purified from SLE patients. Immunization of nonautoimmune mice (Balb/c) with RNAPI(S1)-NT, RNAPI(S1)-BD, or La in the form of GST fusion proteins, induced production of anti-double-stranded (ds) DNA and anti-Sm/RNP. GST-P1 did not induce an anti-dsDNA response in these mice. These results demonstrate that RNAPI(S1)-NT, RNAPI(S1)-BD and La can participate in an anti autoantigen/anti-DNA antibody loop during an SLE-like autoimmune response. PMID- 17364497 TI - Infection and vaccination in chronic fatigue syndrome: myth or reality? AB - Chronic fatigue syndrome (CFS) is characterized by severe disabling fatigue lasting for more than 6 months associated with physical and mental disturbances such as headache, arthralgia, myalgia, memory impairment, sore throat and tender lymph nodes. The exact pathogenesis is still unknown. Several models were proposed to explain its etiology including chronic infection, endocrine dysfunction, autonomic imbalance, depression, decreased immunity states and an aberrant reaction to infection. No convincing evidence was found to support any of the suggested pathogenic mechanisms. The current concept is that CFS pathogenesis is a multi factorial condition in which an infective agent cause an aberrant immune response characterized by a shift to Th-2 dominant response. When the response fails to be switched-off, a chronic immune activation occurs and clinically expressed as the symptomatology of CFS. Vaccinations are used in order to stimulate the immune system to induce a persistent immunity against the favorable antigens. Several syndromes that contain chronic fatigue as one of their symptoms, such as "Gulf war syndrome" and macrophagic myofasciitis were related to vaccinations. Can vaccinations induce the aberrant immune response of CFS? Little is known about this issue. There are some reports on CFS occurring after vaccination, but few prospective and retrospective studies failed to find such an association. A working group of the Canadian Laboratory Center for Disease Control (LCDC) that was founded in order to examine the suspected association between CFS and vaccinations concluded that there is no evidence that relates CFS to vaccination. Further studies are requested to examine this issue since it is very conceivable that if infection can lead to CFS, vaccination may also lead to it in the same immune-mediated pathogenesis. PMID- 17364498 TI - Anti-viral effector T cell responses and trafficking are not dependent upon DRAK2 signaling following viral infection of the central nervous system. AB - The signaling events involved in T cell trafficking into the central nervous system (CNS) following viral infection are not fully understood. Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by an immune-mediated demyelinating disease. Although chemokine signaling is critical in promoting T cell infiltration into the CNS and control of viral replication, additional signaling pathways have not been completely explored. DRAK2, a lymphoid-restricted serine/threonine kinase, prevents spurious T cell activation. Yet Drak2- / - mice are resistant to MOG induced experimental autoimmune encephalomyelitis (EAE), suggesting that DRAK2 may influence T cell trafficking into the CNS. In order to further characterize the molecular mechanisms governing T cell activation and accumulation within the CNS in response to viral infection, MHV was instilled into the CNS of Drak2- / - mice. Drak2-deficient T cells possessed no obvious defects in trafficking into the CNS following MHV infection. Moreover, Drak2-deficient T cell activation, expansion and cytokine production were unimpaired in response to acute MHV infection. These results demonstrate that DRAK2 signaling is dispensable for T cell recruitment into the CNS following viral infection, suggesting that the resistance of Drak2- / - mice to EAE is not due to overt T cell trafficking defects. PMID- 17364499 TI - Detection of autoantibodies to survivin in cervical mucus from patients with human papillomavirus-associated cervical cancer and precursor lesions. AB - OBJECTIVES: To investigate the prevalence of mucosal autoantibodies to survivin in patients with human papillomavirus (HPV)-associated cervical cancer and precursor lesions. METHODS: Cervical mucus from 117 HPV-associated cervical cancer, 102 high-grade squamous intraepithelial lesion (HSIL), 107 low-grade SIL (LSIL), and 80 normal controls were tested by ELISA using either full length recombinant survivin or survivin-derived peptides. Survivin expression in cervical tissue biopsies was studied by Western Blotting. RESULTS: Cervical mucus from 33 cervical cancer (28.2%), 17 HSIL (16.6%), and 8 LSIL (7.4%) patients reacted with recombinant survivin. The IgA-class antibody response was significantly higher than that observed in the normal controls. The level of mucosal anti-survivin response was associated to the level and intensity of survivin expression in the different lesions. Finally, reactivity against a survivin Nt-derived peptide was found more frequently than reactivity against a Ct-derived peptide. CONCLUSIONS: IgA-class autoantibodies against survivin are present in a substantial proportion of cervical mucus from patients with HPV associated cervical cancer, and precursor lesions. Mucosal anti-survivin response is positively associated with the level of survivin expression and the grade of cervical lesion. PMID- 17364500 TI - Anti-68 kDa antibodies in autoimmune sensorineural hearing loss: are these autoantibodies really a diagnostic tool? AB - OBJECTIVES: Autoimmune sensorineural hearing loss (ASNHL) is a relatively rare disorder which can lead to total deafness. At present, no specific laboratory test with adequate sensitivity and specificity is available to confirm the clinical suspicion of ASNHL. The aim of this study was to identify if evaluation of anti-hsp70 antibodies is an accurate diagnostic tool in patients affected by ASNHL. STUDY DESIGN: Prospective study. METHODS: During 4-year (2001-2005), all patients with SNHL who were referred to the Eye, Ear, Nose and Throat Department of Parma University, Italy, underwent specific tests to determine the autoimmune origin of the disease. Patients with a consistent suspicion of ASNHL underwent the routine serologic tests and a test for determination of anti-hsp70 antibodies. The same patients were divided into three groups: (1) idiopathic ASNHL; (2) ASNHL associated with ocular inflammation, i.e. Cogan's Syndrome; (3) ASNHL associated with a systemic autoimmune disease (SAD). The control group included: (1) healthy subjects; and (2) patients affected by SAD, without any ocular or audiovestibular disease. RESULTS: 88 subjects (67 patients, defined as "study group", and 21 controls) were evaluated. Anti-hsp70 antibodies were isolated in 52% of the study group patients, and in 4% of the control group (chi2 = 13.009, p < 0.01). In the idiopathic ASNHL patients, 59.5% were found positive for anti-hsp70 antibodies. About 50% of patients affected by CS and 37.5% of patients affected by SAD with SNHL were found positive. In the control group, anti-hsp70 antibodies were found in 8.3% of healthy subjects and in none of the patients with SAD and no hearing loss. CONCLUSIONS: The present study confirms the value of the anti-hsp70 test in the serological diagnosis of autoimmune hearing loss. It is still the only available diagnostic marker that identifies an autoimmune origin of hearing loss. PMID- 17364501 TI - Celiac disease associated antibodies in persons with latent autoimmune diabetes of adult and type 2 diabetes. AB - BACKGROUND: Celiac Disease (CD) is present in 1-16.4% of patients with type 1 diabetes mellitus. The most important serological markers of CD are anti endomysial (EMA), anti-tissue transglutaminase (tTGA) and antigliadin antibodies (AGA). AIM/HYPOTHESIS: The objective of this work is to determine the frequency of tTGA and/or AGA in latent autoimmune diabetes of adult (LADA) and subjects with type 2 diabetes (T2DM), as well as to evaluate their relation with several clinical and biochemical characteristics. SUBJECTS AND METHODS: Forty three subjects with LADA and 99 with T2DM were studied. The presence of AGA, tTGA was determined in the sera of these patients. The variables: sex, age, duration of diabetes, treatment, body mass index (BMI) and fasting blood glucose concentration were also recorded. RESULTS: No differences were found in the frequency of celiac disease associated antibodies between LADA and T2DM subjects. The presence of celiac disease related antibodies was more frequent in patients with a normal or low BMI. CONCLUSIONS: Celiac disease does not seem to be related with pancreatic autoimmunity in type 2 diabetes. Celiac disease causes a decrease of body mass index in type 2 diabetes while pancreatic islet autoimmunity in this entity masks this effect. PMID- 17364502 TI - Changes in expression of P2X7 receptors in NOD mouse pancreas during the development of diabetes. AB - This study examined the expression of P2X7 receptors in pancreatic islets of the non-obese diabetic (NOD) mouse model of human autoimmune insulin-dependent diabetes mellitus, to determine whether they are involved in islet cell destruction during early- and late-developing diabetes. Pancreatic cells containing glucagon (alpha-cells), insulin (beta-cells) and somatostatin (delta cells) were co-localized with P2X7 receptors. We examined P2X7 receptor expression in normal and diabetic spleens using flow cytometry. In non-diabetic NOD controls, P2X7 receptors were expressed in glucagon-containing cells at the periphery of islets, being consistent with previous studies. In early NOD diabetes (12 weeks), there was migration of peripheral P2X7 receptor positive, glucagon-containing cells into the center of islets. In late NOD diabetes (34 weeks), P2X7 receptor- and glucagon-stained alpha-cells were gone from islets. Migration of macrophages and dendritic cells into islets took place, but they lacked P2X7 immunoreactivity. There was no significant difference in the percentage of splenic macrophages stained for P2X7 receptors from control and diabetic spleens. In conclusion, in the development of early to late diabetes, there is a down-regulation of P2X7 receptors on islet cells and a loss of alpha- and beta-cell populations. P2X7 receptor signalling might be involved in alpha cell clearance from late diabetic islets. PMID- 17364503 TI - Two-year follow-up of anti-transglutaminase autoantibodies among celiac children on gluten-free diet: comparison of IgG and IgA. AB - OBJECTIVES: To investigate the evolution of IgA and IgG autoantibodies against tissue transglutaminase (tTGase) in celiac patients on gluten-free diet (GFD). METHODS: IgA and IgG anti-tTGAse autoantibodies was evaluated in 93 patients (58 girls and 35 boys; mean age 3.56 +/- 3.04 years; range 0.94-17.5 years) at diagnosis of celiac disease and after 1, 2, 4, 6, 12, 18, 24 months of follow-up on GFD. Autoantibodies were measured with a radioassay using in vitro transcribed translated human recombinant tTGAse, and immune complexes were precipitated with protein A- or anti-IgA-agarose for IgG and IgA, respectively. RESULTS: Autoantibody titers started to decline very soon after removal of gluten, and no significant differences in the decrease rate between IgG and IgA antibodies were observed. After 6 months on GFD, 63 and 49% of the patients were negative for IgG and IgA, respectively. Patients who remained autoantibody-positive after 6 months of treatment initially presented with significantly higher titers at the time of diagnosis compared to patients that had lost their antibodies by that time. Children diagnosed before the age of two years presented lower autoantibody titers, while patients positive for HLA-DR7 had higher anti-tTGase levels, especially IgA. CONCLUSIONS: There are no differences in the performance of IgG and IgA class autoantibodies in the evolution of celiac patients. Between 3 and 6 months on GFD, almost half of the patients are negative for anti-tTGase antibodies. In our experience, they can be of help in evaluating compliance with diet, at least during the first two years of treatment. PMID- 17364504 TI - Green tea polyphenols reduce autoimmune symptoms in a murine model for human Sjogren's syndrome and protect human salivary acinar cells from TNF-alpha-induced cytotoxicity. AB - Sjogren's syndrome (SS) is a relatively common autoimmune disorder. A key feature of SS is lymphocytic infiltration of the salivary and lacrimal glands, associated with the destruction of secretory functions of these glands. Current treatment of SS targets the symptoms but is unable to reduce or prevent the damage to the glands. We reported previously that the major green tea polyphenol (GTP) epigallocatechin-3-gallate (EGCG) inhibits autoantigen expression in normal human keratinocytes and immortalized normal human salivary acinar cells (Hsu et al. 2005). However, it is not known whether GTPs have this effect in vivo, if they can reduce lymphocytic infiltration, or protect salivary acinar cells from tumor necrosis factor-alpha (TNF-alpha)-induced cytotoxicity. Here, we demonstrate that in the NOD mouse, a model for human SS, oral administration of green tea extract reduced the serum total autoantibody levels and the autoimmune-induced lymphocytic infiltration of the submandibular glands. Further, we show that EGCG protected normal human salivary acinar cells from TNF-alpha-induced cytotoxicity. This protection was associated with specific phosphorylation of p38 MAPK, and inhibitors of the p38 MAPK pathway blocked the protective effect. In conclusion, GTPs may provide a degree of protection against autoimmune-induced tissue damage in SS, mediated in part through activation of MAPK elements. PMID- 17364505 TI - Salmonella infections: immune and non-immune protection with vaccines. AB - Salmonella enterica in poultry remains a major political issue. S. enterica serovar Enteritidis, particularly, remains a world-wide problem. Control in poultry by immunity, whether acquired or innate, is a possible means of containing the problem. Widespread usage of antibiotics has led to the emergence of multiple antibiotic-resistant bacteria. This problem has indicated an increasing requirement for effective vaccines to control this important zoonotic infection. An attempt is made in the present review to explain the relatively poor success in immunizing food animals against these non-host-specific Salmonella serotypes that usually produce food-poisoning, compared with the success obtained with the small number of serotypes that more typically produce systemic "typhoid-like" diseases. New examinations of old problems such as the carrier state and vertical transmission, observed with S. Pullorum, is generating new information of relevance to immunity. Newer methods of attenuation are being developed. Live vaccines, if administered orally, demonstrate non-specific and rapid protection against infection that is of biological and practical interest. However, from the point of view of consumer safety, there is a school of thought that considers inactivated or sub-unit vaccines to be the safest. The benefits of developing effective killed or sub-unit vaccines over the use of live vaccines are enormous. Recently, there have been significant advances in the development of adjuvants (e.g. microspheres) that are capable of potent immuno-stimulation, targeting different arms of the immune system. The exploitation of such technology in conjunction with the ongoing developments in identifying key Salmonella virulence determinants should form the next generation of Salmonella sub-unit vaccines for the control of this important group of pathogens. There are additional areas of concern associated with the use of live vaccines, particularly if these are generated by genetic manipulation. PMID- 17364506 TI - Differences in pathogenicity among strains of the same or different avian leukosis virus subgroups. AB - An efficient induction of wasting disease in chickens by avian leukosis virus (ALV), particularly ALV subgroup C, requires >102 infectious units virus inoculated in mid embryogenesis. The most conspicuous symptoms of the disease were induced by ALV subgroup C; however, significant differences in the occurrence of wasting disease were found among individual members of this subgroup. Almost comparable pathogenicity was exhibited by ALV subgroup D, whereas viruses of subgroups B and A proved to be moderately and almost non pathogenic, respectively. Using antibodies to cellular antigens, tissue alterations were shown clearly in ALV-C-infected chickens. An essential feature was depletion of lymphocytes in the thymus, bursa and spleen. While the number of dendritic cells in the bursa was increased, their representation in the thymus and spleen was reduced. In the spleen, however, the reduction of dendritic cells concerned only an ellipsoid compartment, which in itself was also markedly reduced. An increased number of macrophages in the thymus and spleen corresponded with the observed general activation of the monocyte-macrophage system. In the spleen, CD4+ T cells were reduced while CD8+ T cells were increased. In agreement with this finding was a failure of chickens to respond to Brucella antigen and an inability of their splenocytes to respond to Concanavalin A, both of which pointed to the damage of immune reactivity. Variation in the pathogenicity among individual ALV strains provides ground for depicting gene sequences playing an important role in ALV acute pathogenicity. PMID- 17364507 TI - Detection of turkey coronavirus in commercial turkey poults in Brazil. AB - Poult enteritis complex has been incriminated as a major cause of loss among turkey poults in other countries. We have observed this in Brazil, associated with diarrhoea, loss of weight gain and, commonly, high mortality. In this study, we have used the reverse transcriptase polymerase chain reaction (RT-PCR) to detect turkey coronavirus (TCoV) in sick poults 30 to 120 days of age from a particular producer region in Brazil. The RT-PCR was applied to extracts of intestine tissue suspensions, and the respective intestinal contents, bursa of Fabricius, faecal droppings and cloacal swabs. Primers were used to amplify the conserved 3' untranslated region of the genome, and the nucleocapsid protein gene of TCoV. Histopathological and direct immunohistochemical examinations were performed to detect TCoV antigen in infected intestine and bursa slides. All the results from stained tissues revealed lesions as described previously for TCoV infection. The direct immunohistochemical positive signal was present in all intestine slides. However, all bursa of Fabricius tissues analysed were negative. RT-PCR findings were positive for TCoV in all faecal droppings samples, and in 27% of cloacal swabs. Finally, the best field material for TCoV diagnosis was faecal droppings and/or intestine suspensions. PMID- 17364508 TI - Virulence characterization of Avibacterium paragallinarum isolates from Uganda. AB - Avibacterium paragallinarum isolates from Uganda were characterized for their virulence by comparison of their pathogenicity and their resistance to serum. Pathogenicity was evaluated using commercial Hisex Brown layer chickens, local indigenous chickens, local turkeys and local guineafowls inoculated with 108 colony-forming units of Av. paragallinarum and comparing their overall mean disease scores over a period of 20 days. Persistence of the bacteria in the host and water was also investigated for a 60-day period by culture and polymerase chain reaction as well as use of sentinel chickens. Serum resistance was measured by comparison of the growth kinetics and survival indices at 3 and 6 h. There was no difference in the virulence of the isolates. Commercial layer chickens and local indigenous chickens were equally susceptible to challenge, while turkeys and guineafowls only showed transient mild signs and did not transmit infection. Turkeys and guineafowls did not acquire the infection when placed in contact with infected chickens. The isolates were resistant in normal chicken serum at both 3 and 6 h of incubation but were resistant at 3 h and sensitive at 6 h in turkey and guineafowl sera. The resistance of the isolates to serum correlated with their pathogenicity in the different hosts. No carrier status was demonstrated in this study using polymerase chain reaction and culture. The present study demonstrates that Ugandan Av. paragallinarum isolates are pathogenic to chickens with only transient signs in turkeys and guineafowls, and that serum resistance could be a subject for further investigation as a predictor of virulence of these bacteria. The role of turkeys and guineafowls in transmission of Av. paragallinarum was not demonstrated in the present investigation. PMID- 17364509 TI - Prevalence and associated risk factors of necrotic enteritis on broiler farms in the United Kingdom; a cross-sectional survey. AB - In order to determine the prevalence and risk factors for necrotic enteritis in broilers, a cross-sectional survey was conducted among 857 farms, rearing broilers for nine UK poultry companies. The main data collection tool was a postal questionnaire directed at farm managers. Additional information on disease occurrence on the farm was collected from veterinary postmortem reports. The response rate to the questionnaire was 75%, ranging from 54% to 90% within companies. During 2001, 32.8% of the respondents indicated that they had observed a case of necrotic enteritis (95% confidence interval, 29.1 to 36.8) in at least one flock. The disease was most often reported during the months October to February. The point prevalence (necrotic enteritis occurrence in the most recently reared flock) reported by farm managers was 12.3% (95% confidence interval, 9.8 to 15.2). Multilevel logistic regression was performed with the poultry company as the random effect, using the occurrence of necrotic enteritis in the farm's most recently reared flock as the dependent variable. Strong associations were found between the outcome variable and the occurrence of wet litter (odds ratio, 2.39; 95% confidence interval, 1.27 to 4.52; P = 0.007) and coccidiosis (odds ratio, 4.68; 95% confidence interval, 1.74 to 12.55; P = 0.002). In addition, the use of ammonia as a disinfectant for coccidial oocysts appeared to be an independent risk factor (odds ratio, 3.44; 95% confidence interval, 1.53 to 7.71; P = 0.003). Finally, the positive association between the use of plasterboard walls in poultry houses and the occurrence of necrotic enteritis might point to an important role of cleaning and disinfection in the epidemiology of this disease (odds ratio, 3.72; 1.38 to 10.00; P = 0.009). PMID- 17364510 TI - Basophilic intracytoplasmic viral matrix inclusions distributed widely in layer hens affected with avian-leukosis-virus-associated tumours. AB - Layer hens (310 days old) affected with subcutaneous tumours were investigated pathologically. Basopholic intracytoplasmic viral matrix inclusions (MIs) were widely distributed in the chickens affected with subcutaneous myxoma rhabdomyosarcoma, perineuroma, glioma, intra-abdominal adenocarcinoma, and nephroblastoma. MIs were observed in the myocardial cells and the impulse conducting-system cells. They were also present in the smooth muscle cells of the arteries in the spleen and lungs, in the smooth muscle of the digestive tract muscular layer (crop, oesophagus, proventriculus, gizzard, duodenum, jejunum, ileum, caecum, and large intestine), and in the smooth muscle of the capsule in the ovary and pancreas. They were also observed in the podocytes of glomeruli and renal epithelium in the kidneys, tumour cells of nephroblastoma, chondrocytes of the trachea, squamous-epithelial cells of the pharynx, and nerve cells of the cerebrum and tumour cells of the glioma in the cerebellum. Histochemically, MIs were stained with RNA, but not with DNA. MIs in the various tissues were strongly positive for the avian leukosis virus (ALV) antigen. Ultrastracturally, MIs were found in the cytoplasm of myocardial cells and podocytes of renal glomeruli. They consisted of electron-dense small granules and ring-shaped particles. Viral particles were observed in the vesicles of the cytoplasm of myocardial cells and glomerular podocytes. The gene product specific for subgroup A of ALV was detected in the livers or tumours by reverse transcription-polymerase chain reaction. This result suggests that MIs can be formed in organs rather than muscular systems in the chickens naturally affected with ALV-associated tumours. PMID- 17364511 TI - Sequence changes of infectious bronchitis virus isolates in the 3' 7.3 kb of the genome after attenuating passage in embryonated eggs. AB - Attenuated infectious bronchitis virus (IBV) vaccines are available but the relationship between sequence and virulence is not clear. In this study, the sequences of the 3' 7.3 kb of the genome, amplified using reverse transcription polymerase chain reaction before and after attenuation, were compared to study the relationship between virulence and the sequences of three IBV strains. After attenuation, two to six amino acid substitutions were found in the spike 1 subunit, and two or three amino acid substitutions were found in the spike 2 subunit. None or one amino acid substitution was found in the small membrane protein, and one or three amino acid substitutions were found in the membrane protein. However, no amino acid substitution was found in the nucleocapsid (N) protein, indicating that the N protein might not be related to this attenuation. The 3' untranslated region after the N gene of one strain was partially deleted after attenuation, and might be correlated with virulence. This study is the first demonstration for IBV comparing sequence changes in the 3' 7.3 kb genome after attenuation. The aforementioned information on amino acid changes might be useful in future virulence studies. PMID- 17364512 TI - Expression of chicken interleukin-2 by turkey herpesvirus increases the immune response against Marek's disease virus but fails to increase protection against virulent challenge. AB - As Marek's disease virus continues to evolve towards greater virulence, more efficacious vaccines will be required in the future. We expressed chicken interleukin-2 (IL-2) from a turkey herpesvirus (HVT) in an attempt to increase the efficacy of HVT as a vaccine against Marek's disease. The recombinant IL 2/HVT was safe for in ovo vaccination, although it replicated less in the birds compared with the parent HVT strain. Expression of IL-2 increased the neutralizing antibody response against HVT but did not increase the protection against virulent Marek's disease virus challenge. PMID- 17364513 TI - Molecular characterization of novel circoviruses from finch and gull. AB - The purpose of this study was to molecularly characterize circoviruses that infect finches and gulls. Circovirus-specific DNAs were isolated using polymerase chain reaction methods from bursa of Fabricius tissues from a Gouldian finch (Chloebia gouldiae) and a herring gull (Larus argentatus) that were known to be circovirus-infected. Nucleotide sequence determination and analysis of cloned genomic DNAs showed that these circoviruses represented novel members of the genus Circovirus of the family Circoviridae, and have been tentatively named Finch circovirus (FiCV) and Gull Circovirus (GuCV). Both new circoviruses shared genome organizational features with previously characterized circoviruses, such that both contained two major, inversely-arranged open reading frames encoding the putative replication-associated and capsid proteins, and both contained a potential stem-loop and nonanucleotide motif. Phylogenetic analyses based on genome nucleotide sequences and involving the seven additional genus members indicated that FiCV and GuCV were more closely related to canary circovirus, beak and feather disease virus and pigeon circovirus, and that FiCV and canary circovirus were the most closely related avian circoviruses. Pairwise comparisons showed that the capsid proteins of FiCV and GuCV shared highest amino acid identity values with those of canary circovirus (62.0%) and pigeon circovirus (40.6%), respectively. The 5' intergenic region of GuCV was longer (207 nucleotides) and contained more direct and inverse repeated sequences than those of other circoviruses, while the 3' intergenic region of FiCV was notable in being longer (307 nucleotides) than its counterparts in other circoviruses and in containing two long repeats of 77 nucleotides. PMID- 17364514 TI - The characteristics of patients who do not seek medical treatment for traumatic brain injury. AB - PRIMARY OBJECTIVE: To identify factors associated with not seeking medical care for traumatic brain injury (TBI). RESEARCH DESIGN: Internet survey. METHODS AND PROCEDURES: The survey consisted of 17 questions related to demographics, TBI case ascertainment, location and mechanism of injury, type of treatment sought, and post-concussive (PC) symptoms. Logistic regression was used to identify factors associated with not seeking medical care. MAIN OUTCOME AND RESULTS: Of the 1381 survey respondents with TBI, 584 (42%) did not seek medical care. TBI respondents were less likely to seek care if they were older (OR 0.98, 95% CI 0.97-0.99), suffered a mild TBI grade 2/3 (OR 0.42, 95% CI 0.31-0.58), or were injured in the home (OR 0.53, 95% CI 0.36-0.78). CONCLUSIONS: Several factors associated with not seeking medical care after TBI were identified. Raising public awareness of the signs and symptoms of TBI, and the benefits of medical care, could help increase the number of TBI patients who seek medical care. PMID- 17364515 TI - A pilot study for rehabilitation of central executive deficits after traumatic brain injury. AB - PRIMARY OBJECTIVE: An impairment of the central executive system (CES) of working memory (WM) is a common consequence of traumatic brain injury (TBI), and may also explain deficits in divided attention, long-term memory and executive functions. Here we investigated the efficacy of a rehabilitative program (working memory training: WMT) targeting the CES in improving WM and other cognitive functions dependent on this system. METHODS AND PROCEDURES: Nine TBI patients with severe WM deficits underwent the WMT (experimental training). The WMT was preceded by a general stimulation training (GST; control training). Patients' cognitive performance was evaluated at the admission, after the GST and at the end of the WMT. MAIN OUTCOMES AND RESULTS: Whereas the GST had no effect on patients' performance, after the WMT patients improved in all the cognitive functions dependent on the CES, but not in those functions not thought to tap this system. Importantly, a beneficial WMT effect was found on patients' everyday life functioning. CONCLUSIONS: The results support the efficacy of the WMT in recovering CES impairments. PMID- 17364516 TI - Computerized working memory training after stroke--a pilot study. AB - AIM: To examine the effects of working memory (WM) training in adult patients with stroke. METHODS: A randomized pilot study with a treatment group and a passive control group; 18 participants (12 males) in a vocational age group (mean age 54 years) were randomized to either the treatment or the control condition. The intervention consisted of computerized training on various WM tasks for five weeks. A neuropsychological test battery and self-rating on cognitive functioning in daily life (the CFQ) were administered both before and after the treatment. RESULTS: Statistically significant training effects were found on the non-trained tests for WM and attention, i.e., tests that measure related cognitive functions but are not identical to tasks in the training programme (Span board p < 0.05; PASAT p < 0.001; Ruff 2&7 p < 0.005). There was a significant decrease in symptoms of cognitive problems as measured by the CFQ (p < 0.005). CONCLUSION: More than one year after a stroke, systematic WM training can significantly improve WM and attention. PMID- 17364517 TI - Post-traumatic growth after head injury: a long-term follow-up. AB - PRIMARY OBJECTIVE: To investigate the time course of any positive psychological changes after traumatic brain injury (TBI) by comparing questionnaire responses in two groups of TBI survivors, early, 1-3 years post-injury and late, 10-12 years post-injury. RESEARCH DESIGN: A cross-sectional, between-group design. METHOD AND PROCEDURE: TBI survivors were selected from the Reading Head Injury out-patient records by date of registration, early survivors from 2002-2004 and late survivors from 1993-1996 and sent a battery of postal questionnaires. These included The Post-traumatic Growth Inventory, The Life Satisfaction Checklist and The Hospital Anxiety and Depression Scale. Individuals were also given the opportunity to answer questions about their perception of their condition and to provide free text responses to reflect best and worst advice received, to describe positive and negative changes in themselves and to identify their most useful coping strategies. RESULTS: 61 'early' and 65 'late' people were contacted with study details and 52 consented to the study, receiving questionnaires which provided 23 'early' and 25 'late' responses. There was a significantly greater degree of post-traumatic growth, as measured on 'The Post-traumatic Growth Inventory', reported by the later group (*p = 0.000), but no other significant differences between the groups in terms of all the other variables. Both groups reported greater life satisfaction pre-injury. CONCLUSION: Measures of Post traumatic Growth (Relating to Others, Personal Strength, New Possibilities, Appreciation of Life and Spirituality) appear to increase over time after head injury. This is a positive message that clinicians should note and reinforce and could help to shape future adjustment. PMID- 17364518 TI - Predictors of subjective impairment after stroke: influence of depression, gender and severity of stroke. AB - PRIMARY OBJECTIVE: The aim of this prospective study was to identify factors that are associated with stroke survivors' own perception of their impairments in various domains. RESEARCH DESIGN: 104 patients were examined twice, both on admission to rehabilitation treatment and one year later. METHODS AND PROCEDURES: Multiple linear regression analyses were used: Gender, age, diagnosis, location, Barthel Index and depression served as predictor variables. The perceived impairments were established with the Patient Competency Rating. MAIN OUTCOMES AND RESULTS: Patients' initial depression was identified as being the main predictor for perceived impairment. Gender differences were also found; men were seen to have suffered from a considerable increase in perceived impairment. CONCLUSIONS: Patients' self-reports can be used as a valid measurement of their disabilities in various domains. The impact of depression and the gender differences indicate that rehabilitation should focus more strongly on interventions that promote emotional coping and reduce depressive symptoms. PMID- 17364519 TI - Attitudes of children towards peers with acquired brain injury (ABI). AB - RESEARCH OBJECTIVE: Children with acquired brain injury (ABI) can experience severe problems in establishing peer relationships. The attitudes peers hold toward a child with an ABI can significantly impact on their willingness to befriend. The present work sought to investigate the attitudes peers hold toward a fictional child with ABI. METHODS AND PROCEDURES: Fifty children from a primary school were compared against a similar number from a secondary school. Gender was evenly split across both groups. A vignette describing a young boy acquiring a brain injury, and his subsequent change in behaviour, was presented to the children. The Friendship Activity Scale (FAS) was then used to judge how likely the children were to befriend the fictional character. OUTCOMES AND RESULTS: Results showed a statistically significant interaction between gender and age [F(1, 96) 6.285, p = 0.014] with older males expressing more positive attitudes than younger males. CONCLUSION: The study suggests that children with ABI are more likely to experience negative attitudes in primary school, and concludes in calling for additional research to more fully explore the social experience of children with ABI. PMID- 17364520 TI - Children and young adults in a prolonged unconscious state after severe brain injury: long-term functional outcome as measured by the DRS and the GOSE after early intensive neurorehabilitation. AB - OBJECTIVE: To investigate the long-term (2-15 years) functional outcome of children and young adults who received an early intensive neurorehabilitation programme (EINP) after a prolonged period of unconsciousness due to severe brain injury; to differentiate between traumatic brain injury (TBI) and non-traumatic brain injury (nTBI); and to compare the results on two different outcome scales: the Disability Rating Scale (DRS) and the Glasgow Outcome Scale Extended (GOSE). SUBJECTS: One hundred and forty-five patients, who were admitted to EINP between December 1987 and January 2001. OUTCOME MEASURES: The Post-Acute Level of Consciousness scale (PALOC-s), the DRS, including categorized scores (DRScat), and the GOSE. RESULTS: The long-term functional level of 90 patients could be determined, of whom 25 were deceased. The mean DRS-score of the surviving patients was 6.8 (SD = 6.6); the mean score on the GOSE was 4.5 (SD = 1.7). There was a significant difference in the outcome amongst traumatic and non-traumatic patients (t88 = 4.21; p < 0.01). The correlation between the DRS and the GOSE was high (Spearman rho = 0.85; p < 0.01), as well as the correlation between the categorized scores of the DRS and the GOSE (Spearman rho = 0.81; p < 0.01). The distribution of outcome scores on the DRScat is more diverse than on the GOSE. Especially item 7 of the DRS, measuring functional independence, showed considerable variance in discriminating between different outcome levels. CONCLUSIONS: More patients with TBI than expected reached a (semi-) independent level of functioning, indicating a possible effect of EINP. Patients suffering from nTBI did not demonstrate these outcome levels. Only a few patients stayed in a vegetative state for more than a couple of years. In this cohort of severe brain-injured young people, the DRS offered the best investigative possibilities for long-term level of functioning. PMID- 17364521 TI - MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents. AB - OBJECTIVES: To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post traumatic brain injury (TBI). METHODS: This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. RESULTS: 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. CONCLUSIONS: Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI. PMID- 17364522 TI - Validation of the behavioral dyscontrol scale-electronic version: sensitivity to subtle sequelae of mild traumatic brain injury. AB - PRIMARY OBJECTIVE: To determine whether a new computer-administered battery (Behavioral Dyscontrol Scale-Electronic Version; BDS-EV) can detect subtle executive weaknesses among individuals with a self-reported history of mild head trauma (MHT), and to compare the utility of this battery to the original, non electronic BDS and other traditional executive measures. Both BDS-EV and BDS are comprised of three factors (motor programming, environmental independence, and fluid intelligence). METHOD: Participants with (n = 19) and without (n = 24) MHT were compared on their performance on the BDS-EV, the non-electronic BDS, and three traditional measures of executive abilities. RESULTS: Participants with MHT differed from those without MHT on the BDS-EV motor programming and environmental independence, but not on any other measures. CONCLUSION: The results show that electronic administration improved the sensitivity of the battery, and support prior findings that traditional executive measures are generally insensitive to subtle executive deficits associated with chronic MHT. PMID- 17364523 TI - Recovery from hemiparesis and unilateral spatial neglect after neonatal stroke. Case report and rehabilitation of an infant. AB - PRIMARY OBJECTIVE: To report rehabilitation of neglect in a child through task contexts. METHODS AND PROCEDURES: A 7-month-old boy with hemiparesis and neglect following neonatal stroke was evaluated with standard assessments during the first year of intervention. The intervention included timely training of each upper limb's movement (reaching, grasping, lifting, rotating, releasing, etc.), balance training and Constraint-Induced Movement Therapy (CIMT). We promoted the storing of spatial representation through enriched environment by meaningful sensory inputs engaging spatial localization/orientation and eye movements. MAIN OUTCOMES: During intervention the child developed reaching and grasping and other new motor behaviours (holding, releasing, lifting, rotating, transferring, pulling, manipulating objects, gesturing, self-feeding, walking). In parallel he also exhibited a decrease of neglect. CONCLUSION: Infants with stroke should be routinely checked for neglect. Especially those with hemiparesis and neglect challenge the rehabilitation team for the complexity of the treatment directly focused on addressing integration at more conscious levels of upper limb paresis and neglect. PMID- 17364524 TI - Gait rehabilitation with body weight-supported treadmill training for a blast injury survivor with traumatic brain injury. AB - BACKGROUND AND PURPOSE: Research supports the use of body weight-supported treadmill training (BWSTT) in patients with hemi-paresis and may show promise as a gait training and neuromuscular re-education intervention in the blast-injured, traumatic brain injury (TBI) population. The purpose of this case study is to document the use BWSTT and goal-directed therapy in the improvement of gait quality, gait speed and maximum distance ambulated in a blast injury survivor with TBI. CASE DESCRIPTION: A 36-year-old male soldier injured by a rocket propelled grenade in Iraq who began physical therapy and gait training incorporating purposeful postural stability and mobility interventions as well as BWSTT. OUTCOMES: Missouri Assisted Gait scores, six-minute walk distances, and maximum distance ambulated all increased post gait training with BWSTT as a component to PT intervention. DISCUSSION: Intensive gait training including BWSTT may have some efficacy in managing significant blast trauma patients with TBI however, further research is necessary to establish efficacy and appropriateness in this patient population. PMID- 17364525 TI - An unexpected recovery from permanent vegetative state. AB - PRIMARY OBJECTIVE: To challenge the Multi-Society Task Force's ruling that a persistent vegetative state (PVS) can be judged to be permanent for non traumatic brain injury after three months. METHOD: We report the case of a 44-year-old man who had recovery of consciousness with persistent severe disability 19 months after a non-traumatic brain injury at least in part triggered and maintained by intrathecal baclofen administration. RESULT: This unexpected and late recovery of consciousness raises an interesting hypothesis of possible effects of partially regained spinal cord outputs on reactivation of cognition. CONCLUSION: Considering that several ethical, legal, and socio-economic issues have been raised about the opportunity of withdrawing treatment and life support in patients with PVS the report of this case might add further documentation to the ongoing debate. PMID- 17364527 TI - A systematic review of the rehabilitation of moderate to severe acquired brain injuries. AB - OBJECTIVE: To conduct a systematic review of the rehabilitation literature of moderate to severe acquired brain injuries (ABI) from traumatic and non-traumatic causes. METHODS: A review of the literature was conducted for studies looking at interventions in ABI rehabilitation. The methodological quality of each study was determined using the Downs and Black scale for randomized controlled trials (RCTs) and non-RCTs as well as the Physiotherapy Evidence Database (PEDro) scale for RCTs only. RESULTS: Almost 14 000 references were screened from which 1312 abstracts were selected. A total of 303 articles were chosen for careful review of which 275 were found to be interventional studies but only 76 of these interventional studies were RCTs. From this, 5 levels of evidence were determined with 177 conclusions drawn; however of the 177 conclusions only 7 were supported by two or more RCTs and 41 were supported by one RCT. CONCLUSION: Only 28% of the interventional studies were RCTs. Over half of the 275 interventional studies were single group interventions, pointing to the need for studies of improved methodological quality into ABI rehabilitation. PMID- 17364528 TI - The efficacy of acquired brain injury rehabilitation. AB - OBJECTIVE: The purpose of this review was to investigate the efficacy of rehabilitation interventions in acquired brain injury (ABI) rehabilitation to provide guidance for clinical practice based on the best available evidence. METHODS AND MAIN OUTCOMES: A systematic review of the literature from 1980-2005 was conducted focusing on rehabilitation interventions for ABI. The efficacy of a given intervention was classified as strong (supported by at least two randomized controlled trials (RCTs)), moderate (supported by a single RCT), or limited (supported by other types of studies in the absence of RCTs). RESULTS: The majority of interventions were only supported by limited evidence. However, there is moderate evidence that inpatient rehabilitation results in successful return to work and return to duty for the majority of military service members, increasing the intensity of rehabilitation reduces length of stay and improves short-term functional outcomes, and that direct patient involvement in neurorehabilitation goal setting results in significant improvements in reaching and maintaining those goals. CONCLUSIONS: There is a need for studies of improved methodological quality into ABI rehabilitation. PMID- 17364529 TI - Motor impairment rehabilitation post acquired brain injury. AB - OBJECTIVE: We sought to investigate the efficacy of treatment strategies used to manage motor impairments following acquired brain injury (ABI) in order to provide guidance for clinical practice based on the best available evidence. METHODS AND MAIN OUTCOMES: A systematic review of the literature from 1980-2005 was conducted focusing on pharmacological, non-pharmacological, and exercise interventions available for motor impairments post ABI. The efficacy of a given intervention was classified as strong (supported by two or more randomized controlled trials (RCTs)), moderate (supported by a single RCT), or limited (supported by other types of studies in the absence of RCTs). RESULTS: Thirty-six studies examining a variety of treatment approaches for motor impairments and activity limitations following ABI were evaluated. The majority of interventions are only supported by limited evidence. However, there is strong evidence that serial casting does reduce ankle plantar contractures due to spasticity of cerebral origin, and strong evidence also suggests that partial body weight supported gait training does not provide any added benefit over conventional gait training. There is also moderate evidence to support the use of functional fine motor control retraining to improve motor coordination, tizanidine for upper and lower extremity spasticity, and specific sit-to-stand training to improve functional ability. There is also moderate evidence that casting alone is as effective as casting and Botulinum toxin injections for plantar contractures. CONCLUSIONS: Although there are a variety of treatment strategies to manage motor impairments and activity limitations following ABI, most are only supported by limited evidence pointing to the need for studies of improved methodological quality in this area. PMID- 17364530 TI - Cognitive interventions post acquired brain injury. AB - OBJECTIVE: Cognitive rehabilitation represents a substantial portion of rehabilitative efforts put forth in increasing independence following an acquired brain injury. MAIN OUTCOMES AND RESULTS: This review examined four major areas of cognitive therapy including: attention/concentration, learning and memory, executive functioning, and general cognitive rehabilitation approaches. In total, 64 studies were evaluated throughout the four major areas, which provided the evidence-base for 18 conclusions. The majority of the conclusions were based on moderate and limited evidence, however three strong and one conflicting conclusions were made. CONCLUSIONS: Future research should explore functional outcome measures and long-term effects of treatment interventions through follow up. PMID- 17364531 TI - Post-traumatic seizure disorder following acquired brain injury. AB - OBJECTIVE: The present study aimed to evaluate the effectiveness of prophylactic anticonvulsant pharmacological strategies for the prevention of seizure disorders following acquired brain injury (ABI) to provide guidance for clinical practice based on the best available evidence. METHODS AND MAIN OUTCOMES: A systematic review of the literature from 1980-2005 was conducted focusing on treatment interventions available for post-traumatic seizures following ABI. The evidence for the efficacy of a given intervention was ranked as strong (supported by at least two randomized controlled trials (RCTs), moderate (supported by a single RCT), or limited (supported by other types of studies in the absence of RCTs). RESULTS: Based on a previous meta-analysis and the findings of this review, there is strong evidence that prophylactic anticonvulsant therapy decreases the occurrence of early seizures but only within the first week post-injury. Moreover, the evidence indicates that prophylactic anticonvulsant therapy does not decrease the incidence of seizure onset more than one week post-injury. In children, there is moderate evidence that prophylactic phenytoin does not reduce the incidence of early or late seizures. The efficacy of anticonvulsants after the development of seizures has not been specifically studied in ABI. CONCLUSIONS: Prophylactic anti-convulsants are effective in reducing seizures in the first week post-injury in adults. However, they do not reduce the occurrence of seizures after the first week. PMID- 17364532 TI - Management of heterotopic ossification and venous thromboembolism following acquired brain injury. AB - OBJECTIVE: To evaluate the effectiveness of interventional strategies for the common complications of heterotopic ossification (HO) and venous thromboembolism (VTE) following acquired brain injury (ABI). METHODS AND MAIN OUTCOMES: A systematic review of the literature from 1980-2005 was conducted focusing on interventions for HO and VTE in the ABI population. Nineteen studies examining a variety of treatment approaches were evaluated. RESULTS: The majority of interventions are supported by limited evidence, defined as an absence of randomized controlled trials (RCTs). All of the treatment approaches for HO are supported with limited evidence. For VTE, there is moderate evidence, defined as at least one positive RCT, indicating that low-molecular-weight heparin is more effective than low-dose unfractionated heparin in preventing VTE, low-molecular weight heparin is as effective and safe as unfractionated heparin for the prevention of pulmonary thromboembolism, low-molecular-weight heparin combined with compression stockings is more effective than compression stockings alone for the prevention of VTE and intermittent pneumatic compression devices are as effective as low-molecular-weight heparin for the prevention of VTE. CONCLUSIONS: There are a variety of intervention and prophylactic strategies that have been postulated to treat and reduce the incidence of these complications, with the goal of improving rehabilitation outcomes. It is therefore important to investigate the efficacy of these treatment strategies to provide guidance for clinical practice based on the best available evidence. PMID- 17364533 TI - Community reintegration following acquired brain injury. AB - OBJECTIVE: To evaluate the interventions and strategies used to enable transition from acute care or post-acute rehabilitation to the community following brain injury. METHODS AND MAIN OUTCOMES: A systematic review of the literature from 1980-2005 was conducted focusing on ABI rehabilitation. Five major aspects of community reintegration, including: independence and social integration, caregiver burden, satisfaction with quality of life, productivity and return to driving were considered. RESULTS: With the exception of one, the majority of interventions are supported by only limited evidence, denoting an absence of randomized controlled trials (RCTs) in the literature. Of 38 studies evaluated for this review, only one RCT was found. That RCT provided moderate evidence that behavioural management, coupled with caregiver education, did not help to improve caregiver burden. CONCLUSIONS: Further research, using an interventional approach, is required to advance the evidence base of reintegration into the community following brain injury. PMID- 17364534 TI - Evaluation of the effects of cage height and stocking density on the behaviour of laying hens in furnished cages. AB - 1. Limited information is available on how changes in horizontal and vertical space within enriched or furnished layer cages (as defined by Directive 1999/74/EC) influence hen behaviour. This study evaluated the effects of varying minimum cage heights and space allowances on the behaviour of laying hens housed in furnished cages. It was conducted on two flocks of medium brown hybrid hens housed in furnished cages with access to perches and nest boxes on a semi commercial scale at ADAS Gleadthorpe. 2. Flock 1 consisted of two layer strains (ISA Brown and Babcock 380), housed at two minimum cage heights (38 and 45 cm) and 5 stocking densities between 609 and 870 cm2/bird, with 12 replicates of each of the 20 strain/cage height/stocking density treatment combinations. Stocking density was varied by varying the number of birds per cage from 10 to 7 in standard full-width cages or housing 7 hens in a narrower cage. As a consequence stocking density, group size and trough width per bird co-varied for 4 out of 5 stocking density treatments. 3. Behaviour of flock 1 was sampled at 33 to 36, 46 and 68 weeks of age. At each age one top-tier, one middle-tier and one bottom tier cage was sampled for each treatment. 4. Few behavioural differences due to cage treatments were detected. Hens at 870 cm2 had shorter feeding bouts than hens at 609 and 762 cm2. Yawning was more common in the cages with greater cage height. 5. Video recordings of flock 1 examined cage height effects on hens' use of vertical space and provided additional data on stretching and self-maintenance activities. No differences in behaviour between 38 and 45 cm cages were found except that scratching head was more common in cages with greater cage height. 6. Flock 2 consisted of two layer strains (Shaver Brown and Hy-Line Brown), housed at 38 and 45 cm and 609, 762 and 1016 cm2/bird, with 18 replicates of each of the 12 strain/cage height/stocking density treatment combinations. Stocking density was varied by housing 10, 8 or 6 hens in standard full-width cages. Behaviour of flock 2 was sampled at 30, 48, 60 and 67 weeks from video recordings. Three cages per treatment from middle-tiers only were sampled at each age. 7. Hens housed at 609 cm2/hen had the longest mean feeding bout, greater than for hens at 762 cm2/hen but not hens at 1016 cm2/hen. More unsuccessful attempts to reach the feeder and sideways and backwards displacements from the feeder occurred at 762 and 609 cm2/hen than at 1016 cm2/hen. A maximum of 8 hens were observed feeding synchronously. 8. These results suggest that changes in horizontal and vertical space over the ranges we studied had little effect on behaviour other than feeding behaviour. Specifying a minimum useable trough space per hen, rather than calculating feeder space from total length of feeder per cage, irrespective of accessibility, might help avoid crowding at the feeder and associated disturbance of feeding bouts. PMID- 17364535 TI - Hagberg falling number and the nutritional value of wheat in broiler chicken diets. AB - 1. Three experiments were performed to study the effect of Hagberg falling number in wheat on performance, nutrient digestibility and AMEN in broilers. In two experiments, one hard and one soft wheat variety were used to study the interaction between falling number and hardness of wheat with regard to nutritional value. In these experiments, wheat batches with high falling number when harvested under dry conditions were used in broiler diets. 2. Wheat with reduced falling numbers (high, medium and low) was obtained by controlled germination. In the third experiment, wheat with reduced falling numbers were obtained by delayed harvesting times. 3. In each experiment, a total of 4 cereal batches with different falling numbers from each wheat variety were used to produce corresponding experimental diets with wheat as the major ingredient. Each diet was fed to broiler chickens ad libitum from d 1 to d 17 of age. 4. There was no consistent effect of falling number on performance. Low falling number did not improve feed utilisation or AMEN compared to the original wheat, despite a higher AMEN associated with higher starch digestibility. This phenomenon was not observed after reduction of falling number by delayed harvesting. Apparently, natural reduction of falling number resulted in enhanced degradation of arabinoxylans compared to controlled germination. PMID- 17364536 TI - Holo-analysis of the efficacy of Bio-Mos in broiler nutrition. AB - 1. This first holo-analysis of the efficacy in broiler nutrition of the saccharide product, Bio-Mos(R) (BM), is part of a comprehensive empirical modelling research programme quantifying and comparing the efficacies and future research needs of the diverse candidates offered as replacements for antibiotics. 2. The data used are from 32 publications with broiler performance data from a world-wide literature collection of 124 (1997-2003) on the use of BM as a broiler feed additive. It contains the results of 82 negatively controlled feeding tests from 21 countries using a total of 85 142 broilers, averaging 401 per treatment. 3. The 82 feed intake, liveweight gain, feed conversion ratio and 44 mortality responses to BM average -12.2 g, 27.6 g, -0.0391 and 0.0311%, respectively, with coefficients of variation of 828, 227, 192 and 8392%. Respective beneficial response frequencies for gain, conversion and mortality are 65, 70 (52% jointly) and 52%. 4. Holo-analytical multiple regression models were elaborated for the effects of BM on feed intake, liveweight gain, feed conversion ratio and mortality, using conventional Por=0.10 out and less stringent Por=0.34 out partial regression coefficient standards, with and without>or=3xroot mean square error outliers, in order to quantify the influences of negative control performance, test duration, BM dosage, cage housing, processed feed, antibiotic feed, year of test and USA test. To date they account for only 5-36% of response variations, due primarily to 52 of the 82 tests having no reported feed formulations. 5. These exploratory models confirm beneficial responses to BM for current broiler performance levels. They also indicate a need to clarify BM dose-response relationships in order to maximise efficient use in praxis and to facilitate cogent comparisons with other pronutrients, including other saccharide products. PMID- 17364537 TI - Holo-analysis of the efficacy of Bio-Mos in turkey nutrition. AB - 1. This holo-analysis of the effects in turkey nutrition of Bio-Mos(R) (BM) (Alltech Inc., Nicholasville, KY) aims to elaborate comprehensive empirical models for the assessment of responses under practical conditions and for its comparison with other potential pronutrient antibiotic replacements. 2. The data bank utilised was obtained from 54 publications on BM in turkeys from a total collection of 57 papers (1995-2003) on the use of saccharide products as turkey feed additives. These yielded 33 start-to-finish negatively-controlled feed intake, liveweight gain and feed conversion and 24 mortality effects in the USA, France and Poland, using 12,723 birds with a mean of 212 birds per treatment. 3. The feed, gain, conversion and mortality responses to BM compared with the relevant negative controls average -243 g, 57.0 g, -0.0156 and 1.29% with coefficients of variation of 451, 451, 705 and 426%, respectively. Beneficial gain, conversion and mortality effects were found in 52, 52 (33% jointly) and 52% of the tests, respectively. 4. Holo-analytical multiple regression models comparing conventional Por=0.10 out and less stringent Por=0.34 out partial regression coefficient standards, with and without>or=1.5xroot mean square error outliers, contain significant independent variables for negative control performance, duration, year of test, not-USA test, discontinuous dosage, cage housing, mash feed, feed antibiotic, feed anticoccidial, disease condition and high control (>10%) mortality. 5. These developmental models indicate fruitful pathways for future developments with an accent on the definition of specific dose-response relationships, whilst also confirming the value and future potential for BM in turkey production in praxis. PMID- 17364538 TI - Chitin utilisation by broilers and its effect on body composition and blood metabolites. AB - 1. Little is known about the ability of farmed poultry to digest chitin and derive nutrients from the ingestion of insects. 2. Commercial chitin derived from crustacean shell waste was found to contain 373 g crude protein, 265 g ash, 23.5 g ether extract, 130 g calcium and 16.4 g phosphorus per kg, on an air-dry basis. 3. It was included in diets at 0, 25, 50 and 75 g chitin per kg and fed to 320 1 d-old broiler males, over a 21-d period. There were no statistically significant treatment effects on weight gain or feed efficiency. Apparent digestibility of chitin protein was 0.48, 0.50 and 0.45, at the 25, 50 and 75 g per kg inclusions, respectively. Mean AME and AMEN values of chitin were determined as 8.97 and 8.86 MJ/kg. 4. In a subsequent study, mean TME and TMEN values of chitin were determined to be 8.23 and 8.21 MJ per kg, respectively. Addition of chitinase to the diet increased TME and TMEN of chitin to 8.81 and 8.79 MJ per kg, respectively (P<0.05). True digestibility of chitin protein was determined to be 0.87. 5. Triglyceride concentrations in liver and breast meat were significantly reduced by chitin inclusion. No significant differences in carcase yield at 21 d of age were found. Serum cholesterol and triglycerol concentrations were reduced significantly by dietary chitin, the lowest levels being observed at the 50 g per kg inclusion level. 6. These findings indicate the ability of modern poultry to digest chitin but suggest that the ingestion of insects is not an important source of nutrients, at least from the exoskeleton. PMID- 17364539 TI - On the interactions between Fusarium toxin-contaminated wheat and non-starch polysaccharide hydrolysing enzymes in turkey diets on performance, health and carry-over of deoxynivalenol and zearalenone. AB - 1. Diets with increasing proportions of Fusarium toxin-contaminated wheat (0, 170, 340 and 510 g CW/kg) were fed to male turkeys (BUT Big 6) from d 21 to d 56 of age. Each diet was tested with or without a non-starch-polysaccharide (NSP) hydrolysing enzyme preparation. Dietary deoxynivalenol (DON) and zearalenone (ZON) concentrations were successively increased up to approximately 5.4 and 0.04 mg/kg, respectively. 2. Weight gain decreased slightly with increasing proportions of CW, by 1.6, 0.7 and 3.6%, whereas other performance parameters remained unaffected. NSP enzyme supplements to the diets had no influence. 3. The weight of the emptied jejunum plus ileum, relative to live weight, decreased in a dose-related fashion whereby the NSP enzyme exerted an additional weight decreasing effect. A similar weight-decreasing NSP enzyme effect was noted for heart weights. Activity of glutamate dehydrogenase in serum was significantly increased in groups fed the diets with the highest CW proportion, whereas gamma glutamyl-transferase remained unaltered. 4. Viscosity in the small intestine was significantly reduced by supplementing the diets with the NSP enzyme. This effect successively decreased with increasing proportions of the CW. 5. Concentrations of DON and of its de-epoxidised metabolite de-epoxy-DON in plasma, liver and breast meat were lower than the detection limits of 2 ng/ml (plasma) and 4 ng/g, respectively, of the applied HPLC method. DON concentration in bile reached up to 13 to 23 ng/ml whereas de-epoxy-DON concentration was lower than 4 ng/ml. 6. ZON or its metabolites were not detectable in plasma, liver or breast meat (detection limits of the HPLC method were 1, 0.5 and 5 ng/g for ZON, alpha-zearalenol (ZOL) and beta-ZOL, respectively). Concentrations of ZON and alpha-ZOL in bile increased with dietary ZON concentration. The mean proportions of ZON, alpha-ZOL and beta-ZOL of the sum of all three metabolites were 19, 77 and 4%, respectively. PMID- 17364540 TI - A comparison of the effects of different yeast products and antibiotic on broiler performance. AB - 1. The objectives of this experiment were to compare the effects of different yeast products, with different nucleotide contents and inclusion rates, on broiler performance and to compare the effects to those observed with an antibiotic growth promoter. 2. Two experiments were carried out over two time replicates, one in individual wire cages and one in group pens. 3. Birds were given a diet based on a commercial formulation, which was split into 7 batches. One batch (C) contained no growth promoter and acted as a negative control, another (AV) contained the antibiotic growth promoter Avilomycin (5 g/tonne) and acted as the positive control. The other batches contained yeast extract 2012 at 100 g/tonne (Y21), yeast extract 2012 at 500 g/tonne (Y25), standard yeast 18 at 100 g/tonne (Y81), standard yeast 18 enriched in nucleotides at 100 g/tonne (Y8N1) and standard yeast 18 enriched in nucleotides at 500 g/tonne (Y8N5). 4. In the penned experiment, 280 Cobb broiler chicks (40 birds/treatment) were randomised to diet and pen position on day of hatch. Birds were fed ad libitum until slaughter at 28 d. Bird performance was monitored during the experimental period. 5. In the individual cage experiment, 63 Cobb broiler chicks (9 birds/treatment) were taken from the pens at 7 d of age and randomised to diet and cage position. Birds were fed ad libitum from d 7 to d 28. A 7-d excreta collection was carried out to determine apparent metabolisable energy (AME) content and nutrient digestibility between d 14 and d 21. Bird intake and weight were monitored weekly during the experimental period. At 28 d the birds were killed and viscosity of jejunal digesta supernatant was determined. 6. In the penned experiment, diet had no significant effect on dry matter intake (DMI), live weight gain (LWG) or gain:feed values during any individual week of the experiment or for the entire experimental period. In the caged experiment, DMI was numerically highest for birds fed Y25 diet over the entire experimental period, however, this only reached significance in the second week. LWG, gain:feed, viscosity of jejunal contents and gizzard weight were not significantly affected by dietary treatment. 7. Diet AV had a significantly higher AME content than diets Y25, Y81, Y8N1 or Y8N5. Also, oil and neutral detergent fibre (NDF) digestibility coefficients were significantly affected by diet treatment. PMID- 17364541 TI - Energy metabolisability and digestibility of amino acids by broilers fed on malted sorghum sprouts supplemented with polyethylene glycol, charcoal, phytase and xylanase. AB - 1. A precision feeding study was conducted to determine the metabolisable energy and amino acid digestibility in broilers fed on malted sorghum sprouts (MSP) supplemented with polyethylene glycol (PEG), charcoal (CH), phytase and xylanase. 2. A total of 64 male Ross broilers housed individually (8 replicates per treatment) were fed 30 g of the feedstuff as follows by gavage: MSP, MSP+1 g PEG/kg, MSP+10 g PEG/kg, MSP+1 g CH/kg, MSP+10 g CH/kg, MSP+3600 IU of evolved E. coli phytase/kg (EC 3.1.3.26) and MSP+1600 IU of bacterial xylanase/kg (EC 3.2.1.8). Another group of birds was used for the assessment of endogenous loss and they were provided with 50 ml glucose solution each by gavage. 3. True dry matter digestibility (TDMD), true nitrogen retention (TNR), total tract digestibility of apparent and true metabolisable energy (AME and TME) and amino acid (AAD and TAAD) were determined. 4. MSP contained 244.4, 24.0, 74.9 and 224.0 g/kg of crude protein, ether extract, ash and neutral detergent fibre, respectively. The total tannin content of the product was 140 g/kg and 99% of this was bound. 5. The various dietary treatments did not significantly affect the TDMD, TNR, AME and TME of MSP. The low values (0.471 g/g, -0.164 g/g, 6.15 MJ/kg and 9.31 MJ/kg, respectively) for the above measurements depicted the low feeding value of un-supplemented MSP for poultry. Also, PEG, CH and enzymes did not improve the AAD and TAAD of MSP for poultry. 6. It was concluded that the tannin content of MSP is high and it appeared to be bound with other nutrients thereby reducing their availability. This may explain its low AME and amino acid digestibility and the lack of effect of the various treatments for poultry. PMID- 17364542 TI - In vitro and in vivo characteristics of bacterial phytases and their efficacy in broiler chickens. AB - 1. Three bacterial phytases derived from Bacillus, Escherichia coli or Klebsiella were compared with a phytase derived from Aspergillus niger in vitro and in vivo. 2. The in vitro results indicated that Aspergillus, E. coli and Klebsiella phytase displayed their activity optima in an acid pH range while Bacillus phytase did so in neutral pH. 3. The trials also revealed that only Bacillus phytase is more resistant to heat treatments, while E. coli and Klebsiella phytases are more stable against proteolytic inactivation. 4. In vivo phytases derived from Aspergillus, Bacillus, E. coli, Klebsiella or a combination of Bacillus and E. coli improved the utilisation of phosphorus (P balance) significantly to 0.54, 0.54, 0.55, 0.55 or 0.58, respectively, compared to 0.42 in the negative control. 5. The phytases used in this study seemed to be equally effective in improving P utilisation regardless of proposed intestinal site of activity. Combination of phytases acting in the gizzard with phytases acting in the intestine seems to be a promising way to further improving in vivo efficacy of phytases in poultry. PMID- 17364543 TI - The effect of dietary calcium source, concentration and particle size on calcium retention, eggshell quality and overall calcium requirement in laying hens. AB - 1. Four different sources of calcium in isonitrogenous and isoenergeric diets were fed to laying hens for 2 weeks when they were 56 and 57 weeks old. The calcium source blends were as follows: 29% fine limestone (LF)+71% large limestone (LG), 32% LF+68% eggshell, 32% LF+68% oyster shell, 50% LF+50% LG. The contents of these blends of calcium in the diets were as follows: 103.3, 93.3, 93.3 and 93.3 g/kg, respectively. 2. The coefficients of calcium retention were significantly higher in 50:50 LF:LG (0.578) and 32:68 LF:eggshell (0.576). The midnight feeding significantly improved the coefficient of calcium retention in all mixtures except 50:50 LF:LG. 3. In the mixtures 29:71 LF:LG and 32:68 LF:oyster shell, there were significantly greater eggshell quality, eggshell weight, eggshell thickness and eggshell strength. Midnight feeding had no significant effect on eggshell quality. 4. In the ration with oyster shells, 96.5% of the retained calcium was deposited in the eggshell, but in rations 32:68 LF:eggshell and 50:50 LF:LG the utilisation was only 73.9 and 78.6%, respectively. 5. To ensure good quality eggshells in the last third of production, the recommendation for calcium is 4.1 g/kg (900 g/kg dry matter, feed intake 110 g/d). As a source of calcium in this stage of production, a feed mixture containing two-thirds large particles should be used (limestone grit or oyster shell). PMID- 17364544 TI - Pharmacological characterisation of the electrically evoked release of monoamines from chicken brain in vitro. AB - 1. A study was conducted to develop an in vitro model for examining the basal and electrical-stimulation-induced release of [3H]monoamines from chicken hyperstriatal neurones in order to demonstrate the presence of presynaptic autoreceptors for the three main monoamine transmitters: noradrenaline, dopamine and 5-HT. 2. Two sets of experiments were carried out: the first was to evaluate the effect of calcium and tetrodotoxin (TTX, sodium channel conductance inhibitor) in order to demonstrate that evoked release of monoamines was a consequence of exocytotic processes; the second to investigate the effect of selective agonists and antagonists on neurotransmitter release. 3. Ross and Cobb broiler chickens of either sex (approximately 7 to 8 weeks old) were used. Slices of hyperstriatal tissue were preincubated with [3H]noradrenaline, [3H]dopamine or [3H]5-hydroxytryptamine (5-HT), washed, perfused and electrically stimulated at three time points (S1, S2 and S3) which released [3H]noradrenaline, [3H]dopamine and [3H]5-HT, as determined by scintillation spectrometry. 4. When calcium was removed from, or TTX added to, the superfusion medium prior to and including the second period of electrical stimulation (S2) the evoked releases of [3H]noradrenaline, [3H]dopamine and [3H]5-HT at S2 were abolished. 5. In the presence of the selective alpha2-adrenoceptor agonist UK 14304 during the S2 period, the S2/S1 ratio was lower than the control ratio due to a reduction in the stimulated release of [3H]noradrenaline. The selective alpha2-adrenoceptor antagonist RX 821002 blocked the UK 14304-induced reduction of evoked release and the S2/S1 ratio was similar to the control ratio. 6. The D2-like receptor agonist quinpirole reduced the S2/S1 ratio for [3H]dopamine release, an effect blocked by the antagonist AJ 76. The 5-HT1B receptor agonist CP 94253 during S2 reduced the S2/S1 ratio due to a reduction in evoked [3H]5-HT. This effect was blocked by the 5-HT1B receptor antagonist GR 55562. 7. The results demonstrate, for the first time, the functional presence of presynaptic alpha2-adrenoceptors, presynaptic 5 HT1B autoreceptors and presynaptic D2-like autoreceptors in broiler chicken hyperstriatal neurones in vitro. PMID- 17364545 TI - Effect of magnesium on reactive oxygen species production in the thigh muscles of broiler chickens. AB - 1. The objective of the present study was to investigate the effect of magnesium (Mg) on reactive oxygen species (ROS) production in the thigh muscles of broiler chickens. A total of 96 1-d-old male Arbor Acre broiler chickens were randomly allocated into two groups, fed either on low-Mg or control diets containing about 1.2 g/kg or 2.4 g Mg/kg dry matter. 2. The low-Mg diet significantly increased malondialdehyde (MDA) concentration and decreased glutathione (GSH) in the thigh muscles of broiler chickens. ROS production in the thigh muscle homogenate was significantly higher in the low-Mg group than in the control group. Compared with the control, muscle Mg concentration of broiler chickens from the low-Mg group decreased by 9.5%. 3. Complex II and III activities of the mitochondrial electron transport chain in broilers on low-Mg diet increased by 23 and 35%, respectively. Significant negative correlations between ROS production and the activities of mitochondrial electron transport chain (ETC) complexes were observed. 4. The low Mg diet did not influence contents of iron (Fe) or calcium (Ca) in the thigh muscles of broiler chickens and did not influence unsaturated fatty acid composition (except C18:2) in the thigh muscles. 5. A low-Mg diet decreased Mg concentration in the thigh muscles of broiler chickens and then induced higher activities of mitochondrial ETC, consequently increasing ROS production. These results suggest that Mg modulates the oxidation-anti-oxidation system of the thigh muscles at least partly through affecting ROS production. PMID- 17364546 TI - Effect of dietary supplementation of astaxanthin by Phaffia rhodozyma on lipid peroxidation, drug metabolism and some immunological variables in male broiler chicks fed on diets with or without oxidised fat. AB - 1. Effects of dietary supplementation of astaxanthin (Ax) provided from Phaffia rhodozyma on lipid peroxidation, hepatic drug metabolism, antibody titres to sheep red blood cells (SRBC) and splenocyte proliferation to mitogens were determined in male broiler chicks. 2. Chicks, one week old, were given diets with or without oxidised fat (0 or 3.7 meq of peroxide value (POV)/kg diet) and/or Ax (0 or 100 mg/kg diet) for 14 d, ad libitum. 3. Lipid peroxidation, estimated by 2 thiobarbituric acid reactants values in liver, spleen, heart, plasma and hepatic microsomes, were increased by feeding a diet containing oxidised fat (P<0.05) but were not affected by Ax feeding. 4. Cytochrome P-450 contents in hepatic microsome tended to be increased by feeding Ax. 5. Anti-SRBC titre was not affected by oxidised fat or Ax feeding, while plasma immunogloblin (Ig) G concentration was increased by Ax feeding but was not affected by oxidised fat feeding. 6. When chicks were fed on the diet without oxidised fat, Ax enhanced splenocyte proliferation stimulated by both concanavalin A and pokeweed mitogen, while in chicks fed on a diet containing oxidised fat, Ax reduced the proliferation (P<0.01 for Ax and oxidised fat interaction). 7. The results indicated that dietary supplementation of Ax from Phaffia rhodozyma had an impact on T cell proliferation and Ig G production as a part of acquired immunity, but was not effective in preventing lipid peroxidation in male broiler chicks. PMID- 17364547 TI - Correlations between breeder age, egg cholesterol content, blood cholesterol level and hatchability of broiler breeders. AB - 1. The research was carried out to investigate correlations between breeder age, egg cholesterol content, blood cholesterol level and hatchability of broiler breeders. 2. Egg cholesterol content increased with increased breeder age. The mean yolk cholesterol contents (mg per g yolk) were 10.47+/-0.28, 15.34+/-0.65 and 15.64+/-0.71 mg/g at 28, 45 and 65 weeks of age, respectively. 3. There were positive correlations between yolk weight and yolk cholesterol content (mg/g yolk) (r=01.941; P<0.01) and egg cholesterol content (mg/egg) (r=0.980; P<0.01). 4. Negative correlations were found between egg yolk cholesterol content and hatchability of fertile eggs (r=-0.345; P<0.05), fertility ratio (r=-0.609; P<0.01) and hatchability of total eggs (r=-0.574; P<0.01). 5. The mean blood cholesterol levels were 165.1+/-11.04, 166.5+/-11.97 and 179.5+/-11.33 mg/dl at 28, 45 and 65 weeks of age, respectively. PMID- 17364548 TI - Effects of supplemental vitamin E in diet of Japanese quail on male reproduction, fertility and hatchability. AB - 1. Two experiments were conducted to examine the effect of feeding higher supplemental vitamin E (VE) concentrations on male reproductive variables, fertility and hatchability of quails. 2. In experiment 1, sixty 5-week-old male quails, reared in individual cages, were fed male breeder diets supplemented with 0, 75, 150, 225 or 300 IU alpha-tocopherol acetate/kg. At 10 weeks, observations on cloacal gland size, foam production, testes weight and blood samples for testosterone estimation were taken. 3. In experiment 2, 50 male and 50 female cage-reared quails (5 weeks old) were fed male breeder and layer rations, respectively, supplemented with 0, 75, 150, 225 or 300 IU/kg. At 13 weeks, 9 different mating pairs (5 pairs/group) were formed. Group 1 contained one control male and one control female in each of 5 pens. In groups 2 to 5, control males were paired with females on supplements of 75, 150, 225 or 300 IU/kg. In groups 6 to 9, control females were paired with males on supplements of 75, 150, 225 and 300 IU/kg. During subsequent adaptation and egg collection periods, each of 10 d, control layer ration was fed to all groups. All the eggs laid during the 10-d egg collection period were incubated artificially to estimate fertility and hatchability. The trial was repeated at 15 weeks. 4. Adult male quails receiving moderate supplemental VE (75 and 150 IU/kg) had a higher cloacal gland index, quantity of foam secretion, testicular weight and plasma testosterone than quails fed on either VE-deficient or more highly supplemented diets (225 and 300 IU alpha-tocopherol acetate/kg). 5. It was concluded that a supplement of 75 IU VE/kg in maize/soybean diet could provide the best reproductive performance of male breeder quails. Cloacal gland index, quantity of foam secretion, testicular weight and plasma testosterone can serve as indirect indicators of testicular activity and fertilising ability in quails. Supplemental VE did not affect the fertility and hatchability of male and female Japanese quails. PMID- 17364550 TI - Computer visualization techniques (CVTs) foster evidence-based target delineation. AB - Computer visualization techniques (CVTs) are an emerging technology that can organize all cancer specialists. This article describes CVTs' ability to maximize the currently untapped advantages of intensity modulated radiotherapy (IMRT). The visual speed and dynamic strategies inherent in CVTs improves IMRT by distilling vast amounts of anatomic, multimodal imaging, textual/meaning, and surgical/outcome data into a large, rigorous, standardized evidence base of storable target delineation plans. This ability to standardize strategies will allow the collection of meaningful evidence based outcome data. PMID- 17364551 TI - The prevention and management of distant metastases in women with breast cancer. AB - About one-third of all women diagnosed with breast cancer face the risk of recurrence, which can occur at any stage of disease, observation time, and after any treatment modality. Most recurrence comes in the form of distant metastasis, which is the major cause of death in women with breast cancer. Treatments shown to decrease the risk of breast cancer recurrence, especially distant metastasis, will likely produce a survival benefit and a potentially significant improvement in quality of life in women with early breast cancer. New third-generation aromatase inhibitors (anastrozole, exemestane, and letrozole) that have been shown to be well tolerated have the potential to contribute to benefits beyond those seen with tamoxifen. PMID- 17364552 TI - The FACE trial: letrozole or anastrozole as initial adjuvant therapy? AB - The adjuvant Femara versus Anastrozole Clinical Evaluation (FACE) trial compares upfront therapy letrozole 2.5 mg with anastrozole 1 mg daily for up to 5 years in postmenopausal, hormone receptor-positive, node-positive breast cancer patients. This phase III b open label, randomized, multicenter study will include 4000. patients from up to 250 international sites. Patients will be stratified by degree of lymph node involvement and HER-2 status. Any efficacy and safety difference of the two drugs will be reported. Primary objective is DFS, secondary objectives are safety, OS, time to distant metastases, time to contralateral breast cancer and breast cancer specific survival. PMID- 17364553 TI - Quantitative analysis of breast cancer tissue microarrays shows high cox-2 expression is associated with poor outcome. AB - Epidemiologic and preclinical studies suggest that cyclooxygenase-2 (Cox-2) may promote tumor growth and spread by affecting angiogenesis and apoptosis in breast cancer. Using a tissue microarray (TMA), we analyzed the expression and subcellular localization of Cox-2 by AQUA and X-tile, our algorithms for quantitative analysis of protein expression and determination of optimal cutpoints. Our TMA consisted of 669 Stage I-III primary breast cancers. The total tumor and subcellular expression of Cox-2 were then correlated with clinicopathologic factors and with survival. Cox-2 expression appeared higher in malignant than in benign tissue and was predominantly membrane/cytoplasmic (i.e. non-nuclear). X-tile determines an optimum cutpoint on a training set then uses this cutpoint on a validation set. This cutpoint was 19.3 (top 44 percent defined as positive) with high nonnuclear Cox-2 expressers having significantly worse survival. Cox-2 expression also was inversely associated with estrogen receptor (ER) and progesterone receptor (PR), and directly associated with nuclear grade. Multivariate analysis showed that Cox-2 remained a significant prognostic factor for survival independent of tumor size, nodal status, ER, Her2/neu, and grade. In summary, Cox-2 is overexpressed in breast neoplasms, is associated with other markers of poor prognosis, and is significantly associated with worse survival independent of known prognostic factors. Furthermore, AQUA and X-tile analysis suggest an optimal cutpoint that may be helpful in future investigations of Cox-2 and specifically, in studies looking at its expression as a predictive biomarker in clinical trials of Cox-2 inhibitors in breast cancer. PMID- 17364554 TI - Results of a phase II study of weekly paclitaxel plus carboplatin in advanced carcinoma of unknown primary origin: a reasonable regimen for the community-based clinic? AB - Optimal treatment for cancer of unknown primary (CUP) can challenge clinicians. This study sought to determine the efficacy and toxicity of weekly paclitaxel and carboplatin in CUP. Forty-two subjects enrolled. Treatment was intravenous paclitaxel (80 mg/m2) plus carboplatin (AUC = 2) on Days 1, 8, and 15 every 28 days. Seven (18 percent) responded (complete = 2, partial = 5); median survival was 8.5 months; estimated survival (12 and 24-month) was 33 and 17 percent, respectively. Median time to progression was 3.7 months, and estimated progression-free survival (12 and 24 months) was 14 and 7 percent, respectively. Median duration of response was 17.3 months. This combination produced modest antitumor activity in advanced CUP. PMID- 17364555 TI - Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells. AB - Although androgen-hypersensitivity is one of the possible pathways of hormone resistance in prostate cancer, the mechanisms of androgen-hypersensitivity are still largely unknown. Using androgen-hypersensitive prostate cancer cells LN TR2, established from androgen-sensitive LNCaP cells by the long term treatment with tumor necrosis factor alpha, we explored the mechanisms of androgen hypersensitivity in prostate cancer cells which may thus play a role in hormone resistance. We examined the androgen receptor (AR) DNA sequence and the expression levels of AR and 8 AR cofactors in LNCaP and LN-TR2 cells. As a result, no novel mutation was developed in AR DNA in LN-TR2 cells. We observed higher expressions of nuclear AR upon androgen-treatment and 2 AR coactivators, ARA55 and TIF2, in LN-TR2 compared to LNCaP cells. An overexpression of ARA55 or TIF2 enhanced androgen-induced AR transcriptional activity in LNCaP cell. In the presence of those AR coactivators, AR activity was observed even at low concentrations of androgen. In 2 of 6 patients, the expression level of ARA55 was higher in cancer cells in hormone-resistant tumor than those in hormone-sensitive tumor. Taken together, our results suggest that prostate cancer cells change androgen-sensitivity by an overexpression of nuclear AR and AR coactivators, thus, resulting in transition from androgen-dependent to androgen-independent prostate cancer cells. An increase in nuclear AR and AR coactivators may cause androgen-hypersensitivity of prostate cancer cells and thus play a role in hormone-resistance, at least in some patients with prostate cancer. PMID- 17364556 TI - Conformal radiotherapy planning for lung cancer: analysis of set-up uncertainties. AB - The objective of this study was to evaluate set-up uncertainties using a portal imaging system in a population of inoperable non-small cell lung cancer. Twenty one patients were treated by a conformal radiotherapy technique with a personalized immobilization cast. The beam was verified by comparison with a corresponding digitally reconstructed radiograph by superimposition of anatomical structures. One thousand eight hundred eighty three images were analyzed. The mean intrafraction and interfraction errors (+/-SD) were 2.17 mm and 0.9 +/- 3.7 mm, 2.3 mm and 0.9 +/- 3.1 mm, 3 mm and 0.7 +/- 3 mm on the lateral (x), cranio caudal (y) and anterior-posterior (z) axes, respectively. The mean systematic error was small, less than 1 mm, in all directions. The random errors were 2.5 mm, 2.4 mm, and 1.8 mm on the x, y, and z axes, respectively. No correlation between errors and the patient's height, weight, age, or sex was found. Set-up errors accuracy depending on practices, each institution should review their own treatments to quantify and reduce set-up errors in clinical practice. PMID- 17364557 TI - Employment and cancer: findings from a longitudinal study of breast and prostate cancer survivors. AB - We discuss how cancer affected the employment of almost 800 employed patients who participated in a longitudinal study. The greatest reduction in patients' labor supply (defined as employment and weekly hours worked) was observed 6 months following diagnosis. At 12 and 18 months following diagnosis, many patients returned to work. Based on these and other findings related to patients' employment situations, we suggest 4 areas for future research: 1) collection of employment information in cancer studies; 2) research into racial and ethnic minority patients and employment outcomes; 3) interventions to reduce the effects of cancer and its treatment on employment; and 4) investigations into the influence of employment-contingent health insurance on cancer treatment and recovery. PMID- 17364558 TI - Hepatitis B virus and intrahepatic cholangiocarcinoma. AB - Intrahepatic cholangiocarcinoma (ICC) is a rare type of primary liver cancer that arises from intrahepatic bile ducts. Its etiopathogenesis has been considered to be independent of the presence of chronic viral hepatitis infections or cirrhosis. These factors, particularly the hepatitis C virus, have been reported to play a role in the development of cholangiocarcinoma in a few studies, with inconclusive results. We report 2 cases of ICC that presented with a background of hepatitis B virus (HBV) infection and discuss the possible pathophysiological relationships between ICC and HBV infection, with an emphasis on the x gene of HBV. PMID- 17364559 TI - Role of pemetrexed in non-small cell lung cancer. AB - Pemetrexed was approved for the treatment of relapsed or chemotherapy refractory non-small cell lung cancer patients, as it produced similar response and survival outcomes and less toxicity as compared to taxotere. Pemetrexed in combination with platinum analogs or with gemcitabine or vinorelbine, produce equivalent responses and overall survival results compared to combinations of platinum analogs with other drugs. The role of bevacizumab and the inhibitors of epithelial growth factor receptor also should be evaluated in selected patients with NSCLC treated with pemetrexed combinations. Further increases in drug dose may be possible using transfer of drug resistance genes in hematopoietic stem cells. PMID- 17364560 TI - Disialoganglioside directed immunotherapy of neuroblastoma. AB - Achieving a cure for metastatic neuroblastoma remains a challenge despite sensitivity to chemotherapy and radiotherapy. Most patients achieve remission, but a failure to eliminate minimal residual disease (MRD) often leads to relapse. Immunotherapy is potentially useful for chemotherapy-resistant disease and may be particularly effective for low levels of MRD that are below the threshold for detection by routine radiological and histological methods. Disialoganglioside (GD2), a surface glycolipid antigen that is ubiquitous and abundant on neuroblastoma cells is an ideal target for immunotherapy. Anti-GD2 monoclonal antibodies currently form the mainstay of neuroblastoma immunotherapy and their safety profile has been well-established. Although responses in patients with gross disease have been observed infrequently, histologic responses of bone marrow disease are consistently achieved in >75 percent of patients with primary refractory neuroblastoma. The advent of highly sensitive and specific molecular assays to measure MRD has confirmed the efficacy anti-GD2 antibody immunotherapy in patients with subclinical disease. Such markers will allow further optimization of other anti-MRD therapies. We review the current status of anti GD2 clinical trials for neuroblastoma and novel preclinical GD2-targeted strategies for this rare but often lethal childhood cancer. PMID- 17364561 TI - Age difference in numeral recognition and calculation: an event-related potential study. AB - In this study, we investigated the age difference in numeral recognition and calculation in one group of school-aged children (n = 38) and one of undergraduate students (n = 26) using the event-related potential (ERP) methods. Consistent with previous reports, the age difference was significant in behavioral results. Both numeral recognition and calculation elicited a negativity peaking at about 170-280 ms (N2) and a positivity peaking at 200-470 ms (pSW) in raw ERPs, and a difference potential (dN3) between 360 and 450 ms. The difference between the two age groups indicated that more attention resources were devoted to arithmetical tasks in school-aged children, and that school-aged children and undergraduate students appear to use different strategies to solve arithmetical problems. The analysis of frontal negativity suggested that numeral recognition and mental calculation impose greater load on working memory and executive function in schoolchildren than in undergraduate students. The topography data determined that the parietal regions were responsible for arithmetical function in humans, and there was an age-related difference in the area of cerebral activation. PMID- 17364562 TI - A longitudinal assessment of executive function skills and their association with math performance. AB - The present study was designed to examine both concurrent and predictive associations between scores on a measure of executive function (EF) skills, the Contingency Naming Test (CNT), during the early school-age years. A secondary aim of the study was to examine the association between EF skills and mathematics performance. We administered tests of mathematics ability, and the CNT, to 178 children at ages 6 to 7, 8 to 9, and 10 to 11 years. From the CNT we obtained measures of response fluency/efficiency, working memory, and inhibition. The results demonstrate main effects of age on all CNT measures of EF, as anticipated, and inconsistent main effects of gender or mathematics learning disability status. Rates of improvement in EF varied as a function of the working memory demands present during a given task. There were differences in concurrent and predictive correlations for different CNT performance measures. EF scores obtained during the first assessment were as strongly associated with each other as they were with EF scores obtained four years later, suggesting a moderately stable source of individual differences on cognitive performance. EF scores at age 6 to 7 years were associated with concurrent and later mathematics scores, and most of these correlations were stronger than the significant associations found between response fluency on a baseline task (with no working memory demand) and mathematics performance. These findings have implications for the stability of EF skills during the school-age years, and the role of EF in early and later elementary school mathematics performance. PMID- 17364563 TI - Developmental and gender differences in future-oriented decision-making during the preschool period. AB - A child version of the Iowa Gambling task was used to explore the developmental and gender differences in decision making of 4-year-olds (N = 141). The task required children to choose between two decks: a deck with higher immediate rewards and a deck with higher future rewards. Developmental differences between young (4.0-4.5) and older (4.6-4.11) children were found, with older 4-year-olds choosing more from the deck with higher future rewards. Gender differences were found for decision-making strategy. It is suggested that these differences in approaches might account for the pattern of gender differences found in past research. PMID- 17364564 TI - Relating children's attentional capabilities to intelligence, memory, and academic achievement: a test of construct specificity in children with asthma. AB - The relationship between attention, intelligence, memory, achievement, and behavior in a large population (N = 939) of children without neuropsychologic problems was investigated in children with mild and moderate asthma. It was hypothesized that different levels of children's attentional capabilities would be associated with different levels of intellectual, memory, and academic abilities. Children ages 6-12 at the eight clinical centers of the Childhood Asthma Management Program (CAMP) were enrolled in this study. Standardized measures of child neuropsychological and behavioral performance were administered to all participants, with analyses examining both the developmental trajectory of child attentional capabilities and the associations between Continuous Performance Test (CPT) scores and intellectual functioning, and measures of memory, academic achievement, and behavioral functioning. Findings demonstrated that correct responses on the CPT increase significantly with age, while commission errors decrease significantly with age. Performance levels on the CPT were associated with differences in child intellectual function, memory, and academic achievement. Overall these findings reveal how impairments in child attention skills were associated with normal levels of performance on measures of children's intelligence, memory, academic achievement, and behavioral functioning, suggesting that CPT performance is a salient marker of brain function. PMID- 17364565 TI - Validity of the Rey Visual Design Learning Test in primary and secondary school children. AB - The Rey Visual Design Learning Test (Rey, 1964, cited in Spreen & Strauss, 1991, Wilhelm, 2004) assesses immediate memory span, new learning, delayed recall and recognition for nonverbal material. Two studies are presented that focused on the construct validity of the RVDLT in primary and secondary school children. In the first study, primary school children performed the RVDLT and the Biber Figural Learning Test, as well as the WISC-R Block design Test, Boston Naming Test, and the Trailmaking Test, to assess discriminant validity. In the second study, the age range was expanded and the subtest Visual Reproductions of the Wechsler Memory Scale with a Delayed recall phase was used to assess the construct validity. A test for visual-motor integration and a test for attention, concentration, and speed of information processing were also added to complete the test battery for assessing discriminant validity. Moderate to high correlations were found between scores on the RVDLT and the tests used to assess construct validity. The correlational pattern of RVDLT scores and the scores on the discriminant tests is discussed. PMID- 17364568 TI - Central nervous system complications of sickle cell disease in children: an overview. AB - Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, "silent cerebral infarcts" are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined. PMID- 17364569 TI - Neurocognitive sequelae of pediatric sickle cell disease: a review of the literature. AB - This literature review summarizes all studies relating neuropsychological performance to neuroimaging findings in pediatric sickle cell disease (N=28; published 1991-2005). Although inconsistencies exist within and across domains, deficits in intelligence (IQ), attention and executive functions, memory, language, visuomotor abilities, and academic achievement have been identified. Overall neurocognitive compromise was revealed to be related to the level of neurological injury and the location of silent infarct. Attentional and executive dysfunction is prevalent and related to frontal lobe abnormalities. PMID- 17364570 TI - Inhibitory control in children with frontal infarcts related to sickle cell disease. AB - Evidence from past studies indicates that children with traumatic brain injury experience difficulties with inhibitory control. Less is known about inhibitory control in children with frontal brain injury related to cerebral infarction. We compared the inhibitory performance of children with frontal infarcts related to sickle cell disease with that of a control group of children with sickle cell disease but no history of cerebral infarction. On a stimulus-response reversal task, children with frontal infarcts made significantly more accuracy errors in the inhibitory condition than controls. Findings from this study and from previous research suggest that impairments in inhibitory control are common following frontal injury in a range of pediatric populations. PMID- 17364571 TI - The association of oral hydroxyurea therapy with improved cognitive functioning in sickle cell disease. AB - This study examined potential cognitive benefits of oral hydroxyurea therapy for children with sickle cell disease (SCD). Cognitive abilities of 15 children with SCD on hydroxyurea were compared to 50 other children with SCD, controlling for demographics and hematocrit. Children on hydroxyurea scored significantly higher on tests of verbal comprehension, fluid reasoning, and general cognitive ability than children not on the drug. The data therefore provide preliminary evidence of cognitive benefits of hydroxyurea. Mechanisms for this effect may be improved blood/oxygen supply to the brain or reduced fatigue and illness. PMID- 17364572 TI - Neuropsychological functioning in preschool-age children with sickle cell disease: the role of illness-related and psychosocial factors. AB - Cognitive and academic deficits have been identified in school-aged children with sickle cell disease (SCD). However, there have been very few identified studies that examine neuropsychological functioning in preschool-age children with SCD. It is important to understand effects of SCD from a developmental perspective and to consider the contribution of environmental factors in this at-risk population. Neuropsychological functioning of preschool-age children with SCD and no history of overt stroke (n = 26) was examined across several domains (language, immediate memory/brief attention, visuospatial/visuoconstructional, motor/visuomotor). The mean Full Scale IQ for the sample was 89.0. Performance on the Immediate Memory/ Brief Attention domain was significantly higher than the other domains, although the pattern of performance was relatively consistent, with mean standard scores ranging from 88.0 to 95.0. Disease severity was not significantly related to cognitive functioning in this group of young children with SCD. Socioeconomic status (SES) was significantly correlated with most domain scores and, based on regression analyses, accounted for 18% to 47% of the variance in functioning. Psychosocial factors, such as number of children living in the home and parental stress levels, were negatively associated with Motor/Visuomotor skills, and weekly hours in school/day care was positively associated with language-related skills. Results suggest that, at this young age, psychosocial risk factors appear to be appropriate targets for intervention, with the goal of improving long-term outcome in children with SCD. Further investigations should include comparison to a matched control group. PMID- 17364573 TI - Peer relationships and emotional well-being of children with sickle cell disease: a controlled replication. AB - We completed a replication study examining the social and emotional functioning of children with sickle cell disease (SCD) who have not had an overt stroke and a group of demographically similar comparison classmates based upon data from multiple informants. Relative to comparison peers, children with SCD were described by teachers as more prosocial and less aggressive. Peers described them as having fewer friends, less athletic, ill more often, and missing more school. No group differences were identified for emotional well-being. Effect size analyses indicated that this study replicated a number of findings from our previous study of children with SCD (Noll et al., 1996). Findings from both studies suggest relative psychological hardiness among children with SCD who have not had an overt stroke. PMID- 17364574 TI - Evaluation of a disease-specific self-efficacy instrument in adolescents with sickle cell disease and its relationship to adjustment. AB - The psychometric properties of a disease-specific instrument used to assess self efficacy in adolescents with sickle cell disease, the Sickle Cell Self-Efficacy Scale, were evaluated in a sample of 131 adolescents ranging from 11 to 19 years of age. This nine-item instrument was associated with a one-item, general self efficacy question and an item of self-control. After controlling for age, gender, highest grade of education completed, and the number of individuals in the household, high levels of self-efficacy were related to fewer physical, psychological, and total symptoms. Using the stress process framework to examine the relationship between self-efficacy and self-reported symptoms in adolescents may lead to the initiation of effective intervention programs capable of increasing levels of self-efficacy in adolescents. These interventions could lead to better outcomes for adolescents with sickle cell disease. Additional longitudinal investigations are needed to evaluate the ability of self-efficacy to predict adolescent adjustment over time. PMID- 17364575 TI - Clock polymorphisms and circadian rhythms phenotypes in a sample of the Brazilian population. AB - A Clock polymorphism T to C situated in the 3' untranslated region (3'-UTR) has been associated with human diurnal preference. At first, Clock 3111C had been reported as a marker for evening preference. However these data are controversial, and data both corroborating and denying them have been reported. This study hypothesizes that differences in Clock genotypes could be observed if extreme morning-type subjects were compared with extreme evening-type subjects, and the T3111C and T257G polymorphisms were studied. The possible relationship between both polymorphisms and delayed sleep phase syndrome (DSPS) was also investigated. An interesting and almost complete linkage disequilibrium between the polymorphisms T257G in the 5' UTR region and the T3111C in the 3' UTR region of the Clock gene is described. Almost always, a G in position 257 corresponds to a C in position 3111, and a T in position 257 corresponds to a T in position 3111. The possibility of an interaction of these two regions in the Clock messenger RNA structure that could affect gene expression was analyzed using computer software. The analyses did not reveal an interaction between those two regions, and it is unlikely that this full allele correspondence affects Clock gene expression. These results show that there is no association between either polymorphism T3111C or T257G in the Clock gene with diurnal preference or delayed sleep phase syndrome (DSPS). These controversial data could result from the possible effects of latitude and clock genes interaction on circadian phenotypes. PMID- 17364576 TI - Daily oscillation and photoresponses of clock gene, Clock, and clock-associated gene, arylalkylamine N-acetyltransferase gene transcriptions in the rat pineal gland. AB - This study was conducted to investigate the circadian rhythms and light responses of Clock and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the environmental conditions of a 12 h light (05:00-17:00 h): 12 h-dark (17:00-05:00 h) cycle (LD) and constant darkness (DD). The pineal gland of Sprague-Dawley rats housed under a LD regime (n=42) for four weeks and of a regime (n=42) for eight weeks were sampled at six different times, every 4 h (n=7 animals per time point), during a 24 h period. Total RNA was extracted from each sample, and the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine temporal changes in mRNA levels of Clock and NAT genes during different circadian or zeitgeber times. The data and parameters were analyzed by the cosine function software, Clock Lab software, and the amplitude F test was used to reveal the circadian rhythm. In the DD or LD condition, both the Clock and NAT mRNA levels in the pineal gland showed robust circadian oscillation (p<0.05) with the peak at the subjective night or at nighttime. In comparison with the DD regime, the amplitudes and mRNA levels at the peaks of Clock and NAT expressions in LD in the pineal gland were significantly reduced (p<0.05). In the DD or LD condition, the circadian expressions of NAT were similar in pattern to those of Clock in the pineal gland (p>0.05). These findings indicate that the transcriptions of Clock and NAT genes in the pineal gland not only show remarkably synchronous endogenous circadian rhythmic changes, but also respond to the ambient light signal in a reduced manner. PMID- 17364577 TI - Effect of light intensity on the oviposition rhythm of the altitudinal strains of Drosophila ananassae. AB - The sensitivity of the circadian photoreceptors mediating entrainment of the eclosion rhythm and phase shifts of oviposition rhythm of the high altitude (HA) strain of Drosophila ananassae originating from Badrinath (5123 m above sea level) in the Himalayas was compared with the low altitude (LA) strain from Firozpur (179 m above sea level). Reduced photic sensitivity of the HA strain is regarded as the result of natural selection, which led to the weakening of the coupling mechanism between the circadian pacemaker and light at the high altitude of origin. The present study was designed to determine whether or not the photic entrainment of the oviposition rhythm of the HA strain of D. ananassae is also altered by the high altitude of its origin, and the results are compared with those of the LA strain. The effects of light intensity on the phase angle difference (Psi), degree of rhythmicity (R), the percent oviposition in photophase, the threshold light intensity (i.e., the intensity at which stable entrainment occurred), and the saturation light intensity (i.e., the intensity beyond which the values of Psi or amplitude of rhythm remained unaltered) were determined. Entrainment was studied in light-dark cycles in which the light intensity of 12 h of photophase varied from 1 to 1000 lux, and complete darkness prevailed in all scotophases. The oviposition rhythm of the HA strain was arrhythmic from 1 to 90 lux, weakly rhythmic at 95 lux, but rhythmic at or above 100 lux, while that of the LA strain was weakly rhythmic at 1 lux but rhythmic at or above 2 lux. Oviposition of the HA strain occurred mostly in the photophase, while that of the LA strain occurred in the scotophase; as a result, the oviposition medians of the HA strain were around the subjective forenoons while those of the LA strain were around the subjective evenings. The percent of oviposition in photophase increased from 68 to 98 in the HA strain and from 5 to 33 in the LA strain as light intensity increased from 1 to 1000 lux. In the HA strain, the Psi values were significantly less and values of R and percent oviposition in photophase were significantly more than those of the LA strain at each level of light intensity. Threshold and saturation intensities for Psi were 100 and 700 lux, respectively, for the HA strain, but just 2 and 45 lux, respectively, for the LA strain. The saturation intensity for R was 650 and 700 lux for the HA and LA strains, respectively. These results extend the confirmation that the reduced photic sensitivity of the HA strain might have been acquired through natural selection in response to environmental conditions at the high altitude of its origin. PMID- 17364578 TI - Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression. AB - This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39 degrees North, 140 degrees East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9+/-1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one-third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6+/-18.4%) than summer (37.2+/-33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light. PMID- 17364579 TI - Disturbance of circadian rhythms in analgosedated intensive care unit patients with and without craniocerebral injury. AB - Melatonin, cortisol, heart rate, blood pressure, spontaneous motor activity, and body temperature follow stable circadian rhythms in healthy individuals. These circadian rhythms may be influenced or impaired by the loss of external zeitgebers during analgosedation, critical illness, continuous therapeutic intervention in the intensive care unit (ICU), and cerebral injury. This prospective, observational, clinical study examined 24 critically ill analgo sedated patients, 13 patients following surgery, trauma, or acute respiratory distress (ICU), and 11 patients with acute severe brain injury following trauma or cerebral hemorrhage (CCI). Blood samples for the determination of melatonin and cortisol were obtained from each patient at 2 h intervals for 24 h beginning at 18:00 h on day 1 and ending 16:00 h on day 2. Blood pressure, heart rate, body temperature, and spontaneous motor activity were monitored continuously. Level of sedation was assessed using the Ramsey Sedation Scale. The severity of illness was assessed using the APACHE-II-score. The time series data were analyzed by rhythm analysis with the Chronos-Fit program, using partial Fourier series with up to six harmonics. The 24 h profiles of all parameters from both groups of patients were greatly disturbed/abolished compared to the well-known rhythmic 24 h patterns in healthy controls. These rhythm disturbances were more pronounced in patients with brain injury. The results of this study provide evidence for a pronounced disturbance of the physiological temporal organization in ICU patients. The relative contribution of analgosedation and/or brain injury, however, is a point of future investigation. PMID- 17364580 TI - Rectal temperature, distal sweat rate, and forearm blood flow following mild exercise at two phases of the circadian cycle. AB - Changes in rectal temperature during mild exercise in the middle of the rising (11:00 h) and falling (23:00 h) phases of the circadian rhythm of resting core temperature have been compared. Seven healthy males were studied at rest, while exercising on a cycle ergometer (60 min at 80 W), and during the first 30 min of recovery. Rectal temperature, forearm blood flow, and forearm sweat rate were measured at 1 min intervals throughout. During exercise, there were significant time-of-day differences in the profiles of all three variables, and in the thresholds for increases in forearm blood flow and sweating. Forearm blood flow and sweat rate were recruited more rapidly and to a greater extent with evening exercise, and rectal temperature rose less. Analysis of covariance, with rectal temperature as the covariate, indicated the associations between it and forearm blood flow or sweating were significantly different (p<0.05) between the two times of day. There were also significant (p<0.05) time-of-day effects for forearm blood flow and sweating that were independent of rectal temperature. During recovery, rectal temperature fell more quickly in the late evening than late morning. Forearm blood flow and sweating also showed time-of-day differences, but these did not co-vary with rectal temperature. Control of rectal temperature during exercise and recovery appears to be more effective in the late evening than late morning, and differences in forearm blood flow and sweating, as well as factors independent of these two variables, contribute to this difference. The results support our "heat-gain/heat-loss modes" hypothesis. PMID- 17364581 TI - Human immune circadian system in prolonged mild hypoxia during simulated flights. AB - An impairment of immunity is reported after long-haul flights, and the mild hypobaric hypoxia caused by pressurization in the passenger airline cabin may contribute to it. In this controlled crossover study, the effects of two levels of hypoxia, equivalent to 8000 and 12,000 feet above sea level, on the rhythm of CD3, CD4, and CD8 lymphocytes and plasma concentrations of the immunoglobulins A, G, and M were assessed. Fourteen healthy male volunteers, aged 23 to 39 years, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), simulating an altitude condition at 8,000 feet. This was followed by an additional 8.5 h study four weeks later simulating altitude conditions at 12,000 feet. The variables were assayed every 2 h over two 24 h cycles (control and hypoxic-exposure cycles). No significant effect of hypoxia on the studied circadian immune profiles were found. Therefore, the authors conclude that mild hypobaric hypoxia does not seem to be responsible for any quantitative changes during long-haul flights in the immune assays commonly used in routine clinical medicine practice. PMID- 17364582 TI - Sleep and sleepiness among working and non-working high school evening students. AB - The aim of this study was to evaluate patterns of sleepiness, comparing working and non-working students. The study was conducted on high school students attending evening classes (19:00-22:30 h) at a public school in Sao Paulo, Brazil. The study group consisted of working (n=51) and non-working (n=41) students, aged 14-21 yrs. The students answered a questionnaire about working and living conditions and reported health symptoms and diseases. For seven consecutive days, actigraphy measurements were recorded, and the students also filled in a sleep diary. Sleepiness ratings were given six times per day, including upon waking and at bedtime, using the Karolinska Sleepiness Scale. Statistical analyses included three-way ANOVA and t-test. The mean sleep duration during weekdays was shorter among workers (7.2 h) than non-workers (8.8 h) (t=4.34; p<.01). The mean duration of night awakenings was longer among workers on Tuesdays and Wednesdays (28.2 min) and shorter on Mondays (24.2 min) (t=2.57; p=.03). Among workers, mean napping duration was longer on Mondays and Tuesdays (89.9 min) (t=2.27; p=.03) but shorter on Fridays and Sundays (31.4 min) (t=3.13; p=.03). Sleep efficiency was lower on Fridays among non-workers. Working students were moderately sleepier than non-workers during the week and also during class on specific days: Mondays (13:00-15:00 h), Wednesdays (19:00-22:00 h), and Fridays (22:00-00:59 h). The study found that daytime sleepiness of workers is moderately higher in the evening. This might be due to a work effect, reducing the available time for sleep and shortening the sleep duration. Sleepiness and shorter sleep duration can have a negative impact on the quality of life and school development of high school students. PMID- 17364583 TI - Elevated plasma homocysteine in older shift-workers: a potential risk factor for cardiovascular morbidity. AB - There is evidence supporting an association between shift work and cardiovascular morbidity, but the underlying mechanisms are unknown. The present paper investigated the levels of cardiovascular biochemical risk factors in shift workers both with (n=26) and without (n=103) sleep complaints, and in day-workers (n=173) working in the same plant. Blood samples were taken in the morning after an overnight fast and analyzed for homocysteine, C-reactive protein, and lipid profile. Biochemical data were compared among groups after stratifying workers by age (i.e., <40 and > or = 40 yrs). Shift-workers who complained about sleep disturbances and who were > or = 40 years of age had significantly higher levels of homocysteine than did their younger counterparts - shift-workers who did not complain of sleep disturbances and day-workers. There were no other between-group differences in any of the biochemical variables. The results of this investigation demonstrate an association between sleep disturbances in older shift-workers and mild hyperhomocysteinemia. The elevated homocysteine levels may play a role in the increased rates of cardiovascular morbidity in shift-workers, and they may have practical implications regarding the nutrition of shift workers. PMID- 17364584 TI - New insights into the circadian rhythm of acute myocardial infarction in subgroups. AB - The aim of this study was to determine the existence of the circadian rhythm (CR) in the onset of acute myocardial infarction (AMI) in different patient subgroups. Information was collected about 41,244 infarctions from the database of the ARIAM (Analysis of Delay in AMI) Spanish multicenter study. CR in AMI were explored in subgroups of cases categorized by age, gender, previous ischemic heart disease (PIHD), outcome in coronary care unit, infarction electrocardiograph (ECG) characteristics (Q wave or non-Q wave), and location of AMI. Cases were classified according to these variables in the different subgroups. To verify the presence of CR, a simple test of equality of time series based on the multiple sinusoid (24, 12, and 8 h periods) cosinor analysis was developed. For the groups as a whole, the time of pain onset as an indicator of the AMI occurrence showed a CR (p<0.0001), with a morning peak at 10:10 h. All the analyzed subgroups also showed CR. Comparison between subgroups showed significant differences in the PIHD (p<0.01) and infarction ECG characteristics (p<0.01) groups. The CR of the subgroup with Q-wave infarction differed from that of non-Q wave subgroup (p<0.01) when the patients had PIHD (23% in Q wave infarction vs. 39.2% in non-Q wave). AMI onset followed a CR pattern, which is also observed in all analyzed subgroups. Differences in the CR according to the Q/non-Q wave infarction characteristics could be determined by PIHD. The cosinor model fit with three components (24, 12, and 8 h periods) showed a higher sensitivity than the single 24 h period analysis. PMID- 17364585 TI - Seasonal variation in occurrence of pulmonary embolism: analysis of the database of the Emilia-Romagna region, Italy. AB - Seasonal variation in the occurrence of cardiovascular and cerebrovascular events, including pulmonary embolism (PE), has been reported; however, recent large-scale, population-based studies conducted in the United States did not confirm such seasonality. The aim of this large-scale population study was to determine whether a temporal pattern in the occurrence of PE exists. The analysis considered all consecutive cases of PE in the database of all hospital admissions of the Emilia Romagna region in Italy at the Center for Health Statistics between January 1998 and December 2005. PE cases were first grouped according to season of occurrence, and the data were analyzed by the chi(2) test for goodness of fit. Then, inferential chronobiologic (cosinor and partial Fourier) analysis was applied to monthly data, and the best-fitting curve for the annual variation was derived. The total sample consisted of 19,245 patients (8,143 male, mean age 71.6+/-14.1 yrs; 11,102 female, mean age 76.1+/-13.7 yrs). Of these, 2,484 were <65 yrs, 5,443 were between 65 and 74, and 11,318 were > or = 75 yrs. There were 4,486 (23.3%) fatal-case outcomes. PE occurred least frequently in spring (n=4,442 or 23.1%) and most frequent in winter (n=5,236 or 27.2%, goodness of fit chi(2)=75.75, p<0.001). Similar results were obtained for subgroups formed by gender, age, fatal/non-fatal outcome, presence/absence of major underlying co morbid conditions, and specific risk factors. Inferential chronobiological analysis identified a significant annual pattern in PE, with the peak between November and December for the total sample of cases (p<0.001), males (p<0.001), females (p=0.002), fatal and non-fatal cases (p<0.001 for both), and subgroups formed by age (<65 yrs, p=0.012; 65-74 yrs, p<0.001; > or = 75 yrs, p=0.012). This pattern was independent of the presence/absence of hypertension (p=0.003 and p<0.001, respectively), pulmonary disease (p<0.001 and p<0.001, respectively), stroke (p<0.001 and p=0.004, respectively), neoplasms (p=0.005 and p=0.001, respectively), heart failure (p=0.022 and p<0.001, respectively), and deep vein thrombosis (p=0.002 and p<0.001, respectively). However, only a non-statistically significant trend was found for subgroups formed by cases of diabetes mellitus, infections, renal failure, and trauma. PMID- 17364586 TI - Chronopharmacological study of cephalexin in dogs. AB - Recent studies have identified a 24 h rhythm in the expression and function of PEPT1 in rats, with significantly higher levels during the nighttime than daytime. Similarly, temporal variations have been described in glomerular filtration rate and renal blood flow, both being maximal during the activity phase and minimal during the rest phase in laboratory rodents. The aim of this study was to assess the hypothesis that the absorption of the first-generation cephalosporin antibiotic cephalexin by dogs would be less and the elimination would be slower after evening (rest span) compared to morning (activity span) administration, and whether such administration-time changes could impair the medication's predicted clinical efficacy. Six (3 male, 3 female; age 4.83+/-3.12 years) healthy beagle dogs were studied. Each dog received a single dose of 25 mg/kg of cephalexin monohydrate per os at 10:00 and 22:00 h, with a two-week interval of time between the two clock-time experiments. Plasma cephalexin concentrations were determined by microbiological assay. Cephalexin peak plasma concentration was significantly reduced to almost 77% of its value after the evening compared to morning (14.52+/-2.7 vs. 18.77+/-2.8 microg/mL) administration. The elimination half-life was prolonged 1.5-fold after the 22:00 h compared to the 10:00 h administration (2.69+/-0.9 vs. 1.79+/-0.2 h). The area under the curve and time to reach peak plasma concentration did not show significant administration-time differences. The duration of time that cephalexin concentrations remained above the minimal inhibitory concentrations (MIC) for staphylococci susceptiblity (MIC=0.5 microg/mL) was>70% of each of the 12 h dosing intervals (i.e., 10:00 and 22:00 h). It can be concluded that cephalexin pharmacokinetics vary with time of day administration. The findings of this acute single-dose study require confirmation by future steady-state, multiple-dose studies. If such studies are confirmatory, no administration-time dose adjustment is required to ensure drug efficacy in dogs receiving an oral suspension of cephalexin in a dosage of 25 mg/kg at 12 h intervals. PMID- 17364587 TI - Comparison of the efficacy of morning versus evening administration of olmesartan in uncomplicated essential hypertension. AB - A total of 18 diurnally active subjects with uncomplicated, mild to moderate, essential hypertension were studied to compare the efficacy of the morning versus evening administration of an oral olmesartan medication. After a two-week, wash out/placebo run-in period, subjects with clinic diastolic blood pressure (DBP) > or = 90 mm Hg and <110 mm Hg began 12 weeks of 20 mg olmesartan medoxomil tablet therapy at 08:00 h daily. Four of the 18 subjects required dose escalation to 40 mg at eight weeks because of clinic DBP > or = 90 mm Hg. After the 12-week period of once-a-day 08:00 h treatment, subjects were immediately switched to an evening (20:00 h) drug-ingestion schedule for another 12-week period without change in dose. Subjects underwent 24 h ambulatory blood pressure monitoring (ABPM) before the initiation of morning treatment and at the end of both the 12-week morning and evening treatment arms. Dosing time did not exert statistically significant differences on the efficacy of olmesartan: the reduction from baseline in the 24 h mean systolic (SBP) and DBP was, respectively, 18.8 and 14.6 mm Hg with morning dosing and 16.1 and 13.2 mm Hg with evening dosing (p>0.152 between groups). The amplitude of the BP 24 h pattern did not vary with dosing time, indicating full 24 h BP reduction no matter the clock hour of treatment. Although, the BP lowering effect was somewhat better with morning dosing, the results of this study suggest that the studied olmesartan medoxomil preparation efficiently reduces BP when ingested in the morning (08:00 h) or evening (20:00 h) in equivalent manner, based on statistical testing, throughout the 24 h. PMID- 17364588 TI - Treatment with beta2-adrenoceptor agonist in vivo induces human clock gene, Per1, mRNA expression in peripheral blood. AB - This study examined whether in vivo exposure to a beta2-adrenoceptor agonist, tulobuterol, induces human Period1 (hPer1) mRNA expression in cells from peripheral whole blood. In one experiment, oral tulobuterol was administered to five healthy volunteers at 22:00 h, while in another, a transdermally tulobuterol patch was applied to the same five subjects at 20:00 h. In each experiment, serum tulobuterol concentrations were measured at four time points, and total RNA was isolated from peripheral blood cells for determinations of hPer1 mRNA expression by real-time polymerase chain reaction. Both the tulobuterol tablet and the transdermal patch increased hPer1 mRNA expression, suggesting that analyses of human peripheral blood cells could reliably represent peripheral clock gene mRNA expression in vivo. PMID- 17364592 TI - Drospirenone and estradiol: a new option for the postmenopausal woman. AB - The efficacy of estrogen with or without a progestogen as hormone replacement therapy (HRT) for menopausal symptoms is well-established. Recent large-scale randomized studies with combined estrogen/progestogen therapy (EPT) have raised a number of safety issues, specifically the potential risk for coronary heart disease. Subsequent analyses and other studies have indicated that HRT may be cardioprotective in younger postmenopausal women. A new continuous EPT combines natural 17beta-estradiol (E2) 1 mg with the novel progestin, drospirenone (DRSP) either 0.5 or 2 mg. DRSP has a physiological profile closer to that of natural progesterone than any other synthetic progestin. This paper reviews recent clinical trial data demonstrating the efficacy and safety of combined DRSP/E2 therapy as EPT in postmenopausal women. DRSP/E2 provides symptomatic relief of vasomotor symptoms and improvement in genitourinary atrophy. DRSP/E2 protects against endometrial hyperplasia and reduces the risk of osteoporosis. Combined DRSP/E2 therapy has a favorable impact on cholesterol and triglyceride levels, and decreases blood pressure in women with elevated blood pressure. The favorable efficacy and safety profile of DRSP/E2, and potential for long-term health benefits, represents a new option for the effective management of menopause and its clinical sequelae. PMID- 17364593 TI - Drospirenone and its antialdosterone properties. AB - Drospirenone is a unique progestogen derived from 17alpha-spirolactone, with a pharmacologic profile very similar to that of endogenous progesterone. In contrast with other available progestins, drospirenone is a progestogen with aldosterone receptor antagonism (PARA) through its affinity for the mineralocorticoid receptor. It is thus able to act on the renin-angiotensin aldosterone system (RAAS), which prevents excessive sodium loss and regulates blood pressure. Estrogen acts on the RAAS to stimulate the synthesis of angiotensinogen, which increases aldosterone levels and promotes sodium and water retention. When these effects are unopposed, for example during estrogen replacement therapy, they can lead to increases in weight and blood pressure. The antialdosterone properties exhibited by drospirenone promote sodium excretion and prevent water retention, conferring potential blood pressure benefits. In addition to its effects on the kidney, aldosterone has effects on the vasculature, myocardium and central nervous system, which may elicit a variety of pathophysiologic processes associated with cardiovascular disease. The antialdosterone properties of drospirenone may therefore confer additional cardiovascular benefits beyond the RAAS system. The combined actions of drospirenone on sodium and water retention and cardiovascular parameters make it a more attractive therapeutic option as a component of hormone replacement therapy than other synthetic progestins. PMID- 17364594 TI - Menopause and cardiovascular disease: the evidence. AB - Menopause is a risk factor for cardiovascular disease (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism. The menopause compounds many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD risk factors have different impacts in men and women. In postmenopausal women, treatment of arterial hypertension and glucose intolerance should be priorities. Observational studies and randomized clinical trials suggest that hormone replacement therapy (HRT) started soon after the menopause may confer cardiovascular benefit. In contrast to other synthetic progestogens used in continuous combined HRTs, the unique progestogen drospirenone has antialdosterone properties. Drospirenone can therefore counteract the water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result in weight gain and raised blood pressure. As a continuous combined HRT with 17beta-estradiol, drospirenone has been shown to significantly reduce blood pressure in postmenopausal women with elevated blood pressure, but not in normotensive women. Therefore, in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol may offer further benefits in postmenopausal women, such as improved CVD risk profile. PMID- 17364595 TI - Drospirenone with 17beta-estradiol in the postmenopausal woman with hypertension. AB - Hypertension is one of the most important risk factors for the development of cardiovascular disease. The prevalence of hypertension increases with age and also after the menopause; therefore, blood pressure monitoring and effective control of elevated blood pressure are very important in postmenopausal women. The knowledge that aldosterone is a dual cardiovascular and endocrine hormone has blurred the once distinct boundary between gynecology and cardiovascular medicine. Aldosterone plays a major role in salt and water homeostasis, but also binds to mineralocorticoid receptors in the cardiovascular system, leading to structural and functional changes and consequent organ damage. Highly selective aldosterone blockade via the mineralocorticoid receptor has long-term antihypertensive effects. Drospirenone is a novel progestogen with aldosterone receptor antagonism (PARA), and therefore has antihypertensive effects through reduced salt and water retention. A new hormone therapy that combines 17beta estradiol with drospirenone has been shown in several clinical studies to have a blood pressure-lowering effect in postmenopausal women with elevated blood pressure, in addition to effectively relieving symptoms of the menopause. These findings suggest a potential additional benefit on the cardiovascular system for the drospirenone/17beta-estradiol combination in the treatment of women with menopausal symptoms and elevated blood pressure. PMID- 17364596 TI - Effects of blood pressure reduction on cardiovascular risk estimates in hypertensive postmenopausal women. AB - Menopause is accompanied by an increased prevalence of hypertension, which may partially explain the corresponding cardiovascular risk observed in postmenopausal women. The relationship between blood pressure and cardiovascular risk is continuous, consistent and independent of other risk factors. There are profound benefits of treating hypertension: antihypertensive therapy has been associated with large reductions in stroke, myocardial infarction and heart failure. Despite these proven benefits, hypertension is inadequately treated, or not treated at all, in the majority of patients. There has been concern regarding the use of hormone therapy in hypertensive postmenopausal women. Drospirenone/17beta-estradiol, a hormone therapy, has been demonstrated to lower blood pressure in hypertensive postmenopausal women either alone or when administered simultaneously with antihypertensive drugs. This might offer a potential advantage in patients with elevated blood pressure. It is also known that the risk for target organ events extends to levels well below the established definition of 140/90 mmHg. High-normal blood pressure carries an increased cardiovascular risk when compared to lower levels of blood pressure. Identification and management of elevated blood pressure are an important component of the successful management of the postmenopausal woman and can help prevent the untoward consequences of elevated blood pressure. PMID- 17364597 TI - Long-term trials of HRT for cardioprotection--is this as good as it gets? PMID- 17364598 TI - Bisphosphonate-associated osteonecrosis of the jaws. PMID- 17364599 TI - IMS reaction to recent breast cancer data. PMID- 17364600 TI - Premature ovarian failure: a review. AB - OBJECTIVES: To present an updated review on the etiology, consequences and management of premature ovarian failure. DESIGN: A search of the English language literature using the Cochrane Library database and Medline 1966-2006, with a hand search of the references. CONCLUSION: Premature ovarian failure is defined as the occurrence of amenorrhea, hypergonadotropinemia and estrogen deficiency in women under the age of 40 years, with the prevalence being 0.9-1.2%. In the majority of cases, the etiology is unknown, but known causes include chemotherapy, radiotherapy, surgery, genetic disorders, particularly involving the X chromosome, associations with autoimmune diseases, infections, smoking and other toxins. The three critical issues of management in these women are the effect of the diagnosis on the psychological health of the patient, the consequent infertility and the long- and short-term effects of estrogen deficiency arising from ovarian decline. Promising methods of screening for premature ovarian failure are being developed. PMID- 17364601 TI - Safety of alternative treatments for menopausal symptoms after breast cancer: a qualitative systematic review. AB - AIM: This qualitative review analyzes systematically the safety of drugs used to alleviate menopausal symptoms, other than hormone replacement therapy, in breast cancer patients. METHODS: We searched systematically studies using tibolone, serotonin reuptake inhibitors, clonidine, veralipride, gabapentin, black cohosh and phytoestrogens in breast cancer patients. We selected five studies for which we evaluated the methodology, characteristics of the studied populations, outcomes in terms of mortality and recurrence rates. RESULTS: Four trials were conducted using tibolone in breast cancer patients: one double-blind, randomized trial, one prospective controlled study, and two uncontrolled studies. They considerably lack power to detect any difference in breast cancer recurrence or mortality between the treated and control patients. Similar conclusions have to be drawn from the only controlled retrospective study analyzing the safety of antidepressants and antihistamines. We were unable to find studies reporting the safety of the other drugs in breast cancer patients. CONCLUSIONS: There are no valuable data indicating the absence of a harmful effect of drugs used to alleviate climacteric symptoms in breast cancer patients. There is a need for randomized trials to assess the safety of these drugs. In the meantime, patients should be informed about the absence of safety data. PMID- 17364602 TI - Relation of body mass and sex steroid hormone levels to hot flushes in a sample of mid-life women. AB - OBJECTIVE: Previous studies indicate that obesity is associated with a higher risk of experiencing hot flushes in mid-life women. The reasons for this association are unknown, although altered hormone levels have been associated with both hot flushes and obesity. Thus, this current study tested the hypothesis that obesity is associated with hot flushes in mid-life women through a mechanism involving levels of total and free androgen, free estrogen, progesterone, and sex hormone binding globulin (SHBG). METHODS: Women aged 45-54 years were recruited from Baltimore and its surrounding counties. Each participant (n=628) was weighed, measured, completed a questionnaire, and provided a blood sample that was used to measure estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone sulfate, progesterone, and SHBG. RESULTS: Obese mid-life women (body mass index (BMI)>or=30.0 kg/m2) had significantly higher testosterone, and lower estradiol, estrone, progesterone, and SHBG levels than normal-weight mid-life women (BMI900 pmol/L or 32 ng/dl) and lowest (<300 pmol/L or 11 ng/dl) range of the morning plasma aldosterone measurements were predictive of the subtype diagnosis in about 50% of PAL cases (31 of 61 patients). The sensitivity, specificity, and accuracy of the PST were >70% on both sodium diets. The PST was also reproducible irrespective of sodium intake. Moreover, one of its components, the supine morning plasma aldosterone, can be used as an indicator for the subtype diagnosis in about half of PAL patients. PMID- 17364613 TI - Acoustic analysis of the speech of children with cochlear implants: a longitudinal study. AB - The aim of the study was to analyse the speech of the children with cochlear implants, and compare it with the speech of hearing controls. We focused on three categories of Croatian sounds: vowels (F1 and F2 frequencies), fricatives (noise frequencies of /s/ and /S/ ), and affricates (total duration and the pattern of stop-fricative components in /ts/ and /tS/ ). Eighteen implanted children, aged between 9;5 and 15;2 years participated in the study. All had been profoundly hearing impaired before implantation. Three recordings per child were made over a 20-month period. The hearing controls were matched for age and sex. Implanted children had a smaller and fronted vowel space, their /s/ and /S/ noise frequencies overlapped, affricates were longer, with a high proportion of incorrect productions and substitutions. With time, there was a small but steady overall improvement in all categories. Early intervention (rehabilitation and implantation) are crucial for good speech acquisition. PMID- 17364614 TI - An acoustic and perceptual study of initial stops produced by profoundly hearing impaired adolescents. AB - This study investigated the role of Voice Onset Time (VOT) as perceptual cue to the aspiration contrast of Cantonese initial stops produced by adolescent profoundly hearing impaired speakers. Speakers with normal hearing signalled the aspiration contrast through VOT differences. Hearing impaired speakers produced initial stops with no significant VOT differences between aspirated and unaspirated stops; the accuracy of perception were above chance level for unaspirated stops but were below chance level for aspirated stops. Discriminant analysis conducted on data from a perceptual task showed that listeners with normal hearing relied on VOT cue for aspiration contrast of initial stops produced by control speakers. By contrast, stops produced by the hearing impaired speakers were not distinguished by listeners on the basis of VOT in that listeners were able to rely on VOT as a perceptual cue only to unaspirated stops, but not to aspirated stops. PMID- 17364615 TI - Feet and syllables in elephants and missiles: a reappraisal. AB - Using data from a case study presented in Chiat (1989), Marshall and Chiat (2003) compare two different approaches to account for the realization of intervocalic consonants in child phonology: "coda capture theory" and the "foot domain account". They argue in favour of the latter account. In this note, we present a reappraisal of this argument using the same data. We conclude that acceptance of the foot domain account, in the specific way developed by the authors, is unmotivated for both theoretical and empirical reasons. We maintain that syllable based coda capture is (still) the better approach to account for the relevant facts. PMID- 17364616 TI - Indicators of theory of mind in narrative production: a comparison between individuals with genetic syndromes and typically developing children. AB - It is a matter of debate whether the development of theory of mind (ToM) depends on linguistic development or is, rather, an expression of cognitive development. The study of genetic syndromes, which are characterized by intellectual impairment as well as by different linguistic profiles, may provide useful information with respect to this issue. The present study compares indicators of ToM in the narrative production of individuals with Cornelia de Lange syndrome, Down syndrome, Williams syndrome and typically developing children, matched on sex and mental age. Statistical comparisons of data obtained from a qualitative analysis of the narrative production of the different groups confirm the presence of distinctive patterns, mainly related to the effective use of personal pronouns. The analysis of correlations among story-telling variables and other cognitive and linguistic variables suggests that the relationship between language development, cognitive development, and the emergence of ToM cannot be reduced to unidirectional causal links. PMID- 17364617 TI - Perspectives on public awareness of stroke and aphasia among Turkish patients in a neurology unit. AB - Recent studies on awareness have drawn attention to the fact that aphasia is a little known disorder to the public, in spite of all the publicity about this frequently occurring neurogenic language disorder. Being a very new concept, studies of awareness are rare in Turkey. This survey study assessed the extent of public awareness of neurological disorders, including aphasia, and information sources to answer questions about such disorders. A survey questionnaire consisting of 22 brief questions divided into three sections of awareness was administered to a convenience sample of 196 adults at a University Hospital in 2004. The results indicated that epilepsy and dementia are "the most well-known", and Multiple Sclerosis (MS) is "the least-known" among the surveyed diseases/disorders. Aphasia awareness was also low. The respondents preferred doctors as the most reliable information source. Speech and language therapists were found to be one of the information sources in advocating publicity as well. Most respondents expected to receive information from the doctors; who, in Turkey, are totally occupied with the physical aspects of health care provision. Neurologists, in collaboration with speech and language therapists, should be in a position to develop educational programmes to increase public awareness. PMID- 17364618 TI - Derivational morphology in children with grammatical-specific language impairment. AB - Although it is well-established that children with Specific Language Impairment characteristically optionally inflect forms that require tense and agreement marking, their abilities with regards to derivational suffixation are less well understood. In this paper we provide evidence from children with Grammatical Specific Language Impairment (G-SLI) that derivational suffixes, unlike tense and agreement suffixes, are not omitted in elicitation tasks. We investigate two types of derivation - comparative/superlative formation and adjective-from-noun formation - and reveal that G-SLI children supply these suffixes at high rates, equivalent to their language matched peers. Moreover, increasing the phonological or morphological complexity of the stimulus does not trigger suffix omission, although it results in non-target forms that are not characteristic of typically developing children. We discuss what these results reveal about the nature of the deficit in G-SLI within the context of three hypotheses of SLI: the Extended Optional Infinitive, Implicit Rule and Computational Grammatical Complexity Hypotheses. PMID- 17364619 TI - Phonological skills in Puerto Rican and Mexican Spanish-speaking children with phonological disorders. AB - The effects of dialectal differences upon the speech production skills of children with phonological disorders are poorly understood. One might predict that the phonological profile of children using a radical dialect (e.g., Puerto Rican Spanish, which alters consonants in the syllable rhyme) will differ from that of children who use a conservative dialect (e.g., Mexican Spanish, which preserves such consonants). This study evaluated the impact of such dialectal differences by comparing the phonological skills of two groups of Spanish speaking children with phonological disorders. Six participants used the Mexican dialect; the other six used the Puerto Rican dialect of North American Spanish. All children were matched on number of segmental errors and age, which ranged from 4;4 to 5;6 (M=4;10). A single-word assessment instrument was used to elicit data, and independent and relational analyses were completed for each child. Measures included phonetic inventory complexity, vowel accuracy, consonant accuracy, sound class accuracy, percentage-of-occurrence of phonological patterns, and frequency and types of substitutions. Significant between-group differences were not found for any measures. These findings do not support the hypothesis of significant phonological differences between phonologically disordered speakers of radical and conservative Spanish dialects. PMID- 17364620 TI - Phonetic complexity and stuttering in Spanish. AB - The current study investigated whether phonetic complexity affected stuttering rate for Spanish speakers. The speakers were assigned to three age groups (6-11, 12-17 and 18-years plus) that were similar to those used in an earlier study on English. The analysis was performed using Jakielski's Index of Phonetic Complexity (IPC) scheme in which each word is given an IPC score based on the number of complex attributes it includes for each of eight factors. Stuttering on function words for Spanish did not correlate with IPC score for any age group. This mirrors the finding for English that stuttering on these words is not affected by phonetic complexity. The IPC scores of content words correlated positively with stuttering rate for 6-11-year-old and adult speakers. Comparison was made between the languages to establish whether or not experience with the factors determines the problem they pose for speakers (revealed by differences in stuttering rate). Evidence was obtained that four factors found to be important determinants of stuttering on content words in English for speakers aged 12 and above, also affected Spanish speakers. This occurred despite large differences in frequency of usage of these factors. It is concluded that phonetic factors affect stuttering rate irrespective of a speaker's experience with that factor. PMID- 17364621 TI - Reliability and confidence in using a paired comparison paradigm in perceptual voice quality evaluation. AB - One of the ways to improve the reliability in perceptual voice quality rating is to provide listeners with external anchors. A paired comparison matching paradigm using synthesized Cantonese voice stimuli that covered a range of rough and breathy qualities were used to investigate the rating reliability. Twenty-five speech pathology students rated the severity of roughness and breathiness of natural pathological voice samples using two paradigms: an eight-point anchored matching (paired comparison) paradigm and an eight-point non-anchored equal appearing-interval (EAI) scale paradigm. The listeners also rated their confidence in judging each testing stimulus on a seven-point EAI scale. The results showed that the paired comparison method specifically improved the inter rater reliability in rating male rough stimuli and mildly dysphonic female stimuli. The intra-rater agreement and confidence ratings remained similar across the two rating paradigms. These results suggest that the paired comparison paradigm may be used as an alternative perceptual voice quality evaluation tool. PMID- 17364622 TI - Sentence comprehension and general working memory. AB - Although the role of working memory in sentence comprehension has received substantial attention, the nature of this relationship remains unclear. The purpose of this study was to examine the interaction between general, nonverbal working memory (WM) and sentence parsing (SP) in normal English-speaking adults. Accuracy and reaction times were recorded for thirty-one young adults during three on-line tasks: nonverbal WM, SP plausibility, and lexical decision (LD). A significant positive correlation was observed between reaction times for WM and SP, but not between LD and SP. These results suggest that SP may be supported by a general WM capacity, and therefore, some sentence comprehension difficulties observed in the clinical population may potentially be related to impairment in general WM. PMID- 17364624 TI - Speech motor control in fluent and dysfluent speech production of an individual with apraxia of speech and Broca's aphasia. AB - Apraxia of speech (AOS) is typically described as a motor-speech disorder with clinically well-defined symptoms, but without a clear understanding of the underlying problems in motor control. A number of studies have compared the speech of subjects with AOS to the fluent speech of controls, but only a few have included speech movement data and if so, this was primarily restricted to the study of single articulators. If AOS reflects a basic neuromotor dysfunction, this should somehow be evident in the production of both dysfluent and perceptually fluent speech. The current study compared motor control strategies for the production of perceptually fluent speech between a young woman with apraxia of speech (AOS) and Broca's aphasia and a group of age-matched control speakers using concepts and tools from articulation-based theories. In addition, to examine the potential role of specific movement variables on gestural coordination, a second part of this study involved a comparison of fluent and dysfluent speech samples from the speaker with AOS. Movement data from the lips, jaw and tongue were acquired using the AG-100 EMMA system during the reiterated production of multisyllabic nonwords. The findings indicated that although in general kinematic parameters of fluent speech were similar in the subject with AOS and Broca's aphasia to those of the age-matched controls, speech task-related differences were observed in upper lip movements and lip coordination. The comparison between fluent and dysfluent speech characteristics suggested that fluent speech was achieved through the use of specific motor control strategies, highlighting the potential association between the stability of coordinative patterns and movement range, as described in Coordination Dynamics theory. PMID- 17364625 TI - An EMA analysis of the effect of increasing word length on consonant production in apraxia of speech: a case study. AB - The effect of increasing word length on the articulatory dynamics (i.e. duration, distance, maximum acceleration, maximum deceleration, and maximum velocity) of consonant production in acquired apraxia of speech was investigated using electromagnetic articulography (EMA). Tongue-tip and tongue-back movement of one apraxic patient was recorded using the AG-200 EMA system during word-initial consonant productions in one, two, and three syllable words. Significantly deviant articulatory parameters were recorded for each of the target consonants during one, two, and three syllables words. Word length effects were most evident during the release phase of target consonant productions. The results are discussed with respect to theories of speech motor control as they relate to AOS. PMID- 17364626 TI - Facilitating use of speech recognition software for people with disabilities: a comparison of three treatments. AB - This study examined the relative benefit of three interventions (i.e. physiological, behavioural, and pragmatic) designed to facilitate speech recognition software use. Participants were 15 adults with dysarthria associated with a variety of aetiological conditions, including cerebral palsy, Parkinson's disease, and motor neuron disease. Results suggested no clear dysarthric profile that would preclude at least some degree of speech recognition system use. Participants demonstrated systematic improvement in their dictation rates regardless of treatment order. The physiological treatment produced significantly higher dictation rates overall than the behavioural--but not the pragmatic- treatment. This finding suggests that improvement was not simply a function of software training, at least for the physiological treatment. This conclusion also was supported by changes in the participants' speech production during a post treatment assessment. PMID- 17364627 TI - Analysis of oral narratives of children who stutter and their fluent peers: kindergarten through second grade. AB - Measures of language sample length (in c-units) and morphological, syntactic, and narrative abilities were obtained from oral narrative transcripts of 22 children who stutter and 22 children who do not stutter; participants attended kindergarten, first, and second grades. A two-way MANOVA yielded significant main effects for grade, with significant differences on some measures evidenced between participants in kindergarten and second grades. No significant differences between groups or group-grade interaction effects on the measures were obtained. Grade-wise comparisons (through t-tests) indicated that the performance of children who stutter did not differ significantly from their typically fluent peers on all dependent measures; however, kindergarten children who stutter obtained the most discrepant (lower) scores than their grade-matched fluent peers on the Narrative Scoring Scheme measure, with group differences approaching statistical significance on this measure. The findings suggest that children who do and do not stutter evidence similar expressive language abilities, even as subgroups of children who stutter may lag behind their grade matched fluent peers in particular language domains. PMID- 17364628 TI - Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. AB - A review of U.S. poison center data for 2004 showed over 40,000 exposures to salicylate-containing products. A guideline that determines the conditions for emergency department referral and pre-hospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidence based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of hospital triage and initial out-of-hospital management of patients with a suspected exposure to salicylates by 1) describing the process by which a specialist in poison information should evaluate an exposure to salicylates, 2) identifying the key decision elements in managing cases of salicylate exposure, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses: 1) Patients with stated or suspected self-harm or who are the victims of a potentially malicious administration of a salicylate, should be referred to an emergency department immediately. This referral should be guided by local poison center procedures. In general, this should occur regardless of the dose reported (Grade D). 2) The presence of typical symptoms of salicylate toxicity such as hematemesis, tachypnea, hyperpnea, dyspnea, tinnitus, deafness, lethargy, seizures, unexplained lethargy, or confusion warrants referral to an emergency department for evaluation (Grade C). 3) Patients who exhibit typical symptoms of salicylate toxicity or nonspecific symptoms such as unexplained lethargy, confusion, or dyspnea, which could indicate the development of chronic salicylate toxicity, should be referred to an emergency department (Grade C). 4) Patients without evidence of self-harm should have further evaluation, including determination of the dose, time of ingestion, presence of symptoms, history of other medical conditions, and the presence of co-ingestants. The acute ingestion of more than 150 mg/kg or 6.5 g of aspirin equivalent, whichever is less, warrants referral to an emergency department. Ingestion of greater than a lick or taste of oil of wintergreen (98% methyl salicylate) by children under 6 years of age and more than 4 mL of oil of wintergreen by patients 6 years of age and older could cause systemic salicylate toxicity and warrants referral to an emergency department (Grade C). 5) Do not induce emesis for ingestions of salicylates (Grade D). 6) Consider the out-of-hospital administration of activated charcoal for acute ingestions of a toxic dose if it is immediately available, no contraindications are present, the patient is not vomiting, and local guidelines for its out-of-hospital use are observed. However, do not delay transportation in order to administer activated charcoal (Grade D). 7) Women in the last trimester of pregnancy who ingest below the dose for emergency department referral and do not have other referral conditions should be directed to their primary care physician, obstetrician, or a non-emergent health care facility for evaluation of maternal and fetal risk. Routine referral to an emergency department for immediate care is not required (Grade C). 8) For asymptomatic patients with dermal exposures to methyl salicylate or salicylic acid, the skin should be thoroughly washed with soap and water and the patient can be observed at home for development of symptoms (Grade C). 9) For patients with an ocular exposure of methyl salicylate or salicylic acid, the eye(s) should be irrigated with room-temperature tap water for 15 minutes. If after irrigation the patient is having pain, decreased visual acuity, or persistent irritation, referral for an ophthalmological examination is indicated (Grade D). 10) Poison centers should monitor the onset of symptoms whenever possible by conducting follow-up calls at periodic intervals for approximately 12 hours after ingestion of non-enteric-coated salicylate products, and for approximately 24 hours after the ingestion of enteric-coated aspirin (Grade C). PMID- 17364629 TI - Compliance for single and multiple dose regimens of superactivated charcoal: a prospective study of patients in a clinical trial. AB - BACKGROUND: Although activated charcoal is widely used for the treatment of self poisoning, its effectiveness is unknown. An important consideration is patient compliance since poor compliance will limit effectiveness. We aimed to describe compliance in a randomized controlled trial (RCT) performed in Sri Lanka, presuming that this would set the upper limits for compliance in routine clinical use. METHOD: 1,103 patients randomized to single or multiple (six doses q4h) 50 g doses of superactivated charcoal were prospectively observed. Charcoal was given by study doctors who recorded the amount ingested and the amount of persuasion required for the patients to drink the charcoal. RESULTS: 559 patients were randomized to receive one dose and 544 to receive six doses. Data was available for 1,071 (97%) patients. Eighty-eight were unable to complete their course; 98 required a NG tube, leaving 885 patients that received the first dose by mouth. The mean estimated amount of the prescribed dose of charcoal taken orally as a single or first dose was 83% (95% C.I. 82-84%). For patients receiving multiple doses, this amount fell over the next five doses to 66% (63-69%). While only 3.2% of patients refused the first dose, 12.3% refused the sixth. Relatively less persuasion was required for patients ingesting the first or single dose; 38% of patients required intense persuasion by the sixth dose. CONCLUSION: Compliance for a single dose of superactivated charcoal among trial patients was good. However, even in the ideal circumstances of a RCT, compliance decreased thereafter for patients taking more than one dose. PMID- 17364631 TI - Active surveillance of abused and misused prescription opioids using poison center data: a pilot study and descriptive comparison. AB - BACKGROUND: Prescription opioids are abused throughout the United States. Several monitoring programs are in existence, however, none of these systems provide up to-date information on prescription opioid abuse. This article describes the use of poison centers as a real-time, geographically specific, surveillance system for prescription opioid abuse and compares our system with an existing prescription drug abuse monitoring program, the Drug Abuse Warning Network (DAWN). METHODS: Data were collected from eight geographically dispersed poison centers for a period of twelve months. Any call involving buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone was considered a case. Any case coded as intentional exposure (abuse, intentional misuse, suicide, or intentional unknown) was regarded as misuse and abuse. Comparative data were obtained from DAWN. RESULTS: Poison center rates of abuse and misuse were highest for hydrocodone at 3.75 per 100,000 population, followed by oxycodone at 1.81 per 100,000 population. DAWN emergency department (ED) data illustrate a similar pattern of abuse with most mentions involving hydrocodone and oxycodone. Poison center data indicate that people aged 18 to 25 had the highest rates of abuse. DAWN reported the majority of ED mentions among 35 to 44 year-olds. Geographically, Kentucky had the uppermost rates of abuse and misuse for all opioids combined at 20.69 per 100,000 population. CONCLUSIONS. Comparing poison center data to DAWN yielded mostly comparable results, including hydrocodone as the most commonly mentioned drug. Our results suggest poison center data can be used as an indicator for prescription opioid abuse and misuse and can provide timely, geographically specific information on prescription drug abuse. PMID- 17364630 TI - The hazards of gastric lavage for intentional self-poisoning in a resource poor location. AB - OBJECTIVE: The 10-20% case fatality found with self-poisoning in the developing world differs markedly from the 0.5% found in the West. This may explain in part why the recent movement away from the use of gastric lavage in the West has not been followed in the developing world. After noting probable harm from gastric lavage in Sri Lanka, we performed an observational study to determine how lavage is routinely performed and the frequency of complications. CASE SERIES: Fourteen consecutive gastric lavages were observed in four hospitals. Lavage was given to patients unable or unwilling to undergo forced emesis, regardless of whether they gave consent or the time elapsed since ingestion. It was also given to patients who had taken non-lethal ingestions. The airway was rarely protected in patients with reduced consciousness, large volumes of fluid were given for each cycle (200 to more than 1000 ml), and monitoring was not used. Serious complications likely to be due to the lavage were observed, including cardiac arrest and probable aspiration of fluid. Health care workers perceived lavage as being highly effective and often life-saving; there was peer and relative pressure to perform lavage in self-poisoned patients. CONCLUSIONS: Gastric lavage as performed for highly toxic poisons in a resource-poor location is hazardous. In the absence of evidence for patient benefit from lavage, (and in agreement with some local guidelines), we believe that lavage should be considered for few patients - in those who have recently taken a potentially fatal dose of a poison, and who either give their verbal consent for the procedure or are sedated and intubated. Ideally, a randomized controlled trial should be performed to determine the balance of risks and benefits of safely performed gastric lavage in this patient population. PMID- 17364632 TI - Methanol mass poisoning in Estonia: outbreak in 154 patients. AB - BACKGROUND: Knowledge of methanol toxicity is based on human data from case series and larger outbreaks. In many of these cases, however, diagnosis was not verified by methanol determinations. We present epidemiological and clinical data from one of the largest methanol outbreaks in which all patients had detectable serum methanol levels. METHODS: Retrospective case series study of hospital and forensic charts from the five hospitals where patients were treated. RESULTS: Of the 147 patients admitted with suspected methanol poisoning, the diagnosis was confirmed in 111, of whom 25 (23 %) died. In addition, 43 patients died outside the hospital, giving a total of 154 patients and a death toll of 68 (44 %). Outcome was related to the degree of metabolic acidosis, serum methanol concentration, coma upon admission, and the patient's ability to hyperventilate. Patients were treated with bicarbonate (85 %), ethanol (87 %), hemodialysis (71 %), and mechanical ventilation (61%) according to clinical features and blood gases, since serum methanol concentrations were analyzed retrospectively. Twenty patients (18 %) survived with permanent sequelae, 18 suffered from impaired vision, and 3 developed permanent brain damage. DISCUSSION: Given limited resources, triage and use age of tertiary care centers allowed a small community hospital to treat a high number of methanol-poisoned patients. Critical resources were ventilators and dialyzing machines, whereas stores of antidote (ethanol) and bicarbonate were sufficient. Many patients were mechanically ventilated by hand and treated with bicarbonate and ethanol during transport to tertiary care centers for hemodialysis. PMID- 17364633 TI - Antigenic cross-reactivity between sixteen venoms from scorpions belonging to six genera. AB - Venoms of 15 scorpion species from Venezuela and one from Brazil were compared in their antigenic cross-reactivity with specific F(ab')2 against Tityus discrepans (Td-antibodies), using the method of King and collaborators (1). Our results show that Tityus venoms cross-reactivity (shared epitopes) with the venoms of other species within the genus tended to be less for a greater distance between the habitat of the species. A nonparametric linear regression of free Td-antibody binding to T. discrepans venom immobilized to a solid phase in the presence of other Tityus venoms versus distance showed binding = a + b x log10 (distance) where: median (95% confidence interval) for a = 0.92 (7.43, 9.80) and b = 17.20 (4.15, 22.57) binding/log10(Km); Spearman rS = 0.783 with associated P = 0.006. Our results show that toxins from different Tityus species, targeting mammalian Na+ and K+ channels, are antigenically very similar. Venoms from species from other genera such as Centruroides, Broteas, Diplocentrus, Chactas, and Rhopalurus did not cross-react with Td-antibodies. PMID- 17364634 TI - Trends in emergency department use of gastric lavage for poisoning events in the United States, 1993-2003. AB - OBJECTIVE: To determine current trends in the use of gastric decontamination for the emergency department (ED) treatment of overdose patients. METHODS: In the National Health Ambulatory Medical Care Survey (NHAMCS), a weighted sampling of U.S. EDs, overdose-related visits were examined using ICD-9 CM E codes and NHAMCS' "reason-for-visit" classification. RESULTS: From 1993 to 2003 there were an estimated 11.68 million ED-treated poisoning events. Some 13.7% of those treated were lavaged. Rates fell significantly, from an annual average of 18.7% of cases during 1993-97 to 10.3% during 1998-2003 (p < 0.001). Controlling for year, urgency, and admission status in multivariate logistic modeling, lavage was significantly and positively associated with private insurance payor status, younger age (<30), female gender, white race, 8 PM-8 AM presentation, and intentional rather than unintentional overdose. CONCLUSION: ED use of gastric lavage in poisoned patients has decreased significantly over the past decade but varies by demographic and non-clinical factors. PMID- 17364635 TI - Lamotrigine-induced seizures in a child: case report and literature review. AB - INTRODUCTION: Lamotrigine is an antiepileptic agent. There is only one previous report of a seizure associated with lamotrigine overdose with laboratory confirmation (a 2-year-old girl, lamotrigine level of 3.8 mg/L). CASE REPORT: A healthy 19-month-old boy ingested an unknown amount of his sister's lamotrigine tablets. Twenty minutes later, the child experienced generalized seizure activity lasting 10 seconds, followed by another brief self-limited seizure. Vitals signs: heart rate 152-207 bpm crying, respiratory rate 26 /min, temperature 95.7 degrees F, and pupils 3mm. The one-hour lamotrigine level = 20.3 mg/L. The child was discharged 24 hours later. LITERATURE REVIEW: Six previous case reports of lamotrigine poisoning with serum levels, as well as a retrospective review of lamotrigine exposures, are discussed. CONCLUSION: A case of lamotrigine-induced seizures in a pediatric patient is reported, with a level approximately five times the upper limit of the therapeutic range. The pediatric population may be at increased risk of seizures following lamotrigine poisoning, and serum levels may not be clinically useful for predicting outcome after overdose. PMID- 17364636 TI - Ruta Graveolens intoxication. AB - We describe a case of unintentional poisoning from Ruta Graveolens, a medicinal herb that is used for heart protection in Taiwan. A 78-year-old woman developed bradycardia, acute renal failure with hyperkalemia, and coagulopathy after three days of consuming a decoction made from Ruta Graveolens for the treatment of palpitations and heart protection. She was treated with hemodialysis in the emergency department for hyperkalemia. Her bradycardia and hypotension improved gradually three days later. Ruta use might cause multi-organ toxicity. We believe this case report helps in the recognition of the systemic toxicity of Ruta Graveolens. PMID- 17364637 TI - Severe hypokalaemic metabolic alkalosis following ingestion of gaviscon. AB - INTRODUCTION: Uncommon metabolic abnormalities in the emergency department could be a result of drug overdose due to uncommon agents. CASE REPORT: A 35-year-old male presented to the emergency department with a Glasgow Coma Scale (GCS) of 3/15 and a normal pulse rate and blood pressure. Subsequent questioning after recovery revealed he had ingested 2 L of Gaviscon over the preceding 48 hours. He had normal haematology, liver, and renal function during admission. The electrocardiogram showed T wave inversion in the inferior leads on admission. Arterial blood gas on air was: pH 7.54, HCO3 50 mmol/L (50 meq/L), Chloride 66 mmol/L, anion gap was 19, pO2 11 kPa (82.5 mmHg), and pCO2 8 kPa (60 mmHg). Serum sodium was 127 mmol/L and serum potassium was 1.6 mmol/L. His GCS improved within one hour of admission with supportive care, and his serum potassium and bicarbonate improved within 24 hours. He subsequently made a full recovery. Discussion. Bicarbonate ingestion in the form of Gaviscon(R) and vomiting made this patient alkalotic, and simple supportive care provided effective management with a complete recovery. CONCLUSION: This case illustrates how a severe metabolic alkalosis can result from a significant ingestion of Gaviscon, and that such presentations can give rise to diagnostic dilemma. PMID- 17364638 TI - Compulsive activity and anterograde amnesia after zolpidem use. AB - BACKGROUND: Zolpidem is a selective GABAAalpha1 receptor modulator used for its hypnotic-sedative properties. Zolpidem has side effects that are similar but not identical to the benzodiazepines. We report the first cases of compulsive activity combined with anterograde amnesia after the use of zolpidem. CASE REPORT: Three women experienced anterograde amnesia and compulsive repetitive behaviors after zolpidem use. These activities consisted of cleaning, shopping, and eating. These behaviors stopped after discontinuation of the zolpidem. CONCLUSION: These reports demonstrate that compulsive activity combined with anterograde amnesia may be associated with the use of zolpidem. Physicians and pharmacists should be aware of this potential side effect. PMID- 17364639 TI - Dyskinesias associated with atomoxetine in combination with other psychoactive drugs. AB - Toxicity experience with atomoxetine, a selective norepinephrine reuptake inhibitor approved for Attention Deficit Hyperactivity Disorder (ADHD), is limited. We report two cases of neurologic complications requiring hospitalization in patients when atomoxetine was added to other psychoactive drugs. A 9-year-old taking clonidine and dextroamphetamine developed psychosis, abnormal involuntary movements, and insomnia. An 18-year-old also initiating venlafaxine developed facial tics, tremors, and speech disturbance. Acute symptoms did not respond to diphenhydramine in either case, but resolved after atomoxetine and other medications were discontinued. Possible explanations include atypical atomoxetine effect, excess atomoxetine or metabolites due to poor metabolizer status (CYP 2D6 polymorphism/deficiency), a drug-drug interaction leading to elevated drug levels or to excess synaptic norepinephrine or dopamine. Serotonin syndrome is a possibility in the second case, but not the first. Clinicians should be aware of emergent dyskinesias when combining atomoxetine with dopaminergic, noradrenergic, or serotonergic medications. PMID- 17364640 TI - Amitriptyline-induced Brugada pattern fails to respond to sodium bicarbonate. AB - This report describes a Brugada electrocardiographic pattern after tricyclic antidepressant intoxication that fails to resolve following sodium bicarbonate treatment. A 50-year-old male ingested 13.6 grams of amitriptyline and presented in cardiopulmonary arrest. After initial resuscitation, the patient developed a Brugada electrocardiographic pattern. The pattern persisted despite intravenous administration of 700 mEq of sodium bicarbonate. Five hours after the last dose of sodium bicarbonate and 18 hours after initial presentation, the Brugada pattern resolved. No co-ingestants were ingested and an ischemic pattern was not seen on electrocardiogram. The serum amitriptyline level was >1000 ng/ml. Response of the tricyclic-induced Brugada pattern to sodium bicarbonate has not been previously reported. PMID- 17364641 TI - Identification of sulfhemoglobinemia after surgical polypectomy. AB - Sulfhemoglobinemia (SHb) is an uncommon cause of cyanosis that is predominantly drug-induced in adults. We report an unusual case of sodium sulfate-induced sulfhemoglobinemia in a 61-year-old woman after surgical polypectomy. Fractional hemoglobin derivates were assayed by spectrophotometry and high-performance liquid chromatography. The SHb ratio was 8.6% in the first sample and 3.77% a month later measured by spectrophotometry. In the blood hemolysate, a new peak was identified as SHb with high-performance liquid chromatography (HPLC). HPLC showed the presence of 9.37% SHb in the first sample and 4.88% a month later. After removing the suspected toxic agent the cyanosis decreased significantly. The findings underline the importance of routine SHb detection in cyanosis of unknown origin especially in emergency cases. PMID- 17364642 TI - Massive elemental mercury ingestion. PMID- 17364643 TI - Use of urine organic acids method for the analysis of gamma-hydroxybutric acid (GHB): importance of urease in eliminating urea interference. PMID- 17364644 TI - Seizures induced by topiramate overdose. PMID- 17364645 TI - Recreational abuse with benzydamine hydrochloride (tantum rosa). PMID- 17364646 TI - Severe neurotoxicity following oral meperidine (pethidine) overdose. PMID- 17364647 TI - Concurrent associations between anxiety sensitivity and perceived health and health disability among young adult daily smokers. AB - The aim of this investigation was to evaluate the incremental validity of anxiety sensitivity (fear of arousal-related physical and psychological sensations) relative to health factors (smoking variables, alcohol use and exercise level), in predicting perceived health and disability among a sample of 225 young adult daily smokers (102 females; M(age) = 23.9 years, SD = 8.8). Consistent with prediction, anxiety sensitivity, relative to smoking-relevant variables, alcohol consumption (a single frequency by quantity composite) and exercise activity, predicted lower perceived general health and impairments in mental health and social functioning; no incremental effects were evident for anxiety sensitivity for predicting impairments in physical functioning, role functioning, or increased healthcare usage. These findings are discussed with respect to better understanding cognitive factors that affect perceptions of health status and functioning among daily smokers. PMID- 17364648 TI - The role of fear of emotion in distress, arousal, and cognitive interference following an emotional stimulus. AB - Diverse theories of psychopathology suggest that reactions to internal experiences, such as emotion, are important in the development and maintenance of psychological distress and symptomatology. This study examines the relationships between one type of reaction to emotion, fear of emotion, and reactivity to, recovery from, and interference of emotional material. As predicted, fear of emotion was related to greater increases in distress, negative affect, and skin conductance in reaction to an emotional film clip, and to greater interference of film-related material in a modified emotional Stroop task. These relationships remained when variance contributed by general negative affect was removed. Findings provide preliminary evidence that fear of emotion may be related to emotional distress and physiological arousal, and that this relationship may exist beyond shared variance due to self-report response style and general negative affectivity. PMID- 17364649 TI - Psychometric properties of the Dutch version of the Automatic Thoughts Questionnaire - Positive (ATQ - P). AB - The role of positive cognitions in psychopathology is increasingly recognized. Several measures of this construct have been devised. The most well-known instrument to measure positive self-referent thoughts is the Automatic Thoughts Questionnaire - Positive (ATQ - P). The present study explored the psychometric properties of the Dutch version of this questionnaire. Data were derived from 257 bereaved adults. Confirmatory Factor Analysis showed that an oblique 5-factor model with items pertaining to Positive Daily Functioning, Positive Self Evaluation, Other's Evaluation of Self, Positive Future Expectations, and Positive Social Functioning fit the data well. This model was a slight modification of the 4-factor model originally proposed by the developers of the ATQ - P, in which items pertaining to Positive Social Functioning were part of the factor Positive Daily Functioning. The internal consistency and the short term temporal stability of the ATQ - P were found to be satisfactory. In addition, the 5 factors as well as the summed total score of the ATQ - P showed adequate discriminative, construct, divergent and convergent validity. In sum, the present study indicates that the Dutch ATQ - P is an effective measure of positive automatic cognitions. PMID- 17364650 TI - Working alliance for clients with social anxiety disorder: relationship with session helpfulness and within-session habituation. AB - It has been suggested that a strong working alliance encourages clients to take risks during therapy (Raue, Castonguay, & Goldfried, 1993). This encouragement may be important for clients who fear negative evaluations as they engage in risk taking elements of therapy. This study examined the relationship between working alliance, session helpfulness and measures of emotional processing in 18 clients undergoing cognitive behavior therapy (CBT) for social anxiety disorder. Results indicate a positive correlation between client-rated, but not observer-rated, working alliance and session helpfulness. Moderate levels of working alliance were associated with higher initial anxiety and deeper within-session habituation. Overall, a strong alliance was associated with clients engaging with the session and finding the session helpful. Implications for the use of CBT for social anxiety are discussed. PMID- 17364651 TI - Implicit associations and social anxiety. AB - The aim of this study was to test whether an Implicit Association Test (IAT) with self- and social anxiety-words is sensitive to differences in trait social anxiety, and to an experimental induction of social anxiety. This was performed in the context of a partial replication of a previous study, in which Mauss et al. (2004) compared high and low trait socially anxious individuals before and after a social anxiety induction (an impromptu speech). Mauss et al.'s findings were replicated; that is, (i) the social anxiety induction produced increases in self-rated anxiety, self-rated physiological responses, and actual physiological arousal; and (ii) higher trait social anxiety was associated with stronger self rated anxiety and stronger self-rated physiological responses, but not with stronger actual physiological responses. In addition, the results showed higher IAT social anxiety scores, both (i) as a result of the social anxiety induction, and (ii) as a function of self-reported trait social anxiety. It is suggested that the IAT may be a useful method for the experimental study of automatic evaluational thought patterns. PMID- 17364652 TI - Measuring fear of movement/(re)injury in chronic low back pain using implicit measures. AB - Fear of movement/(re)injury is assumed to contribute to the development and maintenance of chronic low back pain (CLBP) in a subgroup of patients. Studying fear of movement/(re)injury with implicit attitude measures, without the awareness of the patient, might be a valuable addition to self-report questionnaires. The aims of the current study were to investigate whether CLBP patients demonstrate more implicit fear of movement/(re)injury than healthy controls, and whether 2 implicit measures are related to each other, and to an explicit self-report measure of fear of movement/(re)injury. A group of 66 CLBP patients and 30 healthy controls took part in this study. In addition to self report questionnaires, fear of movement/(re)injury was implicitly assessed by the Extrinsic Affective Simon Task (EAST) and the Go-No-Go-Association Task (GNAT) that aimed to determine the association between back-stressing movements and the evaluation "threatening". On both implicit tasks it was found that neither CLBP patients nor healthy controls demonstrated implicit fear of movement/(re)injury, and that CLBP patients did not differ from healthy controls in their level of implicit fear of movement/(re)injury. In general, no associations were found between the EAST and the GNAT, or between implicitly measured and self-reported fear of movement/(re)injury. One major caveat in drawing inferences from these findings is the poor reliability of these implicit measures. Research towards the psychometric properties of these measures should first be expanded before modifying, and applying, them to more complex domains such as fear of movement/(re)injury. PMID- 17364654 TI - MRI image overlay: application to arthrography needle insertion. AB - Magnetic Resonance Imaging (MRI) offers great potential for planning, guiding, monitoring and controlling interventions. MR arthrography (MRAr) is the imaging gold standard for assessing small ligament and fibrocartilage injury in joints. In contemporary practice, MRAr consists of two consecutive sessions: (1) an interventional session where a needle is driven to the joint space and MR contrast is injected under fluoroscopy or CT guidance; and (2) a diagnostic MRI imaging session to visualize the distribution of contrast inside the joint space and evaluate the condition of the joint. Our approach to MRAr is to eliminate the separate radiologically guided needle insertion and contrast injection procedure by performing those tasks on conventional high-field closed MRI scanners. We propose a 2D augmented reality image overlay device to guide needle insertion procedures. This approach makes diagnostic high-field magnets available for interventions without a complex and expensive engineering entourage. In preclinical trials, needle insertions have been performed in the joints of porcine and human cadavers using MR image overlay guidance; in all cases, insertions successfully reached the joint space on the first attempt. PMID- 17364655 TI - Robot-assisted needle placement in open MRI: system architecture, integration and validation. AB - In prostate cancer treatment, there is a move toward targeted interventions for biopsy and therapy, which has precipitated the need for precise image-guided methods for needle placement. This paper describes an integrated system for planning and performing percutaneous procedures with robotic assistance under MRI guidance. A graphical planning interface allows the physician to specify the set of desired needle trajectories, based on anatomical structures and lesions observed in the patient's registered pre-operative and pre-procedural MR images, immediately prior to the intervention in an open-bore MRI scanner. All image space coordinates are automatically computed, and are used to position a needle guide by means of an MRI-compatible robotic manipulator, thus avoiding the limitations of the traditional fixed needle template. Automatic alignment of real time intra-operative images aids visualization of the needle as it is manually inserted through the guide. Results from in-scanner phantom experiments are provided. PMID- 17364656 TI - Seed localization and TRUS-fluoroscopy fusion for intraoperative prostate brachytherapy dosimetry. AB - OBJECTIVE: To develop and evaluate an integrated approach to intra-operative dosimetry for permanent prostate brachytherapy (PPB) by combining a fluoroscopy based seed localization routine with a transrectal ultrasound (TRUS)-to fluoroscopy fusion technique. MATERIALS AND METHODS: Three-dimensional seed coordinates are reconstructed based on the two-dimensional seed locations identified from three fluoroscopic images acquired at different angles. A seed based registration approach was examined in both simulation and phantom studies to register the seed locations identified from the fluoroscopic images to the TRUS images. Dose parameters were then evaluated and compared to CT-based dosimetry from a patient dataset. RESULTS: Less than 0.2% error in the D90 value was observed using the TRUS-fluoroscopy image-fusion-based method relative to the CT-based post-implantation dosimetry. In the phantom study, an average distance of 3 mm was observed between the seeds identified from TRUS and the reconstructed seeds at registration. Isodose contours were displayed superimposed on the TRUS images. CONCLUSIONS: Promising results were observed in this preliminary study of a TRUS-fluoroscopy fusion-based brachytherapy dosimetry analysis method, suggesting that the method is highly sensitive and calculates clinically relevant dosimetry, including the prostate D90. Further validation of the method is required for eventual clinical application. PMID- 17364657 TI - Tracking endoscopic instruments without a localizer: a shape-analysis-based approach. AB - We present an approach to localizing endoscopic instruments with respect to the camera position, based purely on processing of the endoscope image. No localizers are needed; the only requirement is a colored strip at the distal part of the instrument shaft to facilitate image segmentation. The method exploits perspective image analysis applied to the cylindrical shape of the instrument shaft, allowing measurement of the instrument position and orientation with five degrees of freedom. We describe the method theoretically, and experimentally derive calibration curves for tuning the parameters of the algorithm. Results show that the method can be used for applications where accuracy is not critical, such as workspace measurement, gesture analysis, augmented-reality guidance, telementoring, etc. If this method is used in combination with an endoscope tracker or a robotic camera holder, full localization with respect to the patient reference frame can be achieved. PMID- 17364658 TI - A topologically faithful, tissue-guided, spatially varying meshing strategy for computing patient-specific head models for endoscopic pituitary surgery simulation. AB - This paper presents a method for tessellating tissue boundaries and their interiors, given as input a map consisting of relevant tissue classes of the head, in order to produce anatomical models for finite-element-based simulation of endoscopic pituitary surgery. Our surface meshing method is based on the simplex model, which is initialized by duality from the topologically accurate results of the Marching Cubes algorithm, and which affords explicit control over mesh scale, while using tissue information to adhere to relevant boundaries. Our mesh scale strategy is spatially varying, based on the distance to a central point or linearized surgical path. The tetrahedralization stage also features a spatially varying mesh scale, consistent with that of the surface mesh. PMID- 17364659 TI - System for intraoperative evaluation of soft-tissue-generated forces during total hip arthroplasty by measurement of the pressure distribution in artificial joints. AB - A system for evaluating the soft-tissue-generated forces at the hip joint was developed. The system enabled measurement of contact pressure distribution at hip joint surfaces, as well as evaluation of the artificial hip joint condition during total hip arthroplasty (THA). First, a pressure sensor module that forms part of the artificial joint was constructed. Eight small pressure sensors were installed in the spherical head component of the ball-and-socket joint. Next, software for recording and visualizing the detected pressures at 1-millisecond intervals was developed. The pressure distribution was displayed in real time via 3D computer graphics on a monitor. The system enabled intuitive recognition of the direction of soft-tissue-generated forces and pressure distribution in three dimensions. Accuracy tests were conducted using a high-accuracy 6-degree-of freedom positioning device and digital force gauge. The error between the applied loads and measured forces was 3.42 +/- 3.26 N (mean +/- standard deviation) for each coordinate in 10 trials involving load application from 10 different directions. Next, a clinical evaluation was conducted during THA. The relative positions of the cup and stem component were measured using a surgical navigation system simultaneously with the pressure measurement. The system allowed real-time acquisition of information regarding the artificial hip joint, as well as comparison of the differences in the hip condition when several types of neck were used. Further improvements to the calibration method should enable more accurate measurements. We believe this system will be a useful tool for selecting an appropriate implant that fits a patient's hip joint or for estimating the risk of complications following surgery. PMID- 17364660 TI - Computer aided surgery system for shoulder prosthesis placement. AB - The aim of this research is to provide a light and easy-handling shoulder model for surgeons in order to ease the preoperative and peroperative work required when replacing the shoulder joint with a prosthesis. The digital mock-up of the shoulder is simplified according to the criteria of the surgeon, allowing easy manipulation of the model for a virtual operation. The model can be parameterized from X-rays or CT images. This paper describes the method used to obtain a virtual mock-up that is useful for preoperative simulation. Furthermore, it is shown that a real-time augmented reality system could be achieved for peroperative application. PMID- 17364661 TI - Proteins of insoluble matrix of avian (gallus gallus) eggshell. AB - The protein composition of the insoluble avian eggshell matrix was studied. The determination of these proteins insoluble in water (EDTA-insoluble) was carried out using enzymatic cleavage followed by a high-performance liquid chromatography mass spectrometry method. The influence of various enzymes on the protein splitting also was studied. The distribution of proteins depends on the type of layer (localization within the eggshell): ovocalyxin-32 was found mainly in the outer layer (the cuticle); ovocleidin-116 and 17 and ovocalyxin-36 were found throughout the whole eggshell, whereas ovalbumin was only found in the inner layer, the mammillary. The pigment (protoporphyrin IX) was mainly found in the cuticle and is incorporated into the protein network. PMID- 17364662 TI - Differentiation of tracheal basal cells to ciliated cells and tissue reconstruction on the synthesized basement membrane substratum in vitro. AB - Although lung epithelial cells directly attach to the basement membrane underneath in vivo, harvested epithelial cells are typically cultured on type I collagen gel (Col I-gel) in vitro. Recently we developed new culture substratum, designated as "synthesized Basement Membrane" (sBM), that has bared lamina densa on fibrillar collagen. To validate the usefulness of sBM substratum in airway tissue reconstitution in vitro, we cultured rat tracheal epithelial cells on sBM substratum and Col I-gel. When starting the air-liquid interface culture, most of the epithelial cells were squamous and positive for the basal cell marker cytokeratin 14 (CK14). After 14 days on sBM substratum, CK14-positive cells differentiated not only to Clara and mucous cells, but also to ciliated cells. Those differentiated cells formed pseudostratified-like epithelium and the remaining CK14-positive cells were polarized to the basal side. However, on Col I gel, the CK14-positive cells were still squamous and not polarized, and ciliated cells did not appear. In conclusion, we established a new culture model on sBM substratum in which basal cells could differentiate to ciliated cells. The application of sBM substratum is useful in the study of the airway epithelial cell differentiation in vitro. PMID- 17364663 TI - Alterations in the mechanical properties and composition of skin in human growth hormone transgenic mice. AB - Growth hormone is known to stimulate connective tissue, but the degree to which it influences skin biomechanical properties is unclear. This study tested the hypothesis that human growth hormone transgene expression changes the material properties and structural composition of adult mouse skin. Fracture toughness and elastic modulus were measured on freshly dissected dorsal skin and fixed samples were analyzed histologically. Transgenics had higher elastic moduli than their sex-matched non transgenic littermates, and male transgenics demonstrated increased fracture toughness. Male transgenics also had thicker skin than controls with a selectively increased dermis. In contrast, female transgenics had thinner skin than controls due to a reduced hypodermis. Biomechanical and histological variables were strongly correlated. Significant sex differences were present in nearly all comparisons indicating a dimorphic response to growth hormone in the skin. These data demonstrate that constant low-level growth hormone expression in marrow differentially affects skin layer thickness and concomitantly alters its biomechanical properties. PMID- 17364664 TI - Human articular cartilage proteoglycans are not undersulfated in osteoarthritis. AB - Chondroitin sulfate is the major constituent of cartilage. Inadequate sulfate availability results in the production of undersulfated proteoglycans. In osteoarthritis, there is a net loss of articular cartilage proteoglycans. Theoretically, it is possible that during the progress of disease undersulfated glycosaminoglycans are synthesized producing proteoglycans with poorer biological properties. In this study, we tested whether in early human osteoarthritic articular cartilage (Mankin's score of 2 and 3) or more advanced disease (Mankin's score over 3), there are proteoglycans that contain a higher relative amount of nonsulfated chondroitin disaccharide isomer in their chondroitin sulfate chains by analyzing the molar ratios of chondroitin sulfate disaccharide isoforms with fluorophore-assisted carbohydrate electrophoresis. Our results indicated that the nonsulfated disaccharide of chondroitin sulfate formed in average only 1-2% of the total chondroitin sulfate. More important, the molar ratio of nonsulfated disaccharide did not appear to be increased in the osteoarthritic articular cartilage. We conclude that undersulfation of articular cartilage proteoglycans is not present in the human osteoarthritic joint. PMID- 17364665 TI - Effects of unsaturated free fatty acids on adhesion and on gene expression of extracellular matrix macromolecules in human osteoblast-like cell cultures. AB - To investigate the possible role for unsaturated free fatty acids in osteoblast adhesion, the effects of two polyunsaturated fatty acids (PUFAs), arachidonic (AA) and eicosapentaenoic (EPA) acids, and of one monounsaturated fatty acid, oleic acid (OA), on adhesion to the substrate and on gene expression of three extracellular matrix macromolecules were investigated in an in vitro model system -cultured osteoblast-like human cells. AA, but neither EPA nor OA, diminished bone cell adhesion, whereas both EPA and OA, but not AA, increased gene expression of type I collagen and fibronectin via a transforming growth factor beta-independent mechanism. These results extend previous evidence for unsaturated fatty acids in bone cell metabolism. PMID- 17364666 TI - Amelogenin- and enamelysin (Mmp-20)-deficient mice display altered birefringence in the secretory-stage enamel organic extracellular matrix. AB - Dental enamel is the most mineralized tissue of vertebrate organisms. Enamel biosynthesis is initiated by the secretion, processing, and self-assembly of a complex mixture of proteins. The formation of an ordered enamel organic extracellular matrix (ECM) seems be a crucial step for the proper formation of mineral phase. Polarizing microscopy demonstrates that the ordered supramolecular structure of the secretory-stage enamel organic ECM is strongly birefringent. In the present work we analyzed the birefringence of secretory-stage enamel organic ECM in amelogenin (Amelx)- and enamelysin (Mmp20)-deficient mice. Female Amelx+/- animals showed significant reduction in optical retardation values when compared with the Amelx+/+ subgroup (p=0.0029). The secretory-stage enamel organic ECM of the Amelx-/- subgroup did not exhibit birefringence. The secretory-stage enamel organic ECM of Mmp20-/- mice showed a significant decrease in optical retardation as compared with Mmp20+/+ and Mmp20+/- mice (p=0.0000). Mmp20+/- and Mmp20+/+ mice exhibited similar birefringence (p=1.0000). The results presented here support growing evidence for the idea that the birefringence of secretory-stage enamel organic ECM is influenced by the ordered supramolecular organization of its components. PMID- 17364667 TI - Effects of celecoxib on migration, proliferation and collagen expression of tendon cells. AB - Sports-related tendinopathy is commonly treated with nonsteroidal anti inflammatory drugs including cyclooxygenase-2 inhibitor. Tendon healing requires migration of tendon cells to the repair site, followed by proliferation and synthesis of collagen. This study was designed to determine the effects of COX-2 inhibitor (celecoxib) on the migration, proliferation, and types I and III collagen expression of tendon cells intrinsic to rat Achilles tendon. Using cultured tendon cells, cell migration and proliferation were evaluated by transwell filter migration assay and by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) assay, respectively. The mRNA expression of alpha1(I) procollagen and alpha1(III) procollagen were determined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of types I and III collagen were determined by immunocytochemistry. Dose-dependent celecoxib inhibition was demonstrated for migration of tendon cells through the transwell filter migration assay (p=0.002). Dose-dependent celecoxib inhibition of tendon cell proliferation also was demonstrated by MTT assay (p=0.004). However, both RT-PCR and immunocytochemical staining revealed that mRNA and protein expression of types I and III collagen remained constant after celecoxib treatment. In conclusion, celecoxib inhibits tendon cell migration and proliferation. However, the expression of types I and III collagen remained unchanged. PMID- 17364668 TI - A novel approach to the development of benchmarking parameters for characterizing cartilage health. AB - This article outlines the motivation and preliminary investigations into a novel method of characterizing cartilage health for potential in vivo application. Current in vivo indentation techniques, which primarily rely on stiffness measurements based on axial data, are unable to adequately distinguish between healthy and degraded tissue. The present in vitro study investigates the effects of controlled artificial degradation on the effective surface stretch, comparing the results with those obtained from the peripheral cartilage surrounding focal osteoarthritis. Results suggest that this technique is highly sensitive, showing a maximum range of 14% effective surface stretch in a normal joint compared with 42% for axial strain measurements. We further demonstrated that the technique can discriminate between degenerative changes and the intrinsic variations in cartilage properties across the normal joint. From these investigations we propose that the relationship between indentation and the in-plane strain field under the indenter can better distinguish degraded tissue than the currently used stiffness techniques. PMID- 17364669 TI - JSCTR-CTR Commentary byToshihiko Hayashi. PMID- 17364670 TI - Raising awareness of COPD: a call to action by the readers of COPD. PMID- 17364671 TI - Can we predict depression in COPD? PMID- 17364672 TI - Decline in FEV1 in relation to incident chronic obstructive pulmonary disease in a cohort with respiratory symptoms. AB - Data on the relationship between decline in lung function and development of COPD are sparse. We assessed the decline in FEV1 during 10 years among subjects with respiratory symptoms by two different methods and evaluated risk factors for decline and its relation to incident Chronic Obstructive Pulmonary Disease, COPD. A cross-sectional postal questionnaire was in 1986 sent to 6610 subjects of three age strata. All subjects reporting respiratory symptoms were invited to a structured interview and spirometry. A follow-up survey was performed 10 years later, and totally 1109 subjects performed spirometry in both 1986 and 1996. COPD was defined according to the ATS/ERS standards (FEV1/FVC < or =0.70). The decline in FEV1 was 39 ml/year in men vs. 28 ml/year in women, p = < 0.001 (-1.53 vs. 0.12 change in percent of predicted normal value over 10 years (pp), p = 0.023), among smokers 39 vs. non-smokers 28 ml/year, p < 0.001 (-3.30 vs. 0.69 pp, p < 0.001), in subjects with chronic productive cough 36 vs. not 32 ml/year, p = 0.044 (-2.00 vs. -0.02 pp, p = 0.002). Incident cases of moderate COPD (n = 83) had a decline of 62 ml/year (-12.6 pp) and 22.9% of them had a decline > 90 ml/year (-27.8 pp over 10 years). Gender-specific analysis revealed that smoking was a stronger risk factor in women than in men, while higher age was a significant risk factor in men only. In conclusion, decline in FEV1 was associated with age, smoking, and chronic productive cough, but the risk factor pattern was gender-dependent. Among incident cases of COPD the decline was steeper and close to a quarter had a rapid decline. PMID- 17364673 TI - Mortality and functional performance in severe emphysema after lung volume reduction or transplant. AB - The purpose of this endeavor is to compare the morbidity, mortality and costs of LVRS versus transplantation in severe emphysema. This was a retrospective review of severe emphysema patients who received LVRS (n = 70) from 1994-1999, or transplant (n = 87) from 1994-2004. Change in functional status was calculated by the change in modified BODE (mBODE) score. Financial data included physician, hospital and medication costs. Preoperatively, there was no significant difference between the transplant and LVRS groups (mean +/- SD) in age (57.7 +/- 5.7 vs. 59.1 +/- 8.3 years), BMI, Borg dyspnea score, 6-minute walk distance or mBODE (10.4 +/- 2.6 vs. 9.6 +/- 2.7, p = 0.4). Preoperatively, FEV1% (23.6 +/- 8.5 vs. 31.9 +/- 17.7, p = 0.008) was significantly lower in the transplant group. One year post-operatively, transplantation patients had a significantly greater improvement in mBODE (-5.7 vs. -2.0, p = 0.0004), FEV1% (43.4 vs. 2.2%, p = 0.0004) and Borg score (-3.0 vs. -1.4, p = 0.04). Transplantation patients had lower long-term survival compared to LVRS patients (p = 0.01). The only variable that affected survival was type of surgery favoring LVRS (hazard ratio 1.7, 95% confidence limits 1.05-2.77). During a mean follow-up of 2.4 +/- 2.5 years after transplant and 5.0 +/- 3.1 years after LVRS, transplantation mean total costs were greater ($381,732 vs. $140,637, p < 0.0001). Transplantation patients spent more time in the hospital (74.3 +/- 81.3 vs. 39.5 +/- 66.7 days, p = 0.009) and had more outpatient visits (29.9 +/- 28.8 vs. 12.3 +/- 12.6 visits, p < 0.0001). In patients who survive over 1 year, transplantation provides a higher level of functional status and a greater improvement in airflow obstruction, dyspnea, exercise tolerance, and mBODE score, but costs more and carries greater mortality. PMID- 17364674 TI - Predictors of depressive symptoms in patients with COPD and health impact. AB - While depression is a common co-morbid condition among patients with COPD, little is known about predictors or health impact of depression among these patients. To address these gaps in knowledge we conducted a cross-sectional survey of 207 patients with COPD cared for in a network of primary care clinics affiliated with an urban academic health center. A standardized questionnaire was used to measure demographic characteristics, smoking status, co-morbid medical conditions, current medications, self-efficacy, social support, illness intrusiveness, and self-reported health care utilization during the previous 6 months. Depressive symptoms were assessed using the Centers for Epidemiologic Studies-Depression scale. Overall, the prevalence of moderate to high levels of depressive symptoms was 60.4%. In a multivariate analysis independent predictors of depressive symptoms were being a former smoker (OR = 0.41 (95% CI 0.19-0.89)), higher self efficacy (OR = 0.42 (0.28-0.64)), higher social support (OR = 0.72 (0.52-0.99)), and higher perceived illness intrusiveness (OR = 1.05 (1.02-1.08)). Depressive symptoms were associated with increased physician visits, emergency room visits, and hospitalizations for lung disease. In conclusion, depressive symptoms are common among patients with COPD and associated with an increase in healthcare utilization. These findings suggest that the identification of risk factors for depressive symptoms (e.g., continued smoking) may increase detection and improve management of depression and health outcomes among patients with COPD. PMID- 17364675 TI - Physiologic variables and functional status independently predict COPD hospitalizations and emergency department visits in patients with severe COPD. AB - Using clinical and claims records from the National Emphysema Treatment Trial, we sought to identify factors that accurately predicted COPD exacerbations. This prospective cohort study consisted of subjects with severe emphysema randomized to medical therapy. Exacerbations were defined as a hospitalization or emergency department visit for COPD. Patient characteristics obtained before randomization were entered as independent variables in multivariable logistic regression models to estimate the risk of exacerbation. Discrimination was determined using the area under the receiver operator characteristic curve (AUC). Baseline measures included demographics, body mass index, pulmonary function, arterial blood gases, radiology studies, dyspnea (Shortness of Breath Questionnaire - SOBQ), health related quality of life (St. George's Respiratory Questionnaire - SGRQ), 6-minute walk, exercise capacity, medication use, prior exacerbations and co-morbidity. In 610 participants, 26.6% had a COPD exacerbation over 1-year follow-up. In a model incorporating spirometry, PaO2, dyspnea, prior exacerbations and co-morbidity, a 5-point decrement in percent predicted FEV1 (OR 1.16, 95% CI 1.00-1.34) and a 5 point worsening in SOBQ (OR 1.08, 1.02-1.14) independently predicted exacerbations (AUC for full model 0.68). Combining physiologic variables, dyspnea, prior exacerbations and co-morbidity may be useful in identifying patients at high risk for COPD exacerbations. PMID- 17364676 TI - COPD: magnesium in the plasma and polymorphonuclear cells of patients during a stable phase. AB - Magnesium is one of the most important factors for regulation of inflammatory response as well as muscle function, and COPD is a multicomponent disease characterized by abnormal inflammatory response of the lungs with systemic muscle dysfunction. Because polymorphonuclear (PMN) cells are significantly represented in the pathogenesis of COPD, concentrations of total (tMg) and ionised magnesium (iMg) were determined in plasma and isolated PMN cells in 46 patients in stable phase of COPD (past smokers, current smokers, and non-smokers), 24 healthy smokers and 37 healthy non-smokers. In the same samples concentrations of total (tCa) and ionised calcium (iCa) were determined, due to the antagonism of magnesium towards calcium. We found decreased biological active iMg in PMN compared to the group of healthy non-smokers (5.42, 1.98-17.31 micromol/10(9) cells vs. 7.50, 3.27-15.15 micromol/10(9) cells, p < 0.05). In the plasma and isolated PMN of the patients the ratio of total calcium/total magnesium (tCa/tMg) was significantly increased (2.89, 2.15-3.86 and 1.19, 0.07-9.87) compared to the group of healthy non-smokers (2.65, 2.19-3.44 and 0.67, 0.14-2.40, p < 0.05) and to the group of healthy smokers (2.58, 2.26-3.24 and 0.66, 0.14-2.85, p < 0.05). In the group of patients the concentration of tCa was significantly increased in all samples compared to the healthy group of non-smokers and healthy smokers. The results of univariant logistic regression analysis for smoking, concentration of tCa and ratio of tCa/tMg in PMN showed high odds ratio for COPD status. These results raise a possibility that intracellular polymorphonuclear value of magnesium could be a distinctive marker for COPD risk disclosure among smokers. PMID- 17364677 TI - Lesser used tests of pulmonary function: compliance, resistance and dead space. AB - The measurements of lung compliance, airway resistance and respiratory dead space as clinical tests have gradually fallen into disuse as the standard pulmonary function testing procedures; spirometry, lung volume and diffusing capacity measurement, followed, if necessary, by imaging have become the norm for diagnosis of COPD and other lung diseases. To have a real understanding of what spirometry and lung volume tests measure requires some knowledge of compliance and airway resistance. The respiratory dead space is an important global indicator of ventilation/perfusion relationships that remains of interest in the early detection of pulmonary emboli. There are other situations as well where it is clinically useful to perform the measurements described here, so these techniques, although generally set aside from the commonly used tests, should not be forgotten. PMID- 17364678 TI - Proton MRI in COPD. PMID- 17364679 TI - COPD--the primary care perspective: addressing epidemiology, pathology, diagnosis, treatment of smoking's multiple morbidities and the patient's perspective. PMID- 17364682 TI - GABAA receptors: properties and trafficking. AB - Fast synaptic inhibition in the brain and spinal cord is mediated largely by ionotropic gamma-aminobutyric acid (GABA) receptors. GABAA receptors play a key role in controlling neuronal activity; thus modulating their function will have important consequences for neuronal excitation. GABAA receptors are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are involved in a number of CNS diseases, including sleep disturbances, anxiety, premenstrual syndrome, alcoholism, muscle spasms, Alzheimer's disease, chronic pain, schizophrenia, bipolar affective disorders, and epilepsy. This review focuses on the functional and pharmacological properties of GABAA receptors and trafficking as an essential mechanism underlying the dynamic regulation of synaptic strength. PMID- 17364683 TI - A conspicuous connection: structure defines function for the phosphatidylinositol phosphate kinase family. AB - The phosphatidylinositol phosphate (PIP) kinases are a unique family of enzymes that generate an assortment of lipid messengers, including the pivotal second messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2). While members of the PIP kinase family function by catalyzing a similar phosphorylation reaction, the specificity loop of each PIP kinase subfamily determines substrate preference and partially influences distinct subcellular targeting. Specific protein-protein interactions that are unique to particular isoforms or splice variants play a key role in targeting PIP kinases to appropriate subcellular compartments to facilitate the localized generation of PI4,5P2 proximal to effectors, a mechanism key for the function of PI4,5P2 as a second messenger. This review documents the discovery of the PIP kinases and their signaling products, and summarizes our current understanding of the mechanisms underlying the localized generation of PI4,5P2 by PIP kinases for the regulation of cellular events including actin cytoskeleton dynamics, vesicular trafficking, cell migration, and an assortment of nuclear events. PMID- 17364684 TI - Regulation of bacterial RecA protein function. AB - The RecA protein is a recombinase functioning in recombinational DNA repair in bacteria. RecA is regulated at many levels. The expression of the recA gene is regulated within the SOS response. The activity of the RecA protein itself is autoregulated by its own C-terminus. RecA is also regulated by the action of other proteins. To date, these include the RecF, RecO, RecR, DinI, RecX, RdgC, PsiB, and UvrD proteins. The SSB protein also indirectly affects RecA function by competing for ssDNA binding sites. The RecO and RecR, and possibly the RecF proteins, all facilitate RecA loading onto SSB-coated ssDNA. The RecX protein blocks RecA filament extension, and may have other effects on RecA activity. The DinI protein stabilizes RecA filaments. The RdgC protein binds to dsDNA and blocks RecA access to dsDNA. The PsiB protein, encoded by F plasmids, is uncharacterized, but may inhibit RecA in some manner. The UvrD helicase removes RecA filaments from RecA. All of these proteins function in a network that determines where and how RecA functions. Additional regulatory proteins may remain to be discovered. The elaborate regulatory pattern is likely to be reprised for RecA homologues in archaeans and eukaryotes. PMID- 17364686 TI - Microbial biosynthesis of polyglutamic acid biopolymer and applications in the biopharmaceutical, biomedical and food industries. AB - This review article provides an updated critical literature review on the production and applications of Polyglutamic Acid (PGA). alpha-PGA is synthesized chemically, whereas gamma-PGA can be produced by a number of microbial species, most prominently various Bacilli. Great insight into the microbial formation of gamma-PGA has been gained thanks to the development of molecular biological techniques. Moreover, there is a great variety of applications for both isoforms of PGA, many of which have not been discovered until recently. These applications include: wastewater treatment, food products, drug delivery, medical adhesives, vaccines, PGA nanoparticles for on-site drug release in cancer chemotherapy, and tissue engineering. PMID- 17364687 TI - Bacterial chitinases: properties and potential. AB - Chitin is among the most abundant biomass present on Earth. Chitinase plays an important role in the decomposition of chitin and potentially in the utilization of chitin as a renewable resource. During the previous decade, chitinases have received increased attention because of their wide range of applications. Chito oligomers produced by enzymatic hydrolysis of chitin have been of interest in recent years due to their broad applications in medical, agricultural, and industrial applications, including antibacterial, antifungal, hypocholesterolemic, and antihypertensive activity, and as a food quality enhancer. Microorganisms, particularly bacteria, form one of the major sources of chitinase. In this article, we have reviewed some of the chitinases produced by bacterial systems that have gained worldwide research interest for their diverse properties and potential industrial uses. PMID- 17364688 TI - Hairy root culture for mass-production of high-value secondary metabolites. AB - Plant cell cultivations are being considered as an alternative to agricultural processes for producing valuable phytochemicals. Since many of these products (secondary metabolites) are obtained by direct extraction from plants grown in natural habitat, several factors can alter their yield. The use of plant cell cultures has overcome several inconveniences for the production of these secondary metabolites. Organized cultures, and especially root cultures, can make a significant contribution in the production of secondary metabolites. Most of the research efforts that use differentiated cultures instead of cell suspension cultures have focused on transformed (hairy) roots. Agrobacterium rhizogenes causes hairy root disease in plants. The neoplastic (cancerous) roots produced by A. rhizogenes infection are characterized by high growth rate, genetic stability and growth in hormone free media. These genetically transformed root cultures can produce levels of secondary metabolites comparable to that of intact plants. Hairy root cultures offer promise for high production and productivity of valuable secondary metabolites (used as pharmaceuticals, pigments and flavors) in many plants. The main constraint for commercial exploitation of hairy root cultivations is the development and scaling up of appropriate reactor vessels (bioreactors) that permit the growth of interconnected tissues normally unevenly distributed throughout the vessel. Emphasis has focused on designing appropriate bioreactors suitable to culture the delicate and sensitive plant hairy roots. Recent reactors used for mass production of hairy roots can roughly be divided as liquid-phase, gas-phase, or hybrid reactors. The present review highlights the nature, applications, perspectives and scale up of hairy root cultures for the production of valuable secondary metabolites. PMID- 17364689 TI - L-asparaginase: a promising chemotherapeutic agent. AB - This article comprises detailed information about L-asparaginase, encompassing topics such as microbial and plant sources of L-asparaginase, treatment with L asparaginase, mechanism of action of L-asparaginase, production, purification, properties, expression and characteristics of l-asparaginase along with information about studies on the structure of L-asparaginase. Although L asparaginase has been reviewed by Savitri and Azmi (2003), our effort has been to include recent and updated information about the enzyme covering new aspects such as structural modification and immobilization of L-asparaginase, recombinant L asparaginase, resistance to L-asparaginase, methods of assay of L-asparagine and L-asparaginase activity using the biosensor approach, L-asparaginase activity in soil and the factors affecting it. Also, side-effects of L-asparaginase treatment in acute lymphoblastic leukemia (ALL) have been discussed in the current review. L-asparaginase has been and is still one of the most widely studied therapeutic enzymes by researchers and scientists worldwide. PMID- 17364690 TI - The role of von Willebrand factor in hemorrhagic and thrombotic disorders. AB - von Willebrand factor (VWF) is a multimeric plasma protein that mediates platelet adhesion as well as platelet aggregation at sites of vascular injury and acts as a carrier of factor VIII. Although acquired or inherited VWF deficiency is associated with a bleeding tendency, there is increasing evidence that VWF has a pivotal role in thrombogenesis. In fact, while the presence in the plasma of unusually large VWF multimers, due to a congenital or acquired deficiency of a VWF-cleaving metalloprotease, has been implicated in the pathogenesis of thrombotic thrombocytopenic purpura, high plasma levels of VWF have been associated with an increased risk of both arterial and venous thrombosis. The role of VWF in normal and pathological hemostasis is discussed in this review, and important advances in the pathophysiology, diagnosis, and treatment of VWF associated disorders are also described. PMID- 17364691 TI - Tumor markers in biological fluids associated with pregnancy. AB - Proteins that are expressed by both malignant and healthy fetal tissues are recognized as oncofetal. These antigens are associated with cell proliferation and differentiation and are produced in high concentrations in pregnancy and malignancy. Their biological role in malignancy is the suppression of the host's immune system, while in pregnancy they affect the maternal immune response, generating maternal tolerance toward the embryo. This review describes the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell carcinoma antigen (SCC), cancer antigen 15-3 (CA 15-3), mucin-like carcinoma-associated antigen (MCA), tissue polypeptide-specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), and prostate-specific antigen (PSA) in maternal serum (MS), umbilical cord serum (UC), and amniotic fluid (AF) and outlines their roles in the assessment of pregnancy and malignancy. All antigens studied, except CA 15-3, are oncofetal. The presence of considerable concentrations of AFP, hCG, CEA, CA125, SCC, MCA, TPS, CA 19-9, and PSA in AF during pregnancy may be attributed to their involvement in biological functions associated with fetal development, differentiation, and maturation. MS CEA, CA 15-3, and CA 19-9, in contrast to all the others, are not influenced significantly by pregnancy and thus remain reliable tumor markers in monitoring malignancy in pregnant patients. PMID- 17364692 TI - Tumor-associated proteolytic factors uPA and PAI-1: critical appraisal of their clinical relevance in breast cancer and their integration into decision-support algorithms. AB - This review considers the past, present, and projected future clinical relevance of the serine protease urokinase-type plasminogen activator (uPA), and its inhibitor, plasminogen activator inhibitor-type 1 (PAI-1), in breast cancer. These factors play a key role in tumor invasion and metastasis in many cancers. In primary breast cancer, their prognostic and predictive impact has been validated at the highest level of evidence by a multicenter therapy trial (Chemo N0) and a large European Organisation for Research and Treatment Cancer-Receptor and Biomarker Group EORTC RBG pooled analysis (n = 8377). The greatest clinical use is in node-negative breast cancer, where the test can avoid over-treatment by adjuvant chemotherapy in patients with non-aggressive disease. In intermediate risk patients as defined by the international St. Gallen consensus, it can be used to identify patients who should receive chemotherapy because their tumor is more aggressive than classical pathological factors would suggest. Gene expression signatures are already being used in clinical trials to define the population of patients with breast cancer who should receive chemotherapy. The decision for treatment ignores the highly validated information that could be provided by uPA/PAI-1. A current and future challenge is to integrate the information provided by tumor biological factors, particularly uPA/PAI-1, into refined risk assessment and decision support algorithms incorporating gene expression signatures. This article describes a paradigm ("marker fusion") for doing so and a bioinformatics approach based on this paradigm. This concept could be useful in assessing and maximizing the performance of risk assessment and the quality of therapeutic indications. PMID- 17364693 TI - Fruit ripening phenomena--an overview. AB - Fruits constitute a commercially important and nutritionally indispensable food commodity. Being a part of a balanced diet, fruits play a vital role in human nutrition by supplying the necessary growth regulating factors essential for maintaining normal health. Fruits are widely distributed in nature. One of the limiting factors that influence their economic value is the relatively short ripening period and reduced post-harvest life. Fruit ripening is a highly coordinated, genetically programmed, and an irreversible phenomenon involving a series of physiological, biochemical, and organoleptic changes, that finally leads to the development of a soft edible ripe fruit with desirable quality attributes. Excessive textural softening during ripening leads to adverse effects/spoilage upon storage. Carbohydrates play a major role in the ripening process, by way of depolymerization leading to decreased molecular size with concomitant increase in the levels of ripening inducing specific enzymes, whose target differ from fruit to fruit. The major classes of cell wall polysaccharides that undergo modifications during ripening are starch, pectins, cellulose, and hemicelluloses. Pectins are the common and major components of primary cell wall and middle lamella, contributing to the texture and quality of fruits. Their degradation during ripening seems to be responsible for tissue softening of a number of fruits. Structurally pectins are a diverse group of heteropolysaccharides containing partially methylated D-galacturonic acid residues with side chain appendages of several neutral polysaccharides. The degree of polymerization/esterification and the proportion of neutral sugar residues/side chains are the principal factors contributing to their (micro-) heterogeneity. Pectin degrading enzymes such as polygalacturonase, pectin methyl esterase, lyase, and rhamnogalacturonase are the most implicated in fruit-tissue softening. Recent advances in molecular biology have provided a better understanding of the biochemistry of fruit ripening as well as providing a hand for genetic manipulation of the entire ripening process. It is desirable that significant breakthroughs in such related areas will come forth in the near future, leading to considerable societal benefits. PMID- 17364694 TI - DNA damage, a biomarker of carcinogenesis: its measurement and modulation by diet and environment. AB - Free radicals and other reactive oxygen or nitrogen species are constantly generated in vivo and can cause oxidative damage to DNA. This damage has been implicated to be important in many diseases, including cancer. The assessment of damage in various biological matrices, such as tissues, cells, and urine, is vital to understanding this role and subsequently devising intervention strategies. During the last 20 years, many analytical techniques have been developed to monitor oxidative DNA base damage. High-performance liquid chromatography-electrochemical detection and gas chromatography-mass spectrometry are the two pioneering contributions to the field. Currently, the arsenal of methods available include the promising high-performance liquid chromatography tandem mass spectrometry technique, capillary electrophoresis, 32P-postlabeling, antibody-base immunoassays, and assays involving the use of DNA repair glycosylases such as the comet assay. The objective of this review is to discuss the biological significance of oxidative DNA damage, evaluate the effectiveness of several techniques for measurement of oxidative DNA damage in various biological samples and review current research on factors (dietary and non dietary) that influence DNA oxidative damage using these techniques. PMID- 17364695 TI - An impression of coffee carbohydrates. AB - Coffee is one of the most popular beverages in the world. It is consumed for its refreshing and stimulating properties. Carbohydrates are the major constituents of coffee beans and serve various functions like binding of aroma, stabilization of foam, formation of sedimentation, and increased viscosity of the extract. The principal low molecular weight carbohydrate is sucrose and no evidence of other simple oligosaccharides has been found. Polysaccharide fraction from green coffee is dominated by arabinogalactan, galactomannan, and cellulose. The polysaccharide content is reduced during roasting due to degradation to low molecular weight carbohydrates (viz., mono and oligosaccharide) and become more extractable. Various methods that can be employed to extract the carbohydrate from roasted coffee are sequential extraction, acid hydroloysis, hot water extraction, enzymatic extraction etc. Carbohydrates from coffee can be quantitatively determined by liquid chromatography, high performance anion exchange chromatography, size exclusion chromatography, and high performance liquid chromatography. Besides improving the organoleptic quality of the coffee beverage, carbohydrates also possess various biological activities such as lowering colon cancer risk. Besides their sheer mass, a variety of evidences testify to the important contribution that the polysaccharide content makes to the character of the final brew. Although a number of chemical and enzymatic methods have been devised to isolate and quantify the carbohydrates of R&G coffee, till date hot water extraction is the only method which can be accepted as a most feasible process and hence, there is wide scope of further research for the efficient and economically viable technology for extraction of carbohydrates from coffee. PMID- 17364696 TI - Opportunities and challenges in high pressure processing of foods. AB - Consumers increasingly demand convenience foods of the highest quality in terms of natural flavor and taste, and which are free from additives and preservatives. This demand has triggered the need for the development of a number of nonthermal approaches to food processing, of which high-pressure technology has proven to be very valuable. A number of recent publications have demonstrated novel and diverse uses of this technology. Its novel features, which include destruction of microorganisms at room temperature or lower, have made the technology commercially attractive. Enzymes and even spore forming bacteria can be inactivated by the application of pressure-thermal combinations, This review aims to identify the opportunities and challenges associated with this technology. In addition to discussing the effects of high pressure on food components, this review covers the combined effects of high pressure processing with: gamma irradiation, alternating current, ultrasound, and carbon dioxide or anti microbial treatment. Further, the applications of this technology in various sectors - fruits and vegetables, dairy, and meat processing - have been dealt with extensively. The integration of high-pressure with other matured processing operations such as blanching, dehydration, osmotic dehydration, rehydration, frying, freezing / thawing and solid-liquid extraction has been shown to open up new processing options. The key challenges identified include: heat transfer problems and resulting non-uniformity in processing, obtaining reliable and reproducible data for process validation, lack of detailed knowledge about the interaction between high pressure, and a number of food constituents, packaging and statutory issues. PMID- 17364697 TI - Applications of artificial neural networks (ANNs) in food science. AB - Artificial neural networks (ANNs) have been applied in almost every aspect of food science over the past two decades, although most applications are in the development stage. ANNs are useful tools for food safety and quality analyses, which include modeling of microbial growth and from this predicting food safety, interpreting spectroscopic data, and predicting physical, chemical, functional and sensory properties of various food products during processing and distribution. ANNs hold a great deal of promise for modeling complex tasks in process control and simulation and in applications of machine perception including machine vision and electronic nose for food safety and quality control. This review discusses the basic theory of the ANN technology and its applications in food science, providing food scientists and the research community an overview of the current research and future trend of the applications of ANN technology in the field. PMID- 17364698 TI - Allergenicity of soybean: new developments in identification of allergenic proteins, cross-reactivities and hypoallergenization technologies. AB - Soybean is considered one of the "big eight" foods that are believed to be responsible for 90% of all allergenic reactions. Soy allergy is of particular importance, because soybeans are widely used in processed foods and, therefore, represent a particularly insidious source of hidden allergens. Although significant advances have been made in the identification and characterization of soybean allergens, scientists are not completely certain about which proteins in soy cause allergic reactions. At least 16 allergens have been identified. Most of them, as with other plant food allergens, have a metabolic, storage, or protective function. These allergens belong to protein families which have conserved structural features in relation with their biological activity, which explains the wide immunochemical cross-recognition observed among members of the legume family. Detailed analysis of the structure-allergenicity relationships has been hampered by the complexity and heterogeneity of soybean proteins. A variety of technological approaches have been attempted to decrease soybean allergenicity. This paper provides a comprehensive review of the current body of knowledge on the identification and characterization of soybean allergens, as well as an update on current hypoallergenization techniques. PMID- 17364699 TI - A new approach to saffron aroma. AB - The aroma of saffron has received much attention from scientists in recent years, not only for the compounds that make it up, but also for its glycosidic precursors. Despite it all, the volatile generation mechanisms of the spice are almost completely unknown. Only the generation of safranal, the major compound, from picrocrocin has been established. The great effort carried out to detect and identify the volatile compounds of saffron has not been enough to clarify which compounds are responsible for saffron aroma. In general, scientists has devoted little attention to the sample analyzed, taking for granted that all saffron is the same, something that makes it difficult to establish a comparison between the results obtained by the different authors, to the point that saffron aroma has not been defined yet. It must be clarified whether saffron aroma is what the consumer perceives via nasally when a container of the spice is uncovered, or whether on the contrary, it is the aroma conferred to food, normally after a thermal cooking process, and perceived retronasally. After an extensive bibliographic research, simple assays are suggested to understand what could be considered as saffron aroma, results that may help to delimit the research for future studies. PMID- 17364700 TI - Processing effects for safety and quality in some non-predominant food technologies. AB - Food functionality can be related to nutrient and non-nutrient compounds. Some foods are fortified with various nutrients whereas others are manipulated using their physicochemical properties in order to make them "functional." Texture, color, taste, odor, and other physicochemical properties may affect the overall quality and, hence, acceptance of food products. Since food safety is also an important factor to be considered in food processing, preservation methods are selected taking into account the best compromise between microbial inactivation and preservation of quality attributes. Instrumental and sensory methods, as well as a match between them, are studied and perfected in order to verify how well a specific type of food has been processed to make it "functional" in sensory terms. PMID- 17364701 TI - A study of antioxidant properties of some varieties of grapes (Vitis vinifera L.). AB - Grapes (Vitis vinifera L.) are a major fruit crop in the world. Grapes seem to confer health benefits due to their antioxidant activity. We have evaluated the antioxidant potential of 11 grapes varieties from India and nearby Asian countries. The assays employed involve different levels of antioxidant action like ferric reducing antioxidant power, radical scavenging by 1,1-diphenyl-2 picrylhydrazyl, ferrylmyoglobin/2,2'-azobis-3-ethylbenzthiazoline-6-sulfonic acid, oxygen radical absorbance capacity (ORAC), and inhibition of lipid peroxidation. The total phenolic and flavonoids contents were also estimated. Our study indicates that cv. Mango is the most potent followed by Sharad Seedless. Ethanolic extracts were found to be more effective than aqueous extracts. Cv. Sharad Seedless, Mango, and Manikchaman also had high ORAC values. Their HPLC analysis showed the presence of various antioxidant polyphenols. In conclusion our studies identified some varieties of grapes with high antioxidant activities and showed that their high antioxidant potential may be due to their phenolic and flavonoid contents. PMID- 17364702 TI - History and genesis of the detailed review of thyroid hormone disruption assays. AB - This issue presents the detailed review paper (DRP) on thyroid hormone disruption assays that was prepared for the Organization for Economic Cooperation and Development (OECD) and that exists as an OECD monograph. However, this document is now available here in one issue of Critical Reviews in Toxicology as a series of published articles. The original document has been modified in several ways. First, an overview (now article 2) was added to discuss how new data and new directions for thyroid research will play an important role in shaping thyroid assays as they evolve. Second, each of the original chapters of the thyroid DRP have been separated into individual papers. The appendices of the original DRP were removed and will be merged and published separately. PMID- 17364703 TI - Integrating basic research on thyroid hormone action into screening and testing programs for thyroid disruptors. AB - Thyroid hormone signaling is highly conserved among all the vertebrates, and appears to be present in some invertebrates. Both the components that comprise the system and its general role in development and physiology are evolutionarily conserved, although specific events regulated by thyroid hormones, such as amphibian metamorphosis, may differ among taxonomic groups. The articles in this issue review the thyroid systems of mammals (specifically humans and rodents), fish, amphibians, and birds, and the states of the assays and endpoints used to detect disruption of the thyroid system within a toxicological paradigm. It must be noted that while reptiles represent an enormously important group, they were excluded because there was not enough information in the literature on thyroid toxicology in reptiles at the time that this series of reviews was drafted. Each review highlights the best assays for current regulatory use and those that may be considered for development for future use and research. However, it is important to remember that thyroid research is moving ahead at a fast pace. New thyroid research will impact the design of future thyroid assays used for the detection of thyroid system disruption in ways that may not be anticipated at the time of this writing. Several new areas of exploration are discussed that reveal potential sites of disruption in the thyroid system, including (1) the importance of the neural drive for TSH upregulation, (2) thyroid hormone transport, including cellular transporters like monocarboxylate anion transporter 8 (MCT8) that can regulate thyroid hormone action at the cellular level, and thyroid hormone-binding proteins in the serum that have been shown to differentially bind to environmental chemicals (e.g., certain PCB congeners), and (3) the deiodinases as a target for disruption of thyroid hormone activity in the peripheral thyroid system. The review papers in this issue represent the current state of thyroid assays and endpoints for detection of chemicals that disrupt the thyroid system. PMID- 17364704 TI - General background on the hypothalamic-pituitary-thyroid (HPT) axis. AB - This article reviews the thyroid system, mainly from a mammalian standpoint. However, the thyroid system is highly conserved among vertebrate species, so the general information on thyroid hormone production and feedback through the hypothalamic-pituitary-thyroid (HPT) axis should be considered for all vertebrates, while species-specific differences are highlighted in the individual articles. This background article begins by outlining the HPT axis with its components and functions. For example, it describes the thyroid gland, its structure and development, how thyroid hormones are synthesized and regulated, the role of iodine in thyroid hormone synthesis, and finally how the thyroid hormones are released from the thyroid gland. It then progresses to detail areas within the thyroid system where disruption could occur or is already known to occur. It describes how thyroid hormone is transported in the serum and into the tissues on a cellular level, and how thyroid hormone is metabolized. There is an in-depth description of the alpha and beta thyroid hormone receptors and their functions, including how they are regulated, and what has been learned from the receptor knockout mouse models. The nongenomic actions of thyroid hormone are also described, such as in glucose uptake, mitochondrial effects, and its role in actin polymerization and vesicular recycling. The article discusses the concept of compensation within the HPT axis and how this fits into the paradigms that exist in thyroid toxicology/endocrinology. There is a section on thyroid hormone and its role in mammalian development: specifically, how it affects brain development when there is disruption to the maternal, the fetal, the newborn (congenital), or the infant thyroid system. Thyroid function during pregnancy is critical to normal development of the fetus, and several spontaneous mutant mouse lines are described that provide research tools to understand the mechanisms of thyroid hormone during mammalian brain development. Overall this article provides a basic understanding of the thyroid system and its components. The complexity of the thyroid system is clearly demonstrated, as are new areas of research on thyroid hormone physiology and thyroid hormone action developing within the field of thyroid endocrinology. This review provides the background necessary to review the current assays and endpoints described in the following articles for rodents, fishes, amphibians, and birds. PMID- 17364705 TI - Current and potential rodent screens and tests for thyroid toxicants. AB - This article reviews current rodent screens and tests to detect thyroid toxicants. Many points of disruption for thyroid toxicants are outlined and include: (a) changes in serum hormone level; (b) thyroperoxidase inhibitors; (c) the perchlorate discharge test; (d) inhibitors of iodide uptake; (e) effects on iodothyronine deiodinases; (f) effects on thyroid hormone action; and (g) role of binding proteins (e.g., rodent transthyretin). The major thyroid endpoints currently utilized in existing in vivo assay protocols of the Organization for Economic Cooperation and Development (OECD), Japanese researchers, and U.S. Environmental Protection Agency (EPA) include thyroid gland weight, histopathology, circulating thyroid hormone measurements, and circulating thyroid stimulating hormone (TSH). These endpoints can be added into the existing in vivo assays for reproduction, development, and neurodevelopment that are outlined in this chapter. Strategic endpoints for possible addition to existing protocols to detect effects on developmental and adult thyroid endpoints are discussed. Many of these endpoints for detecting thyroid system disruption require development and additional research before they can be considered in existing assays. Examples of these endpoints under development include computer-assisted morphometry of the brain and evaluation of treatment-related changes in gene expression, thyrotropin-releasing hormone (TRH) and TSH challenge tests, and tests to evaluate thyroid hormone (TH)-dependent developmental events, especially in the rodent brain (e.g., measures of cerebellar and cortical proliferation, differentiation, migration, apoptosis, planimetric measures and gene expression, and oligodendrocyte differentiation). Finally, TH-responsive genes and proteins as well as enzyme activities are being explored. Existing in vitro tests are also reviewed, for example, thyroid hormone (TH) metabolism, receptor binding, and receptor activation assays, and their restrictions are described. The in vivo assays are currently the most appropriate for understanding the potential effects of a thyroid toxicant on the thyroid system. The benefits and potential limitations of the current in vivo assays are listed, and a discussion of the rodent thyroid system in the context of human health is touched upon. Finally, the importance of understanding the relationship between timing of exposure, duration of dose, and time of acquisition of the endpoints in interpreting the results of the in vivo assays is emphasized. PMID- 17364706 TI - The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction. AB - Bony fishes represent the largest vertebrate class and are a very diverse animal group. This chapter provides a thorough review of the available scientific literature on the thyroid system in these important vertebrate animals. The molecular components of the hypothalamic-pituitary-thyroid (HPT) axis in this group correspond closely to those of mammals. The thyroid tissue in the fishes is organized as diffuse follicles, with a few exceptions, rather than as an encapsulated gland as is found in most other vertebrate species. The features of this diffuse tissue in fishes are reviewed with an emphasis on feedback relationships within the HPT axis, the molecular biology of the thyroid system in fishes, and comparisons versus the thyroid systems of other vertebrate taxa. A review of the role of thyroid hormone in fish development and reproduction is included. Available information about the HPT axis in fishes is quite detailed for some species and rather limited or absent in others. This review focuses on species that have been intensively studied for their value as laboratory models in assays to investigate disruption in normal function of the thyroid system. In addition, in vitro and in vivo assay methods for screening chemicals for their potential to interfere with the thyroid system are reviewed. It is concluded that there are currently no in vitro or in vivo assays in fish species that are sufficiently developed to warrant recommendation for use to efficiently screen chemicals for thyroid disruption. Methods are available that can be used to measure thyroid hormones, although our ability to interpret the causes and implications of potential alterations in T4 or T3 levels in fishes is nonetheless limited without further research. PMID- 17364707 TI - The hypothalamic-pituitary-thyroid (HPT) axis in frogs and its role in frog development and reproduction. AB - Metamorphosis of the amphibian tadpole is a thyroid hormone (TH)-dependent developmental process. For this reason, the tadpole is considered to be an ideal bioassay system to identify disruption of thyroid function by environmental contaminants. Here we provide an in-depth review of the amphibian thyroid system with particular focus on the role that TH plays in metamorphosis. The amphibian thyroid system is similar to that of mammals and other tetrapods. We review the amphibian hypothalamic-pituitary-thyroid (HPT) axis, focusing on thyroid hormone synthesis, transport, and metabolism. We also discuss the molecular mechanisms of TH action, including the role of TH receptors, the actions of TH on organogenesis, and the mechanisms that underlie the pleiotropic actions of THs. Finally, we discuss methods for evaluating thyroid disruption in frogs, including potential sites of action, relevant endpoints, candidate protocols for measuring thyroid axis disruption, and current gaps in our knowledge. The utility of amphibian metamorphosis as a model for evaluating thyroid axis disruption has recently led to the development of a bioassay using Xenopus laevis. PMID- 17364708 TI - The hypothalamic-pituitary-thyroid (HPT) axis in birds and its role in bird development and reproduction. AB - This article reviews thyroid function and its hypothalamic-pituitary-thyroid (HPT) axis control in birds with emphasis on the similarities and differences in thyroid function compared to mammals and other vertebrate classes. Thyroid hormones are important in metabolism and the thermogenesis required for homeothermy in birds, as in mammals, the other homeothermic class of vertebrates. Thyroid hormones play important roles in development and growth in birds, as is the case for all vertebrate classes. The developmental effects of thyroid hormones in birds are presented in the context of differences in precocial and altricial patterns of development and growth with emphasis on oviparous development. The sections on thyroid hormone actions include discussion of effects on the development of a number of tissue types as well as on seasonal organismal processes and interactions of the thyroid axis with reproduction. The current picture of how environmental chemicals may disrupt avian thyroid function is relatively limited and is presented in the context of the assessment endpoints that have been used to date. These endpoints are categorized as thyroid and HPT axis endpoints versus target organ endpoints. The final section discusses two recommended assay protocols, the avian two-generation toxicity assay and the avian one-generation assay, and whether these protocols can evaluate thyroid disruption in birds. PMID- 17364709 TI - Implications of research on assays to characterize thyroid toxicants. AB - Many aspects of thyroid endocrinology are very well conserved across vertebrate taxa. These aspects include thyroid hormone chemistry, the mechanism of its synthesis, and the proteins involved in these processes. In addition, the system by which the hormone is delived from the thyroid gland to target cells, including transport and regulation within the hypothalamic-pituitary-thyroid (HPT) axis, and the proteins that regulate the different components of this delivery system appear to be highly conserved across the vertebrates. Finally, the receptors that mediate thyroid hormone action and the roles thyroid hormone plays are very similar among the vertebrates. Thus, the goal of this chapter is to provide a brief synopsis of the literature supporting existing screening and testing strategies in different vertebrate taxa, and to provide insight into the strengths, weaknesses, and likely changes over time. It was determined during this review that, because of the complexity of the thyroid system, it is unlikely that current in vitro assays for thyroid toxicity will be able to sufficiently replace in vivo assays for thyroid toxicants. However, the in vitro assays serve an important purpose in providing mode of action information and could provide potential screening tools, and should continue to be developed for use. Moreover, because in vivo assays are added on to preexisting reproductive or developmental screens and tests, there are no additional animals required for the in vivo assays. Specific in vitro assays were identified for development, including the thyroid receptor binding and activation assays, and in vitro assays to evaluate thyroid hormone action. Some in vivo endpoints suggested for further research included neuronal differentiation and migration, measures of histogenesis, and measures for thyroid gland thyroid hormone content, which may be more sensitive indicators of TSH stimulation. The most commonly used endpoints currently used to monitor thyroid function are thyroid hormone levels (T3 and T4), TSH, thyroid gland weight, and thyroid histology. Thyroid endocrinology is rapidly advancing and new discoveries will certainly warrant incorporation into future assays. The development of additional endpoints that measure thyroid hormone's actions peripheral to the HPT axis and the development of new reagents for nonmammalian vertebrate species will significantly improve the ability of today's assays to detect chemicals that disrupt the thyroid system in multiple vertebrate species. It is our hope that this series of thyroid articles will provide regulators and research scientists the information needed for each individual to identify the assays and endpoints most suited for their specific purposes. PMID- 17364710 TI - 'A shot of his own': the acceptability of a male hormonal contraceptive in Indonesia. AB - Male hormonal contraception has been shown to confer reversible infertility for at least one year; however, while clinical trials refine hormonal regimens, their acceptability, cultural meanings, and implications for study of men's sexualities remain under examined. This paper presents findings from interviews conducted with men and their female partners in a male hormonal contraception clinical trial in Jakarta and Palembang, Indonesia, and describes the ideas expressed about this new contraceptive technology. Fourteen men and their partners in Jakarta and ten men and their partners in Palembang were interviewed about their motivations to participate in the trial and their perceptions of the injection's physical, psychological and social effects. Concerns such as excess fertility and attendant economic liability shaped one quarter of motivations reported by men, while many women highlighted how a male method could help them prevent pregnancy without physical complications. Intimacy and sexual relations between couples were key themes within interpretations of contraceptive acceptability. Taken together, the narratives presented in this study call attention to the need for more nuanced analyses of contraceptive acceptability, as well as to the importance of studies of new male contraceptives for the understanding of masculinities. PMID- 17364711 TI - Straightening out the queer? Same-sex experience and attraction among young people in Norway. AB - The aim of this study was to describe the prevalence of same-sex experience, from deep kissing, through petting to genital contact, same-sex romantic attraction and reported same-sex arousal in a representative sample of young men and women aged 17-18 in Norway. While same-sex experiences were reported as being more prevalent among young women (27.4%) than among young men (6.5%), the gender difference in the case of same-sex genital experiences was smaller (F = 4.6%, M = 2.7%) than in the case of deep kissing (F = 25.7%, M = 3.9%). While same-sex romantic attraction was more prevalent among young men with same-sex experiences than young women, such attraction was confined to a minority of all young men. Results suggest that same-sex experiences among Norwegian youth are not unequivocally tied to same-sex attraction and possible homosexual self-identity. We argue that among young men, same-sex behaviour is more often associated with same-sex orientation whereas young women's same-sex relations seem to be more exploratory. PMID- 17364712 TI - Gender, social background and sexual attitudes among Chinese students. AB - Chinese society is changing rapidly. As a result of the political and economic reforms of the 'socialist market economy', for example, people have more choices than before. To examine current attitudes to sexual behaviour and marriage, 1100 university students from different parts of China were asked to talk about their views on marriage and choosing a marriage partner, and to describe their own sexual behaviours. Views about 'male superiority' in marriage, for age, education and height persisted, especially for women. Overall, attitudes to sexual behaviours were less open then in the West. However, young people from the cities with educated/professional parents showed more liberal attitudes than those from rural backgrounds. While some attitudes are changing, evidence concerning behaviour change is not so clear. There are important implications for the HIV/AIDS awareness programmes and sex education. PMID- 17364713 TI - De-constructing 'choice': the social imperative and women's use of the birth control pill. AB - This paper examines the social construction of 'choice' in women's use of the oral contraceptive birth control pill. Using social and historical critiques of neo-liberalism, it is argued that the contemporary priority placed on 'choice' positions women in contradictory ways-requiring them to be both 'choosing' reproductive subjects and reproductive subjects with very few options. The paper works to de-construct contemporary understandings of choice and finds that women's use of the birth control pill is less an exercise of idealized individual agency than it is an act of repetition, tied to ambiguity around what a lived experience of choice might be. To elaborate elements of the theoretical discussion, findings from a qualitative study of women's use of the oral contraceptive are discussed. These reveal that women's articulations of 'choice' challenge the notion of genuinely available and viable alternatives for women, and demonstrate how the use of a technology can silence understandings of contraception as something other than an individual responsibility. PMID- 17364714 TI - The impact of gender and hierarchy on women's reproductive health in a Kam village, Guizhou Province, China. AB - This paper explores the power hierarchies that shape the reproductive health of Kam village women with the purpose of identifying key potential causes of reproductive morbidity. The analysis is based on one year's fieldwork undertaken in a minority ethnic village in Guizhou in southwest China. Data from women's narratives reveal the ways in which power hierarchies, including the sex/gender system, shape daily life, dominance and resistance as well as actual health outcomes. Findings demonstrate how the sex/gender system intersects with other aspects of the village hierarchy, and how both affect villagers' reproductive decisions and reproductive health. Suggestions are offered on how to improve women's sexual and reproductive health in Kam areas. PMID- 17364715 TI - Culture, changing livelihoods, and HIV/AIDS discourse: reframing the institutionalization of fish-for-sex exchange in the Zambian Kafue Flats. AB - Discussions about the cultural dimensions of the spread of HIV/AIDS in Africa persist. Drawing on data on fish-for-sex deals between local Ila or Tonga women and immigrant fishermen in the Zambian Kafue Flats, we argue against the notion that traditional institutions governing extra-marital sexual relationships are responsible for the spread of HIV/AIDS. We argue that fish-for-sex exchanges are based not on tradition, but on the economic opportunities provided by the fish trade in conditions of poverty and changing livelihoods. Stigmatization of women involved in fish-for-sex deals is, however, on the increase, since they are accused of spreading the disease in their community. Women's inability to follow the sexual prescriptions conveyed by HIV prevention programmes produces shame and moral distress, associated with the fear of social exclusion. In this situation, lubambo, a former customary regulation of extramarital sexual relations among the Ila, may provide women with legitimacy for sexual transactions. Additionally, customary marriage arrangements institutionally secure their access to fish. PMID- 17364716 TI - Migration and HIV transmission in rural South India: an ethnographic study. AB - There is a widespread assumption in Northern Karnataka, India that HIV transmission is due to the large volume of male seasonal labour out-migration. In order to examine this issue, an ethnographic study was conducted in one of the Northern Karnataka districts using a combination of quantitative and qualitative methods. Findings indicate that migration does not seem to be a key factor affecting sexual behaviour among married men. Nearly 35% of married migrant men reported being involved in extramarital sex and 40% of unmarried migrant men were involved in premarital sex. While earlier in the epidemic there was a strong correlation between HIV infection and migration, more recently the correlation seems to be getting weaker. More innovative HIV prevention programmes which take into account the social and cultural characteristics of this region are urgently needed to curtail the rapid development of the epidemic. PMID- 17364720 TI - How can a child be a mother? Discourse on teenage pregnancy in a Brazilian favela. AB - Contemporary research reveals the body as a privileged place for social memory and resistance, especially among those people who are politically and economically marginalized. But what might the body signify within the context of teenage pregnancy in conditions of chronic poverty? To explore these issues, semi structured interviews were conducted with 21 boys and 17 girls living in a favela in Sao Paulo, Brazil. In their responses, young people drew a clear distinction between sex and parenthood. If sex sometimes holds negative connotations, maternity and the physical appearance of pregnancy increases social status. Young people's representations of teenage pregnancy do not portray it as a social or health problem. Instead, they understand it as a consequence of the desire to be visible and active in social life. Findings highlight the importance of investigating the relationship between young people's sexuality and the social imaginary, particularly in conditions of social inequality and suffering. PMID- 17364721 TI - Social organization of sexual-economic networks and the persistence of HIV in a rural area in the USA. AB - In order to determine why high rates of HIV transmission have persisted in a rural area despite community-wide HIV prevention since the mid-1980s, qualitative information was collected about the contexts and social organization of risk behaviour for HIV transmission from residents of a southern Florida community with high HIV prevalence. Original data were collected during 1995-1997 using individual interviews, observations, focus groups, and print media. The research findings were recently reviewed by community members, and the relevance of the data in the present day context was confirmed. We identified risk behaviours including multiple sex partners within heterosexual networks that cross socioeconomic strata and include adults and young people, sex workers, men who have sex with men, prison inmates, truckers, and migrant workers. Crack cocaine was an important feature of some networks. Financial support from multiple male or female sex partners was often part of a personal economic strategy and overlaid traditional social support networks. This type of relationship appears to be historically integrated into the economic fabric of the community and is not likely to receive social censure. Sexual reciprocity may explain, in part, why HIV transmission is rising among women in rural southern communities that have depressed economies. PMID- 17364722 TI - Negotiating cultures: disclosure of HIV-positive status among people from minority ethnic communities in Sydney. AB - Because of the multiple stigma attached to HIV/AIDS, disclosure of HIV-positive serostatus is a considerable social risk for those who disclose. While HIV/AIDS related stigma affects all HIV-positive people, for people from minority cultures additional cultural factors may play a significant role in self-disclosure. This paper draws on data from semi-structured, in-depth interviews with HIV-positive people from minority cultures in Sydney. Disclosure decisions were influenced by gender, sexual orientation, as well as cultural background. Gay men drew on both collectivist and individualist notions of interdependence and self-reliance in different socio-cultural contexts. This enabled them to accommodate the imperative to maintain harmony with the family and meet their individual needs for support. Heterosexual men who had disclosed voluntarily or involuntarily experienced discrimination and avoidance, and interdependence with family and ethnic community was disrupted. Heterosexual women disclosed to no one outside the health care system and were anxious to avoid any disclosure in the future. For all participants, voluntary and involuntary disclosure caused potential and actual disruption of relationships with their families and ethnic communities. The paper concludes by arguing for an ecological perspective of health in which decisions are not located in rational decision making alone but in the broader context of family and community. PMID- 17364723 TI - Challenges for the sexual health and social acceptance of men who have sex with men in Nigeria. AB - Little research exists regarding men who have sex with men and sexual risk in Nigeria. Prior to the implementation of a targeted HIV/STI prevalence study, structured focus groups incorporating anonymous questionnaires were conducted with members of this population in secure locations in Nigeria. A purposive sample of men was recruited by word-of-mouth. Five focus groups were conducted with a total of 58 men. Mean age was 27 years (range 16-58); 60% had post secondary education; 56% were employed full or part-time; 83% were Christian; 16% were Muslim; 66% self-identified as bisexual; 31% as homosexual. Participants' experiences were diverse, with ethnic, religious and class distinctions strongly structuring sexual expression. Same-sex community networks were hidden, with social activities taking place in non-commercial, private venues. Socially ostracized by culture, religion, and political will, the risks embodied within same-sex activity are high. For Nigeria--a nation culturally rich and religiously devout--the implications for public health policy are complex. However, these research findings suggest that immediate action is vital to mitigate the impacts of HIV and other STIs. PMID- 17364724 TI - Representin' in cyberspace: sexual scripts, self-definition, and hip hop culture in Black American adolescent girls' home pages. AB - Despite the importance of media in the lives of girls, sexuality researchers have largely overlooked how Black American adolescent girls engage with media to construct sexual self-definitions and explore their emerging sexuality. This study investigated sexual scripts, self-definition, and hip hop culture in internet home pages constructed by Black girls aged 14-17 years residing in southern states in the USA. Although some girls in the sample constructed sexual self-representations that mirrored sexual scripts portrayed in the media, hip hop, and youth cyberculture, others resisted stereotypical representations of Black female sexuality. This paper discusses the dominant sexual scripts that emerged from in-depth analysis of 27 home pages constructed by girls residing in Georgia. The focus is on 'Freaks', 'Virgins', 'Down-Ass Chicks/Bitches', 'Pimpettes', and Resisters. Findings suggest that a one-size-fits-all approach to sexuality education may fail to address key contextual issues of relevance to girls and young women. Innovative sexuality and media education strategies that respond to the significance of media in the lives of Black American girls and young women are needed. PMID- 17364725 TI - 'Marriage means having children and forming your family, so what is the need of discussion?' Communication and negotiation of childbearing preferences among Bangladeshi couples. AB - This paper explores communication and negotiation regarding contraception and childbearing based on multiple semi-structured interviews with 19 married couples in southwestern Bangladesh. The narratives of three couples are presented to describe how sociocultural context and gender-based norms influence interactions between husbands and wives and their fertility decision-making. Despite national level declines in fertility, the couples' stories illustrate the ongoing struggles to balance their desired number of male and female children with their financial and social well-being. The stories also indicate that the nature of the interactions between spouses evolves throughout the course of their marital and reproductive lifespans, resulting in a shift in fertility decision-making power. Both wives and husbands described the relative powerlessness of new wives in negotiating fertility with husbands and extended family; however, wives' preferences appeared to dominate as they became more established in their households. Many wives acted independently and often contrary to their husbands' desires, through their covert use or non-use of contraception and pregnancy termination. These findings illustrate that, despite efforts to increase contraceptive availability within Bangladesh, without concurrent changes in the opportunities available for women beyond their reproductive capacities, the demand for children, and particularly for male children, is not likely to change. PMID- 17364726 TI - Concerns and experiences of women participating in a short-term AZT intervention feasibility study for prevention of HIV transmission from mother-to-child. AB - This paper describes the experiences and concerns of women participating in a short-term AZT intervention feasibility study to prevent mother-to-child HIV transmission at three sites in India. The study used qualitative methods to examine the experiences of 31 women during late pregnancy, delivery and at post natal visits. It also elicited the perspectives of 19 healthcare providers. Frequent visits required during late-pregnancy and the post-natal period presented concerns for the women in the study. Women's understanding of the long term implications of participating in the intervention study was poor, and living with uncertainty about the HIV status of the newborn was a major concern. The provision of psychosocial support is essential in future intervention studies and should be incorporated on an ongoing basis. Networking with women-centred support groups may be helpful in enabling women to gain the long-term benefits of this type of intervention. PMID- 17364729 TI - Biocompatibility of nanocomposites used for artificial conjunctiva: in vivo experiments. AB - PURPOSE: To evaluate the biocompatibility of nanocomposites used for artificial conjunctiva. METHODS: Fifty New Zealand white rabbits were used for the experiments. Nanocomposites of poly -caprolactone (PCL) and of PCL coated with polyvinyl alcohol (PCL+PVA), polyvinyl pyrrolidone (PCL+PVP), or chitosan (PCL+C), and amniotic membrane (AM) as a control, were cut into small disks with a diameter of 3.5 mm. The disks were inserted underneath the conjunctiva to measure their inflammation-inducing properties. To investigate epithelial adhesion and goblet cell differentiation, the disks were transplanted after round conjunctival excision. Cultivated conjunctival epithelial cells on nanocomposite were then transplanted onto the abdomen of Balb/c athymic mice. The number of inflammatory cells and the density of goblet cells were measured using hematoxylin and eosin, periodic-acid-Schiff, and immunohistochemistry after 2 weeks. RESULTS: The number of inflammatory cells found inside of the inserts was as follows: 21 +/- 4.9 for controls, 21 +/- 15.1 for PCL, 49.6 +/- 26.0 for PCL+PVP, 40.2 +/- 17.1 for PCL+C, and 13.8 +/- 3.9 for PCL+PVA. In PCL+PVA, the accumulation of inflammatory cells was significantly lower than in the controls (p < 0.01, Mann-Whitney U). The reepithelialization of conjunctival cells was accomplished in more than 75% of all disks except for the PCL+C. In addition, we found the differentiation of goblet cells in the following order from greatest to least: amniotic membrane, PCL, and PCL+PVP. CONCLUSIONS: Nanocomposites of PCL were biocompatible in rabbit conjunctiva, suggesting that PCL may be considered as a candidate for use in the development of artificial conjunctiva. PMID- 17364730 TI - Assessment of corneal biomechanical properties and their variation with age. AB - PURPOSE: The aim of this study was to determine the stress-strain behavior of corneal tissue and how the behavior was affected by age. METHODS: Human corneal specimens ranging in age between 50 and 95 years were tested under inflation conditions to determine their stress-strain behavior. The corneas were subjected to two load rates that represent dynamic and static loading conditions. The pressure-deformation results were analyzed using shell theory to derive the stress-strain behavior. RESULTS: The corneas demonstrated clear nonlinear behavior with an initial low stiffness stage and a final high stiffness stage. The transition between the two stages coincided with intraocular pressures between 12 and 20 mmHg. There was a considerable increase in stiffness associated with both age and load rate. Equations were derived to describe the nonlinear stress-strain relationship of corneal tissue for any age between 50 and 95 years, and these equations are presented in a form suitable for use in numerical simulations. CONCLUSIONS: The cornea demonstrates considerable stiffening with age with the behavior closely fitting an exponential power function typical of collagenous tissue. The increase in stiffness could be related to the additional age-related nonenzymatic cross-linking affecting the stromal collagen fibrils. PMID- 17364731 TI - Effects of mobile phones on oxidant/antioxidant balance in cornea and lens of rats. AB - PURPOSE: To investigate the effects of mobile-phone-emitted radiation on the oxidant/antioxidant balance in corneal and lens tissues and to observe any protective effects of vitamin C in this setting. METHODS: Forty female albino Wistar rats were assigned to one of four groups containing 10 rats each. One group received a standardized daily dose of mobile phone radiation for 4 weeks. The second group received this same treatment along with a daily oral dose of vitamin C (250 mg/kg). The third group received this dose of vitamin C alone, while the fourth group received standard laboratory care and served as a control. In corneal and lens tissues, malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured with spectrophotometric methods. RESULTS: In corneal tissue, MDA level and CAT activity significantly increased in the mobile phone group compared with the mobile phone plus vitamin C group and the control group (p < 0.05), whereas SOD activity was significantly decreased (p < 0.05). In the lens tissues, only the MDA level significantly increased in the mobile phone group relative to mobile phone plus vitamin C group and the control groups (p < 0.05). In lens tissue, significant differences were not found between the groups in terms of SOD, GSH-Px, or CAT (p > 0.05). CONCLUSIONS: The results of this study suggest that mobile telephone radiation leads to oxidative stress in corneal and lens tissues and that antioxidants such as vitamin C can help to prevent these effects. PMID- 17364732 TI - Elevated concentrations of kynurenic acid, a tryptophan derivative, in dense nuclear cataracts. AB - PURPOSE: Kynurenines and their glycoside derivatives in the ocular lens absorb ultraviolet radiation and thus possibly help protect the retina from ultraviolet light. The current study analysed kynurenine aminotransferase I (KAT I) activity and kynurenic acid (KYNA) concentrations in human senile cataractous lenses and in experimentally induced cataracts in diabetic rats treated with streptozotocin (STZ). METHODS: KYNA levels and KAT I activity were investigated with HPLC and detected fluorimetrically in the nuclei of 91 human cataractous lenses collected during planned extracapsular extraction. The lenses were classified on the Lens Opacity Classification System III scale and compared with clear lenses regarding KYNA concentrations. Cataractous lenses from STZ-treated rats were compared with control lenses. RESULTS: KYNA concentration was 0.95 +/- 0.22 in human NC0 (nuclear color) control lenses, 0.8 +/- 0.72 in NC1, 1.18 +/- 0.88 in NC2, 1.31 +/- 0.70 in NC3, 1.78 +/- 0.92 in NC4, 8.80 +/- 8.28 (p < 0.05 vs. NC0) in NC5, and 14.0 +/- 11.1 (p < 0.05 vs. NC0) in NC6. A correlation was found between KYNA concentrations and the grade of cataract (r = 0.047, p < 0.001). KAT I activity in human cataracts was 0.44 +/- 0.16 pmol/mg protein- 1 hr- 1. Elevated KYNA concentrations in rat cataractous lenses were also observed (p < 0.05). CONCLUSIONS: KYNA levels are elevated in senile nuclear human cataracts and in cataractous lenses of rats with experimentally induced diabetes. PMID- 17364733 TI - Effects of bicistronic lentiviral vector-mediated herpes simplex virus thymidine kinase/ganciclovir system on human lens epithelial cells. AB - Posterior capsule opacification (PCO) is the most common complication after phacoemulsification cataract surgery. Hyperplasia of the lens epithelial cell after phacoemulsification is thought to be an important feature contributing to PCO. In this study,we investigated the feasibility of killing the human lens epithelial cells (HLECs) by lentivirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene/ganciclovir (GCV) in HLECs and studied the bystander effect. HLECs were infected with lentiviral vectors coexpressing HSV-tk and enhanced green fluorescent protein (EGFP) or expressing EGFP alone and treated with ganciclovir. Infection efficiency was assessed by fluorescence microscopy, fluorescence-activated cell sorting, and reverse transcription PCR. The cytotoxicity of the HSV-tk/GCV suicide gene therapy system was assessed by DNA ladder and electron microscopy. The time effect and bystander effect of HLEC growth inhibition were evaluated with cell proliferation assay. Lentiviral vector mediated stable integration and efficient expression of HSV-tk in HLECs, with infection efficiency exceeding 95% GCV at concentrations of 15 approximately 25 mug/ml, significantly induced apoptosis or necrosis of infected HLECs. GCV also killed normal cells mixed with HSV-tk infected cells. The bystander effect markedly increased the cytotoxicity of the HSV-tk/GCV system. Our results suggest that bicistronic lentiviral vectors can efficiently integrate several genes into HLECs and may be a gene therapy platform. Lentivirus-mediated suicide gene therapy might be a feasible treatment strategy to prevent capsule opacification. PMID- 17364734 TI - Isolation, culture, and characterization of human fetal trabecular meshwork cells. AB - PURPOSE: To isolate and characterize fetal trabecular meshwork (FTM) cells for study in culture. Cultured adult trabecular meshwork (TM) cells often possess a slower rate of growth and restricted number of population doublings, limiting the ability to perform expanded testing. METHODS: Fetal eyes from 24-week gestation abortions were delicately dissected to isolate the developing trabecular meshwork tissue. Three primary cultures were achieved and passaged. Light microscopy was used to compare the FTM cells to two cultured adult TM cell lines. Immunocytochemistry and Western blot analysis were utilized to identify specific protein expression. RESULTS: The FTM cells demonstrated similar microscopic characteristics to adult TM cells, including monolayer formation, cobblestone pattern, and comparable size. FTM cells exhibited faster, more consistent doubling times when compared with adult TM cells. They grew rapidly even after passage 8, whereas their adult counterparts slowed significantly with each successive passage and failed to reach confluence at passages 4 to 5. Immunofluorescent staining was positive for actin, vimentin, fibronectin, laminin, aquaporin-1, CD-44, and myocilin in both FTM and adult TM cells. In both fetal and adult cells, Western blots showed substantial increase in myocilin after exposure to dexamethasone. CONCLUSIONS: Characterization by microscopy and immunocytochemistry suggest that FTM cells have properties similar to adult TM cells. Fetal tissues may be a useful source of abundant, rapidly dividing FTM cells for in vitro investigation. The ability to do expanded research in this field may contribute to a better understanding of the molecular mechanisms in glaucoma development. PMID- 17364735 TI - Midterm response with latanoprost therapy in german ocular hypertension patients. AB - PURPOSE: The purpose of this prospective observational trial was to report the analysis of the midterm efficacy, safety, and discontinuation rates of a cohort of ocular hypertensive patients treated with latanoprost in Germany. METHODS: A subanalysis of patients with ocular hypertension who were previously treated on latanoprost monotherapy and continued within the study on this same medication for at least 6 months. RESULTS: 353 patients with ocular hypertension were included and treated with latanoprost monotherapy historically (1.4 +/- 1.3 years) and within the observational period of the study for a mean of 2.2 +/- 1.1 years. On latanoprost only, the average intraocular pressure at study entry was 18.4 +/- 2.7 mm Hg, and at 6 months the intraocular pressure was 18.3 +/- 2.3 mmHg (p = 0.54). During the observational period, the most common ocular side effect was conjunctival hyperemia (20.7%), and the most common systemic side effect was fatigue (3.1%). Nineteen patients (5.4%) discontinued latanoprost with the most common reason being insufficient efficacy (3.1%). Physician assessments of latanoprost monotherapy were "very good" to "excellent" for patient efficacy (75.2%), tolerability (83.8%), and patient satisfaction (82.1%). CONCLUSIONS: The study suggests that patients with ocular hypertension already treated with latanoprost monotherapy will continue to have, on average, at least midterm stable pressures, low incidence of side effects and discontinuations, as well as "very good" to "excellent" physician ratings of efficacy, tolerability, and patient satisfaction. PMID- 17364736 TI - The effects of caspofungin and voriconazole in experimental Candida endophthalmitis. AB - PURPOSE: To evaluate the efficacy of newly developed antifungal agents caspofungin and voriconazole in Candida albicans endophthalmitis in rabbit eyes. METHODS: Thirty New Zealand white rabbits were divided into four treatment groups and one control group. One eye of each rabbit was infected by inoculation of 1 x 10(4) CFU/ml of C. albicans. Seventy-two hours after the inoculation, caspofungin 100 microg/0.1 ml in group 1 (n = 6), voriconazole 50 microg/0.1 ml in group 2 (n = 6), amphotericin B 10 microg/0.1 ml in group 3 (n = 6), itraconazole 10 microg/0.1 ml in group 4 (n = 6), and 0.1 ml NaCl 0.9% in control group (n = 6) were injected into the vitreous cavity. Clinical and histopathologic examination scores and microbiological analysis of vitreous aspirates were compared. RESULTS: There was statistically significant difference in the clinical scores, histopathologic scores, and mean CFU/ml between the treatment and control groups (p < 0.05). In caspofungin and voriconazole groups, histopathologic scores and mean CFU were lower than other treatment groups and control group. CONCLUSIONS: Intravitreal injection of caspofungin and voriconazole was effective against C. albicans endophthalmitis in this experimental rabbit model. PMID- 17364737 TI - Retinal thickening after successful surgery for macula-off retinal detachment. AB - PURPOSE: To study changes in retinal thickness after reattachment of the retina after scleral buckling surgery for rhegmatogenous retinal detachment. METHODS: In this retrospective study, patients were classified into three subgroups according to preoperative macular status. Retinal thickness within 3 mm of the center was measured with optical coherence tomography. RESULTS: Foveal retinal thickness at a mean of 2 years postoperatively was significantly increased in patients with preoperatively detached macula. Additionally retinal thickness in the fovea and postoperative visual acuity was positively correlated. CONCLUSIONS: Successful surgery for macula-off retinal detachment is associated with significant thickening of the neurosensory retina when examined with optical coherence tomography 6 months postoperatively. PMID- 17364738 TI - Effect of tetramethylpyrazine on rat experimental choroidal neovascularization in vivo and endothelial cell cultures in vitro. AB - PURPOSE: To evaluate the effect of tetramethylpyrazine (TMP) on laser-induced experimental choroidal neovascularization (CNV) in rat model in vivo and on endothelial cell proliferation in vitro. METHODS: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch membrane. TMP was given once daily through intraperitoneal injection after laser treatment for 4 weeks. The development of CNV was determined by angiography performed on week 2 and week 4 using sodium fluorescein (FA) or fluorescein isothiocyanate-dextran (FD70-FA). Human umbilical vein endothelial cells (HUVECs) were tested with proliferation assay with TMP at different concentrations. RESULTS: According to the angiograms of FA, intensity of fluorescein leakage from the photocoagulated lesions decreased significantly after TMP treatment. The number of rats with less leaky points ( Viscoat > Amvisc Plus > Healon. PMID- 17364744 TI - Effects of kallidinogenase on ischemic changes induced by repeated intravitreal injections of endothelin-1 in rabbit retina. AB - PURPOSE: Repeated intravitreal injections of endothelin-1 (ET-1) lead to alterations in the visually evoked potentials (VEPs) and loss of retinal ganglion cells (RGCs) in rabbits. The purpose of this study was to determine whether kallidinogenase can offset the alterations induced by ET-1. METHODS: ET-1 (2.5 x 10(-7) M, 20 microL) was injected into the vitreous of the right eye of rabbits (ET-1-treated eyes, n = 30) twice a week for 4 weeks. The vehicle for ET-1 was injected into the left eye on the same schedule (vehicle treated eyes, n = 30). During this 4 weeks period, kallidinogenase (1.0 unit/kg/day, kallidinogenase treated group) or saline (saline-injected control group) was continuously delivered intravenously by an implanted osmotic pump. VEPs were recorded before, and 2 weeks and 4 weeks after, the first ET-1 injection, and all rabbits were sacrificed at 4 weeks. The number of RGC cells was counted in hematoxylin- and eosin-stained retinal sections. In the analyses, the ET-1 induced alterations were normalized to the values in the vehicle treated control eyes, i.e., kallidinogenase (K) + ET-1/K+ vehicle or saline (S) +ET-1/S + vehicle. Retinal sections were also examined by immunohistochemistry with antibodies to single stranded DNA (ssDNA) or to glial fibrillary acidic protein (GFAP). The effect of kallidinogenase on the ONH blood flow was determined by a hydrogen gas clearance flowmeter. RESULTS: The significant prolongation of the relative VEP implicit times (ITs) 4 weeks after the ET-1 injection (P < 0.01, paired t test; post-ET-1 vs. pre-ET-1) was significantly decreased by kallidinogenase (P < 0.001, t test, K + ET-1/K+ vehicle vs. S +ET-1/S + vehicle). The relative number of RGCs was decreased in the saline-injected group, and this decrease was also decreased by kallidinogenase (P < 0.05, t test, K + ET-1/K+ vehicle vs. S +ET-1/S + vehicle). ssDNA staining showed fewer apoptotic cells in the retina of kallidinogenase treated rabbits. Intravitreal injection of ET-1 also decreased the blood flow in the optic nerve head and increased the GFAP immunostaining and axonal degeneration. These changes were also counteracted by kallidinogenase. CONCLUSION: These results indicate that kallidinogenase can counter the effects of ET-1 and should be considered for the treatment of ischemic retinal and optic nerve disorders related to abnormal ET-1 production. PMID- 17364746 TI - Biomechanical effect of segmental scleral buckling surgery. AB - PURPOSE: The current paper studies the mechanical effect of segmental buckling surgery for treatment of retinal detachment using the finite element (FE) method. The effects of different eye sizes, intraocular pressures, and silicon sponge size and locations are examined. Indicative study on the visual optics from the emmetropia to the myopia by the surgery is also carried out. Ophthalmologists may have an advanced understanding of the possible surgical outcomes from the current study in order to plan better patient-specific surgical procedure. METHODS: The solid tissues in the 3D FE model are modeled by eight-node hexagonal solid elements using a Lagrangian mesh. The inner vitreous and aqueous liquids are modeled by a Eulerian mesh. The eye tissues are treated as hyperelastic solids, and the liquids are represented with linear polynomial equations of state. RESULTS: The segmental scleral buckling procedure induces stress concentrations in the suture region, which may lead to bleeding. A smaller eye sustains relatively higher stress, thus has a greater chance to bleed. Smaller silicon implant leads to much higher stress, and the effect of the relative posterior and anterior positions of the silicon sponge is inconsistent. The surgery causes or aggravates myopia due to the average corneal curvature increase, although the optical length of the eye is reduced at high indentations. Exceptions are eyes with very large or small intraocular pressure at moderate indentation. Eyes with small intraocular pressure may sustain more severe refractive error by the surgery. Astigmatism may be caused or aggravated by the irregular deformation of the cornea and the deflection of the crystalline lens. PMID- 17364745 TI - Protein kinase C-mediated modulation of glutamate transporter activity in rat retina. AB - It has previously been shown that inhibitors of protein kinase C (PKC) attenuate retinal glutamate uptake in situ. The aim of the current study was to determine whether PKCdelta-mediated inhibition differentially reduces the transport of glutamate into retinal Muller cells when compared with retinal neurons. The influence of two different types of PKC inhibitors on the uptake of [3H]D aspartate was therefore compared in the intact retina, mixed retinal cultures, and Muller cell-enriched retinal cultures. It was found that 25 microM of the pan isoform PKC inhibitor, chelerythrine, reduced [3H]D-aspartate uptake by 78%, 71%, and 68% in isolated retinas, mixed neuronal/glial cultures, and Muller cell enriched cultures, respectively. Importantly, 20 microM of the PKCdelta-selective inhibitor rottlerin also reduced the uptake of D-aspartate to similar extents in all three systems, and the reductions were statistically similar to those found for the pan-specific PKC inhibitor. Neither pan-isoform nor PKCdelta-selective activators stimulated glutamate uptake in either culture system or the intact retina. The current results suggest that specific PKC inhibitors are quantitatively similar in reducing the uptake of glutamate into retinal neurons and Muller cells. PMID- 17364747 TI - Porcine Muller glial cells increase expression of BKCa channels in retinal detachment. AB - PURPOSE: To determine whether experimental retinal detachment causes an alteration in Ca2 +-activated, big conductance K+ (BK) currents of Muller glial cells. METHODS: Rhegmatogenous retinal detachment was induced in porcine eyes. Muller cells were acutely isolated from control retinas and from retinas that were detached for 7 days. BK currents were detected by using the BK channel opener and the blocker phloretin and tetraethylammonium, respectively. RESULTS: In addition to cellular hypertrophy and a decrease in inward rectifier K+ currents, Muller cells from detached retinas showed an increase in the amplitude of currents mediated by BK channels (850 +/- 105 pA) when compared with cells from control retinas (228 +/- 60 pA; p < 0.001). Similarly, the density of the BK channel-mediated currents was greater in cells from detached retinas (12.32 +/- 1.52 pA/pF) compared with control cells (4.07 +/- 1.07 pA/pF; p < 0.001). The increase in BK currents was correlated with the decrease of the inward rectifier K+ currents. CONCLUSIONS: It is suggested that an increase in the expression of functional BK channels may be involved in gliotic responses of Muller cells after retinal detachment (e.g., in mitogen-induced Ca2+ responses and cellular proliferation). PMID- 17364748 TI - Does treated systemic hypertension affect progression of optic nerve damage in glaucoma suspects? AB - PURPOSE: To evaluate whether treatment of systemic hypertension has an effect on progression of optic nerve parameters in glaucoma suspects using confocal scanning laser ophthalmoscopy. METHODS: Two hundred eyes of 103 glaucoma suspect patients were included in this retrospective cohort study. Thirty-one patients (of whom 59 eyes were included in the study) had systemic hypertension under treatment (based on medical history). The remaining 72 age-matched normotensive controls (of whom 141 eyes were included in the study) were not on blood-pressure lowering medications. Each patient had a follow-up period of at least 4 years with a minimum of four Heidelberg retinal tomograph tests (one baseline and three follow-up scans). The slopes of progression of optic nerve head parameters with time were studied and compared between these two groups using mixed effects regression models. RESULTS: Patients with systemic hypertension showed a statistically significant increase in cup area (slope 0.2, p = 0.03), cup-to-disk area ratio (slope 0.01, p = 0.007), and decrease in rim area (slope -0.4, p = 0.03), rim-to-disk area ratio (slope -0.01, p = 0.005), and global Retinal Nerve Fiber Layer (RNFL) thickness (p = 0.008) with time. The differences in slopes of progression of many parameters between hypertensives and normotensives were statistically significant. CONCLUSIONS: Systemic hypertension treated with hypotensive medications may be a risk factor for increased progression of optic nerve parameters in glaucoma suspects compared with age-matched normotensive subjects. PMID- 17364749 TI - Oxygen saturation in optic nerve head structures by hyperspectral image analysis. AB - PURPOSE: A method is presented for the calculation and visualization of percent blood oxygen saturation from specific tissue structures in hyperspectral images of the optic nerve head (ONH). METHODS: Trans-pupillary images of the primate optic nerve head and overlying retinal blood vessels were obtained with a hyperspectral imaging (HSI) system attached to a fundus camera. Images were recorded during normal blood flow and after partially interrupting flow to the ONH and retinal circulation by elevation of the intraocular pressure (IOP) from 10 mmHg to 55 mmHg in steps. Percent oxygen saturation was calculated from groups of pixels associated with separate tissue structures, using a linear least squares curve fit of the recorded hemoglobin spectrum to reference spectra obtained from fully oxygenated and deoxygenated red cell suspensions. Color maps of saturation were obtained from a new algorithm that enables comparison of oxygen saturation from large vessels and tissue areas in hyperspectral images. RESULTS: Percent saturation in retinal vessels and from the average over ONH structures (IOP = 10 mmHg) was (mean +/- SE): artery 81.8 +/- 0.4%, vein 42.6 +/- 0.9%, average ONH 68.3 +/- 0.4%. Raising IOP from 10 mmHg to 55 mmHg for 5 min caused blood oxygen saturation to decrease (mean +/- SE): artery 46.1 +/- 6.2%, vein 36.1 +/- 1.6%, average ONH 41.9 +/- 1.6%. The temporal cup showed the highest saturation at low and high IOP (77.3 +/- 1.0% and 60.1 +/- 4.0%) and the least reduction in saturation at high IOP (22.3%) compared with that of the average ONH (38.6%). A linear relationship was found between saturation indices obtained from the algorithm and percent saturation values obtained by spectral curve fits to calibrated red cell samples. CONCLUSIONS: Percent oxygen saturation was determined from hyperspectral images of the ONH tissue and retinal vessels overlying the ONH at normal and elevated IOP. Pressure elevation was shown to reduce blood oxygen saturation in vessels and ONH structures, with the smallest reduction in the ONH observed in the temporal cup. IOP-induced saturation changes were visualized in color maps using an algorithm that follows saturation dependent changes in the blood spectrum and blood volume differences across tissue. Reduced arterial saturation at high IOP may have resulted from a flow dependent mechanism. PMID- 17364750 TI - Evaluation of cyclophotocoagulation effects with 1310-nm contact optical coherence tomography. AB - PURPOSE: The aim of this pilot study was to evaluate whether contact optical coherence tomography (OCT) allows visualization of the effects of cyclophotocoagulation. METHODS: In this pilot study, transscleral contact OCT images (1310-nm wavelength) were generated prior to and immediately after conventional transscleral diode laser cyclophotocoagulation in three eyes of three patients who were suffering from uncontrolled glaucoma. RESULTS: In the region of the ciliary body, transscleral contact OCT revealed two layers: (i) a superficial thick hyperreflective complex representing conjunctiva, the Tenon capsule, episclera, and sclera; and (ii) a thinner hyporeflective layer representing the ciliary body. The ciliary body could be differentiated from the overlying sclera by its marked drop in reflectivity. After cyclophotocoagulation, a marked increase of reflectivity in the treated area of the ciliary body was identifiable. After treatment, the distinct border between the hyperreflective scleral complex disappeared, and the region of the ciliary body appeared hyperreflective. The optical properties of the overlying sclera remained unchanged. On corresponding averaged A-scan images, scleral thickness appeared to be slightly increased, whereas ciliary body thickness remained unchanged. CONCLUSIONS: This pilot study demonstrates the capability of contact OCT for allowing visualization of changes in the ciliary body after transscleral cyclophotocoagulation (TSCPC). Further investigations are planned to clarify the complete significance of these data. PMID- 17364751 TI - Children with movement difficulties. PMID- 17364752 TI - Intervention and the role of theory, empiricism and experience in children with motor impairment. AB - PURPOSE: This paper presents a framework for examining the different approaches to intervention in children with motor impairment such that more informed decisions are made by researchers and clinicians in their respective fields. METHOD: Studies are examined using a framework employing theoretical, empirical and experiential evidence. A range of interventions are analysed and are applied to the conditions of cerebral palsy and developmental coordination disorder. The theoretical, empirical and experiential evidence is analysed by an examination of such methods as constraint induced therapy, Bobath techniques, bimanual coordination methods, sensory integration therapy and functional task approaches, all set within a development and learning context. RESULTS: The results show that evidence from the three parts of the framework, namely theoretical, empirical and experiential are often in conflict with each other and it is not surprising that there is confusion in the field about the efficacy of the various methods. CONCLUSIONS: First, it is recommended that more complete information is required on the methods employed from the three areas of our framework. Secondly, researchers, clinicians and other practitioners should examine the evidence from these three areas and align it to the needs of their research or practice before embarking on action. PMID- 17364753 TI - Motor planning in congenital hemiplegia. AB - PURPOSE: Cerebral Palsy (CP) is a broad definition of a neurological condition in which disorders in movement execution and postural control limit the performance of activities of daily living. In this paper, we first review studies on motor planning in hemiplegic CP. Second, preliminary data of a recent study on eye-hand coordination in participants with hemiplegic CP are presented. Here, the potential role of vision for online and prospective control of action was examined. METHOD: Review and presentation of preliminary data of an eye- and hand movement registration experiment in hemiplegic CP. RESULTS: Deficits in motor planning in hemiplegic CP contribute to limitations of activities of daily living. In the second part, exemplary plots of eye-hand coordination are presented for the affected and unaffected hand in one participant with hemiplegic CP, and for the preferred hand in controls, both as an illustration of the research methodology and to give an impression of the observed gaze patterns. CONCLUSION: Research on CP should not solely focus on low-level aspects of action execution, but also take into account the more high-level aspects of motor control, such as planning. Possible deviations therein may be sought in altered gaze patterns as illustrated in the paper. PMID- 17364754 TI - Functional status in 5 to 7-year-old children with Down syndrome in relation to motor ability and performance mental ability. AB - PURPOSE: To examine the contribution of motor ability and 'performance' mental ability on functional skills in children with Down syndrome (DS). METHOD: A structural equation modelling approach was used to test the relation between motor ability, performance mental ability and functional status. Functional status was assessed with the Pediatric Evaluation Disability Inventory (PEDI), motor ability with the Movement Assessment Battery for Children (M-ABC), and performance mental ability was assessed with the Gross-Form Board (GFB). Sixty five children with DS, selected by the Dutch Down Syndrome Foundation, were asked to participate in the study. Data were analysed with the programme AMOS using the Bollen-Stine bootstrap method. Chi2 and NFI index were used as goodness-of-fit indices. RESULTS: The fit of the model was good (chi2 4 = 1.35, p = 0.85; and NFI = 0.99). 'Functional status' explained 70% of the variance in the model. Standardized regression weights indicated that motor ability was a far better predictor of functional status of children with DS than performance mental ability (0.96 vs. 0.17). CONCLUSIONS: Limitations in functional activities of 5 to 7-year-old children with Down syndrome seem to be more related to the level of motor ability than to the level of performance mental ability. PMID- 17364755 TI - Judgment of action capabilities in children at risk for developmental coordination disorder. AB - PURPOSE: To evaluate the ability to accurately perceive the limits of action capabilities in children at risk for developmental coordination disorder (DCD). METHODS: In Study 1, 9 to 12-year-old children (mean = 10.6 years, SD = 1.09) were identified as at risk for DCD and the accuracy of their perceptual judgments was compared with the judgments of a group of typically developing children (TDC). Two judgment tasks were used: Maximum vertical reach and maximum sitting height. Study 2 tested the hypothesis that a significant correlation would be found between a specific movement task and a related judgment task. Participants were randomly selected (n = 24) 10 and 11-year-old children (mean = 10.5 years, SD = 0.51). RESULTS: Magnitude of judgment error (absolute error) on all tasks was significantly (p < 0.05) greater in the DCD group than in the TDC group. Study 2 revealed a significant (p < 0.05) correlation between the movement task and the related perceptual task (r = 0.70). CONCLUSION: Compared to a typically developing group, children at risk for DCD made less accurate judgments of the limits of their action capabilities. The accuracy of a perceptual judgment was found to correlate with a related movement skill. PMID- 17364756 TI - Attention disengagement in children with developmental coordination disorder. AB - PURPOSE: Previous research has shown that children with Developmental Coordination Disorder (DCD) have poorly developed strategies for allocating attention. This study examines the allocation of attention and integration of visuo-spatial and motor systems in children with DCD in a motor (look+hit condition) and a motor-free (look condition) task. METHOD: Three groups of control children were used to compare the performance of a group of children with DCD. Children were seated in front of a central fixation point and six peripheral targets, and were asked to look at or hit targets when illuminated. Saccade/hand movement latencies were measured on gap trials (gap between fixation offset and target onset) and overlap trials (fixation offset and target onset overlapped). RESULTS: DCD children were not slower than controls to disengage attention during the look condition. However, during the look+hit condition the DCD children showed a prolonged disengagement period, which was also seen in younger control children. CONCLUSIONS: The results suggest that DCD children may have deficits in the allocation of attention for action, in both the speed of onset of a movement and the accuracy of the movement. It is concluded that attention disengagement may contribute to problems of visuo-motor integration in DCD. PMID- 17364757 TI - Can children with developmental coordination disorder adapt to task constraints when catching two-handed? AB - PURPOSE: To compare the nature and extent of inter and intralimb coupling during two-handed catching and the effect of manipulating task constraints in children with Developmental Coordination Disorder (DCD) and their typically developing peers (AMC). METHOD: Twenty children aged 7 - 10 years, ten with DCD and 10 AMC attempted to catch a ball ten times in condition 1 (C1), ball to the midline; condition 2 (C2), ball to the left shoulder and condition 3 (C3), ball to the right shoulder. Both 3D kinematic data and video data were collected. RESULTS: Children with DCD caught fewer balls than the AMC children, regardless of age or condition (p or=60 years compared with those <60 years but they also spend more time completing the task. No gender differences were observed. CONCLUSION: New MET values are derived for these two populations. These values would be useful in planning rehabilitation programmes for Chinese subjects with chronic diseases. PMID- 17364761 TI - Applicability of a toolkit for geriatric rehabilitation outcomes. AB - PURPOSE: To field test the applicability of a multidimensional toolkit for geriatric rehabilitation outcomes which includes nine standardized tools. Applicability is defined as context- and population-specific pragmatic qualities of an assessment tool such as respondent and examiner burden, score distribution and format compatibility. METHOD: A sample of 48 older adults representing four diagnostic groups, as well as 26 caregivers, were assessed at home in the first month after discharge from intensive rehabilitation (T1) and 2 months later (T2). Pre-determined qualitative and quantitative applicability criteria were coded and compared at T1 and T2, as well as responsiveness. RESULTS: A higher respondent burden was found for three self-report tools, as well as a ceiling effect on social functioning tools. Respondent burden, examiner burden and score distribution remained stable or diminished at T2. Format compatibility deteriorated only for the mobility test due to a higher proportion of non ambulatory participants (17%). Low to moderate associations between the tools corroborated that they were not redundant (rPearson or= 0.4) between the examiners for 15 out of the 20 subtests. Using total sum scores, the agreement within the examiners, both short- and long-term, was higher than 0.96 (for Spearman's rho and ICC, respectively). The mean differences were 0.29 - 1.0/80 points within each examiner. Agreement between the examiners at each session was higher than 0.96 (Spearman's rho) and 0.92 (ICC), respectively. Systematic differences (p < 0.05) were, however, found between examiners A and B/C for all sessions. CONCLUSIONS: The Sollerman hand function test seems to be a reliable test in patients with chronic stroke, but we recommend that the same examiner evaluates a patient's hand function pre- and post-treatment. PMID- 17364765 TI - Cross-cultural validation of the Falls Efficacy Scale International (FES-I) in older people: results from Germany, the Netherlands and the UK were satisfactory. AB - PURPOSE: To carry out a cross-cultural validation of the Falls Efficacy Scale International (FES-I), a 16-item modified version of the Falls Efficacy Scale that was developed to assess both easy and more complex physical and social activities, in a range of languages and different cultural contexts. METHOD: Data were collected in Germany (n = 94), The Netherlands (n = 193), and the UK (n = 178) in samples of older people living in the community. Four-week FES-I re-test data were collected in Germany and The Netherlands. Descriptive statistics and reliability estimates were computed as well as FES-I sum scores according to age, sex, falls history and fear of falling. RESULTS: Mean inter-item correlations were all above 0.38 and internal reliability estimates were all 0.90 or above. The intra-class correlation coefficients in the German and the Dutch sample were 0.79 and 0.82, respectively. As expected, FES-I scores were associated with age, sex, falls history and fear of falling. In addition, the FES-I discriminated between sub-groups somewhat better than the original ten-item FES scale. CONCLUSIONS: The FES-I has been shown to have acceptable reliability and construct validity in different samples in different countries and may be used in cross-cultural rehabilitation research and clinical trials. PMID- 17364766 TI - Prevalence of pain in the head, back and feet in refugees previously exposed to torture: a ten-year follow-up study. AB - AIM: To estimate change over 10 years concerning the prevalence of pain in the head, back and feet, among previously tortured refugees settled in Denmark, and to compare associations between methods of torture and prevalent pain at baseline and at 10-year follow-up. METHODS: 139 refugees previously exposed to torture in their home country were interviewed at a Danish rehabilitation clinic on average 8 years after their final release from confinement and re-interviewed 10 years later. Interviews focused on history of exposure to physical and mental torture and on pain in the head, back and feet prevalent at study. RESULTS: The mean number of times imprisoned was 2.5 and the mean cumulative duration of imprisonment 19.4 months. The most frequent physical torture method reported was beating (95.0%) and the main mental torture method deprivation (88.5%). Pain reported at follow-up was strongly associated with pain reported at baseline, and the prevalence of pain increased considerably (pain in the head, 47.5% at baseline and 58.3% at follow-up; back, 48.2% and 75.5%; feet, 23.7% and 63.3%). Predictor patterns at baseline and at follow-up had common traits, so that pain in the head and pain in the feet both were associated with the number of torture methods as well as specific methods, both at baseline and at follow-up. Pain in the back at baseline was associated with torture. CONCLUSION: Two decades after the torture took place, increasing proportions of survivors seem to suffer from pain associated with the type and bodily focus of the torture. This presents a considerable challenge to future evidence-based development of effective treatment programs. PMID- 17364767 TI - Status of the disabled in Turkey. A theoretical approach to the perception of the disabled in Turkey. AB - PURPOSE: Although the ratio of the disabled population is higher in Turkish society than the average value in the world, studies in this issue have been limited to statistical surveys and no firm theoretical bases on investigation of the perception of disability in the perspective of Turkish society have been established. Reliable theses on the form and manners of Turkish society's responses to disability have not been put forward, yet. Therefore, existence of the sociology of disability in Turkey, which is a relatively new field also for western societies, cannot be stated. The purpose of the study is to evaluate the perception of disability and responses to the disabled in Turkish society in the light of the findings of research, which was conducted in 2002, into the disabled in Turkey. METHOD: Theoretical assessment is carried out from the perspective of two viewpoints: The structural-functional and interactional theses. CONCLUSION: It is concluded that the interactional thesis sets a better ground for explanation of the circumstances of the disabled and response of the society to them in Turkey. PMID- 17364768 TI - Everyday physical activity and community participation of adults with hemiplegic cerebral palsy. AB - PURPOSE: To assess the level and potential determinants of everyday physical activity and participation in various life areas of adults with hemiplegic cerebral palsy (CP) in comparison with healthy subjects. METHOD: In a cross sectional study everyday physical activity was measured (Activity Monitor) in 16 adults with CP, aged 28 (3) years, and 16 age/gender matched healthy volunteers, aged 29 (3) years. Participation was assessed by means of validated questionnaires. Age, gender, body fat (skinfold thickness), muscle tone (Ashworth Scale), functional level and participation were assessed as potential determinants of everyday physical activity. RESULTS: In adults with CP mean (SD) duration of dynamic activities during a day (10.6 [3.5]%) was comparable to healthy subjects (11.2 4%) (p = 0.66). In most life areas the level of participation was comparable for both groups, although adults with CP spent more time on non-intensive leisure activities. Participation in sports appeared to be a determinant of everyday physical activity in both groups. CONCLUSIONS: The results indicate that the levels of everyday physical activity and community participation in adults with hemiplegic CP are comparable to levels in healthy comparison subjects. PMID- 17364769 TI - Barriers against returning to work--as perceived by disability pensioners with back pain: a focus group based qualitative study. AB - PURPOSE: The aim of this study was to explore the issue of perceived barriers for returning to work, based on the experiences and beliefs in a group of disability pensioners with back pain. METHOD: Focus groups were used to interview 12 women and five men, aged 38 - 56, who participated in a larger project aiming to help disability pensioners back to work. RESULTS: The barriers appearing were related to earlier negative experiences, poor self-judgement of work ability and low self esteem, lack of support from social security authorities and unsuitable economic arrangements. The pensioners also suggested alternative solutions for making a possible return to work. CONCLUSIONS: Our study provides insight into the perceived barriers of returning to work and might be useful in future efforts aiming to help disability pensioners back to work. PMID- 17364770 TI - Pilot study of a 4-week Pain Coping Strategies (PCS) programme for the chronic pain patient. AB - PURPOSE: A 4-week Pain Coping Strategies (PCS) programme has been developed for chronic pain patients who may still be undergoing medical interventions but who would benefit from learning pain management skills. The long-term negative behaviours associated with chronic pain may be prevented by introducing pain management strategies at an earlier stage. The PCS programme combines all the fundamental aspects of the traditional Pain Management Programme including exercise, relaxation, pacing, medication review, pain pathways, posture and challenging negative thoughts. METHOD: The study compared 31 patients' mood, functional status and physical ability pre and 6 weeks post the programme using the Hospital Anxiety and Depression Scale (HAD), Canadian Occupational Performance Measure (COPM) and a series of physical tests. A paired samples t test showed a significant improvement in levels of depression and anxiety, functional status and physical ability. RESULTS: The results reveal that an early intervention programme may be effective for chronic pain patients by promoting self-management and teaching positive coping strategies. CONCLUSIONS: The current study has found promising results for a brief early intervention for chronic pain, regardless of completion of medical interventions. PMID- 17364771 TI - Use of the International Classification of Functioning, Disability and Health (ICF) to identify preliminary comprehensive and brief core sets for multiple sclerosis. AB - PURPOSE: To identify the preliminary comprehensive and brief core sets for multiple sclerosis (MS), in a Delphi process using the International Classification of Functioning, Disability and Health (ICF). METHOD: Focus groups and a consensus process were used to identify ICF core sets for MS. This included: preliminary ICF studies; empirical patient data collection for 101 MS participants; review of the evidence base and treatment in MS literature followed by a Delphi exercise with 23 physicians and allied health professionals in Melbourne, Australia. RESULTS: One hundred and forty-four (40%) second level ICF categories were selected by 23 participants in three rounds. The comprehensive MS ICF core set includes 34 (24%) categories from the component 'body function', six (4%) categories from 'body structures', 68 (47%) from 'activities and participation' and 36 (25%) from the component 'environmental' factors. Ten categories in 'personal factors' in MS were also suggested by the participants after intensive discussions. The brief set comprises 30 categories, 21% of categories in the comprehensive core set. CONCLUSION: Consensus expert opinion can use ICF categories to identify the core set for MS which reflects disease complexity and care burden for persons' with MS. Further research is needed to identify ICF categories of relevant personal factors to improve our understanding of the large social and cultural variance associated with them. PMID- 17364772 TI - Predictors for successful vocational rehabilitation for clients with back pain problems. AB - PURPOSE: The aim of this study was to identify predicting factors for successful vocational rehabilitation for people with back pain problems. METHOD: The study was based on data from 347 long-term sick-listed clients collected at the onset of vocational rehabilitation. The outcome was measured 6 months after the conclusion of rehabilitation. RESULTS: In a first bi-variate analysis, a considerable number of variables were associated with the rehabilitation outcome. In a second multivariate analysis, only four associations remained. These were age, general health, vitality and internal locus of control. Young vital clients in good general health, with a high internal locus of control were more likely than others to return to work. CONCLUSION: The findings regarding age, general health and vitality are well in line with previous studies. The findings regarding internal locus of control are more unique. PMID- 17364773 TI - Comparing contents of functional outcome measures in stroke rehabilitation using the International Classification of Functioning, Disability and Health. AB - PURPOSE: To examine the content of outcome measures that are frequently used in stroke rehabilitation and focus on activities and participation, by linking them to the International Classification of Functioning, Disability and Health (ICF). Method. Constructs of the following instruments were linked to the ICF: Barthel Index, Berg Balance Scale, Chedoke McMaster Stroke Assessment Scale, Euroqol-5D, Functional Independence Measure, Frenchay Activities Index, Nottingham Health Profile, Rankin Scale, Rivermead Motor Assessment, Rivermead Mobility Index, Stroke Adapted Sickness Impact Profile 30, Medical Outcomes Study Short Form 36, Stroke Impact Scale, Stroke Specific Quality of Life Scale and Timed Up and Go test. Results. It proved possible to link most constructs to the ICF. Most constructs fitted into the activities and participation component, with mobility being the category most frequently covered in the instruments. Although instruments were selected on the basis of their focus on activities and participation, 27% of the constructs addressed categories of body functions. Approximately 10% of the constructs could not be linked. CONCLUSIONS: The ICF is a useful tool to examine and compare contents of instruments in stroke rehabilitation. This content comparison should enable clinicians and researchers to choose the measure that best matches the area of their interest. PMID- 17364774 TI - Path tree analysis as a tool for describing motor recovery following acquired brain injury: an exploratory study. AB - PURPOSE: Knowledge of the likely sequence of motor recovery following brain injury has obvious usefulness within rehabilitation. Research has tended to focus on establishing the linearity of the recovery sequence. This study aimed to ascertain the usefulness of path tree analysis as a graphical means of exploring inter-subject variation in routes followed during motor recovery. METHOD: Data were collected via physiotherapist questionnaire, ascertaining recovery sequence of 14 motor milestones across 80 adults with severe traumatic brain injury (TBI). An adapted version of the Rivermead Mobility Index (RMI) was used. Data were analysed to establish inter-subject agreement regarding recovery sequence. A path tree diagram was then composed to explore inter-subject variation. RESULTS: Putative order of recovery for the 14 motor milestones appeared to have face validity. Guttman coefficients of reproducibility ((0.954) and scalability (0.948) were good, suggesting intrinsic order. Composition of a path tree suggested considerable variation in recovery paths between individuals, with 34 combinations of test items being evident. CONCLUSIONS: Motor recovery following severe TBI follows a distinct pattern, but path tree analysis emphasises the variety of routes which individuals can follow. Additional research should ascertain the scope of this method to document the natural history of the recovery process. PMID- 17364775 TI - Handling dilemmas of self-determination in 'user-centred' rehabilitation. AB - PURPOSE: To describe discursive strategies used by different professionals and parents to handle dilemmas of self-determination versus paternalism during six 'user-centred' team meetings in the Swedish rehabilitation sector. The dilemmas arise when the users' responses do not fully meet the demands of the liberal ideal of self-determination. METHOD: Three cases are used to illustrate three discursive strategies that have been found by means of discourse analysis of transcriptions of the audio-recorded meetings. Four teams consisting of one user each participate in the study. The users have been ascribed physical and/or cognitive disabilities and their ages vary between 14 and 30. RESULTS: The dilemmas were never made explicit. Parents and professionals performed a kind of paternalistic steering termed 'challenging the user's response', 'substituting for the user', or 'dropping the user's response'. CONCLUSIONS: The least paternalistic steering includes making the dilemma explicit and offering the user the opportunity of sharing the responsibility for the handling of the situation. However, due to the complexity of the interactions no strategy can be found to either completely prevent the occurrence of dilemmatic situations, or definitely maintain the user's self-determination during dilemmatic situations. Paternalism may occasionally be a just way of enhancing future autonomy. PMID- 17364776 TI - An introduction to the Korean Employment Promotion Agency for the Disabled. AB - PURPOSE: The main aim of this article is to provide an introduction to the Korean Employment Promotion Agency for the Disabled (KEPAD), and to provide comparative thought regarding government-based vocational rehabilitation service delivery between South Korea and the USA. METHOD: Relevant literature is considered, and current issues and comparative discussion in practice are highlighted. RESULTS: Introductory information in terms of organization, eligibility, services and programmes are presented. In addition, practical problems associated with the KEPAD system and a cross-cultural analysis is elaborated, comparing the USA and South Korean vocational rehabilitation systems. CONCLUSION: KEPAD has successfully derived public support and acknowledgement of its national responsibility in ensuring vocational rehabilitation services for persons with disabilities. The KEPAD system demonstrates a unique approach in implementing vocational rehabilitation services by providing various benefits for both employers and persons with disabilities. However, considerable cautiousness in terms of cross-cultural analyses is required for international application. Furthermore, successive research of rehabilitation infrastructure is warranted. PMID- 17364777 TI - Depression and occupational disability in five diagnostic groups: a review of recent research. AB - PURPOSE: To compare the methodologies and results of research across five diagnostic groups in which there was expected to be a high prevalence of depression and occupational disability. METHOD: A review of research published since 1994 was carried out concerning depression and occupational disability in five diagnostic groups: Major depressive disorder (MDD), spinal cord injuries (SCI), traumatic brain injuries (TBI), chronic back pain (CP) and myocardial infarction/coronary artery bypass grafting (MI/CABG). RESULTS: Prospective longitudinal designs were mostly undertaken in MDD studies. Diagnostic interview schedules were utilized in most MDD studies whereas self-report inventories that tend to confound somatic and depressive symptoms were mostly used in CP, SCI, TBI and MI/CABG studies. In longitudinal MDD studies both depression and occupational disability were related to access to enhanced primary care treatment. On the other hand, CP research reported different results concerning the strength of depressive symptoms, cognitive and psychosocial factors in predicting occupational disability. Different trends across diagnostic groups were evident in relation to depression, occupational disability, co-morbidity, socio demographic factors and psychosocial resources. CONCLUSIONS: Co-morbid, socio demographic and psychosocial factors provide a framework from which to identify those at greater risk of depression and occupational disability. However, more CP, SCI, TBI and MI/CABG studies with diagnostic schedules, prospective designs and longer follow-up are required. PMID- 17364778 TI - Understanding the complex interplay between tourism, disability and environmental contexts. AB - PURPOSE: To explore and describe the complex issues and factors related to participation in tourism as perceived by people with disabilities in Hong Kong. METHOD: Naturalistic inquiry using key informant interviews and focus groups with 86 people with disabilities. Interviews were transcribed, translated and coded to develop themes and relationships. Triangulation of three investigators from different backgrounds occurred. RESULTS: The Process of Becoming Travel Active emerged as a six-stage process, intricately related to the personal/disability context and the environmental/travel context. Personal and environmental factors contribute to the six-stage model explaining the complex interplay between tourism, disability and environmental context. CONCLUSION: Understanding the complexity provides insight into ways to increase active participation in tourism. Health, tourism and disability sectors have a role to play in the development of accessible tourism. PMID- 17364779 TI - Somatosensory recovery: a longitudinal study of the first 6 months after unilateral stroke. AB - PURPOSE: The aim of this study was to characterize the recovery pattern of stroke patients in the first 6 months following stroke. METHOD: Using the Rivermead Assessment of Somatosensory Performance (RASP), the Motricity index and the Barthel Activities of Daily Living (ADL) index, a case series of serial somatosensory and motor measurements was made on 18 patients with a diagnosis of a first ever stroke. Patients comprised 2 distinct groups, acute and subacute. The acute group were seen weekly for the first month post onset and the subacute group were seen monthly for 6 months. Participants were seen at hospital, regional rehabilitation unit and/or the participant's home. Standard local rehabilitation was given. RESULTS: The somatosensory subtest of proprioception demonstrated the greatest level of recovery. No patient achieved full recovery on all somatosensory subtests. Motor and functional recovery demonstrated continual improvement over time, somatosensory recovery showed marked variation in subtests both within and between patients. CONCLUSION: Of the 18 patients tested there were no consistent, generalizable, recognizable patterns of sensory recovery demonstrated. PMID- 17364780 TI - Return to productivity following traumatic brain injury: cognitive, psychological, physical, spiritual, and environmental correlates. AB - PURPOSE: The purpose of this study was to investigate the determinants and correlates of return to productivity (RTP) defined here as return to paid employment and/or school four years following traumatic brain injury (TBI). METHOD: Participants included 46 people with TBI, part of a prospective, cohort study, and 14 friend/family member controls all employed and/or in school at time of injury or inception into the study. Variables were selected for investigation based on two models of recovery. Demographic and injury severity data including time to recover free recall were collected at time of injury, on admission to a trauma unit. Data on other variables (neuropsychological, psychological, physical, spiritual, environmental) were collected concurrent with productivity status at a mean of 4.3 years post-TBI. RESULTS: Time to recover free recall (measured acutely), neuropsychological status, pain severity, depression, and the use of maladaptive coping behaviours were all related to productivity status (p < 0.05). When these variables were entered into exploratory, planned hierarchical logistic regression models time to free recall, pain, and maladaptive coping remained in the models with depression only dropping out because of the high correlation with pain (r > 0.80). CONCLUSIONS: Injury severity (time to free recall), physical status (pain), and psychological status (depression, coping) are important to understanding differences in productivity outcomes. Addressing pain, depression and coping in rehabilitation programs may have a positive impact on outcomes. PMID- 17364781 TI - Validation of the Middlesex Elderly Assessment of Mental State (MEAMS) as a cognitive screening test in patients with acquired brain injury in Turkey. AB - PURPOSE: Assessment of cognitive impairment with a valid cognitive screening tool is essential in neurorehabilitation. The aim of this study was to test the reliability and validity of the Turkish-adapted version of the Middlesex Elderly Assessment of Mental State (MEAMS) among acquired brain injury patients in Turkey. METHODS: Some 155 patients with acquired brain injury admitted for rehabilitation were assessed by the adapted version of MEAMS at admission and discharge. Reliability was tested by internal consistency, intra-class correlation coefficient (ICC) and person separation index; internal construct validity by Rasch analysis; external construct validity by associations with physical and cognitive disability (FIM); and responsiveness by Effect Size. RESULTS: Reliability was found to be good with Cronbach's alpha of 0.82 at both admission and discharge; and likewise an ICC of 0.80. Person separation index was 0.813. Internal construct validity was good by fit of the data to the Rasch model (mean item fit -0.178; SD 1.019). Items were substantially free of differential item functioning. External construct validity was confirmed by expected associations with physical and cognitive disability. Effect size was 0.42 compared with 0.22 for cognitive FIM. CONCLUSION: The reliability and validity of the Turkish version of MEAMS as a cognitive impairment screening tool in acquired brain injury has been demonstrated. PMID- 17364782 TI - Healing care? Rehabilitation of female immigrant patients with chronic pain from a family perspective. AB - PURPOSE: This pilot study aimed to address the social context of rehabilitation by exploring the perspectives of family members regarding rehabilitation of female immigrant patients with a chronic pain condition. METHOD: In-depth semi structured, face-to-face interviews were conducted with family members of nine patients. The interviews were transcribed and subsequently coded and analysed according to themes. RESULTS: All participants acknowledged that their respective relative experiences pain. Pain is considered a symptom of the malfunctioning body and different explanatory notions are given. Participants regarded medication, warmth, rest or gentle exercise to be appropriate treatment options. Most participants had limited awareness of, and involvement in, rehabilitation. The role of family members in illness management lies mainly in providing advice and in taking over or assisting in domestic activities. CONCLUSION: The importance of considering the patient's social context and involving family in the treatment process is indicated in the literature. However, awareness of the aim and content of rehabilitation was limited among most participating family members as was their involvement in the rehabilitation process of their relative. It is recommended that further research needs to look at factors influencing involvement of family members before effective strategies for involving family members of patients of various socio-economic and/or cultural backgrounds can be developed. PMID- 17364783 TI - The association between patients' cognitive status and rehabilitation outcome in a geriatric day hospital. AB - PURPOSE: To assess whether and to what extent cognitive status affects functional gain in mobility and extended activities of daily living (ADL) in patients admitted to a geriatric day hospital. METHODS: During 2003, 135 older patients admitted to a rehabilitation day hospital were evaluated by the Mini Mental State Examination (MMSE) and the Cognitive Functional Independence Measure (FIM). On admission and at discharge, they were assessed by the Nottingham Extended ADL Index (NEAI) and the Timed Get Up and Go test (TUG). RESULTS: Orthopedic and stroke patients achieved significant functional gain in mobility regardless of their cognitive status. Nevertheless, cognitively intact stroke patients achieved higher admission and discharge NEAI scores, manifesting greater absolute functional gain than cognitively impaired patients. The patients' ability to extract their rehabilitation potential was significantly better. CONCLUSIONS: Cognitively impaired patients can improve in mobility and performance of extended ADL during day hospital rehabilitation. Evaluation of the patients' cognitive status may enable the multidisciplinary team to develop suitable individual programs and better allocate resources. Cognitively intact stroke patients may benefit from extended rehabilitation treatment compared to impaired stroke patients as they are more capable of utilizing their potential to achieve independence in daily tasks. PMID- 17364784 TI - Rehabilitation outcome following hip fracture surgery in elderly diabetics: a prospective cohort study of 224 patients. AB - PURPOSE: To characterize the course and outcome of rehabilitation following hip fracture (HF) in elderly diabetic patients. METHOD: A non-interventional prospective cohort study of 224 elderly diabetic patients who were hospitalized for rehabilitation, compared to 738 non-diabetic patients. Stepwise multiple regression was used to assess the relative contribution of the variables to the variance of the rehabilitation outcome. RESULTS: The absolute efficacy of rehabilitation was lower in diabetics vs. non-diabetics (28.8 +/- 20.0 vs. 31.8 +/- 18.4, respectively, p = 0.04). This difference was caused by a significantly lower pre-event Functional Independence Measure (FIM) (112 +/- 17 vs. 115 +/- 14, p = 0.002) and a significantly higher rate of prior stroke with motor impairment (16% vs. 7%, p < 0.0001). No significant difference was found between the study groups for various rehabilitation-related complications, including mortality. None of the 12 specific variables associated with diabetes or its complications was significantly and independently associated with the outcome of rehabilitation among diabetics. CONCLUSIONS: The outcome of rehabilitation in elderly diabetic patients following HF is significantly worse than in non-diabetics. This result stems from the poor pre-event functional state of these patients. The results of this study can help to predict the outcome of rehabilitation in elderly diabetic patients who are candidates for rehabilitation following surgical repair of HF. PMID- 17364785 TI - Independent living following a 'Do Not Resuscitate' order after subarachnoid haemorrhage. AB - PURPOSE: The recovery and psychosocial adjustment of a 41-year-old right handed women (K.E.) following subarachnoid haemorrhage (SAH) with initially poor predicted prognosis is presented. METHOD: A single case report with an early post surgery 'Do Not Resuscitate' order following SAH with a significant period of impaired consciousness is outlined. RESULTS: Following a right frontal craniotomy and clipping of a left distal anterior communicating artery (AcoA) aneurysm, K.E. was unresponsive for 23 days and 'minimally conscious' for a further 5+ weeks post surgery (36 days). At two months post insult, after some neurological improvement, she was transferred for post-acute goal directed neurorehabilitation. At 8 months post insult, after 4 months inpatient and 2 months intensive outpatient neurorehabilitation, K.E. was largely independent, did not require home care services and had made a good psychosocial adjustment to her acquired difficulties. CONCLUSIONS: The potential for recovery following a significant period of reduced consciousness after SAH is highlighted despite initially poor prognostic indicators. PMID- 17364786 TI - Determinants of depression in chronic stroke: a prospective cohort study. AB - PURPOSE: The aim of the study was to identify factors that are significantly related to depression in chronic stroke patients. METHODS: Prospective cohort study of stroke patients admitted for rehabilitation. A total of 165 first ever stroke patients over 18 years of age were assessed at one and three years post stroke. Depression was determined by the Centre for Epidemiologic Studies Depression Scale (CES-D). Patients with scores >/=16 were classified as depressed. Bivariate and multivariate logistic regression analyses were used to identify prognostic factors for depression. RESULTS: At three years post stroke, 19% of the patients were depressed. Bivariate analysis showed significant associations between post-stroke depression and type of stroke, fatigue, motor function of the leg and arm, activities of daily living (ADL) independency and instrumental ADL. Multivariate logistic regression analysis showed that depression was predicted by one-year instrumental ADL and fatigue. Sensitivity of the model was 63%, while specificity was 85%. CONCLUSIONS: The present prospective cohort study showed that depression three years after stroke can be predicted by instrumental ADL and fatigue one year post stroke. Recognition of prognostic factors in patients at risk may help clinicians to apply interventions aimed at preventing depression in chronic stroke. PMID- 17364787 TI - Relationship between self-reported upper limb disability and quantitative tests in hand-arm vibration syndrome. AB - PURPOSE: To establish the relationship between quantitative tests of hand function and upper limb disability, as measured by the Disability of the Arm, Shoulder and Hand (DASH) questionnaire, in hand-arm vibration syndrome (HAVS). METHOD: A total of 228 individuals with HAVS were included in this study. Each had undergone a full HAVS assessment by an experienced physician, including quantitative tests of vibrotactile and thermal perception thresholds, maximal hand-grip strength (HG) and the Purdue pegboard (PP) test. Individuals were also asked to complete a DASH questionnaire. RESULTS: PP and HG of the quantitative tests gave the best and statistically significant individual correlations with the DASH disability score (r2 = 0.168 and 0.096). Stepwise linear regression analysis revealed that only PP and HG measurements were statistically significant predictors of upper limb disability (r2 = 0.178). Overall a combination of the PP and HG measurements, rather than each alone, gave slightly better discrimination, although not statistically significant, between normal and abnormal DASH scores with a sensitivity of 73.1% and specificity of 64.3%. CONCLUSIONS: Measurements of manual dexterity and hand-grip strength using PP and HG may be useful in helping to confirm lack of upper limb function and 'perceived' disability in HAVS. PMID- 17364788 TI - HIV/AIDS and disability: differences in HIV/AIDS knowledge between deaf and hearing people in Nigeria. AB - PURPOSE: Studies both in North America and Europe have found that deaf individuals lack access to AIDS information, due to problems in communication, low literacy and tightly woven social networks within the deaf community. However few comparable studies are available from countries in the Developing World. The present study was undertaken in Nigeria where there is an estimated adult HIV prevalence rate of 5.4%. We sought to compare HIV knowledge among deaf and hearing individuals in order to identify how effectively deaf members of the community are being reached by HIV/AIDS messages. METHODS: A survey comparing knowledge about HIV/AIDS among deaf and hard of hearing adolescents (n = 50) and young adults (n = 50) was undertaken. RESULTS: Significant differences (p < 0.05) in levels of understanding about certain aspects of how AIDS is spread were identified as well as differences in available resources for access to accurate information among deaf members of the population. CONCLUSION: These findings from Nigeria speak strongly to the need for the development of interventions that include people with disabilities in public health and HIV/AIDS strategies and that address their specific vulnerabilities. Evaluating the adaptation of education material and the inclusion of the deaf population in HIV awareness programmes is an urgent 'next step.' PMID- 17364789 TI - Validation of the Dutch Giving Youth a Voice Questionnaire (GYV-20): a measure of the client-centredness of rehabilitation services from an adolescent perspective. AB - PURPOSE: The objective was to validate the Dutch translation of the Canadian Giving Youth a Voice Questionnaire (GYV-20) for use in paediatric rehabilitation settings in The Netherlands. The GYV-20 consists of 20 items (assessing four domains) and was designed to evaluate the client-centredness of rehabilitation services from an adolescent perspective. METHOD: The construct validity, concurrent validity, and reliability of the Dutch GYV-20 were determined. Participants were 116 youngsters aged 11 - 21 years (Mean = 15.9; SD = 2.1) recruited through six paediatric rehabilitation settings in The Netherlands. RESULTS: Correlations between the GYV-20 scale scores were positive (r = 0.69 - 0.78). The GYV-20 showed adequate internal consistency, with Cronbach's alpha ranging from 0.76 - 0.81. The ICCs of test-retest reliability ranged from 0.82 - 0.92, which demonstrated good stability of the GYV-20. Dutch adolescents judged the GYV-20 as a valuable and useful tool to evaluate rehabilitation services in The Netherlands. CONCLUSIONS: The Dutch GYV-20 showed sufficient evidence of construct validity and good reliabilities. The Dutch GYV-20 offers users a useful measurement option for various research and clinical purposes. PMID- 17364790 TI - The immigrant patient having widespread pain. Clinical findings by physicians in Swedish primary care. AB - AIM: Do the clinical findings explain the complaints of longstanding demonstrated widespread pain (DWP) in a group of immigrant patients, or not? SUBJECTS: Consecutive immigrant patients, on long-term sick leave, aged 18 - 45, at a primary healthcare centre in Stockholm, Sweden. METHODS: Interpreters were available. Two primary care physicians jointly, made a somatic status and diagnosed tender-structure locations (> or =3 tender-structure locations or less) and depression (yes or no), and assessed psychosocial stressors (little or much) and pain-related anxiety (yes or no). The patients pointed at their pain parts. This was transferred by one of the doctors to a pain drawing with 18 fields. Five or more fields were defined as DWP. Non-parametric tests were used to detect significant differences between the DWP and non-DWP groups. Cumulative frequencies of the following four categories of explanatory variables of DWP were counted: > or =3 tender-structure locations (could also include the other variables), much psychosocial stress (could include depression and pain-related anxiety), depression (could include pain-related anxiety), or pain-related anxiety alone. RESULTS: Many of the 49 men and 100 women, on average 38 years, spoke little or no Swedish. A fifth of the men (n = 10) and half (n = 56) of the women had DWP. These men often had much stress (p < 0.01) while the women had > or =3 tender-structure locations (p < 0.001). DWP among men was explained to 100% by: > or =3 tender-structure locations (30%), much psychosocial stress (60%), or depression alone (10%). DWP among the women was explained to 96 cum. % by: > or =3 tender-structure locations (59%), much psychosocial stress (25%), or pain related anxiety alone (13%). CONCLUSION: Demonstrated widespread pain was nearly always explained by clinical findings, and especially by numerous tender structure locations in women. There is a need for more studies among men. PMID- 17364791 TI - Goal setting in neurological rehabilitation: patients' perspectives. AB - PURPOSE: Goal setting has been described as the core skill of rehabilitation professionals, but there is little information about patients understanding of goal setting. This study explored how in-patients with neurological impairments experienced two different types of goal setting and identified the issues that underpin individuals' experience of goal setting. METHOD: The study took place in a neurological rehabilitation unit in which two approaches to goal setting were being used that differed in the amount of patient involvement. A qualitative research design was adopted. Six focus groups were convened, three for participants experiencing usual participation and three for those with increased involvement in goal setting. A total of 28 participants (12 women, mean age 49 years) with a variety of deficits were recruited to the study over nine months. Thematic analysis was used to analyse the focus group transcripts. FINDINGS: Four themes were identified which impact on the ways in which in-patients make sense of goal setting: The rehabilitation process; personal response to goal setting; previous experience and disease limitations. CONCLUSIONS: Healthcare professionals working in rehabilitation need to explore patients' understandings of their disease and their experiences and expectations of goal setting to ensure goal setting is a meaningful activity. PMID- 17364792 TI - The effect of perceived adherence to the Bobath concept on physiotherapists' choice of intervention used to treat postural control after stroke. AB - PURPOSE: The Bobath concept is the predominant stroke physiotherapy approach in the UK but there is little literature about its operationalization. The aim of this study was to assess the effect of perceived adherence to the Bobath concept on interventions used by physiotherapists to treat postural control problems after stroke. The physiotherapists' experience, clinical grade and the type of patients treated were also compared. METHODS: The design was a cross sectional survey involving 11 NHS Trusts. The participants were 35 stroke physiotherapists who recorded the treatment of 132 patients in 644 sessions using the Stroke Physiotherapy Intervention Recording Tool. Descriptive statistics, independent t tests and Chi-squares were used in the analysis to describe the physiotherapists and patients, and compare the effects of perceived adherence to the Bobath concept on intervention choice, clinical grade, experience and the type of patient treated. RESULTS: Most physiotherapists perceived their practice to be eclectic but the interventions used followed a traditional Bobath model. Perceived adherence to the Bobath concept had little effect on the choice of intervention. The only significant difference was that 'preparation for treatment' techniques were used more frequently by 'strongly Bobath' physiotherapists then 'eclectic' physiotherapists. There were no other significant differences, nor were there any differences in the physiotherapists' clinical grade, post-graduate training or the type of patient treated except that 'eclectic' physiotherapists' patients were older. Most of the 'strongly Bobath' physiotherapists were experienced and most of the 'eclectic' physiotherapists were novices (p<0.023). CONCLUSIONS: Although most physiotherapists perceived themselves to be eclectic, their actual practice followed a traditional Bobath model; recent developments of the Bobath concept were not incorporated into clinical practice. The reasons for the mismatch between physiotherapists' perception and their actual practice are discussed. PMID- 17364793 TI - Evaluation of a consumer-personal assistant training project. AB - PURPOSE: This study evaluated a personal assistance services (PAS) training programme that aimed to improve the consumer and personal assistant relationship and increase consumer and personal assistant knowledge on health and wellness issues. METHOD: A total of 87 consumers and 53 personal assistants were enrolled in this longitudinal intervention study. Consumers and personal assistants in the intervention group participated in a six-hour in-person PAS training programme. RESULTS: Consumers and personal assistants who participated in the training had increased knowledge at both three and six months post-training compared to consumers and personal assistants who were in the non-treatment group. There were no differences in consumer/personal assistant relationship variables. CONCLUSIONS: Future studies should examine the impact of PAS training programmes on health behaviours needed to decrease secondary conditions. PMID- 17364794 TI - Stress-related sickness absence and return to labour market in Sweden. AB - PURPOSE: To analyse factors influencing chances of returning to work after long term sickness absence with a stress-related psychiatric diagnosis. Primary focus is on employer- and occupational categories as explanatory variables. METHOD: Data was collected from the regional social insurance office in the county of Varmland for 911 individuals, all with stress-related sickness absences during November in the year 2000. Logistic regressions were carried out on outcome states from long-term sickness absence on two follow-up occasions after two and three years. RESULTS: The results indicate that the employer- and occupational categories only had a minor effect on return to work after the long-term sickness absence. Age and health-related factors together with time factors seem to be more relevant in explaining return to work. CONCLUSIONS: The findings suggest that individual labour market position, as occupation, employer, branch etc, seems to be less important than expected in explaining return to work from sickness absence due to stress-related psychiatric disorders. PMID- 17364795 TI - Reduction of disability after stroke is a more informative predictor of long-time survival than initial disability status. AB - PURPOSE: Few studies have evaluated the roles of reducing disability after stroke in predicting survival. This study aimed to investigate the effects of improvement in the Barthel Index (BI) and other prognostic factors on survival in patients with first-time noncardioembolic ischemic stroke. METHOD: BI effectiveness was defined as the improvement of BI between initial stroke (within 3 days) and 2 months after stroke. Cox regression analysis and Kaplan-Meier methods were used to evaluate the predictive roles of various prognostic factors. RESULTS: A total of 111 patients were enrolled. Mean age at the time of stroke was 68 (+ or - 11.2) years. Median follow-up time was 77.4 months. Mean initial BI was 36.1 (+ or - 28.5) and mean BI effectiveness was 46.9 + or - 29.0. Overall, 55 deaths (49.5%) of the cohort were ascertained. The BI effectiveness had significant effects on long-time survival while initial BI was not a significant predictor. Higher BI effectiveness led to lower risk of mortality (hazard ratio = 0.44, 95% CI 0.24 - 0.80, p = 0.007). Elder age was correlated with poor survival (overall p = 0.006). Subjects in the eldest age group (> or = 70 years) showed a significant elevated risk for death (hazard ratio = 3.42, 95% CI 1.18 - 9.92). There was a trend indicating that the smaller the lesion size, the more favourable the prognosis (overall p = 0.057). CONCLUSIONS: BI effectiveness in the first 2 months after first-time noncardioembolic stroke was more informative than initial disability status for predicting long-time mortality. It highlights the potential benefit in maximizing functional performance in patients with stroke. PMID- 17364796 TI - Who cares? - caring for the carers of stroke patients. PMID- 17364797 TI - Economic empowerment and black disabled entrepreneurs: negotiating partnerships in Cape Town, South Africa. AB - PURPOSE: This paper presents a second part reporting on Community Disability Entrepreneurship Project (CoDEP) which was initiated in order to contribute to the development of entrepreneurial skills of disabled people living in informal settlements around Cape Town, South Africa. The aim of CoDEP has been the upliftment and economic empowerment of disabled people. This paper describes the point of departure, the theoretical framework of participatory action research (PAR), the development of research parameters, and continued focus. METHOD: A participatory action research (PAR) approach was initiated in order to monitor and inform the effective development of CoDEP. This cyclic methodology allowed all participants to engage in decision-making and development of the programme. RESULTS: While negotiating partnerships with disabled entrepreneurs, the six spheres within which optimal interaction could take place emerged as: (i) the choice of occupation; (ii) changing a culture of receiving; (iii) nurturing teamwork by negotiating roles and responsibilities; (iv) a focus on ability; (v) understanding the research process; and (vi) organizational development dynamics. Committed interaction emerged as the quintessence of these partnerships. PMID- 17364798 TI - Assessment of degree of satisfaction of cancer patients and their families with rehabilitation and factors associated with it--results of a Japanese population. AB - PURPOSE: To evaluate the effectiveness of rehabilitation from the standpoint of both cancer patients and their families and their degree of satisfaction with it and to assess factors associated with their degree of satisfaction. METHOD: The subjects were 23 inpatients for whom rehabilitation had been prescribed during the period of the survey, and their families. Degree of satisfaction with rehabilitation and associated factors were assessed using questionnaires by both patients and their families twice: Before and 2 weeks after the start of rehabilitation. RESULTS: The mean scores for degree of patient satisfaction and degree of family satisfaction were 8.6 and 7.7 (0-10), respectively. Awareness of rehabilitation (after rehabilitation), willingness for rehabilitation (before and after rehabilitation), emotional state (before and after), effectiveness of rehabilitation, and communication with staff were significantly correlated with degree of patient satisfaction. Emotional state of the patient (before), change in emotional state of the patient, family awareness of rehabilitation (after), change in emotional state of the family, and communication with staff were significantly correlated with degree of family satisfaction. CONCLUSIONS: The results indicated that both the cancer patients and their families were satisfied with rehabilitation. They also suggested a need to understand and provide care for the emotional state of patients and their families in order to increase their degree of satisfaction, and a need for adequate explanation and active involvement to increase awareness and willingness in regard to rehabilitation. PMID- 17364799 TI - From childhood to adult life with juvenile idiopathic arthritis (JIA): a pilot study. AB - PURPOSE: To explore the experiences of the health service provision in the transition process from childhood to adult life from the perspective of young patients with juvenile idiopathic arthritis (JIA) and health professionals working in this field. METHOD: Two groups of young persons with JIA and two groups of health professionals were interviewed in focus groups. The data were analysed according to approved guidelines for qualitative analysis. RESULTS: 'Capability to lead a meaningful adult life' emerged as a core category; capability as a consequence of 'being enabled' from the youths' point of view, and 'enabling the young patients' from the health professionals' perspective. Preparation for the transition and transfer process was perceived as inadequate and seemed dependent on enthusiastic health professionals both in the children's and adult wards. Suggestions for formal improvements were required in four main areas. CONCLUSION: This pilot study has identified inadequacies in the transition management provided for young people with JIA. Acceptance of the young persons as active participants in their own transition process might strengthen these young persons' experience of an autonomous identity and enable participation socially and in society, thus enhancing the ability to achieve a meaningful adult life. Further investigations should focus on adults living with JIA, how they lead their lives physically and psychosocially. PMID- 17364800 TI - Determinants of functioning of adolescents and young adults with cerebral palsy. AB - PURPOSE: To describe the level of functioning of adolescents and young adults with cerebral palsy (CP) and study determinants of their level of functioning. METHOD: In the CP Transition study, adolescents and young adults aged 16-20 years, diagnosed with CP without severe learning disabilities (n =103) participated. In this group we assessed subject characteristics, i.e., age, type of CP, gross motor function (GMFCS), level of education as well as outcome measures on functioning in daily activities and social participation (Life Habits questionnaire, Vineland Adaptive Behavior Scale, Functional Independence Measure). Multivariate regression analyses were performed. RESULTS: About 20-30% of the participants encountered restrictions in daily activities (mobility, self care, nutrition) and social participation (taking responsibility, community living, leisure activities and employment). The GMFCS level, level of education, and age proved to be important determinants of functioning in daily activities and social participation, explaining 70% and 66% of the variance in outcome respectively. CONCLUSION: A significant number of adolescents and young adults with CP without severe learning disabilities are restricted in daily activities and social participation. These problems are mainly attributable to restricted gross motor functioning, a low level of education and younger age. PMID- 17364801 TI - Health-promotion needs of youth with a spinal cord injury in South Africa. AB - PURPOSE: To determine the health promotion needs through an exploration of health related behaviours and the factors that influence the behaviour of physically disabled youth with spinal cord injury. METHODS: A descriptive and exploratory study that utilized a qualitative approach was carried out among ten participants aged between 15 and 29 years who were purposely selected. Information was obtained from individual face-to-face interviews and a focus-group discussion. RESULTS: The participants were involved in risky health behaviours including sedentary lifestyles, use of alcohol, tobacco, and drugs. Various factors that influenced their participation in these behaviours were identified including personal struggles with identity and adjustment issues. CONCLUSIONS: The results emphasize that participants were involved in health-risk behaviours, which are associated with development of secondary conditions such as respiratory problems, heart diseases, and stroke. Health-promotion strategies employed for these individuals should address the psychological impact of spinal cord injury (SCI) on the individual as an influence to participation in health risk behaviours. PMID- 17364802 TI - Social participation after successful kidney transplantation. AB - PURPOSE: To explore and describe the degree of social participation after kidney transplantation and to examine associated factors. METHOD: A cross-sectional study on 239 adult patients 1-7.3 years after kidney transplantation was performed via in-home interviews on participation in obligatory activities (i.e., employment, education, household tasks) and leisure activities (volunteer work, assisting others, recreation, sports, clubs/associations, socializing, going out). RESULTS: Kidney transplantation patients had a lower educational level, spent less time on obligatory activities, had part-time jobs more often, and participated less in sports compared to a control group from the general population. No difference was found in socializing, church attendance, volunteer work and going out. Multivariate regression analysis showed a negative association of age and a positive association of educational status and time since transplantation with obligatory participation. Multivariate logistic regression showed positive associations of education and time since transplantation with volunteer work; age was negatively and education positively associated with sports and going out, whereas living arrangement was also associated with going out. CONCLUSIONS: Although kidney transplantation patients participate less in employment and sports, they do participate in household tasks, volunteer work, going out, socializing and other leisure activities. Participation is associated with factors as age, educational status and time since transplantation. PMID- 17364803 TI - How do people with COPD or diabetes type 2 experience autonomy? An exploratory study. AB - PURPOSE: To develop an empirically grounded conceptualization of personal autonomy in the context of chronic physical illness and to investigate the impact of two chronic illnesses on autonomy. METHOD: Grounded theory study consisting of 13 in-depth interviews with older adults with Chronic Obstructive Pulmonary Disease (COPD) or diabetes mellitus type 2 (diabetes). RESULTS: The results indicate that autonomy involves taking account of current circumstances as the frame of reference in which people can arrange their lives. Chronic illness disturbed autonomy by limiting opportunities and by prompting a reappraisal of the value that people placed on different activities or aspects of life. The participants responded to this disturbance differently, in ways that did not always restore autonomy. Limited opportunities occurred more often with COPD, while reappraisal occurred more often with diabetes. CONCLUSIONS: Personal autonomy in the context of chronic physical illness might be conceptualized as correspondence between the way people's lives are actually arranged and the way people want their lives to be arranged, considering the circumstances. Health professionals could stimulate their clients to prevent and overcome impasses in the realisation of autonomy, while broad self-management interventions might improve people's skills for coping with the impact of chronic illness on autonomy. PMID- 17364804 TI - Targeted early rehabilitation at home after total hip and knee joint replacement: Does it work? AB - PURPOSE: This study evaluates the benefits of targeted early rehabilitation at home after total hip or knee replacement surgery and analyses the cost effectiveness of such a scheme. METHOD: Patients recovering from Total hip replacement (THR, n = 220) and Total knee replacement (TKR, n = 174) were assessed in a NHS District General Hospital setting. Suitability of patients for early rehabilitation at home scheme (RAHS) was assessed at the pre-operative clinic by rehabilitation team. Length of in-patient stay (LOSH), duration on the scheme, number of bed days saved, cost appraisal, readmission rates and complications were recorded. RESULTS: Targeted early rehabilitation resulted in reduced hospital stay (from 14-8.17 days for THR and from 12-8.21 days for TKR), without any increase in complication rates. Significance testing revealed no statistical difference between the patient groups with regards to age, residence status, mobility and transfer ability on their length of stay in hospital or on the rehabilitation scheme. The patients who underwent total knee replacement required significantly more number of visits by the rehabilitation team than those who underwent total hip replacement (p value < 0.05). This resulted in an overall saving of pound 301,124 for the trust over the study period. CONCLUSIONS: Targeted early rehabilitation resulted in reducing the length of hospital stay without an increase in complication rates. The use of such a scheme brought significant savings to the trust without an increase in readmission rates. PMID- 17364805 TI - The effect of two physiotherapy approaches on physical and cognitive functions and independent coping at home in stroke rehabilitation. A preliminary follow-up study. AB - PURPOSE: Activating physiotherapy was used to support the principle of post stroke functional recovery as a learning process which requires both cognitive and physical actions. The purpose of the present preliminary study was to examine the influence of activating physiotherapy on stroke patients' cognitive and physical functions and independent living at home compared with traditional treatment over a 12-month follow-up. METHODS: The 40 patients who received activating physiotherapy were compared with 40 patients receiving traditional therapy. Patients' physical functional capacity was measured one week and 12 months post stroke with the Barthel Index (BI), 10-m gait speed, the Postural Control and Balance for Stroke (PCBS) test, walking distances and patients' abilities to cope without outside help. Cognitive capacity was measured with specific neuropsychological tests: language, visuospatial functions, visual inattention and memory. RESULTS: Physical functional capacity improved significantly (p = 0.001) in both groups at the 12-month follow-up, but no significant differences were found between groups. However, the patients in the activating therapy group coped better without outside help (p = 0.042) and covered longer distances outdoors (p = 0.012). At follow-up all the measured cognitive functions had improved significantly in the activating therapy group and the change in memory in the same group differed significantly from that in the traditional therapy group (p < 0.001), where no significant improvement was observed. CONCLUSIONS: Activating therapy advanced stroke patients' cognitive and physical functional recovery and supported their return to independent life at home more than did traditional physiotherapy. In this respect activating therapy seems to have a beneficial influence on long-term stroke rehabilitation. PMID- 17364806 TI - Psychometric evaluation of a Norwegian version of the Communication Strategies Scale of the Communication Profile for the Hearing Impaired. AB - AIM: To evaluate the Communication Strategies Scale (CSS) in an adult Norwegian sample with hearing loss. SUBJECTS AND METHODS: Of 474 invited patients, a total of 337 consecutive adults admitted to the outpatient Unit of Audiology, ENT Department of a university hospital answered the CSS of the Communication Profile for the Hearing Impaired. The inventory assesses the use of three specific coping strategies; Maladaptive Behaviour, Verbal and Nonverbal Communication Strategies. The psychometric evaluation included construct validity by corrected item-total correlation, the internal consistency reliability by coefficient alpha (Cronbach's) and standard error of the measurement (SEM). Internal structure was evaluated by factor analyses using principal factors followed by a varimax rotation. RESULTS: CSS showed good psychometric properties with acceptable and good internal consistency reliability for the subscales. The internal structure of the entire scale gave main loadings at 24 of 25 items at the same factor as the original one. CONCLUSION: CSS may well be used as a clinical tool in the routine assessment of maladaptive and adaptive communication strategies in an unselected adult population of hearing impaired outpatients. PMID- 17364807 TI - Cloning and characterization of cytochrome c oxidase subunit I (COXI) in Gobiocypris rarus. AB - In study of gene expression profile in cloned embryos which derived from D. rerio embryonic nuclei and G. rarus enucleated eggs, cytochrome c oxidase subunit I (COXI) of G. rarus, exhibiting difference at expression level between cloned embryos and zebrafish embryo, was cloned. Its full cDNA length is 1654 bp and contains a 1551 bp open reading frame, encoding a 5.64 kDa protein of 516 amino acids. The alignment result shows that mitochondrion tRNAser is co-transcripted with COXI, which just was the 3'-UTR of COXI. Molecular phylogenic analysis based on COXI indicates G. rarus should belong to Gobioninae, which was not in agreement with previous study according to morphological taxonomy. Comparison of DNA with cDNA shows that RNA editing phenomenon does not occur in the COXI of G. rarus. PMID- 17364808 TI - cDNA cloning and characterization of the novel genes related to aldehyde dehydrogenase from wild Chinese grape (Vitis pseudoreticulata W. T. Wang). AB - mRNA differential display was employed to study the gene differential expression of wild Chinese grape (Vitis pseudoreticulata W. T. Wang) infected by Uncinula necator in different periods, a cDNA fragment of T11AC/B0319-456 coded by aldehyde dehydrogenase (ALDH) gene has been obtained. 5' RACE and 3' RACE have been used to clone the whole cDNA sequences of ALDH which consists of three cDNA sequences, whose sizes are 1887, 1956 and 1961 bp, and they encoded a polypeptide size of 537, 524 and 477 designated as VpALDH2a, VpALDH2b and VpALDH1a, respectively. The deduced amino acid sequence shared highly identity with other plants and Human ALDH. Both VpALDH2a and VpALDH2b protein contain putative mitochondrial targeting sequence except VpALDH1a, it indicates that VpALDH2a and VpALDH2b are mitochondrial enzymes, and VpALDH1a is cytosolic enzyme. The VpALDH2a was subcloned into the expression vector pGEX-4T-1, transformed into E.coli BL 21-coden plus induced by IPTG, and about Mr. 85 kD of GST-ALDH fusion protein displayed in SDS-PAGE gel. PMID- 17364809 TI - Complete sequence and secondary structure of the large subunit ribosomal RNA from the harmful unarmored dinoflagellate Akashiwo sanguinea. AB - This is the first report of the complete DNA sequence of the gene encoding the ribosomal large subunit (LSU rDNA, 3336 bp) from the naked gymnodinioid dinoflagellate Akashiwo sanguinea. No introns were found in the LSU rDNA coding region and secondary structures were predicted for both the LSU and 5.8S rRNAs. The predicted LSU structure showed most of the features seen in the consensus secondary structure model proposed for the eukaryotic nuclear LSU rRNAs. However, six helices (C1_1, C1_2, C1_3, D10, D20_1 and H1_2) are not present in the A. sanguinea LSU structure. Particularly, the C branch area (or D2 domain), was extremely reduced compared to the eukaryotic consensus sequence due to nucleotide deletion. Phylogenetic resolution against 12 divergent (D) domains and cores in LSU rDNA showed that the D1, D2 and D12 domains were highly variable and could be used as genetic markers within low taxonomic levels, particularly in the gymnodinioid complex. PMID- 17364810 TI - Cloning and sequence analysis of germin-like protein gene 2 promoter from Oryza sativa L. ssp. indica. AB - Germin and germin-like proteins (GLPs) are water soluble extracellular proteins reportedly expressed in response to some environmental and developmental signals. Some enzymatic activities have also been associated with germin/GLPs. However, their role in overall metabolism has not been fully understood. Significant insight into their function may also be gained by analysis of their promoter. During this study, about 1107 bp 5'region of OsRGLP2 gene was amplified, cloned and sequenced. The sequence analysis by BLAST showed that this promoter sequence has five common regions (CR1-CR5) of different sizes, which are repeated at 3-6 other locations in 30 kb region in which this gene driven by its promoter is located. Interestingly, all the genes driven by promoter harboring these common regions are GLPs/putative germins. Analysis of these common regions located on OsRGLP2 indicated presence of many elements including those for light responsiveness, dehydration and dark induced senescence, stresses (pathogen and salt), plant growth regulators, pollen specific expression and elements related to seed storage proteins. Analysis of the 30 kb germin/GLP clustered region by GenScan detected each gene to have a putative 40 bp promoter which contains TATA box and Dof factor which turned out to be a part of CR2. PMID- 17364811 TI - Cloning and characterization of the EIN2-homology gene LeEIN2 from tomato. AB - A full-length cDNA, named LeEIN2 was cloned from tomato (Lycopersicon esculentum) by RT-PCR and RACE. Then the genomic DNA sequence of LeEIN2 was isolated by LA (Long and Accurate) PCR and Inverse PCR. This DNA sequence was 6838 bp including six introns. The LeEIN2 cDNA was 4343 bp and contained a 3951 bp open reading frame, encoding a 142.63 kDa protein of 1316 amino acids. Comparison of this protein sequence with that of Arabidopsis and Petunia showed that the amino acid homology was 66 and 90%, respectively. Northern blotting analysis indicated that the expression level of the LeEIN2 in young leaves was higher than in mature leaves and senescent leaves. During the development of fruits, the expression of the LeEIN2 was detected before mature green stage and got up to maximum at mature green and breaker stages, then reduced rapidly after breaker stage. The expression level of LeEIN2 in wild type tomato fruit at mature green stage did not distinctively change when treated with exogenous ethylene. PMID- 17364812 TI - Cloning and characterization of ovine alphaS1-casein gene promoter: a transfection study in rat mammary gland cell line. AB - Promoter regions of milk protein genes are frequently used to produce pharmaceutically and medically important proteins in the mammary gland of transgenic animals and also can be used for the construction of an inducible eukaryotic expression vector. The aim of the present study was to clone, sequence and characterize the regulatory elements in ovine alphaS1-CSNGP. For the first time we have cloned and sequenced region extending from - 2136 to +49 bp containing 5'-flanking region and exon I. Computational analysis of the sequence showed presence of core promoter elements viz., TATA box, CAAT box and initiator sequence. Mammary gland specific sequences included MGF/STAT 5, MPBF, Yu Lee 2, 4 and 5, Oka box C and hormone responsive elements (HRE) viz., GRE, PRE, PRL, IRE and also Polyoma enhancer 3 sequences. Computational analysis data is validated by following the reporter gene expression studies in rat breast cell line. Six reporter gene constructs under the control of full length, proximal, distal, minimal and proximal-distal fused promoter segments were constructed to assess the effect of presence or absence of few selected regulatory elements on expression ability of the promoter. Based on qualitative evaluation of fluorescence, the pGFP-F/VspI showed highest fluorescence followed by pGFP-P, pGFP-F/SpeI, pGFPminimal and pGFP-D. PMID- 17364813 TI - Sequence analysis of HSPA1A and HSPA1B in a multi-ethnic study population. AB - Two copies of the Hsp70 gene, HSPA1A and HSPA1B, are located on chromosome 6p21. The coding regions of HSPA1A and HSPAIB are intronless and nearly identical, however, promoter and 3' UTR sequences are different. The coding regions and putative promoter regions of HSPAIA and HSPAIB were re-sequenced in an affected and unaffected asthma screening panel of US Caucasians, African Americans, and US Hispanics (n = 72) to identify polymorphisms. HSPAIA and HSPAIB were each amplified in two separate whole-gene fragments. The polymorphisms identified were compared to those reported in dbSNP. Nine polymorphisms (one novel) were identified in HSPAIA, five of which are coding. Fourteen polymorphisms (five novel) were identified in HSPAIB, five of which are coding. One polymorphism (Asp110Glu GAG > GAC) was found in both genes. Two-thirds of the polymorphisms reported in dbSNP were not identified in our screening panel. Although similar in sequence, HSPAIA and HSPAIB do not share common patterns of polymorphisms. PMID- 17364814 TI - Cloning and expression of zebrafish genes encoding the heme synthesis enzymes uroporphyrinogen III synthase (UROS) and protoporphyrinogen oxidase (PPO). AB - Heme is synthesized from glycine and succinyl CoA by eight heme synthesis enzymes. Although genetic defects in any of these enzymes are known to cause severe human blood diseases, their developmental expression in mammals is unknown. In this paper, we report two zebrafish heme synthesis enzymes, uroporphyrinogen III synthase (UROS) and protoporphyrinogen oxidase (PPO) that are well conserved in comparison to their human counterparts. Both UROS and PPO formed pairs of bilateral stripes in the lateral plate mesoderm at the 15-somite stage. At 24 h post-fertilization (hpf), UROS and PPO were predominantly expressed in the intermediate cell mass (ICM) that is the major site of primitive hematopoiesis. The expression of UROS and PPO was drastically suppressed in the bloodless mutants cloche and vlad tepes/gata 1 from 15-somite to 24hpf stages, indicating that both cloche and vlad tepes/gata 1 are required for the induction and maintenance of UROS and PPO expression in the ICM. PMID- 17364815 TI - Expressed sequence tags from the halophyte Limonium sinense. AB - Halophytes can grow under a high salinity condition. Similar to glycophytes, their salt-tolerance possesses a high genetic complexity. There are many morphological and physiological studies on halophytes but very little information is at molecular level why they are salt-tolerant. Limonium sinense is a salt secreting halophyte and can excretes salts by multi-cellular glands. Here, we report the library construction and sequence analysis of a cDNA library made from leaf tissue of L. sinenes. Among those 1082 expressed sequence tag (EST) obtained, 684 unique genes were identified: 429 showed homology to previously identified genes, 255 matched to uncharacterized genes. Compared with other EST databases, some characteristic features such as abundance genes in related to cytoskeleton and intracellular traffic, membrane transporting were observed, which may be specific to halophytes. PMID- 17364816 TI - Identification of a cerulenin resistance gene from Monascus pilosus. AB - Detoxification is essential for the fungal growth in the drug stress environments, and the multidrug transporters play an important role in this process. Here a cerulenin transporter gene (MpMdt, AB206476) was identified from Monascus pilosus. MpMdt mRNA contains 1951 bp and encodes a protein of 559 amino acid residues with 11 trans-membrane domains; and there is no difference in the sequence of MpMdt mRNA between the wild type M. pilosus IFO4520 and its cerulenin resistant mutant MK-1. Up-expression of MpMdt renders the cerulenin resistance of the mutant MK-1. Over-expression of MpMdt could also increase the cerulenin tolerance in the transgenic M. pilosus IFO4520. These results suggested that MpMdt is able to efflux-transport the anti-fungal antibiotic cerulenin and increase the cerulenin resistance of M. pilosus. PMID- 17364817 TI - EFCBP1/NECAB1, a brain-specifically expressed gene with highest abundance in temporal lobe, encodes a protein containing EF-hand and antibiotic biosynthesis monooxygenase domains. AB - Human EFCBP/NECAB family consists of important participants in neuronal calcium signaling, including EFCBP1/NECAB1, EFCBP2/NECAB2 and EFCBP3/NECAB3. In the present study, we identified the full-length 5229 bp EFCBP1 cDNA which was not described before. Human EFCBP1 encodes a 351 amino acid protein containing two EF hand motifs and an antibiotic biosynthesis monooxygenase (ABM) domain, sharing 49.9 and 56.8% global homology with human EFCBP2 and EFCBP3. Northern hybridization revealed that EFCBP1 is specifically expressed in brain and its abundance varies in different brain regions. EFCBP1's abundance in temporal lobe, frontal lobe and occipital pole is about 3.4, 1.9 and 1.5 folds of the average abundance in cerebral cortex, respectively. The expression level of EFCBP1 equals in putamen and cerebral cortex, while no hybridization signal was detected in spinal cord. In addition, we found that EFCBP1, EFCBP2 and EFCBP3 share a similar exon distribution mode, though their chromosomal localizations, genomic sizes and intron sizes are diverse. PMID- 17364818 TI - Molecular cloning and characterization of Hymenolepis diminuta alpha-tubulin gene. AB - To isolate a full-length alpha-tubulin cDNA from an eucestode, Hymenolepis diminuta, a lambda phage cDNA library was constructed. The alpha-tubulin gene was cloned, sequenced and characterized. The H. diminuta alpha-tubulin consisted of 450 amino acids. This protein contained putative sites for all posttranslational modifications as detyrosination/tyrosination at the carboxyl-terminal of protien, phosphorylation at residues R79 and K336, glycylation/glutamylation at residue G445 and acetylation at residue K40. Comparisons of H. diminuta alpha-tubulin with all full-length alpha-tubulin proteins revealed that H. diminuta alpha tubulin possesses 10 distinctive residues, which are not found in any other alpha tubulins. Phylogenetic analysis showed that H. diminuta alpha-tubulin has grouped in a separated branch adjacent eucestode and trematodes branch with 92% bootstrap value (1000 replicates). In conclusion, this is the first report of H. diminuta cDNA library construction, cloning and characterization of H. diminuta alpha tubulin gene. PMID- 17364819 TI - Identification and characterization of a cDNA encoding the acetylcholinesterase of Haematobia irritans (L.) (Diptera: Muscidae). AB - A 2217-nucleotide cDNA presumptively encoding acetylcholinesterase (AChE) of the horn fly, Haematobia irritans (L.) was sequenced. The open reading frame (ORF) encoded a 91 amino acid secretion signal peptide and a 613 amino acid mature protein with 95% identity and 98% similarity to the AChE of Musca domestica (L.). Structural features characteristic of the M. domestica and Drosophila melanogaster AChEs are conserved in the H. irritans AChE. The M. domestica and D. melanogaster AChEs are target sites for organophosphate inhibition as previously shown (Walsh et al. 2001. Biochem. J. 359: 175-181, Kozaki et al. 2002. Appl. Entomol. Zool. 37: 213-218), suggesting that this H. irritans AChE2 may be the target site for organophosphate. PMID- 17364820 TI - Cloning and characterization of a LASS1-GDF1 transcript in rat cerebral cortex: conservation of a bicistronic structure. AB - LASS1 is the mammalian homologue of yeast longevity-assurance gene 1 (LAG1) which is differentially expressed during the yeast replicative life span and was shown to play a role in determining yeast longevity. Growth/differentiation factor 1 (GDF1) is a transforming growth factor-beta family member that was originally isolated from an mouse embryo cDNA library. GDF1 is expressed specifically in the nervous system and functions in left-right patterning of the mouse embryo. To explore the potential role of LASS1 in rat neuron aging, northern blot analysis for LASS1 mRNA was performed and detected a 2.7 kb transcript in adult rat cerebral cortex. Cloning and sequence analysis revealed that this transcript contains two nonoverlapping open reading frames (ORFs), LASS1 and GDF1, which are quite different to the predicted sequences in GenBank (accession number XM_224734 and XM_224733). The alignment with the rat genome database revealed this transcript matches the sequence of rat chromosome 16 genomic contig (GenBank accession number NW_047470) between nucleotide positions 1935060th and 1919439th, which contains eight exons and seven introns. Multiple sequence analysis revealed high conservation of the two ORFs. The phylogenetic analysis showed very close evolutionary relationship among rat, mouse and human. It raises the possibility that this mRNA may give rise to two different proteins and the conserved bicistronic structure might be of unknown significance. PMID- 17364821 TI - A soybean mapping population specific to the early soybean production system. AB - The objective of this research was to create a soybean [Glycine max (L.) Merr] genetic resource in the form of a publicly available, well-characterized mapping population specific to maturity groups (MG) used in the early soybean production system. A total of 568 simple sequence repeat (SSR) markers were tested for polymorphism between soybean breeding line DS97-84-1 (MG IV) and germplasm line DT97-4290 (MG IV). A 90-genotype subset of an F2 population from a cross between these lines was evaluated for genetic linkage using 162 polymorphic SSRs, plant height, pod color (L2/l2), flower color (W1/w1) and stem termination (Dt1/dt1). A 1514 cM (Kosambi) genetic map covering 65% of the soybean genome based on 157 linked SSR markers was created. Comparison with the composite soybean genetic map was used to verify map order. Loci for pod color, flower color and stem termination fell in the expected position on the map indicating this is a normally segregating mapping population. Loci for height were identified on linkage groups C2, D1a, D1b, H, L, M and O. MG IV and V soybean genotypes are critical for the early soybean production system widely used in the midsouthern US. However, only two mapping populations have been reported in Soybase for MG IV and V genotypes. Additionally, the parents used in this cross are known to differ in their response to soybean cyst nematode and charcoal rot, which constitute two major pathology threats to Midsouth soybean production. The population and map reported herein represent an important genetic resource for the early soybean production system. PMID- 17364822 TI - Cloning, sequencing of bone morphogenetic protein from sea urchin, Hemicentrotus pulcherrimus. AB - A cDNA coding for bone morphogenetic protein (BMP) homolog of the sea urchin, Hemicentrotus pulcherrimus, was isolated from mid-gastrula using reverse transcription-polymerase chain reaction (RT-PCR) technique. The 2314 nucleotide sequence contains a 1383 open reading frame corresponding to a translation product of 461 amino acids. Comparison of the nucleotide and deduced amino acid sequence with BMP isolated from Strongylocentrotus purpuratus (SpBMP5-7; accession No. Z48313) shows a high degree of conservation. HpBMP seems to belong to the 60A subgroup as a result. A mRNA coding H. pulcherrimus BMP (HpBMP) was not detected in the unfertilized egg, but it was detected from blastula to prism stages. PMID- 17364823 TI - Heterotopic expression of B-class floral homeotic genes PISTILLATA/GLOBOSA supports a modified model for crocus (Crocus sativus L.) flower formation. AB - For uncovering and understanding the molecular mechanisms controlling flower development in cultivated Crocus sativus and particularly the transformation of sepals in outer whorl (whorl 1) tepals, we have cloned and characterized the expression of a family of five PISTILLATA/GLOBOSA-like (PI/GLO-like) MADS-box genes expressed in the C. sativus flower. The deduced amino acid sequences of the coded proteins indicated high homology with members of the MADS-box family of transcription factors, and particularly with other members of the PI/GLO family of MADS-box proteins that control floral organ identity. PI/GLO expression studies in cultivated C. sativus uncover the presence of PI/GLO transcripts not only in the second and third whorls of flower organs as expected, but also in the outer whorl tepals that are the sepals in most typical flowers. This heterotopic expression of both B-class genes: PI/GLO and AP3/DEF, known to form heterodimers for stamens and petals (petaloid inner whor l-whorl 2-tepals in C. sativus), explains the homeotic transformation of sepals into outer whorl tepals in this species. Analysis of PI/GLO sequences from C. sativus for putative targets to known micro-RNAs (miRNAs) showed that the target site for ath-miRNA167 found in Arabidopsis thaliana PI is not present in C. sativus, however, the PI/GLO sequences may be regulated by an ath-miRNA163. PMID- 17364824 TI - Molecular cloning and characterization of ETHYLENE OVERPRODUCER 1-LIKE 1 gene, LeEOL1, from tomato (Lycopersicon esculentum Mill.) fruit. AB - Recently, ETHYLENE OVERPRODUCER 1 (ETO1) had been cloned and identified as a negative post-transcriptional regulator in the ethylene biosynthesis in Arabidopsis. However, little was known about the role of ETO1 in other species, especially in tomato, which was an ideal model for studying the biosynthesis of ethylene during tomato fruit ripening. In this study, a tomato ETHYLENE OVERPRODUCER 1-LIKE 1 (LeEOL1) was cloned. The LeEOL1 cDNA was 3,515 bp long and carried an ORF that putatively encoded a polypeptide of 886 amino acids with a predicted molecular mass of 95 kDa. It shared 74% identity in amino acid sequence with Arabidopsis EOL1 and had one BTB (Broad-complex, Tramtrack, Bric-a-brac) domain and two TPR (tetratricopeptide repeat) domains, which were also conserved domains in AtEOL1. RT-PCR analysis of the temporal expression of LeEOL1 showed that its transcript decreased companied with increase of ethylene production in tomato ripening. The level of LeEOL1 transcripts in wild type tomato fruit at mature green stage did not distinctively change when treated with exogenous ethylene. PMID- 17364825 TI - Cloning and characterization of a putative 12-oxophytodienoic acid reductase cDNA induced by osmotic stress in roots of foxtail millet. AB - Foxtail millet is a gramineous crop with low water requirement. Cloning of osmotic responses-related genes from foxtail millet is a key step for understanding the mechanism of its tolerance to drought. Here we reported the cloning and characterization of a cDNA (SiOPR1) encoding a putative 12 oxophytodienoic acid reductase 1 from foxtail millet by using RACE methods. Sequence analysis showed that SiOPR1 encoded a polypeptide of 374 amino acids with a predicted molecular mass of 41.9 kDa and pI of 5.14. Multiple alignment result showed that OPR1 protein was very conservative among gramineous crops. RNA gel blot analysis results indicated that SiOPR1 was up-regulated by osmotic stress, and its expression was limited in the roots of foxtail millet. However, SiOPR1 expression was not affected by ABA, NaCl and MeJA treatments both in roots and shoots. Therefore, it is suggested that SiOPR1 gene play an important role in response to drought stress. PMID- 17364826 TI - Cloning and expression of the gene encoding the diapause hormone and pheromone biosynthesis activating neuropeptide of the beet armyworm, Spodoptera exigua. AB - Diapause hormone (DH) and pheromone biosynthesis activating neuropeptide (PBAN), two important insect neuropeptides, regulate insect development and sex pheromone biosynthesis, respectively. DH-like immunoreactivity has been detected in the suboesophageal ganglion (SG) of pharate adult of Spodoptera exigua (Spe) by using an antiserum against Helicoverpa armigera DH. A full-length of Spe-DH-PBAN cDNA was obtained based on reverse transcription-PCR and rapid amplification of cDNA ends strategies. The open reading frame of this cDNA encodes a 197-amino acid precursor protein that contains DH, PBAN, and three other SG neuropeptides, all of which share a conservative C-terminal pentapeptide motif FXPR/KL (X = G, T or S). Northern blot analysis demonstrates the presence of an 800 bp transcript in the SG. The Spe-DH-PBAN mRNA is detectable at high levels at larval and adult stages, suggesting that Spe-DH-PBAN gene might be correlated with larval development and sex pheromone biosynthesis in moths. PMID- 17364827 TI - Elicitin-responsive lectin-like receptor kinase genes in BY-2 cells. AB - The inhibition of elicitor-induced plant defense responses by the protein kinase inhibitors K252a and staurosporine indicates that defense responses require protein phosphorylation. We isolated a cDNA clone encoding Nicotiana tabacum lectin-like receptor protein kinase 1 (NtlecRK1), an elicitor-responsive gene; in tobacco bright yellow (BY-2) cells by a differential display method. NtlecRK forms a gene family with at least three members in tobacco. All three NtlecRK genes potentially encode the N-terminal legume lectin domain, transmembrane domain and C-terminal Ser/Thr-type protein kinase domain. Green fluorescent protein (GFP) fusion showed that the NtlecRK1 protein was located on the plasma membrane. In addition, NtlecRK1 and 3 were responsive to INF1 elicitin and the bacterial elicitor harpin. These results indicate that NtlecRKs are membrane located protein kinases that are induced during defense responses in BY-2 cells. PMID- 17364829 TI - Addiction neuroscience and its relevance to clinical practice. PMID- 17364828 TI - Molecular cloning and characterization of a cDNA encoding a novel antibacterial peptide, defensin, from the mulberry longicorn beetle, Apriona germari. AB - A full-length cDNA clone with high homology (62% mature peptide sequence identity) to an Acalolepta luxuriosa antibacterial gene, possessing a conserved cysteine-stabilized alphabeta motif, was cloned by screening an Apriona germari cDNA library. This gene (AgCRP) had a total length of 360 bp with an open reading frame of 207 bp, and encoded a predicted peptide of 69 amino acid residues. The mature AgCRP peptide was 27 amino acid residues long and had a cysteine stabilized alphabeta motif of C...CXXXC...C...CXC consensus sequence, similar to insect defensins. Northern blot analysis revealed that the AgCRP exhibited fat body-specific expression and was up-regulated by wounding, bacterial or fungal challenge. PMID- 17364830 TI - Therapeutics for alcoholism: what's the future? AB - As with other addictions, human alcoholism is characterised as a chronically relapsing condition. Consequently, the therapeutic goal is the development of clinically effective, safe drugs that promote high adherence rates and prevent relapse. These products can then be used in conjunction with psychosocial approaches. In this review, preclinical studies are highlighted that indicate the mechanism of action of currently used anti-craving medications or demonstrate the potential of novel pharmacological agents for the treatment of alcohol use disorders. While current pharmacological strategies are far from ideal, there are a number of candidate molecules that may ultimately be developed into therapeutic agents. In addition, prescribing clinicians should also consider strategies such as combinations of various drugs to aid in the regulation of aberrant alcohol consumption. PMID- 17364831 TI - MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research. AB - The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') and methamphetamine (METH, 'ice', 'speed') are increasingly popular drugs amongst party-drug users. Studies with humans have investigated the acute and possible long-term adverse effects of these drugs, yet outcomes of such studies are often ambiguous due to a variety of confounding factors. Studies employing animal models have value in determining the acute and long-term effects of MDMA and METH on brain and behaviour. Self-administration studies show that intravenous METH is a particularly potent reinforcer in rats and other species. In contrast, MDMA appears to have powerful effects in enhancing social behaviour in laboratory animals. Brief exposure to MDMA or METH may produce long-term reductions in dopamine, serotonin and noradrenaline in the brain and alterations in the density of various receptor and transporter proteins. However it is still unclear, particularly in the case of MDMA, whether this reflects a 'neurotoxic' effect of the drug. Lasting alterations in social behaviour, anxiety, depressive symptoms and memory have been demonstrated in laboratory rats given MDMA or METH and this matches long-term changes reported in some human studies. Recent laboratory studies suggest that MDMA/METH combinations may produce greater adverse neurochemical and behavioural effects than either drug alone. This is of some concern given recent evidence that party drug users may be frequently exposed to this combination of drugs. PMID- 17364832 TI - Should personality traits be considered when refining substance misuse treatment programs? AB - The interplay between stable personality characteristics and environmental factors is emphasised in most contemporary approaches to individual differences. This interaction appears to be important in understanding the development of substance use and misuse. Impulsivity related personality traits such as sensation-seeking, novelty seeking, reward-sensitivity and behavioural disinhibition, are strongly linked to adolescent and adult substance use and misuse. The role of anxiety-related traits, in the development of substance misuse is less clear. Nonetheless, anxiety disorders are very common amongst adult substance misusers and almost certainly play a critical role in the maintenance of a substance use disorder and influence treatment effectiveness. The data suggest that personality influences treatment outcomes and yet these individual differences are generally not addressed in treatment. We argue in this review that interventions which are matched to these relevant personality traits may improve treatment outcomes for substance misusers. PMID- 17364833 TI - Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. AB - Stress- and drug-related cues are major factors contributing to high rates of relapse in addictive disorders. Brain imaging studies have begun to identify neural correlates of stress and drug cue-induced craving states. Findings indicate considerable overlap in neural circuits involved in processing stress and drug cues with activity in the corticostriatal limbic circuitry underlying both affective and reward processing. More recent efforts have begun to identify the relationships between neural activity during stress and drug cue exposure and drug relapse outcomes. Findings suggest medial prefrontal, anterior and posterior cingulate, striatal and posterior insula regions to be associated with relapse outcomes. Altered function in these brain regions is associated with stress induced and drug cue-induced craving states and an increased susceptibility to relapse. Such alterations can serve as markers to identify relapse propensity and a more severe course of addiction. Efficacy of pharmacological and behavioral treatments that specifically target stress and cue-induced craving and arousal responses may also be assessed via alterations in these brain correlates. PMID- 17364834 TI - Neurocognitive and neuroimaging evidence of behavioural dysregulation in human drug addiction: implications for diagnosis, treatment and prevention. AB - Neuropsychological and neuroimaging studies have generated a wealth of data demonstrating structural and functional brain changes, as well as cognitive deficits in drug addicted populations. Despite this, it is often difficult to make generalisations or conclusive statements about the neuropsychological and neurobiological correlates of chronic drug use given variations in the nature or extent of deficits observed within or across different classes of drugs. In this review, we focus specifically on the evidence for impairments in prefrontally mediated cognitive functions that underlie behavioural regulation, namely decision making and inhibitory control. We argue that impairments in these specific domains, which are often compounded by an earlier initiation of drug use, polydrug abuse, comorbid psychiatric conditions, previous head injury, and acute withdrawal effects can serve to increase the risk for making decisions that are impulsive, focussed on short-terms gains and lack inhibitory control. We further argue that these impairments of prefrontal functioning may underpin the compulsive and 'loss-of-control' pattern of drug-seeking and drug-taking that is characteristic of drug addiction. Finally, we consider the implications of these findings for diagnosis, treatment and prevention, suggesting that a comprehensive understanding of the nature and extent of these cognitive deficits should form a core part of the conceptualization and focus of effective treatment. PMID- 17364835 TI - Parent attitudes on the supply of alcohol to minors. AB - Inappropriate supply of alcohol by parents is often cited as a cause of teenage hazardous drinking. We investigated parental attitudes regarding supply of alcohol to minors, in a country which recently increased alcohol availability and where drinking per se is not prohibited at any age. A postal survey of 748 parents of 13 - 17 year-olds (80% response) in three New Zealand communities was undertaken. Parents indicated agreement/disagreement with statements concerning teenage drinking and sources of alcohol, and described factors they considered in deciding whether to supply alcohol. Four in five parents disagreed with permissive statements such as 'It's okay for parents to give their teenager one or two drinks to take to an unsupervised party', and 59% agreed that 'No one should supply alcohol to someone who is underage'. Recent suppliers commonly said they would only supply if there was suitable adult supervision at the drinking location. Many said they would only supply at home with a meal and reported restrictions on quantity and strength, e.g. 'no spirits or mixed drinks', 'small quantity only'. Parents generally opposed supply to minors or they specified responsible conditions of supply. They favoured legal restrictions on availability and promotion, and greater enforcement of liquor laws. The findings should be interpreted in light of social desirability bias and limitations of generalisability outside the participating communities. PMID- 17364836 TI - The Australian Treatment Outcome Study (ATOS): what have we learnt about treatment for heroin dependence? AB - Opioids make the single largest contribution to illicit drug-related mortality and morbidity worldwide In this paper we reflect upon what has been learnt regarding treatment outcome and the natural history of heroin use from the Australian Treatment Outcome Study (ATOS). We focus on what we knew prior to ATOS, what ATOS revealed that is novel, and the implications for research, practice and policy. ATOS provided strong evidence for sustained improvement attributable to treatment across the three years of the study. It is argued that treatment for heroin dependence is money well spent, and leads to clear and sustained benefits to both heroin users and society. PMID- 17364837 TI - Problem drinking in relation to treatment outcome among opiate addicts in methadone maintenance treatment. AB - This study analyzed indicators of alcohol-related problems in opiate addicts before, during, and after leaving methadone maintenance treatment (MMT), in relation to illicit drug use and retention in treatment. The study was based on 204 patients, admitted to MMT for the first time between 1 January 1995 and 31 July 2000, and followed until 31 December 2000. Three measures were used to indicate alcohol use and alcohol-related problems; records of hospital care with an alcohol-related diagnosis, any treatment with alcohol-sensitizing drugs (disulfiram or calcium carbimide) during MMT, and results of the 5 hydroxytryptophol to 5-hydroxyindoleacetic acid ratio (5HTOL/5HIAA) in urine, a sensitive biomarker for recent drinking. Use of illicit drugs was determined by routine urine drug testing. About one third of the patients (n = 69) had a lifetime prevalence of hospital treatment for an alcohol-related diagnosis, 45 of whom had been hospitalized (mean 4.2 stays) prior to the start of MMT. There was a significant association (p<0.05) between the number of alcohol-related diagnoses prior to treatment and a positive 5HTOL/5HIAA test during MMT. The alcohol indicators first became positive on average 1.6 years after admission to treatment, compared with after about 4 months for illicit drugs. Use of cannabis or benzodiazepines was significantly associated with alcohol use. Female methadone patients with indications of alcohol-related problems relapsed more often into illicit drug use than did women without such indications (3.9 vs. 2.5 relapse periods/year; p<0.005), whereas no significant association was found for men. The results of the present study indicate that drinking problems among patients undergoing MMT is associated with an increased risk of relapse into illicit drug use and with discharge from treatment. Concurrent treatment of alcohol-related problems, including systematic monitoring of alcohol use, therefore should be recommended to reduce the risk for relapse into illicit drug use and improve overall treatment outcome in MMT. PMID- 17364838 TI - Dual diagnosis in Spain. AB - Our aim is to describe the current situation regarding the diagnosis and treatment of addiction in a variety of settings in Spain. Four-hundred and twenty seven physicians known to treat addicted patients in non-private settings were recruited and agreed to participate. Each physician provided clinical and anonymous information on the first 6 consecutive patients who attended on a scheduled day. A total of 2361 patients were interviewed (92.1%) and data were obtained concerning gender, age, work, educational level, civil status, addiction diagnosis, type of treatment and psychiatric comorbidity. Seven-hundred and ninety-eight out of 2361 addicts (33.8%) presented with a dual diagnosis. Depression was the most prevalent disorder (21.6%), followed by anxiety disorders (11.7%). Comorbidity was found to be related to age, female gender, divorce and widowhood, and higher educational levels. Alcoholics who abused other drugs showed the highest rates of comorbidity (48.5%), while opiate addicts were at the lower end of the spectrum (27.4%). No differences were found related to the treatment setting, the doctor's medical specialty, or the geographical area. Finally, doctors tended to perceive that dual diagnosis was related to a worse psychiatric prognosis but not to higher relapse rates. Antidepressants were the most commonly prescribed drugs (62.4% of co-morbid patients) and anticraving agents were prescribed equally to comorbid and non-comorbid patients. Within the limitations of a descriptive study, our data show that comorbidity is a common clinical problem in patients who access addiction treatment. Affective and anxiety disorders are the most common comorbid diseases, and comorbidity rates seem to be unrelated to regional differences, medical settings or doctor's professional background. Dual diagnosis patients thus account for one third of the clinical workload of addiction specialists in Spain. PMID- 17364839 TI - Magazine alcohol advertising compliance with the Australian Alcoholic Beverages Advertising Code. AB - The purpose of this study was to assess the frequency and content of alcoholic beverage advertisements and sales promotions in magazines popular with adolescents and young people in Australia, and assess the extent to which the ads complied with Australia's self-regulatory Alcoholic Beverages Advertising Code (ABAC). Alcohol advertisements and promotions were identified in a sample of 93 magazines popular with young people. The identified items were coded against 28 measures constructed to assess the content of the items against the five sections of the ABAC. Two thirds of the magazines contained at least one alcohol advertisement or promotion with a total of 142 unique items identified: 80 were brand advertisements and 62 were other types of promotional items (i.e. sales promotions, event sponsorships, cross promotions with other marketers and advertorials). It was found that 52% of items appeared to contravene at least one section of the ABAC. The two major apparent breaches related to section B--the items having a strong appeal to adolescents (34%) and to section C--promoting positive social, sexual and psychological expectancies of consumption (28%). It was also found that promotional items appeared to breach the ABAC as often as did advertisements. It is concluded that the self-regulating system appears not to be working for the alcoholic beverages industry in Australia and that increased government surveillance and regulation should be considered, giving particular emphasis to the inclusion of promotional items other than brand advertising. PMID- 17364840 TI - Zopiclone misuse: an update from Dublin. AB - The prevalence of zopiclone misuse in clients attending a methadone maintenance programme in Dublin through detection of its degradation product, 2-amino-5 chloropyridine (ACP) on urinalysis is outlined. Urine samples from all 158 clients were tested for the presence of ACP, opiates, benzodiazepines, cocaine, alcohol and cannabis. Of the 37 (23%) clients who tested positive for ACP, 23 (62%) were interviewed. A profile of zopiclone misusers is outlined, including details of demographics, drug history, viral status, recent urinalysis results and opinions on zopiclone. Of the 14 (38%) clients who were not interviewed, information was obtained from their clinical casenotes and documented urinalysis results. The prevalence of zopiclone misuse was reported as 23%. Benzodiazepines were the most popular drug of misuse with zopiclone followed by heroin/opiates. Zopiclone is being misused by drug users in Dublin in the context of many other drugs. Prescribing of zopiclone should be restricted, especially among drug misusers. PMID- 17364841 TI - A community development approach to deal with public drug use in Box Hill. AB - The use of alcohol and other drugs in public space is one that generates much heat in the public discourse and in the media. Too often the responses called for to reduce the problems of public amenity involve punitive policing and other responses that aim to engineer (mostly) young people out of these public spaces. Often local retailers are a key stakeholder group calling loudest for punitive action. In this Harm Reduction Digest Rogers and Anderson describe a community development approach taken to address these problems in Box Hill in the City of Whitehorse, near Melbourne. This approach which aimed to develop 'bridging social capital' between community retailers and other stakeholders in the area appears to have been effective in reducing harm associated with public drug use. Moreover these changes have become institutionalised and the approach has been expanded to address other public amenity problems in the area. It is a very nice example of how drug related harm can be reduced by grass roots networks of local councils, business people, law enforcement and health and welfare service providers to address these issues. PMID- 17364842 TI - Prevalence of illicit drug use in Asia and the Pacific. AB - This paper reports on the prevalence of drug use in Asia and the Pacific. It is based on the report "Situational analysis of illicit drug issues and responses in Asia and the Pacific", commissioned by the Australian National Council on Drugs Asia Pacific Drug Issues Committee. Review of existing estimates of the prevalence of people who use illicit drugs from published and unpublished literature and information from key informants and regional institutions was undertaken for the period 1998 - 2004. Estimates of the prevalence of people who use illicit drugs were conducted for 12 Asian and six Pacific Island countries. The estimated prevalence of those using illicit drugs ranges from less than 0.01% to 4.6%. Countries with estimated prevalence rates higher than 2% are Cambodia, Hong Kong, Philippines, Thailand, Indonesia, Laos and Malaysia. China, Myanmar and Vietnam have estimated prevalence rates ranging between less than 0.01% and 2%. Data to estimate prevalence rates was not available for Pacific Island countries and Brunei. Estimates of the prevalence of drug use are critical to policy development, planning responses and measuring the coverage of programs. However, reliable estimates of the numbers of people using illicit drugs are rare in Asia, particularly the Pacific. PMID- 17364844 TI - Roadside drug testing: unanswered questions and future challenges. PMID- 17364845 TI - The development and validation of the Indigenous Risk Impact Screen (IRIS): a 13 item screening instrument for alcohol and drug and mental health risk. AB - The study aimed to assess the psychometric properties of the Indigenous Risk Impact Screen (IRIS) as a screening instrument for determining (i) the presence of alcohol and drug and mental health risk in Indigenous adult Australians and (ii) the cut-off scores that discriminate most effectively between the presence and absence of risk. A cross-sectional survey was used in clinical and non clinical Indigenous and non-Indigenous services across Queensland Australia. A total of 175 Aboriginal and Torres Strait Islander people from urban, rural, regional and remote locations in Queensland took part in the study. Measures included the Indigenous Risk Impact Screen (IRIS), the Severity of Dependence Scale (SDS), the Alcohol Use Disorders Identification Test (AUDIT) and the Leeds Dependence Questionnaire (LDQ). Additional Mental Health measures included the Depression Anxiety and Stress Scale (DASS-21) and the Self-Report Questionnaire (SRQ). Principle axis factoring analysis of the IRIS revealed two factors corresponding with (i) alcohol and drug and (ii) mental health. The IRIS alcohol and drug and mental health subscales demonstrated good convergent validity with other well-established screening instruments and both subscales showed high internal consistency. A receiver operating characteristics (ROC) curve analysis was used to generate cut-offs for the two subscales and t-tests validated the utility of these cut-offs for determining risky levels of drinking. The study validated statistically the utility of the IRIS as a screen for alcohol and drug and mental health risk. The instrument is therefore recommended as a brief screening instrument for Aboriginal and Torres Strait Islander people. PMID- 17364846 TI - Pre-operative screening for excessive alcohol consumption among patients scheduled for elective surgery. AB - Pre-operative intervention for excessive alcohol consumption among patients scheduled for elective surgery has been shown to reduce complications of surgery. However, successful intervention depends upon an effective and practical screening procedure. This study examines current screening practices for excessive alcohol consumption amongst patients scheduled for elective surgery in general hospitals. It also examines the appropriateness of potential sites and staff for pre-operative screening. Forms used routinely to assess alcohol consumption in the pre-admission clinics (PAC) of eight Sydney hospitals were examined. In addition, the appropriateness of six staff categories (surgeons, surgeons' secretaries, junior medical officer, anaesthetists, nurses and a research assistant) and of two sites (surgeons' office and PAC) in conducting additional screening was assessed at two hospitals. Outcomes included observed advantages and disadvantages of sites and personnel, and number of cases with excessive drinking identified. There was duplication in information collected routinely on alcohol use in the PACs in eight Sydney Hospitals. Questions on alcohol consumption in patient self-completion forms were not validated. The PAC provided for efficient screening but time to surgery was typically too short for successful intervention in many cases. A validated tool and efficient screening procedure is required to detect excessive drinking before elective surgery. Patients often present to the PAC too close to the time of surgery for any change in drinking to reverse alcohol's effects. The role of the referring general practitioner and of printed advice from the surgeon in preparing patients for surgery needs further investigation. PMID- 17364847 TI - Detection of and intervention for excessive alcohol and tobacco use among adult hospital in-patients. AB - Early detection and intervention for alcohol problems have been shown to reduce subsequent health consequences. However, the extent to which these practices have been implemented is unclear. The study assessed among hospital in-patients (1) the prevalence of at-risk drinking and smoking, (2) current practice in detection and intervention for at-risk drinking and smoking and (3) self-reported effect of any intervention. A brief self-administered questionnaire was administered to adult in-patients addressing alcohol use [Alcohol Use Disorders Identification Test (AUDIT) questionnaire], smoking and self-reported effect of any recent intervention for drinking or smoking. The participant's smoking status and alcohol use as recorded by medical and nursing staff was compared to self reports. Of 448 in-patients, 50% (226) participated in the study; 38% (170) were ineligible and 12% (52) refused. Participants were aged 61.3 (+/-18.9) years. A higher number of problem drinkers (11.9% vs. 3.5%, p < 0.0001) and current smokers (17.3% vs. 9.3%, p < 0.0001) were identified by the questionnaire compared to the medical records. Hospital staff quantified smoking more consistently than alcohol (54% vs. 42%, p = 0.02). Of those who recalled an intervention, 19% of drinkers and 27% of smokers said they had stopped drinking or smoking for a period since that intervention. Further improvement is required in the rates of detection and interventions for alcohol use disorders and smoking in the hospital setting. PMID- 17364848 TI - Time-limited buprenorphine replacement therapy for opioid dependence: 2-year follow-up outcomes in relation to programme completion and current agonist therapy status. AB - Programme completion is predictive of post-treatment abstinence and other improvements in persons with opioid dependence, while continued agonist treatment is associated with better outcomes than no agonist treatment. This study aimed to assess relationships between follow-up outcomes of a 9-month buprenorphine programme, completion and current agonist therapy status. Sixty-eight of 75 opioid-dependent former participants were assessed at study entry and 24 months thereafter. Outcome measures were opioid abstinence, substance use and psychosocial performance. Group comparisons were made between buprenorphine programme completers (n = 38) and non-completers (n = 30), and between participants who were currently in agonist therapy (n = 37) and those who were not. Performance at follow-up was compared to that at study entry. Nine people were abstinent from all opioids at follow-up. Completers and non-completers were similar in follow-up performance and patterns of change, while participants' current agonist therapy status was related to both substance use and psychosocial outcomes. Reductions in street opioid use and injecting were seen regardless of completion and agonist therapy status. Retaining patients in agonist replacement therapy over time is more likely than completion of a time-limited programme to influence long-term outcomes. Time-limited buprenorphine replacement therapy appears to be inappropriate for persons with opioid dependence. PMID- 17364849 TI - Buprenorphine supply by community pharmacists in Victoria, Australia: perceptions, experiences and key issues identified. AB - Buprenorphine is dispensed primarily in community pharmacies in Victoria, with buprenorphine prescribing expanding nationally. The aim of this paper was to examine issues that affect the delivery of buprenorphine in the community setting. A cross-sectional survey was conducted of 282 pharmacies participating in the methadone and buprenorphine programme across Victoria. Dispensing pharmacists completed the survey, designed to canvass issues around buprenorphine diversion and other issues related to the programme. Themes from the results indicated that there was concern from the majority of pharmacies with the issue of the supervision of buprenorphine and diversion of dispensed doses. The rate of suspected diversion was 1.5 times per 100 doses per month or 33 times per 100 clients per month. Seventy-four per cent of pharmacists indicated that this was a negative aspect of buprenorphine treatment. Frequency of suspected and confirmed diversion was associated with the number of pharmacy clients. Pharmacists' perceptions of issues related to buprenorphine appeared to affect opinions of buprenorphine clients and the buprenorphine programme more generally. Pharmacists believe that a significant level of diversion is occurring. This finding warrants serious attention, particularly in light of the increasing use of buprenorphine nationally and internationally. PMID- 17364850 TI - Changes in the use of medical services and prescription drugs among heroin users over two years. AB - The study aimed to determine patterns of use of medical services and prescriptions for pharmaceuticals among 438 heroin users interviewed for the Australian Treatment Outcome Study (ATOS) at baseline, 12 and 24 months. Drug use declined markedly, and there were significant improvements in health. There were declines in the proportion of participants who had attended a general practitioner (GP) (baseline: 60%, 12 months: 53%, 24 months: 52%), who had an ambulance attendance (11%, 7%, 5%), and who were treated in an accident and emergency department (11%, 6%, 5%). While there was no decrease in the proportion who obtained a prescription (47%, 45%, 46%), there was a decrease in the mean number of reported prescriptions obtained (2.3, 1.0, 0.9). There were also differences across follow-up in the reported types of medications obtained, with a significant decrease in the proportion obtaining psychotropic medications (38%, 21%, 19%). In particular, there were large declines in the proportion who reported benzodiazepines (30%, 12%, 10%) or narcotic analgesics (8%, 3%, 4%) on prescription. While ATOS participants continued to be frequent users of health services, the cohort reported reduced levels of drug-seeking and risk commensurate with their reductions in drug use. PMID- 17364851 TI - Socio-demographic factors associated with methamphetamine treatment contact among dependent methamphetamine users in Sydney, Australia. AB - Australia has a sizable population of dependent methamphetamine users, the majority of whom do not receive treatment for their drug use. The aim of the current study was to identify socio-demographic factors related to not having received treatment for methamphetamine use among dependent users of the drug in Sydney, Australia. A cross-sectional survey of methamphetamine users in Sydney was used to identify a sample of dependent methamphetamine users (n = 173). Dependence was defined as a score of four or greater on the Severity of Dependence Scale. Dependent methamphetamine users who had received treatment for their methamphetamine use (n = 57) were compared with those who had never received treatment for their methamphetamine use (n = 116) on socio-demographic characteristics and drug use. After adjusting for severity of methamphetamine dependence, socio-demographic factors that were predictive of not having received methamphetamine treatment included being female, being born outside Australia and being in full-time employment. Methamphetamine smokers were less likely to receive treatment than people who took the drug via other routes of administration, while primary heroin users who were concurrently dependent on methamphetamine were unlikely to receive treatment for their methamphetamine use. Further research is needed to understand the barriers to receiving methamphetamine treatment among these subgroups of dependent methamphetamine users. PMID- 17364852 TI - A pilot study using the internet to study patterns of party drug use: processes, findings and limitations. AB - Since the 1990s there has been a rise in both the prevalence of party drug use in Australia and the use of party drug-related websites. This study investigates whether it is feasible to recruit and survey party drug users via the internet. It took place in Victoria, Australia. Participants were directed to a website where they completed a brief, structured internet-based survey. A total of 460 responses were received over 31 days, 393 of which fitted all inclusion criteria. The sample consisted predominately of young, male polydrug users and is one of the largest samples of party drug users in Australia reported thus far. It was concluded that it is feasible to recruit and survey current party drug users via the internet and that this method is quicker and cheaper than traditional survey methods, although samples are not necessarily representative of the party drug using population. Other limitations and advantages are discussed. PMID- 17364853 TI - Safety in numbers? Tackling domestic abuse in couples and network therapies. AB - Family, network or couples-based therapies have been helping to support people with substance problems for decades. Their value in supporting a person to change their alcohol or drug use is clear. However, as links between substance use and domestic abuse are increasingly recognised, these approaches need to reflect on the potential safety risks they present to people taking part. The prevalence of domestic abuse among people receiving drug and alcohol services is considerably higher than general population estimates, yet this does not appear to have been adequately addressed in network therapies. This article suggests that this needs to change and that safety of service users needs to be at least as important as the intervention itself. It offers for debate a number of potential safety issues raised by network therapies where there is evidence of domestic abuse; it provides examples of three approaches used to marshal social and network support in substance interventions; and offers a number of suggestions for how network therapies can ensure their use remains safe and supportive where there is domestic abuse. PMID- 17364854 TI - Contingency management: perspectives of Australian service providers. AB - Given the very positive and extensive research evidence demonstrating efficacy and effectiveness of contingency management, it is important that Australia explore whether contingency management has a role to play in our own treatment context. Qualitative interviews were conducted with 30 experienced alcohol and drug practitioners, service managers and policy-makers in Victoria. Interviewees were selected to represent the range of drug treatment services types and included rural representation. A semi-structured interview schedule, covering their perceptions and practices of contingency management was used. All interviews were transcribed verbatim and analysed using N2 qualitative data analysis program. The majority of key informants were positively inclined toward contingency management, notwithstanding some concerns about the philosophical underpinnings. Concerns were raised in relation to the use of monetary rewards. Examples of the use of contingency management provided by key informants demonstrated an over-inclusive definition: all the examples did not adhere to the key principles of contingency management. This may create problems if a structured contingency management were to be introduced in Australia. Contingency management is an important adjunctive treatment intervention and its use in Australia has the potential to enhance treatment outcomes. No unmanageable barriers were identified in this study. PMID- 17364855 TI - The influence of structured education and clinical experience on the attitudes of medical students towards substance misusers. AB - Negative attitudes to patients with substance misuse disorders form a well recognised barrier to the implementation of best practice. The influence of structured education and clinical experience on the attitudes of medical students towards substance misusers was investigated at an Australian university. First year students were surveyed before and after 3 weeks of drug and alcohol education and in the same year, fourth-year students were surveyed before and after a 9-week block. Males, older students and those with prior clinical experience tended to have more negative attitudes. Attitudes improved significantly after exposure to interactive learning modules which included contact with patients with substance dependence, including individuals in remission. The level of dislike of problem drinkers significantly decreased after teaching. After fourth-year education, students reported a greater sense of responsibility towards providing intervention and less anticipation of discomfort working with these patients. In particular, confidence and attitudes towards heroin users improved near the end of training after contact with illicit drug users in the small group or individual interview setting. By the end of drug and alcohol education, less than half (42%) of students reported they could not imagine working with substance misusers as a career. Findings support the provision of structured drug and alcohol education and supported clinical experience for every medical student if appropriate evidence-based treatment is to be provided. PMID- 17364856 TI - Alcohol and injuries: a review of international emergency room studies since 1995. AB - This paper provides a review of emergency room (ER) studies on alcohol and injury, using representative probability samples of adult injury patients, and focuses on the scope and burden of the problem as measured by estimated blood alcohol concentration (BAC) at the time of the ER visit, self-report drinking prior to injury, violence-related injury and alcohol use disorders. A computerized search of the English-language literature on MEDLINE, PsychINFO and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Alcohol and Alcohol Problems Science Database (ETOH) was conducted for articles published between 1995 and 2005, using the following key descriptors: (1) emergency room/emergency department/accident and emergency, (2) alcohol/drinking and (3) injuries (intentional and unintentional). Findings support prior reviews, with injured patients more likely to be positive for BAC and report drinking prior to injury than non-injured, and with the magnitude of the association substantially increased for violence-related injuries compared to non-violence-related injuries. Indicators of alcohol use disorders did not show a strong association with injury. Findings were not homogeneous across studies, however, and contextual variables, including study-level detrimental drinking pattern, explained some of the variation. This review represents a broader range of ER studies than that reported previously, across both developed and developing countries, and has added to our knowledge base in relation to the influence of contextual variables on the alcohol-injury relationship. Future research on alcohol and injury should focus on obtaining representative samples of ER patients, with special attention to both acute and chronic alcohol use, and to organisational and socio-cultural variables that may influence findings across studies. In-depth patient interviews may also be useful for a better understanding of drinking in the injury event and associated circumstances. PMID- 17364857 TI - Poppy seed tea and opiate abuse in New Zealand. AB - The opium poppy Papaver somniferum contains an array of opiates. There is a variety of methods of preparation that can be used by people with opiate dependence, with patterns of use determined by numerous factors including cost, safety, potency and legal status. The objective of this study was to determine the frequency and nature of poppy seed tea (PST) use by opiate-dependent patients in the form of a written questionnaire. The study took place at the Community Alcohol and Drug Clinic, Wellington, New Zealand, and comprised 24 opiate dependent patients attending the clinic. A total of 11 of 24 (46%) patients reported having used PST. In five patients currently using PST it represented the major source of opiates, and two had managed to withdraw from use of other opiates with regular PST use. Patients reported a median onset of action of 15 minutes and an effect lasting a median of 24 hours. The major limitation of PST use was the foul taste. PST is used commonly by opiate-dependent patients attending an alcohol and drug clinic in New Zealand. The use of PST as the major source of opiates could be considered favourably within 'harm reduction' philosophies, because of its low cost, legal availability and oral route of administration. Conversely, there is the potential for PST to act as a 'gateway drug' by inducing opioid dependence and introducing people to the culture of drug abuse. PMID- 17364858 TI - Postscript to 'fact or fiction: a critique of the National Aboriginal and Torres Strait Islander Social Survey 2002'. PMID- 17364860 TI - DNA-protein cross-link formation in Burkitt lymphoma cells cultured with benzaldehyde and the sedative paraldehyde. AB - Exposure to aldehydes represents potential risks to human and animal health. Cyclic aldehydes such as benzaldehyde, 2-furaldehyde, and paraldehyde were found to induce formation of stable DNA-protein cross-links (DPXs) in cultured human lymphoma cells. A relationship between increased cytotoxicity and DPX formation was observed with each aldehyde. Paraldehyde is a sedative drug used predominately in treatment of ethanol withdrawal. Paraldehyde was the most potent cross-linking aldehyde studied, yet least cytotoxic. Although DPX formation by aliphatic aldehydes is well-known, this study confirms the potential for cyclic aldehydes to cause formation of DPXs in cultured cells at therapeutically relevant doses. PMID- 17364861 TI - Selective oxidative stress in brain areas of neonate rats exposed to 2,4 Dichlorophenoxyacetic acid through mother's milk. AB - 2,4-Dichlorophenoxyacetic acid (2,4-D) induced disparate alterations on enzymatic activities of the defensive mechanism and/or modifications of the reactive oxygen species levels in specific neonate rat brain regions. The midbrain, striatum, and prefrontal cortex were the areas where the alterations were more remarkable and with similar tendency. The hippocampus did not suffer many alterations, and the hypothalamus was the area where no changes were observed. The current results suggest that the developing brain areas have different susceptibilities to the adverse effect of the herbicide, especially those areas related to the dopaminergic system, and that oxidative stress is one 2,4-D mechanism of toxicity. PMID- 17364862 TI - Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro. AB - In vitro comparison of reactivation efficacy of five currently used oximes - pralidoxime, obidoxime, trimedoxime, methoxime, and HI-6 (at two concentrations: 10-5 and 10-3 M) - against acetylcholinesterase (AChE; E.C. 3.1.1.7) inhibited by six different nerve agents (VX, Russian VX, sarin, cyclosarin, tabun, soman) and organophosphorus insecticide chlorpyrifos was the aim of this study. As a source of AChE in the experiments, rat brain homogenate was used. According to the results obtained, no AChE reactivator was able to reach sufficient potency for AChE inhibited by all nerve agents used. Moreover, oxime HI-6 (the most effective one) was not able to reactivate tabun- and soman-inhibited AChE. Due to this fact, it could be designated as a partially broad-spectrum reactivator. PMID- 17364863 TI - Study of the effects on DNA of two novel nucleoside derivatives synthesized as potential anti-HIV agents. AB - The pursuit of antiviral active compounds against different classes of viruses, in particular HIV, HBV, and HTLV is an area of important and intense research. In the current study, two novel nucleoside derivatives belonging to a new class of isoxazolidine were successfully synthesized as potential anti-HIV agents by replacement of the furanose ring by a N,O-heterocyclic ring Both compounds were investigated for biological activity, namely, mutagenic and antimutagenic properties. Using Salmonella typhimurium strains TA97, TA100, and TA102, both compounds proved to be nonmutagenic, which may be considered an encouraging result to further elucidate other biological activities. Antimutagenic testing of the synthesized compounds revealed that they are active against the base-pair substitution mutagen sodium azide. However, they did not show any indication as antimutagenic agents against hydrogen peroxide and mitomycin C (oxidative mutagens) or against nitrophenylenediamine (a base-pair substitution and frameshift mutagen). Structure-activity relationship is also discussed. Testing these compounds as antiviral agents is highly recommended. PMID- 17364864 TI - Cypermethrin-induced biochemical perturbations in freshwater fish Clarias batrachus at sublethal exposure and after released into freshwater. AB - Cypermethrin-induced alterations in the fish, Clarias batrachus were studied. The fish were exposed to cypermethrin at a concentration of 0.07 mg/L for 10 days. After 10 days, fish were released into freshwater to observe the recovery response. At the end of 1, 5, and 10 days of exposure and after transfer into freshwater, different parameters were estimated in muscle and kidneys. Reduction in proteins was observed in both tissues, and recovery response was seen in muscle and kidneys. Free amino acid and ammonia content was enhanced in muscle and kidney for the 10 days. Transaminases (ALAT and AAT) and glutamate dehydrogenase activities were increased in both tissues for 10 days exposure span. Enzyme activities did not show much of the recovery. PMID- 17364865 TI - Prolonged quercetin administration diminishes the etoposide-induced DNA damage in bone marrow cells of rats. AB - The DNA damage in bone marrow cells induced by etoposide (E) injected intraperitoneally to rats (100 mg/kg b.w.) decreased to the control level when quercetin (Q) was administered subcutaneously for 10 consecutive days (40 mg/kg b.w.per day) before E was injected. The antioxidant power (FRAP assay) increased significantly after Q or E compared with control rats but did not change when Q preceded the E injection. The superoxide dismutase activity significantly increased in Q+E-treated rats compared with quercetin given alone. The study provides evidence that Q protects bone marrow cells against long-lived E-induced DNA damage and alters the redox balance in lung tissue. PMID- 17364866 TI - Genotoxicity assessment of HM10620 containing recombinant human interferon-alpha. AB - HM10620 is a recombinant human interferon-alpha (rhIFN-alpha) linked to immunoglobulin via N-terminal-specific non-peptidyl polyethylene glycol linker to improve the in vivo stability of interferon. Potential genotoxic effects of HM10620 in three short-term mutagenicity assays were investigated, which included the Ames assay, in vitro chromosomal aberration assay, and the in vivo micronucleus assay. HM10620 did not cause any mutation in the Ames assay tested using five tester strains at six concentrations of 6.25, 12.5, 25, 50, 100, and 200 microg/plate. To assess clastogenic effect, the in vitro chromosomal aberration assay and the in vivo micronucleus assay were performed using Chinese hamster lung cells and male ICR mice, respectively. Chromosomal aberration was not induced at the concentrations of 10, 20, and 40 microg/mL. Also, there was no difference in the incidence of micronucleated polychromatic erythrocytes at doses of 10, 20, and 40 mg/kg in male mice compared with the vehicle control group. Therefore, based on the results obtained from the three studies, it is concluded that HM10620 is not a mutagenic agent in bacterial cells and causes no chromosomal damage in mammalian cells both in vitro and in vivo. PMID- 17364869 TI - Nanostructured lipid carriers-containing anticancer compounds: preparation, characterization, and cytotoxicity studies. AB - This article describes the development of nanostructured lipid carriers (NLC) as colloidal carriers for two antitumor compounds that possess a remarkable antineoplastic activity. But their limited stability and low solubility in water could give a very low parenteral bioavailability. Results revealed an enhancement of the cytotoxicity effect of drug-loaded NLC on human prostate cancer (PC-3) and human hepatocellular carcinoma (HuH-6, HuH-7) cell lines with respect to that of both free drugs. Results of characterization studies strongly support the potential application of these drugs-loaded NLC as prolonged delivery systems for lipophilic drugs by several administration routes, in particular for intravenous administration. PMID- 17364870 TI - Formulation and evaluation of ketorolac transdermal systems. AB - The effects of pressure-sensitive adhesives and vehicles on the in vitro permeation of ketorolac and in vivo pharmacokinetics were studied. Duro-Tak 87 2196 showed the highest in vitro permeation profiles, and propylene glycol monolaurate-diethylene glycol monoethyl ether (DGME) (60:40, v/v) and propylene glycol monocaprylate-DGME (60:40, v/v) revealed the most favorable in vitro and in vivo results. The decreased Cmax and prolonged Tmax and half-life were obtained with the ketorolac transdermal systems compared with oral administration, indicating that the ketorolac transdermal systems may have a prolonged effect with reduced toxic event. There was an excellent relationship found between in vitro permeation flux and in vivo AUC0-infinity. PMID- 17364871 TI - Amphiphilic gels as a potential carrier for topical drug delivery. AB - This study involves development of amphiphilic gels consisting solely of nonionic surfactants bearing cyclosporine and characterized for microstructure, gelation temperature, and in vitro drug release into dermis. The formulation is nonirritant and suitable for topical application. Gels consisting of cyclosporine were prepared using different methods by mixing the solid gelator (sorbitan or glyceryl fatty acid esters) and the liquid phase (liquid sorbitan esters or polysorbates) and heating them at 60 degrees C to form a clear isotropic sol phase, and cooling this sol phase to form an opaque semisolid at room temperature. Gel microstructure was examined by phase contrast microscopy while gelation temperatures were measured by melting point apparatus and differential scanning calorimetry. These amphiphilic gels were evaluated in vitro for topical as well as transdermal delivery using rat skin mounted in a Franz diffusion cell. Gel microstructures consisted mainly of clusters of tubules of gelator molecules that had aggregated upon cooling of the sol phase, forming a 3D network throughout the continuous phase. The gels demonstrated thermoreversibility with robust gel network. At temperatures near the skin surface temperature, the gels softened considerably and moreover, it facilitated the drug to accumulate in dermis, thus making an ideal delivery vehicle of cyclosporine topically that can be used in treatment of psoriasis. Thus amphiphilic gels were demonstrated as the ideal vehicle for topical use of cyclosporine. PMID- 17364872 TI - Hydrogels of dextran containing nonsteroidal anti-inflammatory drugs as pendant agents. AB - The oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal tract side effects. To reduce these effects and improve the therapeutic efficacy, NSAIDs are often formulated as controlled release systems. We have prepared a new formulation consisting of dextran hydrogels containing NSAIDs as pendant agents, through ultraviolet irradiation of solutions of dextran functionalized with methacrylic groups in the presence of the drug derivatized in the same way. Release studies of different drugs from this system, carried out in media simulating the gastrointestinal tract, have demonstrated that the amount of released drug is strictly related to the concentration of the polymer in the solution submitted to irradiation as well as to its derivatization degree. Our obtained data confirm that the system is able to realize a colon-specific drug delivery. PMID- 17364873 TI - Reverse micelle-based microencapsulation of oxytetracycline hydrochloride into poly-d,l-lactide-co-glycolide microspheres. AB - The objectives of this study were to solubilize oxytetracycline hydrochloride (HCl) in reverse micelles to prepare poly-d,l-lactide-co-glycolide (PLGA) microspheres and to explore parameters affecting its encapsulation efficiency. Oxytetracycline HCl was dissolved in the reverse micelles consisting of cetyltrimethylammonium bromide, water, and ethyl formate. A PLGA polymer was then dissolved in the reverse micellar solution, and a modified solvent quenching procedure was carried out to prepare PLGA microspheres. Encapsulation efficiencies of oxytetracycline HCl ranged from 2.3 +/- 0.2 to 24.9 +/- 4.6%, depending on experimental conditions. Important parameters affecting its encapsulation efficiency included the amounts of water used to prepare the reverse micelles and PLGA polymer. With regard to microsphere morphology, the reverse micellar process produced the microspheres with smooth and pore-free surfaces. In particular, their internal matrices did not possess hollow cavities that were frequently observed when a typical double emulsion technique was used to make microspheres. In summary, it was possible to encapsulate oxytetracycline HCl into PLGA microspheres via the ethyl formate-based reverse micellar technique. We also anticipate that the use of ethyl formate could avoid environmental and human toxicity issues associated with methylene chloride. PMID- 17364874 TI - Pharmacokinetics and pharmacodynamics of sterylglucoside-modified liposomes for levonorgestrel delivery via nasal route. AB - For emergency contraceptive, the rapid delivery of levonorgestrel (LNG) to plasma is desirable, furthermore, a sustained delivery of LNG along with rapid absorption will be necessary. The pharmacokinetics and pharmacodynamics of LNG entrapped in different kinds of liposome formulations via nasal administration in rats were evaluated and compared with LNG suspension via the oral route. The relative bioavailabilities of these liposome formulations via nasal administration were 100% or higher than 100%. The Cmax and Tmax values of sterylglucoside (SG) and chitosan-contained formulations by nasal administration were 416.84 ng/mL and 1.02 hr, 227.97 ng/mL and 2.02 hr, respectively, compared with that of 334.94 ng/mL and 1.89 hr of oral suspension. Fully 100% contraception was observed for all the formulations. SG could promote the absorption of LNG via the nasal route and may provide a rapid onset of action of LNG for emergency contraception. Chitosan could retain LNG in the nasal cavity for long contact time to sustain delivery of LNG. The rapid onset and sustained delivery of LNG can be achieved via the nasal route using liposomes as the vehicle. PMID- 17364875 TI - Antibacterial activity of dipeptide constructs of acetylsalicylic acid and nicotinic acid. AB - Two dipeptide drugs are synthesized utilizing an acetylsalicylic acid or nicotinic acid molecule for the framework. A D-alanine-D-alanine dipeptide moiety is attached to the carbonyl carbon of acetylsalicylic acid (I) and nicotinic acid (II). Dipeptide derivatives (I) and (II) showed significant reduction of Escherichia coli (E. coli) bacterial growth and colony-forming units. A mixture of (I) and (II) induced growth inhibition of 8%, 17.5%, 28%, and 42.5% at concentrations of 100, 200, 300, and 400 microg/mL, respectively. Ampicillin demonstrated much less growth inhibition of this penicillin-resistant E. coli bacteria. Derivatives (I) and (II) showed significant reduction of colony-forming units at concentrations higher than 200 microg/mL, whereas ampicillin showed no significant affect on colony-forming units. Both (I) and (II) produced no violations of the Rule of 5, indicating favorable characteristics for bioavailability. Molecular properties were determined and showed (I) to have a Log Kow of -0.22 with aqueous solubility of 683.8 mg/L, whereas (II) had a Log Kow of -1.00 and aqueous solubility of 6859 mg/L. A mixture of the parent compounds acetyl salicylic acid and nicotinic acid demonstrated some antibacterial activity. PMID- 17364878 TI - Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes. AB - The mammalian carboxylesterases (CESs) comprise a multigene family which gene products play important roles in biotransformation of ester- or amide-type prodrugs. Since expression level of CESs may affect the pharmacokinetic behavior of prodrugs in vivo, it is important to understand the transcriptional regulation mechanism of the CES genes. However, little is known about the gene structure and transcriptional regulation of the mammalian CES genes. In the present study, to investigate the transcriptional regulation of the promoter region of the CES1 and CES2 genes were isolated from mouse, rat and human genomic DNA by PCR amplification. A TATA box was not found the transcriptional start site of all CES promoter. These CES promoters share several common binding sites for transcription factors among the same CES families, suggesting that the orthologous CES genes have evolutionally conserved transcriptional regulatory mechanisms. The result of present study suggested that the mammalian CES promoters were at least partly conserved among the same CES families, and some of the transcription factors may play similar roles in transcriptional regulation of the human and murine CES genes. PMID- 17364879 TI - What is the objective of the mass balance study? A retrospective analysis of data in animal and human excretion studies employing radiolabeled drugs. AB - Mass balance excretion studies in laboratory animals and humans using radiolabeled compounds represent a standard part of the development process for new drugs. From these studies, the total fate of drug-related material is obtained: mass balance, routes of excretion, and, with additional analyses, metabolic pathways. However, rarely does the mass balance in radiolabeled excretion studies truly achieve 100% recovery. Many definitions of cutoff criteria for mass balance that identify acceptable versus unacceptable recovery have been presented as ad hoc statements without a strong rationale. To address this, a retrospective analysis was undertaken to explore the overall performance of mass balance studies in both laboratory animal species and humans using data for 27 proprietary compounds within Pfizer and extensive review of published studies. The review has examined variation in recovery and the question of whether low recovery was a cause for concern in terms of drug safety. Overall, mean recovery was greater in rats and dogs than in humans. When the circulating half-life of total radioactivity is greater than 50 h, the recovery tends to be lower. Excretion data from the literature were queried as to whether drugs linked with toxicities associated with sequestration in tissues or covalent binding exhibit low mass balance. This was not the case, unless the sequestration led to a long elimination half-life of drug-related material. In the vast majority of cases, sequestration or concentration of drug-related material in an organ or tissue was without deleterious effect and, in some cases, was related to the pharmacological mechanism of action. Overall, from these data, recovery of radiolabel would normally be equal to or greater than 90%, 85%, and 80% in rat, dog, and human, respectively. Since several technical limitations can underlie a lack of mass balance and since mass balance data are not sensitive indicators of the potential for toxicity arising via tissue sequestration, absolute recovery in humans should not be used as a major decision criteria as to whether a radiolabeled study has met its objectives. Instead, the study should be seen as an integral part of drug development answering four principal questions: 1) Is the proposed clearance mechanism sufficiently supported by the identities of the drug-related materials in excreta, so as to provide a complete understanding of clearance and potential contributors to interpatient variability and drug-drug interactions? 2) What are the drug-related entities present in circulation that are the active principals contributing to primary and secondary pharmacology? 3) Are there findings (low extraction recovery of radiolabel from plasma, metabolite structures indicative of chemically reactive intermediates) that suggest potential safety issues requiring further risk assessment? 4) Do questions 2 and 3 have appropriate preclinical support in terms of pharmacology, safety pharmacology, and toxicology? Only if one or more of these four questions remain unanswered should additional mass balance studies be considered. PMID- 17364880 TI - Pharmacogenetic screening of the gene deletion and duplications of CYP2D6. AB - Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively high frequency in several populations. Genotyping of CYP2D6 could therefore be applied to individualize drug therapy to improve therapeutic efficacy and decrease adverse effects in patients. However, a prerequisite for the pharmacogenetic screening of CYP2D6 in a clinical setting is the development of fast, reliable and cost-effective techniques for the routine genotyping of patients. In the case of CYP2D6, besides the general problems that arise in the detection of large gene deletions and multiplications, the presence of two highly homologous pseudogenes, CYP2D7 and CYP2D8, forms an extra challenge. This review provides an overview of the techniques that have been described to detect the CYP2D6 gene deletion and multiplication: Southern-blotting RFLP, long-template PCR, and real-time PCR. Of these techniques, real-time PCR is the only technique giving quantitative information about the exact copy number of the gene. Considering all of the other advantages of this method over other methods, such as cost-effectiveness and suitability for high throughput screening, real-time PCR is the most promising method for the genotyping of large structural alterations in the CYP2D6 gene in a routine clinical setting. PMID- 17364881 TI - State-of-the-art tools for computational site of metabolism predictions: comparative analysis, mechanistical insights, and future applications. AB - In drug design, it is crucial to have reliable information on how a chemical entity behaves in the presence of metabolizing enzymes. This requires substantial experimental efforts. Consequently, being able to predict the likely site/s of metabolism in any compound, synthesized or virtual, would be highly beneficial and time efficient. In this work, six different methodologies for predictions of the site of metabolism (SOM) have been compared and validated using structurally diverse data sets of drug-like molecules with well-established metabolic pattern in CYP3A4, CYP2C9, or both. Three of the methods predict the SOM based on the ligand's chemical structure, two additional methods use structural information of the enzymes, and the sixth method combines structure and ligand similarity and reactivity. The SOM is correctly predicted in 50 to 90% of the cases, depending on method and enzyme, which is an encouraging rate. We also discuss the underlying mechanisms of cytochrome P450 metabolism in the light of the results from this comparison. PMID- 17364882 TI - Carbonyl reductases and pluripotent hydroxysteroid dehydrogenases of the short chain dehydrogenase/reductase superfamily. AB - Carbonyl reduction of aldehydes, ketones, and quinones to their corresponding hydroxy derivatives plays an important role in the phase I metabolism of many endogenous (biogenic aldehydes, steroids, prostaglandins, reactive lipid peroxidation products) and xenobiotic (pharmacologic drugs, carcinogens, toxicants) compounds. Carbonyl-reducing enzymes are grouped into two large protein superfamilies: the aldo-keto reductases (AKR) and the short-chain dehydrogenases/reductases (SDR). Whereas aldehyde reductase and aldose reductase are AKRs, several forms of carbonyl reductase belong to the SDRs. In addition, there exist a variety of pluripotent hydroxysteroid dehydrogenases (HSDs) of both superfamilies that specifically catalyze the oxidoreduction at different positions of the steroid nucleus and also catalyze, rather nonspecifically, the reductive metabolism of a great number of nonsteroidal carbonyl compounds. The present review summarizes recent findings on carbonyl reductases and pluripotent HSDs of the SDR protein superfamily. PMID- 17364883 TI - Application of chimeric mice with humanized liver for predictive ADME. AB - Much effort to extrapolate the in vivo pharmacokinetics of drugs in human from experimental animals or in vitro studies has been made by many researchers. A urokinase-type plasminogen activator+/+/severe combined immunodeficient transgenic mouse line, in which the liver could be replaced by more than 80% with human hepatocytes, was established recently in Japan. This chimeric mouse line is remarkable because the replacement is higher than any other chimeric mouse reported previously. Since the liver is the critical organ involved in the pharmacokinetics of drugs, human liver is essential for the development of new drugs. To predict the human drug metabolism and pharmacokinetics, human hepatocytes and liver microsomes are recognized as better tools and are frequently used. Thus, chimeric mice with humanized liver would have great advantages in studies on drug metabolism and pharmacokinetics. We have evaluated chimeric mice for studies on absorption, distribution, metabolism, and excretion (ADME). In the liver of the chimeric mice, human phase I and phase II enzymes were clarified to be expressed and to have a similar drug metabolizing capacity as the donor. Human specific metabolites could be detected in the serum, suggesting that the chimeric mice might be used as a human ADME model for both in vitro and in vivo studies. For predicting human drug interactions, enzyme induction and inhibition are serious problems. By the treatment with typical inducers, human CYP1A2 and CYP3A4 expressed in the liver of the chimeric mice had induction potencies. After the treatment with quinidine, a specific inhibitor of human CYP2D6, the area under the curve (AUC) of a CYP2D6 metabolite, 4' hydroxydebrisoquin, was significantly decreased in the chimeric mice but not in the control mice. Therefore, it was indicated that the chimeric mice could be used for assessing the drug interactions via enzyme induction and inhibition. As well as drug metabolism, the drug excretion was demonstrated to be humanized because cefmetazole was mainly excreted in urine both in the chimeric mice and human but in feces in control uPA-/-/SCID mice. In this review, basic researches on ADME in the chimeric mice with humanized liver are summarized and the application of the chimeric mice for predictive ADME is proposed. PMID- 17364884 TI - Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. AB - This review brings you up-to-date with the hepatocyte research on: 1) in vitro-in vivo correlations of metabolism and clearance; 2) CYP enzyme induction, regulation, and cross-talk using human hepatocytes and hepatocyte-like cell lines; 3) the function and regulation of hepatic transporters and models used to elucidate their role in drug clearance; 4) mechanisms and examples of idiosyncratic and intrinsic hepatotoxicity; and 5) alternative cell systems to primary human hepatocytes. We also report pharmaceutical perspectives of these topics and compare methods and interpretations for the drug development process. PMID- 17364885 TI - The antioxidant/electrophile response element motif. AB - Cells exposed to oxidative stress or electrophilic xenobiotics respond by transcriptionally up-regulating a battery of genes that contain a cis-acting element in their promoter region known as the antioxidant/electrophile response element (ARE). Mutational analysis of the promoter regions of ARE-containing genes led to the creation of two different models for the ARE; a core ARE (cARE: RTGACnnnGC) and an extended ARE (eARE: TMAnnRTGAYnnnGCAwwww). Using bioinformatic software we have aligned the promoter regions of several ARE-containing genes to produce two position-specific probability matrices that independently describe the cARE and eARE. These matrices can also be used to quantitatively assess putative AREs. PMID- 17364891 TI - Distribution of circulation-derived endothelial progenitors following systemic delivery. AB - Cells with an endothelial phenotype can be cultured from peripheral blood. These cells include cells of a monocytic origin with endothelial features (culture modified mononuclear cells, CMMCs) and, at later time points, blood outgrowth endothelial cells (BOECs). Both are promising candidates for systemic cell-based cardiovascular therapies and each may have unique capabilities. Indeed, the combined use of both cell types has been shown to have synergistic therapeutic features requiring simultaneous delivery. However, the majority of preclinical studies of cell delivery have used splenectomized animals to increase systemic distribution. The goal of this study was to directly compare the distribution of these two cell types following systemic delivery in an intact animal model. A similar pattern of delivery was seen following delivery of both cell types with detection in the lung, liver, bone marrow, and spleen. Taken together, the data suggest that strategies using systemic delivery of circulation-derived cells must consider the distribution and efficiency of delivery in intact animals. PMID- 17364892 TI - Chemokine transport across human vascular endothelial cells. AB - Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma-inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP] 1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface. PMID- 17364893 TI - Elevated glucose attenuates agonist- and flow-stimulated endothelial nitric oxide synthase activity in microvascular retinal endothelial cells. AB - Impaired vasoactive release of opposing vasodilator and vasoconstrictor mediators due to endothelial dysfunction is integral to the pathogenesis of diabetic retinopathy. The aim of this study was to determine the effect of hyperglycemia on the expression of endothelial nitric oxide synthase (eNOS) and the release of nitric oxide (NO) in bovine microvascular retinal endothelial cells (BRECs) under both static (basal and acetylcholine stimulated) and flow (laminar shear stress [10 dynes/cm2 and pulsatile flow 0.3 to 23 dynes/cm2) conditions using a laminar shear apparatus and an in vitro perfused transcapillary culture system. The activity and expression of eNOS, measured by nitrate levels and immunoblot, respectively, were determined following exposure of BRECs to varying concentrations of glucose and mannitol (0 to 25 mM). Under static conditions the expression of eNOS decreased significantly following exposure to increasing concentrations of glucose when compared to osmotic mannitol controls and was accompanied by a significant dose-dependent decrease in nitrate levels in conditioned medium. The acetylcholine stimulated increase in NO release (2.0 +/- 0.3-fold) was significantly reduced by 55% +/- 5% and 65% +/- 4.5% following exposure to 16 and 25 mM glucose, respectively, when compared to osmotic controls. In parallel studies, glucose significantly inhibited both laminar shear stress and pulsatile flow-induced activity when compared to mannitol. We conclude that hyperglycemia impairs agonist- and flow-dependent release of NO in retinal microvascular endothelial cells and may thus contribute to the vascular endothelial dysfunction and impaired autoregulation of diabetic retinopathy. PMID- 17364894 TI - A novel lysophospholipid- and pH-sensitive receptor, GPR4, in brain endothelial cells regulates monocyte transmigration. AB - Abundant evidence documents the highly proinflammatory actions of lysophosphatidylcholine (LPC). Further, LPC, found in high amounts in oxidized low-density lipoprotein (LDL), is implicated as an atherogenic factor. In endothelial cells, LPC impairs endothelial barrier function through GPR4, a novel receptor hypothesized to be sensitive to LPC and protons. The authors investigated the stimulation by LPC or low pH of GPR4 in human brain microvascular endothelial cells (HBMECs) and whether the activated GPR4 regulates in vitro monocyte transmigration. The results indicated that HBMECs stimulated by LPC (5 microM), but not low pH, showed a twofold increase in monocyte transmigration. Using retroviruses containing siRNA to GPR4, a > 60% reduction of GPR4 expression resulted in blockade of the LPC-stimulated transmigration. The inhibited response was restored by co-expression with an small interference RNA (siRNA)-resistant, but functional, GPR4 mutant construct. To investigate potential signaling mechanisms, the siRNA-mediated knockdown of GPR4 also prevented LPC-induced RhoA activation. C3 transferase, a Rho inhibitor, prevented approximately approximately 65% of the LPC-stimulated transmigration. LPC also increased MLC phosphorylation by 5 min, which was inhibited by the Rho kinase inhibitor, Y-27632 (10 microM) or ML-7 (myosin light chain kinase (MLCK) inhibitor). The findings indicate that the proinflammatory and atherogenic LPC stimulated endothelial GPR4, which promoted monocyte transmigration through a RhoA-dependent pathway. PMID- 17364895 TI - Immortalization and characterization of porcine ventricular endocardial endothelial cells. AB - Endocardial endothelial cells (EECs), which form the inner lining of the cavities of the heart, are a distinct cell population whose dysfunction can be critical in pathological conditions of heart. Insights into the role and organization of these cells in pathological states of the heart are limited mainly due to a dearth of experimental models. To date no endocardial endothelial cell line is available. The authors attempted to immortalize porcine ventricular EECs by transfecting the cells with human telomerase reverse transcriptase (hTERT). EECs immortalized by ectopic expression of hTERT exhibit phenotypic and functional characteristics similar to primary EECs. The EE cell line could be useful for the study of mechanisms involved in the interaction of EECs with the underlying myocardium and cardiac interstitium and as useful tools in understanding their role in diseased states of heart. PMID- 17364896 TI - Metalloproteinase-2 and -9 in diabetic and nondiabetic subjects during acute coronary syndromes. AB - The authors hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metalloproteinase (TIMP)-1, -2 would be abnormal in acute coronary syndromes (ACSs). MMP-2, -9, and TIMP-1, -2 plasma levels were measured in diabetic patients with ACSs compared to nondiabetic patients with ACSs. A total of 46 diabetic and 78 nondiabetic patients with ACSs were enrolled. The following parameters were measured: body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high-sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Significant HbA1c, FPG, FPI, HOMA index, DBP, Tg, Hct, and Fg increases were present in the diabetic group with ACSs, whereas hs-CRP was lower in these patients compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic patients with ACSs compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were increased in diabetic patients with ACSs, which may reflect abnormal extracellular matrix metabolism in diabetes during acute event. PMID- 17364897 TI - Epidemiologic and clinical factors associated with chronic kidney disease among Asian Americans and Native Hawaiians. AB - OBJECTIVE: To examine the association between key susceptibility factors and measures of chronic kidney disease in Asian American and Native Hawaiian participants enrolled in the Hawai'i site of the national Kidney Early Evaluation Program (KEEP-2) study community screening program. DESIGN: In 2001-2003, 793 participants from five ethnic groups (Japanese, Native Hawaii an, Chinese, Filipino and Caucasian) were enrolled in the Hawai'i KEEP-2 program. Odds ratios were used as the measure of association and were computed using unconditional logistic regression. Renal susceptibility factors for chronic kidney disease were included in a multivariable model if found to be statistically significant in univariate analysis. The proportion of Hawai'i KEEP-2 study participants manifesting various clinical characteristics were compared by ethnicity with Japanese as the referent group. RESULTS: Significant ethnic differences in the occurrence of chronic kidney disease were found, with Japanese having the lowest occurrence of chronic kidney disease (18%) and Native Hawaiians the highest (40%). Within each ethnic group, the occurrence of chronic kidney disease was associated with a different ethnic-specific clustering of susceptibility factors. Hypertension was associated with chronic kidney disease among four of the five ethnic groups: Japanese, Caucasian, Native Hawaiian and Filipino. Overweight was associated with a decreased occurrence of chronic kidney disease among Caucasians, while diabetes and lower educational attainment were associated with increased occurrence of chronic kidney disease among Native Hawaiians. For Filipinos, diabetes and age 65 years and older were both associated with an increased occurrence for chronic kidney disease while lower educational attainment was associated with a reduced occurrence of chronic kidney disease. Among Chinese, no factors were significantly associated with chronic kidney disease, although trends for all factors paralleled those of the overall study group. CONCLUSIONS: The occurrence of chronic kidney disease in the Hawai'i KEEP 2 study was nearly fourfold greater compared with the general US population. The clustering of susceptibility factors for chronic kidney disease occurrence was found to differ for all five ethnic groups. PMID- 17364898 TI - Variability in pediatric injury patterns by age and ethnic groups in Israel. AB - BACKGROUND: . In Israel, nearly 10,000 children are hospitalized due to injury every year. OBJECTIVES: To define injury patterns in subgroups of the pediatric population, in order to focus prevention programs on vulnerable groups. METHODS: A retrospective study of Israel's National Trauma Registry (ITR) data on patients aged 0-17 years hospitalized between 1 January 1998 and 31 December 2002 due to trauma. Data includes patient demographic details, information on the injury, hospital resource utilization, length of stay and outcome. Descriptive statistics were used to characterize injury patterns and bivariate and multivariate analysis was used to compare injury severity and cause between population groups. RESULTS: A total of 32,009 children were included. Falls were the cause of injury for 51% of the population, 6% of falls sustaining severe injuries (ISS 16+). Road traffic accidents (RTA) injured 23%, of which 14% were severe injuries. Burns (7%) accounted for long hospitalizations -- nearly 20% stayed for over 14 days. Crude data showed that the proportion of severe injuries and inpatient death rate among non-Jewish children was double that of Jewish children (12% vs 6% and 1% vs 0.5%, respectively (chi2, p<0.0001)). When looking at children from low socio-economic status (SES) townships, the difference in proportion of severe injuries between Jewish and non-Jewish children is reduced, yet it remains higher in non-Jewish than among Jewish children (7% vs 5%) (chi2, p=0.0001). These results were verified by multivariate logistic regression analysis adjusting for SES, age, gender and external injury cause. Non-Jewish children had a significantly higher rate of burns (10% vs 6%), falls from heights above 2.5 meters (16% vs 6% of all falls) and pedestrian injuries (51% vs 37% of all injured in RTA). When SES is taken into account, the only outstanding injury among non-Jewish children is fall from height: 13%, n=376 among non-Jewish children vs 8%, n=85 among Jewish children, living in townships with low SES cluster (1-4) (chi2, p<0.0001). CONCLUSIONS: The findings of this study show that there is variability in external cause of injury and severity by age and ethnic group. Falls were most frequent among young children and burns among non-Jews. Non-Jewish children in SES clusters 1-4 are at high risk for falls from height, suggesting intervention and prevention activities should be directed in this direction. PMID- 17364899 TI - Different perspectives on emotional and behavioural problems in unaccompanied refugee children and adolescents. AB - OBJECTIVE: This study aims, firstly, to investigate the prevalence of emotional and behavioural problems in unaccompanied refugee children and adolescents living in Belgium. Secondly, this study compares the perspectives of the adolescents with those of social workers on the adolescents' emotional well-being. DESIGN: A total of 166 unaccompanied refugee children and adolescents, living in different large- and small-scale centres, in foster care or alone, participated in the study. Of them, 142 completed self-report questionnaires on emotional and behavioural problems (HSCL-37A, SDQ-self and RATS) and traumatic experiences (SLE), and for 124 refugee youths, social workers filled in two questionnaires on emotional and behavioural problems (CBCL/6-18 and SDQ-parent). RESULTS: Between 37 and 47% of the unaccompanied refugee youths have severe or very severe symptoms of anxiety, depression and post-traumatic stress. Girls and those having experienced many traumatic events are at even higher risk for the development of these emotional problems. Social workers also report a high prevalence of internalising problems in this population and they also report important externalising problems in unaccompanied refugee youths. CONCLUSION: Being unaccompanied is an important risk factor for the emotional well-being of refugee children and adolescents. Therefore, appropriate measures on reception and care should be taken in order to support these youths. PMID- 17364900 TI - Assessment of two culturally competent diabetes education methods: individual versus individual plus group education in Canadian Portuguese adults with type 2 diabetes. AB - OBJECTIVE: To examine the impact of two culturally competent diabetes education methods, individual counselling and individual counselling in conjunction with group education, on nutrition adherence and glycemic control in Portuguese Canadian adults with type 2 diabetes over a three-month period. DESIGN: The Diabetes Education Centre is located in the urban multicultural city of Toronto, Ontario, Canada. We used a three-month randomized controlled trial design. Eligible Portuguese-speaking adults with type 2 diabetes were randomly assigned to receive either diabetes education counselling only (control group) or counselling in conjunction with group education (intervention group). Of the 61 patients who completed the study, 36 were in the counselling only and 25 in the counselling with group education intervention. We used a per-protocol analysis to examine the efficacy of the two educational approaches on nutrition adherence and glycemic control; paired t-tests to compare results within groups and analysis of covariance (ACOVA) to compare outcomes between groups adjusting for baseline measures. The Theory of Planned Behaviour was used to describe the behavioural mechanisms that influenced nutrition adherence. RESULTS: Attitudes, subjective norms, perceived behaviour control, and intentions towards nutrition adherence, self-reported nutrition adherence and glycemic control significantly improved in both groups, over the three-month study period. Yet, those receiving individual counselling with group education showed greater improvement in all measures with the exception of glycemic control, where no significant difference was found between the two groups at three months. CONCLUSIONS: Our study findings provide preliminary evidence that culturally competent group education in conjunction with individual counselling may be more efficacious in shaping eating behaviours than individual counselling alone for Canadian Portuguese adults with type 2 diabetes. However, larger longitudinal studies are needed to determine the most efficacious education method to sustain long-term nutrition adherence and glycemic control. PMID- 17364901 TI - Cost as a barrier to screening mammography among underserved women. AB - BACKGROUND: Breast cancer is a troublesome health problem, particularly among underserved and minority women. Early detection through screening mammography can reduce the impact of this disease, yet it remains underused. Objective. We examined cost as a barrier to screening mammography and studied the accuracy of women's perceptions of the cost of a mammogram among a rural, low-income, tri racial (white, Native American and African American) population in need of a mammogram. DESIGN: We interviewed 897 women age 40 and older, asking about cost as a barrier to mammography and perceptions about the actual costs of a screening mammogram. Face-to-face interviews were conducted between 1998 and 2000 among women participating in a randomized, controlled study to evaluate a health education intervention to improve mammography screening rates in an underserved population. All data used in these analyses were from the baseline interviews. RESULTS: Cost acted as a barrier to screening mammography for a majority of the participants (53%). More than half of these women (52%), however, overestimated the cost of a screening mammogram, and overestimation of the cost was significantly related to mentioning cost as a barrier (OR 1.56, 95% CI 1.04 2.33). Higher estimates of out-of-pocket costs were associated with reporting cost as a barrier to mammography (OR 2.25, 95% CI 1.43-3.52 for $1-50 and OR 12.64, 95% CI 6.61-24.17 for >$50). Factors such as race, income and employment status were not related to reporting cost as a barrier to screening mammography. CONCLUSIONS: Among a group of tri-racial, low-income, rural women who were in need of a mammogram, cost was a common barrier. Overestimating the cost, however, was significantly and positively associated with reporting cost as a barrier. Providing information about the actual cost women have to pay for mammograms may lessen the role of cost as a barrier to mammography screening, especially for underserved women, potentially improving utilization rates. PMID- 17364902 TI - Molecular genetic studies on relationships among longevity, diseases, and HLA DRB1/DQB1 allelic polymorphism. PMID- 17364903 TI - Mortality and heart rate in the elderly: role of cognitive impairment. AB - Mortality related to heart rate (HR) increase in the elderly has not yet been well established. To ascertain the relationships among cognitive impairment (CI), mortality, and HR increase, the authors prospectively studied a random sample of elderly subjects stratified according to presence or absence of CI. Elderly subjects randomly selected in 1991 (n = 1332) were followed up for 12 years. Mortality was established in 98.1% of the subjects. When HR was stratified in quartiles (< 69, 70-75, 76-80, and > 80 bpm), mortality was linearly associated with increased HR in all (from 47.7 to 57.0; r2 = .43, p = .019) and in subjects without (from 41.7 to 51.1%; r2 = .50, p = .043) but not in those with CI (from 57.5 to 66.1; r2 = .20, p = .363). Cox regression analysis, adjusted for several variables, shows that HR doesn't predict mortality in all subjects (RR 0.69; 95% CI = 0.27-1.73) or in those with CI (RR 0.91; 95% CI = 0.81-1.02). In contrast, HR predicts mortality in subjects without CI (RR 1.10; 95% CI = 1.00-1.22). Hence, HR increase is a predictor of mortality in elderly subjects without CI. However, when considering all elderly subjects and those with CI, HR increase seems to have no effect on mortality. Thus, CI should be considered when focusing on HR increase as risk factor for mortality in the elderly. PMID- 17364904 TI - Adult age differences in errand planning: the role of task familiarity and cognitive resources. AB - This study examines the effects of age, cognitive resources, and task familiarity on planning performance. Fifty-two young and 52 old adults completed one of two errand-planning tasks. The tasks were matched for structure, difficulty, and format, but differed in content, such that one planning task required planning a real-world shopping tour whereas the other involved planning an unfamiliar space tour. In addition, the participants' memory capacity, speed of processing, inhibition, and memory for relevant versus irrelevant task features were assessed. Results revealed no age differences for the real-world planning material. In contrast, old adults performed worse than young adults in the artificial planning task. Data are discussed in the context of old adults possibly being able to compensate for cognitive deficits in speed and inhibition by selectively allocating resources to relevant task elements, but only if they perform a planning task containing elements that approximate their real-world experience with errand-planning problems. PMID- 17364905 TI - How do verbal distractors influence age-related operation span performance? A manipulation of inhibitory control demands. AB - This study examined how different verbal distractors influence (age-related) performance in the operation span working memory task. Forty-six older (M = 68 years, SD = 3.82) and 49 younger adults (M = 27 years, SD = 3.02) performed a conventional operation span task version and three versions with non-related, conceptually related, or phonologically related distracting words. Thus, the amount of inhibitory control demands varied across the task versions. Age effects were found for all versions. Furthermore, age effects in the versions with distracting words were even larger than in the conventional version, indicating that a decline in the ability to inhibit irrelevant verbal information can partly explain age effects in working memory performance. PMID- 17364906 TI - Estimating the effects of right median nerve stimulation on memory in Alzheimer's disease: a randomized controlled pilot study. AB - The goal of the present study was to examine possible effects of right median nerve stimulation (RMNS) on memory in patients in a relatively early stage of probable Alzheimer's disease (AD). Seventeen AD patients were randomly assigned to an experimental group (n = 8) and a control group (n = 9) and treated with RMNS and sham RMNS, respectively, for 30 min a day, 5 days a week, for 6 weeks. Neuropsychological tests were used to assess memory processes. The results show that the various aspects of memory did not respond positively to RMNS. A study with a much longer treatment period is suggested before firm conclusions about the ineffectiveness of RMNS on memory in AD can be drawn. PMID- 17364907 TI - Population inference with mortality and attrition in longitudinal studies on aging: a two-stage multiple imputation method. AB - A major challenge for inference regarding aging-related change in longitudinal studies is that of study attrition and population mortality. Inferences in longitudinal studies can account for attrition and mortality-related change as distinct processes, but this is made difficult when follow-up of all individuals (i.e., age at death) is not complete. This is a common problem because most longitudinal studies of aging either have incomplete follow-up or are still collecting data on subsequent outcomes, including time of death. A statistical approach is suggested for including time-to-death as a predictor in models with incomplete follow-up using a two-stage multiple-imputation procedure. An empirical example using data from the OCTO-Twin study is presented that shows the utility of his procedure for making inferences conditional on mortality when mortality data are incomplete. PMID- 17364908 TI - Short-term cigarette smoke exposure potentiates endotoxin-induced pulmonary inflammation. AB - Long-term cigarette smoke exposure is associated with chronic obstructive pulmonary disease. However, the effects of short-term smoke inhalation are less clear, because it may adversely affect the lung only if underlying disease is present. To test this hypothesis, Syrian hamsters were passively exposed to cigarette smoke for 2 hours per day over a period of 3 days either before or after intratracheal instillation of low-dose (20 microg) Escherichia coli endotoxin. The results indicate that short-term smoke exposure can potentiate endotoxin-induced lung inflammation. They also suggest that nonsmokers with underlying lung disease may be particularly vulnerable to the adverse effects of second-hand smoke. PMID- 17364909 TI - Fibroblast growth factor-2 promotes recovery of pulmonary function in a canine models of elastase-induced emphysema. AB - Bronchoscopic lung volume reduction (BLVR) for severe emphysema is less invasive than lung volume reduction surgery. Fibroblast growth factor-2 (FGF-2) has been reported to enhance fibrogenesis and angiogenesis. The aim of this study was to investigate the feasibility of BLVR with the FGF-2, and ability to reduce lung volume and promote recovery of lung function. The BLVR based on FGF-2 is less invasive than surgical procedures, and can be performed repeatedly if the effectiveness of volume reduction is inadequate. This simple bronchoscopic approach allows selective reduction in the volume of the emphysematous parenchyma, and intratracheal administration of FGF-2 induces an increase in pulmonary blood flow, thus allowing recovery of pulmonary function. PMID- 17364910 TI - Responses of differentiated primary human lung epithelial cells to exposure to diesel exhaust at an air-liquid interface. AB - In vitro responses of potential target cell types to air pollutants under physiological conditions may be useful in understanding the health effects of air pollution exposure. The study evaluated responses of human primary airway epithelial cells to diesel exhaust (DE). Cultures of cells from 3 donors, differentiated by culture on membranes with the apical surfaces exposed to the atmosphere, were exposed to filtered air or DE. Some exposure-related effects were similar among donors, whereas others were affected by the donor, consistent with human population heterogeneity. This model may be useful for mechanistic and comparative toxicology studies. PMID- 17364911 TI - Intake and risk assessment of nitrate and nitrite from New Zealand foods and drinking water. AB - Exposure to excess nitrite is a potential health risk for humans. One hundred meat and processed foods and 100 vegetable samples purchased from New Zealand retail outlets were prepared as for consumption and analysed for nitrite and nitrate concentration using a standard, validated methodology. Nitrate concentrations ranged from less than the limit of detection (LOD = 5 mg kg-1) in cheddar cheese and cream cheese-based dips to 3420 mg kg-1 in lettuce. Nitrite was detected in half the processed foods and meats analysed (levels up to 119 mg kg-1), but detected in only one vegetable sample above the LOD (broccoli at 27 mg kg-1 nitrite). Concentration data were combined with 24 h dietary recall information to generate 4398 individual adult daily exposure scenarios for exogenous nitrite and nitrate including a contribution from water assessed from 1021 drinking water samples. The mean adult daily intake of exogenous nitrate and nitrite from food and water combined was 16 and 13% of the Acceptable Daily Intake (ADI), respectively, and therefore should not pose a health risk for the average consumer. A maximally exposed New Zealand adult is estimated to have an intake of up to seven times the ADI for nitrate. When the endogenous conversion of nitrate to nitrite is taken into account, approximately 10% of people with an average rate of conversion and half of all people with a high rate of conversion are estimated to exceed the ADI. Either the ADI is inappropriate and needs to be re-evaluated, or those individuals who have a high rate of conversion of nitrate to nitrite are at risk to adverse effects of nitrite exposure. PMID- 17364912 TI - Structure determination of new analogues of vardenafil and sildenafil in dietary supplements. AB - New analogues of vardenafil and sildenafil illegally added to dietary supplements were detected by high-performance liquid chromatography (HPLC) analysis with a photodiode array detector (PDA). These compounds were isolated and their structures elucidated by mass spectrometry (MS), infrared (IR) spectroscopy, one- and two-dimensional nuclear magnetic resonance (NMR). One of the new analogues given the trivial name pseudovardenafil (compound 1) was structurally elucidated and shown to be 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1 f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-piperidine. It was a vardenafil analogue isolated from a dietary supplement capsule. Compared with vardenafil, the piperidine ring was substituted for the ethylpiperazine group. The second new analogue, trivially named hydroxyhongdenafil (compound 2), was separated from bulk powder used as a raw material for a dietary supplement. The piperazine and phenyl groups were connected through an acetyl group instead of a sulfonyl group, and hydroxyethylpiperazine was substituted for the methylpiperazine of sildenafil. It was structurally elucidated as 5-[2-ethoxy-5-[[4-(2-hydroxyethyl) 1-piperazinyl]acetyl]phenyl]-1,4-dihydro-1-methyl-3-propyl-7H-pyrazolo[4,3 d]pyrimidin-7-one. PMID- 17364913 TI - Dilute-and-shoot procedure for the determination of mineral constituents in vinegar samples by axially viewed inductively coupled plasma optical emission spectrometry (ICP OES). AB - Samples of commercial wine vinegar were introduced in an axially viewed inductively coupled plasma optical emission spectrometry instrument (AX-ICP OES) equipped with different sample introduction systems: a cross-flow nebulizer combined with a double-path spray chamber (CF-DP) and cone spray associated with a cyclone spray chamber (CS-CC). Samples of white and red wine vinegar were diluted with water before analysis. Higher magnesium Mg II/Mg I ratios (11 and 10 for CS-CC and CF-DP, respectively) were obtained using a nebulization gas flow rate of 0.6 l min-1 and an applied power of 1.3 kW. The background equivalent concentrations (BEC) and signal-to-background ratio (SBR) of analytes were improved using scandium (Sc) as the internal standard. The limits of detection (LOD) and limits of quantification (LOQ) for mineral constituents were similar for both introduction systems. Best recoveries values were obtained using a plasma under robust conditions, CS-CC system and Sc as the internal standard. The concentration determined in 13 commercial samples of wine vinegars varied between 0.2 and 3.0, between 0.02 and 0.4, between 8.5 and 100.0, between 0.01 and 0.05, between 27.0 and 540.0, between 4.0 and 79.0, between 0.4 and 10.0, and between 0.01 and 2.0 for aluminium (Al), barium (Ba), calcium (Ca), copper (Cu), potassium (K), magnesium (Mg), manganese (Mn), and zinc (Zn), respectively. PMID- 17364914 TI - An intercomparison study of the determination of glyphosate, chlormequat and mepiquat residues in wheat. AB - An intercomparison study of the determinations of glyphosate, chlormequat and mepiquat residues in cereals was performed. Four samples comprising one blank, two incurred and one spiked sample were sent to six participating laboratories. For glyphosate, two laboratories reported considerably lower results than the other four. One of the two laboratories with low results also reported low recoveries. The results of a sample spiked with 0.80 mg kg-1 glyphosate and an incurred sample, ranged from 0.23-0.87 mg kg-1 and 0.11-0.25 mg kg-1 respectively. The strong correlation between the two samples (r2 = 0.95) indicates a systematic between-laboratory variation. Several different principles were used for the analysis of glyphosate using different clean-up techniques and GC/MS, HPLC-fluorescence or LC/MS for detection. The results of the chlormequat residues showed more consistency. All but one laboratory obtained comparable results. However the correlation between the results for the sample spiked with 0.38 mg kg-1 (range: 0.26-0.65 mg kg-1) and the incurred samples (range: 0.19 0.45 and 0.15-0.23 mg kg-1, respectively) again showed a strong correlation (r2 = 0.99 and 0.88) indicating a systematic component. For mepiquat, results above the limit of quantification were only reported for the spiked sample. The results ranged from 0.29-0.92 mg kg-1 (spiked concentration = 0.38 mg kg-1). Three laboratories had results that deviated less than 25% from the fortified concentration. Two laboratories reported results 38% and 141% above the fortified concentration, respectively. PMID- 17364915 TI - Variability in captan residues in apples from a Canadian orchard. AB - Apple trees in an orchard in Quebec, Canada were treated, following label directions, with the fungicide captan (1,2,3,6-tetrahydro-N (trichloromethylthio)phthalimide) during the 2003 agricultural season. A total of 142 apples from three rows of trees were selected for determination of captan by GC/MS. Individual apples were found to contain captan levels ranging from 16.9 to 6350 ng g-1. Only two individual apple samples exceeded the Canadian maximum residue limit (5000 ng g-1) for captan in apples. Six composite samples, comprising half portions of eight individual apples, were analysed from each of the three experimental rows. Composite samples ranged in concentration from 166 to 2620 ng g-1. The greatest uncertainty associated with the measured concentrations was due to variability among apples rather than the measurement of residue levels. PMID- 17364916 TI - Comparison of matrix solid-phase dispersion and liquid-liquid extraction for the chromatographic determination of fenthion and its metabolites in olives and olive oils. AB - Matrix solid-phase dispersion (MSPD) methodology has been developed to extract fenthion and its metabolites from olives and olive oils, and the technique compared with conventional liquid-liquid extraction (LLE). The method was applied to olives and olive oil samples obtained from olive groves treated with fenthion. Pesticide residues were analysed by gas chromatography (GC) using a nitrogen phosphorus detector. Both extraction methods gave a linear response over the concentration range assayed (0.03-1 mg kg-1 for MSPD and 0.1-1 mg kg-1 for LLE). Recoveries and RSD (n = 6) values in olives were 85-112% and 2-6% for MSPD, and 68-108% and 4-16% for LLE, respectively. In the case of olive oil, recoveries and RSD (n = 6) values were 67-98% and 5-11% for MSPD, and 63-115% and 6-14% for LLE, respectively. When compared to LLE, the newly developed MSPD method was twice as sensitive and required 10 times less sample weight. PMID- 17364917 TI - Polymerase chain reaction (PCR) identification of Penicillium brevicompactum, a grape contaminant and mycophenolic acid producer. AB - Penicillium brevicompactum is a ubiquitous fungal species that contaminates diverse substrates and commodities and produces an array of metabolites toxic to human and animals. The present work has obtained evidence, by liquid chromatography (LC)-ion-trap mass spectrometry, of the ability of P. brevicompactum strains isolated from grapes to produce mycophenolic acid, a potent immunosuppressor. In order to facilitate early diagnosis of this species on commodities for human and animal consumption, a rapid, sensitive and specific polymerase chain reaction (PCR) assay for P. brevicompactum was developed. The specific primers were designed based on the ITS1-5.8S-ITS2ITS (Internal Transcribed Spacers of rRNA genes) multicopy region. This method provides a useful aid to detect the presence of this fungal species in grapes and other commodities in order to prevent the toxins produced entering the food chain. PMID- 17364918 TI - Simultaneous determination of aflatoxin B1 and ochratoxin A and their natural occurrence in Mediterranean virgin olive oil. AB - Olive oil, the most important dietary fat source of the Mediterranean diet, can be contaminated by mycotoxins. An efficient analytical method for the simultaneous determination of aflatoxin B1 (AFB1) and ochratoxin A (OTA) in olive oil is reported. Thirty commercial samples of virgin olive oil, purchased in olive-press plants and supermarkets in southern Italy and North Africa, were analysed to verify the analytical procedure and monitor mycotoxin contamination. A simple, rapid and economic method was set up and tested for both the extractive step and the clean-up procedures for simultaneous AFB1 and OTA determination in olive oil. Data obtained showed that OTA was detected with high frequency (80%) in samples from both geographical areas (up to 17.0 ng g-1), while AFB1 was found from three of four samples from North Africa (up to 2.4 ng g-1). In addition, 'not labelled' oil samples proved to be more contaminated by OTA then 'labelled' samples (mean values of 2.47 and 0.66 ng g-1, respectively). These findings indicate that olive oil can be significantly contaminated by mycotoxins and confirm that a scrupulous application of European Regulation 1019/2002 (European Commission 2002), which prohibits the sale of non-labelled olive oil, is strongly recommended. Conventional qualitative parameters such as peroxide number, spectrophotometric evaluation and acid values were not correlated with mycotoxin occurrence. PMID- 17364919 TI - Fumonisin B1 contamination of home-grown corn in high-risk areas for esophageal and liver cancer in China. AB - Fumonisin B1 (FB1) is reportedly the causative agent of several animal mycotoxicoses and has etiologically been linked to human oesophageal and liver cancer in certain areas of South Africa and China. To study a possible relationship between exposure to FB1 and human cancer risk, the current status of FB1 contamination in food samples in Huaian and Fusui, where incidences of oesophageal and liver cancer are amongst the highest in China, was investigated. A total of 259 corn samples were collected from individual households in five villages of different townships in Huaian during December 2001 and December 2002, and in four villages of different townships in Fusui during May 2001 and May 2002. Corn samples were also collected from individual households in two villages in Huantai, an area with low incidences of both cancers. Enzyme-linked immunosorbent assays (ELISA) and immunoaffinity-HPLC methods were used for FB1 analysis. In corn samples from Huaian, FB1 was detectable in 95.7% (112/117) of the samples, with an average of 2.84 mg kg-1 (range 0.1-25.5 mg kg-1). FB1 was detected in 83.0% (78/94) of the Fusui samples, with an average of 1.27 mg kg-1 (range 0.1-14.9 mg kg-1), and in 83.3% (40/48) of Huantai samples, with an average of 0.65 mg kg-1 ranging from 0.1 to 5.7 mg kg-1. The level of FB1 in corn samples from Huaian was significantly higher than from Huantai (P < 0.001). In addition, 47 of 112 (42.0%) positive Huaian samples had FB1 level greater than 2.0 mg kg-1, which was significantly higher than 10.0% (4/40) of Huantai samples (P < 0.001). Furthermore, variations were found between samples collected in different years and different villages. The high contamination rates of FB1 found in food from these areas, along with previous reports, suggest a possible contributing role of FB1 in human esophageal- and hepato-carcinogenesis. PMID- 17364920 TI - Dietary intake of polychlorinated dioxins, furans and dioxin-like polychlorinated biphenyls from foods of animal origin in China. AB - Four food groups of animal origin from the Chinese Total Diet Study (TDS) in 2000 were analysed for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 12 dioxin-like polychlorinated biphenyls (PCBs). The samples were from four regions, covering 12 provinces of China. PCDD/Fs, expressed as WHO toxic equivalents (TEQ), ranged from 0.02 to 0.28 pg TEQ g-1 and dioxin-like PCBs ranged from 0.01 to 0.24 pg TEQ g-1 (wet weight, ND = LOD), in all samples. Using food consumption data from a 3-day household dietary survey, daily dietary intake of dioxin-like compounds from foods of animal origin in China was estimated. Daily intake among regions ranged 0.09-0.59 pg TEQ kg-1 body eight day-1. PMID- 17364921 TI - Consumer exposure to substances in plastic packaging. I. Assessment of the contribution of styrene from yogurt pots. AB - A generic methodology for the assessment of consumer exposure to substances migrating from packaging materials into foodstuffs during storage is presented. Consumer exposure at the level of individual households is derived from the probabilistic modeling of the contamination of all packed food product units (e.g. yogurt pot, milk bottle, etc.) consumed by a given household over 1 year. Exposure of a given population is estimated by gathering the exposure distributions of individual households to suitable weights (conveniently, household sizes). Calculations are made by combining (i) an efficient resolution of migration models and (ii) a methodology utilizing different sources of uncertainty and variability. The full procedure was applied to the assessment of consumer exposure to styrene from yogurt pots based on yearly purchase data of more than 5400 households in France (about 2 million yogurt pots) and an initial concentration c0 of styrene in yogurt pot walls, which is assumed to be normally distributed with an average value of 500 mg kg-1 and a standard deviation of 150 mg kg-1. Results are discussed regarding both sensitivity of the migration model to boundary conditions and household practices. By assuming a partition coefficient of 1 and a Biot number of 100, the estimated median household exposure to styrene ranged between 1 and 35 microg day-1 person-1 (5th and 95th percentiles) with a likely value of 12 microg day-1 person-1 (50th percentile). It was found that exposure does not vary independently with the average consumption rate and contact times. Thus, falsely assuming a uniform contact time equal to the sell-by-date for all yogurts overestimates significantly the daily exposure (5th and 95th percentiles of 2 and 110 microg day-1 person-1, respectively) since high consumers showed quicker turnover of stock. PMID- 17364922 TI - Use of a food-consumption database with packaging information to estimate exposure to food-packaging migrants: expoxidized soybean oil and styrene monomer. AB - There is no set protocol for completing refined exposure assessments of food packaging migrants in the European Union. One novel method that could be used to provide more realistic exposure assessments and also reduce uncertainty in the exposure estimation could be the use of food consumption surveys that also have packaging information. The aim of the current study was to estimate exposure to two food-packaging migrants (expoxidized soybean oil (ESBO) and styrene monomer) using a food-consumption database that collected packaging information. The Irish National Children's Food Survey (NCFS) was completed in 2003-04 and it collected information on the type and amount of food consumed by 594 Irish children aged 5 12 years, in addition to the type of packaging used for these foods. The Irish Food Packaging Database (IFPD) was completed in parallel to this food consumption survey and recorded exact information on the contact layer used for the packaging. In a database that combined information from the NCFS and the IFPD, the packaging materials that could contain the target migrants were identified. If a food was packaged in a material that could contain the migrant, it was assumed that the migrant was present in the food. For the exposure assessment of ESBO the 90th percentile migration values of ESBO in foods derived from the literature were used. This was similar to a method as used by the European Food Safety Authority (EFSA) in their exposure assessment of ESBO for adults. Two scenarios of styrene exposure were undertaken in this study. In the first scenario the 90th percentile migration value for styrene found in foods was used; in the second scenario the maximum level of styrene found in foods was used. These migration values were derived from the literature. The mean intake of ESBO for Irish children was 0.023 mg kg-1 body weight day-1, which is well below the tolerable daily intake (TDI) of 1 mg kg-1 body weight day-1 set by the Scientific Committee for Food (SCF) in 1999. The food group that contributed most to ESBO intake was tomato sauces packed in glass jars with polyvinyl chloride (PVC)-lined metal lids (46.8%). For styrene, the mean intake was 0.122 microg kg-1 body weight day-1 when using the 90th percentile migration values and 0.169 microg kg 1 body weight day-1 when using the maximum migration values. These estimated intakes are below the provisional maximum tolerable daily intake (PMTDI) of 40 microg kg-1 body weight day-1, which was established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1984. Therefore, the estimated intakes of the two migrants are not of concern for Irish Children and uncertainty is reduced in the assessment due to the fact that information is available on the type of foods consumed the type of packaging used for these foods. PMID- 17364923 TI - Estimated intake of intense sweeteners from non-alcoholic beverages in Denmark. AB - In 1999, 116 samples of non-alcoholic beverages were analysed for the intense sweeteners cyclamate, acesulfame-K, aspartame and saccharin. High contents of cyclamate close to the maximum permitted level in 1999 of 400 mg l(-1) were found in many soft drinks. The estimated intake of the sweeteners was calculated using the Danish Dietary Survey based on 3098 persons aged 1-80 years. The estimated intake with 90th percentiles of 0.7, 4.0 and 0.2 mg kg(-1) body weight (bw) day( 1) for acesulfame-K, aspartame and saccharin, respectively, was much lower than the acceptable daily intake (ADI) values of 15, 40 and 2.5 mg kg(-1) bw day(-1) for acesulfame-K, aspartame and saccharin, respectively. However, the 90th percentile of the estimated cyclamate intake in 1-3 year olds was close to the ADI value of 7 mg kg(-1) bw day(-1); and the 99th percentile in the 1-10 year olds far exceeded the ADI value. Boys aged 7-10 years had a significantly higher estimated intake of cyclamate than girls. The 90th percentile for the whole population was 1.8 mg kg(-1) bw day(-1). After the reduction in the maximum permitted level in the European Union in 2004 from 400 to 250 mg cyclamate l-1, the exposure in Denmark can also be expected to be reduced. A new investigation in 2007 should demonstrate whether the problem with high cyclamate intake is now solved. PMID- 17364924 TI - Determination of acrylamide levels in selected foods in Brazil. AB - Selected carbohydrate-rich foods available on the Brazilian market (111 samples representing 19 product categories) were analysed for acrylamide content using a liquid chromatography-tandem mass spectrometry method. A limit of detection of 10 microg kg(-1), a limit of quantitation of 20 microg kg(-1) and mean recoveries ranging 100 to 115% were obtained during a laboratory validation procedure. The concentration of acrylamide in the samples ranged from <20 to 2528 microg kg(-1), with a considerable variation between individual foodstuffs within the same food product class. The highest levels were found in potato products processed at high temperature and in instant coffee, while the lowest concentrations were detected in cassava- and maize-based products, bread and beer. These results are comparable with those reported in other countries. PMID- 17364925 TI - Addition of antioxidant from bamboo leaves as an effective way to reduce the formation of acrylamide in fried chicken wings. AB - The efficiency of antioxidant from bamboo leaves on the reduction of acrylamide during thermal processing and optimization of levels of addition of antioxidant from bamboo leaves applied to fried chicken wings are reported. The authors optimized the method of the addition of antioxidant from bamboo leaves to fried chicken wings and the frying processing parameters, and also compared the relationship between the content of total flavonoids in three extracts (EBL(971), EBL(972) and antioxidant from bamboo leaves) and the extent of the reduction of acrylamide. The acrylamide levels were quantified by a validated liquid chromatography coupled with tandem mass spectrometry detection method and the sensory evaluation was performed in a double-blind manner. The results showed that nearly 57.8 and 59.0% of acrylamide in fried chicken wings were reduced when the antioxidant from bamboo leaves addition ratios were 0.1 and 0.5% (w/w), respectively. The maximum inhibitory rate was achieved when antioxidant from bamboo leaves was chosen as the additive with a total flavonoid content of 32% compared with other two extracts and antioxidant from bamboo leaves mixed with flour was selected as the method of addition. Sensory evaluation results showed that the odour and flavour of fried chicken wings with antioxidant from bamboo leaves treatments had no significant difference compared with normal food matrixes (p > 0.05) when the antioxidant from bamboo leaves addition ratio was <0.5% (w/w). Colour acceptability in the study of sensory evaluation was in good correspondence with colour formation of fried chicken wings in each test group. These results suggest that antioxidant from bamboo leaves could significantly reduce acrylamide formation in fried chicken wings and yet still retain the original flavour and odour of the fried products. This study could be regarded as a pioneer contribution to the reduction of acrylamide in various foods by natural antioxidants. PMID- 17364926 TI - Microbiological detection of 10 quinolone antibiotic residues and its application to artificially contaminated poultry samples. AB - To assess if microbiological inhibition tests for detection of antibiotic residues are suitable for routine screening for quinolone residues, the limit of detection (LOD) of 10 different quinolones and fluoroquinolones was determined. Two media were tested, one at pH 6 and the other at pH 8, each seeded with one of the following test strains: Bacillus subtilis, Escherichia coli or Bacillus cereus. LODs of the 10 substances were highest on plates seeded with B. cereus, intended for selective detection of tetracycline residues. The pattern of zones on the other four plates differed for the targeted quinolones: flumequine and oxolinic acid were detected at lower concentrations at pH 6, while the LODs of ciprofloxacin, enrofloxacin, danofloxacin, marbofloxacin, sarafloxacin and norfloxacin were lower at pH 8. Nine of the 10 quinolones were detected more easily with E. coli, but the LOD of difloxacin was lower with B. subtilis. Finally, the three most sensitive media were selected and fluid from chicken meat, spiked with eight quinolones near maximum residue limits (MRL), analysed on each plate. The plate seeded with E. coli at pH 8 detected five of eight quinolones at levels of interest, but an additional E. coli plate at pH 6 was necessary for detection of flumequine in species other than poultry and fish. None of the plates detected oxolinic acid and difloxacin at MRLs in muscle tissue. PMID- 17364927 TI - Survey of nutritional supplements for selected illegal anabolic steroids and ephedrine using LC-MS/MS and GC-MS methods, respectively. AB - Several studies have highlighted that nutritional supplements may contain undeclared substances that are banned by the International Olympic Committee (IOC)/World Anti-Doping Agency (WADA). This paper describes a qualitative liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) method to detect anabolic androgenic steroids (4-androsten-3,17-dion, 4-oestren-3,17 dion, 5alpha-androsten-17beta-ol-3-one, boldenone, nandrolone, nandrolone decanoate, testosterone, and testosterone decanoate) and ephedrine in food supplements. The products are dissolved in methanol and analysed by gas chromatography-mass spectrometry (GC-MS). The methanolic solution was added to testosterone-d(3), evaporated to dryness, mixed with NaOH and extracted with n pentane:diethylether (9:1). LC-MS/MS analyses were performed in selected reaction monitoring (SRM) on an ion-trap equipped with an atmospheric pressure chemical ionization (APCI) probe operating in positive-ion mode. The method was applied to 64 nutritional supplements. A total of 12.5% of the nutritional supplements analysed contained banned substances not declared on the label (anabolic steroids and ephedrine). Detection limits were in the range 1-25 ng g(-1). PMID- 17364928 TI - Simulation of human exposure to benzylpenicillin residues via pork originating from pigs fed with a dairy by-product. AB - The use of food industry by-products for feeding is restricted by European Union by-product regulation (1774/2002). However, the actual public health risks involved in the use of such products are poorly recognized. This study focuses on bovine milk rejected at the dairy because of a positive result in antimicrobial drug testing and thereafter used as feed for finisher pigs in Finland. In theory, this current practice could expose pork consumers to antimicrobial drug residues. Raw bulk milk samples originating from rejected lots were analysed with a multiresidue method detecting five beta-lactams, including benzylpenicillin. Based on the probabilistic simulation model developed, concentrations of benzylpenicillin in pork invariably remained below 1% of the maximum residue limit. Therefore, the use of this by-product as feed with the current practice was considered to pose only a negligible risk to consumers of pork products. PMID- 17364929 TI - Multiresidue pesticide analysis of the medicinal plant Origanum syriacum. AB - Origanum syriacum is a medicinal plant widely used in Jordan both as a folk remedy and in the food and beverage industry. As the plant can be treated with pesticides during commercial production, three different methods for pesticide multiresidue analysis of this plant have been evaluated. One method based on soxhlet extraction followed by acetonitrile/petroleum ether (PE) partitioning was found to be particularly suitable. Extracts were cleaned-up using a Florisil column. Mean recoveries of pesticides from spiked herbal samples were 74-119%, with coefficients of variation between 1.0 and 23.6%. The limits of detection were in the range 0.0008-0.5 mg kg(-1). The method was used for the determination of pesticide residues in O. syriacum samples purchased from the local market. Seven out of eight samples contained detectable levels of dichlorodiphenyltrichloroethane (DDT), folpet, dicofol, hexachlorobenzene (HCB), hecachlorocyclohexane (HCH), quintozene, transchlordane and vinclozolin. PMID- 17364930 TI - Development and validation of an analytical method for total amitraz in fruit and honey with quantification by gas chromatography-mass spectrometry. AB - The EU maximum residue limit (MRL) definition for amitraz is 'the sum of amitraz plus all its metabolites containing the 2,4-aniline moiety, expressed as amitraz'. A rapid and sensitive method has been developed and validated in-house for the determination of total amitraz in pears, strawberries, oranges and honey. Samples were hydrolysed (under acidic followed by alkaline conditions) to convert amitraz to 2,4-dimethyaniline, which was then partitioned into 2,2,4 trimethylpentane prior to quantification by gas chromatography-mass spectrometry. The method was validated at 0.02 and 0.1 mg kg(-1) amitraz (well below MRL requirements) with a lowest calibrated level (LCL) for 2,4-dimethylaniline of 0.002 mg kg(-1) (equivalent to 0.0024 mg kg(-1) amitraz). A single partition step yielded recoveries of approximately 60% (with % CV values in the range 3.3-8.2), which is satisfactory for screening purposes. A second partition increased recoveries by 10-20%, making the method suitable for the quantification of residues. PMID- 17364931 TI - Incidence of ochratoxin A in rice and dried fruits from Rabat and Sale area, Morocco. AB - One hundred samples of dried fruits (20 dried raisins, 20 walnuts, 20 peanuts, 20 dried figs and 20 pistachios) and 20 samples of rice purchased from retail shops in the Rabat and Sale area in Morocco were analysed for ochratoxin A (OTA) by immunoaffinity clean-up (IAC) and liquid chromatography (LC) with fluorescence detection. The limit of quantification (LOQ) (S/N = 10:1) of OTA was 0.02 ng g( 1) in rice, 0.03 ng g(-1) in pistachio, peanut and walnut, and 0.03 ng g(-1) in dried raisins and dried figs. The incidences of occurrence of OTA in dried raisins, walnuts, peanuts, dried figs and rice were 30, 35, 25, 65 and 90%, respectively. Analytical results showed that pistachio samples contained no detectable OTA, but concentrations ranged from 0.02 +/- 0.01 to 32.4 +/- 2.10 ng g(-1) in rice, from 0.10 +/- 0.05 to 2.36 +/- 0.75 in peanut, from 0.03 +/- 0.01 to 1.42 +/- 0.45 in dried figs, from 0.05 +/- 0.02 to 4.95 +/- 0.02 in dried raisins, and from 0.04 +/- 0.01 to 0.23 +/- 0.05 in walnuts. The results also showed that 15% of the total number of rice samples analysed exceeded the 2002 regulatory limit set by European Union regulations for cereals. This is the first report on the occurrence of OTA in dried fruits and rice available in Morocco. PMID- 17364932 TI - Five-year survey of ochratoxin A in processed sultanas from Turkey. AB - The results of surveillance for ochratoxin A (OTA) in 1885 samples of sultanas taken during five crop years between 1999 and 2003 are reported. The analytical method was based on extraction with methanol + sodium bicarbonate and clean-up by immunoaffinity column chromatography followed by high-performance liquid chromatography with fluorescence detection. The limit of detection for OTA was 0.3 microg kg(-1). The results show that 9.3% of the samples contained no detectable levels of OTA, whereas 0.6% had concentrations exceeding 10 microg kg( 1); the remaining 90.3% had levels within the range 0.3-10 microg kg(-1). The overall mean OTA concentration in the total number of 1885 samples taken was 1.36 +/- 2.91 microg kg(-1); the overall median was calculated as 0.90 microg kg(-1). PMID- 17364933 TI - Diarrheic shellfish poisoning due to toxic mussel consumption: the first recorded outbreak in Greece. AB - During the week of 14-20 January 2000, 120 people visited the Emergency Departments of hospitals in Thessaloniki, northern Greece, complaining of acute gastrointestinal illness after eating mussels (Mytilus galloprovincialis). The symptoms indicated diarrhoeic shellfish poisoning, and the toxicity of mussels harvested from Thermaikos Gulf in Thessaloniki during the outbreak was investigated using mouse bioassays. The bioassays revealed toxicity to mice by the mussel samples; while high numbers of toxic algae Dinophysis acuminata were identified in water samples from Thermaikos Gulf. The harvesting of mussels was immediately suspended and a monitoring programme for algal blooms was established from then onwards. During a follow-up of the mussels' toxicity from January 2000 to January 2005, two more mussel samples were found positive for diarrheic shellfish poisoning: one harvested in March 2001 from the area of the outbreak (Thermaikos Gulf) and the other harvested in January 2001 from Amvrakikos Gulf in north-western Greece. However, no sporadic cases or outbreaks were reported during this period. PMID- 17364934 TI - In vivo and in vitro effects of the mycotoxins zearalenone and deoxynivalenol on different non-reproductive and reproductive organs in female pigs: a review. AB - This review summarizes the toxicological data on the effects of the mycotoxins zearalenone (ZON), its metabolites, and deoxynivalenol (DON) on different parameters relating to reproductive and non-reproductive organs in female pigs. In vivo, 22 mg ZON kg(-1) in the diet cause alterations in the reproductive tract of swine such as in the uterus, and affects follicular and embryo development. ZON and its metabolites have been shown to bind competitively to oestrogen receptors in an in vitro system. The feeding of pigs with a 9 mg DON kg(-1) contaminated diet can act on protein synthesis, humoral and cellular immune response depending on dose, exposure and timing of functional immune assay, and affect liver and spleen cell structures. Beside these effects, reproductive alterations were observed in pigs, too. Both in vivo and in vitro exposure to DON decreased oocyte and embryo development. In vitro application of DON to uterine cells inhibits their proliferation rate and modulates the process of translation at a different molecular level when compared with the in vivo application. The histopathological results provide evidence of spleen and liver dysfunction in the absence of clinical signs, especially in pigs fed higher concentrations of Fusarium toxin-contaminated wheat. Prepuberal gilts react more sensitively to DON > ZON feeding compared with pregnant sows. In the liver, histopathological changes such as glycogen decrease and interlobular collagen uptake were only observed in prepuberal gilts, whereas enhancement of haemosiderin was found in both perpuberal gilts and pregnant sows. This review presents some of the current knowledge on the biological activities of ZON and DON in pig. Altogether, ZON affects reproduction of pigs most seriously because it possesses oestrogenic activity. However, DON affects reproduction in pigs via indirect effects such as reduced feed intake, resulting in reduced growth or impairment of function in vital organs such as liver and spleen. PMID- 17364935 TI - Annual variation of deoxynivalenol in Danish wheat flour 1998-2003 and estimated daily intake by the Danish population. AB - The occurrence of deoxynivalenol (DON) in Danish wheat flour was studied during the period 1998-2003 by either capillary gas chromatography with electron capture detection and liquid chromatography coupled to an ion trap mass spectrophotometer. A total of 151 samples were collected from mills and the retail market in Denmark. Contamination levels varied considerably from year-to year with the highest concentrations occurring in samples from the 2002 harvest with mean and median concentrations of 255 and 300 microg kg(-1), respectively. Compared to other harvest years, 2002 had the highest amount of precipitation around flowering time, i.e. from the end of June to the beginning of July covering weeks 25-27. The lowest average levels were found in samples from the 2001 harvest, where weeks 25-27 were dry compared with other harvest years. The highest value (705 microg kg(-1)) was obtained in a flour sample from the 2002 harvest, but none of the tested samples exceeded the maximum limit of 750 microg kg(-1), which has been recently introduced by the European Commission for DON in flour used as raw materials in food products. Calculation of chronic or usual intake by a deterministic approach showed that intake did not exceed the TDI of 1 microg kg(-1) bw day(-1) either for the whole population or for children. A probabilistic approach also showed that intake in general was below the TDI, but intake for children in the 99% percentile amounted to more than 75% of the TDI. The highest intake is calculated to be 2.5 microg kg(-1) bw day(-1). PMID- 17364936 TI - Investigation into the migration potential of coating materials from cookware products. AB - Twenty-six non-stick-coated cookware samples were purchased, covering a variety of products, coating/metal types and food contact applications. The polymer coatings were identified to be polyethersulphone, polytetrafluoroethylene (PTFE), bisphenol A/epichlorohydrin and one coating for which no good match was obtained with infra-red library spectra. All of the products intended for stove-top use had a polymer coating containing PTFE. The coatings were analysed as purchased and after heating at 250 degrees C for 30 min to simulate actual conditions of use. Total solvent extractables were measured and the overall migration was determined into simulants. None of the products exceeded an overall migration limit of 10 mg dm(-2). Coating materials were analysed by headspace gas chromatography-mass spectrometry (GC-MS), by liquid extraction followed by GC-MS and by liquid extraction followed by liquid chromatography-mass spectroscopy with a particle-beam interface. Benzene was detected in two samples, at 1.4 and 2.4 microg dm(-2). These levels in the coatings are too low to give any detectable migration into foods. There was no detectable release of perfluorochemicals. Several other substances were identified and the worst-case migration was calculated. The origin of many of the substances detected was considered to be by pick-up from the printed packaging materials in which the cookware was sold. Potential consumer exposure was calculated. None of the substances identified had the potential to exceed their tolerable daily intake (TDI) value. To confirm these worst-case calculations, the migration of certain phthalates and of bisphenol A was measured into food simulants. Migration levels were very low. PMID- 17364938 TI - Decreased hepatic ischemia-reperfusion injury by manganese-porphyrin complexes. AB - Reactive oxygen and nitrogen species have been implicated in ischemia-reperfusion (I/R) injury. Metalloporphyrins (MP) are stable catalytic antioxidants that can scavenge superoxide, hydrogen peroxide, peroxynitrite and lipid peroxyl radicals. Studies were conducted with three manganese-porphyrin (MnP) complexes with varying superoxide dimutase (SOD) and catalase catalytic activity to determine if the MnP attenuates I/R injury in isolated perfused mouse livers. The release of the hepatocellular enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) was maximal at 1 min reperfusion, decreased rapidly and increased gradually by 90 min. Manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin (MnTE-2-PyP) decreased ALT, AST, LDH at 1 90 min reperfusion, while manganese tetrakis-(N-methyl-2 pyridyl) porphyrin (MnTM 2-PyP) and manganese tetrakis-(ethoxycarbonyl) porphyrin (MnTECP) decreased ALT and LDH from 5 to 90 min reperfusion. The release of thiobarbituric acid-reacting substances (TBARS) was diminished by MnTE-2-PyP and MnTM-2-PyP at 90 min. The extent of protein nitration (nitrotyrosine, NT) was decreased in all three MnPs treated livers. These results demonstrate that MnP complexes can attenuate hepatic I/R injury and may have therapeutic implications in disease states involving oxidants. PMID- 17364939 TI - Xanthine oxidase-derived reactive oxygen species contribute to the development of D-galactosamine-induced liver injury in rats. AB - We examined whether xanthine oxidase (XO)-derived reactive oxygen species (ROS) contribute to the development of D-galactosamine (D-GaIN)-induced liver injury in rats. In rats treated with D-GaIN (500 mg/kg), liver injury appeared 6 h after treatment and developed until 24 h. Hepatic XO and myeloperoxidase activities increased 12 and 6 h, respectively, after D-GalN treatment and continued to increase until 24 h. D-GalN-treated rats had increased hepatic lipid peroxide (LPO) content and decreased hepatic reduced glutathione (GSH) and ascorbic acid contents and superoxide dismutase (SOD), catalase and Se-glutathione peroxidase (Se-GSHpx) activities at 24 h, but not 6 h, after treatment. Allopurinol (10, 25 or 50 mg/kg) administered at 6 h after D-GalN treatment attenuated not only the advanced liver injury and increased hepatic XO activity but also all other changes observed at 24 h after the treatment dose-dependently. These results suggest that XO-derived ROS contribute to the development of D-GaIN-induced liver injury in rats. PMID- 17364940 TI - Postanoxic damage of microglial cells is mediated by xanthine oxidase and cyclooxygenase. AB - Brain ischemia and the following reperfusion are important causes for brain damage and leading causes of brain morbidity and human mortality. Numerous observations exist describing the neuronal damage during ischemia/reperfusion, but the outcome of such conditions towards glial cells still remains to be elucidated. Microglia are resident macrophages in the brain. In this study, we investigated the anoxia/reoxygenation caused damage to a microglial cell line via determination of energy metabolism, free radical production by dichlorofluorescein fluorescence and nitric oxide production by Griess reagent. Consequences of oxidant production were determined by measurements of protein oxidation and lipid peroxidation, as well. By using site-specific antioxidants and inhibitors of various oxidant-producing pathways, we identified major sources of free radical production in the postanoxic microglial cells. The protective influences of these compounds were tested by measurements of cell viability and apoptosis. Although, numerous free radical generating systems may contribute to the postanoxic microglial cell damage, the xanthine oxidase- and the cyclooxygenase-mediated oxidant production seems to be of major importance. PMID- 17364941 TI - Nonenzymatic reduction of thymoquinone in physiological conditions. AB - Thymoquinone (TQ) is the bioactive constituent of the volatile oil of Nigella sativa L. and has been shown to exert antioxidant antineoplastic and anti inflammatory effects. During the study of its possible mechanism of action, we found that TQ reacts chemically (i.e. nonenzymatically) with glutathione (GSH), NADH and NADPH. A combination of liquid chromatography/UV-Vis spectrophotometry/Mass spectrometry analyses was used to identify the products of these reactions. The reaction that occur in physiological conditions indicates the formation of only two products, glutathionyl-dihydrothymoquinone after rapid reaction with GSH, and dihydrothymoquinone (DHTQ) after slow reaction time with NADH and NADPH. Measurement of the antioxidant activity of reduced compounds against organic radicals such as 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) also revealed a potential scavenging activity for glutathionyl-dihydrothymoquinone similar to that of DHTQ. Under our experimental conditions, TQ shows lower scavenging activities than glutathionyl-dihydrothymoquinone and DHTQ; it is very interesting to observe that the reduced compounds apparently show an antioxidant capacity equivalent to Trolox. The results indicate a possible intracellular nonenzymatic metabolic activation of TQ dependent on GSH, NADH or NADPH that may represent a "cellular switch" able to modulate cellular antioxidant defences. PMID- 17364942 TI - Prolonged selenium-deficient diet in MsrA knockout mice causes enhanced oxidative modification to proteins and affects the levels of antioxidant enzymes in a tissue-specific manner. AB - The methionine sulfoxide reductase (Msr) system (comprised of MsrA and MsrB) is responsible for reducing methionine sulfoxide (MetO) to methionine. One major form of MsrB is a selenoprotein. Following prolonged selenium deficient diet (SD), through F2 generation, the MsrA -/- mice exhibited higher protein-MetO and carbonyl levels relative to their wild-type (WT) control in most organs. More specifically, the SD diet caused alteration in the expression and/or activities of certain antioxidants as follows: lowering the specific activity of MsrB in the MsrA -/- cerebellum in comparison to WT mice; lowering the activities of glutathione peroxidase (Gpx) and thioredoxin reductase (Trr) especially in brains of MsrA -/- mice; elevation of the cellular levels of selenoprotein P (SelP) in most tissues of the MsrA -/- relative to WT. Unexpectedly, the expression and activity of glucose-6-phosphate dehydrogenase (G6PD) were mainly elevated in lungs and hearts of MsrA -/- mice. Moreover, the body weight of the MsrA -/- mice lagged behind the WT mice body weight up to 120 days of the SD diet. In summary, it is suggested that the lack of the MsrA gene in conjunction with prolonged SD diet causes decreased antioxidant capability and enhanced protein oxidation. PMID- 17364943 TI - Repeated inhalations of diesel exhaust particles and oxidatively damaged DNA in young oxoguanine DNA glycosylase (OGG1) deficient mice. AB - DNA repair may prevent increased levels of oxidatively damaged DNA from prolonged oxidative stress induced by, e.g. exposure to diesel exhaust particles (DEP). We studied oxidative damage to DNA in broncho-alveolar lavage cells, lungs, and liver after 4 x 1.5 h inhalations of DEP (20 mg/m3) in Ogg1-/- and wild type (WT) mice with similar extent of inflammation. DEP exposure increased lung levels of 8 oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in Ogg1-/- mice, whereas no effect on 8-oxodG or oxidized purines in terms of formamidopyrimidine DNA glycosylase (FPG) sites was observed in WT mice. In both unexposed and exposed Ogg1-/- mice the level of FPG sites in the lungs was 3-fold higher than in WT mice. The high basal level of FPG sites in Ogg1-/- mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Ogg1-/- mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP. PMID- 17364944 TI - Electron paramagnetic spectroscopic evidence of exercise-induced free radical accumulation in human skeletal muscle. AB - The present study determined if acute exercise increased free radical formation in human skeletal muscle. Vastus lateralis biopsies were obtained in a randomized balanced order from six males at rest and following single-leg knee extensor exercise performed for 2 min at 50% of maximal work rate (WR(MAX)) and 3 min at 100% WR(MAX). EPR spectroscopy revealed an exercise-induced increase in mitochondrial ubisemiquinone (UQ*-) [0.167 +/- 0.055 vs. rest: 0.106 +/- 0.047 arbitrary units (AU)/g total protein (TP), P < 0.05] and alpha-phenyl-tert butylnitrone-adducts (112 +/- 41 vs. rest: 29 +/- 9 AU/mg tissue mass, P < 0.05). Intramuscular lipid hydroperoxides also increased (0.320 +/- 0.263 vs. rest: 0.148 +/- 0.071 nmol/mg TP, P < 0.05) despite an uptake of alpha-tocopherol, alpha-carotene and beta-carotene. There were no relationships between mitochondrial volume density and any biomarkers of oxidative stress. These findings provide the first direct evidence for intramuscular free radical accumulation and lipid peroxidation following acute exercise in humans. PMID- 17364945 TI - Cytosolic NADP-isocitrate dehydrogenase of pea plants: genomic clone characterization and functional analysis under abiotic stress conditions. AB - NADPH is an essential electron donor in numerous biosynthetic and detoxification reactions. In animal, yeast and bacteria, the NADP-dependent isocitrate dehydrogenase (NADP-ICDH), which catalyzes the production of NADPH, is being recognized as an essential component of the antioxidative defence mechanisms. In plant cells, there is little information on the antioxidant properties of NADP ICDH. Using a pea cDNA lambdagt11 library, the full-length cDNA of a NADP-ICDH was obtained. In pea leaves, the analyses of activity, protein and transcript expression of NADP-ICDH under six different abiotic stress conditions (CL, continuous light, HLI, high light intensity, D, continuous dark, LT, low temperature HT, high-temperature and W, mechanical wounding) revealed a differential regulation at transcriptional and post-translational level depending on the abiotic stress. The activity and protein expression of NADP-ICDH and catalase increased only under HLI but the NADP-ICDH transcripts were up-regulated by cold stress (70%) and W (40%). Under the same conditions, the transcript analysis of glutathione reductase (GR), monodehydroascorbate reductase (MDAR) and ascorbate peroxidase (APX), key components of the antioxidative ascorbate glutathione cycle, showed similar inductions. These data indicate that in pea plants the cytosolic NADP-ICDH shows a differential response, at mRNA and activity level, depending on the type of abiotic stress and suggests that this dehydrogenase could have a protective antioxidant role against certain environmental stresses in plants. PMID- 17364946 TI - Deterioration of ischemia/reperfusion-induced acute renal failure in SOD1 deficient mice. AB - Reactive oxygen species (ROS) are likely candidates for involvement in ischemia/reperfusion-induced acute renal failure (ARF). In this study, the issue of whether superoxide dismutase (SOD1)-deficiency exacerbates the ischemia/reperfusion-induced ARF was examined. At two weeks after a right nephrectomy of mice, the left renal vessels were clipped to induce renal ischemia and were then released after 45 min. The severe renal damage observed at one day was partially recovered at seven days after the induction of ischemia. SOD1-/- mice suffer from severe ARF compared with SOD1+ - and SOD1+/+ mice. The damage was more evident in aged animals (24-28 week old) than younger ones (10-12 week old). The expression of major antioxidative and redox enzymes, except for CuZnSOD, were substantially unchanged. Thus, the increased ARF in SOD1-/- mice appears to be mainly attributable to a deficiency in CuZnSOD. These data support the view that ROS are exacerbating factors in ischemia/reperfusion-induced ARF. PMID- 17364947 TI - Nitrosative stress inhibits production of the virulence factor alginate in mucoid Pseudomonas aeruginosa. AB - Alginate is a critical virulence factor contributing to the poor clinical prognosis associated with the conversion of Pseudomonas aeruginosa to mucoid phenotypes in cystic fibrosis (CF). An important mechanism of action is its ability to scavenge host innate-immune reactive species. We have previously analyzed the bacterial response to nitrosative stress by S-nitrosoglutathione (GSNO), a physiological NO radical donor with diminished levels in the CF lung. GSNO substantially increased bacterial nitrosative and oxidative defenses and so we hypothesized a similar increase in alginate production would occur. However, in mucoid P. aeruginosa, there was decreased expression of the majority of alginate synthetic genes. This microarray data was confirmed both by RT-PCR and at the functional level by direct measurements of alginate production. Our data suggest that the lowered levels of innate-immune nitrosative mediators (such as GSNO) in the CF lung exacerbate the effects of mucoid P. aeruginosa, by failing to suppress alginate biosynthesis. PMID- 17364948 TI - Which comes first: renal inflammation or oxidative stress in spontaneously hypertensive rats? AB - The present study was undertaken to identify whether inflammation or oxidative stress is the primary abnormality in the kidney in spontaneously hypertensive rats (SHR). Renal inflammation and oxidative stress were evaluated in 2- and 3 week-old prehypertensive SHR and age-matched genetically normotensive control Wistar-Kyoto (WKY) rats. Blood pressure was similar in WKY and SHR rats at 2 and 3 weeks, of age. Renal inflammation (macrophage and nuclear factor-kappaB) was elevated in SHR at 3 weeks, but not at 2 weeks, of age compared with age-matched WKY rats. Renal oxidative stress (nitrotyrosine, 8-hydroxy-2'-deoxyguanosine and p47phox) was also clearly elevated in 3-week-old SHR compared with age-matched WKY rats. Additionally, NADPH oxidase subunit p47phox was found elevated in 2 week-old SHR compared to age-matched WKY rats. Moreover, antioxidant (N-acetyl-L cysteine and Tempol) treatment reduced renal inflammation in prehypertensive SHR. We therefore conclude that the oxidative stress appears before inflammation as a primary abnormality in the kidney in prehypertensive SHR. PMID- 17364949 TI - Kinetics of the lipoperoxyl radical-scavenging activity of indicaxanthin in solution and unilamellar liposomes. AB - The reaction of the phytochemical indicaxanthin with lipoperoxyl radicals generated in methyl linoleate methanol solution by 2,2'-azobis(2,4 dimethylvaleronitrile), and in aqueous soybean phosphatidylcholine unilamellar liposomes by 2,2'-azobis(2-amidinopropane)hydrochloride, was studied. The molecule acts as a chain-terminating lipoperoxyl radical scavenger in solution, with a calculated inhibition constant of 3.63 x 10(5) M(-1) s(-1), and a stoichiometric factor approaching 2. Indicaxanthin incorporated in liposomes prevented lipid oxidation, inducing clear-cut lag periods and decrease of the propagation rate. Both effects were concentration-dependent, but not linearly related to the phytochemical concentration. The consumption of indicaxanthin during liposome oxidation was remarkably delayed, the lower the concentration the longer the time-interval during which it remained in its native state. Indicaxanthin and alpha-tocopherol, simultaneously incorporated in liposomes, exhibited cooperative antioxidant effects and reciprocal protective interactions. The extent of synergism decreased at the increase of the ratio (indicaxanthin)/(alpha-tocopherol). A potential antioxidant mechanism of indicaxanthin is discussed in the context of the chemistry of the molecule, and of the possible reactivity of a short-lived intermediate. PMID- 17364950 TI - The main components of St John's Wort inhibit low-density lipoprotein atherogenic modification: a beneficial "side effect" of an OTC antidepressant drug? AB - Hypericin and pseudohypericin are polycyclic-phenolic structurally related compounds found in Hypericum perforatum L. (St John's wort). As hypericin has been found to bind to LDL one may assume that it can act as antioxidant of LDL lipid oxidation, a property which is of prophylactic/therapeutic interest regarding atherogenesis as LDL oxidation may play a pivotal role in the onset of atherosclerosis. Therefore, in the present paper hypericin, pseudohypericin and hyperforin, an other structurally unrelated constituent in St John's wort were tested in their ability to inhibit LDL oxidation. LDL was isolated by ultracentrifugation and oxidation was initiated either by transition metal ions (copper), tyrosyl radical (myeloperoxidase/hydrogen peroxide/tyrosine) or by endothelial cells (HUVEC). LDL modification was monitored by conjugated diene and malondialdehyde formation. The data show that all compounds (hypericin, pseudohypericin and hyperforin) at doses as low as 2.5 micromol/l are potent antioxidants in the LDL oxidation systems used. The results indicate that the derivatives found in Hypericum perforatum have possible antiatherogenic potential. PMID- 17364951 TI - Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury. AB - This study was undertaken to investigate the inducibility of glutathione (GSH), glutathione reductase (GR) and glutathione peroxidase (GPx) by 3H-1,2-dithiole-3 thione (D3T) in beta-cells, and the resultant cytoprotection against oxidant injury. Incubation of the insulin-secreting RINm5F cells with D3T led to significant induction of GSH, GR and GPx. D3T-mediated induction of GSH was abolished by buthionine sulfoximine (BSO), suggesting a critical involvement of gamma-glutamylcysteine ligase (gammaGCL). Consistently, incubation of RINm5F cells with D3T resulted in increased expression of gammaGCL protein and mRNA. Pretreatment of RINm5F cells with D3T provided remarkable protection against oxidant-elicited cytotoxicity. On the other hand, depletion of cellular GSH by BSO sensitized RINm5F cells to oxidant injury. Furthermore, cotreatment of RINm5F cells with BSO to reverse D3T-mediated GSH induction abolished the cytoprotective effects of D3T on oxidant injury. Taken together, this study demonstrates that upregulation of glutathione system by D3T is effective for protecting against oxidative beta-cell injury. PMID- 17364952 TI - Oxidative stress-inducible antioxidant adaptive response during prostaglandin F2alpha-induced luteal cell death in vivo. AB - Oxidative stress-induced antioxidant adaptive response would be particularly important to cells in high reactive oxygen species (ROS) environments. We aimed to determine the dynamic adaptive response of antioxidant enzymatic systems in sheep corpus luteum (CL) during PGF2alpha-induced luteal cell death. Activities of superoxide dismutase (SOD1 and SOD2), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GSR), and in situ DNA fragmentation were determined in CL at day 10 of the estrous cycle (0 h) and at 12, 24 or 48 h after PGF2alpha injection. A decrease in plasma progesterone concentration was first observed at 6 h after treatment (P < 0.05). Apoptotic cells were rarely observed in the CL at 0 h (less than 0.7%), and their incidence increased (P < 0.01) by 12 h post-PGF2alpha (11.7%) and remained thereafter elevated through 48 h. Activities of SOD1, SOD2, GPX and GSR were not changed at any time points after PGF2alpha treatment. CAT activity increased at 12 h (P < 0.01) and at 24 h (P < 0.05) after PGF2alpha treatment as compared to that at 0 h. These findings demonstrate that PGF2alpha induce luteal cell death without depressing the activity of antioxidant enzymes. It is suggested that transient increase in CAT activity is an adaptive response of the CL to oxidative stress induced by PGF2alpha. PMID- 17364953 TI - 25-Hydroxycholesterol, 7beta-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages. AB - Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7beta hydroxycholesterol (7beta-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL 8), but not IkappaBalpha degradation or tumour necrosis factor-alpha release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25 hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling. PMID- 17364954 TI - Region specific increase in the antioxidant enzymes and lipid peroxidation products in the brain of rats exposed to lead. AB - The objective of this study is to determine the effect of lead (pb) on antioxidant enzymes and lipid peroxidation products in different regions of rat brain. Wistar male rats were treated with lead acetate (500 ppm) through drinking water for a period of 8 weeks. Control animals were maintained on sodium acetate. Treated and control rats were sacrificed at intervals of 1st, 4th and 8th week and the whole brains were dissected on ice into four regions namely the cerebellum, the hippocampus, the frontal cortex and the brain stem. Antioxidant enzymes namely catalase and superoxide dismutase in all the four regions of brain were determined. In addition, lipid peroxidation products were also estimated. The results indicated a gradual increase in the activity of antioxidant enzymes in different regions of the brain and this response was time-dependent. However, the increase was more in the cerebellum and the hippocampus compared to other regions of the brain. The lipid peroxidation products also showed a similar trend suggesting increased effect of lead in these two regions of the brain. The data indicated a region-specific oxidative stress in the brain exposed to lead. PMID- 17364955 TI - Scuba diving enhances endogenous antioxidant defenses in lymphocytes and neutrophils. AB - The aim was to study the effects of a scuba diving session on the lymphocyte antioxidant system, NO synthesis, the capability to produce reactive oxygen species and the antioxidant response in neutrophils. For that purpose seven male divers performed an immersion at a depth of 40 m for 25 min. The same parameters were measured after an hyperbaric oxygen (HBO) treatment at resting conditions in a hyperbaric chamber. Lymphocyte H2O2 production rose after diving and after HBO treatment. Glutathione peroxidase (GPx) and catalase activities increased after diving in lymphocytes, while after HBO exposure only increased GPx activity. Lymphocyte HO-1 mRNA expression increased after diving and after HBO exposure, while iNOS levels and nitrite levels significantly increased after diving. The hyperoxia associated to scuba diving leads to a condition of oxidative stress with increased lymphocyte H2O2 production, HO-1 expression, NO synthesis and antioxidant enzyme adaptations in order to avoid oxidative damage. PMID- 17364956 TI - Acute phase proteins and oxidised low-density lipoprotein in association with ischemic stroke subtype, severity and outcome. AB - OBJECTIVES: The goal of our study was to investigate the associations of oxidized LDL (apoB100 aldehyde-modified form) and acute phase proteins (fibrinogen, CRP) with acute ischemic stroke severity and outcome. MATERIALS AND METHODS: The study included 61 ischemic stroke patients and 64 controls. Strokes were subtyped according to TOAST criteria, the severity and outcome of stroke (at 1 year) were measured. RESULTS: The mean triglyceride, fibrinogen, CRP and glucose values were significantly higher among cases. The median oxLDL value for patients with large artery atherosclerosis (LAA) type of stroke was significantly higher than for other subtypes. The oxLDL values did not correlate with age, stroke severity and outcome. CONCLUSIONS: Inflammatory markers (fibrinogen and CRP) predicted the stroke severity and outcome whereas elevation of oxLDL levels did not. Our data refer to possibility that there may exist some links between the LAA subtype of stroke and elevated oxLDL (apoB100 aldehyde-modified form). PMID- 17364957 TI - Gene-specific oxidative lesions in aged rat brain detected by polymerase chain reaction inhibition assay. AB - An exposure of isolated rat brain genomic DNA to oxidative stress in the form of iron salts (Fe2+) and ascorbate results in gene-specific DNA lesions detectable by a quantitative polymerase chain reaction (PCR) based assay in which PCR amplification efficiency of the affected genes (e.g. beta-actin and p53) is grossly impaired. Such oxidative DNA lesions are prevented by hydroxyl radical scavengers like mannitol (20 mM) and sodium benzoate (20 mM) or by the antioxidant enzyme catalase (50 microg/ml) present in the incubation mixture during exposure to Fe2+ and ascorbate. When brain DNA isolated from young (4-6 months of age) and aged (20-24 months of age) rats are analyzed similarly by the PCR based method, the amplification levels of beta-actin and p53 genes are noticeably decreased in the case of aged rat indicating an accumulation of gene specific DNA lesions during brain aging. PMID- 17364958 TI - The reactivity of carotenoid radicals with oxygen. AB - The possibility that carotenoid radicals react with oxygen to form chain-carrying peroxyl radicals has been postulated to account for the reduction in antioxidant effetiveness displayed by some carotenoids at high oxygen concentrations. The primary objective of the work described in this paper was to measure the rate constants for oxygen addition to a series of carotenoid radicals and to examine any influence of carotenoid structural features on these rate constants. Laser flash photolysis has been used to generate long-lived carotenoid radicals (PhS CAR radical) derived from radical addition reactions with phenylthiyl radicals (PhS radical) in benzene. The PhS-CAR radical radicals are scavenged by oxygen at rates that display a moderate dependence on the number of conjugated double bonds (ndb) in the carotenoid. The rate constants range from approximately 10(3) to approximately 10(4) M- 1 s- 1 for ndb = 7-11. The data also suggest that the presence of terminal cyclic groups may cause an increase in the rate constant for oxygen addition. PMID- 17364959 TI - Modulation of oxidative damage by nitroxide free radicals. AB - Piperidine nitroxides like 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) are persistent free radicals in non-acidic aqueous solutions and organic solvents that may have value as therapeutic agents in medicine. In biological environments, they undergo mostly reduction to stable hydroxylamines but can also undergo oxidation to reactive oxoammonium compounds. Reactions of the oxoammonium derivatives could have adverse consequences including chemical modification of vital macromolecules and deleterious effects on cell signaling. An examination of their reactivity in aqueous solution has shown that oxoammonium compounds can oxidize almost any organic as well as many inorganic molecules found in biological systems. Many of these reactions appear to be one-electron transfers that reduce the oxoammonium to the corresponding nitroxide species, in contrast to a prevalence of two-electron reductions of oxoammonium in organic solvents. Amino acids, alcohols, aldehydes, phospholipids, hydrogen peroxide, other nitroxides, hydroxylamines, phenols and certain transition metal ions and their complexes are among reductants of oxoammonium, causing conversion of this species to the paramagnetic nitroxide. On the other hand, thiols and oxoammonium yield products that cannot be detected by ESR even under conditions that would oxidize hydroxylamines to nitroxides. These products may include hindered secondary amines, sulfoxamides and sulfonamides. Thiol oxidation products other than disulfides cannot be restored to thiols by common enzymatic reduction pathways. Such products may also play a role in cell signaling events related to oxidative stress. Adverse consequences of the reactions of oxoammonium compounds may partially offset the putative beneficial effects of nitroxides in some therapeutic settings. PMID- 17364960 TI - Peroxynitrite oxidizes erythrocyte membrane band 3 protein and diminishes its anion transport capacity. AB - We describe an altered membrane band 3 protein-mediated anion transport in erythrocytes exposed to peroxynitrite, and relate the loss of anion transport to cell damage and to band 3 oxidative modifications. We found that peroxynitrite down-regulate anion transport in a dose dependent relation (100-300 micromoles/l). Hemoglobin oxidation was found at all peroxynitrite concentrations studied. A dose-dependent band 3 protein crosslinking and tyrosine nitration were also observed. Band 3 protein modifications were concomitant with a decrease in transport activity. ( - )-Epicatechin avoids band 3 protein nitration but barely affects its transport capacity, suggesting that both processes are unrelated. N acetyl cysteine partially reverted the loss of band 3 transport capacity. It is concluded that peroxynitrite promotes a decrease in anion transport that is partially due to the reversible oxidation of band 3 cysteine residues. Additionally, band 3 tyrosine nitration seems not to be relevant for the loss of its anion transport capacity. PMID- 17364961 TI - Body iron is a contributor to oxidative damage of DNA. AB - The transition metal iron is catalytically highly active in vitro, and not surprisingly, body iron has been suggested to promote oxidative stress in vivo. In the current analysis we studied the association of serum ferritin concentration and serum soluble transferrin receptor concentration with daily urinary 8-hydroxydeoxyguanosine excretion, a marker of oxidative stress, in 48 mildly dyslipidemic men in East Finland. In multivariate linear regression analyses allowing for age, smoking, body mass index and physical exercise, serum ferritin concentration predicted the excretion rate at B = 0.17 (95% CI 0.08 0.26, P = 0.001), and serum soluble transferrin receptor to ferritin concentration ratio (TfR/ferritin) predicted the excretion rate at B = - 0.13 (95% CI - 0.21 to - 0.05, P = 0.002). Our data suggest that body iron contributes to excess oxidative stress already at non-iron overload concentrations in these subjects. PMID- 17364962 TI - Vitamins C and E prevent AZT-induced leukopenia and loss of cellularity in bone marrow. Studies in mice. AB - A major limitation in the use of AZT for AIDS treatment is the occurrence of side effects, such as leukopenia. The effects of antioxidant vitamins C and E on AZT induced leukopenia were investigated in mice. Mice were divided into four groups: (1) controls; (2) AZT-treated; (3) treated with AZT plus vitamins C and E; and (4) pre-treated with vitamins and then treated with AZT plus vitamins. Our results demonstrate that AZT causes leukopenia in mice, which was abrogated by administration of vitamins C and E in the pre-treated group. These vitamins prevented the decrease in cellular content induced by AZT in bone marrow and diminished peroxide levels in myeloid precursors in bone marrow. AZT also caused an increase in plasma malondialdehyde and blood oxidized glutathione levels, which was prevented by the administration of antioxidant vitamins. In conclusion, oxidative stress is involved in AZT-induced leukopenia which may be prevented by antioxidant treatment. PMID- 17364963 TI - Betanin inhibits the myeloperoxidase/nitrite-induced oxidation of human low density lipoproteins. AB - Production of nitrogen dioxide by the activity of myeloperoxidase (MPO) in the presence of nitrite is now considered a key step in the pathophysiology of low density lipoprotein (LDL) oxidation. This study shows that betanin, a phytochemical of the betalain class, inhibits the production of lipid hydroperoxides in human LDL submitted to a MPO/nitrite-induced oxidation. Kinetic measurements including time-course of particle oxidation and betanin consumption, either in the presence or in the absence of nitrite, suggest that the antioxidant effect is possibly the result of various actions. Betanin scavenges the initiator radical nitrogen dioxide and can also act as a lipoperoxyl radical-scavenger. In addition, unidentified oxidation product(s) of betanin by MPO/nitrite inhibit(s) the MPO/nitrite-induced LDL oxidation as effectively as the parent compound. In the light of betanin bioavailability and post-absorbtion distribution in humans, present findings may suggest favourable in vivo activity of this phytochemical. PMID- 17364964 TI - The flavonoid quercetin induces hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits cell proliferation by depleting intracellular iron. AB - Quercetin, a flavonoid with anti-oxidant, metal chelating, kinase modulating and anti-proliferative properties, can induce hypoxia-inducible factor-1alpha (HIF 1alpha) in normoxia, but its mechanism of action has not been determined. In this study we characterized the induction of HIF-1alpha and the inhibition of cell proliferation caused by quercetin in HeLa and ASM (airway smooth muscle) cells and examined the effect of iron on these processes. Furthermore, we investigated the relevance of the intracellular levels of quercetin to HIF-1alpha expression and cell proliferation. Our data demonstrate that quercetin depletes intracellular calcein-chelatable iron and that supplying additional iron from extracellular or intracellular pools abrogates the induction of HIF-1alpha by quercetin. Moreover, addition of iron reverses the quercetin-induced inhibition of DNA synthesis, cell proliferation and cycle progression, but to different extents, depending on cell type. We propose that quercetin stabilises HIF-1alpha and inhibits cell proliferation predominantly by decreasing the concentration of intracellular iron through chelation. PMID- 17364965 TI - Inhibition of ozone-induced SP-A oxidation by plant polyphenols. AB - Surfactant protein-A (SP-A) is the best studied and most abundant of the protein components of lung surfactant and plays an important role in host defense of the lung. It has been shown that ozone-induced oxidation of SP-A protein changes its functional and biochemical properties. In the present study, eight plant polyphenols (three flavonoids, three hydroxycinnamic acids, and two hydroxybenzoic acids) known as strong antioxidants, were tested for their ability to inhibit ozone-induced SP-A oxidation as a mechanism for chemoprevention against lung damage. SP-A isolated from alveolar proteinosis patients was exposed to ozone (1 ppm) for 4 h. The flavonoids protected SP-A from oxidation in a dose dependent manner. ( - )-Epicatechin was the most potent flavonoid and exhibited inhibition of ozone-induced formation of carbonyls by 35% at a concentration as low as 5 microM. Hydroxybenzoic acids inhibited SP-A oxidation in a dose dependent manner although they were less potent than flavonoids. On the other hand, hydroxycinnamic acids exhibited a different inhibitory pattern. Inhibition was observed only at medium concentrations. The results indicate that inhibition of SP-A oxidation by plant polyphenols may be a mechanism accounting for the protective activity of natural antioxidants against the effects of ozone exposure on lungs. PMID- 17364966 TI - Peroxynitrite mild nitration of albumin and LDL-albumin complex naturally present in plasma and tyrosine nitration rate-albumin impairs LDL nitration. AB - In blood, peroxynitrite (ONOO- ) and CO2 react to form NO2* and CO3* through the short-lived adduct ONOOCO2-, leading to protein-bound tyrosine nitration. ONOO(-) -modified LDL is atherogenic. Oxidatively modified LDL generally appears in the vessel wall surrounded by antioxidants. Human serum albumin (HSA) is one of them, partly associated to LDL as a LDL-albumin complex (LAC). The purpose was to study the effect of a mild nitration on LAC and whether albumin may interfere with LDL nitration. To do so, SIN-1 was used as ONOO- generator in the presence or absence of 25 mM HCO3-. The human serum albumin (HSA)-bound tyrosine nitration rate was found to be 4.4 x 10(-3) mol/mol in the presence of HCO3-. HSA decreased the LAC tyrosine nitration rate from 2.5 x 10(-3) to 0.6 x 10(-3) mol/mol. It was concluded that HSA impaired the apoB-bound tyrosine nitration. These findings raise the question of the patho-physiological significance of these nitrations and their interactions which may potentially prevent both atheromatous plaque formation and endothelium dysfunction in particular and appear to be beneficial in terms of atherogenic risk. PMID- 17364968 TI - Rethinking depression: an ethnographic study of the experiences of depression among Chinese. AB - Relative to studies of patients in the West, little research has focused on the lived experiences of patients with mental illness in non-Western societies. The current understanding of the phenomenology of depression and other psychiatric disorders is almost entirely based on studies of Western populations. The objective of the present study was to examine the experiences of depressive disorders among contemporary Chinese in Guangzhou (Canton), China. A total of 40 patients who had significant depressive symptoms were recruited using quota sampling from the outpatient department of a regional mental health service. The depressive experiences of participants were examined by open-ended, in-depth, ethnographic interviews. The interviews were taped, transcribed, and translated. Content analysis was conducted on both the Chinese and English transcripts. A total of six categories of affective experiences were identified among the participants. Indigenous affective lexicons, embodied emotional experiences, implicit sadness, preverbal pain, distress of social disharmony, and centrality of sleeplessness were regularly observed among the informants. Our findings suggest that psychiatric textbooks and diagnostic systems do not cover the full range of depressive symptoms experienced among contemporary Chinese. More studies are needed to examine how depression is differentially experienced globally--a crucial step in making professional diagnosis, treatment, and research more broadly applicable across cultures. PMID- 17364969 TI - Defensive avoidance of disapproval: the relationship of a defensive style to physical and mental health. AB - This article presents an exploration of a clinically meaningful interpersonal style labeled here as defensive avoidance of disapproval (DAD), which involves a motivated inattention to physiological, affective, or cognitive reactions arising from stressful social transactions, thereby safeguarding a self-image of social competence. First, we discuss conceptual antecedents of DAD derived from post Freudian theories of twentieth-century psychodynamic and interpersonally oriented clinicians. Second, we highlight measurement issues as they relate to DAD. Third, we review research on the association of DAD with psychophysiological stress reactivity and diminished health. Finally, DAD-related clinical implications are considered. Our discussion of DAD invites the (1) assessment of phenomenological "blind spots" regarding the physiological, affective, and cognitive components of disapproval-induced stress, (2) development of strategies to decrease premature therapy termination that may result from a defensive avoidance of social disapproval, and (3) cultivation of interventions to increase the high DAD patient's acknowledgement, rather than rejection, of the signs of social stress. PMID- 17364970 TI - Strategic choices in the psychotherapy of a "fragile" patient. PMID- 17364971 TI - Increasing genetic education for psychiatric residents. PMID- 17364972 TI - An exploratory project on the state of quality measures in mental health at academic health centers. PMID- 17364976 TI - Survivor dragon boating: a vehicle to reclaim and enhance life after treatment for breast cancer. AB - The authors investigated the psychosocial impact of dragon boat participation on women who have been treated for breast cancer. Open-ended qualitative interviews were completed by 10 new members recruited from two breast cancer survivor dragon boat teams. Our findings indicate that the women's experience of survivor dragon boating surpassed their expectations and offered them hope and increased strength and the ability to regain control of their lives. Key themes emerging from the in depth interviews that encapsulate the experiences of women in their first season of dragon boating follow: awakening of the self, common bond, regaining control, being uplifted, and transcending the fear of death. The interview data support the emerging hypothesis that dragon boating is a vehicle for improving women's wellness and post-treatment quality of life. PMID- 17364977 TI - Spirituality in African American and Caucasian women with end-stage renal disease on hemodialysis treatment. AB - This reanalysis of data from a previous investigation in the United States was conducted to compare spiritual well-being scores of African American (n = 31) and Caucasian (n = 27) women on hemodialysis for end-stage renal disease (ESRD). Women, aged 24 to 79, completed the spiritual well-being (SWB) scale and other instruments. Results indicated a strong trend for African American women to score higher on religious well-being than Caucasian women. Comparisons of SWB item scores indicated areas of spiritual strengths for African American women: perceptions of God's concern for them, God's help with loneliness, fulfilling relationship with God, satisfaction with life, and sense of life's purpose. These findings have multidisciplinary implications for factors that may mitigate the illeffects of ESRD. PMID- 17364978 TI - Traditionality and cancer screening practices among American Indian women in Vermont. AB - The study purpose was to examine the relationship between cancer screening and traditionality, using a culturally specific survey instrument. American Indian (AI) women were randomly selected from the Vermont Breast Cancer Surveillance System (VBCSS), a statewide mammography database. The 13 items that assessed traditionality examined identity, cultural beliefs, customs, and health practices. The sample of 115 was predominately married, educated, middle class, insured, and rural. Significant associations were found between traditionality and past mammography and clinical breast examination (CBE) behavior, as well as future mammography intention. Results suggest that traditionality scales can be useful for identifying differences in screening behavior, with further testing of traditionality items with other AI women recommended. International implications of the study findings are also addressed. PMID- 17364979 TI - Human papillomavirus infection in malignant and benign gynaecological conditions: a study in Greek women. AB - HPV infection is by far the most frequent sexually transmitted disease. Our aim in this prospective nonrandomized study was to investigate the frequency with which different subtypes of the human papillomavirus (HPV) are found in gynaecological malignant and benign conditions and to compare the rate of infection between them. Detailed data of 195 women were selected and divided into three groups. The first group consisted of specimens from 68 women with cervical cancer. The second group consisted of specimens from 43 women with endometrial and ovarian cancer. The third group consisted of 84 specimens from women who were operated on for benign gynaecological diseases. Seven oncogenic types of HPV (6, 11 [low-risk subtypes] 16, 18, 31, 33, and 51 [high-risk subtypes]) were investigated by using the in situ hybridization technique. The HPV detection rate was higher in the cervical cancer group (74.8%), compared with the second (27.9%) and third (45.2%) groups. The most common HPV subtypes in the first group were 16 and 18. The most common subtypes in the second group were the 31, 33, and 51, and in the third group the 6 and 11 subtypes. Women developed cervical cancer at a younger age than endometrial or ovarian cancer. Smoking and exposure to multiple sexual partners appeared related to the development of cervical cancer. The use of contraceptive pill, dietary habits, and diabetes did not seem to increase the risk of HPV infection in this population. As it is common in other populations, in this selected population of Greek women we were able to confirm that in women with cervical cancer the most common HPV subtypes are 16 and 18. Education of adolescents on the epidemiological association of smoking and unprotected intercourse with cervical cancer will certainly help to reduce the rates of development of preinvasive and invasive cancer of the cervix in young women. PMID- 17364980 TI - Linking cervical cancer to the human papillomavirus: findings from a qualitative study with Mexican women. AB - Cervical cancer is an important cause of mortality for women in developing countries. Researchers have established a link between cervical cancer and the human papillomavirus (HPV). We explored Mexican women's beliefs about cervical cancer and sexually transmitted infections (STIs), including HPV, to better understand the social implications of this linkage. We conducted eight focus groups with middle-aged and young women in Mexico City. Cervical cancer elicited different social and emotional responses than STIs; participants generally attached less culpability to it and saw it as more life threatening. Information campaigns should take into account differences in lay conceptions of these illnesses. PMID- 17364982 TI - Malawian midwives' perceptions of occupational risk for HIV infection. AB - In this study, Malawian midwives' perceptions of occupational risk of human immunodefiency virus (HIV) infection are described. Knowledge of perceptions of HIV risk in developing countries and consequences on patient care is limited. A qualitative approach using purposive sampling was undertaken with 7 midwives. Participants considered their occupational risk to be high, encompassing these four themes: exposure to body fluids, availability of resources, hand washing practices, and support from management. Additional themes related to the impact of high risk on clinical practice: working in a climate of fear, refraining from touch, loss of interest in midwifery, and improvising care practices. PMID- 17364983 TI - Strategies applied by women in coping with ad-hoc demands for unauthorized user fees during pregnancy and childbirth. A focus group study from Angola. AB - Our aim in this study was to explore women's responses to reported ad-hoc demands for unauthorized user fees during pregnancy and childbirth in Luanda, Angola. Ten focus group discussions were conducted and data were analysed using grounded theory. Women were found to apply six strategies as they "endeavored to cope with demands for unauthorized user fees" (core category): (i) blowing the whistle, (ii) searching for comprehension, (iii) manipulating the system, (iv) bargaining, (v) extending the limits, and (vi) balancing. The system of unauthorized user fees appears to be a symptom of a deeper structural problem, which requires multifaceted and long-term interventions such as insti-tutional reforms and clear policies on accountability and transparency. Better resource availability for the MHC sector is required in order to secure adequate salaries to maternal health care providers. The fact that unethical behavior is unveiled implies that interventions also need to target the national midwifery training. PMID- 17364984 TI - Relationship, power, and other influences on self-protective sexual behaviors of African American female adolescents. AB - This study examined risky sexual behaviors, gender, and power issues affecting risk taking, and factors most likely to promote self-protection among female African American adolescents. A cross-sectional design was used for data collection. The sample included 130 adolescents ranging from 14 to 20 years of age, who completed questionnaires. Multiple regression analysis resulted in two models that accounted for 23% and 37% of the variance. Behavioral intention, partner age, pregnancy status, current substance use, and length of sexual relationship were statistically significant predictor variables. Behavioral intentions, in particular, were found to be a strong predictor of condom use among African American youth. PMID- 17364985 TI - Violence against women, symptom reporting, and treatment for reproductive tract infections in Kerala state, Southern India. AB - In this article we examine factors associated with women's self-reports of reproductive ill health symptoms and factors associated with seeking and receiving treatment for the symptoms. We focus on indicators of women's societal position, especially empowerment (indicated by experience of and attitudes toward violence against women), autonomy, and education. We used data from the National Family Health Survey-2 from Kerala state in Southern India. Based on our results we suggest that violence against women, whether actually experienced or internalized as acceptance of its justification, is associated with increased ill health symptoms, and the acceptance of violence is associated with decreased chance of treatment. Women's higher formal education appeared to reduce treatment seeking for reproductive ill health, perhaps due to the stigma associated with sexually transmitted disease (STD) in this cultural setting. Women's work participation had no significant impact, nor did indicators of women's economic and personal autonomy. PMID- 17364986 TI - Bridges and barriers to health: her story - Emirati women's health needs. AB - Health care services in the United Arab Emirates have developed rapidly in the last 30 years fueled by oil revenues. These services have been planned and provided predominantly by non-nationals, with mixed success. The authors identify aspects of the health care system and the sociocultural environment that create both barriers and bridges to holistic health for Emirati women. Barriers include early/consanguineous marriage, frequent childbearing, polygamy, and care that is lacking in competence and cultural sensitivity. Bridges include Islam, folk medicine, cultural traditions, and the opportunity to travel abroad for health care. Maids are seen as both a barrier and bridge at different times. Recommendations for future improvements include listening to Emirati women and providing more gender-appropriate, holistic, and culturally congruent programs. PMID- 17364987 TI - Hyposplenism: a comprehensive review. Part I: basic concepts and causes. AB - Hyposplenism is not a rare condition and can complicate a remarkable number of illnesses. The two most time-honored diseases associated with the development of hyposplenism are sickle cell anemia and celiac disease. Hyposplenism is relatively easy to recognize by typical changes observed on the peripheral blood smear; including Howell-Jolly bodies, monocytosis, lymphocytosis, and increased platelet counts. Diagnosis can be confirmed by pitted RBC counts or 99Tc-labelled radiocolloid scan of the spleen; wherever available. Diagnosis needs to be made promptly to institute pneumococcal vaccination in a timely fashion and to recognize and treat bacterial infections promptly and aggressively because of the tendency of hyposplenic subject to develop fatal invasive disease. Overwhelming pneumococcal sepsis accounts for the major mortality cases in hyposplenic subjects; however severe infections with other encapsulated bacteria and protozoa have been reported. Hyposplenic individuals may also be at a higher risk for vascular, autoimmune and thrombotic diseases and they may have a higher risk of developing solid tumors. The commonly used pneumococcal polysaccharide vaccine is ineffective in asplenic subjects, because it requires the presence of IgM memory B cells, and should be given before splenectomy. In splenectomized, and functionally hyposplenic subjects, the pneumococcal conjugate vaccine is more effective, because it utilizes a T cell dependent mechanism, and should be the preferred vaccine in these circumstances. PMID- 17364988 TI - Timed-sequential chemotherapy as induction and/or consolidation regimen for younger adults with acute myelogenous leukemia. AB - Increasing the intensity of induction chemotherapy has generated considerable recent interest in the treatment of acute myeloid leukemia. Achieving complete remission is a sine qua non condition for prolonged disease-free survival and may affect long-term outcome. In this setting, administering a repeat course of induction shortly after completion of the first course, known as timed-sequential chemotherapy (TSC), has been tested and may lead to an improved long-term outcome. Whether these results are due to the biologic recruitment of cell cycle specific agents is unknown. However, this strategy to intensify induction may lead to more profound myelosuppression and to potential toxicities. Here we review the results of timed-sequential chemotherapy, used as induction regimen in de novo, relapsed or refractory AML or used as post-remission therapy, and compare them with those from other types of regimens. PMID- 17364989 TI - Serum elastase and antithrombin-3 levels after umbilical cord blood transplantation or bone marrow transplantation. AB - The severity of graft-versus-host disease (GVHD) was compared after cord blood transplantation (CBT) and bone marrow transplantation (BMT). The severity of GVHD was also analyzed in relation to serum elastase and antithrombin-3 (AT-3) levels. There was no significant difference in the average grade of acute GVHD between 49 BMT patients and 20 CBT patients (chi2-test). However, there was a lower incidence of patients without acute GVHD (grade 0) or patients with severe acute GVHD (grade 3 or 4) in CBT compared with BMT group. Linear regression analysis found no significant correlation between the serum elastase level and the grade of acute GVHD, between the serum AT-3 level and the grade of acute GVHD, or between the serum levels of elastase and AT-3 before conditioning and after engraftment. The AT-3 level after engraftment was significantly higher in the CBT group than in the BMT group and it did not fail along with the elevation of elastase in the CBT group (p < 0.01 by the Mann-Whitney U-test vs. the BMT group). In conclusion, the lower risk of severe acute GVHD in the CBT group may have been related to the smaller decrease of AT-3 after transplantation. PMID- 17364991 TI - Expression of apoptosis regulators Bcl-2 and Bax in childhood acute lymphoblastic leukemia. AB - Twenty-five children (19 M:6 F) with newly diagnosed ALL with median age of 5.5 years (1 month-12 years) were enrolled in the study. Apoptosis regulator proteins bcl-2 and bax were measured in all patients using alkaline phosphatase anti alkaline phosphatase method. Twenty-one patients were positive for bcl-2 and 23 cases for Bax, although expression levels varied. Patients who presented with splenomegaly or hepatomegaly < 5 cm expressed significantly higher levels of bcl 2 and bax protein expression. Neither of age ( < or >10 years), sex, generalized lymphadenopathy, WBC ( < or >50,000/mul) or FAB subtype was associated with high levels of bcl-2 or bax protein expression. Patients with higher mean hemoglobin levels (p = 0.009), high blast % in bone marrow (p = 0.02), immature immunophenotype (p = 0.001) exhibited signifxicantly higher bcl-2 levels. Bcl 2/bax ratio correlated inversely with TLC at presentation (p = 0.022; r = - 0.456) and in B-lineage leukemic cells as compared to T-lineage cells (p = 0.002). Bcl-2/bax ratio did not correlate with any other variable measured. Bcl-2 and bax protein co-express in ALL and high bcl-2/bax ratio correlates with good prognosis features. PMID- 17364990 TI - Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias. AB - The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases. PMID- 17364992 TI - Breast lump as an initial manifestation in acute lymphoblastic leukemia: an unusual presentation. A case report. AB - Breast lump as a presenting manifestation of acute lymphoblastic lymphoma (ALL) leukemia is extremely rare. We report a case of a young female who presented with a breast lump clinically suggestive of fibroadenoma. On fine needle aspiration cytology, it was diagnosed as lymphoid malignancy, later confirmed as ALL using hematological investigations. PMID- 17364993 TI - Imatinib-induced immune hepatitis: case report and literature review. AB - Imatinib is one of the most recent medications used for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). It is an orally administered protein-tyrosine kinase inhibitor, an enzyme which is produced by BCR-ABL fusion which results from translocation of 9:22 chromosome (Philadelphia chromosome). Imatinib blocks proliferation and induces apoptosis of BCR-ABL expression in CML. Many side effects produced by imatinib have been documented but its induction of hepatotoxcity has been rarely reported. Only a few cases so far have been reported in the literature and almost all were in females. We describe another case of hepatotoxicity due to imatinib in a 17-year old female with clinical, laboratory and histopathological changes. The case described here suggests that imatinib may also induce immune hepatitis, in some patients. PMID- 17364994 TI - Experience with recombinant-activated factor VII in 30 patients with congenital factor VII deficiency. AB - Recombinant-activated factor VII (rFVIIa) represents a therapeutic advance for the treatment and prevention of haemorrhage in patients with the rare bleeding disorder, congenital FVII deficiency. Thirty-nine cases of the use of rFVIIa in 30 patients with congenital FVII deficiency were identified from the international, internet-based registry haemostasis.com, which is a repository of case reports on the investigational use of rFVIIa that have been voluntarily submitted by physicians worldwide. These registry data have limitations compared with clinical-trial data but give valuable insights into a treatment for a rare disease that is virtually impossible to assess in conventional clinical trials. rFVIIa was used in: elective surgery (13 cases); haematoma (9 cases); emergency surgery (6 cases); epistaxis (4 cases); menorrhagia (2 cases); cover during childbirth (2 cases); disseminated intravascular coagulation (1 case; premature infant); removal of intradermal stitches (1 case); and haematuria (1 case). In 22/39 cases, rFVIIa was used prophylactically. Total dose and dosing schedules varied; median individual dose was 13.3 mug/kg body weight (bw) (range 1.2-223.8 mug/kg bw), median total dose was 38 microg/kg bw (range 1.2-758 microg/kg bw) and median number of doses was 3 (range 1-55). rFVIIa was generally associated with bleeding cessation or markedly reduced bleeding. Two adverse events were reported, but neither was regarded as being related to rFVIIa. These 39 cases support data confirming the safety and efficacy of rFVIIa in its EU-licensed indications, including that for preventing and/or controlling haemorrhage in patients with congenital FVII deficiency. PMID- 17364995 TI - Treatment of thrombotic microangiopathies with plasma exchange. AB - Thrombotic microangiopathy (TMA) is a syndrome characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever and renal dysfunction. This retrospective analysis sought to determine the clinical characteristics and outcome of patients with TMA treated with plasma exchange at the Department of Dialysis, University Hospital Zagreb. From 1982 to July 2005, 17 patients (10 male and 7 female, age ranging from 18 to 74 years) have been diagnosed with TMA. The most common presenting symptom was purpura in 76.5%, followed by neurologic disturbance in 70.5%, renal function abnormality in 41.1%, and fever in 29.4% of patients. Patients were treated with a daily plasma exchange, which was continued until the normalization of platelet count with minimal hemolysis. Plasma exchange treatment was first tapered and later discontinued with careful monitoring of laboratory parameters. Of the 17 patients, 13 achieved complete remission after 5-32 sessions, two had partial response, and two had no response and died of progressive disease. Four patients developed chronic relapsing TMA, and three of them progressed to end-stage renal disease. Survival at 1 year in our series exceeds 88%, but decreased with duration of follow-up. Overall, with the median follow up of 5 years, 6 patients died from consequences of TMA (35.3%); three with chronic TMA, and 2 in the acute phase of progressive disease. A 74-year old male who developed TMA after prostate cancer died from disseminated malignant disease. Our results demonstrate a high incidence of renal function abnormalities in patients with TMA at presentation, but also during long term follow-up. Development of end-stage renal disease was associated with poor prognosis. Further studies, long term follow-up and establishment of international registries are needed to clarify many dilemmas associated with the diagnosis, treatment and outcomes of patients with TMA. PMID- 17364996 TI - Thromboembolism in childhood nephrotic syndrome: a rare but serious complication. AB - The main clinical features of nephrotic syndrome (NS) are heavy proteinuria, hypoalbuminemia, hyperlipidemia and edema. In addition, multiple abnormalities in the coagulation pathway may be a consequence of the NS. Both arterial and venous thromboembolic complications (TEC) are relatively common and serious consequences of NS. In addition, arterial and venous thrombosis might be unexpected events during an exacerbation of NS. Embolic episodes may manifest in different regions of the body such as the brain or the lung. Hence, predisposing factors, personal and family history of TEC, thrombosis location and evolution should be always investigated in children with NS. PMID- 17364997 TI - Interstitial lung disease (ILD) and severe ITP. AB - INTRODUCTION: Platelets play an important role in inflammatory and immune responses. We report interstitial lung disease (ILD) developing during the acute phase of severe thrombocytopenia in 3 patients with severe refractory ITP. METHODS AND RESULTS: We identified 3 cases with severe ITP who developed ILD in the course of refractory chronic ITP. The thrombocytopenia was severe in all cases. ILD was an incidental finding at the presentation and often misdiagnosed as lung infections. ILD was documented by lung biopsy in cases 1 and 2, supplemented by serial chest X-rays and/or CAT scan. As the ITP improved, ILD regressed in case 1, persisted in case 2, and progressed to advanced pulmonary fibrosis in case 3. CONCLUSION: We report an association of ILD with severe refractory ITP. ILD was detected in acute phase of platelet destruction, suggesting that platelet destruction may have triggered inflammation in the lung, leading to ILD. PMID- 17364998 TI - Post-gastrectomy anemia: evaluation of 72 cases with post-gastrectomy anemia. AB - Anemia is common in patients following gastrectomy. The purpose of this study was to document causes of anemias developing during the post-gastrectomy period and to determine the importance of complete blood count parameters on types of anemia. A total of 72 patients (23 women and 49 men) who had previously undergone gastrectomy in the past and who were admitted for the evaluation of anemia were enrolled in study. The patients who were evaluated and treated for anemia in the post-gastrectomy period were excluded. Iron deficiency anemia was present in 68 (94.4%) of 72 gastrectomized patients with anemia. Deficiencies of vitamin B12 and folate were present in 57 (79.2%) and in three patients, respectively. The most common cause of anemia was the combination of iron and vitamin B12 deficiencies. Iron deficiency was present in the majority of patients, followed by vitamin B12 deficiency in frequency. In all combinations of iron deficiency, the values of mean cell hemoglobin and mean cell hemoglobin concentration were either normal or low. In cases who had low white blood cell and platelet counts vitamin B12 deficiency was frequent, while in cases who had high numbers of white cells or platelets iron deficiency was more frequent. In conclusion, gastrectomized patients should be followed for anemia and treated appropriately based on the cause of anemia. PMID- 17364999 TI - The prevalence of G6PD deficiency in blood transfusion recipients. AB - G6PD deficiency is the most common metabolic disorder of red blood cells, involving about 35 million people worldwide. Tropical and subtropical regions in the eastern hemisphere have the highest prevalence, up to 35% in some areas. The prevalence varies in different parts of the world. According to WHO, there is a 10-14.9% prevalence of G6PD deficiency in Iran. With this high prevalence, blood products are not still checked for G6PD deficiency. So, they may be used for transfusion in neonates with jaundice or for patients using oxidants. In this cross-sectional study, we have observed the effects of using this kind of blood in patients receiving blood in the Pediatric and Neonatology Departments of Imam Sajjad's Hospital in Yasuj. Samples were taken from 261 blood bags used for transfusion or exchange, and examined by spot fluorescence for G6PD deficiency. All of the patients receiving blood were examined for hemoglobin, hematocrit, and bilirubin before and after transfusion. They were also examined for hemoglobinuria, factors involved in hemolysis due to G6PD deficiency, and oxidants. RESULTS: From the 261 blood transfusions, 37(14.17%) blood bags had G6PD deficiency. About 81% of these transfusion recipients had at least one risk factor for hemolysis. The complications associated with receiving these red cells were: insufficient rise in hemoglobin (55.9%), hemoglobinuria (35.3%) and rise in bilirubin (8.8%), which were significantly higher than the control group. CONCLUSION: Considering the high prevalence and complications of transfusing G6PD deficient blood to high risk patients, it is recommended that in the form used for requesting blood products, there should be a place for checking G6PD enzyme so that the physician requesting blood could request the test to be done, depending on the risk factors. PMID- 17365000 TI - Thalassemias and other hemoglobinopathies in the Republic of Macedonia. AB - This paper summarizes the results on the epidemiology and molecular basis of thalassemias and other hemoglobinopathies in the Republic of Macedonia. Over the past 40 years, population surveys of more than 22,000 participants (school children and workers) from all over the country, have shown that the average incidence of beta-thalassemia (thal) trait is 2.6%, ranging from less than 1% in the northeast to 10% in the south. The frequency of deltabeta-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.3%. Screening of 9,619 newborns has shown that the frequency of alpha thal trait is 1.5%, of which alpha-thal-2 is 1.45% and alpha-thal-1 is 0.05%. The molecular basis of the different forms of beta-thal and other hemoglobinopathies has been completely defined. Among the Macedonians, over 450 beta-thal chromosomes have been studied. Fifteen different beta-thal mutations have been detected, four of which [IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-I-1 (G-->A), codon 39 (C-->T)] account for 85% of all beta-thal chromosomes. Among the Albanians, 48 beta-thal chromosomes have been studied. Eight different mutations have been detected, four of which [codon 39, -30 (T-->A), IVS-I-110, IVS-I-1] account for 85% of all beta-thal chromosomes. Four new mutations [-101 (C-->A), 87 (C-->G), -30, polyadenylation signal (poly A) (AATAAA-->AATGAA)] have been characterized. Molecular analyses of DNA from over 20 unrelated cases with deltabeta-thal have shown that this condition is caused by a 13 kb deletion (Sicilian type); in two families a deletion of 18 to 23 kb (Macedonian type of deltabeta-thal) was discovered. Molecular analyses of alpha-thal in the Republic of Macedonia have shown the following types of molecular defects: 20.5 kb deletion, 17.5 kb deletion, 3.7 kb deletion, poly A mutation (AATAAA-->AATGAA), and Hb Icaria [alpha142, Term-->Lys, TAA-->AAA (alpha2)]. The incidence of abnormal hemoglobins (Hbs) in the Republic of Macedonia is 0.4%. Three different alpha chain variants among 10 families, seven different beta chain variants among 33 families, two gamma chain variants in two newborns, one variant with an extended alpha chain, and Hb Lepore among 105 families, have been observed. Structural analysis of numerous cases with Hb Lepore showed that the variant was of the Washington-Boston type. PMID- 17365001 TI - Hb Barika [alpha42(C7)Tyr-->His (alpha2)] leads to an alpha+ -Thalassemia-like syndrome. AB - In human deoxyhemoglobin (deoxyHb), the hydrogen bond between Aspbeta99(G1) and Tyralpha42(C7), located in the alpha1beta2 interface, is crucial for the stability of the T structure. All the variants that could arise from a single point mutation affecting codon beta99 have already been observed, leading always to erythrocytosis. Conversely, up to now, Hb Barika is the only example found in a patient in whom the alpha42 is mutated. From a biochemical point of view, for theoretical reasons, this substitution has already been extensively studied on recombinant hemoglobin (rHb). In the patient, Hb Barika is expressed at a level lower than expected for an alpha2 gene variant and leads to an alpha+-thalassemic like syndrome. PMID- 17365002 TI - Hb A2-Pasteur-Tunis [delta59(E3)Lys-->Asn, AAG-->AAC]: a new delta chain variant detected by DNA sequencing in a Tunisian carrier of the codon 39 (C-->T) beta0 Thalassemia mutation. AB - We describe a new delta-globin variant, Hb A2-Pasteur-Tunis [delta59(E3)Lys- >Asn, AAG-->AAC]. This hemoglobin (Hb) displayed an electrophoretic mobility faster than normal Hb A2 and was expressed at 2.2 %. The molecular defect was characterized by DNA sequencing and confirmed by a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)-designed protocol. Hb A2 Pasteur-Tunis was found in a carrier of a codon 39 (C-->T) beta0-thalassemia (thal), presenting with a normal Hb A2 level. Phenotype and genotype investigations revealed that the total Hb A2 level of the patient was that expected for a minor beta-thal (4.8%). PMID- 17365003 TI - A novel beta-Thalassemic allele due to a two nucleotide deletion: beta76 (-GC). AB - We have identified and characterized a novel beta-thalassemic mutation in a North African adult. The molecular defect consists of a two nucleotide (nt) deletion in the beta-globin gene at codon 76 [beta76 (-GC), c.229-230delGC]. This frameshift mutation generates a TGA stop codon at position 89. The carrier presented with mild microcytic anemia (Hb 12.8 g/dL, MCV 60 fL), no detectable Hb F, an elevated Hb A2 level (5.5%) with no other mutation in the beta-globin gene and none of the more common known deletions in the alpha-globin cluster. No abnormal hemoglobin (Hb) was present in routine electrophoresis or in high performance liquid chromatography (HPLC) analyses. Pathologic inclusions were absent in both mature red cells and in reticulocytes. This observation reinforces the hypothesis that nonsense and frameshift mutations that result in a premature stop codon in exon 1 or exon 2 inherited in the heterozygous state do not generate dominant beta thalassemia (thal). This is the first example of a premature stop codon at position 89. PMID- 17365004 TI - An improved flow cytometric approach for isolation of fetal cells from maternal blood for non invasive prenatal diagnosis of hemoglobinopathies. AB - Prenatal diagnosis is an option for couples at risk of having a child affected with hemoglobinopathies. Chorionic villus sampling (CVS) and cordocentesis are accurate but a finite risk of fetal loss exists. A non invasive, risk free strategy that has emerged is isolation of fetal erythroblasts from maternal blood. Enrichment of nucleated red blood cells (nRBCs) from 7.0 mL maternal blood was done using a Percoll discontinuous density gradient and isolation by flow sorting using a combination of three monoclonal antibodies: CD45 per CP, glycophorin A-phycoerythrin (PE) and Hb F-fluorescein isothiocyanate (FITC) in 43 cases between 7 and 21 weeks' gestation. The percentage of nRBCs ranged from 0.0001-2.03%. The presence of dual fluorescence (glycophorin A-PE and Hb F-FITC) was confirmed by confocal microscopy. A sufficient number of nRBCs could be isolated in the first and second trimester of pregnancy to provide a simple flow cytometric approach as a potential for non invasive diagnosis of beta-globin defects. PMID- 17365005 TI - Rapid detection of beta-Thalassemia alleles in Egypt using naturally or amplified created restriction sites and direct sequencing: a step in disease control. AB - beta-Thalassemia (thal), the most common genetic disorder in Egypt, is a major health problem with an estimated carrier rate of 9-10%. This study, aimed at describing the beta-globin gene mutations in the Suez Canal area, an important Egyptian region, to provide a foundation for a disease control program. We studied 44 beta-thalassemic patients (and their relatives) from 35 families living in this region. The commonest mutations were genetically diagnosed using naturally or amplified created restriction sites. Less frequent mutations were characterized by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. Twelve different mutations were identified in 51 unrelated chromosomes. The three most frequent mutations were IVS-I-110 (G-->A), IVS-I-1 (G ->A) and IVS-I-6 (T-->C). The spectrum of rarer mutations was heterogeneous and differed from that reported in other areas of Egypt. We also identified the first homozygous case of a rare mutation, codon 24 (-G; +CAC), displaying a thalassemia major phenotype. Parental consanguinity was high (60.6%) with 35.7% of the compound heterozygous patients having consanguineous parents. These data provide insights for the distribution of beta-thal alleles in this region, and could be used as a basis for genetic counseling and prenatal diagnosis. PMID- 17365006 TI - Study of beta-Thalassemia mutations using the polymerase chain reaction amplification refractory mutation system and direct DNA sequencing techniques in a group of Egyptian Thalassemia patients. AB - The aim of this study was the molecular characterization of beta-thalassemia (thal) mutations in a group of 95 Egyptian thalassemic patients from Fayoum in Upper Egypt, Cairo, Alexandria and Tanta in Lower Egypt and the Nile Delta. To identify these anomalies, the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique was used, complemented by direct DNA sequencing for uncharacterized cases. In 80 of the 95 patients, the beta-thal mutation was detected by PCR-ARMS. The most common allele encountered in our study was IVS-I-6 (T-->C) (36.3%); the second most common mutation was IVS-I-110 (G-->A) (25.8%). In addition, we report three homozygous cases for the promoter region -87 (C-->G) allele with a frequency of 3.2%. DNA sequencing of uncharacterized cases (14 cases, 15 alleles) revealed six cases (six alleles) of codon 27 (G-->T), and three cases (three alleles) of the IVS-II-848 (C-->A) mutation. Codon 37 (G-->A) in the homozygous state was found in one patient with positive consanguinity. The frameshift codon 5 (-CT) mutation was detected in two of our uncharacterized cases. The codon 15 (TGG-->TGA) mutations was detected in one patient (one allele, 0.5%). All studied cases were fully characterized by this strategy. Screening for beta-thalassemic mutations using ARMS-PCR for the seven most frequent alleles in Egypt succeeded in determining the beta-globin genotype in 84.2% of our patients (91.6% of the expected alleles). To improve the efficiency of routine screening, the PCR-ARMS mutation panel should be updated to include the reported rare alleles. Direct DNA sequencing is an additional way to allow a full characterization of beta-thal patients in the Egyptian population. PMID- 17365007 TI - Developmental effect of the XmnI site on Ggamma-globin gene expression among newborn Hb F-Malta-I [Ggamma117(G19)His-->Arg, CAT-->CGT] heterozygotes and adult beta+ -Thalassemia homozygotes. AB - Hb F-Malta-I [Ggamma117(19)His-->Arg, CAT-->CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F-Malta-I homozygotes. The mean proportion of Ggamma-F Malta-I in Hb F was 0.26 +/- 0.03 for the Hb F-Malta-I heterozygotes and 0.58 +/- 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + - - - - - + + -]. Furthermore, the common Mediterranean haplotypes Va, IIIb [- + + + - + + + + -], I [+ + - - - - - + + +] and II [- + - + + - + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes. Different genotypes at the 5' epsilon HincII, Ggamma and Agamma HindIII, and 3'psibeta HincII sites (but not at the 5' Ggamma XmnI site) were found to be linked to significant variations in the proportion of Ggamma-F-Malta-I and Ggamma-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5' Ggamma XmnI site was found to be associated with variations in Hb F and Ggamma-globin levels in a population of adult Maltese beta-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects Ggamma-globin gene expression is active in anemic adults but not in normal infants. PMID- 17365008 TI - Molecular variations linked to the grouping of beta- and alpha-globin genes in neonatal patients with sickle cell disease in the State of Pernambuco, Brazil. AB - Various factors have been described as phenotypic modulators of sickle cell disease, such as levels of fetal hemoglobin (Hb F), presence of alpha-thalassemia (thal), and haplotypes of the beta-globin genes. In order to characterize and determine the frequency of the betaS and betaC mutations and the prevalence of alpha3.7-thal, 74 patients with sickle cell disease detected during neonatal screening in the State of Pernambuco, Brazil, were studied. The haplotypes of the beta gene and -alpha3.7-thal were determined using polymerase chain reaction (PCR), and specific restriction endonucleases were used to establish the polymorphic sites of the haplotypes. The results showed the high frequency of the Central African Republic (CAR) or Bantu haplotype in the State of Pernambuco, Brazil. The low frequency of the Benin haplotype recorded in this study, in comparison with other states in northeast Brazil, suggests the diversity of origins of Afro-Brazilians in this region. PMID- 17365009 TI - Plasma fibrinogen levels in Nigerian homozygous (Hb SS) sickle cell patients. AB - The plasma fibrinogen levels in 50 Nigerian sickle cell disease (Hb SS) patients in steady state and 50 healthy age and sex-matched (Hb AA) control subjects were determined for the purpose of assessing their baseline values. The fibrinogen levels were assessed using two methods, the clot weight and Clauss, on all the samples for the purpose of comparison. It was observed in this study that the Hb SS patients had significantly higher fibrinogen levels than the healthy Hb AA control subjects, both by the clot weight method (p < 0.001) and the Clauss (p < 0.005). The mean fibrinogen levels (4.1 +/- 2.1 g/L) of the Hb SS patients as determined by the clot weight method, were significantly higher than the values (2.2 +/- 0.3 g/L) obtained by the Clauss method. The mean values for the two methods were 2.8 +/- 0.9 and 2.0 +/- 0.08 g/L, respectively, among the control individuals with a statistically significant difference (p < 0.005). Estimation of the plasma fibrinogen levels in sickle cell disease patients might be a useful indicator of hyper coagulability, while early diagnosis may help to prevent vaso occlusive crises in these patients. PMID- 17365010 TI - Further identification of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] in Thailand by the polymerase chain reaction-single-strand conformation polymorphism technique and by amplification refractory mutation system-polymerase chain reaction. AB - Thalassemias and hemoglobinopathies are very common among Southeast Asian populations, particularly in Thailand, where it is estimated that nearly 30% of the population carries at least one such disorder. Moreover, the heterogeneity of different mutant alpha- and beta-globin alleles contributes to the complexity in diagnosis and proper management, as more than 60 thalassemia syndromes and hemoglobinopathies have been described. Herein we report a further case of Hb G Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] (also known as G-Saskatoon, G-Hsin Chu and G-Taegu) in a Thai family in which the mother was found to have an unusual hemoglobin (Hb) anomaly in combination with Hb E [beta26(B8)Glu-->Lys, GAG-->AAG]. We applied our recently described polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to scan the beta-globin genes and found an aberrant pattern in exon 1. The molecular analysis by direct genomic sequencing successfully identified the nucleotide mutation (codon 22, GAA ->GCA), and a novel amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for this variant is described. PMID- 17365011 TI - High oxygen affinity hemoglobin variant in a Canadian family: Hb Bunbury [beta94(FG1)Asp-->Asn, GAC-->AAC]. AB - We investigated a three-generation Canadian family in which individuals displayed varying degrees of erythrocytosis due to a high oxygen affinity beta chain hemoglobin (Hb) variant [Hb Bunbury, beta94(FG1)Asp-->Asn, GAC-->AAC]. This is the fourth reported case of Hb Bunbury. PMID- 17365012 TI - Misdiagnosis of Hb constant spring (alpha142, Term-->Gln, TAA-->CAA in alpha2) in a Hb H (beta4) disease child. AB - Hb Constant Spring (Hb CS; alpha142, Term-->Gln, TAA-->CAA in alpha2) is the most prevalent nondeletional alpha-thalassemia (thal) in Southeast Asian populations. It is difficult to detect on electrophoresis in its heterozygous state because of the low Hb CS levels. We found a case with Hb H (beta4) disease who, at birth, was initially assumed to have deletional alpha-thal mutations, but eventually proved to have a Hb CS defect. PMID- 17365013 TI - Four cases of Hb Q-H disease found in Southern China. AB - Four Chinese patients with Hb Q-H disease were identified during thalassemia screening. The main hematological characteristics of Hb Q-H disease are that Hb A is absent, and Hb Q-Thailand (also known as G-Taichung, Mahidol, Kurashiki-I and Asabara) accounts for the majority of the total hemoglobin (Hb). The phenotype of this disorder is similar to that of deletional Hb H (beta4) disease. PMID- 17365014 TI - Alkylamides from echinacea modulate induced immune responses in macrophages. AB - The ability of Echinacea and its components to alter the immune response was examined in vitro in a macrophage cell line under either basal or immunostimulated conditions. Potential immunostimulatory and inflammatory activity was determined using a nuclear transcription factor (NFkappaB) expression, tumour necrosis factor alpha (TNFalpha) and nitric oxide (NO) production as biomarkers. In the absence of alternate stimulation, the only significant effects seen were a decrease in NFkappaB expression by a 2-ene alkylamide ((2E)-N-isobutylundeca-2-ene-8,10-diynamide (1)) and a decrease in TNFalpha levels by cichoric acid and an Echinacea alkylamide fraction (EPL AA). When the cells were stimulated by lipopolysaccharide (LPS), inhibition of the increased NFkappaB expression levels was caused by cichoric acid, an Echinacea preparation (EPL), EPL AA and a 2,4-diene ((2E,4E,8Z,10Z)-N-isobutyldodeca 2,4,8,10-tetraenamide (2)). Increases in TNFalpha levels were inhibited by cichoric acid, EPL and EPL AA but enhanced by 1 in the presence of LPS, while only EPL AA was able to inhibit the stimulated increases in NO. When using phorbol myristate acetate to stimulate the cells, NFkappaB and NO levels were unaffected by Echinacea or its components while only cichoric acid and 2 inhibited TNFalpha levels. Although cichoric acid was found to have an effect, it is probably not an important contributor to the Echinacea modulation of the immune response in vivo, as it is not bioavailable. Echinacea appears to attenuate the response of macrophages to an immune stimulus and its combination of phytochemicals exhibits different pharmacological properties to one or more of the isolated major individual components. PMID- 17365015 TI - Difference in preventive effects between the phosphodiesterase iv inhibitor rolipram and anti-arthritic drugs on antigen-induced arthritis in mice. AB - The efficacy of the phosphodiesterase (PDE) IV inhibitor rolipram on antigen induced arthritis (AIA) in mice was evaluated in comparison with clinically used anti-arthritic drugs. To induce AIA, DBA/1 mice were immunized with ovalbumin (OVA) emulsified with CFA (day 0) followed by intra-articular injection of OVA on day 21. Rolipram and clinically used anti-arthritic drugs including indomethacin (IND), dexamethasone (DEX), methotrexate (MTX), auranofin (AUR), and D penicillamine (D-PA) were orally administered daily from days 0 to 20. On day 22, anti-OVA IgG in serum, proliferative responses of spleen cells to the OVA, and anti-OVA IgG2a and interferon (IFN)-gamma as indicators of Th1 responses, as well as anti-OVA IgG1 and interleukin (IL)-10 as those of Th2 reactions, were measured. Treatment with rolipram was followed by inhibition of the early phase of AIA associated with downregulation of both OVA-specific splenocyte proliferation and decreases of IFN-gamma released from the spleen cells but no decreases of the amount of IL-10, or levels of anti-OVA IgG, IgG2a, and IgG1. All clinically used anti-arthritic drugs were more effective in suppressing the late phase of AIA compared with the early phase of joint inflammation. The suppression of AIA by clinically used anti-arthritic drugs was associated with down regulation of not only Th1 but also Th2 responses. These results suggest that PDE IV inhibitors such as rolipram may exert their suppressive effects on AIA with relatively selective downregulation of antigen-specific Th1 responses compared with anti-arthritic drugs. PMID- 17365016 TI - Effect of AC II, an herbal formulation in cyclophosphamide-induced immunosuppression in BALB/c mice--Implication in HIV treatment. AB - Effect of AC II, herbal drug formulation in reducing immunosuppression caused by administration of cyclophosphamide was studied. Mice were injected cyclophosphamide (CTX) 50 mg/kg b.wt. for 14 days with or without the drug and total WBC, bone marrow cellularity and alpha-esterase positive cells were determined. On day 15, total WBC count in cyclophosphamide treated mice was 1500 +/- 420 cells/mm3, while in AC II-treated mice it was 7658 +/- 376 cells/mm3. On day 16, administration of cyclophosphamide reduced bone marrow cellularity to 3.42 +/- 0.38 x 10(6) cells/femur from the normal value of 13.83 +/- 0.96 x 10(6) cells/femur. In AC II treated group bone marrow cellularity was increased to 8.05 +/- 0.7 x 10(6) cells/femur. The number of alpha-esterase positive cells was found to be reduced to 177 +/- 25 cells per 4000 cells in CTX treated groups. But in AC II-treated group the number of alpha-esterase positive cells were raised to 843 +/- 86 cells per 4000 cells, which was closer to that of normal (710 +/- 49 cells per 4000 cells). Results indicate the usefulness of AC II to combat immunosuppression induced by chemical and biological agents. PMID- 17365017 TI - Properties of cryptic epitopes and their corresponding antibodies as indicated by the study of human and ovine growth hormones. AB - Antibodies (Ab) directed to hidden antigenic determinants (cryptotopes) are undesirable because they are not neutralizing. Additionally, we have previously demonstrated a close association between the extent of Ab to cryptic determinants and the expression of autoantibodies (autoAb) under some experimental conditions. Thus, the first objective of this work was to establish the physicochemical characteristics of Ab to cryptotopes and the second one was to examine the structural features of cryptic epitopes themselves. Using human and ovine growth hormones (hGH and oGH) as antigenic models and competition ELISA under different conditions of temperature, pH or ionic strength, we did not find any difference between the binding properties of anti-cryptic epitope antibodies (Ab) and anti native epitope Ab. Then, using synthetic peptides and tryptic digests and direct and competition ELISAs we studied the structures of cryptic hGH and oGH epitopes. Isolated peptides either in solution or adsorbed on microplates failed to react. Partially digested hGH was recognized only when insolubilized on microplates, and anti-oGH Ab only reacted with a large fragment of the hormone either in solution or insolubilized. These results indicate that, at least in the case of hGH and oGH, cryptic epitopes are not simple linear sequences, as commonly referred without any evidence, but new exposed conformational structures different from those found in the native antigen. PMID- 17365018 TI - Wheat anaphylaxis in children. AB - Food anaphylaxis is now the leading known cause of anaphylactic reactions treated in emergency departments, and wheat is one of the most common causes of anaphylaxis. Wheat is an important source of food worldwide. Wheat anaphylaxis is increasingly observed in our clinic. The purpose of this study was to describe the clinical features of wheat-induced anaphylaxis in 19 children for better elucidation of this disease. Children with severe reactions after ingestion of small amounts of wheat were referred to our clinic during a 4-year period. A detailed clinical history was recorded for each of the patients and a skin prick test was performed with wheat allergen extracts. The wheat-specific IgE and total IgE were measured. Grading of anaphylaxis episodes was performed according to a specific grading system. We identified 36 episodes of wheat anaphylaxis in 19 patients. All of the first attacks of wheat anaphylaxis occurred in the first time ingestion. The most frequent manifestations of the reactions were skin and respiratory symptoms. In this study 78.9% of reactions were moderate and 21.1% of them were severe. All of our patients had positive skin prick tests to wheat. Mean total IgE level was 853.4 +/- 455.27 IU/ml, and mean wheat-specific IgE was 70 +/- 14.61 Ucs/ml. We conclude that wheat-induced anaphylaxis is a disease that is sufficiently severe, and. prevention of first wheat-induced anaphylaxis episodes is almost impossible. It would, however, probably be good practice to educate physicians to recognize the common clinical manifestations of this disease for early management. PMID- 17365019 TI - In vitro heparan sulfate modulates the immune responses of normal and tumor bearing mice. AB - Tumor-bearing (TB) patients and TB animal models show a wide array of immunologic deficits. Heparan sulfate (HS) has been shown to both improve immune cell proliferative responses and to induce Th1 cytokine responses in normal animals. These HS effects, if harnessed, would be of great benefit to TB patients. The present study focused on replicating previous HS-induced Th1 and proliferative response results as well as extrapolating the beneficial immunomodulatory effects to an experimental model derived from TB animals of Lewis lung cell carcinoma. Lewis Lung Carcinoma (LLC)-TB and control mouse splenocytes were assessed for proliferation and cytokine response to concanavalin A (Con A) with 1 and 3 days' exposure to HS. Our results found HS treatment stimulated splenocyte proliferation to Con A in control mice splenocytes after 1 and 3 days of treatment, although HS proliferative effects were not seen in unfractionated TB cultures. Furthermore, cytokine studies revealed normal splenocytes treated with HS had increased levels of both Th1 and Th2 cytokines. Surprisingly, HS treated TB-splenocytes showed suppressed cytokine levels. Of particular interest was the decreased levels of the Th2 cytokine IL-4 in TB-derived samples. In conclusion, we found that HS did show immune-modulator properties in both normal and TB environments. Our studies reinforced the possibility that HS could one day be used as an immune-modulating therapeutic agent. PMID- 17365020 TI - Anti-inflammatory activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130 in murine macrophage RAW 264.7 cells. AB - This research was undertaken to test the in vitro anti-inflammatory action of 5,7,4'-trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens CMUAc130. The effects of the two coumarins were investigated on the formation of NO, PGE2, and TNF-alpha and also on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar effect was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The inhibitory effects were shown in concentration-dependent manners. The 5,7,4' Trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin also mildly but significantly reduced the formation of TNF-alpha. PMID- 17365021 TI - Induction of auto-reactive regulatory T cells by stimulation with immature autologous dendritic cells. AB - We have shown in ex vivo studies in donor bone marrow-infused kidney transplant recipients, that chimeric cells of either donor or recipient origin taken from the recipient's bone marrow down-regulated the recipient's cellular immune responses. In the present study, we have now induced regulatory T cells from peripheral blood mononuclear cells (PBMC) of renal transplant recipients or laboratory volunteers by multi-stimulation with autologous immature dendritic cell (iDC) enriched populations derived from either bone marrow cells (BMC) of the (immunosuppressed) kidney transplant recipients or PBMC of the laboratory volunteers (i.e., ibDC and ipDC, respectively). These regulatory T cells, induced by ibDC and ipDC, were autoreactive and designated as TAb and TAp with similar phenotypes and functional profiles. They were largely CD4 + CD25high, CD45RA low and CD45RO high, and uniformly expressed intracellular CTLA-4, and message of IL 4, IL-10, Foxp3, and differentially expressed TGFbeta. Their proliferative responses to autologous mature dendritic stimulating cells (mDC) were approximately two-fold stronger than to allogeneic mDC, and to allogeneic mDC were significantly lower than those of (control) autologous TPBL, suggesting an anergic state. TAb and TAp were not cytotoxic to autologous cells expressing Epstein-Barr virus (EBV) antigens, but were able to inhibit (regulate) the effector phase of this TPBL response to both autologous and allogeneic EBV lymphoblasts. This regulation appeared to require cell-to-cell contact. PMID- 17365024 TI - Gas uptake in a three-generation model geometry during steady expiration: comparison of axisymmetric and three-dimensional models. AB - Mass transfer coefficients were predicted and compared for uptake of a formaldehyde-air gas system using an axisymmetric single path model (ASPM) and a three-dimensional computational fluid dynamics model (CFDM) in three-generation model geometry at steady expiratory flow. The flow and concentration fields in the ASPM were solved using Galerkin's finite-element method and in the CFDM using a commercial finite-element software, FIDAP. Numerical results were compared for two different inlet flow rates, wall mass transfer coefficients, and bifurcation angles. The mass transfer coefficients variation with bifurcation unit from the ASPM and CFDM compared qualitatively and quantitatively closely at all flows and lower wall mass transfer coefficients for both 40 degrees and 70 degrees bifurcation angles. However, at higher wall mass transfer coefficients, quantitatively they were within 40% for both the bifurcation angles. Also, at higher flow and wall mass transfer coefficients, they were off qualitatively for a 70 degrees bifurcation angle although the uptake compared qualitatively. This is due to the normalization of uptake within a bifurcation unit with the average of inlet and outlet average concentrations. Both CFDM and ASPM predict the same trends of increase in mass transfer coefficients with inlet flow and wall mass transfer coefficients. Also, the local values of the mass transfer coefficients compared closely at all conditions. These results validate the simplified ASPM and the complex CFDM. Mass transfer coefficients increase with bifurcation angles and with a flat inlet velocity profile compared to a parabolic velocity profile since the flow is non-fully developed and hence, the uptake increases. PMID- 17365026 TI - Heterogeneities in inflammatory and cytotoxic responses of RAW 264.7 macrophage cell line to urban air coarse, fine, and ultrafine particles from six European sampling campaigns. AB - We investigated the cytotoxic and inflammatory activities of size-segregated particulate samples (particulate matter, PM) from contrasting air pollution situations in Europe. Coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particulate samples were collected with a modified Harvard high-volume cascade impactor (HVCI). Mouse RAW 264.7 macrophages were exposed to the samples for 24 h. Selected inflammatory mediators, nitric oxide (NO) and cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 6 [IL-6], macrophage inflammatory protein-2 [MIP-2]), were measured together with cytotoxicity (MTT test), and analysis of apoptosis and cell cycle (propidium iodide staining). The PM10-2.5 samples had a much higher inflammatory activity than the PM2.5-0.2 and PM0.2 samples, but the PM2.5-0.2 samples showed the largest differences in inflammatory activity, and the PM0.2 samples in cytotoxicity, between the sampling campaigns. The PM2.5-0.2 samples from traffic environments in springtime Barcelona and summertime Athens had the highest inflammatory activities, which may be related to the high photochemical activity in the atmosphere during the sampling campaigns. The PM0.2 sample from wintertime Prague with proven impacts from local coal and biomass combustion had very high cytotoxic and apoptotic activities and caused a distinct cell cycle arrest. Thus, particulate size, sources, and atmospheric transformation processes affect the toxicity profile of urban air particulate matter. These factors may explain some of the heterogeneity observed in particulate exposure-response relationships of human health effects in epidemiological studies. PMID- 17365027 TI - Dose and time dependency of inflammatory responses in the mouse lung to urban air coarse, fine, and ultrafine particles from six European cities. AB - We investigated the dose and time dependency of inflammatory and cytotoxic responses to size-segregated urban air particulate samples in the mouse lung. Coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particles were collected in six European cities (Duisburg, Prague, Amsterdam, Helsinki, Barcelona, Athens) in selected seasons using a modified Harvard high-volume cascade impactor. Healthy C57Bl/6J mice were intratracheally exposed to the particulate samples in a 24-h dose-response study (1, 3, and 10 mg/kg) and in 4-, 12-, and 24-h time course studies (10 mg/kg). After the exposures, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: total cell number, cell differential, total protein, and lactate dehydrogenase (LDH) and cytokine (tumor necrosis alpha [TNF alpha], interleukin-6 [IL-6], and keratinocyte-derived chemokine [KC]) concentrations. In general, PM10-2.5 samples had higher inflammatory activity than PM2.5-0.2 samples. PM0.2 samples showed negligible inflammatory activity. PM10-2.5 and PM2.5-0.2 samples caused large increases in BALF cytokine concentrations at 4 h, but not at 12 or 24 h, after exposure. The BALF total cell number and total protein concentrations increased significantly at 12 h for both the PM10-2.5 and PM2.5-0.2 samples, but only PM10-2.5 samples produced consistent, significant increases at 24 h after exposure. There was more heterogeneity in BALF cytokine and neutrophil cell number responses to PM2.5-0.2 samples than to PM10-2.5 samples between the sampling campaigns. Thus, particle size, sources, and atmospheric transformation processes affect the inflammatory activity and response duration of urban air particulate matter in the mouse lung. PMID- 17365028 TI - Incorporation of acute dynamic ventilation changes into a standardized physiologically based pharmacokinetic model. AB - A seven-compartment physiologically based pharmacokinetic (PBPK) model incorporating a dynamic ventilation response has been developed to predict normalized internal dose from inhalation exposure to a large range of volatile gases. The model uses a common set of physiologic parameters, including standardized ventilation rates and cardiac outputs for rat and human. This standardized model is validated against experimentally measured blood and tissue concentrations for 21 gases. For each of these gases, body-mass-normalized critical internal dose (blood concentration) is established, as calculated using exposure concentration and time duration specified by the lowest observed adverse effect level (LOAEL) or the acute exposure guideline level (AEGL). The dynamic ventilation changes are obtained by combining the standardized PBPK model with the Toxic Gas Assessment Software 2.0 (TGAS-2), a validated acute ventilation response model. The combined TGAS-2P model provides a coupled, transient ventilation and pharmacokinetic response that predicts body mass normalized internal dose that is correlated with deleterious outcomes. The importance of ventilation in pharmacokinetics is illustrated in a simulation of the introduction of Halon 1301 into an environment of fire gases. PMID- 17365029 TI - A PBPK modeling assessment of the competitive metabolic interactions of JP-8 vapor with two constituents, m-xylene and ethylbenzene. AB - Jet Propellant 8 (JP-8) is a kerosene-based jet fuel used in the military and is composed of hundreds of hydrocarbons. A PBPK model was developed to assess the metabolic interactions of JP-8 vapor on two prominent constituents of JP-8 vapor, m-xylene (XYL) and ethylbenzene (EBZ). A limited number of rats were exposed to JP-8 vapor in a Leach chamber for 4 h to 380, 1100, or 2700 mg/m3 (total hydrocarbon). Several individual hydrocarbons were monitored in the chamber atmosphere, including XYL, EBZ, and the total hydrocarbon concentration. Blood and liver were harvested and analyzed by a novel headspace SPME/GC-MS method that allowed for identification of individual hydrocarbons and low limits of detection. The PBPK model was able to describe the metabolic interactions between XYL, EBZ, and a lumped aromatic fraction of JP-8 vapor estimated to be 18 to 25% of the fuel vapor. Competitive inhibition of XYL and EBZ metabolism was observed for JP-8 vapor inhalation exposures of 1100 and 2700 mg/m3. Future inhalation studies with jet fuel include aerosol exposures and expansion of the PBPK models to include other hydrocarbons such as n-alkanes and upper respiratory tract dosimetry of aerosol droplets. PMID- 17365030 TI - Prenatal exposure to diesel exhaust impairs mouse spermatogenesis. AB - The effect of prenatal exposure to diesel exhaust (DE) was investigated. Twenty pregnant ICR mice were exposed to DE at the particle concentration of 1.0 mg/m3, from d 2 until d 16 postcoitum. Male offspring were kept alive until 12 wk of age, and then male reproductive organ weight, daily sperm production (DSP), serum testosterone level, and mRNA expression of sex steroid hormone synthesis process related factors were measured. Serum testosterone levels of the exposed group were reduced significantly at 3 wk, whereas they were elevated significantly at 12 wk. DSP was also markedly reduced at 5 and 12 wk. Histological examination showed multinucleated giant cells in the seminiferous tubules of the exposed group as well as partial vacuolation of the seminiferous tubules. Follicle stimulating hormone receptor (FSHR) mRNA expression and steroidogenesis acute regulatory (StAR) protein were significantly increased at 5 wk and 12 wk, respectively. This study suggests that prenatal exposure to DE has detrimental effects on mouse spermatogenesis in offspring. PMID- 17365031 TI - Calcitonin gene-related peptide (CGRP) as hazard marker for lung injury induced by dusts. AB - Calcitonin gene-related peptide (CGRP), which has a function as a growth factor of epithelial cells, is thought to play a role in pulmonary epithelium repair. In order to establish whether or not CGRP is associated with repair in lung damaged by dust, we examined gene expression of CGRP in the lungs of animal models exposed to different dusts. Male Wistar rats were administered 2 mg of crystalline silica, crocidolite, potassium octatitanate whisker (PT-1), and silicon carbide whisker (SiCW) suspended in saline by a single intratracheal instillation and were sacrificed at 3 d, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. Pathological findings of advanced pulmonary fibrosis were present in the rats exposed to crystalline silica and crocidolite through the experiment, whereas findings of mild or reversible pulmonary fibrosis were present in those exposed to SiCW and PT-1. The expression of CGRP in rat lung was observed by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme immunometric assay (EIA). In RT-PCR, CGRP gene expression was decreased at the interval of 3 d and 1 wk in the case of crystalline silica and crocidolite; on the other hand, it was increased at 3 d and 1 wk in SiCW and at 3 d, 1 wk, and 3 mo in PT-1-exposed rats. CGRP protein level in lungs exposed to PT-1 and SiCW was also higher than that to silica and crocidolite at 3 d of recovery time. These data suggest that CGRP is associated with repair in lung damaged by different dusts, and that CGRP could be used as a sensitive biomarker to indicate the pathogenicity of dusts. PMID- 17365032 TI - Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs. AB - Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels. PMID- 17365033 TI - The effect of inhaling thinner and/or cigarette smoke on rat kidneys. AB - Although the effects of cigarette smoking and/or thinner inhalation on various organs have been investigated, there isn't enough study available in literature about their effects on kidneys. Therefore, in this study we investigated the effect of smoking and/or inhalation on the rat kidney. In this study, stand-alone inhalation of thinner and cigarette smoke and their application together were used to determine histopathologic changes, primarily the influences on rat kidneys. The study included 60 Wistar Albino species male rats. The 60 rats were divided into 4 groups of 15 rats each. Of the groups, three were working groups and the fourth was the control group. The rats in the first study group inhaled thinner only (T), those in the second group cigarette smoke only (CS), and the rats in the third group were made to inhale both thinner and cigarette smoke (TC). Each study group was divided into 3 subgroups each comprising 5 rats and inhalation was continued for periods of 2 wk, 4 wk, and 6 wk. Thinner was vaporized into the cage with a millipore pump at a constant pressure twice per day for 1 h for 5 days (toluene 2800-3000 ppm, acetone 500-600 ppm, isobutyl acetate 7000-8000 ppm, and isobutanol 6000-7000 ppm). Cigarette smoke was given 4 times per day for 15 min each, using a mechanism prepared with an aquarium motor (containing 1.2 mg nicotine,13 mg tar, and 13 mg carbonmonoxide; 60 puffs/min). After that, rat kidneys were removed. The kidneys were weighed and were given macroscopic and microscopic examination. There were significant differences for the thinner and thinner + cigarette smoke groups in comparison to the control group, observed in both proximal and distal tubules. However, changes in the cigarette smoke group were only in proximal tubules and were smaller in extent. Thinner has been widely used as a industrial substance. Thinner usage is an important health problem. Those sniffing thinner generally also use cigarettes. The findings of the present study reemphasize the importance of taking immediate measures in order to prevent thinner inhaling among homeless children, who pose an important social problem, and to protect people who work in industrial branches that widely use thinner. PMID- 17365034 TI - Assessment of occupational exposure to cytotoxic drugs with platinum. PMID- 17365035 TI - Do vitreous fibers break in the lung? AB - In order to determine whether breakage of long vitreous fibers in the lung could be responsible for removing significant numbers of these fibers, an intratracheal instillation study was done with a preparation consisting of mostly long fibers of two different types. Following instillation of both fibers, laboratory rats were sacrificed at 6 times up to 14 days. The NK (conventional borosilicate glass) fiber preparation had about 20% short fibers (length < or = 15 microm) initially, and fibers recovered from the lungs remained at that proportion for the entire 14 days. But the HT (a new rock or stone wool) fiber preparation, which had about 5% short fibers initially, jumped to about 50% short fibers at 2 days and remained at that proportion for the rest of the study. The appearance of many short HT fibers where there were few initially is conclusive evidence that these long fibers break, and it explains their rapid removal from the lung. Since the HT fibers dissolve rapidly at acid pH, but slowly at the near neutral pH of the extracellular lung fluid, it is likely that acid attack by phagocytic cells is causing the long fibers to dissolve and break. The long NK fibers dissolve rapidly at neutral pH but slowly at acid pH and thus appear to clear by more or less uniform dissolution without apparent breakage. The long fibers of these two kinds are removed rapidly at about the same rate, but by a different mechanism. PMID- 17365036 TI - Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro. AB - Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to chrysotile asbestos. This study was conducted to investigate the HO-1 expression of lungs in lung injury by chrysotile asbestos in vivo and in vitro. Male Wistar rats were administered 1 mg or 2 mg chrysotile suspended in saline by a single intratracheal instillation and were sacrificed at 3 days, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. The expression of HO-1 was observed by Western blot analysis, reverse-transcription polymerase chain reaction, and immunostaining. Protein levels of HO-1 increased at from 3 days to 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. The mRNA levels of HO-1 increased at 3 mo and 6 mo following intratracheal instillation of 1 or 2 mg chrysotile. HO-1-positive cells were mainly found in the alveolar macrophages during immunostaining. We then examined HO-1 protein expression in human alveolar epithelial cells (A549). A549 cells were incubated with chrysotile at concentrations of 0, 12.5, 25, 50, and 100 microg/ml over 24 h. Increased expression of HO-1 protein was found following exposure to 25 or 50 microg/ml of chrysotile. Increased expression of HO-1 was also found at 6, 12, 24, and 48 h after exposure to 50 microg/ml of chrysotile with a peak at 24 h. These findings suggest that HO-1 is related to lung injury arising from exposure to chrysotile asbestos in vivo and in vitro. PMID- 17365037 TI - Size distribution, pulmonary deposition and chemical composition of Hungarian biosoluble glass fibers. AB - Compared to spherical particles, inhaled fibers may cause enhanced adverse health effects because of their specific shape, thus acting as so-called physical carcinogens. The chemical composition of fibers plays a determining role on the durability and hence may play a potential role in related health effects due to their toxic components. The physical properties, that is, length, diameter, and size distribution, and the chemical composition of fiberglass materials sampled at a Hungarian glass wool factory were investigated. The morphology of the particles was studied by optical microscopy and scanning electron microscopy (SEM), while for the chemical analysis instrumental neutron activation analysis (INAA) and SEM combined with energy-dispersive x-ray analysis (EDX) were used. Deposition fractions of the fibers in different regions of the lung and in the whole human respiratory system were computed by a stochastic lung deposition model for different flow rates and equivalent diameters, using experimentally determined size distributions. PMID- 17365038 TI - Particle size distribution and inhalation dose of shower water under selected operating conditions. AB - Showering produces respirable droplets that may serve to deposit pollutants such as trihalomethane decontamination products, heavy metals, inorganic salts, microbes, or cyanoacterial toxins within the respiratory tract. The extent and importance of this route of indoor exposure depend on the physical characteristics of the aerosol as well as the pollutant profile of the source water. The purpose of this study was to characterize shower-generated aerosols as a function of water flow rate, temperature, and bathroom location. Aerosols were generated within a shower stall containing a mannequin to simulate the presence of a human. Using hot water, the mass median diameter (MMD) of the droplets inside the shower and in the bathroom were 6.3-7.5 um and 5.2-6 microm, respectively. Size was independent of water flow rate. The particle concentration inside the shower ranged from 5 to 14 mg/m3. Aerosols generated using cold water were smaller (2.5-3.1 microm) and concentrations were lower (0.02-0.1 mg/m3) inside the shower stall. No aerosols were detected in the bathroom area when cold water was used. The International Commission on Radiological Protection model was used to estimate water deposition in the respiratory tract. For hot water, total deposition ranged from 11 to 14 mg, depending on water flow rate, with approximately 50% of this deposited in the extrathoracic region during assumed mouth breathing, and greater than 86% when nose breathing was assumed. Alveolar deposition was 6-10% and 0.9% assuming oral and nasal breathing, respectively. The consequences deposition of shower water droplets will depend on the nature and extent of any pollutants in the source water. PMID- 17365039 TI - The big ban on bituminous coal sales revisited: serious epidemics and pronounced trends feign excess mortality previously attributed to heavy black-smoke exposure. AB - The effect of banning bituminous coal sales on the black-smoke concentration and the mortality rates in Dublin, Ireland, has been analyzed recently. Based on the application of standard epidemiological procedures, the authors concluded that, as a result of the ban, the total nontrauma death rate was reduced strongly ( 8.0% unadjusted, -5.7% adjusted). The purpose of this study was to reanalyze the original data with the aim of clarifying the three most important aspects of the study, (a) the effect of epidemics, (b) the trends in mortality rates due to advances in public health care, and (c) the correlation between mortality rates and black-smoke concentrations. Particular attention has been devoted to a detailed evaluation of the time dependence of mortality rates, stratified by season. Death rates were found to be strongly enhanced during three severe pre ban winter-spring epidemics. The cardiovascular mortality rates exhibited a continuous decrease over the whole study period, in general accordance with trends in the rest of Ireland. These two effects can fully account for the previously identified apparent correlation between reduced mortality and the very pronounced ban-related lowering of the black-smoke concentration. The third important finding was that in nonepidemic pre-ban seasons even large changes in the concentration of black smoke had no detectable effect on mortality rates. The reanalysis suggests that epidemiological studies exploring the effect of ambient particulate matter on mortality require improved tools allowing proper adjustment for epidemics and trends. Aspects of harvesting and more recent results derived from a distributed lag model covering the effects of black smoke and temperature are also discussed. PMID- 17365040 TI - Surfactant protein A, exposure to endotoxin, and asthma in garbage collectors and in wastewater workers. AB - Endotoxin causes an inflammation at the bronchial and alveolar level. The inflammation-induced increase in permeability of the bronchoalveolar epithelial barrier is supposed to cause a leakage of pneumoproteins. Therefore, their concentrations are expected to increase in the bloodstream. This study aimed at examining the association between occupational exposure to endotoxin and a serum pneumoprotein, surfactant protein A, to look for nonoccupational factors capable of confounding this association, and examine the relation between surfactant protein A and spirometry. There were 369 control subjects, 325 wastewater workers, and 84 garbage collectors in the study. Exposure to endotoxin was assessed through personal sampling and the Limulus amebocytes lysate assay. Surfactant protein A was determined by an in house sandwich enzyme-linked immunosorbent assay (ELISA) in 697 subjects. Clinical and smoking history were ascertained and spirometry carried out according to American Thoracic Society criteria. Multiple linear regression was used for statistical analysis. Exposure was fairly high during some tasks in wastewater workers but did not influence surfactant protein A. Surfactant protein A was lower in asthmatics. Interindividual variability was large. No correlation with spirometry was found. Endotoxin has no effect on surfactant protein A at these endotoxin levels and serum surfactant protein A does not correlate with spirometry. The decreased surfactant protein A secretion in asthmatics requires further study. PMID- 17365041 TI - Pulmonary inflammation in mice exposed to mainstream cigarette smoke. AB - Male C57Bl/6 (C57) and ICR mice were exposed by nose-only inhalation to mainstream cigarette smoke (MS) from 2R4F reference cigarettes, at concentrations of 75, 250, and 600 microg of total particulate matter (TPM) per liter, for up to 6 mo. Respiratory-tract tissue (nose, larynx, and lung), blood, and bronchoalveolar lavage fluid (BALF) samples were collected and analyzed at several time points. Blood samples were analyzed for biomarkers of exposure (COHb and nicotine). BALF was analyzed for biomarkers of cell injury, inflammation, oxidative stress, enzyme activity, and cytokines. Blood COHb and plasma nicotine concentrations increased in a dose-dependent manner, confirming smoke exposure. Mild emphysema was observed following 28 wk of exposure. Macrophage accumulation and inflammatory infiltrates were observed around the alveolar ducts and adjacent vasculature. There was an approximately 13% increase in mean linear intercept (Lm) only in ICR mice exposed to 600 microg/L TPM. There were no significant changes in biomarkers of oxidative stress secondary to smoke exposures; however, 8-isoprostane significantly increased following the 13-wk post-inhalation period. BALF macrophage and neutrophil counts were rapidly and consistently elevated, while lymphocyte counts gradually increased over time. MS-induced inflammatory responses observed in this study are comparable to changes reported in chronic smokers, supporting the role of chronic inflammation in the pathogenesis of emphysema. However, mild emphysema in minimal numbers of mice suggests that MS exposure concentration and/or duration in the current study were not sufficient to induce a definitive emphysema phenotype. PMID- 17365043 TI - Development of a Taiwanese head model for studying occupational particle exposure. AB - This study reports a method for constructing a head model with a continuous airway passage beginning from the nostrils and continuing through the second generation of bronchi, using computerized tomographic (CT) images of facial features and airway passages from a healthy Taiwanese male adult. When combined with a manikin torso and connected to a cyclic breathing machine, the Taiwanese head model can simulate human breathing movement. This model enables investigation of important parameters of deposition efficiency without the inter- and intrasubject variability that often occurs in human studies. Being an assembly of numerous polymethyl methacrylate (PMMA) plastic slabs, the head model can be applied to study particle deposition at specified respiratory regions. The nasal geometry obtained in this study was compared with those obtained in other studies, which demonstrated this head model to be 36% smaller in nostril cross sectional area than for European Americans. Additionally, this Taiwanese head model was found to be shorter in nasal cavity length, and the minimum cross sectional area was only 50% compared to that of European Americans. This study also measured the nasal inhalation efficiency and deposition for particles ranging from 1.5 to 15 microm under various ventilation levels to test the feasibility of this head model. Future particle deposition studies using this Taiwanese head model can be compared with the currently available data, which are primarily based on Caucasian cast models or human subjects. PMID- 17365044 TI - Air pollution and hospital admissions for chronic obstructive pulmonary disease in a tropical city: Kaohsiung, Taiwan. AB - This study was undertaken to determine whether there is an association between air pollutants levels and hospital admissions for chronic obstructive pulmonary disease (COPD) in Kaohsiung, Taiwan. Hospital admissions for COPD and ambient air pollution data for Kaohsiung were obtained for the period from 1996 to 2003. The odds ratio of hospital admission was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant models, on warm days (> or =25 degrees C) statistically significant positive associations were found in all pollutants except sulphur dioxide (SO2). On cool days (< 25 degrees C), all pollutants were significantly associated with COPD admissions. For the two-pollutant models, CO and O3 were significant in combination with each of the other four pollutants on warm days. On cool days, NO2 remained statistically significant in all the two pollutant models. This study provides evidence that higher levels of ambient pollutants increase the risk of hospital admissions for COPD. PMID- 17365045 TI - Serum dioxin levels in residents living in the vicinity of municipal waste incinerators in Taiwan. AB - This study used data obtained from the Taiwan Environmental Protection Administration to measure the dioxin exposure and the body burden for residents living in the vicinity of 19 municipal waste incinerators (MWIs). A survey was conducted in 1999-2003 for the residents. Approximately 16 ambient air samples and a 60-ml blood samples of 84 to 92 residents aged 18-65 yr were collected randomly in four zones (A, B, C, D) for each MWI site based on the atmospheric dispersion model (ADM). Zone A was defined with the highest pollution level, followed by zones B and C, and zone D (background level). Congeners of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined for each sample. We summarized the PCDD/Fs levels in air samples and serum specimens by zone for these 19 sites. The mean ambient levels of PCDD/Fs fitted the ADM, the highest from zone A and the lowest from zone D (2.74 vs. 0.13 pg I-TEQ/Nm3). However, the mean serum concentration in zones A was not distinct from that in zones D (18.7 vs. 19.0 pg WHO-TEQ/g lipid). The age-specific average serum concentration increased from 13.27 pg WHO-TEQ/g in 18- to 25-yr-old subjects to 23.46 pg WHO-TEQ/g lipid in 56- to 65-yr-old subjects. In conclusion, the serum PCDD/Fs levels among residents did not adhere to the dispersion model for incineration emissions. The dose-response of serum PCDD/Fs by age suggests that the body burden of the chemicals is mainly associated with other sources instead of with inhalation. PMID- 17365046 TI - Histological alterations in male A/J mice following nose-only exposure to tobacco smoke. AB - The incidence and multiplicity of grossly observed and microscopic lesions of the respiratory tract of A/J mice exposed nose-only to mainstream smoke (50, 200, or 400 mg total particulate matter/m3 from 2R4F cigarettes) was compared to those of filtered air controls. Animals were necropsied at the end of exposure (5 mo) or following 4 or 7 mo of recovery. Lungs were visually inspected for tumors at all necropsies and examined histopathologically at 9 and 12 mo. At 5 mo no tumors were recorded. No significant elevations in tumor incidence or multiplicity were recorded although at 9 mo multiplicity was elevated in the mid-exposure group (0.90 versus 0.55 tumors per animal for controls). At 12 mo, multiplicity was increased over the 9-mo necropsy at all exposures except 200 mg/m3; however, there were no dose-related trends in multiplicity or incidence. Histopathological alterations included hyperplasia, metaplasia, and inflammation of the nose and larynx and proliferative lesions of the lungs. At 9 mo, the multiplicity of focal lung lesions was 1.4 per animal in controls but averaged 1.0 among smoke-exposed groups. There was an inverse relation (p < .059) between smoke concentration and the percentage of hyperplastic lesions at 9 mo. At 12 mo the high-exposure group had slightly increased multiplicity of 2.3 lesions compared with 1.6 among controls, while the percentage of hyperplasic lesions was similar between groups. Nose-only inhalation of mainstream tobacco smoke resulted in chronic inflammatory changes of the respiratory tract yet failed to produce statistically significant changes in tumor incidence or multiplicity. PMID- 17365047 TI - Evidence of health impacts of sulfate-and nitrate-containing particles in ambient air. AB - Ambient particulate matter (PM) is a complex mixture of inorganic and organic compounds. The U.S. Environmental Protection Agency (EPA) regulates PM as a criteria pollutant and promulgates National Ambient Air Quality Standards for it. The PM indicator is based on mass concentration, unspecified as to chemical composition, for specific size fractions. The numerical standards are based on epidemiologic evidence of associations between the various size-related particle mass concentrations as indicators and excess mortality and cardiorespiratory health effects as endpoints. The U.S. National Research Council has stated that more research is needed to differentiate the apparent health effects associated with different particle chemical constituents. Sulfate and nitrate constitute a significant portion of the particle mass in the atmosphere, but are accompanied by similar amounts of carbonaceous material, along with low concentrations of various species, including bioactive organic compounds and redox cycling metals. Extensive animal and human toxicology data show no significant effects for particles consisting only of sulfate and nitrate compounds at levels in excess of ambient air concentrations. A few epidemiologic studies, including both short term time-series studies and long-term cohort studies, have included the sulfate content of PM as a specific variable in health effect analyses. There are much less data for nitrate. The results from the epidemiologic studies with PM sulfate are inconsistent. A detailed analysis of the time-series epidemiological studies shows that PM sulfate has a weaker "risk factor" than PM2.5 for health effects. Since sulfate is correlated with PM2.5, this result is inconsistent with sulfate having a strong health influence. However, there are many limitations with these types of studies that warrant caution for any comparison between a chemical component and mass concentration. In total, the epidemiologic and toxicologic evidence provide little or no support for a causal association of PM sulfate and health risk at ambient concentrations. For nitrate-containing PM, virtually no epidemiological data exist. Limited toxicological evidence does not support a causal association between particulate nitrate compounds and excess health risks. There are some possible indirect processes through which sulfate and nitrate in PM may affect health-related endpoints, including interactions with certain metal species and a linkage with production of secondary organic matter. There is insufficient evidence to include or exclude these processes as being potentially important to PM-associated health risk. PMID- 17365048 TI - Long term consequences from exposure to sulfur mustard: a review. AB - Mustard gas (HD) was a widely used chemical warfare agent during World War I and more recently in the Iraq-Iran war (1980-1988). To date, dramatically, 45,000 Iranians are suffering from late respiratory complications due to MG exposure. This review covers two decades of researches on latent pulmonary effects of MG. Findings from clinical manifestations, pathologic examinations, laboratory data, lung function tests, and radiological evaluations are reviewed. From this review we are able to provide a suitable practical plan for workup and management of patients in this setting. PMID- 17365049 TI - Reference zero for the calibration of air-conduction audiometric equipment using 'tone bursts' as test signals. AB - The aim of this study was to determine reference peak-to-peak threshold sound pressure levels for air conduction sound transducers using groups of tone bursts as test signals. For this purpose, threshold measurements with five different earphones and a loudspeaker were carried out on groups of 25 young, otologically normal test subjects in the frequency range between 250 Hz and 8000 Hz, following as closely as possible the ISO Preferred Test Conditions. The dependence of the results on repetition rate, type of sound transducer, gender and age of the test subjects, and on reference pure tone thresholds was investigated. The results mainly depend on the reference equivalent sound pressure levels for pure tones of each sound transducer. Together with the results of another study carried out in Denmark, the data of the present study will form the basis for the International Standard ISO 389 Part 6 on reference hearing thresholds for acoustic test signals of short duration. PMID- 17365050 TI - Real-ear measurement verification for open, non-occluding hearing instruments. AB - Real-ear measurements using the modified pressure method with concurrent (real time) equalization can be inaccurate, when amplified sound leaks out of the ear canal and reaches the reference microphone. In such situations the reference microphone will detect an increased sound level and reduce the output of the loudspeaker to maintain the desired level. The risk of having errors due to leaks increases if digital feedback suppression (DFS) is used, thus achieving higher feedback-free gain levels. The following hypotheses were tested: a) using the concurrent equalization method for fitting hearing instruments with DFS may result in underestimated real-ear insertion gain (especially when using open fittings) and b) as the benefit of the DFS system increases, this error also increases. Real-ear measurements were carried out in twenty-one subjects using the modified pressure method with stored equalization as well as with concurrent equalization. The results of the study supports both hypotheses. As a consequence it is recommended to use a stored equalization method for real-ear measurements of hearing instruments with DFS and open fitting. PMID- 17365051 TI - Prediction of hearing thresholds: comparison of cortical evoked response audiometry and auditory steady state response audiometry techniques. AB - The present study evaluated how well auditory steady state response (ASSR) and tone burst cortical evoked response audiometry (CERA) thresholds predict behavioral thresholds in the same participants. A total of 63 ears were evaluated. For ASSR testing, 100% amplitude modulated and 10% frequency modulated tone stimuli at a modulation frequency of 40Hz were used. Behavioral thresholds were closer to CERA thresholds than ASSR thresholds. ASSR and CERA thresholds were closer to behavioral thresholds at higher frequencies than at lower frequencies. Although predictions based on CERA thresholds are slightly more accurate than ASSR thresholds, the differences may not be clinically significant, particularly when the degree of individual variations is considered. Prediction of hearing thresholds became more accurate when hearing loss increased. Due to variations in prediction across participants, a single correction factor cannot be used. Other factors must be considered in selecting whether to use CERA or ASSR in predicting behavioral thresholds. PMID- 17365052 TI - 80 Hz auditory steady-state responses (ASSR) at 250 Hz and 12,000 Hz. AB - Although measurement of the detection limits of the 80 Hz auditory steady-state response (ASSR) has proven to be a reasonably reliable tool in estimating hearing sensitivity in the mid-conventional audiometric frequencies (e.g. 1000 and 2000 Hz), results in the literature suggest potentially diminishing performance at 500 Hz and above 4000 Hz. The primary goal of this work was to examine the accuracy of threshold estimation via ASSR measurement for carriers more toward the audiometric extremes. At the same time, different stimulus and recording protocols than those commonly employed in ASSR testing were examined. Using a two channel recording system, ASSRs were obtained from 15 normal-hearing young adults for an amplitude-modulated carrier of 250 Hz and repeated tone bursts of 10,000 16,000 Hz, gated using a Blackman window. Results attest to the ability to record ASSRs to a wide range of carrier frequencies but also suggest that accuracy of threshold estimation suffers toward the audiometric extremes. Feasibility of ASSR based high-frequency audiometry is demonstrated in principle, but it is not clear that this method will permit adequate sensitivity and accuracy to support such applications as ototoxicity monitoring. PMID- 17365053 TI - Auditory processing disorders, verbal disfluency, and learning difficulties: a case study. AB - This case study reports the findings of auditory behavioral and electrophysiological measures performed on a graduate student (identified as LN) presenting verbal disfluency and learning difficulties. Results of behavioral audiological testing documented the presence of auditory processing disorders, particularly temporal processing and binaural integration. Electrophysiological test results, including middle latency, late latency and cognitive potentials, revealed that LN's central auditory system processes acoustic stimuli differently to a reference group with normal hearing. PMID- 17365054 TI - Ten(HL)-test results and psychophysical tuning curves for subjects with auditory neuropathy. AB - Auditory neuropathy is a hearing disorder characterized by abnormal or absent auditory brainstem responses, and the presence of otoacoustic emissions and/or cochlear microphonics, indicating normal functioning of the outer hair cells. Here, subjects with auditory neuropathy, with near-normal hearing to moderate hearing loss, were tested using the TEN(HL) test for diagnosis of dead regions and also using psychophysical tuning curves (PTCs). Results for the majority of subjects met the TEN(HL)-test criteria at one or more frequencies (often at several or all frequencies). However, the PTCs did not show shifted tips. Hence, the positive results of the TEN(HL) test should not be interpreted as indicating the presence of dead regions. Rather, it appears that high thresholds in noise are caused by poor processing efficiency, perhaps associated with loss of neural synchrony. PMID- 17365055 TI - Psychometrically equivalent Russian speech audiometry materials by male and female talkers. AB - Despite the large number of individuals who speak Russian, only a limited number of high-quality speech audiometry materials are available in a standard dialect of Russian. Thus, the purpose of this study was to develop and evaluate speech audiometry materials that can be used to measure word recognition and SRT testing in quiet for native speakers of Russian. Familiar monosyllabic and bisyllabic words were digitally recorded by male and female talkers of Russian and subsequently evaluated by native listeners. Using logistic regression, psychometric functions were then calculated for all words. Selected monosyllabic words were digitally adjusted to create word recognition lists which are relatively homogeneous with respect to audibility and psychometric slope. Speech reception threshold materials were developed by selecting twenty-five bisyllabic words with relatively steep psychometric function slopes (12.1%/dB and 9.9 %/dB) and digitally equating their intensity to match the mean PTA of the native listeners. Digital recordings of the resulting psychometrically equivalent speech audiometry materials are available on compact disc. PMID- 17365057 TI - Comparison of MRI findings with traditional criteria in diagnosis of Pendred syndrome. AB - Pendred syndrome, defined as the constellation of goiter, sensori-neural hearing loss, and positive perchlorate discharge test, is the most frequent cause of congenital deafness. Newly introduced diagnostic approaches to the disease are rather expensive and complicated, therefore we evaluated the value of MRI as the sole, or adjunctive diagnostic approach, and compared it with the traditional ones. Presuming the classic triad as the gold standard, we compared MRI findings in six such defined patients with six cases having goiter, hearing loss, and normal perchlorate discharge test. Our results indicated that MRI was 83.6% sensitive and 66.7% specific in patients fulfilling all three criteria (complete), while in the 'partial' group the sensitivity and specificity were 66.7% and 100% respectively. In conclusion, MRI, although impressive as an adjunctive diagnostic tool, may not replace the holistic approach, and the latter may be more convenient, cheaper, and still more accurate. However in 'partial' cases with equivocal findings, and in relatives of the patients, MRI may be a valuable diagnostic adjunct. PMID- 17365058 TI - Connexin 26 mutations in autosomal recessive deafness disorders: a review. AB - This review explores the association between GJB2 gene mutations, encoding connexin 26 (Cx26), and nonsyndromic hearing loss. Connexins are proteins that form intracellular membrane channels and regulate ion movement between contiguous fluid spaces. A family of autosomal gene mutations has been identified that lead to abnormal connexin expression within the inner ear that are associated with hearing loss. The exact mechanism by which this link is elicited remains unclear. We aim to highlight the clinically underestimated prevalence of GJB2 gene mutations, to explore the influential role of ethnic diversity in mutation frequency, and to provide a framework for hearing specialists in considering the differential diagnosis of nonsyndromic hearing loss. By linking an observed phenotype associated with abnormal Cx26 expression to the current understanding of the biological and genetic basis underlying it will allow a more accurate clinical description of associated hearing loss, and therefore enable more effective patient management and genetic counselling. PMID- 17365059 TI - The changing face of Usher syndrome: clinical implications. AB - Usher syndrome is both genetically and phenotypically heterogeneous. Traditionally, the condition has been classified into three clinical types, differentiated by the severity and progression of the hearing impairment and by the presence or absence of vestibular symptoms. Recent advances in molecular genetics have enabled researchers to study the phenotypic expression in confirmed molecular groups of Usher. In response to the expansion of clinical and genetic information on Usher, we report an up to date review of the different clinical forms of Usher in known molecular groups and use the emerging evidence to appraise the diagnostic utility of the traditional classification of Usher. Our findings undermine the traditional view that the clinical types of Usher have distinct genetic causes. The pleiotropic effects of some of the major causes of Usher lead to considerable overlap between the different clinical types, with very little evidence for phenotypic-genotypic correlations. The novel synthesis emerging from this review suggests more productive approaches to the diagnosis of Usher in hearing-impaired children which would provide more accurate prognostic information to families. PMID- 17365060 TI - Permanent t-tube insertion in two patients with Hurler's syndrome. AB - Hearing loss in mucopolysaccharidosis is usually both conductive and sensorineural. The conductive component is attributable to serous otitis media secondary to dysfunction of the eustachian tube and chronic thickening of the mucosa of the middle ear. The conductive component may persist after myringotomy and insertion of short-term or long-term ventilation tubes. In Hurler's syndrome, death usually occurs in the first decade of life. In our study, we present two cases, a three-year-old girl and a four-year-old boy, who were diagnosed with Hurler's syndrome. Both children have a history of otitis media with effusion requiring repeated short-term ventilation tube insertions that were unsuccessful. Permanent t-tubes were inserted in both cases. Results showed an approximate 20 dB improvement in hearing sensitivity postoperatively for each patient. PMID- 17365061 TI - Parents' perspectives on the impact of the early diagnosis of childhood hearing loss. AB - Newborn hearing screening has been widely implemented to improve outcomes for children with permanent hearing loss. This study examined benefits beyond those typically measured clinically, by exploring parents' perceptions of the effects of early/late identification of hearing loss. The parents of 17 children in Ontario, Canada, participated in the study. Seven children were identified through systematic screening and ten through traditional referral practices. All children were in oral rehabilitation programs. The study adopted a qualitative approach, examining parent's views through individual interviews. Purposive sampling was used to select a diverse group of parents to allow a broad range of perspectives to emerge. Benefits of early identification included improved communication development and early access to hearing. Negative aspects of late identification included regret for the family and family stress around the child's language gap. Although, screening programs may offer a seamless transition to audiology services, the transition to intervention services appeared less fluid for some families. Overall, parents strongly support infant hearing screening and identify benefits that are not easily quantifiable through traditional clinical measures. PMID- 17365062 TI - Symmetric sensorineural progressive hearing loss from chronic idiopathic pachymeningitis. AB - We present the case of a 68 year-old man with a diffused hypertrophic pachymeningitis (HP) involving both internal auditory canals. The clinical symptoms were headache, decreased vision in one eye, progressive bilateral and symmetrical sensory-neural hearing loss (PSNHL) responsive to steroid treatment. Although hearing loss is a frequent manifestation of HP, only few studies reported an adequate audiological assessment and follow-up. Mechanisms related to the auditory involvement are discussed on the basis of audiological data. Gadolinium enhanced MRI is the most adequate technique for HP detection and for the differential diagnosis. A delay in the diagnosis of HP seems to be quite common and the consequences may be severe, especially in cases of optic nerve involvement. For these reasons, a cerebral MRI should probably be included in the assessment of PSNHL, especially when neurological signs coexist or are reported in the medical history. PMID- 17365063 TI - Young people: their noise and music exposures and the risk of hearing loss. PMID- 17365064 TI - Survey of mobile phone use and their chronic effects on the hearing of a student population. AB - Mobile phone ownership and usage is now widespread and public concern has developed over possible harmful physiological effects of their use. This study aimed to investigate the prevalence of student mobile phone ownership and any possible chronic effects of usage on hearing, tinnitus and balance. Questionnaires for electronic self-completion were distributed to University of Southampton postgraduates, and 117 out of 160 returned met the criteria for analysis. A total of 94% were current mobile phone users, and only 2% had never used a mobile phone. Duration of ownership and daily usage ranged from 0-7 years and 0-45 minutes respectively. Text-messaging was more popular than talking. High or long-term users reported no worse hearing, tinnitus, or balance than low or short-term users. The results of this study confirm that the prevalence of mobile phone ownership amongst students is extremely high. However there appear to be no harmful effects of mobile phone usage on their audiovestibular systems within the range of exposure of the study, insofar as can be detected by the self-report method employed. PMID- 17365065 TI - The effect of longitudinal noise exposure on behavioral audiograms and transient evoked otoacoustic emissions. AB - The ear vulnerability of a group of combat soldiers was tested. The study initially included 84 soldiers and lasted two years. The soldiers were exposed to the noise of small-arms fire. Measurements included transient-evoked otoacoustic emissions (TEOAE) and pure-tone audiometry. Measurements, initially performed prior to the soldiers' basic training, were repeated several times during the study. In general, TEOAE levels (Em) decreased over time. About 57% of the ears developed a slight hearing loss (SHL) after two years of noise exposure. We define SHL as a threshold shift of 10 dB or greater, in at least at one of the audiometric frequencies 1000, 2000, 3000, 4000, or 6000 Hz. About 63% of the tested ears that had medium TEOAE level (1 or =8 dB SPL), less than 30% developed SHL. We suggest a prediction for ear vulnerability on the basis of Em prior to noise exposure. PMID- 17365066 TI - Can a hearing education campaign for adolescents change their music listening behavior? AB - This study looked at whether a hearing education campaign would have behavioral effects on the music listening practices of high school students. A total of 1757 students participated in a hearing education campaign. Before the campaign and one year thereafter they completed a survey asking for: (1) average frequency of discotheque attendance, (2) average duration of stay in the discotheque, (3) use of earplugs in discotheques, (4) frequency of regeneration breaks while at a discotheque, and (5) mean time per week spent listening to music through headphones. On questions (2), (3) and (5) no relevant post-campaign changes were reported. On question (1) students' answers indicated that the frequency of discotheque attendance had even increased after the campaign. The only change in keeping with the purpose of the campaign was an increase in the number of regeneration breaks when at a discotheque. The effect of hearing education campaigns on music listening behavior is questioned. Additional efforts are suggested to encourage adolescents to adopt protective behaviors. PMID- 17365067 TI - Recognition of digits in different types of noise by normal-hearing and hearing impaired listeners. AB - The objective of the study was to examine the ability to understand digits in different types of noise. Adaptive speech-in-noise tests were developed that measure the speech-reception-threshold (SRTn) i.e. signal-to-noise ratio that corresponds to 50% intelligibility. Digits were presented in continuous noise, 16 Hz interrupted noise, and 32-Hz interrupted noise. Also the standard Dutch triplet SRTn test in continuous noise was included. Results for forty-two ears of normal-hearing and hearing-impaired adult participants are presented. The ratio between the standard deviation in SRTn values between subjects and the measurement error determines the efficiency of the tests. A high efficiency could be achieved by using triplets instead of digits, or by using 16-Hz interrupted noise instead of continuous noise, because this resulted in a large spread in SRTn values. The simple calculation method of averaging presentation levels was highly efficient. The digit SRTn test in 16-Hz interrupted noise was very efficient in discriminating between normal-hearing listeners and hearing-impaired listeners, and might be used to screen for hearing loss as measured by pure-tone audiometry. PMID- 17365068 TI - The listening in spatialized noise-sentences test (LISN-S): test-retest reliability study. AB - The objective of the study was to collect data on the Listening in Spatialized Noise - Sentences Test (LISN-S(R); Cameron & Dillon, 2006) from a group of children with normal hearing, over two test sessions, to determine test-retest reliability. The LISN-S produces a three-dimensional auditory environment under headphones, and is presented using a personal computer. Speech reception threshold (SRT) is determined for target sentences presented in competing speech that is manipulated in respect to location (0 degrees versus+/-90 degrees azimuth) and/or the vocal identity of the speaker/s of the stories (same as, or different to, the speaker of the target sentences). Forty-six children aged five to eleven years took part in the study. Mean changes in performance on retest on the LISN-S conditions and advantage measures ranged from 0.1 dB to 1.1 dB. Reliability (r) ranged from 0.3 to 0.8. All correlations were significant (p < 0.05). Across the range of performance measures, critical differences for test score improvements ranged from 2.5 dB to 4.4 dB, making this test suitable for detecting improvements in performance in an individual child diagnosed with central auditory processing disorder following a period of auditory compensation (such as an FM system), or training. PMID- 17365069 TI - Effects of reverberation and filtering on speech rate judgment. AB - This study investigated the effects of listening condition on speech rate judgment. Four listening conditions, in which a single sentence was presented at 21 speech rates ranging from 90 WPM to 250 WPM, were incorporated. These conditions included non-degraded, reverberation, band-pass filtered, and low-pass filtered conditions, each of which was selected to simulate listening conditions one might encounter in daily life. The participants were 20 young adults (20 to 40 years) with normal hearing. They were asked to make judgments of the rates of speech randomly presented in the four listening conditions using an equal interval 5-step scale from too slow through too fast. Overall, speech rate was judged to be faster in the reverberant condition than in the other three conditions. These findings may have implications for auditory rehabilitation and counseling. PMID- 17365070 TI - What should we mean by empirical validation in hypnotherapy: evidence-based practice in clinical hypnosis. AB - This paper briefly surveys the trend of and controversy surrounding empirical validation in psychotherapy. Empirical validation of hypnotherapy has paralleled the practice of validation in psychotherapy and the professionalization of clinical psychology, in general. This evolution in determining what counts as evidence for bona fide clinical practice has gone from theory-driven clinical approaches in the 1960s and 1970s through critical attempts at categorization of empirically supported therapies in the 1990s on to the concept of evidence-based practice in 2006. Implications of this progression in professional psychology are discussed in the light of hypnosis's current quest for validation and empirical accreditation. PMID- 17365071 TI - Cognitive-behavioral hypnotherapy in the treatment of irritable-bowel-syndrome induced agoraphobia. AB - There are a number of clinical reports and a body of research on the effectiveness of hypnotherapy in the treatment of irritable bowel syndrome (IBS). Likewise, there exists research demonstrating the efficacy of cognitive behavioral therapy (CBT) in the treatment of IBS. However, there is little written about the integration of CBT and hypnotherapy in the treatment of IBS and a lack of clinical information about IBS-induced agoraphobia. This paper describes the etiology and treatment of IBS-induced agoraphobia. Cognitive, behavioral, and hypnotherapeutic techniques are integrated to provide an effective cognitive-behavioral hypnotherapy (CBH) treatment for IBS-induced agoraphobia. This CBH approach for treating IBS-induced agoraphobia is described and clinical data are reported. PMID- 17365072 TI - Cognitive hypnotherapy for depression: an empirical investigation. AB - To investigate the effectiveness of cognitive hypnotherapy (CH), hypnosis combined with cognitive-behavioral therapy (CBT), on depression, 84 depressives were randomly assigned to 16 weeks of treatment of either CH or CBT alone. At the end of treatment, patients from both groups significantly improved compared to baseline scores. However, the CH group produced significantly larger changes in Beck Depression Inventory, Beck Anxiety Inventory, and Beck Hopelessness Scale. Effect size calculations showed that the CH group produced 6%, 5%, and 8% greater reduction in depression, anxiety, and hopelessness, respectively, over and above the CBT group. The effect size was maintained at 6-month and 12-month follow-ups. This study represents the first controlled comparison of hypnotherapy with a well established psychotherapy for depression, meeting the APA criteria for a "probably efficacious" treatment for depression. PMID- 17365073 TI - Hypnotically facilitated treatment of obsessive-compulsive disorder: can it be evidence-based? AB - There are extensive evidence-based guidelines for the treatment of Obsessive Compulsive Disorder (OCD) with medication, behavior therapy, and cognitive therapy. Nevertheless, there remain a significant percentage of patients whose symptoms are more or less refractory to standardized treatments. This situation could be rooted in the phenotypic heterogeneity of the disorder as well as in its high rates of comorbid psychopathology. Studies have also found OCD to be associated with higher levels of dissociation. This paper examines what may be needed to establish evidence-based hypnotically facilitated therapies for treatment-resistant OCD. It provides an introduction to the complexity of the treatment issues surrounding OCD and considers both possibilities for and obstacles to setting up an evidence-base for using hypnotically facilitated psychotherapies for its treatment. PMID- 17365074 TI - Review of the efficacy of clinical hypnosis with headaches and migraines. AB - The 12-member National Institute of Health Technology Assessment Panel on Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and Insomnia (1996) reviewed outcome studies on hypnosis with cancer pain and concluded that research evidence was strong and that other evidence suggested hypnosis may be effective with some chronic pain, including tension headaches. This paper provides an updated review of the literature on the effectiveness of hypnosis in the treatment of headaches and migraines, concluding that it meets the clinical psychology research criteria for being a well-established and efficacious treatment and is virtually free of the side effects, risks of adverse reactions, and ongoing expense associated with medication treatments. PMID- 17365075 TI - The association between climatic factors and childhood illnesses presented to hospital emergency among young children. AB - There has been an increasing concern about the effect of climatic change on human health in recent years. It has been suggested that young children are particularly at risk due to the reduced regulating mechanism against extreme climatic changes. However, few studies on the associations between climatic factors and childhood illness, specifically among young children, have been found in the literature. This epidemiological study utilized data collected on all young patients aged less than 6 years who presented to an emergency department for a period of two years. Information on climate and outdoor air quality variables was obtained from the Bureau of Meteorology. Data were analysed with various ARIMA time series models for each common childhood illness. Results suggested that maximum daily temperature was a significant risk factor for fever (t = 5.29, p < 0.001) with a regression coefficient of 0.37 (SE = 0.07) and gastroenteritis (t = 2.69, p = 0.007) with a regression coefficient of 0.10 (SE = 0.04). The UV index was also found to be significantly but negatively related to gastroenteritis (t = -2.37, p = 0.018). However, none of the climatic variables were associated with respiratory problems after adjusting for other air quality variables and infectious disease. PMID- 17365076 TI - Preventing food-borne illness in food service establishments: Broadening the framework for intervention and research on safe food handling behaviors. AB - Unsafe food handling practices in food service establishments are a major contributor to the transmission of food-borne illness. However, current worker education and training interventions demonstrate only modest success in changing food service worker behavior. We argue for more ecologically-oriented interventions that address both individual and contextual factors that influence safe food handling behaviors. We describe potential predisposing influences (e.g. knowledge, beliefs concerning risk of food-borne illness, perceived control, self efficacy), enabling influences (e.g. intensity and quality of training, work pressure and pace, safety procedures and protocols, appropriate equipment) and reinforcing influences (e.g. management enforcement of policies, incentives for safe food handling, job stress and organizational justice) on worker behavior. Efforts to change food service workers' behaviors are more likely to be effective if they pay greater attention to the ecological context, address multiple influences on worker behavior, and view workers as partners in preventing food borne illness in food service establishments. PMID- 17365077 TI - Seaport as a source of hantavirus: a study on isolated isles. AB - Since small mammals from seaports have relative higher seroprevalences of hantavirus, this seroepidemiologic study was conducted on the isles in Kinmen and Lienchiang Counties along the coast of southern mainland China to determine whether seaport may play the role as a source of hantavirus. Among six species of small mammals trapped in Kinmen County, only male Mus musculus (6.7%) and Rattus losea (5.3%) were found to be positive. In Lienchiang County, five species of small mammals were trapped and positive findings were obtained only in male R. norvegicus (9.3%), male M. musculus (7.7%), and female R. losea (1.6%). There was no significant difference in the seroprevalence between the two counties (Kinmen 3.8% vs. Lienchiang 3.9%). The positive rate in Liaolo (17.9%) of Kinmen County was significantly higher than the remaining trapping stations and those in Matsu Distillery (10.3%) and Fushing (5.8%) of Lienchiang County were significantly higher than the remaining ones. Moreover, a significant inverse correlation was found between the seropositive rate and the distance of small mammal sampling sites to the seaport (p < 0.01). These findings suggest the role of seaport as a source of hantavirus. PMID- 17365078 TI - Chemical exposure among NZ farmers. AB - The objectives were to describe chemical use among farmers; to develop an exposure intensity score for three chemicals of interest: organophosphates (OPs), glyphosate (GP), and phenoxy herbicides (PHs). This was a cross-sectional study of a stratified random sample of farmers. Demographic, health and chemical use information were collected via questionnaire and an exposure level score developed. Within a sample of 586 farmers, 16 - 54% applied one or more of the chemicals. A high proportion of pastoral farmers used all the chemical types with 65% applying GP, 29% OPs and 19% PHs. Mean exposure scores were higher among women OP users, younger PH users, and arable farmers using PHs. This pesticide exposure score based on self-reported work practices among farmers can give an estimate of comparative annual exposure level. It can be used in analytical epidemiological studies and allows the identification of priority areas for intervention. PMID- 17365079 TI - Investigation of micronucleus frequencies in lymphocytes of inhabitants environmentally exposed to chrysotile asbestos. AB - Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. Many of the regions of Turkey have asbestos deposits. People in Doganli village - one of these regions - have been environmentally exposed to chrysotile asbestos since they were born. In this study the effects of asbestos on micronucleus (MN) frequencies of inhabitants exposed to chrysotile asbestos have been examined. Thirty subjects who had been environmentally exposed to chrysotile asbestos and living in Doganli village, and 25 controls were studied to assess the MN frequency. The control group was selected from healthy individuals with no exposure to asbestos and living in similar geographic conditions to Doganli village. Peripheral blood samples were collected from each subject and cultured for MN assay. Cytochalasin-B was added to lymphocyte cultures for evaluation of MN in binucleated (BN) cells. The differences between those exposed to chrysotile asbestos and controls were not statistically significant in terms of BN cells with MN (p > 0.05). There was not a significant relationship between MN frequencies and age, sex, smoking, both in chrysotile asbestos-exposed subjects and in controls (p > 0.05). Although the detection of calcified pleural plaques found in the inhabitants has indicated environmental exposure to chrysotile asbestos, our results show that chrysotile asbestos was not an inducer of MN in subjects exposed to chrysotile asbestos. PMID- 17365080 TI - Peripheral circulation monitored by surface temperature and autonomic nervous function in hypobaric hypoxic environment: effects of submaximal exercise. AB - Hypothermia and frostbite are frequently seen in accidents in remote wilderness environment, especially in hypobaric hypoxic conditions. The aim of this study was to clarify how hypobaric hypoxic conditions affects peripheral circulation. Peripheral skin temperature and autonomic nervous functions were assessed in two 1000-m ascent exercises. Subjects (n = 15) ascended from 1000 m above sea level in Study 1, and ascended from 2400 m in Study 2. Conditions other than environmental oxygen pressure were mostly identical in both studies. The autonomic nervous activities were decreased solely in Study 2. The relative sympathetic activity was significantly increased in the lower barometric pressure in Study 2 (p < 0.01). Peripheral skin temperature was significantly decreased after the exercise in Study 2 (p < 0.01). In conclusion, hypobaric hypoxia itself induced peripheral low temperature during exercise at high altitudes. Relative sympathetic hyperactivity may be responsible for the compromised peripheral circulation. PMID- 17365081 TI - Monitoring progress of the role of integration of environmental health education with water and sanitation services in changing community behaviours. AB - The health benefits of clean water, improved sanitation and better hygiene are now more recognized than ever before. The objective of the present study focused on monitoring the progress of behavioural changes towards appropriate behaviours related to water, environment and sanitation (WES). This was achieved through assessing the baseline community behaviours towards WES, exploring to what extent community hygienic behaviours had changed towards desirable and sustainable behaviours, through monitoring progress. The expected behavioural changes are results of an integrated package; safe water supply, sanitation, and hygiene education interventions produced by governmental and non-governmental organizations. The monitoring progress consisted of three household surveys that were administered over three years in four Egyptian districts within three Governorates; Fayoum, Beni Suef, and El-Menia. Behavioural changes were detected through special observation checklist indicators. These indicators were 7, 6, and 9 indicators each for personal hygienic behaviours, proper handling of drinking water, and proper use and maintenance of simple constructed sanitary latrines. The results from the baseline to mid-term and final surveys suggested improvement in the majority of the household behaviours towards the desirable behaviours. The proportions of the householders who practiced desirable behaviours were not to the same levels in the four districts. The results provide support to the concept that integrated interventions can produce a significant sustainable improvement in health promotion. PMID- 17365082 TI - Molecular identification of environmental bacteria in indoor air in the domestic home: description of a new species of Exiguobacterium. AB - The quality of indoor air in terms of its bioaerosol composition with microorganisms is important due to its potential aetiological role in development of conditions such as Sick Building Syndrome. Hence, laboratory identification of bacteriological components in any bioaerosol from buildings may help elucidate the role of such organisms in disease states, particularly allergy-related conditions. A molecular method was developed employing universal or "broad-range" eubacterial PCR to help identify environmental culturable bacteria from domestic household air. In a "proof of concept" experiment, 16S rDNA PCR was performed on a collection of bacterial isolates originating from indoor air in the domestic home. 16S rDNA PCR was performed using a set of universal primers to successfully generate an amplicon of approximately 1400 bp, which was sequenced to obtain each isolate's identity. Sequence analysis was able to identify 12/13 of the isolates, whereby the majority were Gram-positive (12/13). Nine different genera were identified from the 13 isolates examined, of which, 12/13 were Gram-positive, with the exception being Moraxella osloensis, which was Gram-negative, as well as a novel species of Exiguobacterium. The closest phylogenetic neighbour of the wildtype isolate to a named species within this genus was E. aestuarii (1364/1384 bases; 98.4% homology), followed by E. marinum (97.5%) and with E. acetylicum being the most distantly related of all the described species. On account of this divergence within the 16S rDNA gene operon of the unknown Exiguobacterium isolate, we believe this isolate to represent a novel species of Exiguobacterium, which we have tentatively named Exiguobacterium belfastensis. Although from this study, these organisms are usually unlikely to be clinically significant to healthy individuals with a competent immune system, we recommend that molecular identification methods are used, if considered necessary, as an adjunct to first line phenotypic identification schemes, where a definitive identification is required. When the use of molecular identification methods is justified, employment of partial 16S rDNA PCR and sequencing provides a valuable and reliable method of identification of environmental bacteria in the home. This study demonstrates the usefulness of such methods and a full and comprehensive study is now required to examine the diversity of bacteria in indoor air in the home, with particular emphasis on the risk of such environmental organisms to immunosurpressed patients, such as those with haematological malignancies and who are neutropenic. PMID- 17365083 TI - Pragmatic skills in the early stages of Alzheimer's disease: an analysis by means of a referential communication task. AB - BACKGROUND: Disordered discourse in cases of senile dementia of Alzheimer's type (DAT) has mainly been described in conversation and picture description tasks. The referential communication task provides researchers and clinicians with new insights on the nature of these disorders. AIMS: To study to what extent persons suffering from DAT can benefit from shared experience through trial repetition to achieve common reference. METHODS & PROCEDURES: Thirteen persons suffering from DAT at minimal or mild stage (MMSE score range = 18-27) were compared with 13 healthy elderly adults (64-86 years) in neuropsychological assessment of executive functions and in a referential communication paradigm. To study how the two partners achieve mutual understanding by progressively elaborating a common ground, the task was repeated three times. OUTCOMES & RESULTS: Persons with DAT produced a larger number of words than control participants and they benefited from the task repetition. However, they were less able to take into account previously shared information, used no definite referential expressions and were more idiosyncratic in their descriptions of the referent. This decline of communicative effectiveness was found not to relate closely to executive deficits. CONCLUSIONS: Collaborative exchanges allow healthy elderly persons to ground reference in common experience. This process is severely disturbed in persons with DAT, in relation to poor memory of preceding episodes or to other cognitive impairments. PMID- 17365084 TI - Dysarthria and Friedreich's ataxia: what can intelligibility assessment tell us? AB - BACKGROUND: Friedreich's ataxia is one of the most common hereditary disorders of the nervous system. Dysarthria is a pervasive symptom of Friedreich's ataxia, yet the clinical presentation of speech symptoms remains poorly understood, leaving clinicians without the evidence required to develop therapy interventions. AIMS: The research reported herein had three aims: the first was to document the severity of the intelligibility deficit associated with Friedreich's ataxia dysarthria; the second was to document the phonetic profile of the intelligibility deficit; and the third was to use the results of the phonetic profile to estimate the motor control mechanisms and neurological substrates implicated in Friedreich's ataxia dysarthria. METHODS & PROCEDURES: Eleven adult males with Friedreich's ataxia were recruited. Intelligibility was assessed using a single-word multiple-choice task completed by ten listeners. OUTCOMES & RESULTS: Intelligibility severity ratings ranged from mild to severe. The majority of subjects fell into the mild category. The phonetic errors revealed a distinctive profile, with word-final plosive voicing contrast representing the highest source of error. Involvement of cerebro-cerebellar loops was considered to be compatible with the profile results. CONCLUSIONS: Friedreich's ataxia dysarthria has a distinctive phonetic profile and contains subgroups of different severity. High sources of error identified in the phonetic profile should be considered when developing targets for therapy intervention. Neurological substrates are considered to vary across individuals and to include involvement of cerebro-cerebellar loops. Further research involving acoustic analysis of final plosive voicing contrasts would provide further insights into the neurological substrates involved. PMID- 17365085 TI - Reading comprehension in children with specific language impairment: an examination of two subgroups. AB - BACKGROUND: In reading research, children with specific language impairment (SLI) have tended to be included in groups of children expected to have difficulties with both decoding and reading comprehension (generally poor readers). This is because generally children with specific language impairment display difficulties with phonology as well as syntax and/or semantics. However, children with specific language impairment are a heterogeneous group. Many children with specific language impairment have oral comprehension difficulties that are likely to limit reading comprehension. A subgroup of these children may exhibit intact phonological and decoding skills. If so, they would resemble the children with specific reading comprehension difficulties (poor comprehenders) reported in the literature. AIMS: This study sought to identify a group of children with a poor comprehender reading profile amongst children with specific language impairment. It then compared the phonological and oral comprehension skills of the group of 15 poor comprehenders with a group of 15 generally poor readers with specific language impairment, to identify any differences in language skills. Secondarily, the study wanted to determine which of the language tasks best predicted group membership. METHODS & PROCEDURES: The study was carried out in two phases. In Phase 1, children with specific language impairment were assessed on the Woodcock Word Attack to identify a group with adequate decoding skills. These children had poor reading comprehension on the Neale Analysis of Reading Ability. From the poor decoders on the Word Attack, a second group of children, matched for age and gender, was selected to form the generally poor reader group. In Phase 2, the participants were assessed on a battery of phonological and oral comprehension tasks. OUTCOMES & RESULTS: A group of children exhibiting a poor comprehender reading profile was found to exist amongst children with specific language impairment. As expected, the poor comprehenders performed significantly better than the generally poor readers on phonological awareness tasks. On the oral comprehension tasks, the two groups did not differ at the word and sentence level; however, the poor comprehenders had significantly weaker oral comprehension skills at the paragraph level. CONCLUSIONS: This study found that children with specific language impairment, who have equally poor reading comprehension but which differ in their decoding ability, differ not only in their performance on phonological tasks, but also on oral comprehension at the paragraph level. This indicates a need for paragraph-level oral comprehension to be included in assessment. In addition, educational and clinical intervention programmes for children with specific language impairment should ensure that they are meeting individual needs. PMID- 17365086 TI - Non-word repetition in Spanish-speaking children with Specific Language Impairment (SLI). AB - BACKGROUND: A number of previous studies have revealed that children with Specific Language Impairment have limitations in Phonological Working Memory as revealed by a task that requires them to repeat non-words of increasing syllable length. However, most published studies have used non-words that are phonotactically English. AIMS: The purpose was to examine the repetition of non words that are consistent with the phonotactic patterns of Spanish. The study also examined the relationship between non-word repetition performance and other language measures. METHODS & PROCEDURES: Eleven Spanish-speaking children with Specific Language Impairment and 11 age-matched children with typical language development aged 8;3-10;11, who were part of a larger study of sentence processing, participated in the study. The primary data were the children's repetition of 20 non-words, four at each syllable length (one, two, three, four and five syllables). The children's productions were transcribed and scored for non-word, segmental and cluster accuracy as well as for error type. OUTCOMES & RESULTS: The children with Specific Language Impairment performed more poorly on almost all measures of accuracy, but particularly in their production of three-, four-, and five-syllable non-words. Substitutions were the most frequent error type for both groups. Likelihood ratios indicated that non-word repetition performance is a highly accurate identifier of language status in these preselected groups. The children's non-word repetition was highly correlated with most of the standardized language measures that were administered to the children. CONCLUSIONS: The repetition of non-words consistent with Spanish phonotactics reveals word-length effects and error patterns similar to those found in previous studies. It extends these findings to older school-age Spanish speaking children with Specific Language Impairment. Given the limited choices for instruments that can be used to identify children with Specific Language Impairment, a Spanish Non-word Repetition Task has the potential to be a valuable screening test for clinical and research purposes. PMID- 17365087 TI - Subtyping of children with developmental dyslexia via bootstrap aggregated clustering and the gap statistic: comparison with the double-deficit hypothesis. AB - BACKGROUND: The marked degree of heterogeneity in persons with developmental dyslexia has motivated the investigation of possible subtypes. Attempts have proceeded both from theoretical models of reading and the application of unsupervised learning (clustering) methods. Previous cluster analyses of data obtained from persons with reading disabilities have suffered from the inherent limitations of unsupervised learning methods. Specifically, the reliability and stability of cluster solutions have proven difficult to determine. Recent developments in the clustering literature have addressed these concerns by permitting checks on the internal validity of the solution. Resampling methods produce consistent groupings of the data independent of initialization effects, while the gap statistic provides a confidence measure for the determination of the optimal number of clusters present in the data. Combining these methods produces a robust data-driven classification that can be compared with theoretically based subtypes to produce better-informed models of developmental dyslexia. AIMS: The present study is a novel application of resampling (bootstrap aggregating or bagging) methods and the gap statistic to the subtyping of children with developmental dyslexia. The specific aims of this study are: (1) to illustrate the use of bagging methods and the gap statistic in multivariate data obtained from children with developmental dyslexia; and (2) to compare the bagged clustering thresholded by the gap statistic against the predictions of the double deficit hypothesis. The double-deficit hypothesis is a prominent theoretical model of developmental dyslexia, which predicts three subtypes: phonological, rate, and phonological-rate impaired readers. METHODS & PROCEDURES: Three simulated data sets with known cluster structure were created to check the validity and illustrate the utility of the bagged clustering with the gap statistic in data with known structure. Subsequently, a clinical database of standardized test data (eight tests) from 93 children with developmental dyslexia was clustered using these methods. This procedure was repeated on a database of 93 children without reading disability matched for gender and age as a control. Finally, the clustering was repeated on the entire database of 186 participants. Cluster solutions were obtained for an increasing number of clusters (1-10) and were tested against the null hypothesis that no subtypes were present, i.e. the data represented a single cluster. OUTCOMES & RESULTS: Four clusters were identified in the children with developmental dyslexia. There was no evidence of significant cluster structure in the children without dyslexia. Two clusters were identified when children with and without reading impairments were considered together. Among the participants with developmental dyslexia, there was evidence of a phonological-deficit cluster, a rapid-naming cluster, and a cluster showing both depressed phonological processing and rapid naming. These accounted for 73 of the 93 participants (78%). All three are predicted by the double-deficit hypothesis. The fourth cluster consisted of children with normal phonological and rapid naming ability incommensurate with their high verbal ability. An analysis of variance with post-hoc multiple comparisons demonstrated that the phonological, rapid-naming, and double deficit clusters did not differ significantly in age, but the fourth cluster was comprised of significantly older children. The mixed data set revealed two clusters. One cluster consisted almost entirely of the double-deficit and phonological subtypes. The other consisted of the participants without dyslexia and the children with dyslexia demonstrating either a single rapid naming deficit or standardized test scores in the normal range. A silhouette analysis indicated that the four-cluster solution for the children with developmental dyslexia was superior to the two-cluster solution obtained for the entire data set. CONCLUSIONS: The study provides support for the presence of distinct subtypes in children with developmental dyslexia and for the double-deficit hypothesis. Specifically, this study finds three subtypes predicted by the double-deficit hypothesis without the assumption of an a priori theoretical model of reading. Taken together, these subtypes account for 79% of the participants with dyslexia. Further, the percentages of children in each subtype are in good agreement with previous studies. The participants in the subtype not predicted by the double-deficit hypothesis were significantly older than the other three groups. Recent advances in unsupervised learning can be expected to aid the improvement and refinement of the definition of developmental dyslexia. If reliable and consistent subtypes can be identified among persons with developmental dyslexia, it is reasonable to assume that diagnostic and intervention efforts will be greatly improved. PMID- 17365088 TI - Language impairments in sign language: breakthroughs and puzzles. AB - BACKGROUND: Specific language impairment has previously solely been documented for children acquiring spoken languages, despite informal reports of deaf children with possible sign language disorder. The paper reports the case of a deaf child exposed to British Sign Language (BSL) from birth, who has significant developmental deficits in the comprehension and production of BSL grammar based on formal assessment and linguistic analyses of his sign communication in comparison with age-matched unimpaired signers. RESULTS: It is shown that linguistic difficulties with BSL verb morphology underlie the child's poor performance compared with same-age native signers. CONCLUSIONS: The appearance of linguistic impairments in sign and spoken languages in comparable domains supports cross-linguistic and modality free theories of specific language impairment. PMID- 17365090 TI - Emotional and physiological responses of fluent listeners while watching the speech of adults who stutter. AB - BACKGROUND: People who stutter produce speech that is characterized by intermittent, involuntary part-word repetitions and prolongations. In addition to these signature acoustic manifestations, those who stutter often display repetitive and fixated behaviours outside the speech producing mechanism (e.g. in the head, arm, fingers, nares, etc.). Previous research has examined the attitudes and perceptions of those who stutter and people who frequently interact with them (e.g. relatives, parents, employers). Results have shown an unequivocal, powerful and robust negative stereotype despite a lack of defined differences in personality structure between people who stutter and normally fluent individuals. However, physiological investigations of listener responses during moments of stuttering are limited. There is a need for data that simultaneously examine physiological responses (e.g. heart rate and galvanic skin conductance) and subjective behavioural responses to stuttering. The pairing of these objective and subjective data may provide information that casts light on the genesis of negative stereotypes associated with stuttering, the development of compensatory mechanisms in those who stutter, and the true impact of stuttering on senders and receivers alike. AIMS: To compare the emotional and physiological responses of fluent speakers while listening and observing fluent and severe stuttered speech samples. METHODS & PROCEDURES: Twenty adult participants (mean age = 24.15 years, standard deviation = 3.40) observed speech samples of two fluent speakers and two speakers who stutter reading aloud. Participants' skin conductance and heart rate changes were measured as physiological responses to stuttered or fluent speech samples. Participants' subjective responses on arousal (excited-calm) and valence (happy-unhappy) dimensions were assessed via the Self-Assessment Manikin (SAM) rating scale with an additional questionnaire comprised of a set of nine bipolar adjectives. OUTCOMES & RESULTS: Results showed significantly increased skin conductance and lower mean heart rate during the presentation of stuttered speech relative to the presentation of fluent speech samples (p<0.05). Listeners also self-rated themselves as being more aroused, unhappy, nervous, uncomfortable, sad, tensed, unpleasant, avoiding, embarrassed, and annoyed while viewing stuttered speech relative to the fluent speech. CONCLUSIONS: These data support the notion that stutter-filled speech can elicit physiological and emotional responses in listeners. Clinicians who treat stuttering should be aware that listeners show involuntary physiological responses to moderate-severe stuttering that probably remain salient over time and contribute to the evolution of negative stereotypes of people who stutter. With this in mind, it is hoped that clinicians can work with people who stutter to develop appropriate coping strategies. The role of amygdala and mirror neural mechanism in physiological and subjective responses to stuttering is discussed. PMID- 17365091 TI - Behavioural intervention effects in dysarthria following stroke: communication effectiveness, intelligibility and dysarthria impact. AB - BACKGROUND: Dysarthria is a common post-stroke presentation. Its management falls within the remit of the speech and language therapy profession. Little controlled evaluation of the effects of intervention for dysarthria in stroke has been reported. AIMS: The study aimed to determine the effects of a period of behavioural communication intervention on communication effectiveness and intelligibility, and of the speech disorder's impact on the person with dysarthria. METHODS & PROCEDURES: Eight people with dysarthria following stroke received individually tailored intervention programmes of 16 sessions during an 8 week period. Conversation, and reading aloud of connected speech and of single words were sampled at four points, at intervals of around 2 months: two before intervention and two after intervention. The data were perceptually evaluated by ten listeners, blind to assessment point, for the overall effectiveness of communication (conversation) and for single-word and reading intelligibility. The impact of dysarthria was assessed at the beginning and end of the intervention period. OUTCOME & RESULTS: The level of reliability of listener ratings was high. There was no evidence of group change between assessment points for measures of communication effectiveness during conversation, or for reading and word intelligibility. Individual participant analysis indicated that five speakers improved in at least one of these three measures. In all cases this followed either stability or deterioration during the 2-month pre-intervention period. There was very little evidence of deterioration during the 2 months after withdrawal of treatment. For three participants no intervention-related speech benefit was demonstrated. Age, dysarthria severity or lesion information did not appear to differentiate those who improved from those who did not. Improvement occurred in all who began the intervention phase between 5 and 8 months following stroke onset. Group data indicated no change in the Dysarthria Impact Profile in respect of three sections (The effect of dysarthria on me as a person; How I feel others react to my speech; and How dysarthria affects my communication with others). There was a significant difference between the start and end of intervention for Accepting my dysarthria, suggesting a reduction in the negative impact of dysarthria. CONCLUSIONS: The results demonstrate that some individuals with dysarthria have a capacity to respond positively to intervention, some months after stroke, and to maintain this improvement following 2 months of no intervention. Consideration is given to how the results of the present study may inform subsequent phases of dysarthria stroke research. PMID- 17365092 TI - Causal sentence production in children with language impairments. AB - BACKGROUND: The production of causal sentences (e.g. The house went on fire because the girl was playing with matches) is a key component of the ability to produce explanations, which in turn is an important aspect of children's developing discourse skills. While informal observations by professionals suggest that children with language impairments often have difficulties in producing (and comprehending) causal sentences, there is a dearth of systematic research evidence on the scope and characteristics of such difficulties. AIMS: The study reported herein aimed to establish the scope and characteristics of the difficulties that children with language impairments have with causal sentence production. In particular, it investigated whether they have difficulties with (1) producing causal connectives (because and so), (2) producing semantically appropriate causal sentences, and (3) coordinating the production of more than one clause. METHODS & PROCEDURES: The performance of 5-7-year-old children with language impairments (the LI group, n = 30) was compared with that of typically developing chronological age peers (the CA group, n = 30) on four elicited production tasks designed to encourage children to talk about pictures of causally related events. The tasks required the children to answer causal questions, to complete and imitate causal sentences, and to produce full causal sentences. OUTCOMES & RESULTS: Although the groups did not differ in the overall frequency with which they used causal connectives, the LI group produced fewer causal connectives than the CA group on tasks involving higher processing demands, as well as producing a lower percentage of semantically appropriate responses on most tasks. The LI group found imitating causal sentences more difficult than answering causal questions and completing causal sentences, whereas the CA group showed a similar level of performance across these three tasks. CONCLUSIONS: Although 5-7-year-old children with language impairments have causal expressions in their repertoire, they have marked and extensive problems in using these expressions appropriately and in producing full causal sentences even when these are modelled for them. Given the educational importance of explanation, there is a clear need for interventions to target both the semantic appropriateness of causal sentence production and the frequency of use of causal connectives, especially in contexts where children have to cope with the additional processing demands associated with producing two-clause sentences and/or with producing causal sentences autonomously. PMID- 17365093 TI - Sentence repetition as a measure of early grammatical development in Italian. AB - BACKGROUND: Research on language acquisition and disorders highlights the need to evaluate the early phases of language development for the early identification of children with language problems (screening), and to determine the nature and severity of language disorders (diagnosis). AIMS: The paper presents a new Sentence Repetition Task developed for evaluating language abilities in Italian pre-schoolers. Two studies are reported. The first is aimed at evaluating the power of the Sentence Repetition Task in discriminating the developmental changes in children's capacity to repeat sentences of different length and morphosyntactic complexity. Moreover, the test-retest reliability was assessed. The second study explored the relationship between the Sentence Repetition Task, free speech and verbal memory span. METHODS & PROCEDURES: The test included 27 sentences of different length and complexity. Each sentence was accompanied with a picture reproducing its global meaning. In Study 1, the Sentence Repetition Task was administrated to 100 middle- and lower-class children (balanced for gender) between 2 and 4 years with a test-retest design. Test results were submitted to univariate analysis of variance, using five age levels as independent variables. To evaluate the test reliability, test-retest correlational analyses were conducted. In Study 2, 25 middle- and lower-class children between 2 and 4 years of age, balanced for age and gender, participated. The performance of the children on the repetition test was compared with their spontaneous language data. Moreover, the same children received a Verbal Memory Span test, consisting of a list of ten strings of different number of words. Correlational analyses were conducted to evaluate the relationships between the Sentence Repetition Task, free speech and the Verbal Memory Span test. OUTCOMES & RESULTS: Study 1 showed that 2-year-old children's repeated sentences were highly telegraphic. Between the age of 2.0 and 2.6 the mean length of utterance in the Sentence Repetition Task grew from approximately two to three words, and the number of omissions of articles, prepositions and modifiers significantly decreased. After 3.0 years old, omissions of free function words practically disappeared. The results of Study 2 showed that mean length of utterance, omission of articles and use of the verbs in the Sentence Repetition Task correlated with the same measures of the free speech. Moreover, positive correlations were found between verbal memory span and performance of both the repetition task and the free speech. CONCLUSIONS: Results demonstrate that the repetition test is reliable, discriminates between the different age groups examined, highlights the relevant developmental stages described in the literature, and provides a reliable measure of the mean length of utterance. PMID- 17365094 TI - Modal verbs with and without tense: a study of English- and Cantonese-speaking children with specific language impairment. AB - BACKGROUND: Surprisingly little is known about the use of modal auxiliaries by children with specific language impairment (SLI). These forms fall within the category of grammatical morphology, an area of morphosyntax that is purportedly very weak in children with SLI. AIMS: Three studies were conducted to examine the use of modal auxiliaries by preschool-aged children with SLI. METHODS & PROCEDURES: In each study, probe tasks were designed to create contexts that encouraged the use of modals to express the modality functions of ability and permission. In Studies 1 and 3, English-speaking children participated. In Study 2, the participants were Cantonese-speaking children. In each study, three groups of children participated: A group exhibiting SLI, a group of younger typically developing children (YTD), and a group of (older) typically developing children (OTD) matched with the SLI group according to age. OUTCOME & RESULTS: In Study 1, English-speaking children with SLI were as proficient as YTD children, though less proficient than OTD children in the use of the modal can to express the modality functions of ability and permission. In Study 2, the same modality functions were studied in the speech of SLI, YTD and OTD groups who were speakers of Cantonese. In this language, tense is not employed, and therefore the modality function could be examined independent of formal tense. Results similar to those of Study 1 were obtained. Study 3 again studied SLI, YTD and OTD groups in English to determine whether the children's expression of ability differed across past (could) and non-past (can) contexts. The results for can replicated the findings from Study 1. However, the children with SLI were significantly more limited than both the YTD and OTD groups in their use of could. CONCLUSIONS: The results suggest that most children with SLI have access to modality functions such as ability and permission. However, the findings of Study 3 suggest that they may have a reduced inventory of modal forms or difficulty expressing the same function in both past and non-past contexts. These potential areas of difficulty suggest possible directions for intervention. PMID- 17365095 TI - Development of phonological representations and phonological awareness in children with speech impairment. AB - BACKGROUND: Children with speech impairment are more likely to have difficulty learning to read compared with children with typical speech development. Researchers have hypothesized that a difficulty in accessing good-quality phonological representations of words stored in the memory may constrain these children's performance on phonological awareness tasks and subsequent early reading acquisition. AIMS: The study investigated the following research questions. (1) Do preschool children with moderate or severe speech impairment show persistent difficulty on tasks designed to tap underlying phonological representations? (2) What is the relationship between performance on phonological representation tasks and measures of speech production, phonological awareness and early print decoding? METHODS & PROCEDURES: Utilizing a longitudinal design, the performance of nine children (aged 3.09-5.03 years at initial assessment) with moderate or severe speech impairment and of 17 children of the same age with typical speech development were assessed on three occasions over a 12-month period. Assessments included receptive-based tasks designed to tap underlying phonological representations, speech production and phonological awareness measures. OUTCOMES & RESULTS: Children with speech impairment had greater difficulty judging correct and incorrect productions of words, and had difficulty in reflecting on the accuracy of newly learned non-words. Moderate correlations were observed between performance on phonological representation and phonological awareness tasks. CONCLUSIONS: Poorly specified underlying phonological representations will result in difficulties during listening, speaking and phonological awareness tasks, as well as create additional challenges during the decoding of written words for some children. PMID- 17365096 TI - Memory impairment in methamphetamine dependent patients. AB - The authors examined the verbal memory and visual memory of 19 patients with methamphetamine dependence and 18 normal controls to assess the memory impairment due to the use of methamphetamine. There was no significant difference in the verbal memory, but a significant difference was detected in the visual memory. The results that the methamphetamine selectively impairs visual memory seem to be because visual memory tasks are more sensitive to the damage of the executive function. PMID- 17365097 TI - Classification and regression tree analysis of a neurologically impaired and normal sample using sensory-motor tasks. AB - The ability to differentiate between neurologically impaired and normal individuals is an important component in a valid neuropsychological battery. However, limited research exists regarding the ability of sensory-motor batteries to differentiate between the two groups. This study used Classification and Regression Tree Analysis (CART) to identify which measures of sensory-motor functioning from the Dean-Woodcock Sensory Motor Battery (DWSMB) would best differentiate between neurologically impaired and normal individuals, as well as identify which subtests would provide the best pathognomic power. The results revealed that a number of clinically useful nodes emerged that enabled the differentiation between groups with a small number of tasks. The primary separation variable was the Gait and Station subtest, a measure of subcortical motor functioning. Auditory Acuity and Clock Construction also provide important pathognomic information. A cross validation was conducted to determine the integrity of the generated decision tree, and results revealed that the generated model correctly predicted 84.5% of the normal group and 71.4% of the neurologically impaired sample. The results from the present analysis provides further evidence for the construct validity of the DWSMB. PMID- 17365098 TI - Reelin immunoreactivity and morphological analysis of the human visual cortex. AB - Reelin is a secreted glycoprotein with a crucial role in development of the Central Nervous System. In adults, its function remains unclear but it may be involved in the modulation of synaptic plasticity. Having in mind this possible property of reelin, the authors decided to study the distribution of reelin immunoreactivity in the neurons of the human adult primary visual cortex and compare the findings with morphological analysis (Golgi method) of neuronal networks. The distribution of reelin in the primary visual cortex is different from other cortical area examined; reelin is mostly present in the neurons of second and sixth layer. PMID- 17365099 TI - Chlorpyrifos increases the levels of hippocampal NMDA receptor subunits NR2A and NR2B in juvenile and adult rats. AB - The present study investigated the effect of chlorpyrifos on NMDA receptor subunits NR2A and NR2B in juvenile and adult rats. Chlorpyrifos was administered with the dose of 40 and 70 mg/kg to juvenile and adult rats, respectively. Chlorpyrifos significantly inhibited the AChE activity in juvenile and adult rats (p < .05). NR2A and NR2B levels significantly increased in juvenile and adult rats by chlorpyrifos application (p < .05). Increased NR2A and NR2B levels may reflect increased glutaminergic activity, consequently neuronal damage. In the case of neuronal damage, learning and memory could be affected negatively even though NR2A and NR2B increased. PMID- 17365100 TI - Effects of hostility and stress on affective verbal learning in women. AB - The current experiment investigated the effects of hostility on affective verbal learning and physiological regulation in high and low hostile women. The Auditory Affective Verbal Learning Test (AAVLT) was administered to women in either a cold pressor or no cold pressor condition. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded before and after the cold pressor or no cold pressor manipulation. Results indicated that high hostile women learned fewer words across conditions. The cold pressor primarily influenced neutral learning in high and low hostile participants. Additionally, primacy and recency effects of the AAVLT were replicated. PMID- 17365101 TI - Effects of amino acid antagonists on spontaneous dorsal root activity and evoked dorsal horn field potentials in an isolated preparation of rat spinal cord. AB - Fast and slow dorsal horn field potentials and spontaneous dorsal root activity were recorded from 19-23-day-old rat isolated spinal cord preparations. The effects of GABA, glycine, and glutamate antagonists were tested on these recordings. CNQX, an AMPA/kainate antagonist, reduced all 3 components of the dorsal horn field potential whereas MK801, an NMDA ion channel antagonist, reduced the fast S2 component and the slow wave. Both reduced spontaneous dorsal root activity. NMDA antagonists, D-AP5, 7-chlorokynurenic acid and arcaine, and the metabotropic glutamate antagonists L-AP3 and ethylglutamic acid, while having little effect on the fast components of the field potential, all reduced the slow component. The GABA antagonist, bicuculline, and the glycine antagonist, strychnine, while having no effect on the fast S1 and slow components of the field potential, reduced both the fast S2 component of the field potential and spontaneous dorsal root activity. These results suggest that non-NMDA glutamate receptors are involved in low and high threshold transmission to dorsal horn neurones while NMDA and metabotropic glutamate receptors are primarily involved in high threshold transmission and both GABA and glycine have roles in the transmission or modulation of sensory information within the dorsal horn of the cord. PMID- 17365102 TI - The control of parameters within the therapeutic range in neuromuscular electrical stimulation. AB - The purpose of this article was to investigate the pattern of differences among three parameters according to the increased level of the muscle force obtained in response to neuromuscular electrical stimulation (NMES). Ten healthy subjects were enrolled in this study, which involved applying NMES to the wrist extensor of the nondominant side. The threshold intensity that induced target motion was determined at first and NMES was then applied while changing three parameters. The muscle force was measured by means of a dynamometer for each parameter. Thus, the increased pattern of the muscle force was compared for each parameter. Compared with the duration or the frequency, the increase of the muscle force that accompanied the increase of intensity was more prominent. When the duration was doubled, the increase of muscle force was more evident at threshold intensity than at high intensity (p < .01). When the intensity was doubled, the increase of muscle force was more prominent at 0.2 than at 0.4 milliseconds duration (p < .01). However, there was no such interaction between the increase of the frequency and either the duration or the intensity. The data suggest that stimulus intensity may be the most effective parameter that can be used to enhance the strengthening of the muscle. PMID- 17365103 TI - The eyes of anencephalic babies: a morphological and immunohistochemical evaluation. AB - This study studied the eyes of three anencephalic stillborns to evaluate whether brain degeneration affected eye development and/or survival. The study encompassed histology, scanning electronmicroscopy, and immunocytochemistry. The corneae were otherwise normal except for the presence of blood vessels in the stroma and the posterior surface of the cornea demonstrated wrinkles. Synaechia was present and the lens had occasional vacuolated cells. The retinae had normal layers in most regions except the center where fibroblasts infiltration was observed. The optic nerve was atypical and composed of aggregates of disoriented fibroblasts and disoriented nerve fibers. Anti-cleaved caspase 3 immunocytochemistry revealed only few positive dying cells in the visual cell layer. Antineurofilament 200 reactions demonstrated positive ganglion cells even in the anencephalic eyes. The choroids in anencephaly had more VEGF positive sites, indicating vascularization in both control and anencephalic eyes. If the brains degenerate before retinal maturation, then such degenerations may not have an effect on subsequent retinal development except for the degeneration of the nerve fiber layer. If the brains degenerate after retinal maturation, then the survival of the retinae does not appear to rely on its linkage with the brain at birth, again apart from the degeneration of nerve fibers. PMID- 17365104 TI - Executive functions in morality, religion, and paranormal beliefs. AB - Moral, religious, and paranormal beliefs share some degree of overlap and play important roles in guiding peoples' behavior. Although partly cultural phenomena, they also have neurobiological components based on functional neuroimaging studies and research in clinical populations. Because all three show relationships to prefrontal system functioning, the current study examined whether they related to executive functions as measured by the Executive Function Inventory in a community sample. As in previous research, religious beliefs related positively to both moral attitudes and paranormal beliefs. Moral attitudes, however, did not relate to paranormal beliefs. Paranormal beliefs related inversely to impulse control and organization, whereas small positive correlations occurred between traditional religious beliefs, impulse control, and empathy. Moral attitudes, on the other hand, showed consistent positive correlations with all executive functions measured, independent of demographic influences. These findings concordantly support that prefrontal systems play a role in morality, religion, and paranormal beliefs. PMID- 17365105 TI - A wrist-walker exhibiting no "Uner Tan Syndrome": a theory for possible mechanisms of human devolution toward the atavistic walking patterns. AB - After discovering two families with handicapped children exhibiting the "Uner Tan syndrome," the author discovered a man exhibiting only wrist-walking with no primitive mental abilities including language. According to his mother, he had an infectious disease with high fever as a three months old baby; as a result, the left leg had been paralyzed after a penicilline injection. This paralysis most probably resulted from a viral disease, possibly poliomyelitis. He is now (2006) 36 years old; the left leg is flaccid and atrophic, with no tendon reflexes; however, sensation is normal. The boy never stood up on his feet while maturing. The father forced him to walk upright using physical devices and making due exercises, but the child always rejected standing upright and walking in erect posture; he always preferred wrist-walking; he expresses that wrist-walking is much more comfortable for him than upright-walking. He is very strong now, making daily body building exercises, and walking quite fast using a "three legs," although he cannot stand upright. Mental status, including the language and conscious experience, is quite normal. There was no intra-familiar marriage as in the two families mentioned earlier, and there is no wrist-walking in his family and relatives. There were no cerebellar signs and symptoms upon neurological examination. The brain-MRI was normal; there was no atrophy in cerebellum and vermis. It was concluded that there may be sporadic wrist-walkers exhibiting no "Uner Tan Syndrome." The results suggest that the cerebellum has nothing to do with human wrist-walking, which may rather be an atavistic trait appearing from time to time in normal individuals, indicating a live model for human reverse evolution. It was concluded that pure quadrupeds may sporadically appear due to random fluctuations in genotypes and/or environmental factors (hormonal or nutritional); the human development following the human evolution may be stopped in the stage of transition from quadrupedality to bipedality. That is, the activity of the philogenetically youngest supraspinal centers for bipedal walking responsible for suppression of the older supraspinal centers for quadrupedal gait may be interrupted at the atavistic level due to genetic and/or environmental factors. Consequently, it is assumed that these individuals prefer their natural wrist-walking to move around more quickly and efficiently. PMID- 17365106 TI - A theory of neurophysics and quantum neuroscience: implications for brain function and the limits of consciousness. AB - The authors have assumed there are specific temporal patterns of complex electromagnetic fields that can access and affect all levels of brain space. The article presents formulae and results that might reveal the required field configurations to obtain this access and to represent these levels in human consciousness. The frequency for the transition from an imaginary to real solution for the four-dimensional human brain was the wavelength of hydrogen whereas the optimal distance in space was the width of a proton or electron. The time required to expand one Planck's length as inferred by Hubble's constant for the proton was about 1 to 3 ms, the optimal resonant "point duration" of our most bioeffective magnetic fields. Calculations indicated the volume of a proton is equivalent to a tube or string with the radius of Planck's length and the longitudinal length of m (the width of the universe). Solutions from this approach predicted the characteristics of many biological phenomena, seven more "dimensions" of space between Planck's length and the level of the proton, and an inflection point between increments of space and time that corresponded to the distances occupied by chemical bonds. The multiple congruencies of the solutions suggest that brain space could contain inordinately large amounts of information reflecting the nature of extraordinarily large increments of space and time. PMID- 17365107 TI - Involvement of p42/44 MAPK in the effects of ethanol on secretion of insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-1 in primary cultured rat hepatocytes. AB - This article investigates the effects of ethanol on Insulin-like growth factor (IGF)-I secretion, p42/44 mitogen-activated protein kinase (MAPK) activity, and IGF binding protein (IGFBP-1 secretion) in primary cultured rat hepatocytes. The p42/44 MAPK activity increased with the ethanol concentration compared to control after ethanol treatment. The secretion of IGF-I significantly increased compared to control, but IGFBP-1 secretion was inhibited. Treatment with 4-methylpyrazole blocked the IGF-I and IGFBP-1 secretion and p42/44 MAPK activity. Increased IGF-I secretion and inhibited IGFBP-1 secretion due to ethanol-induced p42/44 MAPK activity (at 30 min) was blocked by treatment with PD98059. Taken together, these results suggest that ethanol is involved in the modulation of the secretion of IGF-I and IGFBP-1 by p42/44 MAPK in primary cultured rat hepatocytes. In addition, inhibition of p42/44 MAPK activity by ethanol occurs via the activity of ADH. PMID- 17365108 TI - Conduction velocity distribution: early diagnostic tool for peripheral neuropathies. AB - In order to get early information on the functional state of smaller myelinated fibers this article investigated the applicability of conduction velocity distribution on compound action potential recorded in experimentally demyelinated frog sciatic nerve. Conduction velocity distribution histograms were estimated by using the mathematical model the authors enhanced. The results suggest that by using appropriate conduction velocity distribution model the diagnosis time in demyelinating neuropathy may be shortened at least three times as compared with conventional conduction velocity assessment. Therefore, it may be concluded that a well-defined model designed for the estimation of the conduction velocity distribution may be used as a diagnostic tool for the early phase of peripheral demyelinating neuropathies. PMID- 17365109 TI - Reproducibility of trial-based functional MRI on motor imagery. AB - The investigation of the reproducibility in functional MRI (fMRI) is an important step in the quantification and analysis of paradigm-related brain activation. This article reports on reproducibility of cortical activation characterized by repeated fMRI runs (10 times) during the performance of a motor imagery and a passive auditory stimulation as a control task. Two parameters, the size of activation and BOLD signal contrast, were measured from regions-of-interest for 10 subjects across different threshold conditions. The variability of these parameters was normalized with respect to the mean obtained from 10 runs, and represented as the intrasession variability. It was found that the variability was significantly lower in the measurement of BOLD signal contrast as compared to the measurement of the size of activation. The variability of the activation volume measurement was greater in the motor imagery task than in the auditory tasks across all thresholds. This task-dependent difference was not apparent from the measurement of the BOLD signal contrast. The presence of threshold dependence in the variability measurement was also examined, but no such dependency was found. The results suggest that a measurement of BOLD signal itself is a more reliable indicator of paradigm-related brain activation during repeated fMRI scans. PMID- 17365110 TI - Peripheral joint cooling increases spinal reflex excitability and serum norepinephrine. AB - To understand better how reflex excitability is altered with peripheral joint cooling, the authors set out to determine whether a cryotherapy treatment applied to the ankle would increase plasma norepinephrine and result in a heightened H:M ratio. Twenty-two adults were admitted to the hospital on two occasions. During one admission, subjects had ice applied to their ankle and in the other admission a bag of room temperature marbles was applied. Soleus Hmax, Mmax, H:M ratio, and plasma norepinephrine were recorded at baseline as well as immediately, 10, and 20 min post application, and 10 and 20 min post removal. Norepinephrine was greater immediately and 10 min post ice application (p < .05). Hmax, Mmax, and the H:M ratio were greater at 10 and 20 min post application and at 10 and 20 min post removal (p < .05). Elevated plasma norepinephrine suggests that peripheral cooling results in release of neurotransmitters from the central nervous system. Joint cooling has both peripheral and central effects. PMID- 17365111 TI - Role of serotonin-1A receptors in restraint-induced behavioral deficits and adaptation to repeated restraint stress in rats. AB - 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-hydroxy tryptamine (5-HT; serotonin)-1A agonist was used to evaluate the role 5-HT-1 A receptors in restraint-induced behavioral deficits and adaptation to repeated restraint stress in rats. Animals were injected with 8-OH-DPAT at a dose of 0.25 mg/kg 1 h before exposing to an episode of 2 h/day restraint stress daily for 5 days. Effects of drug administration and restraint stress on 24 h cumulative food intakes were monitored daily. Intensity of 8-OH-DPAT-induced serotonin syndrome was also monitored each day before submitting animals to the episode of stress. Exposure to the first episode of 2 h restraint stress resulted in a decrease in 24 h cumulative food intake and an attenuation of 8-OH-DPAT-induced serotonin syndrome monitored next day. The deficits attenuated following 2nd and 3rd 2 h/day restraint were not observed following the 4th and 5th 2 h/day restraint. The decreases of food intake following 1st and 2nd day restraint sessions were smaller in 8-OH-DPAT than saline-injected animals. Administration of 8-OH-DPAT on day 6 elicited comparable serotonin syndrome in unrestrained and repeatedly restrained groups. Brain 5-HT metabolism decreased in unrestrained but not repeatedly restrained animals. The results suggest that a decrease in serotonergic neurotransmission is involved in restraint-induced behavioral deficits while a normalization of serotonin neurotransmission due to desensitization of somatodendritic 5-HT-1A receptors may help cope with the stress demand to produce adaptation to stress. PMID- 17365112 TI - Event-related potentials to visual, auditory, and bimodal (combined auditory visual) stimuli. AB - The purpose of this study was to investigate the response properties of event related potentials to unimodal and bimodal stimulations. The amplitudes of N1 and P2 were larger during bimodal evoked potentials (BEPs) than auditory evoked potentials (AEPs) in the anterior sites and the amplitudes of P1 were larger during BEPs than VEPs especially at the parieto-occipital locations. Responses to bimodal stimulation had longer latencies than responses to unimodal stimulation. The N1 and P2 components were larger in amplitude and longer in latency during the bimodal paradigm and predominantly occurred at the anterior sites. Therefore, the current bimodal paradigm can be used to investigate the involvement and location of specific neural generators that contribute to higher processing of sensory information. Moreover, this paradigm may be a useful tool to investigate the level of sensory dysfunctions in clinical samples. PMID- 17365113 TI - Sex differences in human lymphocyte Na,K-ATPase as studied by labeled ouabain binding. AB - Lymphocytes Na,K-ATPase is a plasma membrane enzyme that is up-regulated under lymphocytes activation. It is also studied as a model of brain cells Na,K-ATPase. Data about sex-related specificities of the enzyme are not available. The binding of tritium-labelled ouabain to lymphocyte plasma membrane Na,K-ATPase was studied in healthy volunteers of both sexes. The binding interactions were expressed in terms of K(D) and B(Max). The first parameter is related to the affinity of ouabain for the enzyme whereas the second one is related to its density on the cell membrane. Distinct sex-related differences were found. Whereas in males there is a significant direct correlation between the parameters K(D) and B(Max), in females this is not present. However, in females there is a significantly lower K(D) in the 25-37 age range. The latter result probably reflects the expression of subunit variants giving a greater affinity for ouabain. This circumstance may be relevant both to lymphocytes' ability to be activated and to brain function, if one admits that lymphocyte Na,K-ATPase faithfully represents the brain-borne one. PMID- 17365114 TI - Yellow filters, magnocellular responses, and reading. AB - It has been suggested that yellow filters may increase magnocellular responsivity. This suggestion was, in large part, based on the assumption that the S-cones inhibit the magnocellular system. However, the evidence invoked to justify this assumption is only indirect. A previously reported direct electrophysiological investigation of this issue has found that S-cone input to the magnocellular system actually sum with L-and M-cone inputs. Therefore, the notion that yellow filters enhance magnocellular responses by reducing inhibition from S-cones cannot be maintained. PMID- 17365115 TI - Brief exposures to theta-burst magnetic fields impair the consolidation of food induced conditioned place preference. AB - Theta-burst magnetic fields (1 microT) designed to mimic electrical stimuli employed in vitro to affect long-term potentiation have been previously shown to impair the acquisition of conditioned fear. In the current study, the authors were interested in investigating whether similar magnetic fields could affect the consolidation of food-induced conditioned place preference. Fourteen male Wistar rats were exposed to a theta-burst magnetic field (1 s pulse of 5 trains of an LTP-evoking pattern) continuously or with either a 5 s or 10 s interstimulus interval for 15 min immediately following 6 daily conditioning trials (15 min/day) in a place preference apparatus. Testing demonstrated the durations in the food-paired chamber was significantly shorter for all of the magnetic field exposed groups compared to the sham-exposed group (they remained for longer periods in the food-paired chamber, typical of normal rats). In addition, the group exposed continuously to the LTP-magnetic field (1-ms interstimulus duration) displayed the least time in the food-paired chamber. The treatments explained 80% of the variance in durations within the experimental setting. These results suggest that exposures to theta-burst magnetic fields elicit amnesic effects for contextual stimuli. PMID- 17365116 TI - Development of the Executive Personal Finance Scale. AB - There is accumulating evidence that prefrontal systems play an important role in management of personal finances, based on studies using clinical populations, functional neuroimaging, and both subjective and objective neuropsychological measures. This study developed the Executive Personal Finance Scale (EPFS) as a specific self-rating measure of executive aspects of personal money management. The resulting 20-item scale had good reliability and showed four factors: impulse control, organization, planning, and motivational drive. Validity was evidenced by correlations with income, credit card debt, and investments. The EPFS also showed logical correlations with compulsive buying and money attitudes. Second order factor analysis of the EPFS and other scales revealed two higher-order factors of personal finance: cognitive (e.g., planning, organizing) and emotional (e.g., anxiety, impulse-spending, prestige). The EPFS shows good psychometric properties, is easy to use, and will make a convenient complement to other research methodologies exploring the neural basis of personal finance management. PMID- 17365117 TI - Functional recovery and expression of GDNF seen in photochemically induced cerebral infarction. AB - Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor involved in the survival and proliferation of neurons. However, there have been few reports examining the relationship between GDNF and functional recovery after cerebral infarction. The authors investigated the change in the expression of GDNF proteins during functional recovery in rats following photochemically induced cerebral infarctions. Functional recovery for the first 14 days after the infarction was evaluated using a beam-walking test. The number of GDNF-like immunoreactive cells around the infarction were counted at various times (24 h, 72 h, 7 days, and 14 days) post-infarction. Immunohistochemical analysis of brain sections showed that the expression of GDNF-like immunoreactive cells was significantly increased in the temporal cortex until 7 days on the side ipsilateral to the infarction, and had decreased by 14 days. Likewise, the functional recovery of paralysis was substantial until 7 days post-infarction, after which the improvement was mild. Therefore, the expression of GDNF protein might have some relationship with the functional recovery of paralysis. There are great hopes that GDNF could be used as a therapeutic agent for cerebral infarction. PMID- 17365118 TI - Correlative study of the cognitive impairment, regional cerebral blood flow, and electroencephalogram abnormalities in children with Down's syndrome. AB - The aim of this study was to investigate possible correlations of the cognitive impairment with abnormalities of regional cerebral blood flow and electroencephalogram in children with (Down's Syndrome) DS. Nine patients with DS were evaluated by single photon emission computed tomography (SPECT) in combination with clinical findings, electroencephalography (EEG), and magnetic resonance imaging (MRI). In cases with IQs below 40, there were one or more findings of abnormal EEG/MRI and brain perfusion SPECT. In 6 cases (66.7%) EEG findings were normal, but 3 (33.3%) had abnormal EEG findings. Perfusion abnormalities were most pronounced in the fronto-parieto-temporal region in the form of hypoperfusion (n = 5) and in the right hemisphere (n = 5) than the left hemisphere (n = 1). These findings suggest that the children with DS had varying levels of structural, perfusion, and electrophysiological abnormalities in the brain and these abnormalities were reflected by measurable alterations of the cognitive functions. PMID- 17365119 TI - The effects of neurofeedback training in the cognitive division of the anterior cingulate gyrus. AB - This study examines the efficacy of neurofeedback training in the cognitive division of the anterior cingulate gyrus and describes its relationship with cortical regions known to be involved in executive functions. This study was conducted with eight non-clinical students, four male and four female, with a mean age of twenty-two. Learning occurred in the ACcd at significant levels over sessions and in the anterior regions that receive projections from the AC. There appears to be a multidimensional executive circuit that increases in the same frequency in apparent synchrony with the AC and it may be possible to train this sub-cortical region using LNFB. PMID- 17365120 TI - Normative data and a short form of the Barratt Impulsiveness Scale. AB - The Barratt Impulsiveness Scale is one of the most commonly used scales to measure impulsivity. It has demonstrated validity in several neuropsychiatric populations and correlates with objective neuropsychological measures and impulsivity-related behaviors in healthy individuals. Neuroimaging studies show that BIS scores relate to prefrontal structure and function, as well as central serotonergic function. This study reports normative data and demographic influences in a community sample (n = 700). A 15-item short form of the BIS (BIS 15) is presented that retains the 3-factor structure (nonplanning, motor impulsivity, and attention impulsivity), and maintained good reliability and validity. PMID- 17365121 TI - The role of prefrontal systems in sexual behavior. AB - Research from a variety of methodologies is demonstrating a role for neuroanatomical structures in different aspects of sexual behavior. This article reviews the particular contribution of prefrontal-subcortical systems to sexual behavior, including regions of prefrontal cortex (i.e., dorsolateral, medial, and orbitofrontal cortex), and associated subcortical structures (i.e., basal ganglia and thalamus). Findings are integrated from functional neuroimaging and clinical studies in humans, as well as animal studies, which convergently illustrate the role of different prefrontal systems. In addition to providing a clearer understanding of normal sexual behavior, appreciation of prefrontal systems in sexual behavior has implications for disorders of sexual behavior. Consistent with their role in other forms of cognition, emotion, and behavior, prefrontal systems serve in an executive capacity to regulate sexual behavior. PMID- 17365122 TI - Effect of colloidal silver against the cytotoxicity of hydrogen peroxide and naphthazarin on primary cultured cortical astrocytes. AB - One major pathogenesis in degenerative disorders of the central nervous system (CNS), including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemia, is the oxidative stress induced by reactive oxygen species (ROS). The present study investigated the protective effect of colloidal silver, which is widely marketed as a dietary supplement for diseases like diabetes, AIDS, cancer, and various infections, upon the oxidative brain damage induced by H(2)O(2) or naphthazarin treatment. LDH release from primary cultured astrocytes was enhanced by naphthazarin treatment, and this elevation of the LDH concentration in medium was blocked by colloidal silver treatment. However, hydrogen peroxide was little affected by the colloidal silver. Fluorescence of DCF (peroxides) increased in astrocytes incubated with hydrogen peroxide or naphthazarin compared to the control. When exposed to naphthazarin-induced cells, ROS formation appeared to be reduced by colloidal silver. However, intracellular ROS formation in hydrogen peroxide-treated cells slightly reduced by colloidal silver. These results suggest that colloidal silver has a protective activity against the oxidative stress induced by naphthazarin, but not by hydrogen peroxide. PMID- 17365123 TI - The relationship between teething and handedness. AB - The aim of this study was to evaluate the role of tooth eruption sequences as an indicator of handedness. The investigation was carried out on 92 healthy children. The questionnaire form was filled out for each child. The form consisted of two parts. In the first part there were questions to determine the demographic features of the children. The second part consisted of the questions to clarify the eruption time and sequence of first primary teeth. Hand preference was evaluated by placing colored pencils directly in front of the child, who was asked to write an "X" on a piece of paper with each pencil. According to left-, right-, and indetermined handedness, all children regardless of sex were divided into three groups. The data were analyzed for statistical evaluation using tests for the difference between two population propositions. The mean eruption time of the first tooth in children was 7.5 +/- 1.7 months. The eruption time was found similar in both groups. No statistically significant difference was determined between the teeth eruption time and handedness (p >.05). The first tooth erupted was generally the lower central incisor. There was no difference tooth eruption and sex, gestation week (p >.05). No statistically significant difference was found between the teeth eruption time and sequence of the primary teeth (p >.05). There was statistically significant difference between sequence of the tooth eruption and handedness (p <.001). Consequently, the tooth eruption sequences may play an important role as an indicator in handedness. PMID- 17365124 TI - The investigation of Chlamydophila pneumoniae in patients with multiple sclerosis. AB - Totally 32 cerebrospinal fluid samples from Multiple sclerosis (MS) patients were collected. DNA was extracted by High Pure PCR Template Preparation Kit. Two genomic segments, outer membrane protein genes ompA and omp9, were targeted for the detection of C. pneumoniae DNA in the samples by PCR tests. To detect ompA, a nested-PCR assay was designed, whereas for omp9, a PCR-Enyzme immunoassay (PCR EIA) depending on streptavidin-biotin capture and dig detection of the PCR products was performed. C. pneumoniae DNA was not detected by each assays in patient samples. PMID- 17365125 TI - Ambulatory effects of brief exposures to magnetic fields changing orthogonally in space over time. AB - In a within-subject design adult male rats were exposed for 15 min once per day or night to one of two patterns of complex magnetic fields (0.5 to 1 micro T) rotated in space once every 2 s or 20 s through each of the three spatial dimensions and then simultaneously through all three dimensions. Open field behavior was then measured for ambulation, defecation, and grooming. The rats displayed about twice the ambulation after when the fields had been present compared to when they had not. The burst-firing field elicited the greatest ambulation when presented during the night whereas the frequency-modulated pattern elicited the greatest ambulation when presented during the day. These results suggest that robust behavioral changes can occur when rats are exposed for 15 min to complex spatiotemporal configurations of weak magnetic fields. PMID- 17365126 TI - Attractiveness of natural faces compared to computer constructed perfectly symmetrical faces. AB - Attractiveness of natural faces was compared to perfectly symmetrical faces constructed on the computer from digitized photographs, in order to assess the role of left-right symmetry in beauty assessment. Three different groups of participants viewed separate series of sequentially presented faces (natural faces, left-left, and right-right) and provided attractiveness ratings on a 5 point Likert scale. The results revealed statistically significant lower ratings for the computer constructed left-left and right-right compared to the natural faces. The discussion is in the context of a biological trend away from perfect symmetry in primates consequent to adaptive evolutionary alteration favoring functional asymmetry in the brain, perception, and face. PMID- 17365127 TI - Clinical case: vermis hypoplasia with features of Smith-Lemli-Opitz syndrome. AB - This article attempts to describe a very unusual case of a boy aged 15, who has had intractable epileptic phenomena, mental retardation, megalocephaly, micrognathy, syndactyly, small tongue, hypoplastic genitalia, gynecomasty, obesity, and slight left body hemiatrophy. Neurologically the patient has had hypotonia of the lower limbs, cerebellar dysfunction including horizontal nystagmus, bilateral intention tremor, dysdiadokokinesia, gait ataxia. The clinical investigation revealed low plasma cholesterol and hypoplasia of the vermis in MRI. The epileptic phenomena were intractable and polymorphous. One should have thought that this is an unusual case of Smith-Lemli-Opitz syndrome associated with features of Joubert syndrome. PMID- 17365128 TI - Vagus, hypoglossal, and median nerves in human development. AB - In spite of the wealth of literature on the changes of the neurons in development of the brainstem and the spinal cord in vertebrates, the alterations of the cranial nerves and somatic nerves during the prenatal period was largely neglected. Particularly in humans, little information was available. The article reports the changes in the vagus, hypoglossal, and median nerves in the fetus and term babies. The changes of proportion of different-sized nerve fibers are documented. The patterns were different in the three nerves and the hypoglossal nerve seemed to show "pruning" of fibers during this period. PMID- 17365129 TI - Early social isolation decreases the expression of calbindin D-28k and dendritic branching in the medial prefrontal cortex of the rat. AB - Social isolation in rodents is the most well characterized animal model for early stressful experiences and their neurobehavioral consequences. The present study analyzed the effects of early social isolation on the expression of the calcium binding protein calbindin-D28k (CAD) and dendritic arborization in the medial prefrontal cortex (mPFC) of the rat. Sprague-Dawley male rats were reared either under isolation or social conditions from 21 to 51 postnatal days. At the end of this period the animals were behaviorally evaluated in the open-field test, sacrificed, and mPFC serial sections were processed either for immunocytochemical labeling against CAD or Golgi-Cox-Sholl staining. Isolated-reared rats exhibited a dramatic decrease in the number of CAD immunoreactive neurons and a significant dendritic atrophy of layer II/III pyramidal cells in association with a reduced exploratory behavior. PMID- 17365130 TI - Handedness and cognition across the healthy lifespan. AB - The relationship between handedness and cognitive function varies across studies, perhaps partly due to the many medical and psychiatric conditions with known cognitive impact. This study examined cognitive performance in 643 healthy individuals (age 5-82) who were categorized as strongly right-handed, moderately right-handed, or left/mixed-handed. Cognitive differences emerged, as left/mixed handed individuals demonstrating superior psychomotor speed and cognitive flexibility, and strongly and moderately right-handed individuals exhibiting better time estimation skills. No interaction-among handedness, sex, and age were found. These findings indicate cognitive differences associated with handedness exist independent of medical and psychiatric confounds. Further work is needed to clarify these findings. PMID- 17365131 TI - Executive dysfunction screening test for neuropsychiatric disorders. AB - The Analogies Understanding Test (AUT) was developed as a brief cognitive screening task of executive problem solving. A few of the test items at the beginning are "facilitated" as a means of engaging patients. Individuals with schizophrenia and mild Alzheimer's Disease (AD) made significantly less correct responses than their control groups. The schizophrenia patients, but not AD patients, made significantly more perseverations than controls on the AUT. As expected, AUT performance in schizophrenia patients correlated with the Wisconsin Card Sorting test measures. Preliminary findings suggest that the AUT test may be useful as a measure of executive dysfunction in neuropsychiatric patients. PMID- 17365132 TI - Effectiveness of combined acupuncture therapy and conventional treatment on shoulder range of motion and motor power in stroke patients with hemiplegic shoulder subluxation: a pilot study. AB - The aim of this study was to elucidate the effects of combined conventional rehabilitation therapy and acupuncture on the active shoulder range of motion (ROM) and motor power in stroke patients with hemiplegic shoulder subluxation. Twenty-one patients received a combination of acupuncture and rehabilitation treatment at a hospital, and their active shoulder ROM and motor power were assessed at admission and discharge. The therapy produced significant improvements in joint mobility, such as in flexion, extension, internal rotation, external rotation, abduction, and adduction (p < .001), and in motor power (p < .05) in stroke patients with hemiplegic shoulder subluxation. PMID- 17365133 TI - Inhibitory effect of Yangkyuk-Sanhwa-Tang on inflammatory cytokine production in peripheral blood mononuclear cells from the cerebral infarction patients. AB - Yangkyuk-Sanhwa-Tang (YST) has been used for the Soyangin cerebral infarction (CI) patients according to Sasang constitutional philosophy. This study investigated the effect of YST on production of various cytokines using peripheral blood mononuclear cells (PBMCs) from the Soyangin CI patients group. The amount of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and tumor necrosis factor-alpha increased in the lipopolysaccharide (LPS)-treated cells compared with unstimulated-cells. YST inhibited IL-1alpha, IL-1beta, and IL-8 production in PBMCs stimulated with LPS. These data suggest that YST has a regulatory effect on cytokine production, which might explain its beneficial effect in the treatment of Soyangin CI patients. PMID- 17365134 TI - Comparison of the polymorphisms of androgen receptor gene and estrogen alpha and beta gene between adolescent females with first-onset major depressive disorder and controls. AB - This study was to elucidate the role of genetic variation in androgen receptor (AR) gene, estrogen receptor alpha (ER alpha) and ER beta gene on first-onset major depressive disorder (MDD) in female adolescents. Results showed that AR gene in MDD group have shorter microsatellites' length, and ER beta gene have shorter microsatellites' length and higher rates of S alleles, SS, genotype, and lower rate of LL genotype than control group. The results suggest that shorter length of AR and ER beta gene microsatellites might influence the onset of MDD in female adolescents, a further elucidation of the mechanisms is warranted. PMID- 17365135 TI - Cross-cultural assessment of neuropsychological performance and electrical brain function measures: additional validation of an international brain database. AB - Previous studies have revealed significant differences in performance on nonlanguage dependent cognitive tests across international settings among younger individuals, with less pronounced differences evident among older individuals (>54 years of age). The present study examined a broad range of cognitive performance as well as electrophysiological indices of brain function in a multisite and international context. A total of 200 individuals in the United States, 233 individuals in Europe, and 829 individuals in Australia were administered a standardized computerized neuropsychological battery, and complementary electroencephalogram (EEG) recordings were completed. Results revealed no significant differences in cognitive function or electrophysiology across the three continents. Similarly, although there was a main effect for age, the interaction between age and continent was not significant in any of the omnibus analyses. These findings indicate a high degree of similarity in neurocognitive and electrophysiological function among individuals residing in developed Western cultures, consistent with a traitlike status and the high heritability of the EEG. PMID- 17365137 TI - Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. AB - Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8 week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day 1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to "negative" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED) PMID- 17365138 TI - Final report on the safety assessment of phytantriol. AB - Phytantriol is an alcohol used in around 100 cosmetic products at concentrations ranging from 0.0002% to 1.0%, although uses at concentrations up to 3% are under development. Phytanriol is supplied at 95.2% and 96.0% purity. Impurities include water, sulphated ash, heavy metals, and a diastereomer of Phytantriol, 3,7,11,15 tetramethyl-1,2,3,4-tetrahydroxyhexadecane. Dermal penetration is low; skin permeability was calculated as log Kp = - 1.734. Oral LD50 values in mice and rats were reported to be > 5000 mg/kg. Ocular application of 100% Phytantriol did cause severe corneal damage in some animals, at 23% in diethyl phthalate only slight corneal opacity was seen, and at 10% transient opacity was seen, which resolved by 48 h. Phytantriol at 100% was a severe skin irritant in animal tests. Phytantriol at 3% and 10% in diethyl phthalate produced only slight erythema, which cleared by 48 h. Phytantriol, in the Longhorn egg chorioallantoic membrane assay, was found to have almost no irritation potential when tested at 3% concentration in corn oil. Phytantriol at 25% did produce sensitization in a maximization test, but concentrations of 1% and lower did not cause a sensitization response. Phytantriol is neither phototoxic nor photoallergenic. Phytantriol did not induce aberrations in cultured human lymphocytes, when tested within cytotoxicity limits, nor was it mutagenic in Ames tests, with or without metabolic activation. None of 101 human volunteers reacted initially or to challenge patches of 3% Phytantriol in corn oil. In another investigation of 227 volunteers induced and challenged with 3% Phytantriol in 70:30 ethyl alcohol/water, one person had a mild reaction to the first induction patch; this was the only positive reaction during the induction and challenge phases for all of the volunteers. Phytantriol had no adverse effects in any of 206 volunteer subjects in a repeat insult patch test at 5%. Although data were not available with which to assess reproductive and developmental toxicity and carcinogenic potential, there were no structural alerts suggesting that these end points should be of concern. Dermal penetration is low, and Phytantriol is not genotoxic. Although products containing this ingredient may be aerosolized, typical particle sizes for cosmetic aerosol products are larger than are respirable. Although this ingredient can be irritating and produce sensitization reactions at high concentrations, such effects are absent at lower concentrations. The Panel concluded that cosmetic products could be formulated at concentrations as high as 3% without significant irritation or sensitization. PMID- 17365139 TI - Final report on the safety assessment of polyethylene. AB - Polyethylene is an ethylene polymer used for a variety of purposes in cosmetics as an abrasive, adhesive, binder or bulking agent, an emulsion stabilizer, a film former, an oral care agent, and as a nonaqueous viscosity-increasing agent. Polyethylene is also used in food packaging materials and medical products, including prosthetics. The molecular weight of Polyethylene as used in cosmetics varies over a wide range. The lowest reported molecular weight is 198 Daltons and the highest is 150,000. In any given polymer preparation, there can be a broad range of molecular weights. Cellular and tissue responses to Polyethylene, determined as part of implant biocompatibility testing, include fibrous connective tissue build-up around the implant material that varies as a function of the physical form of the implant material. Specific assays for osteoblast proliferation and collagen synthesis demonstrated a reduction as a function of exposure to Polyethylene particles that is inversely related to particle size. The effect of Polyurethane particles on monocyte-derived macrophages, however, had a stimulatory effect, prolonging the survival of these cells in culture. The LD50 for Polyethylene, with an average molecular weight of 450, in rats was > 2000 mg/kg. For Polyethylene with an average molecular weight of 655, the LD50 was > 5.0 g/kg. Toxicity testing in rats shows no adverse effects at Polyethylene (molecular weight not given) doses of 7.95 g/kg or at 1.25%, 2.50%, or 5.00% in feed for 90 days. Dermal irritation studies on rabbits in which 0.5 g of Polyethylene (average molecular weight of 450) was administered in 0.5 ml of water caused no irritation or corrosive effects; Polyethylene with an average molecular weight of 655 was a mild irritant. Polyethylene (average molecular weight of 450) did not cause dermal sensitization in guinea pigs tested with 50% Polyethylene (w/w) in arachis oil BP. Polyethylene, with a molecular weight of 450 and a molecular weight of 655, was a mild irritant when tested as a solid material in the eyes of rabbits. Rabbit eyes treated with a solution containing 13% Polyethylene beads produced minimal irritation and no corneal abrasions. No genotoxicity was found in bacterial assays. No chemical carcinogenicity has been seen in implantation studies, although particles from Polyethylene implants can induce so-called solid-state carcinogenicity, which is a physical reaction to an implanted material. Occupational case reports of ocular irritation and systemic sclerosis in workers exposed to Polyethylene have been difficult to interpret because such workers are also exposed to other irritants. Clinical testing of intrauterine devices made of Polyethylene failed to conclusively identify statistically significant adverse effects, although squamous metaplasia was observed. The Cosmetic Ingredient Review (CIR) Expert Panel did not expect significant dermal absorption and systemic exposure to large Polyethylene polymers used in cosmetics. The Panel was concerned that information on impurities, including residual catalyst and reactants from the polymerization process, was not available. The Panel considered that the monomer unit in Polyethylene polymerization is ethylene. In the United States, ethylene is 99.9% pure. The other 0.1% includes ethane, propylene, carbon dioxide, carbon monoxide, sulfur, hydrogen, acetylene, water, and oxygen. The Panel believed that the concentration of these impurities in any final polymer would be so low as to not raise toxicity issues. Safety tests of cosmetic-grade Polyethylene have consistently failed to identify any toxicity associated with residual catalyst. Although it was reported that one process used to cross-link Polyethylene with an organic peroxide, this process is not currently used. In addition, cosmetic-grade Polyethylene is not expected to contain toxic hexanes. The Panel was concerned that the only genotoxicity data available was nonmammalian, but taking this information in concert with the absence of any chemical carcinogenicity in implant studies suggests no genotoxic mechanism for carcinogenicity. The solid state carcinogenicity effect was not seen as relevant for Polyethylene as used in cosmetics. The available data support the conclusion that Polyethylene is safe for use in cosmetic formulations in the practices of use and concentrations described. PMID- 17365141 TI - 2006 American College of Toxicology Distinguished Service Award Lecture: Has quantitative risk assessment been of benefit to the science of toxicology? AB - Quantitative approaches to evaluating the risks of chemical toxicity entered the lives of toxicologists in the mid-1970s, and the continuing interaction of toxicology and risk assessment has been of benefit to both disciplines. I will summarize the origins of the interaction, the reasons for it, and the difficult course it has followed. In doing so, I will set the stage for a discussion of how the type of thinking that informs risk-based decision-making provides important benefits to the continuing development of the science of toxicology. There will continue to be societal pressure for the development of reliable knowledge about the public health importance of the enormous variety of chemical exposures we all incur, from conception to death. Risk assessment is the framework used to organize and convey that knowledge. Toxicology is the principle discipline used to give scientific substance to that framework. Social acceptance of every manifestation of the modern chemical age requires high assurance that the public health is not threatened, and that assurance depends upon continued improvements in these two mutually dependent disciplines. PMID- 17365142 TI - The "low dose" hypothesis: validity and implications for human risk. AB - In the late 1990s, a "low dose" hypothesis was proposed based on studies that purported to show that hormonally active environmental agents were causing a variety of effects, mainly reproductive and developmental, at "low doses." The supporters of this hypothesis claim that traditional "high-dose" toxicity studies are not adequate to assess adverse effects from these hormonally active agents in that they do not detect effects that are occurring at "low doses." In addition, it is claimed that these "low dose" effects are occurring at levels comparable to those to which humans are being exposed. These claims have been controversial and expert panels evaluated the evidence behind them in the early 2000s. Although these panels generally concluded that such "low dose" effects were not conclusively established, proponents of the "low dose" hypothesis assert that a large number of more recent studies now provide clear support for their hypothesis. This review carefully examines both recent and older studies that have been cited to support the "low dose" hypothesis, including their relevance for the human population. These include in vivo and in vitro laboratory studies as well as a very limited number of epidemiological investigations. Based on the evidence, it is concluded that these "low dose" effects have yet to be established, that the studies purported to support these cannot be validly extrapolated to humans, and the doses at which the studies have been performed are significantly higher than the levels to which humans are exposed. PMID- 17365143 TI - Effect of clebopride, antidopaminergic gastrointestinal prokinetics, on cardiac repolarization. AB - The inhibition of the potassium current I(Kr) and QT prolongation has been known to be associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. In this study, the authors investigated the cardiac electrophysiological effects of clebopride, a class of antidopaminergic gastrointestinal prokinetic, that has been reported to prolong the QT interval by using the conventional microelectrode recording techniques in isolated rabbit Purkinje fiber and whole-cell patch clamp techniques in human ether-a-go-go related gene (hERG)-stably transfected Chinese hamster ovarian (CHO) cells. Clebopride at 10 microM significantly decreased the Vmax of phase 0 depolarization (p < .05) and significantly prolonged the action potential duration at 90% repolarization (APD90) (p < .01), whereas the action potential duration at 50% repolarization (APD50) was not prolonged. For hERG potassium channel currents, the IC50 value was 0.62 +/- 0.30 microM. Clebopride was found to have no effect on sodium channel currents. When these results were compared with Cmax (1.02 nM) of clinical dosage (1 mg, [p.o.]), it can be suggested that clebopride is safe at the clinical dosage of 1 mg from the electrophysiological aspect. These findings indicate that clebopride, an antidopaminergic gastrointestinal prokinetic drug, may provide a sufficient "safety factor" in terms of the electrophysiological threshold concentration. But, in a supratherapeutic concentration that might possibly be encountered during overdose or impaired metabolism, clebopride may have torsadogenic potency. PMID- 17365144 TI - Potential side effects of dendritic cells pulsed with allogenic melanoma cell lysate in mice. AB - An attempt has been made to investigate the toxicity of cancer immunotherapy based on the dendritic cells pulsed with lysate of allogenic melanoma cell, DM401. Dendritic cells pulsed with lysate of clone M3 were subcutaneously administered once a week eight times to C57BL/6 mice at 0, 2.5, 5, and 10 x 10(7) cells/kg. No changes attributable to the administration were observed in clinical signs and food and water consumption. The administration induced slight increases in body weights, white blood cells, total protein, total cholesterol, triglyceride, phospholipids, and absolute spleen weights, but a slight decrease in albumin/globulin ratio. Microscopic examinations revealed the infiltration of inflammatory cells in the lung, mainly in the pulmonary arteriole, in which the tunica media thickened, and in the pulmonary alveoli and alveolar space. Thickened tunica media of pulmonary arteriole was observed in both males and females at all selected doses. In addition, the subcutis at the test substance application site showed inflammation and fibrosis. In conclusion, lung is a target organ of DM401, and most of the changes including the findings in lung are considered as the immunomodulatory functions of dendritic cells. PMID- 17365145 TI - Polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase P1 in a male Turkish population. AB - Polymorphic genes encoding drug-metabolizing enzymes may account for interindividual differences in certain types of diseases especially cancer. In this study, microsomal epoxide hydrolase (EPHX1) and glutathione S-transferase P1 (GSTP1) gene polymorphisms were determined among 133 healthy males of a Turkish population. Frequencies of EPHX1 and GSTP1 gene polymorphisms were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) method. The observed genotype frequencies of EPHX1 exon 3 were Tyr113Tyr:50.4%, Tyr113His: 42.1%, His113His: 7.5% and EPHX1 exon 4 were His139His: 69.2%, His139Arg: 28.6%, Arg133Arg: 2.2%. GSTP1 exon 5 genotype frequencies were Ile105Ile: 58.7%, Ile105Val: 35.3%, Val105Val: 6.0% and GSTP1 exon 6 genotype frequencies were Ala114Ala: 85.0%, Ala114Val: 14.3%, Val114Val: 0.7%. These results reveal that the frequencies of EPHX1 and GSTP1gene polymorphisms in a small sampling of males within a Turkish population are similar to European Caucasian populations. PMID- 17365146 TI - Inhibitory effects of histone deacetylase inhibitor depsipeptide on benzo(a)pyrene- and cyclophosphamide-induced genotoxicity in Swiss albino mice. AB - Depsipeptide (FK228 or FR901228) was evaluated in the mouse bone marrow micronucleus test for its possible protective effect against chromosomal damage induced by benzo(a)pyrene and cyclophosphamide. Three doses of depsipeptide (0.5, 1, and 1.5 mg/kg body weight) were given intravenously to mice for 7 consecutive days prior to administration of genotoxins under investigation. All the three doses of depsipeptide were effective in exerting a protective effect against both benzo(a)pyrene and cyclophosphamide. A significant suppression (34.9% to 67.5%) in the micronuclei formation induced by benzo(a)pyrene and (25.7% to 71.5%) cyclophosphamide was observed following intravenous administration of depsipeptide at doses of 0.5, 1, and 1.5 mg/kg in Swiss albino mice. PMID- 17365147 TI - Safety assessment of castoreum extract as a food ingredient. AB - Castoreum extract (CAS NO. 8023-83-4; FEMA NO. 2261) is a natural product prepared by direct hot-alcohol extraction of castoreum, the dried and macerated castor sac scent glands (and their secretions) from the male or female beaver. It has been used extensively in perfumery and has been added to food as a flavor ingredient for at least 80 years. Both the Flavor and Extract Manufacturers Association (FEMA) and the Food and Drug Administration (FDA) regard castoreum extract as generally recognized as safe (GRAS). Acute toxicity studies in animals indicate that castoreum extract is nontoxic by both oral and dermal routes of administration and is not irritating or phototoxic to skin. Skin sensitization has not been observed in human subject tests. Castoreum extract possesses weak antibacterial activity. A long historical use of castoreum extract as a flavoring and fragrance ingredient has resulted in no reports of human adverse reactions. On the basis of this information, low-level, long-term exposure to castoreum extract does not pose a health risk. The objective of this review is to evaluate the safety-in-use of castoreum extract as a food ingredient. PMID- 17365148 TI - Mercury activates vascular endothelial cell phospholipase D through thiols and oxidative stress. AB - Currently, mercury has been identified as a risk factor of cardiovascular diseases among humans. Here, the authors tested the hypothesis that mercury modulates the activity of the endothelial lipid signaling enzyme, phospholipase D (PLD), which is an important player in the endothelial cell (EC) barrier functions. Monolayers of bovine pulmonary artery ECs (BPAECs) in culture, following labeling of membrane phospholipids with [32P]orthophosphate, were exposed to mercuric chloride (inorganic form), methylmercury chloride (environmental form), and thimerosal (pharmaceutical form), and the formation of phosphatidylbutanol as an index of PLD activity was determined by thin-layer chromatography and liquid scintillation counting. All three forms of mercury significantly activated PLD in BPAECs in a dose-dependent (0 to 50 microM) and time-dependent (0 to 60 min) fashion. Metal chelators significantly attenuated mercury-induced PLD activation, suggesting that cellular mercury-ligand interaction(s) is required for the enzyme activation and that chelators are suitable blockers for mercury-induced PLD activation. Sulfhydryl (thiol protective) agents and antioxidants also significantly attenuated the mercury induced PLD activation in BPAECs. Enhanced reactive oxygen species generation, as an index of oxidative stress, was observed in BPAECs treated with methylmercury that was attenuated by antioxidants. All the three different forms of mercury significantly induced the decrease of levels of total cellular thiols. For the first time, this study revealed that mercury induced the activation of PLD in the vascular ECs wherein cellular thiols and oxidative stress acted as signal mediators for the enzyme activation. The results underscore the importance of PLD signaling in mercury-induced endothelial dysfunctions ultimately leading to cardiovascular diseases. PMID- 17365149 TI - Differential effect of 7,12-dimethylbenz[a]anthracene on human and mouse CYP1B1 from livers of castrated transgenic mice. AB - Humanized transgenic mice coexpressing tetracycline-controlled transactivator (tTA) and human cytochrome P450 1B1 (CYP1B1) (hCYP1B1) have been created by this group. The aims of this study was to determine if 7,12-dimethylbenz[a]anthracene (DMBA) functions as testosterone or doxycycline in its ability to induce or reduce expression of hCYP1B1 or endogenous mouse CYP1B1 (mCYP1B1). This was tested in the livers by treating castrated transgenic males and hCYP1B1/luciferase-transfected cells with DMBA. Herein, DMBA-treated group exhibited (i) gradual reduction of hCYP1B1 expression at the transcript, protein, and activity levels but gradually induced its transcript level during DMBA release; (ii) gradual reduction of hCYP1B1 at the transcript and protein levels, as in the case of doxycycline or testosterone; (iii) gradual induction of mCYP1B1 expression at the transcript and protein levels but gradually reduced its transcript level during DMBA release. In parallel, DMBA-treated transfected cells exhibited gradual increase in luciferase activity in a time-and dose-dependent manner. Thus, castrated transgenic males or in vitro system could be useful as models for the detection of polycyclic aromatic hydrocarbons (PAHs) or environmental toxicants by measuring either hCYP1B1 or mCYP1B1 expressions. PMID- 17365150 TI - Protective role of melatonin and coenzyme Q10 in ochratoxin A toxicity in rat liver and kidney. AB - Melatonin (MEL) and coenzyme Q10 (CoQ10) both display antioxidant and free radical scavenger properties. In the present study, the effect of MEL and CoQ10 on the oxidative stress and fibrosis induced by ochratoxin A (OTA) administration in rats was investigated. Rats were divided into five equal groups, each consisting of seven rats: (1) controls; (2) OTA-treated rats (289 microg/kg/day); (3) OTA+MEL-treated rats (289 microg/kg/day OTA + 10 mg/kg/day MEL); and (4) OTA+CoQ10-treated rats (289 microg/kg/day OTA + 1 mg/100 g/day body weight (bw) CoQ10). After 4 weeks of treatment, the level of malondialdehyde (MDA), glutathione peroxidase (GPx), and hydroxyproline (Hyp) were measured in the homogenates of liver and kidney. In the OTA-treated group, the levels of MDA and Hyp in both liver and kidney were significantly increased when compared with the levels of control, whereas GPx activities decreased. In OTA+MEL-treated rats, the levels of MDA and Hyp in both liver and kidney were significantly decreased when compared with the levels of OTA-treated rats; however; GPX activities increased. In the OTA+CoQ10-treated group, the levels of MDA and Hyp were decreased when compared with the levels of OTA-treated rats, whereas GPx activities increased. In the OTA+CoQ10-treated group, the levels of MDA, Hyp, and GPx were not significantly changed in kidney when compared with OTA-treated group. MEL has a protective effect against OTA toxicity through an inhibition of the oxidative damage and fibrosis both liver and kidney. Although CoQ10 has protective effect against OTA toxicity in liver tissue, it has no effect in kidney tissue. PMID- 17365153 TI - Psychotherapy in psychiatry: integration and assimilation. PMID- 17365154 TI - Psychotherapy in psychiatry. AB - The relationship between psychotherapy and psychiatry has become a beleagured one in recent years. The swing of the pendulum in the direction of biological psychiatry has led to a marginalization of psychotherapy within the discipline of psychiatry as a whole. However, psychotherapy continues to be a basic science of psychiatry with application in all clinical settings. It must be regarded as a biological treatment that works by changing the brain and is therefore just as important as pharmacotherapy in terms of overall treatment planning. The combined treatment of medication and psychotherapy has become the most common mode of psychiatric treatment planning in current practice. Both the two-treater model and the single-treater model have a set of advantages and disadvantages that are explicated. Further research is needed to identify clinical situations in which psychotherapy is essential, whether alone or in combination with medication. Moreover, as greater insights are gained into the brain mechanisms responsible for therapeutic changes, more specifically targeted psychotherapies can be developed. PMID- 17365155 TI - Psychosis and the dynamics of the psychotherapy process. AB - The role of psychotherapy in the treatment of psychoses remains controversial but there is improving acceptance that an understanding of the dynamics of the psychological processes involved in treatment and in the disorder itself may be important. Psychosis is understood as a detachment of the 'self' from the 'world which results in changed abilities in inter-subjective relating to oneself and others. This understanding has led to guidelines for psychotherapists who engage in treatment of psychoses and these are summarized in this article. As a result of the disturbance in the inter-subjective process, a therapeutic relationship is disrupted and a therapeutic alliance is not assured. Therapists have to pay particular attention to the empathic aspects of the interaction as they attempt to integrate affects to restore meaning to the inner life of the patient. The psychodynamics of this process are described with additional discussion about the role of cognitive interventions and their limitations. PMID- 17365156 TI - The efficacy of various modalities of psychotherapy for personality disorders: a systematic review of the evidence and clinical recommendations. AB - The aim of this paper is to review the level of empirical evidence for four different formats and settings that are available for psychotherapy delivery, i.e., group psychotherapy, out-patient individual psychotherapy, day hospital psychotherapy, and in-patient psychotherapy. The focus is on studies which include a wide range of DSM-IV-TR Axis II personality disorders. The results show that various psychotherapeutic treatments have proven to be efficacious with respect to reducing symptomatology and personality pathology, and improving social functioning in patients with Cluster A, B, C, or not-otherwise-specified personality disorders. This is especially true for cognitive-behaviorally or psychodynamically oriented out-patient individual psychotherapies. However, some evidence indicates that this also applies to (1) long-term, psychodynamically oriented group psychotherapy, (2) short-term, psychodynamically oriented psychotherapy in a day hospital setting, and (3) various duration variants of psychodynamically oriented, in-patient psychotherapy programmes. The available evidence mostly applies to borderline, dependent, avoidant and not-otherwise specified personality disorder, and perhaps also paranoid, obsessive-compulsive, and schizotypal personality disorder. It is unknown whether these conclusions also apply to schizoid, antisocial, narcissistic, and histrionic personality disorder. PMID- 17365157 TI - From general day hospital treatment to specialized treatment programmes. AB - Approximately one third of day hospitals in Europe can be designated as predominantly psychotherapeutic. They address mainly patients with personality disorders (PD), but also eating disorders and chronic mood and anxiety disorders without PD. As day treatment programmes tend to become associated with mental health centers, their treatment intensity also tends to become reduced. Available data suggest that approximately 10 hours of treatment a week is sufficient. Is such treatment more effective than specialized outpatient treatment? This research question will probably set the agenda in the years to come. In response to this challenge, day treatment should become more specialized. Data from the Norwegian Network of Psychotherapeutic Day Hospitals (n = 2.205) demonstrate that the majority of day treatment patients suffer from borderline and avoidant PD. Programmes for patients with borderline PD are well developed. The authors call for programme development for patients with avoidant PD. PMID- 17365158 TI - Psychotherapy for borderline personality disorder: mentalization based therapy and cognitive analytic therapy compared. AB - Mentalization Based Therapy (MBT) and Cognitive Analytic Therapy (CAT) are among a small number of psychotherapy approaches offering specific methods for the treatment of Borderline Personality Disorder (BPD). They share a number of features, notably both seek to integrate ideas and methods from psychoanalysis and cognitive psychology, pay attention to early attachment experiences and see harsh and inconsistent care, in combination with biological vulnerability, as playing an important part in the genesis of BPD offer treatment based on a developmental understanding of BPD, taking account of recent developments in observational research seek to provide therapy appropriate for use in the public service. These similarities, however, conceal a number of differences in underlying assumptions and emphases and are linked with contrasting therapeutic techniques. In this paper we present a discussion of key features of our models of normal and pathological development and a consideration of the conceptual underpinnings and of how far they are compatible with what is reliably known in the general field of psychology and how far it offers a model accessible to patients and clinician. Where our views diverge significantly, the reader will have some of the evidence on which to make a personal choice. PMID- 17365159 TI - Psychotherapy and mental health teams. AB - Mental health teams in different configurations and settings are under increasing pressure to offer formal psychotherapies as well as psychologically informed management to large numbers of 'difficult' patients with severe and complex presentations. This pressure has arisen variously from consumers, governmental agencies and commissioning bodies. Although these teams are an important resource, they receive limited training, supervision or support in models of psychotherapy, especially those incorporating a relational dimension and offering a coherent 'common language'. This commonly results in impairment of collective team function, including the quality and consistency of assessments, and may result in stress, splitting and 'burn out' for team members. This situation is due in part to their burden of casework and responsibility but also to prevailing, largely symptom-based and biomedical, models of mental disorder which tend to minimize the importance of psychosocial dimensions in either aetiology or treatment. Formulating and delivering appropriate, evidence-based and robust models of psychotherapy in generic team settings represents a significantly different challenge from that posed by delivery of psychotherapy in specialist settings. Approaches to this important challenge are discussed and summarized drawing on general considerations and the limited direct research evidence, and are illustrated by a cognitive analytic therapy (CAT)-based training project. PMID- 17365160 TI - The organization and delivery of psychological treatments. AB - This article reviews the major issues which face health providers when they seek to organise the delivery of psychological treatments to best effect. A lack of consensus on efficacy, efficiency and acceptability makes policy decisions difficult. Streamlined focused services offering evidence based interventions for a limited target group are compared with broader enterprises offering comprehensive provision of a range of therapies. The dilemmas that the relative strengths and weaknesses of these two models pose are compared in relation to setting, cost efficiency, patient acceptability, equitable access and the pragmatics of staff training, service delivery and clinical governance. It is suggested that changes in the structure of health service provision more generally and the potential inherent in new technology and innovative ways of working may provide new solutions to some of these difficulties and the successive restructurings of a department of psychological treatments are adduced as an example. PMID- 17365161 TI - Psychotherapy training for psychiatrists: UK and global perspectives. AB - Psychotherapy training for psychiatrists has often been honoured more in the breach than the observance. While most training schemes pay lip service to psychotherapy, few provide the comprehensive training to which national and international bodies aspire. Recent educational changes, especially the move from course completion to competency evaluation, and the implementation of 'requirements' as opposed to 'recommendations', provide an opportunity for psychotherapy to become more central to psychiatric training. Based on international systematic enquiry and specific experience in the UK, this article makes a number of theoretical and practical suggestions: (a) mentalization as a relevant indicator of psychological mindedness for trainees and ways in which it might be measured (b) the importance of identifying the small number of trainees at risk for dangerous practice and remedial measures (c) the importance of local and national leadership if change is to be initiated and followed through over a number of years (d) ways in which the paradox of underdevelopment of psychotherapy training can be overcome via the reinforcement of existing expertise and values as well as the use of visiting 'experts' and modern IT aids. PMID- 17365163 TI - From the editor - notes from a conference on trauma and violence in our communities. PMID- 17365164 TI - The relationships among health functioning indicators and depression in older adults with diabetes. AB - A common health problem among the elderly with diabetes is the onset of depressive symptoms that can adversely affect self-care and control of diabetes. The study examined the relationships of gender, race, comorbid conditions, symptom distress, and functional status with depression in a sample (N = 55) of older adults with diabetes. Most participants were female and black; mean age was 73 years. Gender and symptom distress were the strongest predictors of depression, accounting for 53% of the variance in depression. Although the sample was reasonably high functioning with only moderate levels of symptom distress, these findings serve as an important reminder for nurses that even moderate levels of symptom distress may be an indicator of depressive symptomatology among older diabetic adults. PMID- 17365165 TI - An exploration of the meaning of spirituality voiced by persons living with HIV disease and healthy adults. AB - Spirituality has been documented in several studies as having a positive effect on chronic disease progression and as being efficacious in improving quality of life and well being. In many studies, researchers have used predetermined definitions of spirituality and have proscribed the variable by the selection of measures. This study examines the meaning of spirituality as voiced by participants in two ongoing intervention studies, a sample of healthy adults and a sample of persons living with HIV disease. The findings resulted in six themes for each sample. Exhaustive statements were written depicting the summary relationships of themes. The findings support spirituality as an essential human dimension. PMID- 17365166 TI - Walking back to health: a qualitative investigation into service users' experiences of a walking project. AB - The relationship between physical activity and mental health is well documented and has led to the inclusion of physical activity into the treatment of people with mental health problems within heath care. However, little research has been conducted on the outcomes these programmes have for the people who participate in them. This study investigated the perceived health outcomes of people with mental health problems who had successfully participated in a walking project. The research is a descriptive qualitative study that used individual interviews and the constant comparative method of analysis. Findings conclude that physical activity programmes have a significant part to play in the quality of life of people with mental health problems and have the potential to be an integral part of their health care. PMID- 17365167 TI - Transition to mental health nursing through specialist graduate nurse programs in mental health: a review of the literature. AB - Specialist graduate nurse programs (GNPs) in psychiatric/mental health nursing have been widely implemented across public healthcare services throughout Victoria, Australia. Broadly, these programs aim to assist newly graduated nurses during the transition from nursing student to registered nurse. This paper presents a review of the literature relevant to GNPs; specifically focusing on graduate transition. An adequate orientation to clinical areas and ongoing support throughout the transition process were identified as significant determinants of new graduates" satisfaction with the initial post-qualification period. However, the literature suggests that the inadequacy of psychiatric/mental health nursing content in undergraduate nursing courses creates additional difficulties within this specialty area of practice. Moreover, the current literature review emphasises the need for further research to evaluate the effectiveness of GNPs for nursing in general and for psychiatric/mental health nursing in particular. PMID- 17365168 TI - Self-efficacy and locus of control affect management of aggression by mental health nurses. AB - The safe and effective management of aggression has become an increasingly critical skill for mental health nurses, particularly those working in acute inpatient settings. There is considerable evidence to suggest that the psychological constructs of self-efficacy and locus of control are closely related to work performance in a variety of occupations. By drawing upon literature published in the past 15 years, this paper highlights this evidence and draws attention to the relationship between self-efficacy and locus of control. The central argument of the paper is that there may be direct relationships among mental health nurses" self-efficacy, their degree of internality or externality in relation to locus of control, and their ability to safely and effectively manage aggressive incidents. We argue the need to further investigate these relationships and discover whether these variables can be modified through professional development activities. PMID- 17365169 TI - Cultural competence column: what else is necessary? PMID- 17365170 TI - Psychopharmacology column: why choose selegiline transdermal system for refractory depression? PMID- 17365171 TI - Comments, critique, and inspiration: the disappearance of "one-to-ones" in acute psychiatric care. PMID- 17365172 TI - Nontraditional psychiatric practice issues: my time in prison with women survivors of IPV. PMID- 17365173 TI - The Sep15 protein family: roles in disulfide bond formation and quality control in the endoplasmic reticulum. AB - Disulfide bonds play an important role in the structure and function of membrane and secretory proteins. The formation of disulfide bonds in the endoplasmic reticulum (ER) of eukaryotic cells is catalyzed by a complex network of thiol disulfide oxidoreductases. Whereas a number of ER-resident oxidoreductases have been identified, the function of only a few of them is firmly established. Recently, a selenocysteine-containing oxidoreductase, Sep15, has been implicated in disulfide bond assisted protein folding, and a role in quality control for this selenoprotein has been proposed. This review summarizes up-to-date information on the Sep15 family proteins and highlights new insights into their physiological function. PMID- 17365174 TI - Defining the roles of T cell membrane proteinase and CD44 in type 1 diabetes. AB - Membrane type-1 matrix metalloproteinase (MT1-MMP) shedding of the signaling and adhesion CD44 receptor plays a significant role in stimulating cancer cells locomotion. Similarly, and unexpectedly, MT1-MMP-dependent shedding of CD44 plays an equally significant role in regulating the adhesion to the pancreatic vasculature and also in the concomitant transendothelial migration and intra islet homing of the diabetogenic, cytotoxic, T cells. Inactivation of the T cell MT1-MMP functionality by clinically tested, synthetic inhibitors leads to an extended immobilization of the T killer cells on the pancreatic vasculature and, subsequently, to immunosuppression because of the cessation of the T cell transmigration and homing. Injections of insulin jointly with an MT1-MMP inhibitor stimulated the regeneration of functional, insulin-producing, beta cells in acutely diseased non-obese diabetic (NOD) mice. After insulin injections were suspended and inhibitor injections continued, diabetic NOD mice maintained mild hyperglycemia and did not require further insulin injections for survival. Overall, these data provide a substantive mechanistic rationale for clinical trials of the inhibitors of MT1-MMP in human type 1 diabetes. PMID- 17365175 TI - Functional effects of mutations identified in patients with multiminicore disease. AB - Multiminicore disease is a recessive congenital myopathy characterized by the presence of small cores or areas lacking oxidative enzymes, in skeletal muscle fibres. From a clinical point of view, the condition is widely heterogeneous and at least four phenotypes have been identified; genetic analysis has revealed that most patients with the classical form of multiminicore characterized by rigidity of the spine, early onset and respiratory impairment harbour recessive mutations in the SEPN1 gene, whereas the majority of patients belonging to the other categories, including patients with ophthalmoplegia or patients with a phenotype similar to central core disease, carry recessive mutations in the RYR1. In the present review we discuss the most recent findings on the functional effect of mutations in SEPN1 and RYR1 and discuss how they may adversely affect muscle function and lead to the clinical phenotype. PMID- 17365176 TI - Role of glutathiolation in preservation, restoration and regulation of protein function. AB - Glutathiolation has emerged as an important post-translational modification that regulates protein function. Reduced glutathione remains bound to reactive cysteine side chains of several intracellular proteins even under basal conditions and the abundance of glutathiolated proteins increases upon oxidant challenge. Although protein glutathiolation was considered primarily to be a protective mechanism for preventing irreversible oxidation of protein thiols, recent evidence suggests that controlled glutathiolation reactions can also be used to modify protein structure and function. Several growth factors and cytokines promote protein glutathiolation and glutathiolated proteins have been shown to increase upon physiological stimulation of NO production. Given the high affinity of some nitrosylated proteins for glutathione, glutathiolation may also be a significant metabolic fate of nitrosylated proteins. Enzymatic pathways of protein de-glutathiolation have also been described; indicating that both glutathiolation and de-glutathiolation may be tightly regulated processes. In this review, we discuss the mechanisms of protein glutathiolation and how physiologic glutathiolation of specific proteins could regulate glucose metabolism, calcium homeostasis and changes in cell shape and contraction. We propose that glutathiolation represents a discrete sub-state within complex thiol based redox circuits, relays and switches that regulate protein function basally and, upon oxidative stress, elicit adaptive responses or trigger cell death. PMID- 17365177 TI - Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3-E1 cells. AB - Oxidative stress regulates cellular functions in multiple pathological conditions, including bone formation by osteoblastic cells. However, little is known about the cellular mechanisms responsible for the effects of oxidative stress on osteoblast functions in senescence. To clarify the inhibitory effects of oxidative stress on osteoblastic mineralization, we examined the relationship between the antioxidant system and bone formation in MC3T3-E1 cells. After a single exposure to H2O2 within range of a non-toxic concentration for cells, the mineralization level was diminished half. Under the same conditions, gene expression of the transcription factor Nrf2, which regulates antioxidant enzymes, was up-regulated. In addition, gene expression for the osteogenic markers Runx2, ALP, and BSP was lower than that in non-treated cells, whereas expression of the osteocalcin gene was up-regulated following H2O2 exposure. These results suggest that reduced mineralization by MC3T3-E1 cells after H2O2 exposure is the result of an up-regulated antioxidant system and altered osteogenic gene expression. PMID- 17365178 TI - Chemical, thermal and pH-induced equilibrium unfolding studies of Fusarium solani lectin. AB - The effect of urea, guanidine thiocyanate, temperature and pH was studied on the conformational stability of Fusarium solani lectin. Equilibrium unfolding with chemical denaturants showed that the lectin was least stable at pH 12 and maximally stable at pH 8.0 near its pI (8.7). Guanidine thiocyanate (the concentration of denaturant at which the protein is half folded, D1/2 = 0.49 M at pH 12) was found to be an eight times stronger denaturant than urea (D1/2 = 3.88 M at pH 12). The unfolding curves obtained with fluorescence and CD measurements showed good agreement indicating a monophasic nature of unfolding and excluded the possibility of formation of any stable intermediate. The effect of pH on the lectin was found to be unusual as at acidic pH, the lectin showed a flexible tertiary structure with pronounced secondary structure, and retained its hemagglutinating activity. On the other hand, the lectin did not show any loss of conformation or activity upto 70 degrees C for 15 min. Moreover, thermal denaturation did not result in the aggregation or precipitation of the protein even at high temperatures. Thermal denaturation was also carried out in the presence of a low concentration of guanidine thiocyanate. Change in the enthalpy of transition (DeltaHm) varied linearly with transition temperature (Tm), which indicated that the heat capacity (DeltaCp = 3.95 kJ . mol-1 . K-1) of the lectin remained constant during the unfolding. PMID- 17365179 TI - Many membrane proteins undergo ectodomain shedding by proteolytic cleavage. Does one sheddase do the job on all of these proteins? PMID- 17365180 TI - Bill Slater at 90. PMID- 17365181 TI - A new meroditerpenoid from Mayodendron igeum. AB - A new meroditerpenoid, igeumone (1), together with 18 known compounds (2-19), were isolated from ethanolic extract of the bark of Mayodendron igeum. Their structures were determined by analysis of spectral data or comparison with authentic samples. X-ray crystallographic analysis was employed to unambiguously determine the structure of 1. PMID- 17365182 TI - Two new triterpenoids from the carpophore of Xanthoceras sorbifolia Bunge. AB - Two new triterpenoids were isolated from the dried carpophore of Xanthoceras sorbifolia Bunge (Sapindaceae). By means of spectroscopic data (1D and 2D NMR, ESI-MS) and chemical evidence, their structures were established as 16-O-acetyl 21-O-(3',4'-di-O-angeloyl)-beta-D-fucopyranosyl theasapogenol B (1) and 3beta,23 dihyroxy-lup-20(29)en-28-oic acid -23-caffeate (2). PMID- 17365183 TI - Three major urinary metabolites of sinomenine in rats. AB - Urinary metabolites of sinomenine were investigated in rats after intragastric administration. Three major metabolites were obtained and characterised as 4 hydroxy-3,7,7-trimethoxy-17-methyl-(9alpha,13alpha,14alpha)-morphinan-6-one (1), 7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methyl-N-oxide-(9alpha,13alpha,14alpha) morphinan-6-one (2), and 7,8-didehydro-4-hydroxy-3,7-dimethoxy (9alpha,13alpha,14alpha)-morphinan-6-one (3). Their structures have been elucidated on the base of spectral analysis, among which 1 and 2 were new compounds. PMID- 17365184 TI - Two new arylbenzofurans from the roots of Hedysarum multijugum. AB - Two new arylbenzofurans, hedysarimbenzofuran A (1) and hedysarimbenzofuran B (2), were isolated from the roots of Hedysarum multijugum. The structures were determined by spectroscopic methods. PMID- 17365185 TI - Total synthesis of two new dihydrostilbenes from Bulbophyllum odoratissimum. AB - A total synthetic route of two new dihydrostilbenes 5-(2-benzo[1,3]dioxole-5 ylethyl)-6-methoxy benzo[1,3]dioxole-4-ol (1) and 5-(2-benzo[1,3]dioxole-5 ylethyl)benzo[1,3]dioxole-4,7-diol (2), which were isolated from Bulbophyllum odoratissimum Lindl. with significant cytotoxicity toward human cancer cell lines, was developed via Horner reaction etc. The natural products 1 and 2 were obtained in 10.5% and 3.3% overall yield, respectively. PMID- 17365186 TI - Cyclobakuchiol C, a new bakuchiol derivative from Psoralea coryllfolia. AB - A new compound, cyclobakuchiol C (1), together with four known bakuchiol derivatives, 2-5, was isolated from the non-polar fraction of the seeds of Psoralea corylifolia, and compounds 3-5 were identified from this plant for the first time. The structure of 1 was determined by spectroscopic methods, especially 2D NMR experiments. PMID- 17365187 TI - Triterpenoid saponins from Platycodon grandiflurum. AB - A new bisdesmosidic saponin, named deapio-platycoside E (1), together with two known triterpenoid saponins (2, 3) were isolated from the roots of Platycodon grandiflorum (Jacq.) A. D.C. Their structures were elucidated by spectroscopic and chemical methods. PMID- 17365188 TI - Studies on the chemical constituents of Psoralea corylifolia L. AB - A new isoflavone, corylinin (1), along with six known compounds, isopsoralen (2), psoralen (3), sophoracoumestan A (4), neobavaisoflavone (5), daidzin (6) and uracil (7), have been isolated from the dried fruits of Psoralea corylifolia L. The structure of 1 was established as 7,4'-dihydroxy-3'-[(E)-3,7-dimethyl-2,6 octadienyl]isoflavone on the basis of the spectroscopic methods. Structures of the known compounds were identified by comparison of the literature. PMID- 17365189 TI - A new flavonol from Sophora tonkinensis. AB - A new flavonol, tonkinensisol, was isolated from the roots of Sophora tonkinensis, together with three known compounds named as bayin, vitexin and lupeol. Their structures were elucidated on the basis of spectroscopic evidence. Additionally, tonkinensisol showed moderate cytotoxicity suppressing the proliferation of HL-60 cells in vitro. PMID- 17365190 TI - Effect of octadecanoyl acetal sodium sulphite series with different numbers of double bonds on their immunological and surface activities. AB - The relationship between the immunological activities and their surface activities of octadecanoyl acetal sodium sulphite series containing different numbers of double bonds (HOU-C18:n; n = 1, Delta9; n = 2, Delta9,12; n = 3, Delta9,12,15) were studied. The results showed that HOU-C18:n were able to increase the carbon granular clearance rate K, the NK cell activity in spleen and the activity of lysozymes in serum as well as inhibit Staphylococcus aureus and lysozymes in vitro to some degree. As the number of double bonds in HOU-C18:n increased along with the hydrophobic properties and the ability to improve the immune activity, NK cell activity and lysozyme activity decreased, but the bacteriostatic activity increased. It is speculated that HOU-C18:n could improve immunity and bacteriostasis realised by the interaction between the hydrophobic chain and membranes of cells. From the results of the effects of HOU-C18:n on lysozymes in vivo and in vitro, it is speculated that HOU-C18:0 could initiate and greatly enhance lysozyme activity in serum by increasing the amount of lysozymes, while unsaturated HOU-C18:n might do so mainly by increasing the number of lysozymes. PMID- 17365191 TI - Bioactive coumarins from Boenninghausenia sessilicarpa. AB - Bioassay guided fractionation of Boenninghausenia sessilicarpa (Rutaceae) resulted in the isolation of a new dimeric coumarin glucoside 9'-methoxyl rutarensin (1) and a cytotoxic compound rutamarin (4), as well as an antivirus component leptodactylone (8), together with six known coumarins. Their structures were elucidated by 1D- and 2D NMR spectroscopy and ESI-MS analyses, respectively. Rutamarin (4) showed significant inhibitory activities against A-549, Bel-7402, HepG-2 and HCT-8 tumour cell lines with IC50s of 1.318, 2.082, 2.306 and 2.497 microg/ml. In addition, leptodactylone (8) showed potent protective activity on cells infected by SARS-CoV with ratio of 60% at 100 microg/ml. PMID- 17365192 TI - Oleanane-type triterpenes from Ludwigia octovalvis. AB - Two new oleanane-type triterpenes, (23Z)-feruloylhederagenin (1) and (23E) feruloylhederagenin (2), together with two known oleanane-type triterpenes, beta amyrin acetate and beta-amyrin palmitate, have been isolated from the whole plant of Ludwigia octovalvis. The structures of 1 and 2 were characterised on the basis of spectral evidence. PMID- 17365193 TI - Semi-synthetic modification of nimbolide to 6-homodesacetylnimbin and 6 desacetylnimbin and their cytotoxic studies. AB - A new C-seco tetranortriterpenoid named as 6-homodesacetylnimbin 2, has been synthesised for the first time through semi-synthetic modification of nimbolide 1, a potent molecule with anticancer activity. Attempts were made to transesterify the -COOMe moiety in nimbolide using titanium (IV) isopropoxide and ethanol so as to obtain a molecule with -COOEt moiety. However, a novel product was envisaged during the course of the reaction, which was identified as 6 homodesacetylnimbin, a higher homologue of 6-desacetylnimbin 3 through spectroscopic and crystallographic methods. Also, 6-desacetylnimbin has been synthesised through acid hydrolysis of nimbolide. The compounds were screened for their cytotoxic properties through brine shrimp lethality bioassay method using Artemia salina. PMID- 17365194 TI - Chemical constituents of Cistanche sinensis. AB - One new phenylethanoid glycoside, cistansinenside A and one new oligosaccharide, cistansinensose A1/A2, were isolated from the stems of Cistanche sinensis, together with six known compounds. The structures of the new compounds were elucidated on the basis of spectral data. PMID- 17365195 TI - Three new C-flavonoids from Corallodiscus flabellata. AB - Three new C-glycosylflavones, named 5,7,4'-trihydroxy-6-methoxy-8-C-[beta-D xylopyranosyl- (1 --> 2)]-beta-D-glucopyranosyl flavonoside (1), 5,7,4' trihydroxy-8-methoxy-6-C-[beta-D-xylopyranosyl-(1 --> 2)]-beta-D-glucopyranosyl flavonoside (2), and 5,3',4'-trihydroxy-7,8-dimethoxy-6-C-[beta-D-xylopyranosyl (1 --> 2)]-beta-D-glucopyranosyl flavonoside (3), along with two known compounds 5,4'-dihydroxy-7-methoxy-6-C-glucopyranosyl-flavonoside (4), 3-methoxy-4 hydroxymethyl benzoate (5) were isolated from 70% acetone extract of Corallodiscus flabellata. Their structures were identified on the basis of spectroscopic techniques and chemical methods. PMID- 17365196 TI - Two new trans-clerodane diterpenoids from Otostegia limbata. AB - Two new tricyclic clerodane-type diterpenoids, limbatolide D (1) and limbatolide E (2), have been isolated from the roots of Otostegia limbata. Their structures and the relative configuration were established on the basis of spectral methods, especially two-dimensional (2D) NMR techniques. PMID- 17365197 TI - Evidence-based selection of inhaled corticosteroid for treatment of chronic asthma. AB - Published literature relevant to comparison of various inhaled corticosteroids (ICSs) was reviewed. Marked heterogeneity was found in the reported results. The efficacy and side effects of ICSs depend on their formulation, dosing and device used, and the subjects' age, severity of asthma, and inhaler technique. All these factors have not been included uniformly in most study designs. Notwithstanding this limitation, it appears that fluticasone is generally very effective and safe in low-to-medium doses and may be used for most patients. Budesonide is the only Pregnancy Category B ICSs, all others being Category C, and it is available as nebulizer suspension suitable for use in children over 6 months of age. Budesonide, also available as dry powder inhaler, and beclomethasone, available as metered-dose inhaler, are equal in efficacy, and side effects and may be chosen according to the patient's ability to handle the device. Flunisolide causes fewer side effects but is also relatively less effective. Triamcinolone is generally less effective and causes more side effects than most of the other ICSs. Mometasone may be preferred if once-daily dosing is desired. Ciclesonide has been found highly effective in once-daily dose and without side effects even in high doses. Further studies comparing it with other ICSs over longer periods of use will determine its place in treatment of chronic asthma. PMID- 17365198 TI - Psychogenic cough in an asthmatic child: case report with unusual findings. AB - A 9-year-old girl with known mild intermittent asthma presented with a persistent cough. Her cough exhibited a four-beat staccato rhythm, was nonproductive, and persisted only while awake. On physical examination, she displayed several unique findings not previously described. An extensive yet non-diagnostic medical workup coupled with absence of aggressive medical treatment for the more usual causes of cough lead to psychologic investigation and intervention with subsequent cough resolution. The appropriate use of psychologic consultation, testing, and success with supportive reinforcement therapy confirmed a psychogenic etiology. Extended medical follow-up of the patient concerning cough reoccurrence remains uneventful. PMID- 17365199 TI - Idiopathic pulmonary arterial hypertension misdiagnosed as asthma. AB - Idiopathic pulmonary arterial hypertension (IPAH) is a rare disorder that is progressive and often leads to right heart failure if left untreated. Because of the vague nature of symptoms at presentation, IPAH may take several months to diagnose. The most common presenting complaint in patients with IPAH is dyspnea with exertion, which is also commonly seen with asthma. This report describes an adult female with refractory exertional dyspnea who was diagnosed with asthma 2 years earlier but was ultimately diagnosed with IPAH. Exclusion of other etiologies is a necessity for refractory dyspnea in the setting of asthma. PMID- 17365200 TI - Skin sensitization in school children in northern and southern Norway. AB - It has been suggested that environmental exposures and living conditions can explain some of the worldwide variation in atopic disorders. Norway has large environmental contrasts within the country. We compared skin prick sensitization rates among school children living in the southern subarctic and in the northern arctic part of Norway. Approximately one quarter of the children were sensitized, mostly against pollen and animal dander, while mite and mould sensitization seemed to be a minor problem. Sensitization rates and profiles were similar in the north and south despite differences in living conditions and environmental exposures. PMID- 17365201 TI - Accuracy of Arabic versions of three asthma symptoms questionnaires against the clinical diagnosis of asthma. AB - Validation studies of asthma symptom questionnaires against provocation tests of bronchial hyperresponsiveness have shown comparable performances of written and video taped questionnaires. This study aimed to determine the test characteristics of Arabic versions of two written and one video taped questionnaires when compared to the clinical diagnosis of asthma made by two respiratory physicians. The written International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire had higher sensitivities and greater accuracy than the other two questionnaires. Comparisons between corresponding questions and scenes in the ISAAC questionnaires in general revealed no significant differences in performance. The ISAAC written questionnaire had test characteristics consistent with its potential use as a screening instrument for asthma in this population of children. PMID- 17365202 TI - Comparison of Delta FVC (% decrease in FVC at the PC(20)) between cough-variant asthma and classic asthma. AB - The percentage decrease in forced vital capacity (FVC) at the methacholine PC(20) (Delta FVC) has been proposed as a surrogate marker of maximal airway response. The aim of this study was to compare the Delta FVC between patients with cough variant asthma (CVA) and those with classic asthma (CA). We performed a retrospective analysis of methacholine challenge test data from 47 children who were diagnosed as having CVA and from 75 children who had CA of mild severity. The mean (+/- SD) Delta FVC was significantly (p = 0.001) lower in the CVA group (14.7 +/- 3.4%) compared with the CA group (17.1 +/- 4.4%), whereas PC(20) was not different between the two groups. Our results suggest that CVA is associated with a lower level of maximal airway response than CA. PMID- 17365203 TI - The pediatric asthma intervention: a comprehensive cost-effective approach to asthma management in a disadvantaged inner-city community. AB - OBJECTIVE: To compare three pediatric asthma interventions for their impact on improving the health status of inner-city asthmatic children and in achieving cost savings. STUDY DESIGN: A total of 212 children 1 to 16 years of age were randomized into three groups: group 1 (n = 74) received one individualized asthma education session; group 2 (n = 68) received reinforced asthma education; group 3 (n = 70) received reinforced asthma education plus case management. Asthma related health resource utilization and cost were primary outcomes. The cost benefit analysis sought to estimate the expected cost savings to the Illinois Department of Healthcare and Family Services (Medicaid administrator) associated with the intervention. RESULTS: Participants in all three groups used significantly fewer emergency health care services in the follow-up year. Averaged across all three groups, the magnitudes of declines were substantial: 81% for hospitalizations, 69% for hospital days, 64% for emergency department visits, and 58% for clinic visits. Although there were no statistically significant differences between study groups for three of the four main outcome measures, group 3 participants consistently improved to the greatest degree. All three interventions were associated with considerable cost savings ranging from $4,021/child/year for group 1 to $4,503/child/year for group 3. CONCLUSION: Asthma education with or without case management services enhances the health of children with asthma thereby reducing associated costs. PMID- 17365204 TI - The prevalence of atopy and asthma among university freshmen in Seoul, Korea: association with obesity. AB - The aims of this study were to investigate the prevalence of atopy, asthma, and obesity in university freshmen and to determine whether leptin is associated with bronchodilator reversibility in obesity. A total of 537 university freshmen completed International Study of Asthma and Allergies in Children (ISAAC) questionnaire and underwent skin prick testing and bronchodilator reversibility test. The prevalences of asthma, wheeze, and atopy were 10 (1.9%), 84 (15.6%), and 198 (36.9%), respectively. The mean (+/- SD) bronchodilator response (5.1 +/- 4.4%) was higher in the overweight/obese men than in the normal male subjects (3.7 +/- 3.2%, p < 0.05). The mean leptin level in the overweight/obese men was 5.55 +/- 3.48 ng/mL, which was significantly higher than that (2.78 +/- 1.65 ng/mL) of the normal male subjects. The prevalence of asthma among university freshmen is seriously under-diagnosed and leptin may play a role in bronchodilator reversibility in overweight/obese young men. PMID- 17365205 TI - Pediatric asthma: caregiver health literacy and the clinician's perception. AB - Health literacy was assessed in pediatric asthma caregivers attending a university-based clinic. The medical provider's perception of caregiver health literacy was also examined. Eighty-six percent of the caregivers had adequate health literacy, 4% and 10% had marginal and inadequate health literacy, respectively. Health literacy was significantly higher for caregivers who were younger (p = 0.039) and had a higher level of education (p = 0.037). An agreement analysis revealed moderate agreement between provider perception of caregiver's health literacy and measured health literacy (Kappa = 0.51). The results suggest that medical providers may not accurately assess caregivers' actual health literacy level. PMID- 17365206 TI - Interactive small-group asthma education in the community pharmacy setting: a pilot study. AB - BACKGROUND: This study aimed to compare the effects of two small-group asthma education interventions (one delivered by specially trained pharmacists (group A) and one delivered by a pharmacist researcher trained as an asthma educator (group B)) with usual care provided by community pharmacists (group C) on clinical and humanistic outcomes for people with asthma. METHODS: Pharmacies were randomly selected to provide either group A, B, or C interventions. Data were collected at baseline, post intervention (groups A and B) and at 6 and 12 weeks (final visit). RESULTS: Forty-eight people with asthma were recruited into groups A (n = 16), B (n = 16), and C (n = 16) and there were no significant differences between the groups at baseline. At 12 weeks there was a significant decrease in the proportion of patients with severe asthma/poor control in groups A and B compared with group C (56%, 44% and 50% to 25%, 13% and 50% [n = 48, p < 0.05], respectively). In Groups A and B, the proportion of patients with optimal metered dose inhaler (MDI) technique improved from 9% and 14%, respectively, at baseline to 82% and 93% (n = 11, p = 0.02, n = 14, p < 0.001), respectively, at 12 weeks. The proportion of patients with optimal dry powder inhaler (DPI) technique improved in Groups A and B from 0% and 8%, respectively, at baseline to 86% and 92% (n = 7, p < 0.001; n = 13, p = 0.002), respectively, at 12 weeks. No change in inhaler technique was observed for Group C. There were significant improvements in asthma knowledge scores in Groups A and B compared to Group C over time. CONCLUSIONS: Small-group asthma education delivered by pharmacists appears to be more effective than usual care in improving clinical and humanistic asthma outcomes. PMID- 17365207 TI - Asthma incidence: data from the National Health Interview Survey, 1980-1996. AB - OBJECTIVE: To obtain historical estimates of US asthma incidence from 17 years of health survey data. METHODS: The 1980 through 1996 National Health Interview Survey contained a question asking about the time of asthma onset in persons with asthma. Annual past year incidence estimates were calculated from self-reports of asthma status. RESULTS: Incidence increased from 2.5 per 1,000 (SE 0.37) in 1980 to 6.0 per 1,000 (SE 0.75) in 1996. Incidence increased faster in children than in adults and increased in females but not in males during this time. CONCLUSION: These findings suggest that increasing asthma incidence contributed to the increasing prevalence during this time. PMID- 17365217 TI - Special issue on active controlled clinical trials: guest editor's note. PMID- 17365218 TI - Issues with statistical risks for testing methods in noninferiority trial without a placebo ARM. AB - Noninferiority trials without a placebo arm often require an indirect statistical inference for assessing the effect of a test treatment relative to the placebo effect or relative to the effect of the selected active control treatment. The indirect inference involves the direct comparison of the test treatment with the active control from the noninferiority trial and the assessment, via some type of meta-analyses, of the effect of the active control relative to a placebo from historical studies. The traditional within-noninferiority-trial Type I error rate cannot ascertain the statistical risks associated with the indirect inference, though this error rate is of the primary consideration under the frequentist statistical framework. Another kind of Type I error rate, known as across-trial Type I error rate, needs to be considered in order that the statistical risks associated with the indirect inference can be controlled at a small level. Consideration of the two kinds of Type I error rates is also important for defining a noninferiority margin. For the indirect statistical inference, the practical utility of any method that controls only the across-trial Type I error rate at a fixed small level is limited. PMID- 17365219 TI - Use of the Fieller-Hinkley distribution of the ratio of random variables in testing for noninferiority. AB - We address the noninferiority assessment problem defined in terms of the ratio of population means in a parallel group design analysis of variance setting. The sample ratio as a point estimate of the corresponding population ratio has been considered. It has been shown that the Fieller-Hinkley distribution of the ratio of two correlated normally distributed random variables readily provide a technique for constructing confidence intervals comparable to the bootstrap percentile and Fieller's confidence intervals. A finite parameter space based level alpha test of an inferiority hypothesis formulated in terms of a fixed margin has been derived. We illustrate our approach using the forced vital capacity (FVC) data. We claim that it is easy to construct and straight forward to interpret our bootstrap equivalent confidence intervals that are used to assess noninferiority. We discuss appropriate methods for calculation of sample sizes. PMID- 17365220 TI - New tests for null hypothesis of non unity ratio of proportions. AB - Testing for noninferiority and equivalence between an experimental therapy and a standard therapy in terms of the ratio of binomial proportions is considered. New tests based on the Fieller-Hinkley distribution of the ratio of random variables are proposed. Restricted maximum likelihood estimates of the null variances are used to derive the tests. Sample size determination is discussed. The proposed test procedure is extended to multiple tables. The tests are applied to numerical examples. PMID- 17365221 TI - Simultaneous test for superiority and noninferiority hypotheses in active controlled clinical trials. AB - Two stage switching between testing for superiority (SUP) and noninferiority (NI) has been an important statistical issue in the design and analysis of the active controlled clinical trials. Tsong and Zhang (2005) has shown that the Type I error rates do not change when switching between SUP and NI with the traditional generalized historical control (GHC) approach, however, they may change when switching with the cross-trial comparison (X-trial) approach. Tsong and Zhang (2005) further proposed a simultaneous test for both hypotheses to avoid the problem. The procedure was based on Fieller's confidence interval proposed by Hauschke et al. (1999). Since with the X-trial approach, using the simultaneous test, superiority is tested using all four treatment arms (current test and active control arms, active control and placebo arms in historical trials), the Type I error rate and power are expected to be somewhat different from the conventional superiority test (using the current test and active control arms only). Through a simulation study, we demonstrate that the Type I error rate and power between simultaneous test and the conventional superiority test are compatible. We also examine the impact of the assumption of equal variances of the current trial and the historical trial. PMID- 17365222 TI - Simultaneous testing of noninferiority and superiority increases the false discovery rate. AB - It is well recognized that multiplicity adjustment is not necessary in simultaneous testing for noninferiority and superiority. However, Ng (2003) argued that there will be more experimental treatments that are expected to have the same effect as the active control tested for superiority in simultaneous testing than would occur if only one null hypothesis is tested, thereby increasing erroneous claims of superiority. This leads to an increase in the false discovery rate for superiority. PMID- 17365223 TI - Test for the consistency of noninferiority from multiple clinical trials. AB - A testing procedure is proposed to assess the consistency of noninferiority from a collection of trials based on simultaneous t lower confidence bounds or Scheffe's lower confidence bounds. Methods for simultaneous inferences on pairwise or many-to-one comparisons among multiple noninferiority trials are also discussed. To avoid bias due to subjective trial exclusion a tuning parameter k is embedded into the testing procedure to provide flexibility to quantify the "consistency of noninferiority" when the total number of trials is large. The size and power of the proposed test are discussed. The method is illustrated using simulations and real data analysis. PMID- 17365224 TI - Choice of delta noninferiority margin and dependency of the noninferiority trials. AB - For a two-arm active control clinical trial designed to test for noninferiority of the test treatment to the active control standard treatment, data of historical studies were often used. For example, with a cross-trial comparison approach (also called synthetic approach or lambda-margin approach), the trial is conducted to test the hypothesis that the mean difference or the ratio between the current test product and the active control is no larger than a certain portion of the mean difference or no smaller that a certain portion of the ratio of the active control and placebo obtained in the historical data when the positive response indicates treatment effective. For a generalized historical control approach (also known as confidence interval approach or delta -margin approach), the historical data is often used to determine a fixed value noninferiority margin delta for all trials involving the active control treatment. The regulatory agency usually requires that the clinical trials of two different test treatments need to be independent and in most regular cases, it also requires to have two independent positive trials of the same test treatment in order to provide confirmatory evidence of the efficacy of the test product. Because of the nature of information (historical data) shared in active controlled trials, the independency assumption of the trials is not satisfied in general. The correlation between two noninferiority tests has been examined which showed that it is an increasing function of (1 - lambda ) when the response variable is normally distributed. In this article, we examine the relationship between the correlation of the two test statistics and the choice of the noninferiority margin, delta as well as the sample sizes and variances under the normality assumption. We showed that when delta is determined by the lower limit of the confidence interval of the adjusted effect size of the active control treatment (muC - muP) using data from historical studies, dependency of the two noninferiority tests can be very high. In order to control the correlation under 15%, the overall sample size of the historical studies needs to be at least five times of the current active control trial. PMID- 17365225 TI - Noninferiority testing beyond simple two-sample comparison. AB - In order to fulfill the requirement of a new drug application, a sponsor often need to conduct multiple clinical trials. Often these trials are of designs more complicated than a randomized two-sample single-factor study. For example, these trials could be designed with multiple centers, multiple factors, covariates, group sequential and/or adaptive scheme, etc. When an active standard treatment used as the control treatment in a two-arm clinical trial, the efficacy of the test treatment is often established by performing a noninferiority test through comparison of the test treatment and the active standard treatment. Typically, the noninferiority trials are designed with either a generalized historical control approach (i.e., noninferiority margin approach or delta-margin approach) or a cross-trial comparison approach (i.e., synthesis approach or lambda-margin approach). Many of the statistical properties of the approaches discussed in the literature were focused on testing in a simple two sample comparison form. We studied the limitations of the two approaches for the consideration of switching between superiority and noninferiority testing, feasibility to be applied with group sequential design, constancy assumption requirements, test dependency in multiple trials, analysis of homogeneity of efficacy among centers in a multi center trial, data transformation and changing analysis method from the historical studies. Our evaluation shows that the cross-trial comparison approach is more restricted to simple two sample comparison with normal approximation test because of its poor properties with more complicated design and analysis. On the other hand, the generalized historical control comparison approach may have more flexible properties when the variability of the margin delta is indeed negligibly small. PMID- 17365226 TI - Noninferiority tests based on concordance correlation coefficient for assessment of the agreement for gene expression data from microarray experiments. AB - Microarray is one of the breakthrough technologies in the twenty-first century. Despite of its great potential, transition and realization of microarray technology into the clinically useful commercial products have not been as rapid as the technology could promise. One of the primary reasons is lack of agreement and poor reproducibility of the intensity measurements on gene expression obtained from microarray experiments. Current practices often use the testing the hypothesis of zero Pearson correlation coefficient to assess the agreement of gene expression levels between the technical replicates from microarray experiments. However, Pearson correlation coefficient is to evaluate linear association between two variables and fail to take into account changes in accuracy and precision. Hence, it is not appropriate for evaluation of agreement of gene expression levels between technical replicates. Therefore, we propose to use the concordance correlation coefficient to assess agreement of gene expression levels between technical replicates. We also apply the Generalized Pivotal Quantities to obtain the exact confidence interval for concordance coefficient. In addition, based on the concept of noninferiority test, a one sided (1 - alpha) lower confidence limit for concordance correlation coefficient is employed to test the hypothesis that the agreement of expression levels of the same genes between two technical replicates exceeds some minimal requirement of agreement. We conducted a simulation study, under various combinations of mean differences, variability, and sample size, to empirically compare the performance of different methods for assessment of agreement in terms of coverage probability, expected length, size, and power. Numerical data from published papers illustrate the application of the proposed methods. PMID- 17365227 TI - An alternative approach to assess exchangeability of a test treatment and the standard treatment with normally distributed response. AB - In order to assess the equivalence of two treatments, clinical trials are designed to test against the null hypothesis that the difference (or ratio) of two means (proportions) is either smaller than a pre-specified lower equivalence limit or larger than a pre-specified upper equivalence limit. For example, in generic drug evaluation, such approach is defined as average bioequivalence. However, average equivalence type test is often criticized as lack of the ability to assess the exchangeability of the two treatments. In this article, we restate the statistical hypotheses in the form of stochastic inequalities. The stochastic statement can then be generalized to define the probability of exchangeability (i.e., coverage percentage) of the two treatments. The approach will be illustrated with a numeric example. PMID- 17365228 TI - Mixed noninferiority margin and statistical tests in active controlled trials. AB - In an active controlled noninferiority trial without a placebo arm, one of the major considerations is the selection of the noninferiority margin. Although the ICH E10 guideline provides general principles for the selection of appropriate noninferiority margins, there are no established rules or gold standards for the selection of noninferiority margins in active control trials. Hung et al. (2003) proposed a margin selection based on relative risk. However, with relative risk, it is difficult to adjust for covariates. On the other hand, Chow and Shao (2006) proposed a method for selecting noninferiority margins based on treatment difference. The determination of noninferiority margin based on either a test for treatment difference or a test for relative risk would be critical. In this paper, we propose a method for noninferiority testing with the use of a mixed null hypothesis. The mixed null hypothesis consists of a margin based on treatment difference and a margin based on relative risk. Both noninferiority margins will simultaneously satisfy the principles as described in the ICH E10 guideline. Statistical tests for mixed noninferiority margin are also derived. An example concerning the efficacy of a test therapy to an active control on a clinical adverse event in the target patient population with cardiovascular disease is presented to illustrate the proposed method. Simulation studies were also conducted to assess the type I error rate and the power. PMID- 17365232 TI - Imaging sequences for first pass perfusion --a review. AB - Myocardial perfusion imaging sequences and analysis techniques continue to improve. We review the state-of-the-art in cardiovascular magnetic resonance first pass perfusion pulse sequences including the application of parallel imaging. There are a wide range of sequence designs and parameters to consider when optimizing an acquisition protocol. The interdependence of these parameters forces the user to make compromises. We describe the technical issues and provide insights into the various performance tradeoffs. We also review the basic design for T1-weighted first pass myocardial perfusion imaging and go on to discuss the tradeoffs associated with various schemes to provide multi-slice coverage. Artifact mechanisms are discussed and related to sequence design and parameters. The selection of quantitative versus qualitative analysis affects various performance requirements, such as spatial and temporal resolution and linearity of enhancement. Understanding the interaction between the pulse sequence parameters and resulting image quality is important for improving myocardial perfusion imaging. PMID- 17365233 TI - How we perform myocardial perfusion with cardiovascular magnetic resonance. AB - Cardiovascular magnetic resonance first-pass perfusion imaging has developed considerably over the past decade. Several studies have shown that this technique is accurate for the detection of myocardial ischemia. In this article we outline the procedure of myocardial perfusion imaging with cardiovascular magnetic resonance as it is performed at our centers, describe the sequences that are currently used in more detail, review our process of image interpretation, and highlight potential pitfalls that we have encountered in our experience with performing this technique in over 2000 patients. PMID- 17365234 TI - A combined method for the determination of myocardial perfusion in experimental animals using microspheres and CMR. AB - A convenient method is introduced for myocardial perfusion research by combining multislice short-axis cine cardiovascular magnetic resonance (MSA-CMR) and colored microspheres (CM). In canine control-ischemia-reperfusion (n = 11), Cardiac output (CO) was measured using MSA-CMR (COMSA), Phase Contrast CMR (PC CMR, COPC) and CM (from reference blood samples, COmicro) in 3 experimental periods per animal. COmicro significantly and systematically overestimated COMSA (median deviation: 291 mL/min, p < 0.01), while there was excellent agreement between PC-CMR and MSA-CMR without significant over-or underestimation (median deviation: -14 ml/min, p = NS). In quantitative myocardial perfusion assay by CM, CMR should be used instead of reference blood sampling. This should improve the accuracy of absolute regional perfusion measurement. PMID- 17365235 TI - Validation of a high-resolution, phase contrast cardiovascular magnetic resonance sequence for evaluation of flow in coronary artery bypass grafts. AB - The aim was to validate a magnetic resonance high-resolution, phase-contrast sequence for quantifying flow in small and large vessels and to demonstrate its feasibility to measure flow in coronary artery bypass grafts. A breathhold, echo planar imaging (EPI) sequence was developed and validated in a flow phantom using a fast field echo (FFE) sequence as reference. In 17 volunteers aortic flow was measured using both sequences. In 5 patients flow in the left internal mammary artery (LIMA) and aorta was measured at rest and during adenosine stress, and coronary flow reserve (CFR) was calculated; in 7 patients, vein graft flow velocity was measured. In the flow phantom measurements, the EPI sequence yielded an excellent correlation with the FFE sequence (r = 0.99; p < 0.001 for all parameters). In healthy volunteers, aortic volume flow correlated well (r = 0.88; p < 0.01), with a minor overestimation. It was feasible to measure flow velocity in the LIMA and vein grafts of the 12 patients. The high-resolution, breathhold cardiovascular magnetic resonance velocity-encoded sequence correlated well with a free-breathing, FFE sequence in a flow phantom and in the aortae of healthy volunteers. Using the EPI sequence, it is feasible to measure flow velocity in both LIMA and vein grafts, and in the aorta. PMID- 17365236 TI - Fluorine cardiovascular magnetic resonance angiography in vivo at 1.5 T with perfluorocarbon nanoparticle contrast agents. AB - While the current gold standard for coronary imaging is X-ray angiography, evidence is accumulating that it may not be the most sensitive technique for detecting unstable plaque. Other imaging modalities, such as cardiovascular magnetic resonance (CMR), can be used for plaque characterization, but suffer from long scan and reconstruction times for determining regions of stenosis. We have developed an intravascular fluorinated contrast agent that can be used for angiography with cardiovascular magnetic resosnace at clinical field strengths (1.5 T). This liquid perfluorocarbon nanoparticle contains a high concentration of fluorine atoms that can be used to generate contrast on 19F MR images without any competing background signal from surrounding tissues. By using a perfluorocarbon with 20 equivalent fluorine molecules, custom-built RF coils, a modified clinical scanner, and an efficient steady-state free procession sequence, we demonstrate the use of this agent for angiography of small vessels in vitro, ex vivo, and in vivo. The surprisingly high signal generated with very short scan times and low doses of perfluorocarbon indicates that this technique may be useful in clinical settings when coupled with advanced imaging strategies. PMID- 17365237 TI - Feasibility of cardiovascular magnetic resonance of angiographically diagnosed congenital solitary coronary artery fistulas in adults. AB - OBJECTIVE: To evaluate the use of cardiovascular magnetic resonance (CMR) to visualize angiographically-detected congenital coronary artery fistulas in adults. METHODS: CMR techniques were used to study 13 patients, recruited from the Dutch Registry, with previously angiographically diagnosed fistulas. RESULTS: Coronary fistulas were detected in 10 of 13 (77%) patients by CMR and, retrospectively, in two (92%) more. In 93% of these, it was possible to determine the origin and the outflow site of the fistulas. Cardiovascular magnetic resonance allowed demonstration of dilatation of the fistula-related coronary artery in all cases. Tortuosity of fistulas was detected in all visualized patients. Uni-or bilaterality of fistulas as seen on CAG was proven on CMR in all patients. Flow measurement could be performed in 8 patients. A fairly good correlation (r = 0.72) was found between angiographic (mean 6.2 mm, range 1-16) and cardiovascular magnetic resonance (mean 6.3 mm, range 3-15) measured fistulous diameters. CONCLUSIONS: Cardiovascular magnetic resonance of congenital fistulas with clinical significant shunting is feasible and can provide additional physiological data complementary to the findings of conventional coronary angiography. PMID- 17365238 TI - Visualization of vascular hemodynamics in a case of a large patent ductus arteriosus using flow sensitive 3D CMR at 3T. AB - Comprehensive flow velocity acquisition based on time-resolved three-dimensional phase-contrast CMR with three-directional velocity encoding was employed to assess arterial hemodynamics in a patient with a large patent ductus arteriosus with Eisenmenger's physiology. Computer-aided visualization of blood flow characteristics provided detailed information about temporal and spatial distribution of left and right ventricular outflow. Main findings included the depiction of the location and extent of two flow channels for systolic aortic filling, a relatively large amount of pulmonary artery to aortic flow confirming Eisenmenger's physiology, and a slight phase difference between right and left ventricular ejection. These results illustrate the feasibility of flow sensitive 3D CMR at 3T in relation to a potential field of clinical application such as congenital heart disease with abnormal vascular connections or shunt flow. PMID- 17365239 TI - Follow up in a case of cardiac contusion using cardiovascular magnetic resonance. PMID- 17365240 TI - Myocarditis associated with clozapine studied by cardiovascular magnetic resonance. PMID- 17365241 TI - Extent of myocardial hyperenhancement on late gadolinium-enhanced cardiovascular magnetic resonance correlates with q waves in hypertrophic cardiomyopathy. AB - PURPOSE: Despite several electrocardiographic, echocardiographic, electrophysiologic and pathologic studies, the cause of abnormal Q waves in patients with HCM remains unclear. Cardiovascular magnetic resonance (CMR) is a powerful in vivo diagnostic tool for evaluating cardiac morphology and function. We hypothesized that estimation of segmental and transmural extent of myocardial enhancement by late gadolinium enhancement (LGE) CMR could clarify the basis of Q waves. The purpose of this prospective study was to evaluate the morphological basis of abnormal Q waves in hypertrophic cardiomyopathy (HCM) as assessed by CMR. METHODS: Thirty-eight patients with HCM underwent gadolinium-enhanced CMR and 12 lead electrocardiography (ECG). Left ventricular function, volumes, segmental and transmural extent of myocardial LGE were assessed and analysed in relation to the presence of abnormal Q waves. RESULTS: Twelve (31%) of the 38 patients had abnormal Q waves on the ECG. Patients with Q waves exhibited significantly more myocardial LGE segmentally as well as transmurally than patients without Q waves. As the segmental and the transmural extent of LGE increased, the probability of Q wave increased (anterior: segmental extent chi2 = 10, p = 0.0013, transmural extent chi2 = 10, p = 0.0013; inferior: segmental extent chi2 = 13, p = 0.0003, transmural extent chi2 = 15, P < 0.0001: lateral: segmental extent chi2 = 10, p = 0.0016, transmural extent chi2 = 10, p = 0.0012). Additionally, the ratio of septal to posterior wall thickness was significantly higher in patients with Q waves than in patients without Q waves (2.3 vs. 1.6, p = 0.012). CONCLUSIONS: It seems that segmental and transmural extent rather than the mere presence of myocardial LGE is the underlying mechanism of abnormal Q waves in HCM. Additionally, distribution of hypertrophy as indicated by differences in the ratio of septal to posterior wall thickness seems to play an important role. PMID- 17365242 TI - Fat deposition in the myocardium of the left ventricle. AB - We present a case of post-myocardial infarction fat deposition of the left ventricle in a 68-year-old-man. Fat deposition and myocardial infarction are demonstrated using pre-and post-contrast magnetic resonance. PMID- 17365243 TI - Comparison of SSFP and IR GRE techniques for measurement of total myocardial mass influence of applied contrast dosage and implication for relative infarct size assessment. AB - OBJECTIVE: To compare total left ventricular mass assessment using steady state free precession (SSFP) and inversion recovery fast gradient echo (IR GRE) imaging and further to assess the influence of contrast dosage on mass by IR GRE and its implications on relative infarct size assessment with both methods. METHODS: Forty-three patients with first documented myocardial infarction and single vessel disease underwent measurement of total myocardial mass using SSFP technique and an IR GRE sequence. As part of a Phase 2 multi-center dose ranging study for infarct identification patients received 1 of 4 possible dosages (0.05, 0.1, 0.2 or 0.3 mmol/kg body weight) of the contrast agent gadoversetamide (OptiMARK, Tyco Healthcare Mallinckrodt, St. Louis, MO, USA). RESULTS: Left ventricular mass assessment using IR GRE resulted in a slightly greater detection of myocardial mass than from the SSFP images (160.1 and 156.4 g, respectively, p < 0.001). The overall good correlation of both methods (R2 = 0.97 for the total study group, p < 0.001) was further improved by using gadoversetamide at doses of 0.2 or 0.3 mmol/kg (R2= 0.99, p < 0.001), mainly as a result of a considerably higher blood-myocardial contrast-to-noise ratio (CNR) in the IR GRE images. Bland Altman analysis in these subgroups showed very little scatter of the residuals over the mean (3.5 +/- 5.4 g and 1.3 +/- 6.9 g respectively, 95% confidence interval). The observed differences in total mass calculation, while statistically significant, were not correlated with clinically relevant differences in estimation of relative infarct size. CONCLUSION: Total LV mass calculations using SSFP and IR GRE techniques are interchangeable when using appropriate contrast media, such as gadoversetamide. Late gadolinium enhancement results in good blood myocardial CNR. Hence, for relative infarct size assessment either method for calculation of total myocardial mass can be used. PMID- 17365244 TI - Validation study of a semi-automated program for quantification of atherosclerotic burden. AB - Practical implementation of cardiovascular magnetic resonance (CMR) for the noninvasive screening of atherosclerosis is limited by inter-and intra-observer variability and labor intensity of morphometric analysis by manual planimetry (MANU). We assessed the hypothesis that a semi-automated quantification program (AUTO) for CMR would be faster and more accurate than MANU without loss of reliability. In the analysis of carotid atherosclerosis in asymptomatic hypercholesterolemic patients (n = 17), AUTO was superior to MANU in speed and histopathologic correlation without significant differences in inter-and intra observer variability. Implementation of AUTO may facilitate CMR for the screening of the burden of atherosclerotic disease. PMID- 17365245 TI - Cardiac fibroelastoma: cardiovascular magnetic resonance characteristics. PMID- 17365246 TI - Functional assessment of isolated right heart failure by high resolution in-vivo cardiovascular magnetic resonance in mice. AB - Precise and noninvasive characterization of the development of the cardiac phenotype in murine models of heart failure has been widely demanded in modern cardiovascular research. High-resolution cardiovascular magnetic resonance (CMR) has been proven to be a powerful tool for the accurate and reproducible assessment of LV and RV parameters in healthy mice. Whereas changes in LV parameters in models of heart failure have been thoroughly evaluated, RV dysfunction has not. Purpose of this study was to characterize a model of isolated RV failure induced by pulmonal banding by in vivo CMR at 7T. RV parameters differed significantly from those of normal mice in terms of RV end diastolic volume (EDV: 85 +/- 14 microL vs. control 36 +/- 3 microL, p < 0.0001), RV end-systolic volume (ESV: 121 +/- 10 microL vs. control 84 +/- 4 microL, p < 0.005) and RV ejection fraction (EF: 31 +/- 6 % vs. control 57 +/- 2 %, p < 0.001). With regard to EDV, ESV, SV and EF LV parameters, there were no significant differences between pulmonary banded and control mice indicating overt isolated RV failure. PMID- 17365247 TI - Neuropsychological correlates of manganese exposure: a meta-analysis. AB - The hypothesized effect of recurrent low-dose manganese (Mn) exposure on neuropsychological function is controversial because of inconsistent findings across three decades of research. We conducted a meta-analysis on 41 variables from nineteen neuropsychological studies of Mn-exposed workers. The results showed: Large effect size (ES) for biological markers of Mn and lead levels; thirteen of 26 neurocognitive measures showing a small average ES; only one of 26 tasks showed a moderate ES; and small to medium ES for confounding/competing variables such as education and aptitude. Tasks with the highest ES included clerical substitution tasks, digit span, tapping endurance, and Swedish Performance Evaluation System "Additions" reaction time, but none exceeded the ES for education or aptitude. The mean ES of dose-response relationships was zero. The data did not support a theory of preclinical ("early") neuromotor or cognitive dysfunction. Overall, the pooled data are more consistent with covariate effect than toxic effect, insofar as the pooled exposure group showed demographics less favorable to neuropsychological performance than the pooled referent groups. Future consideration of demographic and biological covariates is necessary before inferring subtle toxin-induced brain damage because neuropsychological tests are nonspecific. PMID- 17365248 TI - Mapping the connections between education and dementia. AB - Explanations for the association between educational attainment and the risk of dementia fall into three main categories. It may arise as an artefact of study methods; education may predict broader socioeconomic circumstances and exposures, or education may reflect brain reserve or cognitive capacity that protect against dementia. Data from the Canadian Study of Health and Aging (N=6646, giving 44,676 person-years of follow-up) are analyzed to test a series of hypotheses reflecting these explanations. Years of education showed a strong association with the risk of dementia (relative risk [RR] 2.1 for those with less than 6 years of education compared to those with 13 or more years; RR=2.9 among survivors). Possible artefactual factors were detected, but were insufficient to invalidate the association. Adjustments for a range of other socioeconomic indicators, health problems and lifestyle factors reduced, but did not remove, the association. Adjustments for intelligence and for an indicator of lifetime mental activity also appeared to account for some but not all of the association. The conclusion is that there appears to be a real association between educational attainment and the risk of dementia 50 to 60 years later; this influence appears to run through a number of different, and sometimes complementary, pathways. PMID- 17365249 TI - MS vs. HD: can white matter and subcortical gray matter pathology be distinguished neuropsychologically? AB - This study was conducted to examine the neuropsychological effects of white matter and subcortical gray matter pathology. Nineteen patients with multiple sclerosis (MS), 16 with Huntington's disease (HD), and 17 normal controls (NC) participated. Participants completed the California Verbal Learning Test (CVLT), Rotary Pursuit (RP) and Mirror Tracing (MT) tasks, and the Symbol Digit Modalities Test (SDMT). The principal findings pertain to a dissociation in procedural memory: on RP, the HD group demonstrated impaired sequence learning compared to the MS group, which performed similarly to the NC group, yet on MT, the MS and HD groups demonstrated normal perceptual-motor integration learning. On the CVLT, both patient groups performed better on recognition than on recall. On the SDMT, both patient groups performed worse than the NC group, with the HD group performing more poorly than the MS and NC groups. These results suggest that involvement of white and subcortical gray matter may produce different neuropsychological effects. PMID- 17365250 TI - Executive functions among individuals with methamphetamine or alcohol as drugs of choice: preliminary observations. AB - Substance dependent individuals (SDIs) are frequently, but not invariably, impaired on tasks of executive functions. In this study, we examine patterns of executive performance among subjects with different self-reported "drug of choice" (defined as substance used>80% of the time prior to abstinence). Subjects were 33 abstinent SDIs receiving inpatient treatment and 19 non-SDI normal controls (NC) well-matched on age, sex, ethnicity, and VIQ, who were assessed using the Iowa Gambling Task (GT) and a delayed non-match to sample task (DNM): measures of decision making and working memory, respectively. Seventeen SDIs identified alcohol (AL group) and 16 SDIs identified methamphetamine (METH group) as their drug of choice. Overall, the METH group performed more poorly than the NC and AL groups on both tasks, with the largest differences observed in working memory. The AL group was not significantly impaired overall compared to NCs on either task, but showed subtle abnormalities of GT performance similar to the METH group. These preliminary findings suggest that self-reported drug of choice on admission to treatment may be associated with different patterns of executive performance during early recovery. PMID- 17365251 TI - Comparing Mattis Dementia Rating Scale--initiation/perseveration subset and frontal assessment battery in stroke associated with small vessel disease. AB - Forty-two controls and 32 patients with stroke associated with small vessel disease (SSVD) were administered the Mattis Dementia Rating Scale Initiation / Perseveration subset (MDRS I/P) and Frontal Assessment Battery (FAB). Both tests showed comparably good ability in Receiver Operating Characteristics curves analysis (AUCMDRS I/P=0.887; AUC FAB=0.854, p=.833) in discriminating between controls and patients and correctly classified over 78% of subjects. Verbal fluency and motor programming contributed most to the discriminating power in the two tests. The MDRS I/P and FAB are useful in discriminating between controls and SSVD patients in a hospital setting. PMID- 17365252 TI - Cognitive and executive functions in anorexia nervosa ten years after onset of eating disorder. AB - In a longitudinal study, the authors explore the course of general cognition in anorexia nervosa (AN) over time and compare general cognitive problems, executive function deficits, attentional problems and visuomotor dysfunctions across AN individuals and healthy controls. A community-based sample of adolescent onset AN cases (n=40-47) was contrasted with an age-, sex- and school matched comparison group (n=47-51) on the Wechsler Adult Intelligence Scale-Revised, the Wisconsin Card Sorting Test and Luria word recall test at a mean age of 24 years. Only two of the cases tested were underweight at the time of the study. The Wechsler scale had also been administered when the groups had a mean age of 21 years. There were few differences across the two groups even though the comparison group performed significantly better on the Object Assembly subtest of the WAIS-R. IQ increased slightly but significantly over time in both groups. There was no relationship between level of starvation and poor results on tests in the AN group. A subgroup of the subjects had autism spectrum disorders. In this subgroup there were cases with test profiles similar to those observed in autism and Asperger syndrome, just as there had been on testing three years previously. Ten years after AN onset, the former AN cases showed no major neuropsychological deficits. A subgroup with autistic features had test profiles similar to those observed in autism spectrum disorders. The AN group as a whole showed poor results on the object assembly subtest indicating weak central coherence with a tendency to focus on details at the expense of configural information. This cognitive style may account for their obsession with details, with implications for psychoeducational approaches in treatment programmes/interventions. PMID- 17365253 TI - Central and peripheral aspects of writing disorders in Alzheimer's disease. AB - It is currently assumed that lexical and phonological dysgraphia emerge in different stages of Alzheimer's disease (AD) as a consequence of the progressive impairment of lexical and phonological knowledge. We studied patients affected by mild and severe dementia. No differences emerged in the distribution of surface and orthographic errors in the two groups of patients. Attention and memory disorders correlated with central and peripheral errors and language disorders with central errors. Our data suggest that AD dysgraphia is firstly produced by a reduction of general cognitive resources and only marginally by disorders of specific spelling sub-components. PMID- 17365254 TI - Verbal learning and memory deficits in Mild Cognitive Impairment. AB - Criteria for amnestic MCI rely on the use of delayed recall tasks to establish the presence of memory impairment. This study applied the California Verbal Learning Test to detail memory performance in MCI patients (n=70), as compared to control subjects (n=92) and AD patients (n=21). Learning across the 5 trials was different among the 3 groups. Learning strategy was also different, the MCI group showing less semantic clustering than the control group. However, both MCI patients and controls could benefit from semantic cueing. This study showed that beyond consolidation deficits, MCI patients have marked difficulties in acquisition and recall strategies. PMID- 17365255 TI - Age differences in concept formation. AB - In order to identify the source of age-related deficits in concept formation, older and younger adults completed a new Concept Matching Test, tests of selective attention, and the Sorting Test, a standardized test of concept formation (Delis, Kaplan, & Kramer, 2001). Older adults showed intact concept identification, the ability to generate abstract concepts from stimulus features, but age differences were observed when irrelevant features were present. In addition, selective attention, but not concept identification ability, predicted age-related declines on the Sorting Test. Thus, reduced concept formation in older adults may stem from declines in abilities other than the capacity for abstraction. PMID- 17365256 TI - Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis. AB - Multiple sclerosis (MS) is a disease of the central nervous system that causes cognitive impairment with a frequency of roughly 50%. While processing speed and memory defects are most commonly observed, a substantial number of patients also have deficiency in higher executive ability. Two tests, the Wisconsin Card Sorting Test (WCST) and the Sorting Test from the Delis-Kaplan Executive Function System (DKEFS), have been recommended for evaluation of neuropsychological impairment in MS. We investigated the validity of these tests in 111 MS patients and 46 age- and education-matched controls. MS patients performed more poorly on both measures, but only the DKEFS discriminated the groups after controlling for depression. Both tests were modestly or strongly correlated with MRI indices of brain atrophy or lesion burden and discriminated between employed and disabled patients. While both tests appear to have good validity in the MS population, the availability of alternative forms makes the DKEFS an attractive alternative to the WCST, as was suggested by a consensus panel. PMID- 17365258 TI - Misunderstandings. PMID- 17365259 TI - Melasma and its impact on health-related quality of life in Hispanic women. AB - OBJECTIVES: Melasma poses a substantial emotional and psychosocial burden on patients. Even though melasma is prevalent in Hispanic women, its impact on health-related quality of life (HRQOL) has been under-reported. The purpose of this review is to evaluate the impact of melasma on the HRQOL of Hispanic women. METHODS: An extensive literature review of articles published in English and Spanish over the last 15 years (1991-2006) was conducted. The search terms used to obtain relevant information were 'melasma', 'women', 'health-related quality of life', HRQOL', 'treatment', 'Hispanic', and 'Latino'. Specific issues covered include HRQOL issues in melasma, instruments used and treatment modalities available for melasma. RESULTS: The literature search revealed that melasma has a deleterious impact on the HRQOL. It severely affects social life, emotional well being, physical health and money matters in Hispanic women. CONCLUSION: Patient education, awareness and counseling are needed to improve HRQOL outcomes. PMID- 17365260 TI - A long-term gluten-free diet as an alternative treatment in severe forms of dermatitis herpetiformis. AB - BACKGROUND: A long-term gluten-free diet (GFD) as a first-choice treatment for dermatitis herpetiformis (DH) has been used successfully. The aim of the present study is to evaluate the possibility of treating all severe skin manifestations of DH by a GFD only. METHODS: Seventy-two patients with DH were subdivided in two groups: group A (18 patients) underwent a GFD and received dapsone; group B (54 patients) underwent a GFD. Patients were subdivided into slight, moderate and severe forms. RESULTS: A total of 88.9% of patients treated with dapsone and a GFD (group A) had remission of skin manifestations and the remaining 11.1% were improved. In group B, 87% of patients showed complete remission of skin manifestations after 18 months of a GFD; 13% showed improvement. With regard to severe forms, after an 18-month treatment, 70.4% of patients in group B; 66.6% in group A. CONCLUSION: Our study shows that a GFD, if administered steadily and for a long period, can be a valid treatment for severe forms of DH. Dapsone can be useful to control the inflammatory phase of the disease. PMID- 17365261 TI - Alefacept in corticosteroid refractory graft versus host disease: early results indicate promising activity. AB - Steroid refractory graft versus host disease (GVHD) presents a significant therapeutic challenge due to the limited efficacy and safety of second-line treatments. Three patients with extensively pretreated, refractory GVHD were treated with a targeted anti-T-cell agent, alefacept, and demonstrated rapid and clinically significant improvement in their GVHD, facilitating tapering of corticosteroids. The pathological and immunohistochemical findings of GVHD also improved, validating our clinical impression. These preliminary findings indicate that alefacept may have beneficial activity in GVHD warranting further study. PMID- 17365262 TI - Blood concentrations of pimecrolimus in adult patients with atopic dermatitis following intermittent administration of pimecrolimus cream 1% (Elidel) for up to 1 year. AB - OBJECTIVES: To determine blood concentrations of pimecrolimus after long-term intermittent administration of pimecrolimus cream 1% in adult patients with extensive atopic dermatitis (AD). METHODS: This was an open-label, multiple topical dose study in adults with moderate to severe AD and a total body surface area (TBSA) involvement of at least 20%. Pimecrolimus cream 1% was administered twice daily according to treatment need for up to 12 months to all lesions, including the neck and face. Blood samples were collected at regular time points and pimecrolimus concentrations were measured using a radioimmunoassay with a limit of quantitation (LoQ) of 0.5 ng/ml. RESULTS: Forty patients (19 females), aged from 19 to 59 years, with moderate to severe AD entered the study. Twenty patients completed 6 months and 13 completed 1 year in the study. The individual blood concentrations of pimecrolimus were consistently low and there was no sign of drug accumulation. In 900 of the 918 samples examined (98%), pimecrolimus concentrations remained below the LoQ. The maximum concentration observed throughout the entire study was 0.8 ng/ml. CONCLUSION: Long-term intermittent treatment of adult patients with extensive AD with pimecrolimus cream 1% is associated with minimal systemic exposure and no evidence of drug accumulation. PMID- 17365263 TI - Comparative efficacy of cetirizine and levocetirizine in chronic idiopathic urticaria. AB - H1 receptor antagonists are the mainstay of treatment for chronic idiopathic urticaria. Newer hydroxyzine derivatives such as cetirizine and levocetirizine have been found to be equally efficacious in preclinical studies in patients with chronic idiopathic urticaria. In this study, the clinical efficacy of cetirizine and levocetirizine has been studied sequentially in individual patients. Fifty chronic idiopathic urticaria patients received 10 mg of levocetirizine daily for 6 weeks. Some 45 patients out of these showed reasonably good clinical efficacy on a visual analog scale to qualify for comparison with levocetirizine. A total of 30 patients completed the study period of 6 weeks each of cetirizine and levocetirizine sequentially. Thus, the clinical efficacy of cetirizine and levocetirizine was comparable with a marginal advantage of better antipruritic effect with levocetirizine, probably at the cost of increased sedation. PMID- 17365264 TI - Adalimumab treatment is associated with improvement in health-related quality of life in psoriasis: patient-reported outcomes from a phase II randomized controlled trial. AB - BACKGROUND: Psoriasis substantially impairs the health-related quality of life (HRQOL) of patients, and a comprehensive evaluation of treatment includes HRQOL measures. OBJECTIVE: To assess the impact of adalimumab on patient-reported outcomes (PROs) of patients with moderate to severe psoriasis. METHODS: In a Phase II, randomized, controlled trial, the efficacy and safety of two dosages of adalimumab (40 mg weekly or every other week) versus placebo were assessed for 12 weeks in the treatment of moderate to severe plaque psoriasis. Patients completed the Dermatology Life Quality Index (DLQI), Short-Form 36 (SF-36) Health Survey, and EuroQOL-5D (EQ-5D) at baseline and 12 weeks. The primary endpoint was the percentage of patients achieving a > or =75% reduction in the Psoriasis Area and Severity Index score (PASI 75). Investigators assessed PASI and Physician's Global Assessment (PGA) scores. RESULTS: Adalimumab patients (either dosage) displayed significantly greater improvements versus placebo patients in DLQI, EQ 5D, and SF-36 Mental Component Summary scores, as well as in Bodily Pain, Vitality, Social Functioning, Role-Emotional, and Mental Health domains. The adalimumab 40-mg weekly group also reported significantly greater improvements in SF-36 Physical Component Summary scores versus the placebo group. CONCLUSION: Both adalimumab dosages were efficacious in improving dermatology-specific and general PROs in patients with moderate to severe psoriasis. PMID- 17365265 TI - Pulsed dye laser versus treatment with calcipotriol/betamethasone dipropionate for localized refractory plaque psoriasis: effects on T-cell infiltration, epidermal proliferation and keratinization. AB - BACKGROUND: Selective photothermolysis of diseased capillaries by pulsed dye laser (PDL) treatment has been described as a mechanism for long-lasting clearance of psoriatic plaques. AIM: To evaluate PDL and a two-compound formulation of calcipotriol/betamethasone dipropionate ointment for the treatment of localized, recalcitrant plaque psoriasis. METHODS: Eight psoriatic patients were treated for 4 weeks with both PDL and topical calcipotriol/betamethasone dipropionate in an open, intra-patient, left-right comparison. Biopsies were analyzed for T-cell subsets, cells expressing NK-receptors, epidermal proliferation, differentiation and epidermal thickness. RESULTS: After active treatment, both treatments showed statistically significant but comparable improvements of T-cell subsets, epidermal proliferation, differentiation and epidermal thickness. In line with the clinical results, after an 8-week follow-up period statistically significant further reductions were observed for dermal CD3(+), CD4(+), CD45RO(+), CD2(+) T cells, epidermal CD3(+), CD8(+), CD45RO(+), CD2(+), CD25(+) T cells and the epidermal parameters for the PDL-treated plaques, in contrast to the topically treated plaques. CONCLUSION: After 8 weeks of follow up, PDL treatment for localized and recalcitrant plaque psoriasis resulted in persistent reductions of activated and memory effector T-helper cells in the dermis, cytotoxic T cells in the epidermis, and normalization of epidermal proliferation and keratinization, in contrast to treatment with calcipotriol/betamethasone dipropionate ointment. PMID- 17365266 TI - A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis. AB - Dithranol is infrequently used in psoriasis in spite of excellent efficacy due to its local adverse effects. We have synthesized a novel formulation of dithranol in which the drug is entrapped in phospholipid liposomes. This formulation has shown markedly low irritation and minimal staining of skin and clothes in preliminary studies. Twenty patients with bilaterally symmetrical stable plaque psoriasis applied 0.5% dithranol lipogel to lesions over one side of the body. On the other side, 10 patients were randomized to apply pure liposomal base and 10 applied a conventional cream containing 1.15% dithranol, 1.15% salicylic acid and 5.3% coal tar in a 30-minute, short contact regimen for 6 weeks. Patients were assessed for disease severity, perilesional erythema and skin staining, pruritus and any other adverse effects at baseline, 2, 4 and 6 weeks. Both lipogel and the cream significantly reduced the total severity score compared to the liposomal base at 4 (p = 0.004) and 6 (p = 0.01) weeks. There was no significant difference in the clinical response of dithranol cream and lipogel. Markedly low incidence and severity of perilesional erythema (p<0.001) and skin staining (p<0.05) was seen with the lipogel in comparison with the cream. PMID- 17365267 TI - Management of actinic keratosis patients: a qualitative study. AB - OBJECTIVES: In order to reinforce the appropriate UV-related behaviour of patients with actinic keratosis (AK), it is of importance to understand the underlying psychological aspects of having AK. MATERIALS AND METHODS: Open and systematic explorative interviews were conducted with 15 AK patients. Open, single interviews (n = 6) were made and summarized. Partly based on topics found by the single interviews, two qualitative group interviews (n = 7) with AK patients were performed. The topics of general importance were identified through analysis of the statements given at the group interviews. A third group interview (n = 2) was made to confirm the analytical results from the former interviews. RESULTS: Important topics for patients with AK were found to relate to the way to act in the sun (leisure time and outdoor work), a changed appearance, the seriousness of the AK diagnosis, control of the disease, and the sense of illness due to AK. Emotional reactions included worry, fear, irritation, doubt, guilt, and a relaxed attitude. CONCLUSION: It is suggested that the topics touched upon form psychological and pedagogical reference points for patient behaviour. Awareness of these topics is therefore recommended in the management of patient information related to AK. PMID- 17365268 TI - Cutaneous granulomatous reaction to injectable hyaluronic acid gel: another case. AB - We report a case of a granulomatous reaction in the melolabial folds, occurring 10 days after treatment with Restylane. The patient, who had previously been treated with the same product in the last 2 years without any adverse effect, developed an unusual early fibrotic reaction that we hypothesized related to hypersensitivity after repeated use. The lesions slowly disappeared with topical steroid therapy. An improved knowledge of the modality of these uncommon adverse effects is necessary to assess the long-term safety and efficacy of this product. PMID- 17365271 TI - Recent advances in delivery systems for anti-HIV1 therapy. AB - In the last years, different non-biological and biological carrier systems have been developed for anti-HIV1 therapy. Liposomes are excellent potential anti-HIV1 carriers that have been tested with drugs, antisense oligonucleotides, ribozymes and therapeutic genes. Nanoparticles and low-density lipoproteins (LDLs) are cell specific transporters of drugs against macrophage-specific infections such as HIV1. Through a process of protein transduction, cell-permeable peptides of natural origin or designed artificially allow the delivery of drugs and genetic material inside the cell. Erythrocyte ghosts and bacterial ghosts are a promising delivery system for therapeutic peptides and HIV vaccines. Of interest are the advances made in the field of HIV gene therapy by the use of autologous haematopoietic stem cells and viral vectors for HIV vaccines. Although important milestones have been reached in the development of carrier systems for the treatment of HIV, especially in the field of gene therapy, further clinical trials are required so that the efficiency and safety of these new systems can be guaranteed in HIV patients. PMID- 17365272 TI - Establishment of subcellular fractionation techniques to monitor the intracellular fate of polymer therapeutics II. Identification of endosomal and lysosomal compartments in HepG2 cells combining single-step subcellular fractionation with fluorescent imaging. AB - As they are often designed for lysosomotropic, endosomotropic and/or transcellular delivery, an understanding of intracellular trafficking pathways is essential to enable optimised design of novel polymer therapeutics. Here, we describe a single-step density gradient subcellular fractionation method combined with fluorescent detection analysis that provides a new tool for characterisation of endocytic traffic of polymer therapeutics. Hepatoma (HepG2) cells were used as a model and cell breakage was optimised using a cell cracker to ensure assay of the whole cell population. After removal of unbroken cells and nuclei, the cell lysate as a post-nuclear supernatant (PNS) was layered onto an iodixanol (OptiPrep) density gradient optimised to 5-20%. Early endosomes, late endosomes and lysosomes were identified from gradient fractions by immunoblotting for marker proteins early endosome antigen 1 (EEA 1) and lysosomal associated membrane protein 1 (LAMP 1) using horseradish peroxidase or fluorescently labelled secondary antibodies. Lysosomes were also detected using N-acetyl-beta glucosamindase (Hex A) activity. In addition, cells were incubated with Texas-red labelled transferrin (TxR-Tf) for 5 min to specifically label early endosomes and this was directly detected from SDS-PAGE gels. Internalised macromolecules and colloidal particles can potentially alter vesicle buoyant density. To see if typical macromolecules of interest would alter vesicle density or perturb vesicle traffic, HepG2 cells were incubated with dextran or a polyethyleneglycol (PEG) polyester dendron G4 (1 mg/ml for 24 h). The PEG-polyester dendron G4 caused a slight redistribution of endocytic structures to lower density fractions but immunofluorescence microscopy showed no obvious dendron effects. In conclusion, the combined subcellular fractionation with fluorescent imaging approach described here can be used as a tool for both fundamental cell biology research and/or the quantitative localisation of polymer therapeutics in the endocytic pathway. PMID- 17365270 TI - Matrix metalloproteases: underutilized targets for drug delivery. AB - Pathophysiological molecules in the extracellular environment offer excellent targets that can be exploited for designing drug targeting systems. Matrix metalloproteases (MMPs) are a family of extracellular proteolytic enzymes that are characterized by their overexpression or overactivity in several pathologies. Over the last two decades, the MMP literature reveals heightened interest in the research involving MMP biology, pathology and targeting. This review describes various strategies that have been designed to utilize MMPs for targeting therapeutic entities. Key factors that need to be considered in the successful design of such systems have been identified based on the analyses of these strategies. Development of targeted drug delivery using MMPs has been steadily pursued; however, drug delivery efforts using these targets need to be intensified and focused to realize the clinical application of the fast developing fundamental MMP research. PMID- 17365273 TI - Synthesis and characterization of RGD-fatty acid amphiphilic micelles as targeted delivery carriers for anticancer agents. AB - Novel amphiphilic conjugates consisting of an Arg-Gly-Asp (RGD) peptide binding motif and aliphatic fatty acids of varying chain length (C10-C18) were synthesized and evaluated for their ability to form micelles and bind specifically to alphaVbeta3 integrin over-expressing tumor cells. The aphilphiles were characterized by IR, proton NMR and mass spectrometry. The size and zeta potential of the resultant micelles were ranged from 178 to 450 nm and - 13.5 to 39.6 mV, respectively. The critical micellar concentration (CMC), drug loading efficiency and tumor cell binding of these amphiphiles were determined. The CMC values, determined by pyrene fluorescent probe method, ranged from 0.02 to 0.12 mM for C14-RGD, C16-RGD and C18-RGD. The C18-RGD micelles with lowest CMC were found to increase the solubility of taxol, a model anticancer drug, by 87%. C18 RGD amphiphiles also exhibited significantly higher (12.1 +/- 1.14%, P < 0.05) binding to alphaVbeta3 integrin over-expressing human breast cancer cells (HTB 129) when compared to normal human epidermal keratinocyte (NHEK) cells (6.68 +/- 0.34). The results from this study demonstrated the feasibility of designing RGD fatty acid amphiphiles as micellar drug delivery carriers to target to cancer cells. PMID- 17365274 TI - Nose-to-brain delivery of TS-002, prostaglandin D2 analogue. AB - This study was conducted to investigate the possibility of performing nose-to brain delivery of TS-002, which is an analog compound of prostaglandin D2 (PGD2) and thus would be a natural sleep inducer. The absolute bioavailability (BA) and sleep-inducing effect (SIE) following intranasal (IN) administration of TS-002 dry powder to cynomolgus monkeys were evaluated in comparison with intravenous (IV) administration. The SIE was evaluated as the accumulated time of sleeping posture for 3 h. The brain distribution of TS-002 following IN administration of the dry powder was examined in rats. The absolute bioavailability (BA) in monkeys following IN administration of the dry powder (0.4-1.2 mg/body) was comparatively high (43.4-78.0%). The SIE following IN administration (0.05-0.4 mg/body) showed dose-dependency and its effect at 0.4 mg/body was twice as strong as that for IV administration (P < 0.05). The brain concentrations in rats following IN administration (0.1 mg/kg) were obviously higher than that for IV administration at the same dose. The highest content was observed in the olfactory bulb. These results demonstrated that TS-002 was directly transported from the olfactory region to brain, thereby showing that it may be possible to develop a novel sleep inducing drug based on nose-to-brain delivery. PMID- 17365275 TI - P-glycoprotein mediates brain-to-blood efflux transport of buprenorphine across the blood-brain barrier. AB - The involvement of P-glycoprotein (P-gp) in buprenorphine (BNP) transport at the blood-brain barrier (BBB) in rats was investigated in vivo by means of both the brain uptake index technique and the brain efflux index technique. P-gp inhibitors, such as cyclosporin A, quinidine and verapamil, enhanced the apparent brain uptake of [3H]BNP by 1.5-fold. The increment of the BNP uptake by the brain suggests the involvement of a P-gp efflux mechanism of BNP transport at the BBB. [3H]BNP was eliminated with an apparent elimination half-life of 27.5 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [3H]BNP across the BBB was 0.154 ml/min/g brain, which was calculated from the elimination rate constant (2.52 x 10- 2 min- 1) and the distribution volume in the brain (6.11 ml/g brain). The efflux transport of [3H]BNP was inhibited by range from 32 to 64% in the presence of P-gp inhibitors. The present results suggest that BNP is transported from the brain across the BBB via a P-gp-mediated efflux transport system, at least in part. PMID- 17365276 TI - Delivery of viral vectors to hepatic stellate cells in fibrotic livers using HVJ envelopes fused with targeted liposomes. AB - Hepatic stellate cells (HSC) are a major target for antifibrotic therapies in the liver and in particular gene delivery to these cells would be relevant. Previously, we demonstrated that mannose 6-phosphate human serum albumin (M6P HSA) coupled liposomes accumulate in HSC in fibrotic livers. Here we prepared a M6P-HSA modified viral vector that allows the targeted delivery of plasmid DNA to HSC. Therefore, UV inactivated hemagglutinating virus of Japan (HVJ) containing plasmid DNA was fused with M6P-HSA liposomes to yield HVJ liposomes targeted to HSC. These new particles had a diameter of approximately 200 nm, as determined by electron microscopy. In a carbon tetrachloride mouse model of liver fibrosis, M6P HSA-HVJ-liposomes associated with HSC. In conclusion, our results demonstrate that fusion of M6P-HSA liposomes with HVJ envelopes results in HVJ particles that accumulate in HSC, allowing for new possibilities to interfere with fibrosis in the liver. PMID- 17365277 TI - Toxicogenomics of drug delivery systems: Exploiting delivery system-induced changes in target gene expression to enhance siRNA activity. AB - Synthetic siRNAs are typically formulated with drug delivery systems (DDS) that improve cellular uptake for optimal gene silencing activity. Here, we show that two PAMAM dendrimer DDS, differing only in their structural architecture, elicit many different gene expression changes in human cells including opposing effects on the expression of epidermal growth factor receptor (EGFR), a gene targeted for silencing by siRNA. Despite providing similar improvements in siRNA uptake, these two formulations led to a approximately 10-fold variation in anti-EGFR siRNA activity. These data show that gene expression changes induced by DDS, separate from their ability to enhance cell uptake, determine 'apparent' siRNA potency and thus offer the possibility of tailoring delivery system-siRNA combinations for additive or synergistic effects on gene silencing. PMID- 17365278 TI - Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro. AB - Cells of the mononuclear phagocytic system, in particular monocytes/macrophages (Mo/Mac) serve as a reservoir for human immunodeficiency virus (HIV) and are believed to be responsible for its dissemination throughout the body and especially into the brain. Treatment of HIV infection, therefore, must reach these cells in addition to the lymphocytes. The purpose of the present study is to develop poly(propyleneimine) (PPI) dendrimer-based nanocontainers for targeting of efavirenz (EFV) to Mo/Mac. Fifth generation PPI dendrimer, t-Boc glycine conjugated PPI dendrimer (TPPI) and mannose conjugated dendrimers were synthesized and characterized. While the haemolytic activity and cytotoxicity of PPI dendrimer was found to be very high, the toxicity of t-Boc-glycine conjugated dendrimer and mannose conjugated dendrimers were found to be negligible. The entrapment efficiency of mannose conjugated dendrimer was found to be 47.4%, followed by that of PPI dendrimer (32.15%) and t-Boc-glycine conjugated dendrimer (23.1%). The in vitro drug release profile shows that while PPI dendrimer releases the drug by 24 h, the dendrimer-based nanocontainers prolong the release rate up to 144 h (83 +/- 0.4% in case of t-Boc-glycine conjugated dendrimer and 91 +/- 0.3% in mannose conjugated dendrimer). The cellular uptake of EFV was found to be both concentration and time dependent. Significant increase in cellular uptake of EFV by Mo/Mac cells were observed in case of mannose conjugated dendrimer which is 12 times higher than that of free drug and 5.5 times higher than that of t-Boc-glycine conjugated dendrimer. While mannose conjugated dendrimer was taken up by the lectin receptors of the cells, phagocytosis of t-Boc-glycine conjugated dendrimer might be responsible for its enhanced uptake. Results suggest that the proposed carriers hold potential to increase the efficacy and reduce the toxicity of antiretroviral therapy. PMID- 17365280 TI - Liposomes and niosomes as potential carriers for dermal delivery of minoxidil. AB - The aim of this work was to formulate minoxidil loaded liposome and niosome formulations to improve skin drug delivery. Multilamellar liposomes were prepared using soy phosphatidylcholine at different purity degrees (Phospholipon 90, 90% purity, soy lecithin (SL), 75% purity) and cholesterol (Chol), whereas niosomes were made with two different commercial mixtures of alkylpolyglucoside (APG) surfactants (Oramix NS10, Oramix CG110), Chol and dicetylphosphate. Minoxidil skin penetration and permeation experiments were performed in vitro using vertical diffusion Franz cells and human skin treated with either drug vesicular systems or propylene glycol-water-ethanol solution (control). Penetration of minoxidil in epidermal and dermal layers was greater with liposomes than with niosomal formulations and the control solution. These differences might be attributed to the smaller size and the greater potential targeting to skin and skin appendages of liposomal carriers, which enhanced globally the skin drug delivery. The greatest skin accumulation was always obtained with non-dialysed vesicular formulations. No permeation of minoxidil through the whole skin thickness was detected in the present study irrespective of the existence of hair follicles. Alcohol-free liposomal formulations would constitute a promising approach for the topical delivery of minoxidil in hair loss treatment. PMID- 17365281 TI - Fibrin targeting of tissue plasminogen activator-loaded echogenic liposomes. AB - We recently reported entrapment of tissue-plasminogen activator (tPA) into echogenic liposomes (ELIP) with retention of echogenicity and thrombolytic effect. Integral to the potential of this agent for ultrasound-detectable local drug delivery is the specific binding of tPA-ELIP to clots. tPA contains fibrin binding sites; we hypothesized that tPA when associated with ELIP, will maintain fibrin binding properties, rendering further manipulation for targeting of the tPA-ELIP unnecessary. We demonstrated strong fibrin binding of the ELIP associated tPA. Fibrin binding for ELIP-associated tPA was twice that of free tPA. This strong affinity for fibrin was confirmed using echogenicity analysis of porcine clots in vitro. Both objective (mean gray scale analysis) and subjective (visual estimation by two experienced echocardiographers) evaluation of the clots showed enhanced highlighting of clots treated with tPA-ELIP when compared to control. The findings in this study represent new approaches for fibrin-targeted, ultrasound-directed and enhanced local delivery of a thrombolytic agent. PMID- 17365282 TI - DNA delivery to the mitochondria sites using mitochondrial leader peptide conjugated polyethylenimine. AB - Some genetic diseases are associated with the defects of the mitochondrial genome. Direct DNA delivery to the mitochondrial matrix has been suggested as an approach for mitochondrial gene therapy for these diseases. We hypothesized that a mitochondrial leader peptide (LP) conjugated polyethylenimine (PEI) could deliver DNA to the mitochondrial sites. PEI-LP was synthesized by the conjugation of LP to PEI using disulfide bond. The complex formation of PEI-LP with DNA was confirmed by a gel retardation assay. In this study, DNA was completely retarded at a 0.4/1 PEI-LP/DNA weight ratio. In vitro delivery tests into isolated mitochondria or living cells were performed with rhodamin-labeled DNA and PEI-LP. In vitro cell-free delivery assay with isolated mitochondria showed that PEI LP/DNA complexes were localized at mitochondria sites. Furthermore, the PEL LP/DNA complexes were localized at the mitochondrial sites in living cells. However, a control carrier, PEI, did not show this effect. In addition, MTT assay showed that PEI-LP showed lower cytotoxicity than PEI. These results suggest that PEI-LP can deliver DNA to the mitochondrial sites and may be useful for the development of mitochondrial gene therapy. PMID- 17365283 TI - In vitro evaluation and pharmacokinetics in dogs of guar gum and Eudragit FS30D coated colon-targeted pellets of indomethacin. AB - A pH- and enzyme-dependent colon-targeted multi-unit delivery system of indomethacin was developed by coating guar gum and Eudragit FS30D sequentially onto drug-loaded pellets in a fluidized bed coater. In vitro studies showed that smaller coating weight gain of guar gum resulted in reduced release lag time t10 (10% release time), but favored degradation by enzymes (galactomannanase). A cumulative weight gain (CWG) of 44% provided sufficient enzymatic sensitivity and protection of the core. Under gradient pH conditions (pH = 1.2, 6.8, 7.4 and 6.5 for 2, 2, 1 and 15 h, respectively), indomethacin was released from Eudragit FS30D-coated pellets quickly after changing pH to 7.4. For guar gum/Eudragit FS30D double-coated pellets, only about 5% of the drug was released after another 1 h, showing retarding effect by guar gum coating. After changing pH to 6.5 and addition of galactomannanase, enzyme-dependent drug release was observed. Pharmacokinetic study in beagle dogs showed that fastest absorption with the smallest Tmax and Tlag was observed for uncoated pellets. The Tmax and Tlag of Eudragit FS30D-coated pellets were postponed to about 2.5 and 1 h, respectively. After a further guar gum coating, Tlag was further postponed to about 2.8 h, about 2 h of additional lag time on the basis of Eudragit FS30D coating. It is indicated that the guar gum/Eudragit FS30D-coated system has potential to be used to deliver drugs to the colon. PMID- 17365284 TI - Enhanced transport of P-glycoprotein substrate saquinavir in presence of thiolated chitosan. AB - It was the aim of this study to investigate the effect of chitosan-4 thiobutylamidine (Ch-TBA) and reduced glutathione (GSH) on the absorption of P glycoprotein (P-gp) and multidrug resistance protein (MRP) substrate saquinavir in vitro and in vivo. Bidirectional transport studies were performed with Caco-2 cell monolayers and additionally with freshly excised rat small intestinal mucosa mounted in Ussing type chambers. Furthermore, a delivery system based on Ch-TBA and GSH was evaluated in vivo in rats. The functional activity of the efflux pumps in Caco-2 cells and rat intestinal mucosa during the experiment was proven by the efflux ratio of saquinavir, which was 6.4 for Caco-2 cells and 2.1 for rat intestinal mucosa, respectively. Ch-TBA and particularly the combination of Ch TBA with GSH enhanced apical (AP) absorption and decreased the secretory transport of saquinavir. In presence of 0.5% Ch-TBA and 0.5% GSH, the uptake of saquinavir was 1.6-fold improved in Caco-2 monolayer and 2.1-fold improved in rat intestinal mucosa. In vivo, the area under the plasma concentration time curve (AUC) of saquinavir was 1.4-fold and Cmax 1.6-fold increased, in comparison with control. Results of this study showed that Ch-TBA in combination with GSH can be an interesting tool for increasing the oral bioavailability of actively secreted compounds. PMID- 17365285 TI - Preparation, characterization, and optimization of pancreas-targeted 5-Fu loaded magnetic bovine serum albumin microspheres. AB - The magnetic bovine serum albumin (BSA) microspheres (MS) were prepared by emulsification/solidification method. In this experiment, two kinds of magnetic MS, e.g. BSA MS and PEG-incorporated BSA microspheres (PMS) were prepared. The obtained MS were characterized by Malvern laser particle sizer and scanning electron microscopy (SEM). The obtained MS were spherical and about 1.3 microm in size. The magnetic responsivity and in vitro release behavior of these MS were studied in detail. The in vivo distribution and targeting delivery of 5 fluorouracil (5-Fu) magnetic MS after artery administration were studied in rat. The results showed that PMS could efficiently delivery 5-Fu to the targeted site compared with BSA MS without PEG MS and free drug. PMID- 17365286 TI - Biological characterization of folic acid-conjugated poly(H2NPEGCA-co-HDCA) nanoparticles in cellular models. AB - The folate receptor (FR) is a highly selective tumor marker over expressed in many human cancers and it constitutes a useful target for tumor-specific drug delivery. Thus, the conjugation of folic acid to different drugs or drug carriers may enhance the delivery of the therapeutic agent to FR-positive tumor cells. The aim of this study was to investigate the interactions of folate-conjugated polyalkylcyanoacrylate nanoparticles with tumor cells overexpressing the FR. For this purpose, nanoparticles were prepared by nanoprecipitation of the poly[aminopoly(ethylene glycol) cyanoacrylate-co-hexadecyl cyanoacrylate] [poly(H2NPEGCA-co-HDCA)] copolymer and labeled with the hydrophobic fluorescent dye nile red. Nile red-loaded nanoparticles were then conjugated to folic acid via the PEG terminal amino groups. Four human cancer cell lines were then tested by western blot in order to evaluate the FR expression levels. KB3-1 cell line showed the higher expression level, while MCF-7 cells were taken as a control. After measuring the cytotoxicity of the nanoparticles on these two cell lines, fluorescent folate-nanoparticles were incubated with them and the cellular uptake was evaluated by confocal microscopy and flow cytometry. KB3-1 cells showed a greater nanoparticle internalization, when compared to MCF-7 cells. PMID- 17365287 TI - 1-O-alkylglycerol stabilized carbamazepine intravenous o/w nanoemulsions for drug targeting in mice. AB - Carbamazepine (CBZ) is used in the treatment of generalized tonic clonic and partial seizures. In seizure disorder the focal point of treatment is brain. At present no commercial parenteral formulation of CBZ is available. We developed o/w nanoemulsions of CBZ stabilized by 1-O-alkylglycerol/lecithin for intravenous administration and evaluated the brain targeting potential of these formulations. The nanoemulsions were characterized for globule size, zeta potential (ZP), CBZ content and in vivo tissue distribution in mice. The in vivo data revealed a significant uptake of CBZ in all tissues. Among the nanoemulsions, 1-O decylglycerol stabilized system showed significantly higher tissue levels and availability of CBZ. Particularly for this system 2.37 times higher brain availability and a brain/serum concentration ratio of 3.0 at 30 min is an important finding. This indicates the brain targeting potential. A systematic formulation development of CBZ nanoemulsions employing 1-O-alkylglycerols might pave way to achieve selective brain delivery of this important antiepileptic drug. PMID- 17365288 TI - Effects of derivatization on solar-induced decomposition of polycyclic aromatic hydrocarbons in aqueous media. AB - The solar-induced decomposition of 10 polycyclic aromatic hydrocarbons (PAHs) was observed in aqueous media. All 10 PAHs observed were half-decomposed within 120 min. Among anthracene derivatives, the decomposition rates were: anthracene = 1 methylanthracene < 2-methylanthracene < 9-methylanthracene < 9,10 dimethylanthracene approximately 2-aminoanthracene. The addition of commercial humic acid had no effect on the decomposition rates of these PAHs. Deuterium water also hastened the decomposition of PAH. The products obtained by the solar radiation of PAH after extraction to DCM were mainly ketone and hydroxyl derivatives. To explain these results, reactivities and electron charges at the constituent carbon atoms in each anthracene derivative were examined by an ab initio molecular orbital calculation method. PMID- 17365289 TI - Polycyclic aromatic hydrocarbons (PAHs) in surface waters of Rackevei-Soroksari Danube Branch, Hungary. AB - Concentrations of polycyclic aromatic hydrocarbons (PAHs) in the surface waters of Rackevei-Soroksari Danube (RSD) branch, Hungary were determined at ten sites during eight sampling events from October 2002-April 2004. Low and medium molecular weight PAHs (2-4 rings) varied from a few ng/L to hundreds of ng/L while high molecular weight PAHs (5-6 rings) were present at much lower concentrations (< 0.5-31 ng/L). Generally, concentrations of most of the individual PAHs were not significantly different (p > 0.05) during the different seasons. Concentrations of anthracene, fluoranthene, and pyrene were significantly lower (p < 0.005) in the winter month whereas concentrations of benzo(a) anthracene, chrysne, and benzo(b)fluoranthene were significantly lower (p < 0.05) in the fall season. Possible causes of such distribution in the surface waters of RSD include nature of the inputs of organic matter and different systems of winds or rains of the seasons. Of the total PAHs, the 2-3 ring PAHs contributed to about 78% while 4-6-ring PAHs accounted for 22%. This suggests that the incomplete combustion of fossil hydrocarbons may be the predominate source of PAHs in surface water of RSD. Seasonally, petroleum and heavy fuel combustion were main sources of PAHs in summer and winter seasons, respectively. However, both sources contribute to PAHs in the spring season. The levels of PAHs in our study were compared with other regions of the world. Concentrations of PAHs in our study were higher than most of the surface waters of Europe, North America, and Australia, but similar to some parts of European and Asian regions. PMID- 17365290 TI - Emissions of tar-containing binders: a laboratory study. AB - In Switzerland, hot recycling of tar-containing pavements is a subject of much dispute between environmentalists, road authorities and constructors. The main reason for this controversy comes from a lack of knowledge about the amount of hazardous compounds emitted, especially polycyclic aromatic hydrocarbons (PAHs), and the resulting health risk for road workers. On this background we decided to initiate a research project to study the emission behaviour of tar-containing materials. Mixtures of tar and bitumen with variable PAH content were heated in an open reactor flask at different temperatures to identify and quantify the key parameters of PAH emissions. The expected linear correlation between PAH concentration in the fumes and in the binder was found only for binder mixtures with PAH concentrations above 5000 ppm. This was traced back to the problem that a change of the PAH content in the binder was always accompanied by a change of other parameters, like viscosity. In the experiments with temperature variation, emissions of individual PAHs correlated well with vapor pressure. However, for Naphthalene and, in a lesser degree, for 3-ring PAHs too, a partial depletion of these compounds in the vapour was observed in some experiments. The effect is a slower increase with temperature for these compounds compared to 4-6-ring PAHs. This is one reason why the commonly used set of EPA-PAHs, which includes naphthalene and 3-ring PAHs, is considered inappropriate for the assessment of the health hazard in the case of tar-containing materials in hot recycling. PMID- 17365291 TI - Differences in the isomer composition of perfluoroctanesulfonyl (PFOS) derivatives. AB - Perfluorooctanesulfonyl (PFOS)-based materials and related compounds are an emerging group of environmental pollutants. Perfluorooctanesulfonyl fluoride, the key intermediate for the production of these materials, was manufactured by an electrochemical fluorination process that resulted in complex mixtures containing linear and branched PFOS derivatives and other perfluorinated compounds. This study uses 19F-NMR spectroscopy to investigate differences in the composition between commercial samples of PFOS and PFBS (perfluorobutanesulfonyl) derivatives. While PFBS derivatives, which are under evaluation as substitutes for PFOS-based materials, contained no detectable levels of branched impurities, all PFOS derivatives contained significant levels of branched and other impurities. Analysis of the NMR data reveals that PFOS fluorides typically have a higher content of internally branched and similar levels of isopropyl branched PFOS isomers compared to PFOS potassium salts. Furthermore, the isomer distribution of PFOS derivatives may vary depending on their source. These findings suggest that it is important to determine the isomer composition of PFOS samples used in both environmental and toxicological studies. PMID- 17365292 TI - Effects of oxidative coupling reaction of 4-chlorophenol with manganese oxide on the phenanthrene sorption. AB - The objective of this study was to evaluate the abiotic transformation rate of 4 chlorophenol (4-CP) by manganese oxide. Sorption and desorption characteristics of polycyclic aromatic hydrocarbons (PAHs) on manganese oxide were also investigated in the presence of 4-CP. Results show that manganese oxide is effective for the transformation of 4-CP and initial reaction rate is the first order with respect to the 4-CP and manganese oxide. Also, 4-CP transformation rates by manganese oxide are highly dependent upon solution pH and concentration of humic acid. At pH near the point of zero charge (PZC) of manganese oxide, the maximum reaction rate of 4-CP was observed. Sorption of phenanthrene on manganese oxide is significantly increased as a result of 4-CP transformation and subsequent generation of byproducts. Also, sorbed phenanthrene on manganese oxide in the presence of 4-CP showed high degree of desorption resistance. PMID- 17365293 TI - Kinetic hindrance of Fe(II) oxidation at alkaline pH and in the presence of nitrate and oxygen in a facultative wastewater stabilization pond. AB - To better understand the dynamics of Fe2 + oxidation in facultative wastewater stabilization ponds, water samples from a three-pond system were taken throughout the period of transition from anoxic conditions with high aqueous Fe2 + levels in the early spring to fully aerobic conditions in late spring. Fe2 + levels showed a highly significant correlation with pH but were not correlated with dissolved oxygen (DO). Water column Fe2 + levels were modeled using the kinetic rate law for Fe2 + oxidation of Sung and Morgan.[5] The fitted kinetic coefficients were 5 +/- 3 x 10(6) M(- 2) atm(-1) min(-1); more than six orders of magnitude lower than typically reported. Comparison of four potential Fe redox couples demonstrated that the rhoepsilon was at least 3-4 orders of magnitude higher than would be expected based on internal equilibrium. Surprisingly, measured nitrate and DO (when present) were typically consistent with both nitrate (from denitrification) and DO levels (from aerobic respiration) predicted from equilibrium. Although the hydrous Fe oxide/FeCO3 couple was closest to equilibrium and most consistent with the observed pH dependence (in contrast to predicted lepidocrocite), Fe2 + oxidation is kinetically hindered, resulting in up to 10(7)-fold higher levels than expected based on both kinetic and equilibrium analyses. PMID- 17365294 TI - Electrokinetically enhanced bioremediation of creosote-contaminated soil: laboratory and field studies. AB - Creosote is a toxic and carcinogenic substance used in wood impregnation. Approximately 1,200 sites in Finland are contaminated with creosote. This study examined the possibility of enhancing bioremediation of creosote-contaminated soil with a combination of electric heating and infiltration and electrokinetic introduction of oxygenated, nutrient-rich liquid. Preliminary tests were performed in the laboratory, and a pilot test was conducted in situ at a creosote contaminated former wood impregnation plant in Eastern Finland. Wood preservation practices at the plant were discontinued in 1989, but the soil and the groundwater in the area are still highly contaminated. The laboratory tests were mainly performed as a methodological test aiming for upscaling. The soils used in these tests were a highly polluted soil from a marsh next to the impregnation plant and a less polluted soil near the base of the impregnation building. The laboratory test showed that the relative degradation was significantly higher in high initial contaminant concentrations than with low initial concentrations. During the first 7 weeks, PAH-concentrations decreased by 68% in the marsh soil compared with a 51% reduction in the building soil. The field test was performed to a ca. 100 m3 soil section next to the former impregnation building. Nutrient and oxygen levels in the soils were elevated by hydraulic and electrokinetic pumping of urea and phosphate amended, aerated water into the soil. The DC current introduced into the soil raised the temperature from the ambient ca. 6 degrees C up to between 16 and 50 degrees C. Total PAH concentrations decreased by 50-80% during 3 months of treatment while mineral oil concentrations decreased approximately 30%. Electrokinetically enhanced in situ - bioremediation, which also significantly raised the soil temperature, proved to be a promising method to remediate creosote-contaminated soils. PMID- 17365295 TI - Modeling the Hydrology and water quality using BASINS/HSPF for the upper Maurice River watershed, New Jersey. AB - Results of developing a watershed model for the Upper Maurice River watershed are presented. The model was calibrated against observed stream-flow using local coastal plain meteorology as input, for the ultimate purpose of estimating future development impacts on local hydrology, stream-flow and water quality. Due to insufficient data, the model has not been validated yet. Typically, development impacts expected to include are more frequent peak flows, flooding, increased channel-bed erosion, loss of wetlands, loss of forested land and more surface runoff, while water quality impacts expected to occur are an increase in nuisance vegetation in lakes and streams, and stream/lake-water quality degradation due to increased loads of pollutants. This paper reveals that a significant decrease in recharge of the Kirkwood-Cohansey unconfined aquifer system, lying below the watershed, will occur with further development, because development will alter the land-use toward more urbanization resulting in less water infiltration, hence less recharge of the aquifers below. Hydrologic Simulation Program, Fortran (HSPF), within the USEPA's BASINS-3 software system, was the modeling program used. PMID- 17365296 TI - Modeling and assessing the impact of reclaimed wastewater irrigation on the nutrient loads from an agricultural watershed containing rice paddy fields. AB - Two models were used in concert to predict nutrient loads in a waterbody receiving irrigation return flows from a rice paddy production system. Two irrigation scenarios were simulated, one using reclaimed wastewater as the irrigation water source, the other using water from a surface reservoir designed to supply irrigation water. Total nitrogen (TN) and total phosphorus (TP) loads in irrigation return flows from the rice paddy fields were simulated using the field-scale water quality model Chemical, Runoff and Erosion from Agricultural Management System model for rice paddy fields (CREAMS-PADDY). The output from CREAMS-PADDY was then used as input data for Hydrological Simulation Program FORTRAN (HSPF) model. HSPF was used to evaluate TN and TP loads in the receiving waterbody at the watershed-scale. CREAMS-PADDY and HSPF were calibrated for both hydrology and water quality using observed data. Both CREAMS-PADDY and HSPF showed good agreement between the observed and simulated data during the calibration and validation periods. Simulation indicated that TN and TP loads from the study paddy fields increased by 207% and 1022% when reclaimed wastewater was used for irrigation compared to conventional irrigation. Irrigating paddy fields (18.8% of the 385 ha study watershed) with reclaimed wastewater increased the TN load at the watershed outlet by 10.3% and TP by 14.0%. The increase in nutrient loads was the result of the high nutrient concentration in the reclaimed wastewater. The procedures used in this research can be used to develop wastewater reuse strategies that minimize environmental impacts on watershed water quality. PMID- 17365297 TI - Mass transport in groundwater near hanging-wall interceptors. AB - This study investigated mass transport near trenches designed to capture contaminated groundwater. Numerical models simulated migration of contaminant plumes toward trenches oriented perpendicular to regional groundwater flow, partially penetrating a hypothetical unconfined aquifer. Plumes originated at the top of the simulated groundwater flow system. The smallest trench necessary to capture a contaminant plume was identified for various sets of mass transport parameters. Results suggest that, in predominantly horizontal flow systems such as those simulated here: (i) vertical hydraulic conductivity has relatively little effect on downward propagation of contaminant plumes and required trench size, (ii) transverse vertical dispersivity exerts significant control on plume and trench depth, and (iii) recharge dilutes and thus reduces plume and trench width, but may induce downward vertical hydraulic gradients that deepen plumes and trenches. For all cases considered, trenches oriented perpendicular to regional groundwater flow, placed close to the leading edge of a contaminant plume, and sized slightly larger than the plume (in transverse cross-section) facilitate plume capture. PMID- 17365298 TI - Leaching properties of electric arc furnace dust prior/following alkaline extraction. AB - This study was carried out to determine the appropriate treatment of electric arc furnace (EAF) dust prior to permanent disposal. The total heavy metal content as well as heavy metal leaching from EAF dust was investigated in five composite samples obtained from three Croatian and Slovenian steelworks. In order to recover zinc and reduce its leaching from the dust, all five samples were submitted to alkaline extraction with 10 M NaOH. Reduction of Cr (VI) to Cr(III) was conducted using FeSO4 x 7H2O solution. The elements Mn, Fe, Cu, Ni, and notably Zn and Pb, exhibited highest mobility during toxicity characteristic leaching procedure (TCLP). Comparing to TCLP extracts of initial EAF dust, zinc was found to be over 15 times lower and lead over 200 times lower in TCLP extracts of EAF dust processed by the alkaline leaching method. Since Cr (VI) exceeded its permissible level in the DIN 38414-S4 extracts of both initial and alkaline digested dust, its reduction to Cr (III) prior to permanent disposal is necessary. The recovery of zinc from EAF dust treated with alkaline agent ranged from 50.3% to 73.2%. According to phase analysis, recovery yield showed dependence on zincite/franklinite ratio. The results of the study indicate that permanent disposal of EAF dust require the following procedure: alkaline digestion (followed by leachate purification and alkaline zinc electrolyses), chromate reduction (if necessary), solidification of leaching residue and its testing using the leaching analyses. PMID- 17365299 TI - Activated sludge process control--development of operational diagrams. AB - Hindered batch settling experiments were performed on activated sludge generated from dairy wastewater and combined (Dairy-Domestic mixture 1:3) wastewater for different initial Mixed Liquor Suspended Solids (MLSS) concentrations from 2g/L to 20 g/L for varied Mean Cell Residence Time (MCRT) for 5 to 15 days. Bio kinetic coefficients of combined wastewater were determined using a bench scale Continues Flow Stirred Tank Reactor (CFSTR). Vesilind parameters were also determined experimentally. Operational diagrams for long-term fluctuations in plant inflow and substrate concentration have been prepared. The allowable overflow rate to prevent process failure can be predicted from the chart. The adjustments to be made in recycling ratio and MCRT in case of fluctuations could also be predicted from the operational diagrams. From the operating diagrams plotted for both dairy and combined wastewater, it was noticed that, combined wastewater treatment provide greater operational flexibility than treating dairy waste separately. PMID- 17365300 TI - Development of biological process with pure bacterial cultures for effective bioconversion of sewage treatment plant sludge. AB - Forty-six bacterial strains were isolated from nine different sources in four treatment plants namely Indah Water Konsortium (IWK) sewage treatment plant (STP), International Islamic University Malaysia (IIUM) wastewater treatment plant-1,-2 and -3 to evaluate the bioconversion process in terms of efficient biodegradation and bioseparation. The bacterial strains isolated were found to be 52.2% (24 isolates) and 47.8% (22 isolates) in the IWK and IIUM treatment plants, respectively. The results showed that higher microbial population (9-10 x 10(4) cfu/mL) was observed in the secondary clarifier of IWK treatment plant. Among the isolates, 23 isolates were gram-positive bacillus (GPB) and gram-positive cocci (GPC), 19 isolates were gram-negative bacillus (GNB) and gram-negative cocci (GNC), and the rest were undetermined. Gram-negative cocci (GNC) were not found in the isolates from IWK. A total of 15 bacterial strains were selected for effective and efficient sludge bioconversion. All the strains were tested against sludge (1% total suspended solids, TSS) to evaluate the biosolids production (TSS% content), chemical oxygen demand (COD) removal and filtration rate (filterability test). The strain S-1 (IWK1001) showed lower TSS content (0.8% TSS), maximum COD removal (84%) and increased filterability (1.1 min/10 mL of filtrate) of treated sludge followed by the strains S-11, S-14, S-2, S-15, S-13, S-7, S-8, S-4, S-3, S-6, S-12, S-16, S-17 and S-9. The pH values in the fermentation broth were affected by the bacterial cultures and recorded as well. Effective bioconversion was observed during the first three days of sludge treatment. PMID- 17365301 TI - Synthesis of zeolites from paper sludge ash and their ability to simultaneously remove NH4+ and PO43-. AB - The objective of this study was to investigate the synthesis of zeolites from paper sludge ash, and to evaluate their applications for water purification to simultaneously remove NH4+ and PO43- in aqueous solution. Paper sludge ash had a low abundance of Si and a significant Ca content, due to the presence of calcite that was used as paper filler. Na2SiO3 was added to the NaOH solution to increase Si content in order to synthesize zeolites with high cation exchange capacity. The original ash without addition of Si yielded hydroxysodalite with a cation exchange capacity of ca. 50 cmol/kg. Addition of Si to the solution yielded Na-P1 (zeolite-P) with a higher cation exchange capacity (ca. 120 cmol/kg). The observed concentrations of Si and Al in the solution during the reaction explain crystallizations of these two phases. The product with Na-P1 could simultaneously remove NH4+ and PO43- from the solution between pH 4 and 9. PMID- 17365302 TI - Landfilling of pretreated municipal solid waste by natural convection of air and its effects. AB - The problems of leachate treatment and landfill gas (LFG) emissions are increasing gradually. Reducing the hazard before emplacement, pretreatment of municipal solid waste (MSW) prior to landfilling has become very important for the conventional landfill. In this study, pretreated mixed un-shredded MSW by the natural convection of air was employed to assess the aerobic pretreatment suitability. To study the effects of pretreated waste on landfill behavior, landfill simulation reactor (LSR) was developed at laboratory scale; pretreated MSW was placed in it. In a LSR, the behavior of aerobically pretreated waste disposal on a landfill was simulated. The LSR was operated for more than 9 months. The LSR operating phases were analyzed together with the consolidation of the leachate and gas production. The leachate collected was analyzed for pH, BOD (biochemical oxygen demand), COD (chemical oxygen demand), NH3-N and trace metals. The gas collected was analyzed for CH4 and CO2. The COD and BOD values were reduced to 1850 mg/L and 235 mg/L respectively within 5 months respectively. The maximum landfill gas (LFG) generation was observed about 60 m3 per ton dry matter (DM) of MSW. This work demonstrates that pretreatment is significantly effective in reducing the landfill emissions that is LFG; and leachate quality was improved in terms of COD and BOD. PMID- 17365303 TI - Characteristics of a twice-fed sequencing batch reactor treating swine wastewater under control of aeration intensity. AB - The changes of nitrogen (NH4+-N, NO2- -N, and NO3- -N), chemical oxygen demand (COD), dissolved phosphorus (DP), dissolved oxygen (DO), oxidization and reduction potential (ORP), and pH were tracked in a twice-fed sequencing batch reactor (SBR) treating swine wastewater at aeration intensities of 2.1, 4.2, and 6.3 L/m3 x s, with two alternating non-aeration/aeration phases. The SBR was fed at the beginning of each non-aeration phase with a volume ratio of 3:1. The results show that aeration intensity has positive effects on DO breakthrough and the maximum DO concentration during aeration. Additionally, nitrification, proceeding in an aerated environment with non-detectable DO, can be accelerated when aeration intensity increases from 2.1 to 4.2 L/m3 x s, while the COD and DP removals increase at the end of the aeration phase for higher aeration intensities (4.2 and 6.3 L/m3 x s). Online monitoring results indicate that pH is more sensitive than ORP in revealing the nitrification termination with non detectable DO, whereas minimal ORP in the non-aeration phase has potential to be used as a control parameter for feeding. PMID- 17365304 TI - Source identification and spatial variability of nitrogen, phosphorus, and selected heavy metals in surface water and sediment in the riverine systems of a peri-urban interface. AB - This study was conducted, using an elaborate sampling activity of surface water and sediment within an industrially developed peri-urban interface with a riverine system in Wuxi, Taihu Lake area, China, to address the following objectives: (i) to identify possible sources of selected nutrients such as N and P, and heavy metals such as Cu, Zn, Pb, Cr, and Cd in surface water and sediments, and (ii) to determine the spatial variability of these elements around the source areas. The results showed that concentrations of N and P in the surface water and Cu, Zn, Cr, and Pb in most of sediments had exceeded trigger levels established by the nation, while all metal concentrations in surface water were still below the levels. The source identification of these pollutants in water and sediments in terms of their spatial distribution pattern and principal component analysis showed that: (i) Pb, N and organic carbon (OC) were closely related to the influence of urban runoff and domestic wastewater; (ii) Cu and Cr were related to the influence of industries; and (iii) P and Zn were related to the effect of both urban and industries. The results of this study showed that urbanization is the main contributor for N and P in the peri-urban interface instead of agricultural sources. The concentrations of N, P, Cu, Zn, Pb, and Cr in the sediment along the main river decreased with the distance away from the source area. The concentrations of these elements decreased to the background levels at about 4.5-5.5 km downstream of the source of origin. PMID- 17365305 TI - Induction of metallothionein in chick embryos as a mechanism of tolerance to platinum group metal exposure. AB - Recent data show that platinum group metals (PGMs), primarily platinum (Pt), palladium (Pd) and rhodium (Rd), from automobile catalytic converters are being deposited in the environment. We investigated the PGM neurotoxicity and tolerance mechanism by induction of metallothionein (MT) in developing chick embryos. Chick embryos were injected on the 7th and 14th days of incubation with different concentrations of Pt and mixture of Pt, Pd and Rh (PGM mix) solutions. It is documented that induction of MT by zinc (Zn+2) protects against metal and non metal hepatotoxicity. In this study the MT induction was examined through pretreatment of the two highest Pt(IV) exposure levels with exogenous Zn2+ on the 4th and 11th days of incubation. SDS-PAGE assay and digital image system were used to identify and quantify MT in homogenized brain and liver tissues. Quantitative analysis revealed an increase of MT in the 5 ppm Pt exposure as compared to controls. The 10 ppm Pt treatment was a lethal dose for exposed embryos. There was increased mortality at the 1.0 PGM mix level. The interaction of Pt, Pd and Rh in the mixture seems to favor metal accumulation and MT induction in the liver but not the brain. Pretreatment with exogenous Zn2+ increased chick survival. These results indicate that induction of MT plays a protective role against PGM toxicity. Metal analysis using atomic absorption spectrometer in graphite furnace mode (GFAAS) revealed PGM accumulation in chick embryo liver and brain tissues proportional to exposure concentration. Our results may imply that MT has an important role as a tolerance mechanism against PGM toxicity. The presence of Pt(IV) in brain tissue suggests that the undeveloped blood-brain barrier is permeable to PGMs. This raises concerns regarding the implication of these metals on neural injury. PMID- 17365307 TI - Combined effects of temperature and lead concentration on the competition between the rotifers Brachionus havanaensis and Brachionus rubens (Rotifera: Brachionidae). AB - The combined effects of temperature (22 and 32 degrees C) and the concentration of Pb (0, 0.05, 0.1 and 0.2 mg L- 1) on the competition between B. havanaensis and B. rubens using population growth was evaluated. At 22 degrees C, increase in Pb concentration had little effect on the population growth of B. havanaensis, while it had adverse effect on B. rubens. At this temperature, the presence of B. rubens had adversely affected the growth of B. havananensis. However, under similar conditions, B. rubens was not influenced by B. havanaensis. Increase in Pb concentration decreased the population growth of B. havanaensis at 32 degrees C regardless whether the population was alone or together with B. rubens. When grown alone, B. havanaensis was numerically more abundant than B. rubens. B. havanaensis grown at 32 degrees C had population growth rates of 0.32 to 0.56 day 1, depending on Pb level and the presence of competitor. At this temperature, B. rubens had mostly negative growth rates. Further, our study showed that Pb at a concentration as low as 0.05 mg L- 1 had adverse effect on B. rubens at both the temperatures. Though B. rubens is known to occur naturally at wide temperature range, in our study this species appeared to have adapted to low temperature. PMID- 17365306 TI - Cobalt-induced alterations in hamster testes in vivo. AB - The purpose of this study was to assess the effects of cobalt on the testicular structure of adult golden hamsters. Hamsters in group A received cobalt (CoCl2) in single intraperitoneal dose 20 mg/kg, in group B 10 mg/kg and in group C 5 mg CoCl2/kg body weight and were killed fourty eight hours after cobalt administration. Afer a preparation of histological samples the results were compared with control. After a cobalt administration dilatation of blood capillaries in interstitium, undulation of basal membrane and occurrence of empty spaces in seminiferous epithelium was detected. Morphometric analysis showed that in all cobalt-treated groups the relative volume of seminiferous epithelium was significantly decreased. In the relative volume of interstitium a significant increase was found between control group and experimental groups. After cobalt administration we have found linear non-significant decrease. Evaluation of diameter seminiferous tubules found increase of this parameter in the all experimental group in comparison with control. Height of seminiferous epithelium was relatively constant and in all groups but the difference between control and group A was significant (P < 0.05). Analysis of the lumen diameter of seminiferous tubules detected significantly increase mainly group B. Evaluation of the number of cell nuclei per a constant area detected an increase of this parameter in experimental group. Results of this study report a negative effect of cobalt on structure and function of testes. PMID- 17365308 TI - Polycyclic aromatic hydrocarbons in sediments from Rodrigo de Freitas Lagoon in the urban area of Rio de Janeiro, Brasil. AB - Regular (non-alkylated) polycyclic aromatic hydrocarbons (PAHs) and their alkylated homologues were determined in sediments from Rodrigo de Freitas Lagoon using gas chromatography with mass selective detector (GC-MSD). Concentrations varying from 405 to 11734 ng x g(-1) were found for total PAHs (regular and alkylated homologues). The study showed a pyrogenic and petrogenic contribution, probably due to the incomplete burning of fossil fuels as a result of the intense traffic of boats and motor vehicles added to the anthropogenic activity of several gas stations present in the region of Rodrigo de Freitas Lagoon. According to the National Oceanic and Atmospheric Administration (NOAA) Sediment Quality Guide, PAHs concentration should not exceed 4000 ng x g(-1) (Long et al., 1995) The obtained data present values above the NOAA limit for some sampling points indicating chronic contamination of those sites probably due to anthropogenic activities related to petroleum and its derivatives. PMID- 17365309 TI - Partitioning and removal of Cd and Mn using a simulated mangrove wastewater treatment system. AB - A greenhouse experiment was conducted to study the partitioning and removal of Cd and Mn from wastewater using constructed mangrove (Kandelia candel) wetland treatment system. Three different strengths of artificial wastewater passed through the system in fixed quantities. Artificial seawater was used as a control. Three different compositions were natural wastewater concentration (C1), medium wastewater concentration (C5) and concentrated wastewater concentrations (C10). C1 had the characteristics and strength similar to natural municipal wastewater while C5 and C10 contained five and ten times of the nutrients and heavy metals in C1, respectively. Results showed that the major portion of the Cd and Mn entering the simulated wastewater treatment system entered the sediment pool where approximately 88% to 95% of the Cd, and between 63% and 89% of Mn, was retained. The amount of added Cd and Mn in the wastewater found in plants were between 0.16% to 1.1%, and 1.7% to 13.9%, respectively. Within the total plant pool, roots accounted for between 30% and 39% of Cd, and from 0.65% to 7.3% of Mn; leaves contained between 19.9% to 30.5% of Cd, and from 7.8% to 41.0% of Mn; litterfall contained 12.3% to 20.6% of Cd, and from 15.2% to 70.3% of Mn, respectively. The averaged accumulative coefficients concentration in plant tissues/concentration in sediment in plant for Cd and Mn were 1.22 to 2.40 and 0.02 to 0.08, respectively. Assimilated Cd and Mn were stored in non-activity plant zones such as cell wall, supplimentary cells of the lenticel, stone cells, cell gaps in root and stem, etc. Kandelia candel seedlings had a relative high toxicity resistance to the two heavy metals. PMID- 17365310 TI - Degradation of aniline in Weihe riverbed sediments under denitrification conditions. AB - Three groups of microcosm tests were conducted to study the possibility of aniline degradation and the effects of organic matter and hydrous metal oxides on the degradation in Weihe riverbed sediments under denitrification conditions. After the riverbed sediments (20 g) and groundwater (800 ml) were put into bottles, aniline, nitrate and other reagents were added, and then the bottles were flushed with N2 for 30 minutes to create microcosms. Samples from the microcosms were employed for the analysis of aniline, nitrate, and chemical oxygen demand (COD). In the first test group, the concentration of aniline remained unchanged when NaN3 (500 mg/L) was added. When there was no nitrate or NaN3, the concentration of aniline also remained unchanged, although COD declined. However, the concentration decreased when nitrate (50 mg/L) was added. Therefore, aniline can be biodegraded under denitrification conditions. In the second test group, when the concentration of nitrate reached 50 mg/L, 300 mg/L or 400 mg/L, either the external or internal organic matter or both of them in Weihe raw sediments inhibited aniline degradation. In the sediments where organic matter alone or organic matter plus hydrous metal oxides were removed, the organic matter still inhibited the degradation when the concentration of nitrate reached 300 mg/L or 400 mg/L, but the external organic matter could accelerate the degradation when the concentration of nitrate was 50 mg/L. The result of the third test group showed that hydrous metal oxides can accelerate degradation. By analyzing the mechanism of the aniline degradation, we conclude that aniline is degradable by microbes in their growth metabolism, in which deamination is involved. PMID- 17365311 TI - Organic and inorganic pollution of the Vistula River basin. AB - The main aim of this work is focused therefore on water quality assessment of the Vistula river and its primary tributaries. The study presents the analytical results of the contamination level of different organic and inorganic pollutants as well as the chemometric evaluation of the entire data set. A broad spectrum of compounds have been determined, including pesticides, polichlorinated biphenyls (PCBs), phenols, polycyclic aromatic hydrocarbons (PAHs), heavy metals, inorganic ions and some aggregate parameters like BOD. Majority of the organic xenobiotics have been analyzed for first time in the Vistula region on a large, long-term scale. Chemometric evaluation allowed the determination of natural clusters and groups of monitoring locations with similar pollution character. Chemometric analysis confirmed the classification of water purity of the Vistula River basin is related to the land utilization character in this region. PMID- 17365312 TI - Performance reconnaissance of stormwater proprietary best management practices. AB - This paper presents a study to investigate the relative pollutant removal effectiveness of three proprietary end-of-pipe Best Management Practices (BMPs), namely, Baysaver, CDS, and Stormceptor. In this study, controlled conditions were used in order to provide documentation for the performance of the BMPs. For that purpose, a prototype facility was constructed at the University of Central Florida. For each BMP, five tests were conducted with five different flow rates: 1.6, 1.28, 0.96, 0.64, and 0.32 cfs. The monitored pollutants were sediments, nutrients, metals, and litters such as organic leaves, soda cans, plastic bottles, and cigarette butts and boxes. The results showed that some of the pollutants decreased in concentration while others increased between the influent and the effluent of the units. TSS load reductions for Baysaver, CDS and Stormceptor were 62.2%, 71.2%, and 83%, respectively. The performances of the studied BMPs for the pollutants were different. All the studied BMPs had good performance in removing the large sediment particles and litter. However, CDS had lower average inflow velocities in all tests than Baysaver and Stormceptor, causing sediment accumulation in the CDS inlet pipe. This study also showed that there was an increase in the total nitrogen concentration in Stormceptor while the nitrate/nitrite concentration increased in Baysaver and CDS. Other factors that should be considered in BMP evaluation are also presented in this paper. PMID- 17365313 TI - Assessment of reclaimed wastewater irrigation impacts on water quality, soil, and rice cultivation in paddy fields. AB - The objective of this research was to monitor and assess the impact of reclaimed wastewater irrigation on water quality, soil, and rice cultivation by comparing the effects of various wastewater treatment levels on the growth and yield of rice. A randomized complete block design was used for the application methods of the wastewater effluents to paddy rice, with five treatments and six replications. The treatments were: control with groundwater irrigation (GW); irrigation with polluted water form a nearby stream (SW); and three treatments of reclaimed wastewater irrigation at different treatment levels. The three levels of wastewater treatments included wastewater effluents: (i) directly from the wastewater plant (WW); (ii) after passing through a sand filter (WSF); and (iii) after passing a sand filter followed by an ultraviolet treatment (WSFUV). Each plot was 4 x 4 m and was planted with rice (Oryza sativa L.) in 2002 and 2003. The results indicated that irrigation of rice with reclaimed municipal wastewater caused no adverse effects on the growth and yield of rice. The chemical compositions of the rice from all plots were within the normal ranges of brown rice quality in Korea. No adverse effects were observed on chemical concentrations including the heavy metals Cu, As, Cd, Zn, Hg, and Pb, in either the brown rice or the field. The results showed that treated municipal wastewater can be safely used as an alternative water source for the irrigation of rice, although continued monitoring will be needed to determine the long-term effects with regard to soil contamination and other potential health concerns. PMID- 17365314 TI - Removal of arsenic from contaminated soils using different salt extractants. AB - This study presents an environmental-friendly and cost effective method for the extraction of arsenic from contaminated soils. Laboratory experiments using inorganic salts, potassium phosphate (KH2PO4), potassium chloride (KCl), potassium nitrate (KNO3), potassium sulfate (K2SO4), and sodium perchlorate (NaClO4) were evaluated as arsenic extractants. An Andosol soil was artificially contaminated with arsenite [As(III)] and arsenate [As(V)]. The soil was washed in a batch process with different salt solutions in the pH range 3-11 for 24 hours at 20 degrees C. Among the various potassium and sodium salts tested, KH2PO4 was found to be highly effective in extracting arsenic from As(III)-soil attaining more than 80% and 40% from As(V)-soil in neutral pH range. Other salts were particularly ineffective in extraction of arsenic from both soils. More arsenic was extracted more from the As(III)-soil than the As(V)-soil. PMID- 17365315 TI - Arsenic removal from aqueous solutions by adsorption on laterite soil. AB - Laterite soil was used as an adsorbent for arsenic removal from contaminated groundwater. Effects of pH, adsorbent dose, adsorbent size, contact time, initial arsenic concentration and presence of interfering species on arsenic removal were found out. Laterite soil was found to be very effective for arsenic adsorption. It was found that 4 h contact time was sufficient for approximately 98% and approximately 95% removal from the contaminated water samples at an adsorbent dose of 10 g/L and 20 g/L for As(III) and As(V) respectively at an initial concentration level of 0.5 mg/L at a pH of 5.7 +/- 0.2. Although there was no significant interference from Cl(-), NO3(-), SO4(-2), Ca(2+) and Fe(2+/3+) on arsenite removal but its removal was little affected due to the presence of HPO4( 2) and SiO3(-2). Arsenate removal efficiency, however, was decreased to a large extent in presence of HPO4(-2) and SiO3(-2). The other ions Cl(-), NO3(-), SO4( 2), Ca(2+) and Fe(2+/3+) had no significant interference on arsenate removal. The common organic contaminants such as 2,4-dichlorophenoxyacetic acid (2,4- D), atrazine, endosulfan and humic acid had no effect on As(III) removal, but they (excepting 2,4-D) cause decrease in the removal efficiency for As(V). Both Langmuir and Freundlich adsorption isotherm models fitted well and the maximum adsorption capacity was estimated to be 1.384 mg/g and 0.04 mg/g for arsenite and arsenate respectively. The real arsenic contaminated groundwater was also tested and it was found that laterite soil is very effective for arsenic removal from real groundwater sample, and up to approximately 99% removal could be achieved under normal condition. The advantage of the material is that the pH of the raw water did not change after arsenic removal, and iron was not leached. PMID- 17365316 TI - Arsenic(V) adsorption mechanism using kaolinite, montmorillonite and illite from aqueous medium. AB - The present work investigates the adsorptive behavior of As(V) ions with kaolinite, montmorillonite and illite in aqueous medium as a function of As(V) concentration, pH, contact time and temperature. As(V) adsorption on studied clays were pH dependent and maximum adsorption were achieved in the pH range 2.0 5.0. The adsorption data gave good fits with Langmuir isotherm and yielded Langmuir monolayer capacity of 0.86, 0.64 and 0.52 mg As(V) /g of kaolinite, montmorillonite and illite, respectively. An increase in adsorption temperature resulted in a decrease in the amount of As(V) adsorbed. The results of leaching study showed that, kaolinite was very active clay constituent regarding both As(V) adsorption and mobility. The electrokinetic behavior of both the kaolinite and montmorillonite were modified in the presence of As(V). The shift in isoelectric point indicated that adsorption involves inner sphere surface complexation and strong specific ion adsorption. Kaolinite was successfully tested as an adsorbent for the removal of arsenic from two contaminated groundwater samples containing arsenic in the range 1.36-1.41 mg/L. PMID- 17365317 TI - Nitrate removal and denitrification affected by soil characteristics in nitrate treatment wetlands. AB - Several small-scale surface flow constructed wetlands unplanted and planted (monoculture) with various macrophytes (Phragmites australis, Typha orientalis, Pennisetum purpureum, Ipomoea aquatica, and Pistia stratiotes) were established to continuously receive nitrate-contaminated groundwater. Soil characteristics and their effects on nitrate removal and soil denitrification were investigated. The results showed that planted wetland cells exhibited significantly higher (P < 0.05) nitrate removal efficiencies (70-99%) and soil denitrification rates (3.78 15.02 microg N2O-N/g dry soil/h) than an unplanted covered wetland cell (1%, 0.11 microg N2O-N/g/h). However, the unplanted uncovered wetland cell showed a nitrate removal efficiency (55%) lower than but a soil denitrification rate (9.12 microg N2O-N/g/h) comparable to the planted cells. The nitrate removal rate correlated closely and positively with the soil denitrification rate for the planted cells, indicating that soil denitrification is an important process for removing nitrate in constructed wetlands. The results of nitrogen budget revealed that around 68.9 90.7% of the overall nitrogen removal could be attributed to the total denitrification. The soil denitrification rate was found to correlate significantly (P < 0.01) with the extractable organic carbon, organic matter, and in situ-measured redox potential of wetland soil, which accordingly were concluded as suitable indicators of soil denitrification rate and nitrate removal rate in nitrate treatment wetlands. PMID- 17365318 TI - Biomethanization of mixtures of fruits and vegetables solid wastes and sludge from a municipal wastewater treatment plant. AB - The possible management of Fruit and Vegetable Solid Wastes (FVSWs) through their simultaneous digestion with the primary sludge of Municipal Wastewater Treatment plants is investigated. This alternative allows the recovery of energy and a solid product that can be used as an amendment for soils that generated the residue, while is not expensive. Results indicate that the ratio of FVSWs to sludge and the pH control are the main variables determining the methane production and concentration. NaHCO3 was selected to achieve the pH control. The results for a ratio of 50% sludge together with 10 g NaHCO3/kg of residue are among the best obtained, with a methane yield of about 90 L per kg of volatile solids, and a methane concentration of 40% (v/v) of the biogas. A 50% reduction of the total solids; 21% reduction of the volatile solids (in terms of total solids); and a pH value of the sludge, which is 6.9 indicate that the digested sludge can be a good material for soil amendment. PMID- 17365319 TI - Study of microfiltration behaviour of oily wastewater. AB - Crossflow microfiltration experiments were carried out with oily wastewater using alpha-Al(2)O(3) membranes with 0.05 microm pore size. The influence of parameters such as transmembrane pressure (TMP), crossflow velocity (CFV), oil concentration, pH and salt concentration on the microfiltration behaviors were studied based on the measurements of permeate flux, total organic carbon (TOC) removal efficiency, and size and zeta potential of the emulsion droplets. The results showed that there were different degrees of effect on the membrane separation performance by these parameters. The TOC removal efficiencies higher than 92.4% were achieved under all experimental conditions. A non-steady model of accumulation volume of permeation was developed. It was found that the calculated values were in good agreement with the experimental results. Sensitivity analysis was also conducted to identify the degree of influence of the parameters on the accumulation volume of permeation. The results indicated that the accumulation volume of permeation was significantly affected by the TMP. PMID- 17365320 TI - Efficiency of the UV/H2O2 process for the disinfection of humic surface waters. AB - The efficiency of the UV/H2O2 process for the disinfection of total coliforms and the prevention of bacterial regrowth in humic surface waters were investigated. Inactivation of total coliforms was determined in water samples containing various concentrations ranging from 0-10 mg/L dissolved organic carbon (DOC) of fulvic acid, which were exposed to various doses (68-681 mWs/cm2) of UV radiation in the presence of 0.125 mg/L and 3.000 mg/L of hydrogen peroxide. Disinfection efficiencies of the UV radiation and the UV/H2O2 processes were compared. The results of bacterial inactivation experiments showed that the performances of the UV and the UV/H2O2 (0.125) were comparable whereas the UV/H2O2 (3.000) process showed significant improvement in performance, especially, in highly humic waters. Inactivation coefficient appeared to be almost doubled by the addition of 3.000 mg/L hydrogen peroxide during the treatment of highly humic waters. In contradiction to significant regrowth which occurred in the single UV radiation treatment, residual bacteria following the UV/H2O2 (0.125) and the UV/H2O2 (3.000) treatments were completely inactivated during dark incubation indicating the elimination of possible bacterial regrowth. PMID- 17365321 TI - Selective recovery of Mo, Co and Al from spent Co/Mo/gamma-Al2O3 catalyst: effect of calcination temperature. AB - A combination of pyro and hydrometallurgical process has been proposed to selectively recover molubdenum, cobalt and aluminium from the spent catalyst containing 12.3% Mo; 31.8% Al; 2.38% Co; 9.5% S and 2.9% C. Before a two-stage alkali-acid leaching process to selectively target Mo, Co and Al from the uncrushed sample, the spent catalyst was calcined at different temperatures. Characterization of different calcined samples was carried out by different instrumental analysis like XRD, TG/DTA, IR and SEM in order to understand the structural changes and dissolution behavior of spent catalyst. It was found that calcination at 500 degrees C preferred for spent catalyst roasting since the surface and pore structures obtained by roasting at this temperature facilitated dissolution of calcined spent catalyst in the leachant. Mo was selectively separated and recovered from the leach liquor by carbon adsorption method; whereas, Al and Co were separated by an organo-phosphinic-based extractant, Cyanex 272. In the whole process, 95.9% Mo, 89.6% Co and 39.8% Al was recovered from the spent catalyst. Finally, a complete process flowsheet has been presented. PMID- 17365322 TI - Identification of nitrifiers in a full-scale biological treatment system using fluorescent in situ hybridization. AB - Diversity of nitrifying bacterial population was investigated in sludge samples taken from a full-scale biological wastewater treatment plant (WWTP) treating domestic wastewater by fluorescent in situ hybridization (FISH) during seasonal operation. Duplicate grab samples were collected in March 2003, June 2003, December 2003 and May 2004 from the aerobic tank of the treatment plant. FISH results were interpreted with system performance in terms of BOD5, TKN and NO3-N removals and also with operational parameters such as wastewater temperature and sludge age. BOD5 removal efficiencies were always greater than 90% whilst TKN removal in a range of 69-95% were achieved during the monitoring period. Although there were variations in operational conditions of the biological treatment system both Nitrosomonas and Nitrosospira genera from AOB and Nitrobacter genus from NOB were found to be present in all samples examined. PMID- 17365323 TI - Evaluation of acute copper toxicity during early life stages of gilthead seabream, Sparus aurata. AB - In this study, the effects of exposure to copper (mortality and morphological alterations) on the early life stages of the gilthead seabream, Sparus aurata, were examined. Eggs/embryos and larvae were exposed to nominal concentrations of copper ranging from 0.0001 to 10 mg/L Cu (II) in the tests with eggs/embryos and 0.025 to 0.5 mg/L Cu (II) in the test with larvae. Duration of the assays was 48 hours for embryos and 96 hours for larvae. A high percentage of mortality was observed in embryos exposed to 0.1 mg/L (97.2%) and in larvae exposed to 0.5 mg/L (100%). The embryos proved the most sensitive to copper for the same duration of exposure. The acute toxicity expressed as LC(50) 48 hours was 0.054 (0.048-0.058) mg/L for embryos and 0.261 (0.182- 0.375) mg/L for larvae. Morphological alterations or abnormalities in embryos included irregular shapes of chorion, opacity and vitellus retraction/degeneration. In larvae we observed poor capacity to swim, trembling, myoskeletal defects, opacity and exophthalmia. Histopathological alterations are observed in S. aurata larvae. Mucous cells of the digestive tissue present a severe alteration with an increment of exudates. A great cellular disorganization in the renal tissue is observed. Results from this work indicate the high sensitivity of early life stages of Sparus aurata to copper (II) and the persistence of sublethal effects. PMID- 17365324 TI - Immobilization of EAFD heavy metals using acidic materials. AB - This study was undertaken to determine the chemical and leaching characteristics of the Electric Arc Furnace Dust (EAFD) generated by a Greek plant and to investigate various acidic materials efficiency on the EAFD stabilization. In order to investigate how [OH(-)] neutralization influences EAFD heavy metals leachability, Na HCO3(-), HNO3 and H3PO4 were used as acidic materials. The concentration of Pb in leachate was found between 40 and 3.7 x 10(3) mg Pb/kg of EAFD, exceeding in all EAFD samples the maximum acceptable limit (MAL) 25 mg/kg for landfill disposal. Neutralization of [OH(-)] with HCO3(-) decreased Pb concentration in leachate at 350 mg Pb/kg of EAFD, while excess over a stoichiometry in HCO3(-) addition increased leachability of Pb, Cd, Cr, Cu as well as F. Using HNO3 as an acidic material decreased leachability of almost all the parameters concerning the EC directive 33/19-01-2003 in a pH value up to 7.2, in exception of Zn. Zinc leachability showed a U shape curve as a function of pH value. The concentration of Zn was minimized in a concentration lower than 1 mg Zn/kg EAFD in a pH range 10.5 to 9 and exceeded the MAL 90 mg/kg at a pH value 7.2. However, the major disadvantage of HNO3 was proved to be its leachability, since NO3(-) concentration in leachate was equal to HNO3 dose. H3PO4 was found the most promising acidic material for the chemical immobilization of heavy metals, since it decreased their leachability in a concentration significantly lower than MAL at a pH value up to 7.1. Finally, the concentration of Cl(-) ranged between 18 and 33 x 10(3) mg Cl(-)/kg EAFD exceeding in all EAFD samples the MAL 17 x 10(3) mg/kg. This high concentration of Cl(-) is attributed to the scrap and it could be reduced only by modification of its composition. PMID- 17365325 TI - Effects of the density of carboxyl groups in organic compounds on the photocatalytic reduction of Cr(VI) in a TiO2 suspension. AB - Photocatalytic reduction (PCR) of Cr(VI) in a TiO2 suspension was studied at pH 4 in the presence of organic compounds containing different numbers of carboxyl groups. The compounds studied were glycine (Gly), iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA). In all the cases, near complete Cr(VI) removal was observed after 60 minutes. During PCR process, the aqueous Cr(VI) concentration measured with both Ion Chromatography and Atomic Absorption Spectrophotometery was different in the presence of IDA and EDTA as reaction proceeded while little difference was observed in a control test. This result suggests that a greater portion of reduced Cr(III) species was possibly dissolved through complex formation with IDA (Cr(III)-IDA) and EDTA (Cr(III)-EDTA) or with reaction intermediates (Cr(III)-organic complexes) during PCR compared to the control test. As the number of carboxyl group increased Cr(VI) reduction increased and showed a good linear relationship between initial rates of Cr(VI) reduction and adsorption density of carboxyl group of the surface of TiO2. The initial rate of Cr(VI) reduction in the presence of EDTA was 5 times greater than that in control. When the PCR process was applied in the treatment of real wastewater, an effective Cr(VI) reduction was observed with addition of EDTA. PMID- 17365326 TI - Effects of glyphosate and foliar amendments on activity of microorganisms in the soybean rhizosphere. AB - A field study was conducted to determine the effects of glyphosate on microbial activity in the rhizosphere of glyphosate-resistant (GR) soybean and to evaluate interactions with foliar amendments. Glyphosate at 0.84 kg ae ha(-1) was applied GR soybean at the V4-V5 development stages. Check treatments included a conventional herbicide tank mix (2003 study only) and no herbicides (hand weeded). Ten days after herbicide application, a commercially available biostimulant and a urea solution (21.0% N) were applied to soybean foliage at 33.5 mL ha(-1) and 9.2 kg ha(-1), respectively. Soil and plant samples were taken 0, 5, 10, 15, 20 and 25 days after herbicide application then assayed for enzyme and respiration activities. Soil respiration and enzyme activity increased with glyphosate and foliar amendment applications during the 2002 growing season; however, similar increases were not observed in 2003. Contrasting cumulative rainfall between 2002 and 2003 likely accounted for differences in soil microbial activities. Increases in soil microbial activity in 2002 suggest that adequate soil water and glyphosate application acted together to increase microbial activity. Our study suggests that general soil microbial properties including those involving C and N transformations are not sensitive enough to detect effects of glyphosate on rhizosphere microbial activity. Measurements of soil plant-microbe relationships including specific microbial groups (i.e., root associated Fusarium spp.) are likely better indicators of impacts of glyphosate on soil microbial ecology. PMID- 17365327 TI - Retention and rainfastness of mancozeb as affected by physicochemical characteristics of adaxial apple leaf surface after enhanced UV-B radiation. AB - It is not clear so far whether alteration of leaf micromorphology and surface wax chemistry due to the impact of environmental factors, such as UV-B radiation, affects retention and rainfastness of applied pesticide solutions. In this study; UV-B treated and untreated adaxial leaf surfaces of apple seedlings (Malus domestica Borkh.) were characterized in terms of chemical composition, micromorphological fine structure, hydrophobicity, and wettability. Furthermore, the retention and rainfastness of applied fungicide mancozeb were studied. The samples were examined 0, 24 and 48 h after ultraviolet (UV)-B radiation (0.022 kW m(-2) for 150 min) The total wax mass, recovered from the adaxial leaf surface, amounted from 0.38 microg cm(-2) (control) up to 0.49 microg cm(-2) (24 h). Chemical composition of surface wax altered, whereas the contact angle of applied water droplets on leaf surface of UV-B treated plants did not change significantly compared to the control. The alteration of surface wax quantity and quality significantly affected retention of a.i.; it increased at a sampling time of 24 h after UV-B irradiation, whereas rainfastness of the fungicide spray solution was not significantly influenced. PMID- 17365328 TI - Decomposition of phorate in aqueous solution by ozonation. AB - Phorate (O,O-diethyl S-ethylthiomethyl phosphorodithioate) dissolved in aqueous solution was almost completely decomposed by ozonation to form various species within 10 minutes of reaction time for the experimental conditions examined in this research. The generation rate of sulfate was found to be fairly independent of solution pH value. However, the formation of phosphate and carbonate was more favorable for alkaline solutions where hydroxyl free radical is the primary oxidative species. The reaction rates increased with initial gaseous ozone concentrations, indicating the reaction was mass transfer-controlled within the experimental range of this research. Combining the analytical results by various instruments, including gas chromatograph equipped with an electron ionization detector (GC-EID), high performance liquid chromatography (HPLC), ion chromatography (IC), and total organic carbon (TOC), the temporal sequence of phorate ozonation was proposed in this study. The oxidation of sulfur atoms on the phosphorus-sulfur double bond or carbon-sulfur-carbon bond by ozonation was found to occur at first to form sulfate and various intermediates. PMID- 17365329 TI - Assessment of oxidative stress due to exposure to pesticides in plasma and urine of traditional limited-resource farm workers: formation of the DNA-adduct 8 hydroxy-2-deoxy-guanosine (8-OHdG). AB - The objective of this study was to assess the risk of genotoxicity caused due to oxidative stress using plasma and urinary levels of 8-hydroxy-2-deoxyguanosine (8 OHdG) in farm workers for six months during a growing season. Blood and urine samples were collected once a month for six months (June to November 2003) from farm workers (n = 15) and urban unexposed controls (n = 10). Plasma and urinary levels of 8-OHdG were evaluated by Enzyme Linked Immunosorbent Assay (ELISA) technique. There was no significant difference in the urinary levels of 8-OHdG between the farm workers and the control group, but there was an approximately four-fold increase in mean values of plasma 8-OHdG levels in the farm worker group (P < or = 0.05). PMID- 17365330 TI - The effects of fenvalerate on different tissues of freshwater fish Cirrhinus mrigala. AB - The histopathological changes of fenvalerate on the gill, kidney, liver and intestine tissues of the Cirrhinus mrigala were determined by light microscopy. The fish were exposed to two sub-lethal concentrations of fenvalerate (1.5-3.0 ppb). The most common gill changes at all concentrations of fenvalerate were epithelial hyperplasia, epithelial necrosis, desquamation and lamellar fusion. Besides, epithelial lifting, oedema, swelling at the tips of secondary lamellae and curling of secondary lamellae were other histopathological changes. Necrosis of tubular epithelium, pycnotic nuclei in the hematopoietic tissue, hypertrophied epithelial cells of renal tubules, narrowing of the tubular lumen, expansion of space inside the Bowman's capsule and contraction of the glomerulus were observed in kidney tissues of fish. Hepatic lesions in the liver tissues of fish exposed to fenvalerate were characterized by congestion, cloudy swelling of hepatocytes and focal necrosis. Atrophy of epithelial cells, necrosis of epithelial cells, desquamation of mucosal epithelium and infiltration of lymphocytes into the lamina propria were detected in intestine tissues of fish after exposure to fenvalerate. PMID- 17365331 TI - Effect of humic acids on photodegradation of chloroacetanilide herbicides under UV irradiation. AB - The effects of two humic acids (HAs) of different origins on the photodegradation of the chloroacetanilide herbicides acetochlor, propisochlor and butachlor were investigated in this study. One of the tested HAs was a standard sample that was purchased from a commercial source, and the other was isolated from the black soil of Northeast China. The photolysis of all three herbicides followed pseudo first-order kinetics under ultraviolet (UV) irradiation conditions, regardless of whether HAs were present or not. Both HAs improved the photolysis rates of acetochlor in a dose-reversed way, whereas they inhibited butachlor degradation under all experimental concentrations. The two HAs differed in their effects on propisochlor photolysis, changing from enhancement to inhibition, depending on the origin and concentration of HAs. Element and Fourier Transform Infrared spectroscopy analyses showed that the isolated HAs had more polysaccharides and less aliphatic groups than the commercial HAs, and it was indicated that some characteristic radicals (C=O, O-H and phenolic hydroxyls) in HAs were involved in the photolysis of the herbicides. Gas chromatography/mass spectrometry (GC/MS) analyses indicated that the presence of HAs had no effects on the photolysis pathway and photoproduct species of the three herbicides. PMID- 17365332 TI - Application of an enzyme-linked immunosorbent assay for the detection of clenbuterol residues in swine urine and feeds. AB - The present study outlines applications of an enzyme-linked immunosorbent assay (ELISA) for the analysis of clenbuterol residues. Antisera were raised from rabbits immunized with diazotized clenbuterol-bovine serum albumin (BSA) conjugate. The assay was specific to clenbuterol with a half-maximum inhibition concentration (IC(50)) of 1.8 ng/mL and 2.5 ng/mL in blank swine urine and phosphate buffer solution, respectively. The assay had high cross-reactivity (86%) with mabuterol, but low with other adrenergic agonists and antagonists. The average recovery of clenbuterol, as measured with the ELISA, ranged from 90% to 112% in swine urine samples and from 86% to 95% in feeds, respectively. This new assay was compared with commercial ELISA test kits. An excellent correlation (r(2) = 0.98) between the two methods and satisfactory recoveries suggest that the new assay can be suitable for the determination of clenbuterol residues in real samples. The assay was used to analyze clenbuterol residues in 103 swine urine samples and 68 feed samples collected from northern China. Approximately 50% of the urine samples and 25% of the feed samples analyzed were found positive (concentration of clenbuterol > or = 1 ppb). The results indicate that clenbuterol was misused in some of the areas surveyed. PMID- 17365333 TI - Multiresidue analysis of pesticides in fruits and vegetables by gas chromatography-mass spectrometry. AB - A multiresidue method was assessed for the determination of several pesticides (organochlorine, organophosphorus, pyrethroids, triazole, amidine) using gas chromatography/mass spectrometry. The extraction of pesticides was carried out by liquid-liquid extraction (LLE) and solid-phase extraction (SPE) using two types of columns (CN and C18). The extracts were cleaned by the addition of florisil, the pesticides were separated by capillary column gas chromatography and detected by mass spectrometry in the electron impact mode. The extraction using C18 column provided the best results for most of the analyzed pesticides. The majority of pesticides recoveries from the four fruits and vegetables (apples, pears, tomatoes and pepper) were greater than 60%. Linearity and precision were satisfactory. The estimated limits of detection and limits of quantification ranged from 0.01 to 0.1 mg/kg and from 0.02 to 0.3 mg/kg, respectively. The proposed procedure was found to be useful for the multiresidue analyses of pesticides in agricultural products for routine monitoring programs. PMID- 17365334 TI - Treatment of carbofuran-bearing synthetic wastewater using UASB process. AB - In the present study, fate of carbofuran in anaerobic environments and the adverse effects of carbofuran on conventional anaerobic systems were evaluated. Carbofuran degradation studies were carried out in batch reactors with varying carbofuran concentrations of 0 to 270.73 mg/L corresponding to a sludge-loading rate (SLR) of 2.12 x 10(-6) to 3.83 x 10(-3) g of carbofuran/g of volatile suspended solids (VSS)/d. Carbofuran concentration was reduced to undetectable levels at the end of 8 and 13 days in the batch reactors operated with a SLR of 2.12 x 10(-6) and 3.33 x 10(-5) g of carbofuran/g of VSS/d, respectively. Performances of two anaerobic reactors i.e. upflow anaerobic sludge blanket (UASB) and modified UASB (with tube settlers) were evaluated in the presence and absence of carbofuran using synthetic wastewater. In the absence of carbofuran, the soluble chemical oxygen demand (COD) removal efficiency in the conventional UASB reactor at 8 h and 6 h hydraulic retention time (HRT) was nearly 88% and 76%, respectively, whereas in modified UASB reactor it was increased to 90% at 8 h HRT and 78% at 6 h HRT. When 28 mg/L (SLR of 1.19 x 10(-2) g of carbofuran/g of VSS/d) of carbofuran was introduced in the reactors, the COD removal efficiency was reduced to 41% and 44% in conventional and modified UASB reactors respectively. However, the reactor could maintain around 80% COD removal efficiency at a carbofuran concentration of 7.84 mg/L (SLR of 3.64 x 10(-3) g of carbofuran/g of VSS/d). The reactor efficiency was also measured in terms of specific acetoclastic methanogenic activity (SMA). The toxic effect of carbofuran was reversible to a certain extent. Carbofuran removal efficiency in the conventional UASB reactor at carbofuran concentrations of 7, 13 and 28 mg/L were 40 +/- 3%, 27 +/- 3%, and 11 +/- 3%, respectively. In modified UASB reactor, carbofuran removal efficiency was almost uniform at 7 and 13 mg/L but it was reduced nearly by 56% at 28 mg/L. The major metabolite of carbofuran i.e. 3-keto carbofuran was found in all the reactors. PMID- 17365335 TI - Risk of polycyclic aromatic hydrocarbon (PAH) exposure from ingested food: the Azerbaijan case study. AB - Risks due to polycyclic aromatic hydrocarbons (PAHs) exposure from food consumption for the population of Azerbaijan were determined using deterministic and probabilistic methods. The guidelines and methods described and presented in the United States Environmental Protection Agency (U.S. EPA) Risk Assessment Guidance for Superfund (RAGS) Part A was used in performing the risk assessments. The current study utilized concentration data from different sources representing international studies performed over the past decade to determine those food products that contribute the most exposure to PAHs through ingestion for the Azeri population. Due to lack of concentration data from middle-Eastern countries, only European countries were considered and used for this analysis. Using the benzo[a]pyrene (BaP) toxicity equivalency factors (TEFs) to adjust the concentrations of the individual PAH compounds to BaP equivalent concentrations, risk analyses were performed. Deterministic risk estimates fell within probabilistic risk estimates. Child risks were consistently four to seven times higher in magnitude than adult risks. Risk potentials determined for the food exposure pathway were also determined to be up to ten times higher in magnitude than risks determined from exposures due to other pathways such as soil contamination. It was observed that three major factors contributed to the variability in the assessment results, which were child and adult body weights, consumption rates of the different food groups, and the variances of the input data. The most prevalent pathways of PAH exposure from the dietary patterns of the Azerbaijani population were determined to be from bread and bakery products, milk and dairy products, and egg products. PMID- 17365336 TI - Radiocaesium activity concentrations in potatoes in Croatia after the Chernobyl accident and dose assessment. AB - Systematic investigations of (137)Cs and (134)Cs activity concentrations in potatoes (Solanum tuberosum) for the post-Chernobyl period (1986-2005) in the Republic of Croatia are summarized. The correlation between (137)Cs activity concentrations in fallout and potatoes, has been found to be very good, the correlation coefficient being r = 0.88 with P(t) < 0.001 for 18 degrees of freedom. As the radiocaesium levels in potatoes decreased exponentially, the mean residence time of (137)Cs in potatoes was estimated by fitting the measured activity concentrations to the exponential curve. The mean residence time was found to be 6.8 +/- 1.1 years, the standard deviation being estimated by the Monte Carlo simulations. The initial observed (134)Cs:(137)Cs activity ratio in potatoes has been found to be quite variable, but slightly lesser than the theoretically predicted value of 0.5, calculated by applying the known inventory of these radionuclides in the Chernobyl reactor to the equation for the differential radioactive decay. This can be explained by presence of the pre Chernobyl (137)Cs in soil that originated from nuclear fallout. The annual effective doses received by (134)Cs and (137)Cs intake due to consumption of potatoes estimated for an adult member of the Croatian population were found to be very small, as the per caput Dose for the entire 1986-2005 period was calculated to be about 2.9 microSv, (134)Cs accounting approximately for 1/3 of the entire dose. Therefore, after the Chernobyl accident consumption of potatoes was not the critical pathway for human intake of radiocaesium from the environment in Croatia. PMID- 17365337 TI - Effects of soil properties on heavy metal accumulation in flowering Chinese cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee) in Pearl River Delta, China. AB - This study was conducted to investigate the effects of soil properties on the heavy metal accumulation in flowering Chinese cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee) at the field scale. The concentrations of cadmium (Cd), mercury (Hg), and chromium (Cr) in topsoil and vegetable samples from Nanhai district of Foshan city in the Pearl River Delta (PRD) were analyzed. The results showed that 56.5% of the soil samples exceeded the grade II of the Chinese Soil Environmental Quality Standard (GB 15618-1995) for Hg concentrations, while 8.70% and 17.4% of the vegetable samples exceeded the criteria of the Chinese Safety Qualification of Agricultural Products (GB 18406.1 2001) for Cd and Hg concentrations, respectively. The calculated bio concentration factor (BCF; i.e., the ratio of the metal concentration in the edible parts of flowering Chinese cabbage to that in soil) values were ranked as: Cd (0.1415) > Cr (0.0061) > Hg (0.0012) (p < 0.01), which demonstrated that Cd was easier to be accumulated in the edible parts of flowering Chinese cabbage than Hg and Cr. Furthermore, the following relationships between (bio concentration factor) BCF values (BCFs) and soil physicochemical properties were concluded from our results: i) the mean BCFs of coarse-textured soils were higher than those of fine-textured soils; ii) the BCFs decreased with increasing soil pH; iii) the soils with high organic matter(OM) and Cation exchange capacity (CEC) have low BCFs, resulting from their high sorption capacities for Cd, Hg, and Cr. The stepwise linear multiple regression analyses showed that total metal concentrations and available calcium in soils were two main factors controlling the accumulation of Cd, Hg, and Cr in the flowering Chinese cabbage. PMID- 17365338 TI - The incidence of fungi and mycotoxins in South African barley and barley products. AB - Barley is grown as a crop in South Africa, mainly for use in the barley beer (lager) industry, particularly in the production of barley malt. This investigation was done to find out what fungal infection and mycotoxin contamination this barley and the malt contained. The survey, done in 2005, not only covered barley and malt but also the final product in the form of several brands of beer purchased from retail outlets. Analysis was done using a range of methodologies including chromatography, immunoaffinity/fluorimetry and cytotoxicity testing. The results show that barley, which also includes barley sold directly to the public, and malt, contain various fungi, sometimes at high incidence and also a range of mycotoxins which persisted through, although at low levels, to beer. The malt showed a different pattern of micro flora, as compared to the barley, which indicates infection during the malting process, which is not uncommon. Interestingly, fumonisin B1 was found in some of the samples, as well as the beer, although in the latter case these were at very low levels. Recent studies have shown that the immunoaffinity/fluorimetry method can give false positives for the fumonisins, so these results were confirmed by high performance liquid chromatography. As is the case with other cereals grown in South Africa, there is the concern that the public is exposed to mycotoxins on a regular basis through the consumption of products made from them. PMID- 17365339 TI - A full-scale sequencing batch reactor system for swine wastewater treatment. AB - A full-scale sequencing batch reactor (SBR) system was evaluated for its ability to remove carbon and nitrogen from swine wastewater. The SBR was operated on four, six-hour cycles each day, with each cycle consisting of 4.5 hours of "React," 0.75 hours of "Settling", 0.75 hours for "Draw" and "Fill." Within each cycle, an amount of wastewater equivalent to about 5% of the reactor volume (5,500 litres) was removed and added. The SBR system was able to remove 82% of biochemical oxygen demand (BOD) and more than 75% of nitrogen. Even though the SBR effluent, with an average effluent BOD5 of about 588 mg L(-1), did not meet the discharge criteria, it enabled a reduction of the land base required for land application of swine wastewater by about 75%. Results indicated that the SBR system was a viable method for the treatment of swine wastewater. PMID- 17365340 TI - Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective. AB - Arsenic can cause cancerous and non-cancerous human diseases. Inorganic arsenic from drinking water is the most common source of human exposure. Pentavalent arsenate can be reduced to trivalent arsenite in the blood, which is taken up mainly in the liver and metabolized by a sequence of reduction and oxidative methylation. A proportion of the inorganic arsenicals together with methylated metabolites are excreted in urine. Analyses of the urinary arsenic profile can give a hint to the methylation capacity of exposed individuals. All studies evaluating the association between urinary arsenic profiles and human diseases nowadays measure mainly the inorganic arsenate and arsenite and the two organic forms of methylated metabolites: the pentavalent form of monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV). A review of the current literature suggests that reduced methylation capacity with increased MMAV percentage, decreased DMAV percentage, or decreased DMAV/MMAV is associated with skin lesions, skin cancer, bladder cancer, peripheral vascular disease, muscle cramps and structural chromosome aberrations in peripheral lymphocytes obtained from exposed subjects. The detection of the recently identified more toxic trivalent forms of methylated metabolites in urine awaits further confirmation. PMID- 17365341 TI - Systematic review and meta-analysis of cyclodiene insecticides and breast cancer. AB - Cyclodienes are a group of organochlorine pesticides that have been the focus of increasing numbers of breast cancer etiology studies in recent years. The aim of this systematic review and meta-analysis was to summarize and pool the results of breast cancer and cyclodiene insecticide contamination studies. We used databases from 1966 to 7/2006 and included 21 case-control studies. Pooled odds ratios or differences in means as geometric means ratios were calculated. Meta-analysis of the chemicals did not reveal any statistically significant association except for heptachlor. The heterogeneity among the different studies and the methodology limitations are discussed. PMID- 17365342 TI - The expanding role of predictive toxicology: an update on the (Q)SAR models for mutagens and carcinogens. AB - Different regulatory schemes worldwide, and in particular, the preparation for the new REACH (Registration, Evaluation and Authorization of CHemicals) legislation in Europe, increase the reliance on estimation methods for predicting potential chemical hazard. To meet the increased expectations, the availability of valid (Q)SARs becomes a critical issue, especially for endpoints that have complex mechanisms of action, are time-and cost-consuming, and require a large number of animals to test. Here, findings from the survey on (Q)SARs for mutagenicity and carcinogenicity, initiated by the European Chemicals Bureau (ECB) and carried out by the Istituto Superiore di Sanita' are summarized, key aspects are discussed, and a broader view towards future needs and perspectives is given. PMID- 17365344 TI - Leadership in health: a renewed opportunity. PMID- 17365345 TI - Age analysis of newspaper coverage of mental illness. AB - In this study, we examine newspaper coverage of mental illness in children and adults taken from 6 weeks during a 1-year period. Articles were coded for (1) type of article; (2) types of disorders named or described; (3) themes related to crime, attributions of the disorder, treatments, and critiques of the mental health system; and (4) "elements of responsible journalism," including inclusion of perspectives from mental health experts, statistics related to mental illness, referrals to additional sources of information, and avoidance of slang terminology. We examine how these variables differ by the age of the group discussed in the article: children/adolescents and adults/older adults. One thousand two hundred fifty-two articles were coded for these four clusters as well as age of group discussed in the article. Inter-rater correlations of two independent judges were satisfactory for 10% of the stories. Age group comparisons revealed that the child articles contained a significantly higher proportion of feature articles; were significantly more likely to discuss behavior and conduct disorders, and alcohol and drug abuse, attention deficit hyperactivity disorder (ADHD), anxiety disorders, and eating disorders, and to contain themes of causation, treatment, and critiques of the mental health system. The adult articles contained a significantly higher proportion of episodic news stories and were significantly more likely to present themes of dangerousness and crime. Our analysis found that child articles were significantly more likely to incorporate elements of responsible journalism, while adult articles were significantly more likely to use stigmatizing terminology. Our report encourages journalists to develop contextually comprehensive and informative presentations of mental illness and issues surrounding the mental health system for all population groups in order to provide readers with accurate information within the context of general social trends and relevant expert opinion. PMID- 17365346 TI - Exploration of the construct of reliance among patients who talk with their providers about internet information. AB - Three hundred fifty participants, recruited from Internet health message boards, completed online surveys about their experiences talking with health care providers about Internet health information. Two distinct dimensions of reliance emerged from the data, one regarding the patient's reliance on the health care provider for decision making and the other regarding the patient's reliance on the health care provider to stay healthy. Self-reliant patients tended to be female, have lower incomes, and report less frequent visits to the health care provider than did health-care-provider-reliant patients. Age, comfort level, and frequency of talking about Internet health information were not related to reliance level. PMID- 17365347 TI - Pharmaceutical websites and the communication of risk information. AB - This study examines the pharmaceutical websites of 44 leading direct-to-consumer (DTC) advertised drugs to determine the extent to which risk information was completely communicated. Three operational definitions of "completeness" were used: communication of the single highest incidence side effect, communication of top three highest incidence side effects, and communication of side effects with incidence of >or= 10% (all measured in terms of absolute percentage). Results indicated that regardless of the measures used, pharmaceutical websites are unlikely to completely communicate risk information. About two thirds of all sites communicated the single highest incidence side effect or all top three side effects. For drugs with side effects at >or= 10% incidence, only about half of their websites fully reported all effects at this level of incidence. Implications for advertisers and regulatory agencies are presented. PMID- 17365348 TI - Public (Mis)understanding of the UV Index. AB - The ultraviolet index (UVI) has been regularly reported in Australia for a decade but utilisation remains extremely low ( approximately 5%). Blunden, Lower, and Slevin, in a 2004 Journal of Health communication article, suggest that Australians' understanding of the UVI is "good," and education to increase awareness of the index is therefore no longer warranted. To test this position, focus groups were conducted followed by an intercept survey of 404 residents of Perth, Western Australia, aged 16-44 years, to explore understanding and familiarity with the UVI. Results suggested that far from being "good," the familiarity and understanding of the UVI of at least half of Australians is poor. This was exemplified by the following: mean estimations of average UVI values in summer and winter being highly exaggerated (19.8 and 11.8, respectively); 61.2% not appreciating that the UVI is independent of temperature; at least 55.0% not appreciating that UV conditions peak at solar noon; and 23.3% of 22-44 year olds confusing the UVI with a "burn-time" measure. People who do not understand the UVI are unlikely to utilise it effectively. It therefore remains possible that utilisation of the UVI remains low because understanding is poor. Future efforts to improve utilisation of the UVI, particularly among those looking at new display formats, may therefore be ineffective, unless they also incorporate strategies to facilitate understanding of the measure. PMID- 17365349 TI - A computer-based approach to preventing pregnancy, STD, and HIV in rural adolescents. AB - A computer- and Internet-based intervention was designed to influence several variables related to the prevention of pregnancy, sexually transmitted diseases (STDs), and human immunodeficiency virus (HIV) in rural adolescents. The intervention was guided by the extended parallel process model and was evaluated using a pretest-post-test control group design with random assignment at the school level. Three hundred and twenty-six tenth-grade males and females enrolled in two rural Appalachian public high schools completed the survey at both points in time. Results indicate the vast majority (88.5%) of students in the experimental school completed at least one activity (M = 3.46 for those doing at least one activity). Further, both the overall program and all but one of the activities were rated positively by participants. Regarding the effects of the intervention, results indicate that students in the experimental school were less likely to initiate sexual activity and had greater general knowledge, greater condom negotiation self-efficacy, more favorable attitudes toward waiting to have sex, and greater situational self-efficacy than in the control school. In tandem, the results suggest that the computer-based programs may be a cost-effective and easily replicable means of providing teens with basic information and skills necessary to prevent pregnancy, STDs, and HIV. PMID- 17365350 TI - Acceptability of a bilingual interactive computerized educational module in a poor, medically underserved patient population. AB - We evaluated the acceptability and impact of an audiovisual, bilingual, interactive computer module relating to appropriate antibiotic use. In winter 2001, adults seeking urgent care for acute respiratory infections at an inner city urgent care clinic were invited to complete the computer module and survey (N = 296). After responding to questions about their symptoms, patients were provided information about their illness and appropriate antibiotic use, and then asked several questions about the acceptability of the module. The main outcomes, reflecting qualities known to enhance diffusion of innovations, were "learning something new about colds and flu" and trusting the computer information. Spanish language respondents (16%) were much less likely to report prior computer experience, more likely to need help, and strongly preferred answering to a person compared with English-language respondents. In multivariable analysis, Spanish-language respondents were more likely to report learning something new (OR = 5.0; 95% CI: 2.0, 12.4) and trusting the information (OR = 2.5; 95% CI: 1.0, 6.0). We conclude that an interactive computer module was well received among a medically underserved urgent care clinic population. Benefits appear greatest among populations having the least experience with this medium. PMID- 17365353 TI - An informed patient - an oxymoron in an information restricted society. PMID- 17365354 TI - Media usage as health segmentation variables. AB - The purpose of this research is to contrast a traditional audience segmentation model that uses demographics and health evaluations against a model that uses these same variables plus media usage variables. The goal was to determine whether media usage variables - typically not used in health segmentation studies - add predictive power in determining health behaviors and attitudes. The results of the analysis showed an increase in the ability to predict health behaviors such as aspirin use, vitamin use, diet, and exercise, and suggest that there is predictive value for including media variables as part of the segmentation process. Implications for public health education and campaign planning are discussed. PMID- 17365355 TI - Fighting AIDS among adolescent women: effects of a public communication campaign in Brazil. AB - In 2003, Brazil's Ministry of Health launched a national campaign aimed at promoting the use of condoms by adolescent women. The Carnival Campaign was broadcast on television and radio between February 16 and March 3 and targeted young women, between 13 and 19 years of age, a social group that previously had registered a growth in the number of cases of AIDS and other sexually transmitted diseases (STDs). The Ministry hired Kelly Key, a Brazilian pop singer, to deliver the campaign messages. One of the objectives was to empower the girls and encourage them not to be ashamed to buy condoms and to demand that their partners use them. The article presents the results of a national survey conducted with 1,006 adolescent women, which was sponsored by the Ministry of Health. The results show that campaign materials reached the main target public and that they were very positively received. Moreover, the survey data show that the Carnival Campaign had important effects, generating discussions in the adolescents' social environments and reinforcing a social norm that favors the participation of women in the purchase and use of condoms. PMID- 17365356 TI - The "choose with care system" - development of education materials to support informed Medicare health plan choices. AB - People aging into Medicare need to choose a health plan. Several challenges exist for consumers in choosing a Medicare health plan, including limited knowledge of Medicare, limited experience in using comparative health plan quality information, and limited experience and ability to pull together and use plan information from different sources like employers and the Medicare program. The Choose with Care System was developed to help consumers aging into Medicare make informed Medicare health plan choices. Choose with Care is an innovative decision support tool for employers to use to assist people approaching age 65 to learn about their Medicare health plan options and how to incorporate information on the quality of care and services offered by health plans into their choices. Employers are the targeted channel for distributing the Choose with Care materials because they are one of the most recognized and accessible formal intermediaries for information about health insurance. We used multiple methods to test the Choose with Care products. Product testing showed that the Choose with Care materials increase older consumers' knowledge of Medicare and how it relates to retiree health insurance and improves their comprehension and use of comparative quality information when choosing a health plan. PMID- 17365357 TI - The effectiveness in utilizing Chinese media to promote breast health among Chinese women. AB - To increase the awareness and practice of breast health guidelines, a media-based education campaign on breast health was launched among immigrant Chinese community in San Francisco. The media campaign included airing two public service announcements (PSAs) on Chinese television and radio stations and publishing the same message in Chinese newspapers during 2000. Seven-hundred-ten face-to-face interviews were conducted with women who were recruited from various settings in the city of San Francisco to evaluate the impact of the campaign. Survey participants were asked to describe the content of the PSAs. Having viewed the PSA was significantly associated with the ability to identify all four guidelines (OR = 1.96; 95% CI: 1.35-2.85), knowing how to perform breast self-exam (BSE; OR = 2.25; 95% CI: 1.53-3.29), having performed BSE within the past month (OR = 3.12; 95% CI: 2.05-4.74), and having a clinical breast exam (CBE; OR = 2.98; 95% CI: 1.82-4.90) and mammogram (MAM; OR = 1.97; 95% CI: 1.16-3.36) in the past year. The study findings support that a media campaign utilizing PSAs is effective in improving knowledge of breast health guidelines, teaching Chinese women how to (BSEs), and increasing breast health practices. PMID- 17365358 TI - Healthy or unhealthy slogans: that's the question... AB - An experiment was conducted to examine the effect on adolescents of different health appeals (healthy versus unhealthy) in ads for healthy and unhealthy perceived foods. The results did not reveal a main effect of product or slogan, but indicated a significant interaction effect between slogan and product. The healthy slogan only led to significantly more positive attitudes and purchase intentions when it promoted a healthy food product. An unhealthy food product received better results in combination with an unhealthy slogan than with a healthy one. This indicates that adolescents react better to ads in which the health appeal is congruent with the health perception of the product. Moreover, we took into account gender and health concern as potential moderators in the relationship between slogan and ad responses. Gender did not lead to different responses to healthy or unhealthy food ads, whereas health concern did interact significantly with the slogan type. Highly concerned adolescents responded more favorably to a healthy slogan in terms of attitudes. A necessary first step seems to be making adolescents more health conscious. A following step is to reinforce their positive attitudes toward healthy foods and turn these into real behavior. PMID- 17365359 TI - Social support and social undermining as correlates for alcohol, drug, and mental disorders in American Indian women presenting for primary care at an Indian Health Service hospital. AB - The purpose of this study was to determine the relationship of two types of social support (emotional and instrumental) and two types of social undermining (critical appraisal and isolation) with five categories of alcohol, drug, or mental disorders (ADM; any mood, any anxiety, any substance abuse, any disorder, and two or more disorders) in 169 American Indian women presenting for primary care at an Indian Health Service facility. Social support and social undermining are often treated as opposite poles, but in fact they are distinct factors with independent effects. The findings illustrate that social support and undermining variables have a significant relationship with ADM outcomes even when controlling for confounding demographic variables. Any substance abuse was associated with all four social variables, while two or more disorders were associated with instrumental support and isolation. Any anxiety (isolation), any mood (critical appraisal), and any disorder (isolation) were each associated with one social variable. Overall, social undermining appears to have a stronger relationship with mental health than with social support. PMID- 17365362 TI - Parental appraisal of the family impact of childhood developmental disability: times of sadness and times of joy. AB - BACKGROUND: Parental positive and negative appraisals of the family impact of childhood disability are tested as early predictors of parental self-esteem and overall family adjustment in households with young children with intellectual and developmental disabilities. METHOD: Within 103 Canadian families, 103 mothers and 55 fathers independently completed interviews in their home at two time points: 6 months after their child entered childhood disability services (T1), and one year later (T2). RESULTS: Longer-term family adjustment was found to be predicted by level of parental negative appraisal of the family impact of disability, and by level of self-esteem, for both mothers and fathers. For mothers, positive appraisal of childhood disability was also found to predict early family adjustment and was related to enhanced self-esteem. CONCLUSIONS: Gender differences in parental appraisal of the family impact of childhood disability appear to merge over time. Both positive and negative appraisals appear to coexist and are predictive of mothers' and fathers' perceived overall family adjustment in the longer term. PMID- 17365363 TI - Work integration of people with disabilities in the regular labour market: what can we do to improve these processes? AB - BACKGROUND: It is important to ensure that regular processes of labour market integration are available for all citizens. METHOD: Thematic content analysis techniques, using semi-structured group interviews, were used to identify the principal elements contributing to the processes of integrating people with disabilities into the regular labour market. Thirty-two professionals from 17 agencies provided information regarding the role of the family, training, workplace monitoring, the work setting, and personal resources of the worker. RESULTS: The results indicated that family, training (prior to and during the integration service), monitoring of the worker in the workplace, and work setting were relevant and contributing aspects of the process of work integration. CONCLUSIONS: A real and effective commitment on the part of the government is required to regulate and provide resources to create supported employment services and to allow these services to plan their own interventions, keeping in mind the relevance of and relationship between aspects such as family, training, workplace monitoring, the work setting and personal resources of the worker. PMID- 17365364 TI - Effects of an awareness program on attitudes of students without an intellectual disability towards persons with an intellectual disability. AB - BACKGROUND: We tested whether social and educational integration combined with training in awareness of disability for secondary school students resulted in more positive, long-lasting attitudes about educational and social inclusion of people with an intellectual disability. METHOD: Attitudes of 259 participants (116 males, 143 females) were assessed by questionnaire. Effects of awareness of disability programs (ADPs) were tested by comparing attitudes of current secondary school students participating in a 3-session or 8-session ADP (n = 67) and past students who had participated in a 10-session ADP 8 years prior to the present study (n = 46), with same-age controls without training (n = 146). RESULTS: Students completing 8-session ADPs reported more favourable attitudes than students in the 3-session ADP and peers without training. Past students' attitudes were also highly positive, compared with same-age controls without training. CONCLUSIONS: ADP programs can promote positive attitudes towards people with an intellectual disability. Such training may have long-term benefits. PMID- 17365365 TI - Perspectives of constraining and enabling factors for health-promoting physical activity by adults with intellectual disability. AB - BACKGROUND: Physical activity influences health in individuals and within populations. This study explored factors perceived as enabling or inhibiting participation in physical activity by adults with intellectual disability from a health promotion perspective. METHOD: Six focus group interviews were conducted: adults with intellectual disability (1 group, n = 9), direct care workers (1 group, n = 5), group home supervisors (2 groups, n = 9 and n = 6), managers (1 group, n = 4), and parents (1 group, n = 7). RESULTS: Three major themes were identified from the focus group interviews: motivation for participation, social support, and political and financial support. CONCLUSIONS: The most critical issue was the lack of clear policies. Both day training centres and accommodation services would benefit from development of policies related to health-promoting physical activity. Flowing on logically from the development of policy would be much needed training and support of staff. PMID- 17365366 TI - Multiple versus single maintaining factors of challenging behaviours as assessed by the QABF for adults with intellectual disabilities. AB - BACKGROUND: The Questions About Behavioral Function (QABF) correctly identifies maintaining variables of challenging behaviour. However, for adults who have a long history of challenging behaviours, identifying one clear function of the maladaptive behaviour is difficult. Additionally, the person may develop multiple functions of their maladaptive behaviour. METHOD: Characteristics of single versus multiple maintaining factors were evaluated using the QABF for 88 adults with intellectual disabilities (ID). The reliability of single versus multiple maintaining factors for aggression and self-injurious behaviour was analysed. Multiple factors were analysed in terms of type of maintaining factors, and their order of importance by challenging behaviour was noted. RESULTS: The majority of behaviours examined were maintained by multiple functions. Reliability was higher for behaviours with a single maintaining variable when compared to behaviours with multiple maintaining variables. CONCLUSION: These data appear to have implications for aetiology, assessment, and treatment of challenging behaviours in individuals with ID. PMID- 17365367 TI - Clinical audit of gastrointestinal conditions occurring among adults with Down syndrome attending a specialist clinic. AB - BACKGROUND: Adults with Down syndrome (DS) are predisposed to syndromic and environmental gastrointestinal conditions. METHOD: In a hospital-based clinic for adults with DS, a chart audit was conducted to assess the range and frequency of gastrointestinal conditions. RESULTS: From January 2003 to March 2005, 57 patients attended the clinic, average age 37 years (SD = 13, range 17-63), 34(60%) male, and 12(21%) with a history of institutionalisation. Of these, 56 were found to have at least one gastrointestinal concern. Of the genotypic conditions, the prevalence was as follows: 6(12%) of 51 tested had likely celiac disease, 1(2%) had achalasia, 1(2%) inflammatory bowel disease, 1(2%) cholelithiasis, 2(4%) unexplained abnormal liver function tests, 1(2%) extrinsic oesophageal compression, and 5(9%) gastro-oesophageal reflux. Of the environmental conditions, 29(67%) of 43 tested had H. pylori infection; 13(25%) of 53 tested had hepatitis B infection (including 2 HbsAg positive, 0 HbeAg positive), 22(42%) non-immune and 4(7%) not tested; 17(36%) of 47 tested were immune to hepatitis A, 30(64%) non-immune and 10(18%) not tested. Of the conditions of uncertain link with Down syndrome, 11(19%) of the 57 patients had unexplained constipation; 11(19%) had unexplained chronic diarrhoea; 1(2%) had haemochromatosis; and 39(68%) presented with overnutrition. CONCLUSION: On specific enquiry, a majority of adults with DS have a gastrointestinal condition. As many of the conditions require hospital services, specially designed protocols in this setting should be developed. PMID- 17365368 TI - Meeting the health needs of people with disability living in the community. PMID- 17365369 TI - Working together for health. PMID- 17365370 TI - Pessimism and optimism in inter-professional working: the Sedgefield Integrated Team. AB - The literature on inter-professional working tends to be dominated by explanations for lack of progress rather than accounts of achievements. This paper develops two models, termed the optimistic and pessimistic models respectively, to understand the factors that may underpin different rates of interprofessional achievement. A case study of the Sedgefield Integrated Team in County Durham, UK is used to test out aspects of the models. It is concluded that the grounds for pessimism have been overstated and that the scope for professional integration is greater than tends to be assumed. PMID- 17365371 TI - Comparison of language used and patterns of communication in interprofessional and multidisciplinary teams. AB - Can the language used and the patterns of communication differentiate a multidisciplinary team from an interprofessional team? This research question arose from an unexpected outcome of a study that investigated clinical reasoning of health professional team members in the elder care wards of two different hospitals. The issue at stake was the apparent disparity in the way in which the two teams communicated. To further explore this, the original transcribed interview data was analysed from a symbolic interactionist perspective in order that the language and communication patterns between the two teams could be identified and compared. Differences appeared to parallel the distinctions between multidisciplinary and interprofessional teams as reported in the literature. Our observations were that an interprofessional team was characterized by its use of inclusive language, continual sharing of information between team members and a collaborative working approach. In the multidisciplinary team, the members worked in parallel, drawing information from one another but did not have a common understanding of issues that could influence intervention. The implications of these communication differences for team members, team leaders and future research are then discussed. PMID- 17365372 TI - Meaning of language differences between doctors and educators in a collaborative discourse. AB - This study of an ethnographic discourse examines the language of professionals - teachers and psychiatrists - working in collaboration in a special education school. The research objectives were examination of the meanings of recurring key words and the role of language in the verbal interaction between educators and doctors in their daily professional life. Data were collected from formal meetings, informal meetings, semi-constructed ethnographic interviews and documents published in the course of the school year. The paper offers two models for analyzing the interprofessional discourse. The first examines how key words reflect the perceptions of the speaker and his/her discipline, looking at the purpose of the communication. The second allows the researcher to examine the transferability of these concepts to the other discipline, focusing on the results of the communication. The findings reveal areas of discontent in the work of staff members with pupils, as well as the process of language transferability between professionals. PMID- 17365373 TI - Time used on interprofessional collaboration in child mental health care. AB - This study investigates a sample of professionals (N = 134) who work with children with mental health problems, in the western part of Norway. A 48-item questionnaire was designed to measure different aspects of interprofessional collaboration. Two demographic questions in the questionnaire focused on how much time professionals use on interprofessional collaboration on a regular working day and results from these two questions are reported. How much time do professionals use on interprofessional collaboration within the context of helping children with mental health problems? Do professionals collaborate more within their own organization than with professionals from external organizations? The results show that professionals, on average, use about 40% of their time on collaboration activities. Professionals, as expected, collaborate more with professionals from their own organization than with professionals from other health care services. PMID- 17365374 TI - Capturing the concealed: Interprofessional practice and older patients' participation in decision-making about discharge after acute hospitalization. AB - The aim of this paper is to investigate ways in which the dynamics of interprofessional work shaped older patients' "participation" in decision-making about discharge from acute hospital care in a medical directorate of a District General Hospital in Scotland. Twenty-two purposively selected older patients and their key professional hospital carers in three different ward environments participated in the study. An ethnographic approach was adopted, involving semi structured interviews with patients and staff combined with rigorous observation of the practical context for staff and patient interactions during the discharge planning process over a 5-month period. Patients' and staff's understanding of "decision-making" and their priorities for discharge were different, but patients' perspectives fragmented and became invisible. Care routines, which centred around assessments and the decisions that flowed from these tended to exclude both staff and patients from active decision-making. Research and practice on patient involvement in discharge decision-making needs to focus on the organizational context, which shapes patients', unpaid carers' and staff's interactions and the dynamics by which some views are privileged and others excluded. Procedurally driven care routines and their impact on patients', carers' and staff's opportunity to actively engage in decision-making should be re-considered from an empowerment perspective. PMID- 17365375 TI - Developing collaborative person-centred practice: a pilot project on a palliative care unit. AB - Maximizing interprofessional collaborative patient-centred practice holds promise for improving patient care and creating satisfying work roles. In Canada's evolving health care system, there are demands for increased efficiency, cost effectiveness, and quality improvement. Interprofessional collaboration warrants re-examination because maximizing interprofessional collaboration, especially nurse-physician collaboration, holds promise for improving patient care and creating satisfying work roles. A palliative care team seized the opportunity to pilot a different approach to patient and family care when faced with a reduction in medical staff. Grounded in a collaborative patient-centred practice approach, the Canadian Hospice Palliative Care Association's National Model to Guide Hospice Palliative Care (2002), and outcomes from program retreats and workgroups, a collaborative person-centred model of care was developed for a 12 bed pilot project. Preliminary findings show that the pilot project team perceived some specific benefits in continuity of care and interprofessional collaboration, while the presence of the physician was reduced to an average of 3.82 hours on the pilot wing, compared with 8 hours on the non-pilot wings. This pilot study suggests that a person-centred model, when focused on the physician nurse dyad, may offer improved efficiency, job satisfaction and continuity of care on a palliative care unit. Incorporating all team members and developing strategies to successfully expand the model across the whole unit are the next challenges. Further research into the impact of these changes on the health care professionals, management and patients and families is essential. PMID- 17365376 TI - Negotiation of interprofessional culture shock: the experiences of pharmacists who become physicians. AB - Professions generally operate within a shared set of values, symbols, and norms; in short, professions may be characterized as having somewhat unique sub cultures. As inter-professional teamwork and collaboration gain prominence, understanding the inter-cultural dimensions of professional interactions may be useful in explaining how and why such teams function. One way of examining the unique (and common) elements of professional sub-cultures is to study the experiences of professionals who have "migrated" from one field to another. In this paper, the "culture shock" experience of pharmacists who have become physicians is described and discussed. Results from interviews with 32 pharmacist physicians were used to frame four major themes that depict salient and unique characteristics of the cultures of pharmacy and medicine. PMID- 17365377 TI - Exploring physiotherapy students' experiences of interprofessional collaboration in the clinical setting: a critical incident study. AB - Effective interprofessional collaboration is considered essential for optimum healthcare delivery. Studies have investigated interprofessional education (IPE) as a means for improving collaborative practice, and evidence suggests that the clinical setting offers opportunities for interprofessional learning (IPL). Little is known, however, about the aspects of clinical practice that students perceive as meaningful to their IPL. This study explores physiotherapy students' experiences of collaborative working, and identifies their perceptions of the skills used and factors affecting interprofessional interactions in the clinical setting. Twenty second-year physiotherapy students studying in London provided written critical incident reports describing good and poor interprofessional collaborative encounters in the clinical setting. The data were subjected to thematic content analysis. Students identified communication and interprofessional relationships as the main factors affecting collaboration and perceived teamwork in formal contexts (e.g., team meetings) as generally effective with positive outcomes for professionals and patients. Informal collaboration was perceived to be poor and attributed primarily to insufficient direct contact and communication. The wide range of described experiences and learning outcomes indicate that clinical placements provide potentially valuable IPL opportunities. Facilitating the development of informal (ad hoc) collaborative teamwork skills is proposed as an important consideration when planning and implementing IPE in this setting. PMID- 17365378 TI - Structuring communication relationships for interprofessional teamwork (SCRIPT): a Canadian initiative aimed at improving patient-centred care. PMID- 17365386 TI - The journey to publication. PMID- 17365387 TI - Comparison of self, physician, and simulated patient ratings of pharmacist performance in a family practice simulator. AB - The Family Practice Simulator (FPS) was piloted as a teaching, learning, and assessment opportunity for pharmacists making the transition into primary care practice. During this one-day simulation of a typical day in a family physician's office, nine pharmacists rotated through a series of 13 OSCE stations where they interacted with physicians, patients, nurses and office staff while completing primary care activities and receiving performance evaluations. Pharmacists' performance ratings from self, physician, and standardized patient evaluations were compared using Global Rating Scales (GRS) scores and station-specific key points checklists. The mean (SD) overall GRS scores obtained by pharmacists across all stations in the FPS were 4.56 (SD = 0.60) from standardized patients, 3.95 (SD = 0.63) from physicians, and 3.60 (SD = 0.63) from self-assessment (out of a maximum score of 5). Agreement between pharmacists' and patients' GRS ratings ranged from moderate to good (generalizability coefficient (G) = 0.45 to 0.72) for all except one station. Agreement in GRS scores between pharmacists and physicians was at most fair for every station (G = 0.02 - 0.26). There was fair agreement on key points scores between pharmacists and patients (weighted kappa = 27%; 95% CI 7%, 47%) and moderate agreement between pharmacists and physicians (weighted kappa = 45%; 95% CI 21%, 70%). Although there was at best moderate agreement in rating scores between pharmacists, standardized patients, and physicians, the FPS provided an important opportunity to measure expectations regarding the professional role, responsibilities, and performance of pharmacists from a multi-professional perspective, thus better preparing pharmacists for integration into primary care practice. Differences in agreement may have been due to different preconceptions and expectations among raters. PMID- 17365388 TI - Linking social work agency perspectives on interprofessional education into a school of nursing and midwifery. AB - Recent policy documents have highlighted the importance of developing interprofessional education to support interprofessional practice. In particular improving communication between health and social care agencies has been highlighted as an educational and practice priority. This study set out to explore the interprofessional training needs of social work practitioners with social work agencies in North East London to ensure that the interprofessional courses were relevant to social work. Findings from 15 qualitative interviews with key health and social care professionals in eight London boroughs will be presented. The findings suggest that there is great diversity in the budgets, resources and approaches taken to post qualifying training across the boroughs and between agencies and that training needs analysis for experienced practitioners is at an early stage of development workforce planning to the commissioning of education. Social work services identified bespoke training and the accreditation of their existing programmes as important. Responding to rapid organizational change and immediate training needs was a key priority in the services interviewed. However, limited funding to release social workers to take up interprofessional post-qualifying training remains a constraint for training officers, and how training was planned and organized by both practitioners and providers was considered important. PMID- 17365389 TI - Knowing your allies: medical education and interprofessional exposure. AB - Collaborative, team-based, interprofessional approaches to patient management are becoming increasingly recognized as beneficial to health outcomes. This project aimed to develop interprofessional skills among 134 third year medical students that were of clinical educational value to the students, and through activities that directly benefited the rural health professionals in their daily work. Placements were undertaken during a six week rural clinical attachment, mainly throughout South-West Queensland. Pre- and post-placement self-report questionnaires completed by both students and health professionals were used to evaluate the project. Results showed that over 80% of the health professional group reported the medical student placements were useful. Similarly, almost 80% of medical students reported positive changes in their attitude to other health professionals from the placement, and 91% indicated they had derived clinical educational benefit from their interprofessional activity. Despite difficulties due to poor communication between the various parties involved, the project proved successful in improving medical students' skills, knowledge and perceptions concerning interprofessional practice, through a placement and educational project which delivered practical benefits to rural health professionals and rural communities. PMID- 17365390 TI - Patients, doctors, and therapists perceptions of professional roles in spinal cord injury rehabilitation: do they agree? AB - Spinal cord injury is a devastating condition, requiring extensive rehabilitation from a range of health care professionals. However, it is unclear if patients view the professionals' input into their rehabilitation in the same way as those professionals. This paper presents findings from a qualitative study into patient participation in spinal cord injury rehabilitation. The aim of the part of the study reported here was to identify whether there is agreement between health care professionals and patients perceptions of professional roles in spinal cord injury rehabilitation. Results are presented from semi-structured interviews conducted with five doctors, five physiotherapists, three occupational therapists and 20 patients in a spinal cord injury unit in England. Findings suggest considerable agreement between professionals and patients about the role those professionals play in their rehabilitation. Physiotherapists are perceived to be key to rehabilitation, occupational therapists focus on hand function but physiotherapists and occupational therapists complement each other. Doctors coordinate the team yet reduce their input as patients move out of the acute phase into rehabilitation. There are some tensions but the early input of these professionals into patients' rehabilitation may help to develop understanding of roles. Congruence between patients and professionals may mean that patients have realistic expectations and encourage a more equal relationship between them. PMID- 17365391 TI - Transforming care at the bedside: patient-controlled liberalized diet. AB - A 2003 partnership between the Institute for Healthcare Improvement and the Robert Wood Johnson Foundation created an initiative to redesign medical-surgical inpatient care - Transforming Care at the Bedside (TCAB). TCAB is intended to transform the elements that affect care on medical/surgical units by rapidly creating, testing, and measuring new ideas. TCAB began as a pilot with three hospitals nationwide, including the University of Pittsburgh Medical Center (UPMC) Shadyside in Pittsburgh, Pennsylvania. UPMC Shadyside initiated its TCAB efforts with an interdisciplinary initiative, involving registered nurses (RNs), nursing assistants, registered dietitians (RDs), and medical doctors (MDs), to transform nutritional services for medical-surgical inpatients. The Patient Controlled Liberalized Diet Program, piloted in late 2003 and rolled-out house wide in August, 2004, puts the patient in control. The goal is to improve nutritional status and satisfaction among inpatients by empowering them to make menu selections and providing individualized nutrition education. Positive quantitative and qualitative outcomes have resulted, leading to plans for system wide (19-hospital) spread and further programmatic evolution. PMID- 17365392 TI - "Who's on the team today?" The status of briefing amongst operating theatre practitioners in one UK hospital. AB - Accidents in health care are mainly due to systemic communication errors. Errors occur more frequently in the operating theatre (OT) than other clinical settings. Hence, it is important that preventive communication practices are adopted in OT teams. Formal team pre-briefing has been shown to improve safety in high risk settings such as aviation, but such briefing is not common practice in OT teams. This paper reviews key literature demonstrating the value of briefing in high risk practices; presents and analyses the results of a questionnaire survey on the status of briefing after its introduction to OT teams in one UK hospital; and analyses processes that frustrate widespread adoption of briefing. In comparison with other OT practitioners, surgeons generally reported differing perceptions of the meaning and value of briefing, often holding broad notions of what constitutes a "brief", but also showing scepticism towards briefing. However, surgeons who had introduced briefing reported positive results such as greater efficiency, shared understanding, and increased team morale. Collaborative briefing that extends beyond the technical to include the interpersonal could be initiated in principle by any member of the OT team, but a number of factors inhibit this, and surgeons play a pivotal role in establishing briefing. PMID- 17365393 TI - Primary care - mental health collaboration: an example of assessing usual practice and potential barriers. AB - Practice guidelines include recommendations for collaboration between primary care (PC) and mental health (MH) to improve the quality of depression management within primary care. There is little research, however, assessing usual care relationships between PC and MH providers, or providers' perceptions regarding collaboration. Based on the literature, we conceptualize a continuum of collaborative activities and strategies. We describe the extent of collaboration and perceived barriers in selected outpatient clinics. We conducted semi structured interviews with 22 PC and MH clinical leaders from 10 outpatient facilities. Topics included existing referral, consultation, and collaboration practices between PC and MH, beliefs and barriers related to collaboration. Informants generally described good relationships between providers, and PC providers reported satisfaction with referrals to MH. Informal consultation also occurred, although it was not universal. There was little evidence of collaboration beyond this basic level. The leaders identified several potential barriers to collaboration, including inadequate staffing and resources for both services. In contrast with practice guidelines, the clinics we studied incorporated little collaboration with MH providers into PC management of depression. We identify strategies that can help overcome the barriers to collaboration that our informants most commonly identified. PMID- 17365394 TI - Roles and expectations of a primary care team. PMID- 17365395 TI - The knowledge and perception of general practitioners about chiropractic as a factor that may influence inter-professional communication: a South African perspective. PMID- 17365401 TI - The four doctors. AB - The Four Doctors (1906) represented not only one of the best paintings of the noted artist John Singer Sargent (1856-1925) but a dominant change in the practice of American medicine of the day. The Four Doctors were the four distinguished founders of the Johns Hopkins Medical School: William Welch (1850 1934), William Osler (1849-1919), William Halsted (1852-1922) and Howard Kelly (1858-1943). The Four Doctors were the essence of the best medicine and surgery practiced in the United States. They were a new sophisticated group of medical professionals. They were the force behind significant developments in the medicine of America and the medicine of the world. In preparing for this monumental canvas, Sargent brought the four founders to his studio in London. With careful attention to detail, the four professors, were depicted in their solemn academic gowns, with a Venetian globe and the El Greco replica of St. Martin and the Beggar forming a most impressive background. "We have got our picture," the pleased master painter exclaimed. With the completion of this remarkable work of art, the medical establishment was left with a clear and memorable example of the medical and surgical pioneers of modern American medicine. PMID- 17365402 TI - Contribution of insulin-like growth factor I to the healing of colonic anastomoses in rats. AB - The aim of this experimental study was to investigate the contribution of insulin like growth factor I (IGF)-I in the colonic healing process when injected intraperitoneally after colon resection. Forty male Wistar rats were used. Rats in the control group were injected with 3 mL of a solution of 0.9% NaCl intraperitoneally after the operation and on postoperative day 2, 4, and 6. Rats in the IGF-I group received recombinant human IGF-I in a dose of 2 mg/kg body weight intraperitoneally, immediately after the colonic anastomosis was performed and on postoperative day 2, 4, and 6. All rats were killed on postoperative day 7. The hydroxyproline tissue content was significantly higher in the IGF-1 group than in the control group. The bursting pressures were also significantly higher in IGF-1 group than in the control group. The weight change between the groups differed significantly; in the control group the average weight decreased about 5% postoperatively, while in the IGF-1 group the average weight increased about 6%. The average inflammatory cell infiltration score was significantly higher in the control group. Neoagiogenesis did not differ significantly between the two groups. The fibroblast activity differed significantly between the two groups, as the control group had significantly less fibroblasts compared to the IGF-1 group. In conclusion, IGF-I when given intraperitoneally stimulates the healing of colonic anastomoses in the rats. Further studies are required in order to determine whether this effect is dose related. PMID- 17365403 TI - The role of dura mater and free peritoneal graft in the reinforcement of colon anastomosis. AB - Anastomotic leakage is the most important complication leading to morbidity and mortality in colorectal surgery. To prevent anastomotic leakage, a number of drugs with different mechanisms of action were tested, and autogenic grafts and various synthetic materials were used for reinforcement of the anastomotic region. In this experimental study aimed at preventing anastomotic leakage and dehiscence, we used dehydrated, lyophilized human dura mater and free peritoneal graft for reinforcement of anastomotic region after primary repair in rats, and investigated whether they are superior to primary anastomosis. The rats were sacrificed 3 and 7 days postoperatively. The anastomotic region was observed macroscopically for adhesions, bursting pressure of bowel was measured for tensile strength of the anastomosis, and histopathologic evaluation was performed for anastomotic healing. Compared to the control group, dura mater and free peritoneal graft groups displayed a lower bowel bursting pressure (p < .05), worse anastomotic healing (p < .05), a higher number of adhesions, and presence of anastomotic stricture. In conclusion, both human dura mater and free peritoneal graft reinforcement groups had worse anastomosis healing. The results could be attributed to avascularity of grafts and to aggravated adhesions between anastomosis and intra-abdominal organs, which created a favorable environment for reproduction and dispersion of bacteria and consequently led to decreased anastomosis healing. PMID- 17365404 TI - Genetic deletion of JNK1 and JNK2 aggravates the DSS-induced colitis in mice. AB - The c-Jun N-terminal kinases (JNKs) are considered as novel targets for therapy of inflammatory bowel diseases (IBD). However, the relevant JNK isoforms have to be elucidated. Here, we analyze the individual contribution of the JNK1 and JNK2 isoforms in a dextran sulfate sodium (DSS) model of experimental colitis. JNK1 and JNK2 knockout mice (JNK1 ko, JNK2 ko) and their wild-type controls (WT1, WT2) received three cycles of DSS treatment, each consisting of 1.7% DSS for 5 days, followed by 5 days with water. Animals were daily evaluated by a disease activity index (DAI) comprising measurement of body weight, estimation of stool consistency, and test for occult blood/gross rectal bleeding. After 30 days all animals were sacrificed, and the inflamed intestine was histologically evaluated by a crypt damage score. Unexpectedly, neither JNK1 ko nor JNK2 ko prevented mice from developing a chronic colitis when compared to wild-type controls WT1 and WT2, respectively. On the contrary, DAI and mortality were aggravated in JNK2 ko compared to WT2. DAI and mortality did not differ between JNK1 ko and WT1, but the histological crypt damage score was significantly enhanced in the cecum of JNK1 ko mice. Genetic deletion of JNK2 worsens the disease outcome in an experimental model of murine colitis. We hypothesize that the functional deletion of the otherwise proapoptotic JNK2 prolongs the activity of proinflammatory immune cells with deterioration of disease activity. PMID- 17365405 TI - Evaluation of postinjury hepatocyte function by central amino acid clearance. AB - It has been demonstrated by other investigators that central plasma clearance of amino acids accurately predicts hepatocyte function in patients with liver disease and correlates with clinical outcome. This methodology has not heretofore been studied in the trauma patient. It is our hypothesis that central amino acid clearance in trauma patients is more reflective of hepatocyte function than traditional liver function tests. We examined the plasma amino acid clearance rates using L-[1-13C]phenylalanine. Clearance rates were compared to standard liver function tests (LFTs) and the sensitivity and predictability of the technique were determined. The study was conducted on uninjured control subjects and in seriously injured patients, both with and without significant liver injuries. Compared to baseline values in the control group, initial phenylalanine breath scores were reduced in the injured, but exceeded control levels at 7 days postinjury. These changes were statistically significant. There was no difference between those with and without liver trauma. LFTs showed inconsistent and conflicting results. Thus, central amino acid clearance measured by L-[1 13C]phenylalanine oxidation is depressed immediately following injury but reaches supranormal levels at 7 days postinjury. Compared to LFTs, amino acid clearance suggests initial hepatocyte suppression followed by hyperactivity and is a more accurate determinant of hepatocyte function. PMID- 17365406 TI - Comparing reconstruction with ileocecal graft to jejunal interposition pouch after total gastrectomy in rats. AB - After total gastrectomy, the ileocecal graft may act as a reservoir and protect against reflux but give rise to transposition of the ileum and cause possible changes in bile acid metabolism and nutrition. This study compared the ileocecal graft and jejunal pouch. Male Wistar rats weighing 265 +/- 22 g were submitted to sham operation (S), ileocecal interposition graft (IIG), and jejunal pouch interposition graft (JP) after total gastrectomy. Eight weeks later, the esophagus was examined for evidence of esophagitis. Nutritional biochemistry and weight profile were documented preoperatively and 8 weeks after surgery. The oral glucose tolerance test was performed. Thirty-three rats were operated on and 30 survived for 8 weeks. Esophagitis occurred in seven JP rats. Body weight was significantly higher in IIG than in JP rats (p < .05). Normal glucose tolerance to intragastric glucose load was observed in sham and operated rats. JP rats had a significant decrease in serum albumin, glucose, transferrin, hemoglobin, iron, folate, and calcium, compared to sham (p < .05). Cobalamine was significantly lower in IIG rats than in JP rats (p < .05). In the IIG and JP groups, serum/hepatic total bile acid did not differ significantly from preoperative and sham values. In conclusion, the IIG interposition graft in rats prevented esophagitis, preserved nutrition, and did not interfere with enterohepatic total bile acid circulation. PMID- 17365407 TI - Endothelial nitric oxide synthase gene intron 4 (VNTR) polymorphism and vascular access graft thrombosis. AB - Vascular access thrombosis is a leading cause of vascular access failure in hemodialysis patients. Thrombosis is a multifactorial condition and genetic makeup can affect thrombosis risk. We conducted a study to investigate for possible associations between ecNOS gene intron 4 variable-number tandem repeat (VNTR) polymorphism and thrombosis of polytetrafluoroethylene hemodialysis arteriovenous access grafts (AVG) in Turkish patients. Fifty-five patients with end-stage renal disease who had AVGs implanted between 2000 and 2002 and 167 healthy individuals representing our healthy population were enrolled in this prospective study. Each subject provided a venous blood sample from which DNA was isolated, and polymerase chain reaction analysis was done to identify genotypes (aa, bb, ab) for ecNOS gene intron 4 VNTR polymorphism. All grafts were placed in brachioaxillary position. The subjects were divided into two groups based on duration of graft patency. The thrombosis group (Group I) comprised 26 patients who developed AVG thrombosis in the first 12 months after placement. The no thrombosis group (Group II) comprised 29 patients whose grafts remained patient for at least 12 months. The frequency of the aa genotype in Group I was significantly higher than that in Group II (p = .005). At 6, 12, and 24 months, the primary patency rates for the AVGs in patients with the aa genotype were significantly lower than the corresponding rates for the bb and ab genotype groupings (p = .01, p = .01 and p = .04 for the three respective time points; Kaplan-Meier). ecNOS gene intron 4 VNTR polymorphism is linked with the pathogenesis of vascular access thrombosis in Turkish patients undergoing hemodialysis. PMID- 17365408 TI - Orthotopic total aortic root replacement model in adult sheep. AB - Prosthetic heart valves undergo mandatory preclinical animal testing prior to human clinical trials. Historically, a non-site-specific placement of a valve prosthesis has been commonly performed; however, recently site-specific placement continues to attract interest. Various animal models have been used for preclinical evaluation of both aortic and mitral valve prostheses; however, a universally accepted animal model for orthotopic total aortic root replacement with acceptable early and late mortality for long-term evaluation has been lacking. This article reports a successful orthotopic model for placement of tissue valve conduit prosthesis for total aortic root replacement in adult sheep. This model utilized preoperative echocardiographic assessment, specific intraoperative surgical techniques, and both early and late postoperative management therapies. The combination of all of these components resulted in a successful model for orthotopic placement of a tissue valve prosthesis for total aortic root replacement in adult sheep for potential long-term assessment. PMID- 17365410 TI - Consumer-driven health care: legal and policy implications. A symposium introduction and overview. PMID- 17365411 TI - Consumer-driven health care. Questions, cautions, and an inconvenient truth. PMID- 17365412 TI - Applying the "do no harm" principle to health policy. PMID- 17365413 TI - Consumer-driven health care. Why it won't solve what ails the United States health system. PMID- 17365414 TI - Consumer-driven health care. But nobody knows the rules of the road. PMID- 17365415 TI - Patient autonomy in the age of consumer-driven health care: informed consent and informed choice. PMID- 17365416 TI - "Vanity tax". How New Jersey has opened Pandora's box by elevating its moral judgment about cosmetic surgery without consideration of fair health care policy. PMID- 17365417 TI - Protecting the right to medical treatment from the War on Terror. The status of Guantanamo Bay detainees. PMID- 17365420 TI - Electrical impedance plethysmography technique in estimating pulmonary function status. AB - An attempt has been made to study the appropriateness of electrical impedance plethysmography (EIP) in detecting pulmonary health status. A feasibility study was conducted on normal, obstructive and restrictive subjects aged between 20 and 60 years. Quantitative assessment of pulmonary function was made by way of both EIP and pulmonary function tests (PFT). Amongst the various EIP parameters, a statistically significant difference was observed for the respiratory band power, between normal (129.7) and obstructive (35.8) subjects, indicating that this EIP variable can be used to distinguish between the two pulmonary function states. A significant positive correlation was observed between a spirometry parameter, peak expiratory flow rate (PEFR), and an EIP parameter, respiratory amplitude (r = 0.372, p < 0.05), thereby indicating that EIP information by way of respiratory amplitude is comparable to that provided by PEFR. Hence, both respiratory amplitude and respiratory band power were seen to provide useful information on pulmonary health status. PMID- 17365421 TI - Novel totally implantable trans-ventricular and cross-valvular cannular pump with rolling bearings and purge system for recovery therapy. AB - In the early 1990s, Yamazaki et al. developed a partly intra-ventricular pump, which was inserted into the left ventricle via the apex and then into the aorta through the aortic valve. The pump delivered blood flow directly from the left ventricle to the aorta, like a natural heart, and needed no inflow and outflow connecting tubes; it could be weaned off after the left ventricle had been recovered. The shortcomings were that the driving DC motor remained outside of the ventricle, causing an anatomic space problem, and the sealing and bearing were not appropriate for a durable device. Recently, a totally implantable trans ventricular pump has been developed in the authors' laboratory. The device has a motor and a pump entirely contained within one cannula. The motor has a motor coil with iron core and a rotor with four-pole magnet; the pump has an impeller and an outflow guide vane. The motor part is 60 mm in length and 13 mm in diameter; the pump part is 55 mm in length and 11 mm in diameter. The total length of the device is therefore 115 mm. The total weight of the device is 53 g. The motor uses rolling bearing with eight needles on each side of the rotor magnets. A special purge system is devised for the infusion of saline mixed with heparin through bearing to the pump inlet (30 - 50 cc per hour). Thus neither mechanical wear nor thrombus formation along the bearing will occur. In haemodynamic testing, the pump can produce a flow of 4 l min-1 with 60 mmHg pressure increase, at a pump rotating speed of 12,500 rpm. At zero flow rate, corresponding to the diastolic period of the heart, the pump can maintain aortic blood pressure over 80 mmHg at the same rotating speed. This novel pump can be quickly inserted in an emergency and easily removed after recovery of natural heart. It will be useful for patients with acute left ventricular failure. PMID- 17365422 TI - A data acquisition and analysis system for the biomechanical evaluation of patient moving and transferring equipment and procedures. AB - Patients and people with various disabilities are frequently moved and transferred by nurses and carers and consequently it is important to assess the risks involved when undertaking such tasks. People with disabilities are often able to bear some of their weight and this has led to the development of non mechanical aids designed to reduce the load on the nurse or carer when undertaking a transferring manoeuvre. It is essential that aids are assessed thoroughly in order to ensure that transfers are safe and that advice and guidance can be given on the most appropriate equipment in a given situation. This paper describes a data acquisition and analysis system that has been developed to assist in such assessments. The system integrates measurements of spine movements, foot pressure and knee flexion with video recording of a transferring manoeuvre. A biomechanical model provides an estimate of the loading at the bottom of the lumbar spine for comparison with National Institute for Occupational Safety and Health (NIOSH) guidelines. A pilot assessment of non mechanical aids prior to a full user trial demonstrated that such a system can provide valuable data from which to assess risk during patient transferring manoeuvres. PMID- 17365423 TI - Micro robot prototype for colonoscopy and in vitro experiments. AB - For actively diagnosing the colon's pathologies micro-invasively or non invasively, an autonomous prototype of the earthworm-like robot for colonoscopy was designed according to the principle of bionics, and manufactured using precision process technology. In vitro experiments in pig colon were carried out. The micro robot was driven directly by an electromagnetic linear driver. The mobile cells were joined with joints of two degrees of freedom, and the whole body was flexible. The direction of movement and the angle of imaging can be controlled by the shape memory alloy (SMA). In experiments, locomotion efficient and locomotion ability was analysed carefully. Locomotion force and velocity were tested. In vitro experiments in pig colon demonstrated that the micro robot can navigate though the colon by itself reliably and freely, which will be useful for the application of the robot to colonoscopy in the clinic. PMID- 17365424 TI - Modified SPIHT wavelet compression for ECG signal. AB - This paper presents a modified version of Set Partitioning In Hierarchical Trees (SPIHT) wavelet compression method, which has been developed for ECG signal compression. Two more steps in the existing technique have been added to achieve higher compression ratio (CR) and lower percentage rms difference (PRD). The method has been tested on selected records from the MIT-BIH arrhythmia database. Even with two more steps, the method retains its simplicity, computational efficiency and self-adaptiveness, without compromising on any other performance parameter. PMID- 17365425 TI - Online fingerprint verification. AB - As organizations search for more secure authentication methods for user access, e commerce, and other security applications, biometrics is gaining increasing attention. With an increasing emphasis on the emerging automatic personal identification applications, fingerprint based identification is becoming more popular. The most widely used fingerprint representation is the minutiae based representation. The main drawback with this representation is that it does not utilize a significant component of the rich discriminatory information available in the fingerprints. Local ridge structures cannot be completely characterized by minutiae. Also, it is difficult quickly to match two fingerprint images containing different number of unregistered minutiae points. In this study filter bank based representation, which eliminates these weakness, is implemented and the overall performance of the developed system is tested. The results have shown that this system can be used effectively for secure online verification applications. PMID- 17365426 TI - A set of EEG parameters to predict clinically anaesthetized state in humans for halothane anaesthesia. AB - This article evaluates all the EEG parameters suggested in the literature that undergo changes due to anaesthetic dose, and suggests a set of EEG parameters that act as best signatures of anaesthetic state of a patient. This set of EEG parameters is validated by an artificial neural network. PRIMARY OBJECTIVE: The purpose of this study is to arrive at a set of EEG parameters that 'best' distinguish between awake and anaesthetized states of human patients for halothane anaesthesia. METHODS AND PROCEDURES: A total of 21 EEG parameters were evaluated for 40 patients. Stepwise discriminant analysis (SDA) pruned them to a set of five parameters. They were fed to a 5-3-1 artificial neural network (ANN) for classification into awake and anaesthetized state. To confirm the results, variance analysis was applied to the set of 21 parameters. Five parameters were finalized after validation by the ANN. MAIN OUTCOMES AND RESULTS: The classification accuracy of the ANN with SDA parameters was found to be 96%. With variance analysis parameters, it returned an accuracy of 100%. CONCLUSION: The set of five EEG parameters - approximate entropy, average frequency, Lempel Ziv (LZ) complexity, delta power and beta power forms the best set to distinguish between awake and anaesthetized state of human patients. Variance analysis is a better tool to converge at the optimal set than SDA. PMID- 17365427 TI - A hybrid ECG compression algorithm based on singular value decomposition and discrete wavelet transform. AB - Increasing use of computerized ECG processing systems requires effective electrocardiogram (ECG) data compression techniques which aim to enlarge storage capacity and improve data transmission over phone and internet lines. This paper presents a compression technique for ECG signals using the singular value decomposition (SVD) combined with discrete wavelet transform (DWT). The central idea is to transform the ECG signal to a rectangular matrix, compute the SVD, and then discard small singular values of the matrix. The resulting compressed matrix is wavelet transformed, thresholded and coded to increase the compression ratio. The number of singular values and the threshold level adopted are based on the percentage root mean square difference (PRD) and the compression ratio required. The technique has been tested on ECG signals obtained from MIT-BIH arrhythmia database. The results showed that data reduction with high signal fidelity can thus be achieved with average data compression ratio of 25.2:1 and average PRD of 3.14. Comparison between the obtained results and recently published results show that the proposed technique gives better performance. PMID- 17365428 TI - A re-evaluation of modelling of the current flow between electrodes: consideration of blood flow and wounds. AB - Electrical stimulation has been used for exercise, healing wounds, relieving pain, and strengthening muscle. The assumption is that current will flow predictably between electrodes and, therefore, there will be predictability in the clinical response to electrical stimulation. This may not be the case. The present investigation shows that considerable channelling of current occurs when the skin is heated or when there is a wound between the electrodes. By studying current movement in nutrient agar (a homogenous medium), blood agar and layered blood and nutrient agar to simulate areas of increased blood flow, it was found that areas of high or low resistance, especially in the surface layer, caused significant current movement toward (low resistance area) or away (high resistance area) from those areas. When a resister model was used to measure dispersion characteristics of current in a three-dimensional array, it was shown that if even a single resister value was lowered by 20% in the upper layer, current sinking occurred in all three layers of the array. The results seem to imply that where the tissue is non homogeneous due to injury or inflammation, electrode design or current delivery systems need to be modified appropriately to have the intended effect of the electrical stimulation. PMID- 17365432 TI - Novel diamond-coated tools for dental drilling applications. AB - The application of diamond coatings on cemented tungsten carbide (WC-Co) tools has been the subject of much attention in recent years in order to improve cutting performance and tool life in orthodontic applications. WC-Co tools containing 6% Co metal and 94% WC substrate with an average grain size of 1 - 3 microm were used in this study. In order to improve the adhesion between diamond and WC substrates it is necessary to etch cobalt from the surface and prepare it for subsequent diamond growth. Alternatively, a titanium nitride (TiN) interlayer can be used prior to diamond deposition. Hot filament chemical vapour deposition (HFCVD) with a modified vertical filament arrangement has been employed for the deposition of diamond films to TiN and etched WC substrates. Diamond film quality and purity has been characterized using scanning electron microscopy (SEM) and micro Raman spectroscopy. The performances of diamond-coated WC-Co tools, uncoated WC-Co tools, and diamond embedded (sintered) tools have been compared by drilling a series of holes into various materials such as human tooth, borosilicate glass, and acrylic tooth materials. Flank wear has been used to assess the wear rates of the tools when machining biomedical materials such as those described above. It is shown that using an interlayer such as TiN prior to diamond deposition provides the best surface preparation for producing dental tools. PMID- 17365433 TI - Beat to beat analysis of mechanical heart valves by means of return map. AB - Three mechanical heart valves (two bileaflet prostheses and a tilting one) were investigated in a basic hardware setup in order to evaluate with a hydrophone their opening and closing action in time and in amplitude of each beat. The recorded signal was then segmented into the series of cycles xi(t) having a temporal duration equal to the working period imposed on the valve. Two return maps were defined, in order to evaluate the degree of dispersion of the resulting scatter plot: (i) the amplitude map xi(t) versus xi+1(t); (ii) the delay map for the closure of the valve within each beat versus the successive ones. To evaluate the results obtained, two indices were proposed based on both the degree of dispersion and the deviation of the regression line of the resulting scatter plot with respect to the bisector of the map plane. The tilting disc valve showed a lower degree of dispersion, both in the amplitude signal and in the closure time delays, with respect to the other two bileaflet heart valves. The methodology proposed here could be regarded as an alternative non-invasive tool to investigate the dynamic behaviour of prosthetic heart valves, especially in the case of their suspected failure. PMID- 17365434 TI - Detection of previously unrecognized daytime desaturation in children with chronic lung disease. AB - PRIMARY OBJECTIVE: The prime rationale of this research is to investigate the possible occurrence of previously unrecognized episodes of desaturation apparent in preterm infants with chronic lung disease as they freely move around a non artificial environment. RESEARCH DESIGN: The study comprises 58 hours of telemetric recordings of SpO2, heart rate, body movement and temperature, along with full ECG and photoplethysmographic waveforms for eight preterm subjects in their home environment. MAIN OUTCOME/RESULTS: The data is analysed for remarkable events, more particularly periods of spontaneous desaturation. Statistical results for all case studies are collated into a table along with examples of graphical analysis. CONCLUSIONS: This study has shown that some patients are prone to episodes of hypoxemia during the course of normal daily activity or daytime sleep that would usually go unrecognized and that more effective management of supplemental oxygen treatment may be possible with continual unobtrusive monitoring. PMID- 17365435 TI - DWT-DCT hybrid scheme for medical image compression. AB - With the development of communication technology the applications and services of health telemetics are growing. In view of the increasingly important role played by digital medical imaging in modern health care, it is necessary for large amount of image data to be economically stored and/or transmitted. There is a need for the development of image compression systems that combine high compression ratio with preservation of critical information. During the past decade wavelets have been a significant development in the field of image compression. In this paper, a hybrid scheme using both discrete wavelet transform (DWT) and discrete cosine transform (DCT) for medical image compression is presented. DCT is applied to the DWT details, which generally have zero mean and small variance, thereby achieving better compression than obtained from either technique alone. The results of the hybrid scheme are compared with JPEG and set partitioning in hierarchical trees (SPIHT) coder and it is found that the performance of the proposed scheme is better. PMID- 17365436 TI - Non-invasive method to detect and locate haemorrhagic focus of GI tract. AB - Traditional diagnostic methods do not work well for gastrointestinal bleeding, and location of the haemorrhagic focus is even more difficult. Here a novel method with a microelectronic system is presented effectively to detect and locate the haemorrhagic focus. The outstanding advantage of this method is that it is non-invasive. The composition and working principles of the system are described in detail. Key to this system is the development of a haemoglobin (Hb) sensor. Through MEMS technology a micro haemoglobin sensor is developed and fabricated. The sensor's response performance, pH dependence and temperature dependence are tested experimentally. Initial tests suggest that the device is sufficiently sensitive to Hb concentration and insensitive to pH and temperature changes in the working range. As a result, the system has potential for development of an advanced instrument for detecting, localizing and treating gastrointestinal bleeding. PMID- 17365437 TI - Optimization of block size for DCT-based medical image compression. AB - In view of the increasing importance of medical imaging in healthcare and the large amount of image data to be transmitted/stored, the need for development of an efficient medical image compression method, which would preserve the critical diagnostic information at higher compression, is growing. Discrete cosine transform (DCT) is a popular transform used in many practical image/video compression systems because of its high compression performance and good computational efficiency. As the computational burden of full frame DCT would be heavy, the image is usually divided into non-overlapping sub-images, or blocks, for processing. This paper aims to identify the optimum size of the block, in reference to compression of CT, ultrasound and X-ray images. Three conflicting requirements are considered, namely processing time, compression ratio and the quality of the reconstructed image. The quantitative comparison of various block sizes has been carried out on the basis of benefit-to-cost ratio (BCR) and reconstruction quality score (RQS). Experimental results are presented that verify the optimality of the 16 x 16 block size. PMID- 17365438 TI - Strategies to identify changes in SEMG due to muscle fatigue during cycling. AB - Detection, quantification and analysis of muscle fatigue are crucial in occupational/rehabilitation and sporting settings. Sports organizations such as the Australian Institute of Sports (AIS) currently monitor fatigue by a battery of tests including invasive techniques that require taking blood samples and/or muscle biopsies, the latter of which is highly invasive, painful, time consuming and expensive. SEMG is non-invasive monitoring of muscle activation and is an indication of localized muscle fatigue based on the observed shift of the power spectral density of the SEMG. But the success of SEMG based techniques is currently limited to isometric contraction and is not acceptable to the human movement community. This paper proposes and tests the use of spectral analysis of narrow windows of SEMG near the peak of a cyclic activity to identify the onset of muscle fatigue during cyclic activities. The results demonstrate a highly significant relationship of reduction of the median frequency with the onset of muscle fatigue. The paper also reports the validation of the SEMG study using biochemical analysis of muscle biopsy and blood tests and further verified using power output of the cycle and speed of pedalling. PMID- 17365439 TI - Performance of glucose dehydrogenase (GDH) based and glucose oxidase (GOX) based blood glucose meter systems at moderately high altitude. AB - OBJECTIVE: Self-monitoring of blood glucose (SMBG) is a fairly efficient method of preventing hypoglycaemia in diabetic patients. Blood glucose meters (BGMs) are influenced by factors such as altitude, temperature, blood oxygen concentration, low atmospheric pressure or humidity. In this study we aimed at evaluating the performance of glucose dehydrogenase (GDH) or glucose oxidase (GOX) based glucometers at moderately high altitude. METHOD: A total of 286 female or male patients, most of whom had type 2 diabetes, were included in this study. The simultaneous readings made by two different glucometers were compared with the readings made at the reference laboratory. RESULTS: Blood glucose levels measured by a GDH based glucometer at moderately high altitude were significantly (p=0.007) higher compared to those measured at the reference laboratory. Although blood glucose levels measured by a GOX based glucometer were lower compared to those measured at the reference laboratory, the difference was not significant (p=0.54). The difference between GOX and GDH readings with regard to blood glucose levels was also significant (p=0.001). Blood glucometers were influenced by moderately high altitude. CONCLUSION: The use of a GOX based glucometer at moderately high altitude may be useful in detecting hypoglycaemia at these conditions, since significantly higher blood glucose levels were measured with a GDH based glucometer compared to reference readings. PMID- 17365442 TI - Towards a professional ethics model of clinical ethics. PMID- 17365443 TI - Health versus harm: euthanasia and physicians' duties. AB - This essay rebuts Gary Seay's efforts to show that committing euthanasia need not conflict with a physician's professional duties. First, I try to show how his misunderstanding of the correlativity of rights and duties and his discussion of the foundation of moral rights undermine his case. Second, I show aspects of physicians' professional duties that clash with euthanasia, and that attempts to avoid this clash lead to absurdities. For professional duties are best understood as deriving from professional virtues and the commitments and purposes with which the professional as such ought to act, and there is no plausible way in which her death can be seen as advancing the patient's medical welfare. Third, I argue against Prof. Seay's assumption that apparent conflicts among professional duties must be resolved through "balancing" and argue that, while the physician's duty to extend life is continuous with her duty to protect health, any duty to relieve pain is subordinate to these. Finally, I show that what is morally determinative here, as throughout the moral life, is the agent's intention and that Prof. Seay's implicitly preferred consequentialism threatens not only to distort moral thinking but would altogether undermine the medical (and any other) profession and its internal ethics. PMID- 17365444 TI - Whoever could get rid of the context of discovery/context of justification dichotomy? A proposal based on recent developments in clinical research. AB - In his Art and Illusion, art historian Ernst Gombrich argues that the emergence and development of styles of pictorial representation depend on the availability of certain schemata, which can be documented. He himself documents the schemata responsible for the emergence and development of several styles. Nothing of this kind has been done as far as the growth of scientific knowledge is concerned. In this article we discuss whether is it possible to document something analogous to Gombrich's schemata that can be of crucial relevance for the development of clinical research. PMID- 17365445 TI - Should a good healthcare professional be (at least a little) callous? AB - The term "callous" has not, to this point, been studied empirically or considered philosophically in the context of healthcare professionalism. It should be, however, because its uses seem peculiar. Sometimes "callous" is used to suggest that becoming callous confers a benefit of some protection against emotional distress, which might be considered expedient in the healthcare work environment. But, "callous" also refers to a person's unappealing demeanor of hardened insensitivity. The tension between these different moral connotations of "callous" prompts several empirical, psychological, and moral questions; I introduce and entertain a few here. I also suggest a distinction between callousness and inurement and argue for why this distinction is important to appreciate and uphold in health professions education. PMID- 17365446 TI - Constructing a systematic review for argument-based clinical ethics literature: the example of concealed medications. AB - The clinical ethics literature is striking for the absence of an important genre of scholarship that is common to the literature of clinical medicine: systematic reviews. As a consequence, the field of clinical ethics lacks the internal, corrective effect of review articles that are designed to reduce potential bias. This article inaugurates a new section of the annual "Clinical Ethics" issue of the Journal of Medicine and Philosophy on systematic reviews. Using recently articulated standards for argument-based normative ethics, we provide a systematic review of the literature on concealed medication for the management of psychiatric disorders. Four steps are completed: identify a focused question; conduct a literature search using key terms relevant to the focused question; assess the adequacy of the argument-based methods of the papers identified; and identify conclusions drawn in each paper and whether they apply to the focused question. We identified seven papers and provide an assessment of them. While none of the papers fully meet the standards of argument-based ethics, they did provide rationales for the use of concealed medications, with the important requirement such a practice be accountable in explicit organizational policy to prevent abuse of patients with mental illness or dementia. PMID- 17365447 TI - Peripartum cardiomyopathy: time for another look? PMID- 17365448 TI - An ethically justified, clinically comprehensive approach to peri-viability: gynaecological, obstetric, perinatal and neonatal dimensions. AB - Peri-viability, 22-26 completed weeks' gestational age, has generated ongoing clinical ethical controversies concerning the roles of abortion, caesarean delivery for fetal indication, neonatal resuscitation and limits on life sustaining treatment of neonates. This paper provides a comprehensive, ethically justified approach to the clinical management of peri-viable fetuses and infants. We reviewed available data about the outcomes of peri-viable fetuses and developed an outcomes-based ethical framework that appeals to the ethical principles of beneficence, autonomy and justice. We identified beneficence-based, autonomy-based and justice-based considerations that should guide clinical judgement, the informed consent process, and decisions about termination of pregnancy, caesarean delivery and setting justified limits on life-sustaining treatment of neonatal patients. Ethics is an essential component of perinatal medicine because it provides physicians with an evidence-based, ethically justified, comprehensive approach to the gynaecological, obstetric, perinatal and neonatal dimensions of peri-viability. PMID- 17365449 TI - Use of chaperones by obstetricians and gynaecologists: a cross-sectional survey. AB - The Royal College of Obstetrics and Gynaecologists (RCOG) recommends that a chaperone should be offered to every patient for an intimate examination. The use of chaperones has risen in primary care, but little is known about the practice of obstetricians and gynaecologists. Our aim was to determine the current attitudes and practices of Fellows and Members of the RCOG regarding chaperones during intimate examinations, both in public and private practice. A total of 800 Fellows and Members were asked to complete a 45-item questionnaire on their use of chaperones and how important a range of issues were in deciding whether or not to offer and provide a chaperone. A total of 449 questionnaires were returned. In summary, 23% of respondents never or occasionally offered a chaperone; 24% of NHS units have no agreed NHS policy and a further 16% did not know if a policy existed. In NHS practice, 77% used a chaperone with only 62% of women using a chaperone. Of those who did private practice, 34% never or occasionally offered a chaperone with 31% actually using a chaperone. In conclusion, obstetricians and gynaecologists use chaperones more than general practitioners but there is significant room for improvement. Chaperones are used more in NHS than private practice. PMID- 17365450 TI - Maternal intra-partum fever. AB - Maternal intra-partum fever commonly complicates the process of labour. Its occurrence is often regarded as being synonymous with the presence of chorioamnionitis. This inevitably results in the administration of antibiotics to the affected mother. Review of the literature however suggests that this approach is not always appropriate. Non-infective causes of this condition that are often overlooked include the use of epidural analgesia for pain relief, normal thermal physiological changes in women not using any form of analgesia and delivery in an overheated room. Women with certain risk factors such as nulliparity and a long latent phase of labour are also more prone to developing maternal intra-partum fever. Irrespective of its aetiology, maternal intra-partum fever carries risks both for the mother and her unborn child. Putting more thought into the care of these patients will go a long way in reducing the maternal and neonatal morbidity associated with this complication. PMID- 17365451 TI - Premature ovarian failure. AB - Premature ovarian failure (POF) is gonadal failure before the age of 40 years. Several rare causes have been discovered yet we still fail to identify the cause in many cases. Although it was once thought to be a permanent condition, a substantial number of patients experience spontaneous remissions and even pregnancy. HRT remains the cornerstone of treatment and the only proven method of achieving pregnancy in these patients is by ovum donation. New alternatives to HRT and fertility preservation are under development. Basic understanding of ovarian physiology and pathogenesis of POF is necessary for the development of newer therapies. PMID- 17365452 TI - Chemotherapy-induced female infertility and protective action of gonadotropin releasing hormone analogues. AB - This review aimed to critically discuss the current protocols using gonadotropin releasing hormone analogue (GnRHa) for the management of chemotherapy-induced premature ovarian failure. In in-vitro experiments, GnRHa retards doxorubicin induced granulosa cell damage, suggesting an additional GnRH's activity to protect the gonads during chemotherapy through GnRH receptor-mediated mechanism(s). GnRHa acts to protect the gonads during radiation and/or chemotherapy by preferentially steering cells into cell cycle arrest with a decline in response to the chemotherapeutic agents. The ovarian protection by GnRHa co-treatment against chemotherapy can enable the preservation of future fertility in survivors and prevent the bone demineralisation and osteoporosis associated with hypooestrogenism and ovarian failure. PMID- 17365453 TI - Maternal mortality due to eclamptic and non-eclamptic hypertensive disorders: a challenge. AB - Eclamptic and non-eclamptic hypertensive disorders are responsible for high maternal and perinatal mortality, especially in developing countries. The present study was done in order to understand the trends of maternal deaths due to non eclamptic and eclamptic hypertensive disorders by analysis of case records of women who died due to these disorders over a period of 20 years. Overall, hypertensive disorders contributed to 31% of maternal deaths, 24.7% due to eclampsia with a decreasing trend from 43% in block A to 8.8% in block E. Case fatality rate (CFR) among eclampsia decreased from 23.3% in block A to 5.7% in block E; 32.7% among ante-partum and 9.9% postpartum and 23.9% in term and 8.9% in pre-term cases. Although the contribution of hypertensive disorders to maternal mortality has reduced significantly (from 43% in block A to 29% in block E), deaths due to non-eclamptic hypertensive disorders have increased from 3% in block C to 23% in block E. Over the years, the contribution of patients<20 years of age has decreased from 8% to 2%, 32% of women who died due to eclampsia were below the age of 20 years. The most common cause of mortality in cases of pre eclampsia was haemolysis, elevated liver enzymes, and low platelet count (HELLP) or partial HELLP syndrome (83.33%) and in eclampsia, pulmonary oedema. Even with resource constraints, mortality due to eclampsia can be reduced with appropriate and timely therapy. Evidence-based critical care is essential as even seemingly milder forms of pregnancy induced hypertension can lead to mortality. PMID- 17365454 TI - Myasthenia gravis and pregnancy. AB - Myasthenia gravis (MG) is a chronic autoimmune disorder of neuromuscular transmission characterized by varying degrees of weakness and easy fatigability of the skeletal muscles. Precipitants of myasthenic symptoms or crises include physical and emotional stress, systemic illness, infections, hypo or hyperthyroidism, pregnancy, any type of surgery with general anaesthesia as well as corticosteroids. The authors report two cases of MG in pregnancy and discuss briefly the various aspects of the disease course and management in pregnancy. As MG occurs predominantly in women of reproductive years, it is important that obstetricians are aware of this condition and its management in pregnancy. PMID- 17365455 TI - Antenatal corticosteroid prescribing: a complete audit cycle. AB - We undertook an audit of the practice of antenatal steroid prescribing. Data were collected over a prospective 12-week period in an initial audit (2002). Deviations from compliance with guidelines published by the Royal College of Obstetricians and Gynaecologists were identified and a report highlighting the audit findings was disseminated to all maternity units in Glasgow. A repeat audit (2004) was performed over a further prospective 12-week period. A total of 111 women in the initial and 188 women in the repeat audits received corticosteroids. Steroid courses per eventual delivery between 24-36 weeks' gestation increased from 0.64 to 1.18. Repeat courses of steroid decreased from 5% to <1%. Potentially effective courses of steroid increased from 24% to 35%. The proportion of potentially effective steroid courses varied according to the indication. Few steroid courses were potentially effective where the indication was pre-term labour. The findings of this audit are generally encouraging but continuing education regarding the appropriate prescription of antenatal corticosteroids is necessary to maintain and possibly improve upon the findings of this audit. PMID- 17365456 TI - Pre-term premature rupture of fetal membranes: the dilemma of management in a developing nation. AB - This study aims at evaluating the outcome of pregnancies complicated by pre-term premature rupture of membrane (PPROM) in a developing country and to highlight the problems of managing such cases and ways of improving future management. This was a retrospective review of 344 patients with PPROM at a University of Nigeria Teaching Hospital Enugu, Nigeria over a 10-year period (January 1994-December 2003). The prevalence of PPROM in this study was 25 per 1,000 births and patients of low parity (para 0-2) accounted for the highest number (56.4%). Previous abortion was significantly more among these women of low parity and may be a factor in the aetiology of PPROM. The gestational age range 28-30 weeks recorded the highest incidence (29.7%) of PPROM. The most common associated aetiological factor was cervical incompetence (11.6%), while chorioamnionitis, a major complication in the patients showed a statistically significant reduction with early antibiotic administration (p<0.05). About 72% (n=248) of the patients arrived at the hospital within 24 h of membrane rupture. Perinatal mortality was high (520 per 1,000 births) due to prematurity and perinatal infections. Better fetal outcomes were recorded among patients with PPROM at gestational age above 30 weeks, fetal weight above 2 kg, normal delivery, absence of maternal infection and latent period of not more than 5 days (p<0.05). The parity of the women did not significantly affect fetal outcome (p>0.05). Two (0.6%) maternal deaths were recorded. Prompt patient referral, early institution of antibiotics and improvement of neonatal facilities in tertiary health institutions in developing countries is advocated as a way of improving fetal survival in PPROM. PMID- 17365457 TI - Obstetric outcome in women complaining of reduced fetal movements. AB - Reduction of fetal movements causes concern and anxiety and is a common indication for the assessment of fetal well-being. The aim of this study was to review the outcome of women who presented primarily with reduced fetal movements and to compare with women of similar age and gestation who did not present with reduced fetal movements (controls). Some 19% of intrauterine growth restricted babies were found in the study group, compared with none in the control group. In the study group, 32% of women needed intervention solely due to fetal compromise compared with 21% in the control group. There was no perinatal or neonatal death in either group. We suggest that these women should be carefully investigated and monitored to improve the obstetric outcome. PMID- 17365458 TI - Peripartum hysterectomy for primary postpartum haemorrhage: incidence and maternal morbidity. AB - This was a retrospective analysis of postpartum emergency hysterectomy performed between 1988-2003, to study incidence indicators, risk factors and complications. We included any women who required emergency hysterectomy to control major postpartum haemorrhage (PPH) after delivery, following a pregnancy of at least 24 weeks' gestation, regardless of the mode of delivery. We excluded cases that required a hysterectomy for gynaecological reasons. There were 18 cases of emergency hysterectomy (14 caesarean hysterectomy and four postpartum hysterectomy, after vaginal delivery), giving a rate of 0.36/1,000 deliveries. Overall, the most common indication for hysterectomy was placenta accreta (28%) and uterine atony (28%). Although there was no maternal death, intra- and postoperative complications were prevalent including cardiac arrest (1), disseminated intravascular coagulopathy (4), pulmonary oedema (1), septicaemia (1), and bladder injury (1). Placenta accreta is becoming a leading cause of emergency postpartum hysterectomy. Although hysterectomy is a life saving operation, it is associated with high maternal morbidity. PMID- 17365459 TI - Compliance with the RCOG's guidelines on medical record keeping in female sterilisation: a complete audit cycle. AB - Female sterilisation is a major cause of litigation, accounting for 25% of all claims notified to the Medical Defence Union, suggesting that the practice surrounding female sterilisation is less than perfect. Inadequate documentation has been identified as the major cause for complaints and litigation. RCOG published guidelines have emphasised the need for adequate documentation during preoperative counselling. This retrospective audit was carried out with the primary objective to determine whether RCOG's guidelines had been adhered to. Failure to comply with the RCOG guidelines in our study highlights the fact that awareness of published guidelines may not be enough to improve the quality of documentation. This evidence would strongly support the use of a standardised proforma that would improve the quality of documentation during preoperative counselling. PMID- 17365460 TI - Sterilisation counselling: a role for the gynaecology nurse-practitioner. AB - A recent publication of an evidence-based clinical guideline for male and female sterilisation by the Royal College of Obstetrics and Gynaecology (RCOG) created a stimulus for a review of our female sterilisation service. We arranged for a gynaecology nurse-practitioner (A.O.) with extensive experience in general gynaecology and contraception to undergo additional training in counselling female sterilisation. She then took over the daily running of the sterilisation clinic using a care pathway and pre-printed letters. She had open access to a consultant (R.F.) for advice. A review of 100 consecutive referrals showed that the nurse followed the guidelines extremely closely both in terms of referral to the medical team for advice and/or further counselling and quality of documentation. A total of 59% of the women attending the clinic were cared for by the nurse-practitioner alone. Only four had to see a consultant. All women questioned expressed very positive comments about the style and content of counselling and just one stated she preferred to see a doctor. PMID- 17365461 TI - Assisted hatching is more effective when embryo quality was optimal in previous failed IVF/ICSI cycles. AB - Assisted hatching (AH) was developed as a possible solution to repeated implantation failure. The aim of this analysis was to examine the relationship between the morphology of embryos in a previous cycle on outcome in a subsequent cycle with AH. A total of 175 AH cycles performed after previous failed ART without hatching were divided into group A with optimal and group B with suboptimal embryos transferred previously. The groups were similar in terms of demographic and cycle characteristics. In group A, there was a significant improvement (p<0.001) in implantation (28.8 vs 5.1%), clinical pregnancy (41.9 vs 12.1%) and live birth rate (38.5 vs 8.6%) compared with group B. The data suggest that the prognosis for treatment is better if AH is performed after failure despite optimal embryos compared with failure associated with suboptimal embryos and embryo quality is the most significant factor affecting outcome. PMID- 17365462 TI - Intrauterine insemination with controlled ovarian stimulation for treatment of infertility: an audit of a new IUI programme in a low resource setting. AB - This study is an audit of a new intrauterine insemination (IUI) programme in a low resource private fertility practice in southeast Nigeria. IUI was performed using a Wallace flexible catheter 1 day before or on the day of ovulation after ovarian stimulation with clomiphene citrate. The 18 couples treated had either male (16) or unexplained (2) infertility. The women were between 25 and 49 years and 13 (72.2%) of the couples had primary infertility while the duration of infertility ranged from 3 to 15 years. All the women had tubal patency confirmed by laparoscopy and dye test before undergoing IUI. The pregnancy rates per couple and per insemination cycle and the effect of maternal age and source of semen (partner or donor) were determined. The 18 couples had a total of 48 treatment cycles and five became pregnant (confirmed by early ultrasound scan) giving a pregnancy rate of 27.8% per couple or 10.4% per treatment cycle. The pregnancy rate was 41.7% per couple, 15.6% per treatment cycle for the donor group and 0% for the partner group (p<0.01). Poor sperm quality was responsible for the poor pregnancy outcome in the partner group. The pregnancy rate per couple was 36.5% in women<35 years compared with 14.3% in those>or=35 years (p=0.02). Similarly, the cycle pregnancy rate was significantly higher in women<35 years (16.0% vs 4.4%; p<0.02). There was one (20%) case of twin pregnancy and no miscarriage. Four of the women had a live birth (80%) at term and one had an intrauterine death following severe pre-eclampsia at 29 weeks' gestation. In conclusion, the overall couple and cycle pregnancy rates at our centre is comparable with the rates in many centres. Younger age and good quality semen are good indicators of a successful outcome. Infertile couples should therefore be evaluated early and recommended for this treatment option before advanced female age. PMID- 17365463 TI - Preoperative assessment of deep myometrial and cervical invasion in endometrial carcinoma: comparison of magnetic resonance imaging and histopathologic evaluation. AB - This study aimed to evaluate the accuracy of magnetic resonance imaging (MRI) in the detection of deep myometrial invasion and cervical extension by endometrial carcinoma. This prospective study included 101 patients with histologically documented endometrial carcinoma, between July 1998 and April 2004. The findings of preoperative pelvic MRI were compared with histological diagnosis. From 101 cases studied by pelvic MRI, 43 were classified as deep myometrial invasion (>or=50% of myometrium), where the pathological evaluation confirmed as having deep myometrial invasion. Cervical extension in the MRI study was found in 19 cases. Pathologic study found cervical extension and/or invasion in 31 cases including all cases identified by MRI. The accuracy, sensitivity and specificity of MRI were 95%, 89%, 100%, detecting deep myometrial invasion and 88%, 61%, 100%, detecting cervical invasion, respectively. The high accuracy achieved makes MRI an adequate method for determine the depth of myometrial and cervical invasion in endometrial carcinoma. PMID- 17365464 TI - Histological grading of epithelial ovarian carcinomas. AB - The grade of an ovarian epithelial neoplasm provides useful information. However, different approaches to grading exist and many ovarian cancers are not graded. We examined primary ovarian cancers from patients treated at our hospital and applied the 'universal' grading system. We found a significant association between grade and clinical stage, with a survival difference between grades for low-stage tumours. The application of grade is discussed in the light of developments in the grading of other gynaecological cancers. PMID- 17365465 TI - Factors associated with domestic violence in south-east Nigeria. AB - A cross-sectional survey was carried out at two tertiary health institutions in south-east Nigeria from 1 January 2005 to 31 March 2005 to determine the factors associated with domestic violence (DV). The study group comprised of 600 consecutive men seen at the General Outpatient department of the two hospitals during the study period. More than two-thirds (70%) of respondents reported abuse in their family, with 92% (n=385) of the victims being female partners and the remaining 8% (n=35) male. DV was significantly associated with lower social class, alcohol consumption, increasing age disparity between couples and spouse unemployment (p<0.05). The male victims of DV are associated with financial disparity in favour of the female, influential in-laws, educated women and couples within the same age group. The most common form of abuse was shouting at partner (93%), slapping or pushing (77%) and punching or kicking (46%). A total of 348 (83%) respondents reported physical abuse. Only one-fifth (21%) of the abuse occurred during pregnancy and financial constraints was the major reason. There was gross under-reporting (8.1%) of DV because of cultural factors, embarrassment and the repercussions that follow such reports. PMID- 17365466 TI - Atypical presentation of cardiomyopathy in pregnancy. PMID- 17365467 TI - Subarachnoid haemorrhage in pregnancy. PMID- 17365468 TI - Severe tinnitus in pregnancy, necessitating caesarean delivery. PMID- 17365469 TI - Use of erythropoietin in a pregnant Jehovah's Witness with sickle-cell disease. PMID- 17365470 TI - Pregnancy complicated by a large intracranial arachnoid cyst: multidisciplinary approach to safe delivery. PMID- 17365471 TI - Intra-partum transvaginal cranial decompression of intracranial teratoma. PMID- 17365472 TI - An acute presentation of coeliac disease in the puerperium. PMID- 17365473 TI - An unusual case of tear in the pouch of Douglas following spontaneous vaginal delivery in a previously scarred uterus. PMID- 17365474 TI - Ureteric stricture following vaginal hysterectomy and caused by endometriosis. PMID- 17365475 TI - Goserelin administration causing an acute abdomen in a patient with a fibroid uterus. PMID- 17365476 TI - Leiomyoma appearing in the vaginal vault following hysterectomy. PMID- 17365477 TI - Delayed presentation of small bowel trauma during insertion of tension free vaginal tape (TVT) sling. PMID- 17365478 TI - Pelvic schwannoma: a retroperitoneal tumour mimicking uterine leiomyoma. PMID- 17365479 TI - Mesh erosion and prolapse recurrence following repeat anterior repair with Prolene mesh. PMID- 17365480 TI - Increased serum carcinomic antigen 19-9(CA 19-9) in a dermoid cyst. PMID- 17365481 TI - Struma ovarii with pseudo-Meigs' syndrome and elevated CA125 levels. PMID- 17365482 TI - Bartholin's gland carcinoma from Crohn's disease. PMID- 17365483 TI - Preoperative diagnosis of early fallopian tube carcinoma. PMID- 17365484 TI - Ovarian leiomyosarcoma with co-existing fibroid. PMID- 17365486 TI - How competent are obstetrics and gynaecology trainees in managing maternal cardiac arrests? Another view on training issues from the South Thames. PMID- 17365492 TI - Occupational noise levels during emergency relief operations in the aftermath of Hurricane Katrina. PMID- 17365494 TI - Correction of sampler-to-sampler comparisons based on aerosol size distribution. AB - This article explains a simple method for correcting a sampler-to-sampler ratio for changes in size distribution by computing a bias factor that relates the measured ratio with a ratio determined from equations that describe the collection efficiency curves of the samplers while taking size distribution into account. Laboratory trials were conducted to determine whether the resulting bias factor is independent of aerosol size distribution. During these studies, a 3 piece cassette and respirable cyclone were compared with an inhalable sampler in both a still-air chamber and a moving-air chamber operated at 0.2 m/sec and 1.0 m/sec. An ISO test dust of various size fractions was generated to produce an aerosol with mass median aerodynamic diameter ranging from 1.4 microm to 10.1 microm. An organic dust consisting of ground grain material was also applied to the still-air chamber to demonstrate differences between dust types. Results showed that the bias value was significantly different between dust types for both the cyclone/ inhalable (p=0.001) and cassette/inhalable (p=0.033) comparisons but was not different between wind conditions for either comparison. All but one comparison had insignificant slopes when comparing the bias value with median diameter, indicating that the bias value could be used to correct for size distributions in most conditions. However, bias values determined when comparing the cyclone with the inhalable sampler in the still-air condition produced a positive slope for median diameters less than 4 microm (p=0.008). Further research is needed to determine why the actual cyclone/inhalable ratio decreases relative to the expected ratio as the proportion of respirable particles increases. These results suggest that, for most conditions, the size distribution compensation can be applied to sampler-to-sampler correlations provided that the original comparison was performed with the same dust type. PMID- 17365495 TI - Indoor air quality in restaurants with and without designated smoking rooms. AB - Indoor air quality in restaurants was studied in two cities in northwest Ohio after clean indoor air ordinances had been enacted. Carbon dioxide and ultrafine particles were measured in two restaurants in Toledo and two restaurants in Bowling Green. One restaurant in each city was smoke free, and one restaurant in each city contained a dedicated smoking room. A smoke free office space was also assessed as a reference site. Measurements were collected with datalogging instrumentation simultaneously in both the designated smoking room, if present, and in the nonsmoking section. For smoke free establishments, datalogging instrumentation was also used. Carbon dioxide levels were elevated in all four restaurants, with only 32% of the measurements meeting the American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) criterion level of 1000 ppm. Ultrafine particles currently do not have any formal standard or guideline. Statistically significant differences were evident between all four restaurants and the reference site. The largest differences were found between the two designated smoking rooms and the reference site (p < 0.001), with the mean levels in the smoking rooms up to 43 times higher than in the reference site. The results from this study indicate inadequate fresh air supply in all four restaurants, particularly in the designated smoking rooms, and the possibility that the designated smoking rooms were not containing the environment tobacco smoke, based on the ultrafine particle concentrations measured in the nonsmoking areas of the smoking restaurants. PMID- 17365496 TI - A comparison study using a mathematical model and actual exposure monitoring for estimating solvent exposures during the disassembly of metal parts. AB - The objective of this research was to compare the airborne solvent concentrations measured during the disassembly of solvent-coated metal parts with concentrations predicted by a mathematical model. The study involved three test simulations where cyclohexane, used as a penetrating solvent, was squirted onto a gate valve while the valve was subsequently disassembled. Three test simulations were performed to evaluate the effect of varying the speed of random air movement in the work area. For statistical considerations, six replicate solvent application trials were conducted for each simulation. Area and personal air samples were collected during the trials performed under each test simulation. Cyclohexane was applied to the valve at a consistent rate to obtain, to the greatest extent possible, a constant generation rate of solvent vapors. The Near Field-Far Field (NF-FF) model, applied using a constant solvent generation rate, was selected to predict the solvent vapor concentrations, and Monte Carlo analysis was used to quantify uncertainty in the input parameters of the model. Solvent concentration predictions obtained from the modeling process were within a multiplicative factor of 0.1 to 1.5 of the arithmetic mean of the actual air sample results for all three NF and FF conditions in each simulation. Application of the NF-FF model under the conditions described suggests there is a reasonable degree of reliability in forecasting airborne contaminant levels in the workplace environment. Given the limited resources faced today by many industrial hygienists, exposure modeling can serve as a valuable tool for generating the information needed to make informed decisions about employee exposure. PMID- 17365497 TI - Continuous versus episodic hydration in encapsulating protective coveralls. AB - Work in warm environments while wearing respiratory protective masks can result in progressive dehydration. The purpose of this study was to evaluate the use of a portable hands-free, through-the-gas mask hydration system on workers in encapsulating protective coveralls (EPC) in the heat. Ten participants performed four trials of simulated "moderate" intensity industrial work (300 Kcal/min) at a wet bulb glove temperature WBGT of 23 degrees C while wearing impermeable (two trials) and semipermeable (two trials) EPC. Participants performed the trials under two conditions: (1) drinking ad libitum from a portable hands-free system (PHFS) using a through-the-gas mask drinking device, and (2) using typical rest only, wherein participants worked until a termination criterion was met, then were removed from the work environment and permitted to drink as much as they desired. When using the PHFS, for the impermeable EPC trial, participants drank 242% of what they drank during the drinking-during-rest trial. Total work times were unchanged between trials for either condition, but there was a trend for walk time to be longer in PHFS for semipermeable EPC. Dehydration with PHFS was only 21% (dehydration was 4.7 times greater without the PHFS) in impermeable EPC and in semipermeable EPC only 41% of that without hydration available (dehydration was 2.5 times greater without the PHFS). Under these conditions, hypohydration was effectively mitigated using the portable system. PMID- 17365498 TI - Relationships between inhalable, thoracic, and respirable aerosols of metalworking fluids. AB - The aim of the study described in this companion paper was to assesses relationships among inhalable, thoracic, and respirable aerosol fractions of metalworking fluids. A RespiCon sampler, which simultaneously collects all three fractions, was used at four Ontario plants to collect 37 samples of 120 to 400 min duration. The ratios of the slopes of the lines of a regression model forced through the origin between inhalable and thoracic, inhalable and respirable, and thoracic and respirable were 1.38, 1.51, and 1.13, respectively. These ratios would be useful in assessing metalworking fluid airborne exposure data based on different aerosol fractions and for interpreting occupational exposure standards based on different fractions. PMID- 17365499 TI - Control of methyl methacrylate during the preparation of orthopedic bone cements. AB - The use of methyl methacrylate (MMA) bone cement during orthopedic procedures has been seen as a potential exposure hazard to health care professionals. However, that assessment is based on a number of investigations with problems in experimental design, analysis, and data interpretation. The current investigation quantified differences in MMA vapors produced during the preparation of competing bone cements using various methods of preparation. Unlike previous investigations, this effort employs modern validated sampling and analytical methods, and considers the affect of censored results. Measurements of sufficient quality and number were collected to allow for a statistical treatment of the data. The ability of two controlled preparation techniques to reduce MMA emissions were compared with a traditional open container. The results confirmed that the preparation of bone cement releases MMA vapors into the breathing zone of the preparer. One preparation technique (Stryker Bowl) controlled emissions during mixing and curing and affected a 73% reduction in measured MMA concentrations. In addition to mixing and curing, the second technique (UltraMix System) also controlled the MMA during pouring of the monomer and affected a 90% reduction in MMA concentrations. An ANOVA test of interaction indicates that the reductions are attributable to the preparation technique regardless of the type of cement being used. Both a Fisher's PLSD and Games/Howell post hoc test of the results indicate that the mean differences between the uncontrolled open container and the controlled preparation techniques are significant (p < 0.05). PMID- 17365500 TI - A web tool for the identification of potential interactive effects of chemical mixtures. AB - This project was undertaken to develop a toxicological database allowing the identification of possible additive or other interactive effects of mixtures present in the work environment. In the first phase of the project, whose findings have already been published, critical toxicological data were compiled for each of the 695 chemical substances in the Quebec Occupational Health Regulation, allowing the prediction of potential additivity among components of a mixture. In the second phase of this project, the types of interactions for mixtures most likely to be found in workplaces and for which primary literature data are available were specified. The toxicological data were evaluated only for realistic exposure concentrations up to the short-term exposure limit or ceiling value or five times the 8-hr time-weighted average (TWA) permissible exposure limit (PEL) for human data and up to 100 times the 8-hr TWA PEL or ceiling value for animal studies. In total, 675 studies were evaluated covering 209 binary mixtures of substances. For the majority of cases where potential additivity was identified in Phase 1, there is a lack of toxicological data in the primary literature. In these cases, the results of the first phase will be useful as the default hypothesis. The resulting database integrates the results from both phases of the project. A web-based computer tool allows the user to determine whether there is potential additivity or interaction among components of a mixture. PMID- 17365501 TI - Metalworking fluid mist--strategies to reduce exposure: a comparison of new and old transmission case transfer lines. AB - Three studies were performed to assess the effectiveness of various techniques to control metalworking fluid (MWF) mist. The studies consisted of a detailed main study that determined the effect of degree of enclosure on personal exposures and area concentrations of MWF mist on two machining transfer lines. One ancillary study was conducted to determine the effect of shutting off MWF delivery during down time; the second ancillary study investigated the effectiveness of improved retrofitted enclosure. In the main study, the two operations were identical except for degree of enclosure. Personal and area sampling results for the new line were about half those found in the old line. Measurements at the new operation exhibited significantly less variability. Personal exposures and area concentrations were significantly less at the new operation than at the older, less enclosed operation, demonstrating that the total enclosure in the new operation provides better and more consistent control of the mist. The first ancillary study was conducted to determine if shutting off MWF delivery to the parts being machined reduced area MWF mist concentration during downtime at a partially enclosed transfer machining line. A significant reduction in concentration of 80% was measured with machining off/MWF off. Mist concentrations measured with machining off/MWF on were not significantly different from mist levels measured during machining on/MWF on. The second ancillary study investigated the reduction of mist concentration achieved through improved enclosure of an existing set of machines. Area mist concentrations were measured at a machining operation before and after the installation of an improved enclosure. Area mist concentrations were reduced by 87% with the improved enclosure. PMID- 17365502 TI - Overexposure and control of methylene chloride in a furniture stripping operation. PMID- 17365503 TI - Erythema and conjunctivitis: investigation of an outbreak in a school gymnasium caused by unintentional exposure to ultraviolet radiation from metal halide lamps. PMID- 17365506 TI - Fundamental factors affecting upper-room ultraviolet germicidal irradiation - part I. Experimental. AB - The objective of this research was to study the factors that relate to the effectiveness of upper-room ultraviolet germicidal irradiation for inactivating airborne microorganisms. The work was conducted in a room-sized chamber designed and furnished for investigations of this nature. Nebulized Serratia marcescens, Bacillus subtilis spores, and vaccinia virus were used as test aerosols. Most data were collected from steady-state experiments comparing the number of viable organisms in the chamber air remaining with UV lamps turned on to the number with UV lamps turned off, but some decay experiments were conducted to compare the two methods. UV power level had a strong influence but was fully effective only in the presence of air mixing that produced vigorous vertical air currents. A conclusion of the study is that an upper-room ultraviolet installation is a complex system that requires careful integration of UV luminaires, UV power, and room ventilation arrangements. PMID- 17365507 TI - Perspectives on mathematical modeling for receptor-mediated processes. AB - Mathematical modeling is a potent in silico tool that can help investigate, interpret, and predict the behavior of biological systems. The first step is to develop a working hypothesis of the biology. Then by "translating" the biological phenomena into equations, models can harness the power of mathematical analysis techniques to explore the dynamics and interactions of the biological components. Models can be used together with traditional experimental models to help design new experiments, test hypotheses, identify mechanisms, and predict outcomes. This article reviews the process of building, calibrating, and using mathematical models in the context of the kinetics of receptor and signal transduction biology. An example model related to the androgen receptor-mediated regulation of the prostate is presented to illustrate the steps in the modeling process and to highlight the potential for mathematical modeling in this area. PMID- 17365508 TI - Dominance of the alpha1B-adrenergic receptor and its subcellular localization in human and TRAMP prostate cancer cell lines. AB - The function and distribution of alpha1-adrenergic receptor (AR) subtypes in prostate cancer cells is well characterized. Previous studies have used RNA localization or low-avidity antibodies in tissue or cell lines to determine the alpha1-AR subtype and suggested that the alpha1A-AR is dominant. Two androgen insensitive, human metastatic cancer cell lines DU145 and PC3 were used as well as the mouse TRAMP C1-C3 primary and clonal cell lines. The density of alpha1-ARs was determined by saturation binding and the distribution of the different alpha1 AR subtypes was examined by competition-binding experiments. In contrast to previous studies, the major alpha1-AR subtype in DU145, PC3 and all of the TRAMP cell lines is the alpha1B-AR. DU145 cells contained 100% of the alpha1B-AR subtype, whereas PC3 cells were composed of 21% alpha1 A-AR and 79% alpha1B-AR. TRAMP cell lines contained between 66% and 79% of the alpha1B-AR with minor fractions of the other two subtypes. Faster doubling time in the TRAMP cell lines correlated with decreasing alpha 1B-AR and increasing alpha1 A- and alpha1D-AR densities. Transfection with EGFP-tagged alpha1B-ARs revealed that localization was mainly intracellular, but the majority of the receptors translocated to the cell surface after extended preincubation (18 hr) with either agonist or antagonist. Localization was confirmed by ligand-binding studies and inositol phosphate assays where prolonged preincubation with either agonist and/or antagonist increased the density and function of alpha 1-ARs, suggesting that the native receptors were mostly intracellular and nonfunctional. Our studies indicate that alpha1B-ARs are the major alpha1-AR subtype expressed in DU145, PC3, and all TRAMP cell lines, but most of the receptor is localized in intracellular compartments in a nonfunctional state, which can be rescued upon prolonged incubation with any ligand. PMID- 17365509 TI - Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling. AB - The Ca2+ sensor calmodulin (CaM) regulates numerous proteins involved in G protein-coupled receptor (GPCR) signaling. CaM binds directly to some GPCRs, including the dopamine D2 receptor. We confirmed that the third intracellular loop of the D2 receptor is a direct contact point for CaM binding using coimmunoprecipitation and a polyHis pull-down assay, and we determined that the D2-like receptor agonist 7-OH-DPAT increased the colocalization of the D2 receptor and endogenous CaM in both 293 cells and in primary neostriatal cultures. The N-terminal three or four residues of D2-IC3 were required for the binding of CaM; mutation of three of these residues in the full-length receptor (I210C/K211C/I212C) decreased the coprecipitation of the D2 receptor and CaM and also significantly decreased D2 receptor signaling, without altering the coupling of the receptor to G proteins. Taken together, these findings suggest that binding of CaM to the dopamine D2 receptor enhances D2 receptor signaling. PMID- 17365510 TI - Analysis of proteins binding to the ITAM motif of the beta-subunit of the high affinity receptor for IgE (FcepsilonRI). AB - Aggregation of the multichain (alphabetagamma2) high-affinity IgE receptor (Fcepsilon RI) initiates a signaling cascade that results in the release of allergic mediators. The cytoplasmic tails of the FcepsilonRI-beta and -gamma subunits contain immunoreceptor tyrosine-based activation motifs (ITAMs). Phosphorylation of the gammaITAM mediates activation of Syk kinase and is sufficient for triggering the responses induced by Fcepsilon RI crosslinking. Phosphorylation of the betaITAM is insufficient to mediate cell activation. The rat betaITAM contains three tyrosines (Tyr218, Tyr224, and Tyr228) with an intermediate noncanonical tyrosine. Synthetic peptides based on the ITAM of the FcepsilonRI-beta subunit were used to investigate the role of each phosphotyrosine in the binding of signaling proteins to this motif. Among the proteins that bind to phosphorylated beta ITAM are Syk, Grb2, Shc, SHIP, and SHP 1, and binding does not depend on previous cell activation. Nonphosphorylated peptides do not bind these proteins. Syk binding to beta-peptides is dependent on the number and position of phosphotyrosines in the ITAM. Phosphorylation of Tyr218 seems to be most important for Syk binding. Recruitment of Syk and other signaling proteins to the beta-subunit might be important for its amplifier role. PMID- 17365511 TI - G protein-coupled receptor-mediated ERK1/2 phosphorylation: towards a generic sensor of GPCR activation. AB - The development of new analytical methods, aimed at profiling G protein-coupled receptor (GPCR) ligands, regardless of the G protein-coupling pattern of their respective receptor, remains a key goal in drug discovery. Considerable evidence has recently revived the central role that could be played by extracellular signal-regulated kinase (ERK), the cornerstone protein kinase of the first tyrosine kinase receptor-mediated pathway identified, in response to the activation of various types of GPCRs. Here we reveal a conceptual study in which the potential of ERK phosphorylation is evaluated as a generic readout in response to three different receptors activating three main classes of G proteins: Galphas, Galphai and Galphaq. GPCR-mediated ERK phosphorylation was compared with different readouts such as GTPgammaS, CAMP, or Ca2 +. We propose the measurement of GPCR-activated ERK phosphorylation as an alternative assay to better understand the molecular pharmacology of ligands of promiscuous GPCRs. PMID- 17365512 TI - Intimacy, orgasm likelihood, and conflict predict sexual satisfaction in heterosexual male and female respondents. AB - Anonymous data provided by 417 female and 179 male sexually active heterosexual respondents showed that in long term sexual relationships, sexual satisfaction was positively correlated with two different intimacy variables, the respondent's orgasm likelihood, and negatively correlated with conflict in the relationship. Multiple linear regression permitted us to measure the effect sizes of these variables as predictors of sexual satisfaction. These findings have important implications for treatment of symptomatic couples. PMID- 17365513 TI - Sex therapy through the internet for men with sexual dysfunctions: a pilot study. AB - Results are described of a pilot study of the efficacy of sex therapy through the Internet for thirty-nine men with erectile dysfunction or rapid ejaculation. Treatment consisted of sex therapy (Masters & Johnson, 1970), had a duration of three months, and was conducted entirely through e-mail. Forty-six percent of the participants dropped out. Fourteen (67%) participants reported an improvement of their sexual functioning. Seven (47%) participants reported the improvement had sustained one month after termination, eight (53%) participants reported no further change. We conclude that sex therapy through the Internet may yield positive results and that further controlled studies are warranted. PMID- 17365514 TI - The effect of male erectile dysfunction on the psychosocial, relationship, and sexual characteristics of heterosexual women in the United States. AB - Using Internet-based survey data, this study compared the demographic, psychosocial, relationship, and sexual characteristics of three groups of U.S. women: (a) women whose partners had erectile dysfunction (ED) and were taking medication to treat ED; (b) women whose partners had ED in the previous 3 months and were not taking medication to treat ED; and (c) a control group of women whose partners did not have ED. Results indicate that women are affected by their partners' ED and that ED treatment benefits women's sexual self-efficacy, communication about sexual issues, and sexual and relationship satisfaction. PMID- 17365515 TI - Premature ejaculation: the scope of the problem. AB - Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Successful treatment of PE has been hampered by the existence of a variety of definitions and diagnostic criteria and the lack of large, long-term studies of treatment efficacy. Numerous, diverse treatment approaches with varying degrees of efficacy have been used; these include behavioral, cognitive, and sex therapy techniques, and pharmacologic management with anti-depressants, phosphodiesterase 5 inhibitors, and topical anesthetics. The approach most likely to provide success is a combination of cognitive and sex therapy with a pharmacologic agent of proven efficacy that has an easy-to-follow dosing regimen. PMID- 17365522 TI - BASES 2006: From education to application. Abstracts of the annual conference of the British Association of Sport and Exercise Sciences. September 11-13, 2006. University of Wolverhampton, United Kingdom. PMID- 17365516 TI - Itch and burning pain in women with partial vaginismus with or without vulvar vestibulitis. AB - Fifty-three women with partial vaginismus with or without vulvar vestibulitis and 27 asymptomatic women estimated sensations of burning pain and itch at 20 standardized moments during a standardized penetration situation, including vaginal muscle contractions. Forty-three women with partial vaginismus (81.1%) reported burning pain, 23 (43.4%) itch, and 22 (41.5%) both complaints, compared to 0% of the asymptomatic women. In 17 of 22 cases, burning pain preceded the appearance of itch and in four cases the two complaints coincided. The median time from the moment when burning pain started until itch appeared was 150 seconds. PMID- 17365523 TI - Kinanthropometry - the interdisciplinary discipline. PMID- 17365524 TI - A new device for estimating active drag in swimming at maximal velocity. AB - A new device was designed to measure the active drag during maximal velocity swimming based on the assumption of equal useful power output in two cases: with and without a small additional drag. A gliding block was used to provide an adjustable drag, which was attached to the swimmer and measured by a force transducer. Six swimmers of national standard (3 males, 3 females) participated in the test. For the males, the mean active drag ranged from 48.57 to 105.88 N in the front crawl and from 54.14 to 76.37 N in the breaststroke. For the females, the mean active drag ranged from 36.31 to 50.27 N in the front crawl and from 36.25 to 77.01 N in the breaststroke. During testing, the swimmer's natural stroke and kick were not disturbed. We conclude that the device provides a useful method for measuring and studying active drag. PMID- 17365525 TI - The continuous measurement of the springboard reaction force in gymnastic vaulting. AB - A new method was established for the continuous measurement of force applied from a springboard to a gymnast in vaulting (board reaction force). Male gymnasts performed a handspring vault using a springboard mounted on force platforms. A high-speed video camera sampled the springboard motion at 500 Hz. The springboard was initially partitioned into 29 segments. The force due to the accelerative motion of the springboard was determined by summing the forces of the individual segments. The board reaction force acting on the gymnast was calculated by subtracting the force due to the accelerative motion of the springboard and weight from the force recorded by the force platform. The new method succeeded in illustrating transient changes of the board reaction force. The horizontal and vertical components of the peak values of the board reaction force were three and two times greater respectively than the average values. A series of tests was conducted to determine whether the number of segments of the springboard model could be reduced without affecting accuracy. A model consisting of only four segments produced almost the same accuracy as the 29-segment model. The simplified model is recommended as a more efficient method to measure board reaction force. PMID- 17365526 TI - The influence of lower limb amputation level on the approach in the amputee long jump. AB - In this study, we investigated the adjustments to posture, kinematic and temporal characteristics of performance made by lower limb amputees during the last few strides in preparation for long jump take-off. Six male unilateral trans-femoral and seven male unilateral trans-tibial amputees competing in a World Championships final were filmed in the sagittal plane using a 100-Hz digital video camera positioned so that the last three strides to take-off were visible. After digitizing using a nine-segment model, a range of kinematic variables were computed to define technique characteristics. Both the trans-femoral and trans tibial athletes appeared to achieve their reduction in centre of mass during the flight phase between strides, and did so mainly by extending the flight time by increasing stride length, achieved by a greater flexion of the hip joint of the touch-down leg. The trans-tibial athletes appeared to adopt a technique similar to that previously reported for able-bodied athletes. They lowered their centre of mass most on their second last stride (-1.6% of body height compared with 1.4% on the last stride) and used a flexed knee at take-off on the last stride, but they were less able to control their downward velocity at touch-down (-0.4 m x s(-1)). Both this and their restricted approach speed (8.9 m x s(-1) at touch down), rather than technique limitations, influenced their jump performance. The trans-femoral athletes lowered their centre of mass most on the last stride ( 2.3% of body height compared with -1.6% on the second last stride) and, as they were unable to flex their prosthetic knee sufficiently, achieved this by abducting their prosthetic leg during the support phase, which led to a large downward velocity at touch-down (-0.6 m x s(-1)). This, combined with their slower approach velocity (7.1 m x s(-1) at touch-down), restricted their performance. PMID- 17365527 TI - Effect of stroke rate on the distribution of net mechanical power in rowing. AB - The aim of this study was to assess the effect of manipulating stroke rate on the distribution of mechanical power in rowing. Two causes of inefficient mechanical energy expenditure were identified in rowing. The ratio between power not lost at the blades and generated mechanical power (P(rower)) and the ratio between power not lost to velocity fluctuations and P(rower) were used to quantify efficiency (e(propelling) and e(velocity) respectively). Subsequently, the fraction of P(rower) that contributes to the average velocity (chi(boat)) was calculated (e(net)). For nine participants, stroke rate was manipulated between 20 and 36 strokes per minute to examine the effect on the power flow. The data were analysed using a repeated-measures analysis of variance. Results indicated that at higher stroke rates, P(rower), chi(boat), e(propelling), and e(net) increase, whereas e(velocity) decreases (P < 0.0001). The decrease in e(velocity) can be explained by a larger impulse exchange between rower and boat. The increase in e(propelling) can be explained because the work at the blades decreases, which in turn can be explained by a change in blade kinematics. The increase in e(net) results because the increase in e(propelling) is higher than the decrease in e(velocity). Our results show that the power equation is an adequate conceptual model with which to analyse rowing performance. PMID- 17365528 TI - Graduated compression stockings: physiological and perceptual responses during and after exercise. AB - The aim of this study was to examine the effect of wearing graduated compression stockings on physiological and perceptual variables during and after intermittent (Experiment 1) and continuous (Experiment 2) running exercise. Fourteen recreational runners performed two multi-stage intermittent shuttle running tests with 1 h recovery between tests (Experiment 1). A further 14 participants performed a fast-paced continuous 10-km road run (Experiment 2). Participants wore commercially available knee-length graduated compression stockings (pressure at ankle 18 - 22 mmHg) beneath ankle-length sports socks (experimental trials) or just the latter (control trials) in a randomized counterbalanced design (for both experiments). No performance or physiological differences were observed between conditions during intermittent shuttle running. During the 10-km trials, there was a reduction in delayed-onset muscle soreness 24 h after exercise when wearing graduated compression stockings (P < 0.05). There was a marked difference in the frequency and location of soreness: two participants in the stockings trial but 13 participants in the control trial indicated soreness in the lower legs. Wearing graduated compression stockings during a 10-km road run appears to reduce delayed-onset muscle soreness after exercise in recreationally active men. PMID- 17365529 TI - Quantification of Spinning bike performance during a standard 50-minute class. AB - Spinning is a type of indoor fitness activity performed on stationary bikes by participants who pedal together to the rhythm of music and the motivating words of an instructor. Despite worldwide popularity of this type of recreational activity, to date there have been few, mainly non-scientific, studies of the impact of spinning on metabolic, respiratory, and cardiovascular functions. The main aim of this study was to evaluate a number of metabolic and cardiovascular variables during a standard 50-min class performed by Spinning instructors of both sexes: six males (age 30 +/- 4.8 years, body mass index 24 +/- 2.5 kg x m( 2); mean +/- s) and six females (age 34 +/- 6.3 years, body mass index 21 +/- 1.9 kg x m(-2)). The mean power output, heart rate, and oxygen uptake during the performance were 120 +/- 4 W, 136 +/- 13 beats x min(-1), and 32.8 +/- 5.4 ml x kg(-1) x min(-1) respectively for males, and 73 +/- 43 W, 143 +/- 25 beats x min( 1), and 30 +/- 9.9 ml x kg(-1) x min(-1) respectively for females. Analysis of individual performances showed that they were compatible with physical exercise that ranged from moderate-to-heavy to very heavy, the latter conditions prevailing. The results show that this type of fitness activity has a high impact on cardiovascular function and suggest that it is not suitable for unfit or sedentary individuals, especially the middle aged or elderly, who are willing to begin a recreational physical activity programme. PMID- 17365530 TI - Effect of intermittent normobaric hypoxic exposure at rest on haematological, physiological, and performance parameters in multi-sport athletes. AB - The aim of this study was to determine whether 3 weeks of intermittent normobaric hypoxic exposure at rest was able to elicit changes that would benefit multi sport athletes. Twenty-two multi-sport athletes of mixed ability were exposed to either a normobaric hypoxic gas (intermittent hypoxic training group) or a placebo gas containing normal room air (placebo group). The participants breathed the gas mixtures in 5-min intervals interspersed with 5-min recovery periods of normal room air for a total of 90 min per day, 5 days per week, over a 3-week period. The oxygen in the hypoxic gas decreased from 13% in week 1 to 10% by week 3. The training and placebo groups underwent a total of four performance tests, including a familiarization and baseline trial before the intervention, followed by trials at 2 and 17 days after the intervention. Time to complete the 3-km run decreased by 1.7%[95% confidence interval (CI) = -0.6 - 3.9%] 2 days after, and by 2.3% (CI = 0.25 - 4.4%) 17 days after, the last hypoxic episode in the training relative to the placebo group. Substantial changes in the training relative to the placebo group also included increased reticulocyte count 2 days (23.5%; CI =-1.9 to 44.9%) and 12 days (14.6%; CI = -7.1 to 36.4%) post-exposure. The effect of intermittent hypoxic training on 3-km performance found in this study is likely to be beneficial, which suggests non-elite multi-sport athletes should expect such training to enhance performance. PMID- 17365531 TI - Effect of shoulder angle on physiological responses during incremental peak arm crank ergometry. AB - This study examined the effect of shoulder angle and gender on physiological and perceptual responses during incremental peak arm ergometry. Healthy adults (nine males, seven females) volunteered for the study and completed an incremental arm ergometry test on two separate occasions at two different shoulder angles (90 degrees and 45 degrees). Initial work rate was set at 16 W x min-1 and was increased progressively until exhaustion. Cardiorespiratory and perceptual responses were recorded at the end of each minute and compared using separate three-way (position x work rate x gender) repeated-measures analyses of variance. The systematic bias of peak responses was examined using separate two-way (position x gender) analyses of variance, while reproducibility of these parameters was explored using intraclass correlation coefficients, measurement bias/ratio, and 95% ratio limits of agreement. Despite a significantly greater peak heart rate for the 45 degrees position, cardiorespiratory and perceptual responses were similar at peak exercise for both positions. Peak values for all variables, although similar, demonstrated similar and large inter-test variability for men and women. Reduction of the shoulder joint angle to 45 degrees did not enhance peak work rate and peak oxygen consumption during seated upper body exercise. Due to the large inter-test variability, arm ergometry should be conducted using the same seated position. PMID- 17365532 TI - The effects of arm crank strategy on physiological responses and mechanical efficiency during submaximal exercise. AB - The purpose of this study was to compare submaximal physiological responses and indices of mechanical efficiency between asynchronous and synchronous arm ergometry. Thirteen wheelchair-dependent trained athletes performed eight steady state incremental bouts of exercise (0 to 140 W), each lasting 4 min, using synchronous and asynchronous arm-cranking strategies. Physiological measures included oxygen uptake (VO2), heart rate, and blood lactate concentration. The power outputs corresponding to fixed whole blood lactate concentrations of 2.0 to 4.0 mmol x l(-1) were calculated using linear interpolation. Mechanical efficiency indices - gross efficiency, net efficiency, and work efficiency - were also calculated. An analysis of variance with repeated measures was applied to determine the effect of crank mode on the physiological parameters. Oxygen uptake was on average 10% lower (P < 0.01), and both net efficiency (P < 0.01) and gross efficiency (P < 0.01) were higher, during the asynchronous strategy at both 60 and 80 W (gross efficiency: 16.9 +/- 2.0% vs. 14.7 +/- 2.4% and 17.5 +/- 1.8% vs. 15.9 +/- 2.6% at 60 and 80 W respectively). There were no differences in heart rate, blood lactate concentration or power output at either of the blood lactate reference points between the asynchronous and synchronous strategies (P > 0.05). In conclusion, test specificity is an important consideration. If a synchronous strategy is to be adopted, it is likely to result in lower efficiency than an asynchronous strategy. The exercise testing scenario may help dictate which method is ultimately chosen. PMID- 17365533 TI - Time - motion analysis of professional rugby union players during match-play. AB - The aim of this study was to quantify the movement patterns of various playing positions during professional rugby union match-play, such that the relative importance of aerobic and anaerobic energy pathways to performance could be estimated. Video analysis was conducted of individual players (n=29) from the Otago Highlanders during six "Super 12" representative fixtures. Each movement was coded as one of six speeds of locomotion (standing still, walking, jogging, cruising, sprinting, and utility), three states of non-running intensive exertion (rucking/mauling, tackling, and scrummaging), and three discrete activities (kicking, jumping, passing). The results indicated significant demands on all energy systems in all playing positions, yet implied a greater reliance on anaerobic glycolytic metabolism in forwards, due primarily to their regular involvement in non-running intense activities such as rucking, mauling, scrummaging, and tackling. Positional group comparisons indicated that while the greatest differences existed between forwards and backs, each positional group had its own unique demands. Front row forwards were mostly involved in activities involving gaining/retaining possession, back row forwards tended to play more of a pseudo back-line role, performing less rucking/mauling than front row forwards, yet being more involved in aspects of broken play such as sprinting and tackling. While outside backs tended to specialize in the running aspects of play, inside backs tended to show greater involvement in confrontational aspects of play such as rucking/mauling and tackling. These results suggest that rugby training and fitness testing should be tailored specifically to positional groups rather than simply differentiating between forwards and backs. PMID- 17365534 TI - Main and interactive effects of attribution dimensions on efficacy expectations in sport. AB - In this study, I examined the main and interactive effects of attribution dimensions on efficacy expectations in sport. A sample of 162 athletes (102 males, 60 females) aged 20.9 years (s = 3.4) from various sports were recruited. The participants, who were of club to international standard, completed the Causal Dimension Scale II (McAuley et al., 1992) in relation to their most recent performance. They then completed a 7-item measure of efficacy expectations in relation to their upcoming performance. The key predictors of efficacy expectations were stability and personal control, but their function differed after more or less successful performances. After more successful performances, attributions to stability and personal control were associated with main effects upon efficacy expectations, in a positive direction; after less successful performances, attributions to stability and personal control were associated with an interactive effect upon efficacy expectations. The form of this effect was such that the participants were more likely to have high efficacy expectations only when they viewed the cause of their performances as both personally controllable and stable. PMID- 17365535 TI - Multidimensional performance characteristics and standard of performance in talented youth field hockey players: a longitudinal study. AB - To identify performance characteristics that could help predict future elite field hockey players, we measured the anthropometric, physiological, technical, tactical, and psychological characteristics of 30 elite and 35 sub-elite youth players at the end of three consecutive seasons. The mean age of the players at the end of the first season was 14.2 years (s = 1.1). Repeated-measures analyses of covariance, with standard of performance and measurement occasion as factors and age as a covariate, showed that the elite players fared better than the sub elite players on technical and tactical variables. Female elite youth players also scored better on interval endurance capacity, motivation, and confidence. Future elite players appear to have excellent tactical skills by the age of 14. They also have good specific technical skills and develop these together with interval endurance capacity better than sub-elite youth players in the subsequent 2 years. To verify our conclusions, we will be tracking these players into adulthood. PMID- 17365537 TI - Current status of observational learning research and the role of demonstrations in sport. PMID- 17365538 TI - From visuo-motor interactions to imitation learning: behavioural and brain imaging studies. AB - We review three areas of research and theory relating to the involvement of motor processing in action observation: behavioural studies on imitation learning, behavioural work on short-term visuomotor interactions, and related neurophysiological and neuroimaging work. A large number of behavioural studies now indicate bi-directional links between perception and action: visual processing can automatically induce related motor processes, and motor actions can direct future visual processing. The related concept of direct matching (Rizzolatti et al., 2001) does not, however, imply that observed actions are transduced into a corresponding motor representation that would guarantee an instant and accurate imitation. Rather, studies on the mirror neuron system indicate that action observation engages the observer's own motor prototype of the observed action. This allows for enhanced action recognition, imitation recognition, and, predominantly in humans, imitation and observational learning. Despite the clear impact of action observation on motor representations, recent neuroimaging work also indicates the overlap of imitation learning with processes of non-imitative skill acquisition. PMID- 17365539 TI - Influence of the perception of biological or non-biological motion on movement execution. AB - The perception of a human actor performing movements may involve processes related to action execution. This resonance of the motor system may support observational learning and imitation, and could also explain the fact that observers'/actors' movements are disturbed by the observation of a human model making different movements (Kilner et al., 2003). In this study, we tried to specify what information available in the model's behaviour triggers this influence on an observer's behaviour. In two experiments, we had participants make horizontal or vertical arm movements while observing similar movements. In the first experiment, the observers' pattern of behaviour was affected by the observation of a human model making incongruent movements. In the second experiment, similar results were obtained with participants observing a moving dot depicting either biological or non-biological motion. Movement execution was affected differentially by biological and non-biological motion observation. These results show that an observer's behaviour is sensitive to information available in biological motion. PMID- 17365540 TI - What is modelled during observational learning? AB - In this article, we examine the question of what information is processed during observational learning by evaluating a variety of methods, theories, and empirical data. Initially, we review work involving neuroimaging techniques and infant imitation. We then evaluate data from behavioural experiments involving adults, wherein a variety of attempts have been made to isolate the critical or minimal information constraining the acquisition of coordination. This body of research has included comparisons between video and point-light displays, manipulations to the amount and type of information presented in the display, the collection of point-of-gaze data, and manipulations to the task context in terms of outcome goals. We conclude that observational learning is governed by specific features of the model's action (i.e. motions of the end effector) and the task (i.e. outcome constraints) and, in contrast with traditional theoretical modelling, more global aspects of a model (i.e. the relative motions within and between joints) do not appear to be the primary method for constraining action execution. PMID- 17365541 TI - Developmental effects influencing observational modelling: a meta-analysis. AB - A meta-analysis was conducted on the observational modelling literature (n = 55 studies) to quantify overall between-participant treatment effects (deltau Bi) gained for child and adult populations. The overall observational modelling treatment estimate obtained from movement dynamics (i.e. form) data was larger for adults (deltau Bi = 0.80) than children (deltau Bi = 0.24); the modelling advantage over a practice-only control condition was significant for adults only. In contrast, the overall observational modelling treatment estimate obtained for movement outcome data (i.e. task goal) was negligible (deltau Bi = -0.02) for adults, whereas it was more substantial (deltau Bi = 0.48) and significant for children. These findings are consistent with the suggestion that, as a result of observation, children show a greater tendency to achieve movement outcome goals (e.g. task accuracy) than adults, who tend to focus more on matching existing intrinsic dynamics with the observed task dynamics. We suggest that the developmental effects influencing observational modelling result from differences in individuals' intrinsic dynamics, and hence the opportunity to replicate the observed motor skill. The current meta-analysis describes reasons for equivocality in the extant observational modelling literature and elucidates a research agenda for pedagogists aiming to better understand the benefits of modelling techniques. PMID- 17365542 TI - The efficacy of demonstrations in teaching children an unfamiliar movement skill: the effects of object-orientated actions and point-light demonstrations. AB - In Experiment 1, adult and child participants were instructed to imitate a video model performing a bowling action with or without a ball. Participants imitated the action with greater accuracy without a ball and in general adults were more accurate than children. In Experiment 2, adults and children were shown a video or point-light display of the bowling action. There was no difference in movement form between the adult point-light and video groups. In contrast, children were poorer at reproducing the action when viewing point-light compared with video sequences (P < 0.05). The novel point-light display hindered the children's ability to provide conceptual mediation between the presented information and action requirements. In Experiment 3, a child point-light group was provided with perceptual-cognitive training. The perceptual-cognitive training group demonstrated better movement reproduction than a group who viewed the point-light displays with no training (P < 0.05), although there were no differences between participants who received training and those who viewed a video. Children are able to perceive and use relative motion information from a display after some general training, and the effectiveness of demonstrations needs to be judged relative to the task context. PMID- 17365543 TI - The impact of self-as-a-model interventions on children's self-regulation of learning and swimming performance. AB - We compared two self-as-a-model interventions: self-modelling (viewing oneself perform an adaptive behaviour) and self-observation (viewing oneself perform at current skill level). Operating within Zimmerman's (1989, 2000) theory of self regulated learning, we examined the effect of the modelling interventions on three self-regulatory processes (self-efficacy, intrinsic motivation, and self satisfaction), as well as physical performance. Thirty-three children were randomly assigned to one of three experimental groups. The two self-as-a model groups received the modelling intervention just before physical practice, whereas the control group received physical practice only. Analyses of the retention scores revealed significant differences for all dependent measures. Post hoc testing showed consistently that the self-modelling group performed better than the self-observation and control groups, and that the two latter groups performing similarly. These results provide support for the implementation of self-modelling interventions with children when teaching motor skills. PMID- 17365545 TI - Demonstration as a rate enhancer to changes in coordination during early skill acquisition. AB - We compared the nature and rate of change in intra-limb coordination in participants who observed a video model (model) with those who practised based on verbal guidance only (control). Sixteen male novices threw a ball towards a target with maximal velocity using a back-handed, reverse baseball pitch. Participants in the model group immediately changed their intra-limb relative motion to more closely resemble the model's relative motion pattern. This new coordination pattern, and concomitant changes in ball speed, was maintained throughout acquisition, without further change. In contrast, the control group showed no change in coordination or ball speed across acquisition. Our findings suggest that demonstrations act as a rate enhancer, conveying an immediate movement solution that is adopted early in acquisition. A model may constrain the learner to perceive and imitate the model's relative motion pattern as suggested by Scully and Newell (1985). The stability of this new movement pattern questions accounts of learning, which suggest that prescriptive, directed learning may result in the "soft assembly" of an inaccurate and temporary movement solution. PMID- 17365544 TI - A comparison of modelling and imagery in the acquisition and retention of motor skills. AB - Although many researchers have examined the effects of imagery and/or modelling interventions, it is unclear which of the two interventions is more effective. In two experiments, novice learners assessed over multiple trials of a free weight squat lifting or a stabilometer balancing task were given modelling, imagery, a combination of modelling and imagery, or control interventions. Group differences indicated, in general, that groups receiving modelling (modelling, combination) evidenced a more appropriate form than groups that did not receive modelling (imagery, control). When apparent, these differences were already in place after the first of several interventions. Practical implications are that even a single bout of modelling can have immediate beneficial effects on movement form (Experiments 1 and 2) and outcome (Experiment 1). PMID- 17365548 TI - European influence on Russian neurology in the eighteenth and nineteenth centuries. AB - In this study we consider the development of clinical neurology in the eighteenth and the nineteenth centuries focusing on European influence on Russian medicine. Russian physicians readily accepted newly described clinical signs, theories, and classification of nervous diseases designed in Europe. This influence initiated neurology's separation from general medicine and its transformation into a new clinical discipline. In Russia this happened already in the 1860s, decades before the similar trend in Europe. The Russian example is nearly unknown in the general history of neurology. It illustrates the relationships between physiology and practical neurology at the moment of establishment of the new discipline. It also shows that the Russian physicians of the time readily accepted European medical knowledge putting it immediately into medical practice and education. PMID- 17365549 TI - I.m. Sechenov: the patriarch of Russian physiology. AB - Using quotations from Russian (e.g., Mechnikov and Pavlov) and western European (e.g., Ludwig) sources of his friends and colleagues, as well as from his autobiography, this paper describes the life and personality of Ivan Mikhailovich Sechenov (1829-1905), who became well known because of his central inhibition theory (1862). He trained in several European centers, including Vienna, were he worked with Carl Ludwig (1816-1895), with whom he corresponded for several decades. PMID- 17365550 TI - I.M. Sechenov (1829 - 1905) and the scientific self-understanding for medical sciences. AB - There is no discussion about the historic relevance of I. Sechenov for physiology and neurosciences as the "father of Russian modern physiology". But he is relevant for modern natural science too because of his basic epistemological and ontological work. He did not accept the up to now basic paradigm of "Ignorabimus" which can be seen as the reason to exclude even the generalizable aspects of individuality, creativity and spontaneity from natural science. He developed techniques for empirical based science to deal with materialistic and idealistic aspects of the comprehensive person the "ignoramus" according to the actual stay of knowledge and the acceptable ontologies. He demonstrated that ontologies ("paradigms") can be used as tools according to the given problem which should be solved. So Sechenov can be seen as a precursor of the so efficient philosophical positions of Einstein and Th. Kuhn. The stay of the art in physiology and neurosciences changed since the time of Sechenov dramatically. Therefore the philosophical positions of the 19th century should be discussed. Maybe this is indispensable for the needed linkage between materialistic and idealistic aspects of a person. For this the proposals of Sechenov are helpful up to now but nearly unknown. There is no discussion about the historic relevance of I. Sechenov as the "father of Russian physiology." But he is relevant for modern natural science too because of his epistemological and ontological work. He did not accept the up to now basic paradigm of "Ignorabimus" that can be seen as the reason to exclude even the generalizable aspects of individuality, creativity, and spontaneity from natural science. He demonstrated that ontologies ("paradigms") and epistemology can be used as tools according to the given problem. So Sechenov can be seen as a precursor of the so efficient philosophical positions of Einstein and Th. Kuhn. The state of the art changed dramatically. Therefore, the philosophical positions of the nineteenth century should be questioned. Maybe this is indispensable for the needed link between materialistic and idealistic aspects of a person as a whole. In this respect the proposals of Sechenov are helpful for medical science in the twenty-first century too but nearly unknown. PMID- 17365551 TI - The Moscow clinic for nervous diseases - walking along the portraits. AB - The history of the Clinic for Nervous Diseases of the Moscow University reflects in its entirety the history of the Moscow neurological school itself. A.Ya. Kozhevnikov, the founder of the clinic, was the first professor of neurology in Russia. The clinic opened its doors in 1890 and became the first specialized medical facility in Europe devoted to the treatment of neurological disorders. Kozhevnikov brought up a number of talented followers, who later worked all over Russia, and some of them became in charge of the Clinic for Nervous Diseases. This paper looks into contributions Kozhevnikov, his pupils V.K. Rot, V.A. Muratov, G.I. Rossolimo, E.K. Sepp, and some others who were responsible for the development of the neurological science. PMID- 17365552 TI - Sergey S. Korsakov and the beginning of Russian psychiatry. AB - Sergey Sergeievich Korsakov (1854-1900) was an outstanding Russian psychiatrist, founder of the Moscow psychiatric school, a talented clinician and teacher, and a supporter of the nosological approach in the understanding and systematization of psychiatric illnesses. He described alcoholic polyneuritis with distinctive mental symptoms, which later on was coined "Korsakov's disease." He was the first to give a clear account of paranoia. Korsakov was a leader in more humane patient management by applying no-restraint principles. PMID- 17365553 TI - G.I. Rossolimo (1860-1928) neurologist and public benefactor. AB - G.I. Rossolimo was attracted to neurology as a medical student in the late nineteenth century and remained affiliated with Moscow University most of his life. His training included psychiatry, neuropathology, and laboratory research in his postgraduate years. The domain of his neurological clinical interests was vast. His most enduring efforts were directed toward neurological illnesses and developmental delay. He established a children's institute for neurology and psychology that was the first of its kind in Russia. In addition he developed a neuropsychologic examination for assessing cognitive function. His sustained interests were pursued during and after revolutionary changes in his government. PMID- 17365554 TI - Ivan Petrovich Pavlov (1849-1936). AB - This article contains a brief description of the scientific biography of the first Noble Prize laureate in the area of Neurosciences, I.P. Pavlov. Special attention is paid to the concept of neurism, which infused Pavlov's research on circulation, digestion, and higher nervous activity. The sources of Pavlov's interest in studying psychological processes and phases of "hard intellectual struggle" in the development of a new chapter of physiology are traced to their beginnings. PMID- 17365555 TI - The history of neurology in St. Petersburg. AB - This article expounds the history of the formation and development of neurology in St. Petersburg and emphasizes the original character of St. Petersburg school of neurology. The authors state that many prominent neurologists of St. Petersburg dedicated their work to the development of neurological concepts and have made an important contribution to different areas of neurology, including vascular and demyelinating diseases, diseases of the peripheral nervous system, neuroinfections, epilepsy, etc. PMID- 17365556 TI - Vladimir Mikhailovich Bekhterev. AB - V.M. Bekhterev (1857-1927) was an outstanding Russian neurologist, psychiatrist, psychologist, morphologist, physiologist, and public figure, who authored over 1000 scientific publications and speeches. At the beginning of the twentieth century he created a new multidimensional multidisciplinary scientific branch - psychoneurology, which included the objective knowledge of the anatomy and physiology of the nervous system, psychology, psychiatry, neurology, philosophy, sociology, pedagogy, and other disciplines. Psychoneurology in V.M. Bekhterev's understanding has furthered the introduction into the idea of a "biosocial" essence of man of a third - psychological - component, thus having created a "biopsychosocial" model in the interpretation of human diseases. PMID- 17365557 TI - The history of Kazan neurological school. AB - The historical prerequisites for the foundation and teaching of neurology at Kazan University are described; the relationship between the history of Kazan Imperial University Kazan medical university and neurology school is shown. Brief biographies of outstanding representatives of Kazan Neuroscience (D.P. Skalozubov, V.M. Bekhterev, L.O. Darkshevich, N.O. Kovalevsky, N.A. Mislavsky, A.V. Kibyakov, A.S. Dogel, A.V. Favorsky, L.I. Omorokov, and Y.Y. Popelyansky) are presented. The description of scientific interests of the Kazan neurological school and its specific features related to the one century period since 1885 are described. PMID- 17365558 TI - Emergence and early development of Russian neurosurgery (1890s-1930s). AB - This paper is a case study of specialization in clinical medicine - it is a story of the difficult and complicated birth of a neurosurgery clinic in Russia and the Soviet Union. It demonstrates the futile attempt to institute a new specialty as surgical neurology advocated by neuro(patho)logist V.M. Bekhterev (1857-1927) and implemented by his pupils L.M. Pussep (1875-1942) and A.G. Molotkov (1874-1950). However, surgical neurology was gradually replaced by neurological surgery performed by general surgeons N.N. Burdenko (1875-1946), A.L. Polenov (1871 1947), and V.N. Shamov (1882-1962). Part of my paper is dedicated to the institutional history (emergence of the Institute of Surgical Neurology in Leningrad (in 1926) and the Central Institute of Neurosurgery in Moscow (in 1934). The Moscow Neurosurgical School was focused on lesions of the central nervous system whereas the Leningrad neurosurgical school dealt primarily with peripheral nerve surgery. In the 1930s neurosurgical clinics were established beyond the two capitals - in Rostov-on-Don, Kharkov, and Gorky. Similar to the centralized five-year planning in the Soviet economy, a new discipline of neurosurgery was also centralized and planned from Moscow in the 1930s. It was characterized by kompleksnost' - concentration of several auxiliary disciplines (neuroradiology, neuroophthalmology, neurophysiology, etc.) within neurosurgical research institutions in Leningrad and Moscow. Particular stress was made on the experimental nature of a new discipline, which was viewed as a sort of applied neurophysiology. PMID- 17365559 TI - Pantheon of brains: the Moscow Brain Research Institute 1925-1936. AB - The investigation of Lenin's brain by the German neurobiologist Oskar Vogt and his Russian collaborators in Moscow is one of the most exciting and simultaneously questionable chapters in the history of medicine. With the bizarre claim to be able to detect the material substrate of genius it provoked as much unrealistic expectations in the public as strong criticism by the scientific community of brain researchers. The following paper deals in a brief survey with the foundation and the early history of the Moscow Brain Research Institute (INSTITUT MOZGA) and its initial task - the collecting and mapping the brains of famous (Russian) persons in general and the investigation of Lenin's brain in particular. PMID- 17365560 TI - Mental hygiene for geniuses: psychiatry in the early Soviet years. AB - In this paper, I deal with one episode from the early history of Soviet psychiatry, the project of the Institute of Genius. Though the project never materialized, the idea was characteristic of the very beginning of the Soviet era, when the wildest experiments in the human sciences seemed possible. The author of the project, the psychiatrist Grigorii Vladimirovich Segalin (1878 1960), followed in the steps of another prominent psychiatrist, the architect of the Soviet mental health care system, Lev Markovich Rozenshtein (1884-1934). Rozenshtein, a proponent of social medicine, introduced a new system of psychiatric help that, by contrast with the prerevolutionary one, was preventive and based on outpatient units - neuropsychiatric dispensaries. In a similar way, Segalin planned dispensaries for geniuses, where these otherwise "socially ill adapted" people would receive professional help and care. Having failed to establish such an institution, he founded a journal, the Clinical Archive of Genius and Talent (of Europathology), where he and his like-minded colleagues discussed the supposed pathological origins of talent and published pathographies of outstanding figures. The article traces Segalin's project till its end in the early 1930s. PMID- 17365561 TI - Nikolai V. Konovalov (1900-1966): his role in the development of neurology and the creation of the Institute of Neurology of the Russian Academy of Medical Sciences. AB - Nikolai V. Konovalov (1900-1966) has left a significant imprint in the history of Russian neuroscience. He was among the coryphaei of international and national neurology. Along with the large number of fundamental scientific papers that have determined several aspects of the development of neuroscience, his contribution has been equally important to the establishment and development of one of the distinguished Russian scientific centers - the Institute of Neurology of the Russian Academy of Medical Sciences, which he headed from 1948 until 1966. PMID- 17365562 TI - A.R. Luria and the history of Russian neuropsychology. AB - This paper analyzes Russian contributions to neuropsychology from the eighteenth up to the twenty-first century. Various approaches to the problem of the organization and localization of mental functions in the Pre-Lurian and Luria's periods are discussed. Comparisons with European and North American contributions and with contributions from subsequent Russian literature (post-Lurian period) are presented to demonstrate their interconnections in shaping the course of Russian neuropsychology and the main tendencies in its development. PMID- 17365563 TI - L.A. Orbeli - outstanding physiologist and science leader of the twentieth century. AB - L.A. Orbeli and his school developed new directions in physiology: evolutionary physiology, the theory of adaptational-trophic functions of the sympathetic nervous system, the theory of coordination of functions, and neuroendocrine regulations in the body. Orbeli enriched the study of the physiology of the cerebellum, the sensory organs, the kidneys, and the study of pain. His name is associated with the development of the foundation of physiology of extreme states (the physiology of deep-sea exploration, high altitude, and high velocity flight). PMID- 17365564 TI - Theory of functional systems in the scientific school of P.K. Anokhin. AB - In this paper we present brief biographical data of the outstanding Russian physiologist P.K. Anokhin and the stages of formation of the theory of functional systems, proposed by him. Furthermore we will deal with the architectonics of system organization of behavioral acts, underlying principles of the theory of functional systems as a part of the general theory of systems and the evolution of the theory of functional systems in the Anokhin Scientific School. PMID- 17365565 TI - The loyal dissident: N.A. Bernstein and the double-edged sword of Stalinism. AB - Nikolai Aleksandrovich Bernstein (1896-1966) studied movement in order to understand the brain. Contra Pavlov, he saw movements (thus, the brain) as coordinated. For Bernstein, the cortex was a stochastic device; the more cortexes an animal species has, the more variable its actions will be. Actions are planned with a stochastic "model of the future," and relevance is established through blind mathematical search. In the 1950 neoPavlovian affair, he came under strong attack and had to stop experimenting. It is argued that the consistency of his work derived both from both dialectical materialism and the relentless attacks of the neoPavlovians. PMID- 17365569 TI - Comparative in vitro toxicity of grape- and citrus-farm dusts. AB - Agricultural workers are exposed to a variety of airborne dusts, including crystalline silica and other inorganic minerals. This study was designed to characterize the organic and inorganic components of agricultural dusts in California grape- and citrus-farm fields and to compare their cytotoxicity using in vitro toxicity bioassays as predictors of pathogenicity. Aerosolized dusts collected from farm fields were characterized by scanning-electron-microscopic energy-dispersive x-ray analysis, x-ray diffraction, trace metal analysis by plasma emission spectroscopy, and surface area measurements. As indicators of cytotoxicity, cell viability, release of alveolar enzymes activities (lactate dehydrogenase, N-acetyl glucosaminidase), production of reactive oxygen species (ROS), such as H2O2 and hydroxyl radical (OH), and lipid peroxidation were monitored after exposure of cells to grape- and citrus-farm dusts or inorganic components of these dusts. In addition, activation of nuclear factor kappa B and activator protein-1 were evaluated at the peak time for response of 36 h postexposure. All toxicity studies were done in comparison with crystalline silica of similar particle size and diameter using the same mass concentrations as farm dusts. The results showed that inorganic minerals in the aerosolized farm dust fractions were mostly composed of aluminum silicates, crystalline silica, and free iron. Crystalline silica used in these studies was more cytotoxic than grape- and citrus-farm dusts. However, in general, citrus farm dust exhibited the greatest ability to generate ROS and induce lipid peroxidation. These results support human epidemiologic studies, reporting an increased incidence of pulmonary fibrosis in farm workers, by documenting the potential of farm dusts to induce oxidative stress and initiate disease development. PMID- 17365570 TI - The impact of a poison control center on the length of hospital stay for patients with poisoning. AB - While previous research suggests that poison control centers (PCCs) significantly reduce the number of emergency room visits and resultant health care costs for poisonings, little is known regarding the potential impact of the PCC on the length of hospital stay. The aim of this study was to examine whether assistance from a PCC is associated with a shorter length of hospital stay for patients admitted with poisonings. The cases reported to our PCC were matched over a period of 1 yr with the hospital admissions E-coded as poisonings in the Uniform Billing (UB) data maintained by the state health department. The length of hospital stay was then compared between the cases for which a PCC provided assistance (matches) and the cases for which a PCC was not contacted. During the study period, there were 32,245 hospitalizations for poisoning in the UB data and 52,498 poisonings reported to the PCC. The matching process yielded 1719 nonfatal cases. The length of hospital stay for patients who received assistance from a PCC ranged from 0 to 126 d (median = 2.0) and was significantly different compared to a range of 0 to 220 days (median = 5.0) for cases that were never called in to a PCC. The results of this study suggest that patients admitted to hospitals with poisonings who receive PCC assistance have measurable reductions in average hospital stay. Such a decrease may translate into substantial savings in health care costs and resources. PMID- 17365571 TI - Air pollution and hospital admissions for asthma in a subtropical city: Taipei, Taiwan. AB - This study was undertaken to determine whether there is an association between exposure to air pollutants levels and number of hospital admissions for asthma in Taipei, Taiwan. Hospital admissions for asthma and ambient air pollution data for Taipei were obtained for the period from 1996 through 2003. The relative risk of hospital admission for asthma was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-air-pollutant model, on warm days (> or = 25 degrees C) statistically significant positive associations were found for SO2, NO2, and CO levels with an increase in asthmatic admissions. On cool days (< 25 degrees C), all air pollutants were significantly associated with elevated asthma admissions except SO2. For the two-air-pollutant model, CO significantly increases hospital admissions for asthma in combination with each of the other four pollutants on warm days. On cool days, NO2 and O3 significantly elevated asthma rates in all the two-air-pollutant models. This study provides evidence that higher levels of ambient air pollutant concentrations increase the risk of hospital admissions for asthma. PMID- 17365573 TI - Does lipophilicity per se induce adjuvant effects? Methyl palmitate as model substance does not affect ovalbumin sensitization. AB - Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al(OH)3 served as control groups. Exposures were performed 5 times/wk for 2 wk followed by a weekly exposure for 10 wk. Finally, the mice were challenged with a high-dose OVA aerosol for 3 consecutive days. Neither OVA-specific immunoglobulin (Ig) G1, IgE, or IgG2a production, nor inflammatory cells in BAL, nor respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is, additional structural properties are required. PMID- 17365572 TI - Cell- and isoform-specific increases in arginase expression in acute silica induced pulmonary inflammation. AB - Arginase induction was reported in several inflammatory lung diseases, suggesting that this may be a common feature underlying the pathophysiology of such diseases. As little is known regarding arginase expression in silicosis, the induction and cellular localization of arginase were elucidated in lungs of Sprague-Dawley rats 24 h following exposure to varying doses of silica by intratracheal instillation. Arginase expression was evaluated by activity assay, quantification of arginase I and arginase II mRNA levels using real-time polymerase chain reaction (PCR), and immunohistochemistry. Analyses of cells and fluid obtained by bronchoalveolar lavage (BAL) showed that markers of pulmonary inflammation, tissue damage, activation of alveolar macrophages (AM) and NO production were significantly increased by all silica doses. Arginase activity was increased also in AMs isolated from BAL fluid of silica-treated rats. Silica produced two- and three-fold increases in arginase activity of whole lung at doses of 1 and 5 mg/100 g body weight, respectively. Levels of arginase I mRNA, but not of arginase II mRNA, were similarly elevated. In control lungs, arginase I immunoreactivity was observed only in AMs sparsely dispersed throughout the lung; no inducible nitric oxide synthase (iNOS) immunoreactivity was detected. In silica-treated lungs, arginase I and iNOS were co-expressed in most AMs that were abundantly clustered at inflammatory foci. The rapid induction of arginase I expression in inflammatory lung cells, similar to induction of arginase in other inflammatory lung diseases, implicates elevated arginase activity as a factor in the development of lung damage following exposure to silica. PMID- 17365574 TI - An environmental androgen, 17beta-trenbolone, affects delayed-type hypersensitivity and reproductive tissues in male mice. AB - Recently, a growth promoter for farm animals, trenbolone acetate, was identified as an environmental androgen that potentially affects reproduction. Because androgens also suppress immunity, it was hypothesized that an active metabolite of trenbolone acetate, 17beta-trenbolone (TB), might impair immune responses. Castrated adult CD-1 mice were injected daily with either one of two different doses of 17beta-trenbolone (TB), testosterone propionate (TP), or corn oil (vehicle). The antigen-specific immune response was assessed by measuring delayed type hypersensitivity (DTH) responses. Reproductive response was assessed by measuring reproductive tissue mass and determining testosterone concentrations. Mice treated with TB or TP displayed larger reproductive tissue mass than males treated with corn oil. Furthermore, males exposed to the highest dose of TB displayed a reduced DTH response compared to vehicle-treated animals. In comparison, TP, at a similar dose, only minimally reduced the DTH response. These data support the reproductive and potentially immunosuppressive effects of this environmental androgen, and raise the possibility of health concerns for individuals or populations in contact with high concentrations of TB. PMID- 17365575 TI - Organophosphate exposures in the United States: a longitudinal analysis of incidents reported to poison centers. AB - The implementation of the Food Quality Protection Act of 1996 resulted in a decision by the U.S. Environmental Protection Agency to phase out and eliminate the use of organophosphate insecticides in residential environments. The phase out and cancellation process began in the year 2000 and was complete in 2005. The purpose of this investigation was to utilize national Poison Control Center data to assess whether the risk mitigation decision had an impact on the number of incident cases involving organophosphates in the United States. Organophosphate exposure incident data were extracted from Annual Reports of the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) for the years 1995 to 2004. The number of organophosphate exposure incidents peaked at 20,135 in 1997, and declined in each subsequent year. A statistically significant decrease was observed in the average annual number of organophosphate exposure incidents when comparing data from the time periods before (1995-1999) and after (2000-2004) the commencement of the phase-out process. The decrease in organophosphate incident cases was observed for all age categories, as well as for the circumstances surrounding the exposure (unintentional and intentional exposure incidents). TESS data showed a significant decrease in incident cases involving organophosphates in association with the phase-out from residential uses. The results of this investigation are consistent with other studies that have reported that regulatory restriction of access to pesticide formulations may have a significant impact on the number of human exposure incidents. PMID- 17365576 TI - Toenails as a biomarker of inorganic arsenic intake from drinking water and foods. AB - Toenails were used recently in epidemiological and environmental health studies as a means of assessing exposure to arsenic from drinking water. While positive correlations between toenail and drinking-water arsenic concentrations were reported in the literature, a significant percentage of the variation in toenail arsenic concentration remains unexplained by drinking-water concentration alone. Here, the influence of water consumption at home and work, food intake, and drinking-water concentration on toenail arsenic concentration was investigated using data from a case-control study being conducted in 11 counties of Michigan. The results from 440 controls are presented. Log-transformed drinking-water arsenic concentration at home was a significant predictor (p < .05) of toenail arsenic concentration (R2 = .32). When arsenic intake from consumption of tap water and beverages made from tap water (microg/L arsenic x L/d = microg/d) was used as a predictor variable, the correlation was markedly increased for individuals with >1 microg/L arsenic (R2 = .48). Increased intake of seafood and intake of arsenic from water at work were independently and significantly associated with increased toenail arsenic concentration. However, when added to intake at home, work drinking-water exposure and food intake had little influence on the overall correlation. These results suggest that arsenic exposure from drinking-water consumption is an important determinant of toenail arsenic concentration, and therefore should be considered when validating and applying toenails as a biomarker of arsenic exposure. PMID- 17365577 TI - Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic. AB - Methylation is the primary route of metabolism of inorganic arsenic in humans, and previous studies showed that interindividual differences in arsenic methylation may have important impacts on susceptibility to arsenic-induced cancer. To date, the factors that regulate arsenic methylation in humans are mostly unknown. Urinary arsenic methylation patterns and genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) were investigated in 170 subjects from an arsenic-exposed region in Argentina. Previous studies showed that subjects with the TT/AA polymorphisms at MTHFR 677 and 1298 have lower MTHFR activity than others. In this study, it was found that subjects with the TT/AA variant of MTHFR 677/1298 excreted a significantly higher proportion of ingested arsenic as inorganic arsenic and a lower proportion as dimethylarsinic acid. Women with the null genotype of GSTM1 excreted a significantly higher proportion of arsenic as monomethylarsonate than women with the active genotype. No associations were seen between polymorphisms in GSTT1 and arsenic methylation. This is the first study to report (1) associations between MTHFR and arsenic metabolism in humans, and (2) gender differences between genetic polymorphisms and urinary arsenic methylation patterns. Overall, this study provides evidence that MTHFR and GSTM1 are involved in arsenic metabolism in humans, and polymorphisms in the genes that encode these enzymes may play a role in susceptibility to arsenic-induced cancer. PMID- 17365578 TI - Induction of uterine calbindin-D9k through an estrogen receptor-dependent pathway following single injection with xenobiotic agents in immature rats. AB - Various environmental chemicals, both natural and synthetic, are believed to act as endocrine disruptors (EDs) in mammals. In this study, a new in vivo model of immature rats was used to explore the induction of calbindin-D9k (CaBP-9k) following a single injection of EDs. In a time-dependent experiment, immature rats at postnatal day 16 were treated with high doses (600 mg/kg body weight [BW]) of 4-tert-octyphenol (OP), p-nonylphenol (NP), or bisphenol A (BPA), and euthanized at different time points (3, 6, 12, 24, or 48 h). For a dose-dependent study, immature rats were given different doses (200, 400, or 600 mg/kg BW) and euthanized at 24 h after injection. After treatment with these EDs, the effects on CaBP-9k mRNA and protein were examined by Northern and Western blot analyses, respectively. An anti-estrogen, ICI 182,780, was employed to examine the potential involvement of estrogen receptor (ER) in the induction of estrogen receptor-mediated physiologic responses in vivo. A single treatment with each of the chemicals, at 600 mg/kg BW, resulted in a significant increase in the expression of CaBP-9k mRNA and protein 24 h after injection. In addition, treatment with OP, NP, or BPA resulted in a positive uterotrophic response. Cotreatment with the ER antagonist ICI 182,780 completely prevented the ED induced uterine weight gain. Taken together, these results demonstrate that a single injection of OP, NP, or BPA results in an increase of CaBP-9k mRNA and protein via an ER-dependent pathway in the uterus of immature rats. This new model may be important to elucidate the mechanism of action of xenoestrogens on estrogen-sensitive tissue. PMID- 17365580 TI - Strategies for clean air and health. AB - An international colloquium, "Strategies for Clean Air and Health," was organized by the Network of Environmental Risk Assessment and Management (NERAM) and the AIRNET European Network on Air Pollution and Health to identify directions for air quality policy development and research priorities to improve public health. A conference statement was prepared to provide guidance from the perspective of an international group of scientists, regulators, industries, and interest groups on a path forward to improve the interface between science and clean air policy strategies to protect public health. The statement represents the main findings of two breakout group discussion sessions, supported by perspectives of keynote speakers from North America and Europe on science-policy integration and views of the delegates expressed in plenary discussions. NERAM undertook a carefully considered process to try to ensure that the statement would accurately reflect the conference discussions, including documentation of supporting comments from the proceedings and inviting delegates' comments on two draft versions of the statement. PMID- 17365581 TI - Assessing sources of PM2.5 in cities influenced by regional transport. AB - The human health effects of fine particulate matter (PM2.5) have provided impetus for the establishment of new air quality standards or guidelines in many countries. This has led to the need for information on the main sources responsible for PM2.5. In urban locations being impacted by regional-scale transport, source-receptor relationships for PM2.5 are complex and require the application of multiple receptor-based analysis methods to gain a better understanding. This approach is being followed to study the sources of PM2.5 impacting southern Ontario, Canada, and its major city of Toronto. Existing monitoring data in the region around Toronto and within Toronto itself are utilized to estimate that 30-45% of the PM2.5 is from local sources, which implies that 55-70% is transported into the area. In addition, there are locations in the city that can be shown to experience a greater impact from local sources such as motor vehicle traffic. Detailed PM2.5 chemical characterization data were collected in Toronto in order to apply two different multivariate receptor models to determine the main sources of the PM2.5. Both approaches produced similar results, indicating that motor-vehicle-related emissions, most likely of local origin, are directly responsible for about 20% of the PM2.5. Gasoline engine vehicles were found to be a greater overall contributor (13%) compared to diesel vehicles (8%). Secondary PM2.5 from coal-fired power plants continues to be a significant contributor (20-25%) and also played a role in enhancing production of secondary organic carbon mass (15%) on fine particles. Secondary fine particle nitrate was the single most important source (35%), with a large fraction of this likely related to motor vehicle emissions. Independent use of different receptor models helps provide more confidence in the source apportionment, as does comparison of results among complementary receptor-based data analysis approaches. PMID- 17365582 TI - Modeling the intraurban variability of ambient traffic pollution in Toronto, Canada. AB - The objective of this paper is to model determinants of intraurban variation in ambient concentrations of nitrogen dioxide (NO2) in Toronto, Canada, with a land use regression (LUR) model. Although researchers have conducted similar studies in Europe, this work represents the first attempt in a North American setting to characterize variation in traffic pollution through the LUR method. NO2 samples were collected over 2 wk using duplicate two-sided Ogawa passive diffusion samplers at 95 locations across Toronto. Independent variables employed in subsequent regression models as predictors of NO2 were derived by the Arc 8 geographic information system (GIS). Some 85 indicators of land use, traffic, population density, and physical geography were tested. The final regression model yielded a coefficient of determination (R2) of .69. For the traffic variables, density of 24-h traffic counts and road measures display positive associations. For the land use variables, industrial land use and counts of dwellings within 2000 m of the monitoring location were positively associated with NO2. Locations up to 1500 m downwind of major expressways had elevated NO2 levels. The results suggest that a good predictive surface can be derived for North American cities with the LUR method. The predictive maps from the LUR appear to capture small-area variation in NO2 concentrations. These small-area variations in traffic pollution are probably important to the exposure experience of the population and may detect health effects that would have gone unnoticed with other exposure estimates. PMID- 17365583 TI - Two-years of fine and ultrafine particles measurements in Rome, Italy. AB - Long-term aerosol measurements have been conducted at two sites in Rome, Italy, April 2001 through March 2003, in a traffic-oriented site, and at an urban background site, close to the city center. The main objective was to establish validated and consistent data sets of particle number concentrations (PNC) in Rome to be used for epidemiological analyses of cardiovascular health effects. Particle number concentrations were measured by a condensation particle counter (CPC 3022A, TSI). Other pollutants (PM10, PM2.5, CO, NO2, NO, NOx, O3) were simultaneously measured at the traffic-oriented site. During the study period, the mean (standard deviation) 24-h PNC values were 4.69 x 10(4) (1.99 x 10(4)) cm(-3) and 2.46 x 10(4) (1.10 x 10(4)) cm(-3), respectively, at the traffic oriented site and at the urban background site. Mean (standard deviation) 24-h mass concentration of PM2.5 was 23.1 (11.9) microg m(-3), while for PM10 it was 41.3 (17.9) microg m(-3). Higher values for all the pollutants, except ozone, were recorded during the winter period in comparison with the summer period, and a higher variability of the results was also observed during cold months. The comparison between the daily PNC measured at the two sites showed a good correlation (r = .74). CO (r = .77), NO (r = .82), and NOx (r = .83) were all highly correlated with PNC (simultaneous obs. number 576). The diurnal and seasonal pattern of PNC can be attributed to the combined effect of motor vehicle emissions and meteorological conditions. PMID- 17365584 TI - Impact of iron and steel industry and waste incinerators on human exposure to dioxins, PCBs, and heavy metals: results of a cross-sectional study in Belgium. AB - We evaluated the impact of two iron and steel plants and two municipal solid waste incinerators (MSWI) in Wallonia (Belgium) on the exposure of residents to dioxins, polychlorinated biphenyls (PCBs), and heavy metals. In total, 142 volunteers living around these facilities were recruited and compared with 63 referents from a rural area with no industrial source of pollution. Information about smoking habits, dietary habits, anthropometric characteristics, residential history, and health status was obtained from a self-administered questionnaire. The volunteers provided blood under fasting conditions in order to evaluate the body burden of dioxins (17 polychlorinated dibenzo-p-dioxins/dibenzofurans [PCDD/Fs] congeners) and PCBs. Samples of blood and urine were also taken for the determination of cadmium, mercury, and lead. After adjustment for covariates, concentrations of cadmium, mercury, and lead in urine or blood were not increased in subjects living in the vicinity of MSWIs or sinter plants by comparison with referents. Residents around the sinter plants and the MSWI located in the industrial area had concentrations of dioxins and PCBs in serum similar to that of referents. By contrast, subjects living in the vicinity of the MSWI in the rural area showed significantly higher serum levels of dioxins (geometric mean, 38 vs. 24 pg TEQ/g fat) and coplanar PCBs (geometric mean, 10.8 vs. 7.0 pg TEQ/g fat). Although age-adjusted dioxin levels in referents did not vary with local animal fat consumption, concentrations of dioxins in subjects living around the incinerators correlated positively with their intake of local animal fat, with almost a doubling in subjects with the highest fat intake. These results indicate that dioxins and coplanar PCBs emitted by MSWIs can indeed accumulate in the body of residents who regularly consume animal products of local origin. PMID- 17365585 TI - Health effects associated with exposure to ambient air pollution. AB - The World Health Organization has identified ambient air pollution as a high public health priority, based on estimates of air pollution related death and disability-adjusted life years derived in its Global Burden of Disease initiative. The NERAM Colloquium Series on Health and Air Quality was initiated to strengthen the linkage between scientists, policymakers, and other stakeholders by reviewing the current state of science, identifying policy relevant gaps and uncertainties in the scientific evidence, and proposing a path forward for research and policy to improve air quality and public health. The objective of this paper is to review the current state of science addressing the impacts of air pollution on human health. The paper is one of four background papers prepared for the 2003 NERAM/AirNet Conference on Strategies for Clean Air and Health, the third meeting in the international Colloquium Series. The review is based on the framework and findings of the U.S. National Research Committee (NRC) on Research Priorities for Airborne Particulate Matter and addresses key questions underlying air quality risk management policy decisions. PMID- 17365586 TI - Sources of uncertainty in calculating mortality and morbidity attributable to air pollution. AB - Quantifying the burden of illness and mortality from air pollution exposure relies on statistical estimates and other assumptions that have inherent uncertainties. Through an intensive study in Hamilton, Canada, this study illustrates for policymakers the sensitivity of health effect estimates to a wide range of possible uncertainties. Dose-response relationships were derived based on pooled and averaged estimates published in the scientific literature from 1997 to 2001. These estimates were applied to local air pollution, mortality, and hospital admissions data for the years 1995-1999. The data were adjusted to reflect uncertainties in the current state of knowledge, including (1) baseline pollution, (2) single versus multipollutant effects, (3) local or pooled estimates, and (4) chronic effects. The estimates of mortality ranged from 96 to 374 annual deaths, while admissions ranged from 139 to 607 respiratory and from 479 to 2000 cardiovascular admissions. Chronic fine particle exposure resulted in 232 annual deaths. As conclusions, first, there should be an effort to reach a consensus on reporting scientific findings from air pollution studies using standardized study designs and reporting formats. Second, given the sensitivity of the estimates to underlying assumptions, an immediate need exists for widely accepted burden of illness and mortality estimation conventions. Third, many areas of air pollution research require considerable refinement before complete estimates can be ascribed. PMID- 17365587 TI - Urban air pollution and respiratory emergency visits at pediatric unit, Reggio Emilia, Italy. AB - Short-term effects of air pollution on daily mortality and hospital admissions for respiratory causes are well documented. Few studies, however, explore the association between exposure to air pollution and daily emergency room visits for respiratory disorders, particularly in Italy and particularly among children as a susceptible population. A time-series analysis was conducted to explore the short term association between air pollutants (PM10, total suspended particulates [TSP], NO2, SO2, CO, O3) and pediatric emergency room (ER) visits in a small city of northern Italy, Reggio Emilia, during the period 03/01/2001-03/31/2002. There were 1051 ER visits included in the study. Data were analyzed using generalized additive models (GAM), adjusting for various confounding variables, including temperature, humidity, and pollens (Graminaceae). The analyses were also stratified according to the nationality of children (Italians and foreigners). In single-pollutant models, the strongest associations were observed at lag 3 for a 10-microg/m3 increase of TSP (2.7% increase in ER, 95% CI 0.7-4.6) and PM10 (3.0% increase, 95% CI 0.4-5.7), and at lag 4 for a 10-microg/m3 increase of NO2 (11.0% increase in ER, 95% CI 3.6-18.8). At lag 3, the percentage increase in ER visits is similar for the 2 groups of children (Italians and foreigners) for TSP and PM10. The results of the study support the findings that air pollution is a relevant determinant of deterioration of respiratory health among children. PMID- 17365588 TI - Urban air pollution and emergency visits for respiratory complaints in Pisa, Italy. AB - Emergency room visits for respiratory complaints, considered an indicator of deterioration of respiratory health, have been positively correlated to traffic related air pollution. This is an ecological study to evaluate the association between daily levels of urban air pollutants and emergency visits for respiratory complaints, in children and the elderly residing in Pisa, Italy. Daily records of emergency department visits for respiratory complaints were selected from computerized registries, and paper medical reports were identified. Pollutant daily means were computed from hourly values obtained from the public network. Poisson regression, allowing for overdispersion and autocorrelation, was used to evaluate the percent change in daily visits associated with variations of air pollution measures. Among children, an increase in emergency visits of 10% (95% CL: 2.3; 18.2) was associated with a 10-microg/m3 increase in PM10 concentrations of the previous day and an increase of 11.8% (95% CL:1.4; 23.3) was associated with an analogous increment of NO2 during the 2 previous days. Among elderly the same increment of PM10 level during the 2 previous days was correlated with a 8.5% (95% CL: 1.5; 16.1) increase in the risk of recurring emergency department visits for respiratory complaints; this risk increased to 26.5% (95% CL: 3.4; 54.8) if the daily level of CO over the 4 previous days increased by 1 mg/m3. Evidence of morbidity related to short- and long-term air pollution exposures provided in this small study and larger studies conducted in other countries suggests the need for actions to improve air quality in any urban context. PMID- 17365589 TI - Increase of exhaled nitric oxide in children exposed to low levels of ambient ozone. AB - Ozone (O3) is known to induce lung function impairment and airways inflammation during episodes of photochemical smog. The aim of the present study was to assess the inflammatory effect of ambient O3 in healthy children using nitric oxide in exhaled air (eNO) as a noninvasive test. The study was performed on 6 groups of children (n = 11-15), aged 6.5 to 15 yr, who attended summer camps in rural areas of the south of Belgium in 2002. Ambient O3 concentrations continuously monitored in the camps ranged from 48 to 221 microg/m3 (1-h maximal concentration). Children remained outdoors during the experimental days, doing various recreational activities but no sports. Lung function tests (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) and eNO were measured twice in each child in the morning and in the evening. While lung function tests did not show any consistent pattern of decrease at these O3 levels, a highly significant increase in eNO was found in all subjects from an ambient 1-h O3 level of 167 microg/m3. A multivariate analysis did not reveal any influence of age, gender, height, weight, and body mass index (BMI) of the children. The threshold for this O3-induced increase in eNO estimated benchmark dose analysis was 135 microg/m3 for 1-h exposure and 110 microg/m3 for 8-h exposure. These observations suggest that ambient ozone produces early inflammatory changes in the airways of children at levels slightly below current air quality standards. PMID- 17365590 TI - Ambient air pollution and population health: overview. AB - In November 2003 approximately 200 researchers, stakeholders, and policymakers from more than 40 countries gathered to discuss the science and policy implications of air pollution and human health as part of the AIRNET/NERAM Strategies for Clean Air and Health initiative. The purpose of this paper is to review the more than 35 research posters presented at the conference, including exposure, toxicological, and epidemiological studies of air pollution. Collectively, these papers support previous evidence that both short- and long term exposures to particulate air pollution have adverse population health impacts, including effects on children. Cellular studies also suggest that air pollution can cause mutagenic and oxidative effects, raising concerns about carcinogenicity and cellular regeneration. Studies of biomarkers, such as Clara cell proteins and lymphocyte damage assessment, provide further evidence of air pollution effects at the cellular level. Other studies have focused on improvements to measurement and sources of air pollution. These studies suggest that particle mass rather than particle composition may be a more useful indicator of potential human health risk. It is well known that emissions from transportation sources are a major contributor to ambient air pollution in large urban centres. Epidemiologic researchers are able to reduce bias due to misclassification and improve exposure assessment models by allocating air pollution exposure according to distance from traffic sources or land-use patterns. The close association between traffic patterns and air pollution concentrations provides a potential basis for the development of transport policies and regulations with population health improvements as a primary objective. The results of the research presented here present opportunities and challenges for the development of policies for improvements to air quality and human health. However, there remains the challenge of how best to achieve these reductions. PMID- 17365591 TI - Lung permeability, antioxidant status, and NO2 inhalation: a selenium supplementation study in rats. AB - Little is known about antioxidant status, selenium status in particular, and lung response to NO2, which acts as a proinflammatory air pollutant. The effects of a low selenium diet (1.3 microg Se/d) with or without selenium supplementation were therefore studied in 128 Wistar rats, 2 mo old, male exposed to either acute (50 ppm, 30 min), intermittent subacute (5 ppm, 6 h/d, 5 d), intermittent long-term NO2 (1 ppm, 10 ppm, 6 h/d, 5 d/wk, 28 d), or normal atmospheric air (controls). Following sacrifice, measurements of lipid peroxidation (thiobarbituric acid reactive substances, chemiluminescence), antioxidative protective enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD], glutathione S transferase [GST], ceruloplasmin), lung damage (lactate dehydrogenase, alkaline and acid phosphatases), lung permeability (total protein, albumin), and inflammation (cell populations), along with the determination of new biomarkers such as CC16 (Clara-cell protein), were performed in serum and bronchoalveolar lavage fluid (BALF). While selenium-supplemented animals had increased GPx activity in serum prior to inhalation experiments, they also had decreased BALF CC16, blood SOD, and GST levels. Nevertheless, the protective role of normal selenium status with respect to NO2 lung toxicity was evident both for long-term and acute exposures, as the increase in BALF total proteins and corresponding decrease in serum (indicating increased lung permeability) was significantly more pronounced in selenium-deficient animals. During the various inhalation experiments, serum CC16 demonstrated its key role as an early marker of increased lung permeability. These findings corroborate the important role of selenium status in NO2 oxidative damage modulation, but also indicate, in view of its negative impact on CC16, a natural anti-inflammatory and immunosuppressor, that caution should be used prior to advocating selenium supplementation. PMID- 17365592 TI - Air quality modeling for policy development. AB - Atmospheric models constitute the best tools available for the setting of policy, and may, in some cases, be the only tools that are available. The best examples of their kind bring together all current knowledge of pollutant behavior in the atmosphere, making it possible to unravel the often complex interactions between pollutants and atmospheric dynamics. They also allow the possibility of evaluating hypothetical changes in emissions and other conditions to evaluate potential abatement strategies, or to assess the impact of proposed new emission sources. This paper provides an overview of mathematical atmospheric models and their application to the development of air quality policy. The paper discusses the types of atmospheric models currently in use, categorized by spatial scale, and the requirements for credible modeling. Issues associated with model validity and accuracy are described and case studies are reviewed to illustrate atmospheric model use in policy development and the need for careful analysis in interpreting model predictions. PMID- 17365593 TI - Bayesian model averaging in time-series studies of air pollution and mortality. AB - The issue of model selection in time-series studies assessing the acute health effects from short-term exposure to ambient air pollutants has received increased scrutiny in the past 5 yr. Recently, Bayesian model averaging (BMA) has been applied to allow for uncertainty about model form in assessing the association between mortality and ambient air pollution. While BMA has the potential to allow for such uncertainties in risk estimates, Bayesian approaches in general and BMA in particular are not panaceas for model selection., Since misapplication of Bayesian methods can lead to erroneous conclusions, model selection should be informed by substantive knowledge about the environmental health processes influencing the outcome. This paper examines recent attempts to use BMA in air pollution studies to illustrate the potential benefits and limitations of the method. PMID- 17365594 TI - Improving policy responses to the risk of air pollution. AB - This paper offers a brief review of the need for cost-benefit analysis (CBA) and the available policy instruments for air pollution. To prioritize different possible actions, one needs to know which source of pollution causes how much damage. This requires an impact pathway analysis, that is, an analysis of the chain emission --> dispersion --> dose-response function --> monetary valuation. The methodology for this is described and illustrated with the results of the ExternE (External Costs of Energy) project series of the European Commission. Two examples of an application to CBA are shown: one where a proposed reduction of emission limits is justified, and one where it is not. It is advisable to subject any proposed regulation to a CBA, including an analysis of the uncertainties. Even if the uncertainties are large and a policy decision may have to take other considerations into account, a well-documented CBA clarifies the issues and provides a basis for rational discussion. One of the main sources of uncertainty lies in the monetary valuation of premature mortality, the dominant contribution to the damage cost of air pollution. As an alternative, an innovative policy tool is described, the Life Quality Index (LQI), a compound indicator comprising societal wealth and life expectancy. It is applied to the Canada-wide standards for particulate matter and ozone. Regardless of monetary valuation, a 50% reduction of PM10 concentrations in Europe and North America has been shown to yield a population-average life expectancy increase on the order of 4 to 5 mo. PMID- 17365595 TI - Analysis of PM2.5 using the Environmental Benefits Mapping and Analysis Program (BenMAP). AB - As epidemiological work from around the world continues to tie PM2.5 to serious adverse health effects, including premature mortality, the U.S. Environmental Protection Agency (U.S. EPA) has developed a number of policies to reduce air pollution, including PM2.5. To assist in the benefit-cost analyses of these air pollution control policies, the U.S. EPA has developed the Environmental Benefits Mapping and Analysis Program (BenMAP). BenMAP is meant to (1) provide a flexible tool for systematically analyzing impacts of changes in environmental quality in a timely fashion, (2) ensure that stakeholders can understand the assumptions underlying the analysis, and (3) adequately address uncertainty and variability. BenMAP uses a "damage-function" approach to estimate the health benefits of a change in air quality. The major components of the damage-function approach are population estimates, population exposure, adverse health effects, and economic costs. To demonstrate BenMAP's ability to analyze PM2.5 pollution control policy scenarios, we assess two sample applications: (1) benefits of a national-level air quality control program, and (2) benefits of attaining two annual PM2.5 standards in California (annual average standards of 15 microg/m3 and 12 microg/m3). In the former, we estimate a scenario where control of PM2.5 emissions results in $100 billion of benefits annually. In the analysis of alternative standards, we estimate that attaining the more stringent standard (12 microg/m3) would result in approximately 2000 fewer premature deaths each year than the 15 microg/m3 achieves. BenMAP has a number of features to help clarify the analysis process. It allows the user to record in a configuration all of the choices made during an analysis. Configurations are especially useful for recreating already existing policy analyses. Also, BenMAP has a number of reporting options, including a set of mapping tools that allows users to visually inspect their inputs and results. PMID- 17365596 TI - Air quality improvements using European environment policies: a case study of SO2 in a coastal region in Portugal. AB - The European Union (EU) has defined several efforts for preventing and controlling air pollution that have led to a generalized reduction of health risks and environmental effects. One example of these efforts was the establishment of legislation that imposed a reduction of sulfur content in fuels, switching to cleaner fuels for industry and motor vehicles (Auto-Oil Directives). The goal of this study was to evaluate the first trends in the air quality of Oporto Metropolitan Area (Oporto-MA) related to implementation of these directives in Portugal since 2000. Therefore, sulfur dioxide (SO2) concentration data from air quality monitoring sites were analyzed for the period 1999 through 2003. It was observed that daily SO2 concentrations in the industrial area are much higher than those of the urban and rural areas, reflecting the influence of the industrial sector. The annual SO2 concentrations for the consecutive years of analysis decreased considerably for all the monitoring sites. A considerable decrease in SO2 emissions was also observed for the same period. According to EU legislation, the exceedances of the SO2 recommended limit values decreased significantly. In conclusion, this analysis shows evidence that SO2 concentrations are decreasing, and that this is consistent with the implementation of the legislation and control of the sources of pollution. Nevertheless, the potential for human health risks still persists, particularly in industrialized areas. It is expected that SO2 concentration levels in ambient air of Oporto-MA will continue to decrease in the coming years, following the present European trends. PMID- 17365597 TI - Developing risk-based priorities for reducing air pollution in urban settings in Ukraine. AB - Ukraine, when part of the former Soviet Union, was responsible for about 25% of its overall industrial production. This aging industrial infrastructure continues to emit enormous volumes of air and water pollution and wastes. The National Report on the State of Environment in Ukraine 1999 (Ukraine Ministry of Environmental Protection [MEP], 2000) shows significant air pollution. There are numerous emissions that have been associated with developmental effects, chronic long-term health effects, and cancer. Ukraine also has been identified as a major source of transboundary air pollution for the eastern Mediterranean region. Ukraine's Environment Ministry is not currently able to strategically target high priority emissions and lacks the resources to address all these problems. For these reasons, the U.S. Environmental Protection Agency set up a partnership with Ukraine's Ministry of Environmental Protection to strengthen its capacity to set environmental priorities through the use of comparative environmental risk assessment and economic analysis--the Capacity Building Project. The project is also addressing improvements in the efficiency and effectiveness of the use of its National Environmental Protection Fund. The project consists of a series of workshops with Ukrainian MEP officials in comparative risk assessment of air pollutant emissions in several heavily industrialized oblasts; cost-benefit and cost-effectiveness analysis; and environmental finance. Pilot risk assessment analyses have been completed. At the end of the Capacity Building Project it is expected that the use of the National Environmental Protection fund and the regional level oblast environmental protection funds will begin to target and identify the highest health and environmental risk emissions. PMID- 17365598 TI - Health impact assessment of PM10 exposure in the city of Caen, France. AB - Air pollution in Caen, a city in northwestern France, comes mainly from motor vehicles. The aim of this study was to assess the public health impact of both acute (with immediate or short-term effects) and chronic (with long-term effects) exposure to PM10 (particulate matter <10 microm). The standard World Health Organization (WHO) methodology for a health impact assessment (HIA) was used to calculate the attributable deaths and hospital admissions. Population exposure was estimated from PM10 concentrations collected by the local air quality measurement network. The relative risks were modeled with exposure-risk functions established in epidemiologic studies in the general population. The APHEA-2 program, which combines European time-series studies, was used to assess effects from acute exposures and a meta-risk was calculated from cohort studies to assess the effects of chronic exposure. The health impact of chronic exposure from 1998 through 2002 was estimated at 168 (101-238) deaths. Acute exposure (relative to a baseline level of 10 microg/m3) led to 26 (17-35) deaths and 43 (22-67) hospital admissions during this period. A 10% daily decrease in pollution would reduce the number of expected deaths from short-term exposure by 19%, while achieving compliance with European Union regulations (daily mean in 2010: 50 microg/m3) would reduce them by less than 3%. Because the health impact of the pollution in Caen is due mainly to relatively moderate levels, reducing everyday pollution levels through long-term regulation would be more beneficial than avoiding pollution peaks. PMID- 17365599 TI - Fine particles: from scientific uncertainty to policy strategy. AB - Gaps in our knowledge should not be a reason for not making policy decisions. How can we define robust policy strategies, given the various uncertainties in the sources, exposure, and causes of health effects? Which uncertainties are most important? What are its policy implications? This contribution will describe policy strategies for particulate matter (PM) abatement that are consistent with certain sets of assumptions, as well as the risks that are associated with such strategies. What is an optimal strategy assuming that the fine particles (PM2.5) are the main cause of health effects? And what would be the "mistake" of such a strategy, if "in the end" PM10 or carbonaceous particles prove to be the "real" cause? How can we make the policy strategy more robust and minimise its financial risks and health risks? This contribution describes a systematic way of dealing with the knowledge gaps in the policy process. PMID- 17365600 TI - Clean air strategies: an environmental nongovernmental organization perspective on the science-policy interface. AB - Environmental nongovernment organisations (ENGOs) in Europe have been hardly involved in AIRNET, in part because the technicalities deter access. However, ENGOs should be seen as representing the public as well as acting as stakeholders in their own right. ENGOs can be intimately involved in assessing the public information, as in the UK example criticized here, and can spotlight an issue like ultrafine particulate pollution that is being avoided for reasons of institutional inertia and special interests. For risk analysis and integrating a precautionary approach, ENGO participation within a stakeholder process is vital. Policies designed to combat air pollutants have to change profoundly how people live, travel, and work (Maynard et al., 2003), yet policymakers tend to duck the hard choices. Winning the public to make such changes requires enrolling the major campaigning ENGOs as allies, in the context of effective stakeholder communication and accountability in public information and policy setting. PMID- 17365601 TI - Closing the gap between science and policy on air pollution and health. AB - This paper discusses critical issues underlying the interface between air quality science, stakeholder participation, and policy development within the context of the European AIRNET Network multistakeholder project. The paper argues that it is not only the content of air pollution and health issues that stakeholders consider important, but also the process and mechanisms by which the interface operates. A visual representation of the interaction between science, society, and stakeholders in the development, dissemination, and evaluation of effective air quality policy strategies is provided. The paper discusses the role of AIRNET in supporting the Clean Air for Europe (CAFE) program and assesses the AIRNET experience in establishing a network to bridge the gap between air quality policy, stakeholders, the public, and scientific communities. PMID- 17365602 TI - A survey methodology for collecting fish consumption data in urban and industrial water bodies (part 1). AB - The potential human health risks associated with consuming fish containing hazardous substances are related to the frequency, duration, and magnitude of exposure. Because these risk factors are often site specific, they require site specific data. In anticipation of performing a risk assessment of the lower 6 miles of the Passaic River in New Jersey (Study Area), a year-long creel/angler survey collected such site-specific data. The lower Passaic River is urbanized and industrialized, and its site conditions present unique survey design and sampling challenges. For example, the combined population of the municipalities surrounding the Study Area is nearly 330,000, but because the Study Area is tidal, state law does not require fishing licenses for anglers to fish or crab in the Study Area. The sampling challenges posed by the lack of licensing are exacerbated by the industrialization and lack of public access in the lower half of the Study Area. This article presents a survey methodology designed to overcome these challenges to provide data for accurately estimating the Study Area's angling population and the fish and crabs they catch, keep, and eat. In addition to addressing the challenges posed by an urban and industrial setting, the survey methodology also addresses the issues of coverage, avidity, and deterrence, issues necessary for collecting a representative sample of the Study Area's anglers. This article is a companion to two other articles. The first companion article describes the analytical methodology designed to process the data collected during the survey. The second presents, validates, and interprets the survey results relating to human exposure factors for the lower Passaic River. PMID- 17365603 TI - A statistical method for analyzing data collected by a creel/angler survey (part 2). AB - This article describes a unique analytical method employed to characterize angler activities on the lower 6-mile stretch of the Passaic River in New Jersey. The method used data collected by a creel/angler survey that was designed to capture the information necessary to calculate the exposure factors needed to characterize the fish consumption pathway for recreational anglers in a human health risk assessment for the river. The survey used two methods to address the challenges of conducting a creel/angler survey in an urban and industrial setting with limited river access. While unique, the analytical method described in this article is based upon accepted methods of interpreting survey data and basic laws of probability. This article was written as a companion to two other articles, also in this issue and cited here, of which one describes in detail the survey methodology designed for the lower Passaic River creel/angler survey to meet various challenges unique to conducting such a survey in urban and industrialized rivers, and the other presents, validates, and interprets the results of the lower Passaic River work relating to human exposure factors using the methodology described in this article. PMID- 17365604 TI - Human health exposure factor estimates based upon a creel/angler survey of the lower Passaic River (part 3). AB - The results of an analysis of site-specific creel and angler information collected for the lower 6 miles of the Passaic River in Newark, NJ (Study Area), demonstrate that performing a site-specific creel/angler survey was essential to capture the unique characteristics of the anglers using the Study Area. The results presented were developed using a unique methodology for calculating site specific, human exposure estimates from data collected in this unique urban/industrial setting. The site-specific human exposure factors calculated and presented include (1) size of angler population and fish-consuming population, (2) annual fish consumption rate, (3) duration of anglers' fishing careers, (4) cooking methods for the fish consumed, and (5) demographic information. Sensitivity and validation analyses were performed, and results were found to be useful for performing a site-specific, human health risk assessment. It was also concluded that site-specific exposure factor values are preferable to less representative "default values." The results of the analysis showed that the size of the angling population at the Study Area is estimated to range from 154 to 385 anglers, based on different methods of matching intercepts with anglers. Thirty four anglers were estimated to have consumed fish; 37 people consumed fish from the river. The fish consumption rate for anglers using this area was best represented as 0.42 g/day for the central tendency and 1.8 g/day for the 95th percentile estimates. Anglers fishing at the river have relatively short fishing careers with a median of 0.9 yr, an average of 1.5 yr, and a 95th percentile of 4.8 yr. Consuming anglers tend to fry the fish they caught. The demographics of anglers who consume fish do not appear to differ substantially from those who do not, with no indication of a subsistence angling population. PMID- 17365605 TI - Dermal exposure to beryllium: a pilot case study. AB - The issue of dermal absorption of beryllium (Be) particles through intact healthy skin has not yet been demonstrated. The interest in Be dermal exposure as a potential pathway for toxic effects was emphasized in Quebec (Canada) when a recycling industry processing spent pot lining (SPL) related to the aluminum industry was recently requested by health authorities to conduct a Be particle size study and to provide a Tyvek coverall for full skin protection of workers. This study aimed to (1) calculate the dermal and inhalation exposures and (2) apply the results to the case study of a recycling SPL industry. Airborne dust was sampled in order to determine Be particles size. Exposure assessment via the skin and the respiratory routes was measured over a working day using standard calculations. The assessment of workers' clothing protection was obtained by swiping the skin on the forearm and upper front leg before and after exposure. Respirable Be (0.044 microg) was 23% of the total Be (0.19 microg). Be particles with a median mass aerodynamic diameter (MMAD) of 0.93 and below totaled 0.0103 microg (5% of BeT). The daily dose for the respiratory route was calculated to be 0.022 microg/kg/d, while the daily doses for the dermal route varied between 0.027 x 10(-7) microg/kg/d and 0.025 x 10(-3) microg/kg/d. After exposure, no Be was found on the skin of workers wearing a cotton coverall protection. When using a polyester coverall, minor amounts of Be were found. These results showed that dermal daily dose exposure is negligible. However, note that the case study did not involve handling of contaminated items by the workers, which lead to significant dermal exposure if care is not taken. Although daily dermal exposure may be small, because of uncertainties, a precautionary principle should be applied in an active sense. PMID- 17365606 TI - Oxycodone abuse in Texas, 1998-2004. AB - Oxycodone is frequently abused, and this abuse appears to be increasing. The purpose of this study was to describe the patterns of oxycodone abuse identified by Texas poison control centers. All oxycodone calls received by Texas poison control centers during 1998-2004 were identified. Annual trends and geographic distributions were determined for drug identification (ID) calls and abuse calls. The distribution of abuse calls was then compared to the distribution of all other types of human exposure calls for a variety of factors. Both drug ID and abuse calls involving oxycodone increased over the 7-yr period. The numbers of abuse calls were higher than expected in the central part of Texas, while drug ID calls were higher than expected in eastern and central Texas. A higher proportion of oxycodone abuse than other types of oxycodone exposures involved males, adolescents, exposures at other residences and public areas, referral by the poison control center to a health care facility, and some sort of clinical effect. Oxycodone abuse calls in Texas are increasing. The proportion of calls varies by geographic region. Oxycodone abuse calls differ from other types of exposures with respect to both demographic factors and clinical management and outcome. PMID- 17365607 TI - Primary intracerebral hemorrhage mortality reduction after installation of a tap water supply system in an arseniasis-endemic area in southwestern Taiwan. AB - Mortality and morbidity of vascular diseases, including stroke, are known to be associated with chronic exposure to inorganic arsenic through drinking water. A tap-water supply system was implemented in the early 1960s in the blackfoot disease (BFD) endemic areas of Taiwan. The objective of this study was to examine whether mortality attributed to stroke decreased among residents living in the BFD-endemic areas after the curtailment of arsenic exposure. Further it was of interest to determine whether arsenic exposure was related to a specific type of stroke. Standardized mortality ratios (SMRs) for stroke were calculated for the BFD endemic area for the years 1971-2000. The study results show that mortality due to primary intracerebral hemorrhage (PIH) declined gradually after the improvement of drinking-water supply system by elimination of arsenic exposure through removal of artesian well water. Based on the reversibility and specificity criteria, the association between arsenic exposure and mortality due to PIH is likely to be causal. PMID- 17365608 TI - Effects of in ovo exposure to PCBs 126 and 77 on mortality, deformities and post hatch immune function in chickens. AB - In laboratory experiments, planar PCBs produce immune organ atrophy in chicken embryos. To study the immunotoxic effects of PCBs in birds, the coplanar congeners 3,3',4,4',5-pentachlorobiphenyl (PCB 126) and 3,3',4,4' tetrachlorobiphenyl (PCB 77) were injected into the air cell of fertile white leghorn chicken eggs before incubation at doses of 0.25 and 0.5 ng/g egg PCB 126 and 0.64 ng/g egg PCB 77. Mortality and deformities were assessed during incubation of the eggs, and immune function was analyzed post-hatch using phytohemagglutinin (PHA) skin test for T-cell mediated immunity, antibody titers to sheep red blood cells (SRBC), mitogenesis of peripheral blood lymphocytes, and immune organ mass and cellularity. Exposure to 0.25 ng/g PCB 126 elevated mortality (61% and 69%) and deformities (31% and 32%), three or more times higher than controls. Two-fold suppression of antibody titers was observed in 28 day old chicks exposed to PCB 126 or PCB 77. No consistent alterations in PHA skin response or lymphocyte proliferation were observed. In 14 day old chicks in experiment two, PCB 126 decreased thymus and bursa cellularity by 33% and 35%, respectively. Immune organ atrophy was transient, recovering to control levels by 42 days of age. These experiments demonstrate that PCB 126 and 77 suppress antibody responses in juvenile chickens following an in ovo PCB exposure. Results reinforce the need for measuring multiple immune endpoints to detect immunotoxicity. PMID- 17365609 TI - Toward understanding the influence of soil metals and sulfate content on plant thiols. AB - Plants respond to increased concentrations of metals by a number of mechanisms, including chelation with phytochelatins (PCs). Soil specimens and plants (Veronica anagalis-aquatica, Typha domingensis, Cynodon dactylon, Chenopodium album, Rumex dentatus, Amaranthus gracilis, Chenopodium murale, Inula viscosa) leaves were collected from two sites in northern Jordan and subsequently metals (cadmium, copper, and lead), sulfate, and PC (from leaves) levels were determined. One of these sites was contaminated with metals and the other served as a control site. The contaminated site had elevated cadmium, copper, lead, and sulfate levels. This increase of metal and sulfate levels in the soil at the contaminated site correlated with a rise in plant total glutathione (GSH(T)) and cysteine (CYS(T)). These increases were not attributed to an elevation in total phytochelatin levels. However, a significant increase in the ratio of short-chain phytochelatins to the total phytochelatin stores was observed. The individual effects of metals and sulfate on glutathione, short-chain PCs and long-chain PCs levels were dissimilar. PMID- 17365610 TI - Oleandrin produces changes in intracellular calcium levels in isolated cardiomyocytes: a real-time fluorescence imaging study comparing adult to neonatal cardiomyocytes. AB - Oleanders are common, hardy shrubs that grow throughout the southern United States. They contain cardiotonic steroids formed from cardenolides and bufadienolides, making the plant poisonous to both animals and humans. Aliquots of both commercially available oleander and fresh oleander extracts were prepared. Fresh, rod-like, calcium-tolerant adult rat cardiomyocytes and cultured neonatal cardiomyocytes were isolated and treated with 0-4 ng/ml of both preparations, challenged with verapamil and ouabain, and real-time spectrophotometric calcium transients and images were acquired. A number of effects were observed with the adult cells: (1) intracellular calcium levels were increased in a concentration-dependent manner: (2) reduced calcium transient heights and eventual cessation of beating resulted; and (3) increased sparking intensity led to subsequent beating and eventual calcium overload. In the spontaneously beating cultured neonatal myocytes increased intramyocytic calcium levels were also seen, with retention of this calcium rise leading to overload and, as in the adult myocytes, cessation of beating. These observations demonstrate that oleander extract is markedly potent with respect to the elevation of calcium concentrations in cardiomyocytes, and that the inability of the cardiomyocytes to release the accumulated calcium possibly indicates a role for oleandrin in inhibition of ryanodine receptor calcium release channels, calcium uptake via Na+,K+-ATPase inhibition [EC 3.6.1.3], and/or dysfunction of sarcolemmal calcium release channels. PMID- 17365611 TI - Cadmium induces apoptosis in the human osteoblast-like cell line Saos-2. AB - Human exposure to the heavy metal cadmium has been associated with the development of bone diseases, including osteoporosis and osteomalacia. The mechanisms by which cadmium exerts a direct effect on bone remain unclear. Bone cells go through apoptosis for proper bone remodeling; therefore, it was hypothesized that cadmium disrupts this normal balance by inducing apoptosis. Human osteoblast-like cells (Saos-2) were treated with 10-200 muM cadmium chloride (CdCl2) and evaluated by trypan blue staining and phase-contrast microscopy. Exposure to CdCl2 resulted in decreased cell viability and changes in cell morphology characteristic of apoptosis. The role of apoptosis in cadmium induced toxicity was further evaluated using the fluorescent marker annexin V, which detects externalization of cell membrane phosphatidylserine. Nuclear changes associated with apoptosis were assessed by Hoechst staining and a DNA fragmentation assay. A significant increase in annexin V-positive cells was observed following CdCl2 treatment. Nuclear changes associated with apoptosis, including marginalization and condensing of chromatin and DNA fragmentation, were also observed following CdCl2 treatment. Cadmium-induced apoptosis in Saos-2 cells was also accompanied by an increase in caspase-3 activity. The addition of the caspase-3 inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) or the known cadmium chelating agent potassium bis(2-hydroxyethy)dithiocarbamate, (K[bhedtc]), blocked caspase-3 activation induced by cadmium. Collectively, this study has identified a role for apoptosis in cadmium-induced toxicity in bone cells, and provides insight for future studies on mechanisms underlying the disruption of apoptotic signaling cascades in bone and the relationship to bone disease. PMID- 17365612 TI - Disposition of orally and intravenously administered methyltetrahydrofuran in rats and mice. AB - The disposition of [14C]methyltetrahydrofuran (14C-MTHF) in rats and mice was determined by following changes in the radioactivity in tissue and excreta with time after dosing. MTHF administered orally (1, 10, or 100 mg/kg) or intravenously (1 mg/kg) to either rats or mice was rapidly metabolized and excreted with <8% (mice) or 8-22% (rats) of the dose remaining in the body after 24 h (1 and 10 mg/kg doses) or 72 h (100 mg/kg dose). Based on recovery of radioactivity in excreta (other than feces) and tissues (other than the gastrointestinal [GI] tract), absorption of orally administered MTHF was essentially complete (93-100%). There were no overt signs of toxicity observed at any dose studied. The major route of excretion in mice was in urine followed by exhaled CO2. In rats the major route of excretion was exhaled CO2 followed by urinary excretion. The excretion of exhaled volatile organic compounds (VOC) was dose-dependent in both species; at lower doses exhaled VOC represented 1-5% of dose, but at the highest dose (100 mg/kg) this proportion rose to 14% (mice) and 27% (rats). Analysis of the VOCs exhaled at the high dose indicated that the increase was due to exhalation of the parent compound, 14C-MTHF. Analysis of urine showed three highly polar peaks in the mouse urine and two polar peaks in the rat urine. Because the 14C label in MTHF was in the methyl group, the polar metabolites were considered likely due to the one-carbon unit getting into the metabolic pool and labeling intermediate dietary metabolites. PMID- 17365613 TI - Adequacy and consistency of animal studies to evaluate the neurotoxicity of chronic low-level manganese exposure in humans. AB - The adequacy of existing animal studies to understand the effects of chronic low level manganese exposures in humans is unclear. Here, a collection of subchronic to chronic rodent and nonhuman primate studies was evaluated to determine whether there is a consistent dose-response relationship among studies, whether there is a progression of effects with increasing dose, and whether these studies are adequate for evaluating the neurotoxicity of chronic low-level manganese exposures in humans. Neurochemical and behavioral effects were compared along the axis of estimated internal cumulative manganese dose, independent of the route of exposure. In rodents, motor effects emerged at cumulative doses below those where occupationally exposed humans start to show motor deficits. The main neurochemical effects in rodents were an increase in striatal gamma-aminobutyric acid (GABA) concentration throughout the internal cumulative dose range of 18 to 5300 mg Mn/kg but a variable effect on striatal dopamine concentration emerging at internal cumulative doses above approximately 200 mg Mn/kg. Monkey studies showed motor deficits and effects on the globus pallidus at relatively low doses and consistent harmful effects on both the globus pallidus and the caudate and putamen at higher doses (> 260 mg Mn/kg). Internal cumulative manganese doses of animal studies extend more than two orders of magnitude (< 1 to 5300 mg Mn/kg) above the doses at which occupationally exposed humans show neurological dysfunction (10-15 mg Mn/kg). Since the animal data indicate that manganese neurotoxicity may be different at low compared to elevated exposures, most existing animal model studies might be of limited relevance for the risk assessment of chronic low-level manganese exposure to humans. PMID- 17365614 TI - Alteration of brain and interrenal StAR protein, P450scc, and Cyp11beta mRNA levels in atlantic salmon after nominal waterborne exposure to the synthetic pharmaceutical estrogen ethynylestradiol. AB - Pharmaceuticals are ubiquitous pollutants in the aquatic environment, where their potential effects on nontarget species like fish has only recently become subject of systematic investigations. Recently, it was shown that the documented xenoestrogen nonylphenol produced variations in brain steroidogenic acute regulatory (StAR) protein, cytochrome P-450-mediated cholesterol side-chain cleavage (P450scc), and cytochrome P-45011beta hydroxylase (CYP11beta) gene transcripts of exposed juvenile salmon (Arukwe, 2005). In the present study, experiments were undertaken to examine the effect of the synthetic pharmaceutical endocrine disruptor ethynylestradiol (EE2), given in water at 5 or 50 ng/L and sampled at d 0 (control), 3, and 7 after exposure, on these key and rate-limiting brain and interrenal steroidogenic pathways of juvenile salmon using quantitative (real-time) polymerase chain reaction (qPCR). Our data, which are based on nominal exposure concentrations, show that brain and head kidney StAR and P450scc expression were modulated by EE2 in a time- and concentration-specific manner. While the StAR protein and P450scc showed EE2 concentration-dependent transcriptional increases in the brain and head kidney at d 3 after exposure, no significant effect was observed at d 7. The EE2 induced effects at d 7 were underscored because the carrier solvent (dimethyl sulfoxide, DMSO) produced significant induction of the StAR protein and P450scc in both the brain and head kidney at d 7 compared to d 3 postexposure. CYP11beta transcript was detected in the brain and head kidney, where the expression patterns were modulated by EE2 in a concentration-and time-specific manner. In the brain, DMSO produced significant changes in the CYP11beta gene expression at d 7 compared to d 3 after exposure. These changes in the levels of StAR, P450scc, and CYP11beta mRNA levels in important steroidogenic organs suggest that the experimental animals are experiencing a time-dependent impaired steroidogenesis. Thus, the StAR protein, P450scc, and CYP11beta might represent sensitive diagnostic tools for short-term and acute exposure to endocrine disrupting chemicals. In view of the present study and high concentrations of EE2 reported in effluents and surface waters from Europe and the United States, pharmaceuticals in the environment represent potentially more serious health concern both to humans and wildlife than earlier anticipated. PMID- 17365615 TI - Effects of short-term exposure to the DDT metabolite p,p'-DDE on bone tissue in male common frog (Rana temporaria). AB - Experimental studies as well as studies in free-ranging animals have shown that endocrine-disrupting chemicals (EDCs) impair bone tissue composition and strength. The aim of the present study was to expand our studies on bone tissue in a new group of animals by investigating whether bone tissue in frogs is an additional potential target of EDCs. Adult male European common frogs (Rana temporaria) were divided into 5 groups (n = 20) and injected (sc, single injection) with p,p'-DDE, a total dose of 0.01, 0.1, 1, or 10 mg of p,p'-DDE/kg body weight, respectively. A control group was treated with the vehicle (corn oil). Two weeks after injection the frogs were euthanized and samples taken. The diaphysis of the excised left femur was scanned using peripheral quantitative computed tomography (pQCT) and cortical variables, such as cortical bone mineral density (BMD), cortical cross-sectional area (CSA), and periosteal circumference, were determined. In addition, biomechanical three-point bending of the bones was conducted, with the load being applied to the same point as where the pQCT measurement was performed. The results from the pQCT measurements show that bone tissue in male frogs exposed to p,p'-DDE is negatively affected. A significant decrease in cortical BMD at the diaphysis was observed in frogs exposed to 1 mg p,p'-DDE. However, the biomechanical testing of the bones showed no significant differences between exposed and control group. Although this is the only study performed to date examining the possible relationships between EDCs and negative effects on frog bones, it supports both previous experimental findings in rodents and findings in free-ranging animals. PMID- 17365616 TI - Tissue distribution and oral dose effects of microcystin in the freshwater pulmonate snail Lymnaea stagnalis jugularis (Say). AB - Microcystin (MC) concentrations were measured in the alimentary tract, digestive gland, and remaining visceral mass of adult pulmonate snails (Lymnaea stagnalis) exposed to cyanobacteria known to contain MC. The highest proportion of total body MC content was measured within the alimentary tract (83%), though an appreciable proportion (17%) was also found within the digestive gland tissue. This provides conclusive evidence for the limited digestion of toxic cyanobacteria and subsequent uptake and accumulation of MC by the digestive gland of L. stagnalis. Additionally, pure microcystin-LR was orally administered to adult L. stagnalis to investigate the potential for toxic effects. Exposure to microcystin-LR induced histopathological alterations of the digestive glands consistent with those reported elsewhere for mammals and fish, indicating a common mode of toxicity to both vertebrates and invertebrates. PMID- 17365617 TI - Estimating risk during showering exposure to VOCs of workers in a metal degreasing facility. AB - The incremental risk of workers in a metal-degreasing facility exposed to volatile organic compounds (VOCs) present in the water supply during showering was estimated. A probabilistic and worst-case approach using specific-site concentration data and a generalized multipathway exposure model was applied. Estimates of hazard index and lifetime cancer risk were analyzed for each chemical and each route of exposure (inhalation and dermal absorption). The results showed that dermal exposure to trichloroethylene (TCE) and tetrachloroethylene (perchloroethylene, PCE) represented the main contribution to total risk. Although the inhalation route did not produce significant exposure, it was mainly influenced by the liquid flow rate of the shower. Lower values of this parameter during showering resulted in a significant reduction of both carcinogenic and noncarcinogenic risk, while decreasing water temperature produced a minimal effect on exposure by this pathway. The results obtained in the present study indicated that significant exposures of workers may be produced during showering in metal degreasing installations where releases to water of VOCs occur. A sensitivity analysis was developed for investigating the effect of scenario parameters on exposure. Although site-specific data were employed, the exposure of workers was assessed in a model scenario and thus the quantification of risk is associated with uncertainty. Considering that occupational exposure to organic solvents of workers in metal-degreasing facilities may also be significant, risk assessment must be included in the planning of this kind of industrial installation. PMID- 17365618 TI - Antinuclear antibodies and bromoxynil exposure in a rural sample. AB - Previous research suggests that farmers may have an increased risk of developing autoimmunity and that exposure to certain pesticides may alter immune function. Little is known, however, about the immunologic effects of farming and pesticide exposures. As part of the Prairie Ecosystem Study, associations between detection of antinuclear antibodies (ANA), an autoimmunity indicator, and exposure to the herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) were investigated in a cross-sectional study of 208 residents (94 women, 114 men) of a cereal-producing region in Saskatchewan, Canada, during spring herbicide application, 1996. The ANA were assayed in serum by indirect immunofluorescence on HEp-2 cells. Bromoxynil was measured in plasma by gas chromatography/mass spectrometry analysis. Associations were explored between ANA detection and detection of bromoxynil in plasma, self-reported use of bromoxynil and other pesticides, farming exposures, gender, age, body mass index (BMI), and residency. The mean age (SD) of the participants was 50.8 (13.6) yr [women: 49.7 (13.5) yr, men: 51.6 (13.6) yr]. ANA prevalence was 37.5% (women: 39.4%, men: 36%,) at 1:40 serum dilution, 17.3% (women: 20.2%, men: 14.9%) at 1:80, and 10.1% (women: 13.8%, men: 7%) at 1:160. In the multiple-variable Generalized Estimating Equation (GEE) logistic regression analyses, female gender was a positive predictor of ANA detection and gender differences were observed in the relative importance of other study factors. None of the variables examined in the multiple-variable GEE analysis were statistically significant predictors of ANA detection for women. For many of these variables, however, the point estimates for women are similar to those seen in men. For men, with adjustment for age, ANA presence was inversely associated with detection of concentrations of bromoxynil in winter or spring samples and recent occupational use of 2,4-dichlorophenoxyacetic acid, and the positive ANA predictors included having a BMI in the obese (BMI > 30.04 kg/m2) category, recent occupational use of trifluralin or fungicides, and current exposure to oilseed, poultry, or dairy production. The inverse association between ANA detection and bromoxynil exposure observed in farmers in this study is consistent with earlier empirical observations that certain pesticides may suppress immune function. Further research is needed to examine whether these findings are confirmed in other populations and to elucidate the biological mechanisms involved. PMID- 17365619 TI - Adderall abuse in Texas, 1998-2004. AB - Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and is subject to abuse. This study describes the patterns of Adderall abuse calls received by several poison control centers in Texas during 1998-2004. Drug abuse calls were assessed by call year and geographic location. Drug abuse calls were then compared to all other human exposure (nonabuse) calls with respect to various factors. Of all Adderall exposure calls, 12% involved abuse. The number of drug abuse calls received per year increased during the first part of 7-yr period but then declined. Male patients accounted for almost 60% of both drug abuse and nonabuse calls. Adolescent patients comprised 69% of drug abuse calls and children less than 13 yr old comprised 66% of nonabuse calls. Although the majority of both types of human exposures occurred at the patient's own residence, drug abuse calls were more likely than nonabuse calls to involve exposures at another residence (6% vs. 3%), school (22% vs. 5%) and public areas (2% vs. 0.4%). Drug abuse calls were less likely than nonabuse calls to be managed outside of a health care facility (18% vs. 51%) and to be classified as no adverse effect (23% vs. 48%). Adderall abusers are more likely to be adolescents. Adderall abuse as compared to other exposures is more likely to occur outside of the person's home and involve more serious medical outcomes. PMID- 17365620 TI - Methods for bias reduction in time-series studies of particulate matter air pollution and mortality. AB - In many cities of the United States, measurements of ambient particulate matter air pollution (PM) are available only every sixth day. Time-series studies conducted in these cities that investigate the relationship between mortality and PM are restricted to using a single day's PM as the measure of PM exposure, rather than using measurements taken over several consecutive days. Studies showed that using a single-day PM as the measure of PM exposure can result in estimates that have a negative bias, sometimes in the order of over half of the value being estimated. In this article two methods are introduced that can be used to obtain estimates that can in some situations reduce the bias to negligible proportions when only every-sixth-day PM concentrations are available. Using one of these methods, the national average PM mortality effect estimates obtained for total mortality and cardiovascular and respiratory mortality, respectively, correspond to 0.27% and 0.39% increases in mortality per 10 microg/m3 increment in PM. The corresponding effect estimates obtained using the single-day lag-1 PM concentration are 0.18% and 0.23%. The estimates obtained using the lag-1 PM concentration were the most widely reported results from the recent multicity National Morbidity, Mortality, and Air Pollution Study (NMMAPS) analyses. The more accurate estimates obtained from the methods introduced in this article will enable more accurate quantification of the increased incidence in mortality due to elevation in PM levels and the benefit of current or more stringent regulatory standards. PMID- 17365621 TI - Oxidative stress induced in PCB 126-exposed northern leopard frogs, Rana pipiens. AB - Northern leopard frogs Rana pipiens exposed to PCB 126 (3,3',4,4',5 pentachlorobiphenyl) were examined for hepatic oxidative stress. In a dose response study, northern leopard frogs were injected intraperitoneally with either PCB 126 in corn oil (0.2, 0.7, 2.3, or 7.8 mg/kg body weight) or corn oil alone. In a time-course study, frogs received 7.8 mg/kg or corn oil alone, and were examined at 1, 2, 3, and 4 wk after dosing. Hepatic concentrations of reduced glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), and total sulfhydryls (total SH), as well as activities of glutathione peroxidase (GSH-P), GSSG reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PDH), and glutathione S-transferase (GSH-S-T) were measured. In the dose-response experiment, few effects were apparent 1 wk after dosing. In the time-course experiment, significant changes were observed in the 7.8-mg/kg group at 2 wk or more posttreatment. Hepatic concentrations of GSH and TBARS were higher than in corresponding controls at wk 3 and 4; the activities of GSSG-R and GSH-S-T were higher than in controls at wk 2 and 4; and the activity of G-6-PDH was increased at wk 2 and 4. These data collectively indicate that altered glutathione metabolism and oxidative stress occurred and were indicative of both toxicity and induction of protective mechanisms in frogs exposed to PCB. A similar delay in response was reported in fish and may relate to lower metabolic rate and physiological reactions in ectothermic vertebrates. PMID- 17365622 TI - Effects of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) exposure on reproduction and hatchling development in Northern bobwhite quail. AB - Adult Northern bobwhite quail (Colinus virginianus) were exposed via food to octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), an energetic compound found in soils at military training installations. Depuration of HMX into eggs was examined in an initial study, and effects on egg production, hatching, growth, development, and survival of chicks were examined in a follow-up study. HMX was readily and rapidly transferred from female quail into eggs. Marked weight loss was observed in quail exposed to 125 and 250 mg/kg HMX in food, likely due to reductions in food intake rather than a toxic mechanism. In the second study, significant alterations in body mass occurred among quail at concentrations >52.5 +/- 9.3 mg/kg but not at 12.3 +/- 1.1 mg/kg in food. Treatment-related reductions in food consumption and decreases in egg laying rates were observed. No HMX-related effects were found in chick growth or survival. Quail inhabiting HMX-contaminated sites could possibly be exposed to HMX and therefore deposition of HMX into eggs is also possible. However, results of these studies further suggest that the potential for reproductive toxicity of HMX to birds is low. PMID- 17365623 TI - Exposure of pregnant mice to an air pollutant aerosol increases asthma susceptibility in offspring. AB - Air pollution contributes to both exacerbation and development of bronchial asthma. Studies showed that coexposure to air pollution directly promotes sensitization to inhaled allergen in neonatal mice. The aim of this study was to investigate whether prenatal exposure to air pollution could also increase susceptibility to development of asthma in early life. Pregnant female BALB/c mice were exposed to aerosolized leachate of residual oil fly ash (ROFA, 50 mg/ml, 30 min) at 5, 3, and 1 d before delivery. Offspring were treated once at 3 d of age with ovalbumin (OVA, 5 mug) and alum (ip), an intentionally suboptimal dose for sensitization, exposed to aerosolized OVA (1%, 10 min) at 12-14 d or 32 35 d of age, and evaluated 2 d after the final exposure. The offspring of ROFA exposed mothers (ROFA group) revealed increasing airway hyperresponsiveness (higher enhanced pause [Penh] to methacholine challenge) and elevated substantial numbers of eosinophils in the bronchoalveolar lavage flued (BALF). Histopathology revealed prominent inflammation in the lungs of ROFA group and showed increased allergen-specific IgE and IgG1 levels. Their cultured splenocytes showed an enhanced interleukin (IL)-4/interferon (IFN)-gamma cytokine, indicating Th2 skewed immunity. Data indicate that exposure of pregnant female mice to an air pollutant aerosol increased asthma susceptibility in their offspring. PMID- 17365624 TI - Effects of vanadium(V) and/or chromium(III) on L-ascorbic acid and glutathione as well as iron, zinc, and copper levels in rat liver and kidney. AB - This study investigated the selected parameters of the antioxidant system in liver and kidney after in vivo administration of vanadium and/or chromium in rats. Outbred 2-mo-old albino male Wistar rats received drinking water for 12 wk with either sodium metavanadate (SMV; group II); chromium chloride (Cr; group III); or sodium metavanadate and chromium chloride (SMV-Cr; group IV); and group I (control) received deionized water. Chronic treatment with V alone or in combination with Cr produced a significant increase in kidney relative weight. Further, giving rats V alone also led to a significant elevation in liver relative weight. An increase in hepatic Fe concentration and renal Zn content occurred after treatment with V or Cr, respectively. The rats coadministered V and Cr had significantly higher levels of Fe in liver and Zn in kidneys. Simultaneous administration of these two elements resulted in a significant decrease in renal L-ascorbic acid concentration. V given alone significantly decreased GSH content and GSH/GSSG ratio in liver and kidney as well as increased GSSG concentration in liver, whereas Cr alone produced a significant decrease in GSH content in kidney and GSH/GSSG ratio in both organs. In the SMV-Cr-treated group a significant decrease in renal GSH concentration and GSH/GSSG ratio in both organs occurred. A significant increase in liver GSSG content was also found. The observed significant changes in kidney GSH content and in GSH/GSSG ratio in both rat tissues after Cr might result from the pro-oxidant actions of this metal. Thus, oxidative stress, which is a major pathway for V-induced toxicity, might also be associated with Cr(III)-induced adverse effects in rats. PMID- 17365625 TI - Pattern of proton pump inhibitor calls to Texas poison centers, 1998-2004. AB - There is little information on the management of potentially adverse exposures to proton pump inhibitors. This study examined the distribution of 2943 proton pump inhibitor exposures reported to Texas poison control centers during 1998-2004. In particular comparisons were made between exposures among pediatric (age < or =5 yr) and adult (age > or =20 yr) patients. Of the total exposures, 1813 (62%) were to the proton pump inhibitor alone. Of exposures to proton pump inhibitors alone, 66% were age < or =5 yr, 7% 6-19 yr, and 27% > or =20 yr. Pediatric and adult patients differed with respect to patient gender, exposure reason, exposure site, management site, final medical outcome, report of specific adverse clinical exposures, and listed treatments. Proton pump inhibitor exposures differed with patient age. In the majority of instances, potentially adverse proton pump inhibitor exposures reported to poison control centers may be successfully managed at home with favorable outcome. PMID- 17365626 TI - Sulfhydryl-reactive metals in autism. AB - This study examined the difference between sulfhydryl-reactive metals (mercury, lead, arsenic, and cadmium) in the hair of 45 children with autism (1-6 yr of age) as compared to 45 gender-, age-, and race-matched typical children. Hair samples were measured with inductively coupled mass spectrometry. Some studies, such as Holmes et al. (2003), suggested that children with autism may be poor detoxifiers relative to normally developing children. Metals that are not eliminated sequester in the brain. Our study found that arsenic, cadmium, and lead were significantly lower in the hair of children with autism than in matched controls. Mercury was in the same direction (lower in autism) following the same pattern, but did not achieve statistical significance. The evidence from our study supports the notion that children with autism may have trouble excreting these metals, resulting in a higher body burden that may contribute to symptoms of autism. PMID- 17365627 TI - Handedness and earnings. AB - We examine whether handedness is related to performance in the labour market and, in particular, to earnings. We find a significant wage effect for left-handed men with high levels of education. This positive wage effect is strongest among those who have lower than average earnings relative to those of similar high education. This effect is not found among women. PMID- 17365628 TI - Writing with the non-dominant hand: cross-handedness trainability in adult individuals. AB - Adult volunteers (8 males and 13 females) aged 20-56 years, both right- and left handed, were asked to train their non-preferred hand to write two standard sentences by practising daily over a 28-day period. At the end of this period their non-preferred-hand writing was of good quality and participants felt quite comfortable performing this task. The quality of non-preferred-hand writing achieved was unrelated to age. We postulate that handedness, in terms of actual performance, may be less pronounced than is suggested by studies of hand preference. PMID- 17365629 TI - The rate of handedness conversion and related factors in left-handed children. AB - The rate of handedness conversion was 2.7% to 11.8% in prior studies based on the total population including innately right-handed people. However, the conversion rate of innately left-handed people has not been reported. The purpose of this study was to investigate the percentage of handedness conversion in children who are innately left-handed. The data in the present study showed that 59.3% (121/211) of left-handed children had been forced to convert to right-handedness. Current handedness was also reported by 114 of the 121 informants, and the rates of right-, left-, and mixed-handedness were 56.1% (64/114), 26.3% (30/114), and 17.5% (20/114) respectively. More than half had successfully changed from left to right. Some variables, especially the educational level of the parents and the child's grade level, were related to this conversion intention. The children whose parents had less education were more likely to be forced to change handedness. Additionally, the rate of handedness conversion in younger children was lower than in older children. However, even for the children whose parents had higher education, or for the children who were younger, there was a high percentage (45.7% and 41.8% respectively) who had changed their handedness. Therefore, preventing the possible side effects for children who have undergone hand conversion should be emphasised in the future. PMID- 17365630 TI - Effects of memory load on hemispheric asymmetries of colour memory. AB - Hemispheric asymmetries in colour perception have been a matter of debate for some time. Recent evidence suggests that lateralisation of colour processing may be largely task specific. Here we investigated hemispheric asymmetries during different types and phases of a delayed colour-matching (recognition) memory task. A total of 11 male and 12 female right-handed participants performed colour memory tasks. The task involved presentation of a set of colour stimuli (encoding), and subsequent indication (forced choice) of which colours in a larger set had previously appeared at the retrieval or recognition phase. The effect of memory load (set size), and the effect of lateralisation at the encoding or retrieval phases were investigated. Overall, the results indicate a right hemisphere advantage in colour processing, which was particularly pronounced in high memory load conditions, and was seen in males rather than female participants. The results suggest that verbal (mnemonic) strategies can significantly affect the magnitude of hemispheric asymmetries in a non-verbal task. PMID- 17365631 TI - A right hemisphere bias towards false memory. AB - We extend to English Ito's (2001) demonstration of a hemispheric asymmetry in a false recognition and list-learning paradigm in Japanese. We show for English a significant interaction between the hemifield to which the probe word was presented and the probe type (non-studied but semantically related to the studied words versus non-studied and semantically unrelated to the studied words). The right hemisphere performed less well in rejecting the semantically related "lures"; the left hemisphere performed better in rejecting the semantically novel unstudied words. We discuss the results in terms of a model of fine semantic coding in the LH and coarse semantic coding in the RH, together with the dependence on memory probes that retain the representational signature of the hemisphere to which they were initially projected. Sex of the participants was also included as an independent variable; the results suggested that most of the effect lay with the female participants. PMID- 17365632 TI - The formation of cataract is earlier in the dominant eye. AB - Relations among handedness, eye dominance, and lateralisation in the formation of cataract were investigated in 35 male and 21 female patients with cataract. In right-handed patients, cataracts formed earlier in the right eyes than in the left eye; this was reversed in left-handed patients. For both right- and left-eye dominant patients, cataracts formed earlier in the dominant eye. PMID- 17365633 TI - Test-retest stability of an experimental measure of human turning behaviour in right-handers, mixed-handers, and left-handers. AB - Animals turn away from the hemisphere with the more active dopamine (DA) system. For humans, a similar relationship has been assumed, albeit that side preferences obtained from different measures are inconsistent. Given the important role of DA on human behaviour and cognition, a stable human turning measure is of significant experimental value. We assessed the stability (test and retest 4 weeks apart) of veering behaviour (lateral deviations during blindfolded straight ahead walking) in 20 healthy right-handers, 20 mixed-handers, and 20 left handers. Veering behaviour did not differ between groups, and did not reveal any particular side preference in any group. Relationships of side preferences between testing sessions for the different handedness groups was low for right handers, and showed some minor consistency for the mixed-handed group. Neither handedness nor footedness was significantly related to preferred veering side. These findings, if not related meaningfully to DA-mediated conditions (e.g., clinical populations, pharmacological studies, personality) in the future, suggests that veering behaviour is an inappropriate alternative to the animal turning model. These findings challenge the reliability of human turning measures, and invite more broadly for a critical evaluation of turning measures as an indicator of hemispheric DA asymmetries in human populations. PMID- 17365634 TI - Foot preferences during resting in wildfowl and waders. AB - Footedness in birds has been reported, e.g., in parrots and chickens, but the direction of footedness remained unclear. Is a bird left-footed because it uses its left foot for holding and handling food, or is it right-footed because it uses the right foot for stabilisation and balancing while perching? In 2004 and 2006 I examined footedness in wildfowl and waders while the birds were performing a single task: roosting on the ground on one foot. Avocet (Recurvirostra avosetta), northern shoveller (Anas clypeata), oystercatcher (Haematopus ostralegus), and Eurasian curlew (Numenius arquata) were right-footed. Another 21 species did not show any significant foot preferences. This study provides some evidence that asymmetries in preferential foot use in birds may be triggered by a preference during postural control. PMID- 17365635 TI - Editorial: medical anthropology in and of these times. PMID- 17365636 TI - Navigating HIV, pregnancy, and childbearing in South India: pragmatics and constraints in women's decision making. AB - Based on ethnographic research conducted in 2004 and 2002-3, this article examines how poor women living with HIV in Tamilnadu, India navigate decisions about pregnancy and birth, and demonstrates that these decisions are influenced by a complex web of sociocultural factors. I argue that these decisions are informed by: 1) institutional interests of the state, NGOs, and international aid donors; 2). cultural constructions of gender and of the self; 3). Christian-based organizations; and 4). support group organizations, known as "networks" for people living with HIV/AIDS. Childbearing decisions emerged through a synthesis of coexisting structures and discourses which sometimes converged at the same conclusion despite differences in their underlying logics. I argue that the discourse of "positive living" fostered by the networks provided women with a framework for making reproductive decisions that was enabling. The article highlights how women pragmatically negotiated these various factors as they engaged in reproductive decision-making. PMID- 17365637 TI - Switching between traditional chinese medicine and viagra: cosmopolitanism and medical pluralism today. AB - Based on the fieldwork in China in the Viagra era, this paper examines the reluctance to embrace Viagra as well as the willingness to switch back and forth between taking Viagra and taking Chinese medicine among impotence patients. Through the notion of "switching" as a framework, this paper discovers the conflict between Viagra and herbs not only as two types of medicine but also as representing two types of economy of potency and ethics of sexuality, and the difficulty in replacing the latter by the former. Nonetheless, switching back and forth so as to absorb them together in the body creates possibilities to cross the line between the Viagra regime revolving around desire and the regime of Chinese medicine revolving around the cultivation of life. Out of switching is the possibility of hybridization of Chinese medicine and biomedicine as well as a hybridized economy of sexual potency and ethics of sexuality. PMID- 17365639 TI - Electronic health records: is the evidence base any use? AB - Information-technology policies in many countries are full of aspirational statements and not generally based on the available evidence. This paper aims to contribute to a proper discussion of the evidence on electronic health records (EHR). The paper describes the methods we used in a review of the impact of EHR on clinical work and administration, summarizes our findings, and discusses their relevance in the context of policy makers' information requirements. We argue that the literature has, to date, largely failed to deliver usable findings. PMID- 17365640 TI - Using artificial intelligence to bring evidence-based medicine a step closer to making the individual difference. AB - The vision of evidence-based medicine is that of experienced clinicians systematically using the best research evidence to meet the individual patient's needs. This vision remains distant from clinical reality, as no complete methodology exists to apply objective, population-based research evidence to the needs of an individual real-world patient. We describe an approach, based on techniques from machine learning, to bridge this gap between evidence and individual patients in oncology. We examine existing proposals for tackling this gap and the relative benefits and challenges of our proposed, k-nearest-neighbour based, approach. PMID- 17365641 TI - Progress towards automated detection and characterization of the optic disc in glaucoma and diabetic retinopathy. AB - The shape and appearance of the optic nerve head region are sensitive to changes associated with glaucoma and diabetes that may be otherwise asymptomatic. The changes can be diagnostic of the diseases, and tracking of the changes in sequential images can be used to assess treatment and the progress of the illness. At present, change detection and tracking are performed manually, which can be a cause of poor repeatability. We are concerned with developing automated techniques of generating quantitative descriptions of the retinal images that might be used in diagnosis and assessment. In this paper, we investigate the use of images that have been collected and stored remotely, as this will replicate capture and automated processing by outreach clinics. Normal and abnormal images were collected from a range of sources, to simulate the mass screening process. The images were processed using simple signal-processing methods and divided into two groups. Using a chi-squared test, the separation of normal and abnormal images using this test was found to be highly significant (p < 0.05, n = 60). PMID- 17365642 TI - Integrating health information: a case study of a health information service for thalidomide survivors. AB - Thalidomide damage comprises a range of rare and complex disorders rarely encountered in normal clinical practice. Specific problems associated with the condition include chronic pain and medical procedures including taking blood. The benefit of international networking and the findings of recent research are mentioned. This leads to the establishment of four key requirements for a specialist database, and four priority issues to be included in the planning of a health information service for this group, of which the creation of a database is first. The other three priority issues are the creation of a web-based delivery system, the need to consolidate the specialist information available, and the need to create a system for evaluating and approving the information to be delivered. System design and implementation are discussed and key tasks identified, showing how the four key components of the service will be developed. Difficulties encountered have included decisions about standards to be adopted and identifying commercial organizations capable of completing different aspects of the work. This study illustrates the relevance and possibility of specialist reference centres for other rare disease groups. PMID- 17365643 TI - Addressing the need for adaptable decision processes within healthcare software. AB - In the healthcare sector, where the decisions made by software aid in the direct treatment of patients, software requires high levels of assurance to ensure the correct interpretation of the tasks it is automating. This paper argues that introducing adaptable decision processes within eHealthcare initiatives can reduce software-maintenance complexity and, due to the instantaneous, distributed deployment of decision models, allow for quicker updates of current best practice, thereby improving patient care. The paper provides a description of a collection of technologies and tools that can be used to provide the required adaptation in a decision process. These tools are evaluated against two case studies that individually highlight different requirements in eHealthcare: a breast-cancer decision-support system, in partnership with several of the UK's leading cancer hospitals, and a dental triage in partnership with the Royal Liverpool Hospital which both show how the complete process flow of software can be abstracted and adapted, and the benefits that arise as a result. PMID- 17365644 TI - Use of OWL-based tools to aid message development and maintenance. AB - The National Health Service National Programme for Information Technology is currently developing messaging standards to make available key information about an individual patient's care across and within different health-care settings. The complexity of this task makes it imperative that adequate tooling support is made available so as to aid consistency of design, implementation, conformance testing, and maintenance. Connecting for Health commissioned a proof of concept study to investigate whether the Object Web Language (OWL) and its associated tools could provide a basis for the message development and implementation environments. This study indicated that OWL is very much suited to such a task and should be seriously considered. PMID- 17365645 TI - Using Unified Modelling Language (UML) as a process-modelling technique for clinical-research process improvement. AB - The Primary Care Data Quality programme (PCDQ) is a quality-improvement programme which processes routinely collected general practice computer data. Patient data collected from a wide range of different brands of clinical computer systems are aggregated, processed, and fed back to practices in an educational context to improve the quality of care. Process modelling is a well-established approach used to gain understanding and systematic appraisal, and identify areas of improvement of a business process. Unified modelling language (UML) is a general purpose modelling technique used for this purpose. We used UML to appraise the PCDQ process to see if the efficiency and predictability of the process could be improved. Activity analysis and thinking-aloud sessions were used to collect data to generate UML diagrams. The UML model highlighted the sequential nature of the current process as a barrier for efficiency gains. It also identified the uneven distribution of process controls, lack of symmetric communication channels, critical dependencies among processing stages, and failure to implement all the lessons learned in the piloting phase. It also suggested that improved structured reporting at each stage - especially from the pilot phase, parallel processing of data and correctly positioned process controls - should improve the efficiency and predictability of research projects. Process modelling provided a rational basis for the critical appraisal of a clinical data processing system; its potential maybe underutilized within health care. PMID- 17365646 TI - Using XML and XSLT for flexible elicitation of mental-health risk knowledge. AB - Current tools for assessing risks associated with mental-health problems require assessors to make high-level judgements based on clinical experience. This paper describes how new technologies can enhance qualitative research methods to identify lower-level cues underlying these judgements, which can be collected by people without a specialist mental-health background. Content analysis of interviews with 46 multidisciplinary mental-health experts exposed the cues and their interrelationships, which were represented by a mind map using software that stores maps as XML. All 46 mind maps were integrated into a single XML knowledge structure and analysed by a Lisp program to generate quantitative information about the numbers of experts associated with each part of it. The knowledge was refined by the experts, using software developed in Flash to record their collective views within the XML itself. These views specified how the XML should be transformed by XSLT, a technology for rendering XML, which resulted in a validated hierarchical knowledge structure associating patient cues with risks. Changing knowledge elicitation requirements were accommodated by flexible transformations of XML data using XSLT, which also facilitated generation of multiple data-gathering tools suiting different assessment circumstances and levels of mental-health knowledge. PMID- 17365647 TI - Yeast identification--past, present, and future methods. AB - The focus of this review is the evolution of biochemical phenotypic yeast identification methods with emphasis on conventional approaches, rapid screening tests, chromogenic agars, comprehensive commercial methods, and the eventual migration to genotypic methods. As systemic yeast infections can be devastating and resistance is common in certain species, accurate identification to the species level is paramount for successful therapy and appropriate patient care. PMID- 17365648 TI - Effect of ostreolysin, an Asp-hemolysin isoform, on human chondrocytes and osteoblasts, and possible role of Asp-hemolysin in pathogenesis. AB - Aspergillus fumigatus, a pathogenic mould causing a wide range of diseases including aspergillosis, produces a series of toxic substances which appear to act in an additive and/or synergic way on cells. Aspergillosis generally occurs in immunocompromised hosts or is associated with organ transplantation. From the muscul skeleton system the vertebrae, ribs and orbit are the most commonly affected, while the joints are less frequent targets. The cytolytic protein Asp hemolysin is one of the toxins produced by Aspergillus fumigatus during infection. It belongs to the aegerolysin protein family and shares 43% identity in amino acid sequence with ostreolysin, a cytolysin from the mushroom Pleurotus ostreatus. In this work, ostreolysin was used in an experimental model to study the in vitro effects of aegerolysin-like proteins on human chondrocytes and osteoblasts. Immunostaining analyses showed selective binding and clustering of the protein on chondrocyte membranes, pointing to its association with distinctive membrane microdomains. Consequently, ostreolysin can induce effective permeabilization of both chondrocytes and osteoblasts. Based on sequence similarities of ostreolysin and Asp-hemolysin, their comparable cytolytic effects towards different cells, and similar signs of intoxication in experimental animals, our results indicate that Asp-hemolysin might be considered as a possible virulence factor of Aspergillus fumigatus during the infection of bone and cartilage. PMID- 17365649 TI - Analysis of the dermatophyte species isolated in the British Isles between 1980 and 2005 and review of worldwide dermatophyte trends over the last three decades. AB - Infections of the skin, hair and nails by dermatophyte fungi are common in developed and developing countries alike. However, the species involved and the resulting clinical entities vary both geographically and with time. We have surveyed 15,333 dermatophytes obtained from primary isolations at the Mycology Reference Laboratory, Bristol, UK from 1980 through 2005. Several striking trends in dermatophyte prevalence were apparent over this period. The relative frequencies of isolations of Microsporum canis (cat and dog ringworm), Trichophyton verrucosum (cattle ringworm), T. mentagrophytes var. mentagrophytes (rodent ringworm) and Epidermophyton floccosum (a cause of human groin and foot infections) all decreased by 90%. Conversely, the contributions of T. tonsurans and T. violaceum (two anthropophilic scalp-infecting species) to total dermatophyte isolations increased by 1000% over the same period. Finally, T. rubrum and T. mentagrophytes var. interdigitale, the two common causes of foot infection comprised 80% of all dermatophytes isolated in 1980 and 90% of isolations in 2005. Similar trends in dermatophyte prevalence were evidenced throughout the British Isles, based on the voluntary reporting of isolations from a large number of British laboratories at 5-yearly intervals over the same period. The implications of these changing patterns of dermatophyte species, and the clinical entities they produce are discussed in the context of a review of worldwide dermatophyte isolations over the last three decades, with emphasis on the causal agents of tinea capitis. PMID- 17365650 TI - A novel murine model of pharyngeal candidiasis with local symptoms characteristic of pharyngeal thrush produced by using an inhaled corticosteroid. AB - We established a novel murine model of pharyngeal candidiasis maintaining stable yeast population and local symptoms characteristic of pharyngeal thrush. The persistent Candida-infection was prolonged by inhalation of beclomethasone dipropionate corticosteroid. The severity of infection lesions was evaluated by determining viable cell number of Candia albicans and scores representing symptomatic curd-like white patch on pharyngeal tissue. The utility of this model was shown by the disappearance of lesions and fungal cells after treatment with fluconazole (FLCZ). The model would be useful for evaluating new chemotherapeutic or immunotherapeutic approaches against pharyngeal candidiasis, as well as in pathological studies. PMID- 17365651 TI - Infection stages of the dermatophyte pathogen Trichophyton: microscopic characterization and proteolytic enzymes. AB - Dermatophytes are pathogenic fungi that infect human skin, nails and hair and cause dermatophytosis. Trichophyton mentagrophytes is one of the most widespread species that belong to this group. Infection of the skin tissues include several stages, i.e., adhesion to the surface of the skin, invasion into the sublayers by the penetration of fungal elements and secretion of enzymes that degrade the skin components. In this study we have followed the morphology of the fungal elements, such as arthroconidia and hyphae, during the adhesion and invasion stages. Skin explants were inoculated with the dermatophyte and observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Skin explants were also inoculated with a transgenic isolate of T. mentagrophytes expressing the green fluorescent protein (GFP). The infected sublayers were investigated by confocal scanning laser microscopy (CSLM). As an adaptation to the tissue environment, the dermatophyte produced long fibrils when it is on the open surface of the stratum corneum, while short and thin fibrils are produced inside the dense sublayers. The short and long projections might have a role in adhesion. Invasion may be produced by mechanical and biochemical means. Invasion of the tissue showed hyphal branching and growth in multiple directions. The proteolytic profile was assayed by substrate gel and proteolytic activity. Two serine proteases of similar molecular weight were secreted during growth on the epidermal matrix components keratin and elastin. The dermatophyte may use the proteolytic enzymes to invade the surface and also the deep layer of the skin in immunocompromised patients. Dermatophytes, which are well adapted infectious agents, seem to use their mechanical and biochemical capabilities to invade the skin tissue effectively. PMID- 17365652 TI - Induction of a high affinity fibronectin receptor in Candida albicans by caspofungin: requirements for beta (1,6) glucans and the developmental regulator Hbr1p. AB - Candida albicans expresses at least two biochemically distinct fibronectin receptors. Hemoglobin induces expression of a low affinity receptor recognizing the fibronectin cell-binding domain, whereas growth in complex media induces a high affinity receptor recognizing the collagen-binding domain. We now show that sub-inhibitory concentrations of caspofungin and nikkomycin Z, but not fluconazole, induce the high affinity fibronectin receptor in a dose-dependent manner. Macromolecular complexes mechanically sheared from caspofungin-treated cells retained high affinity fibronectin binding that was sensitive to protease, disulfide reduction, and beta (1,3) glucanase digestion. The high affinity fibronectin receptor was not inducible in a Kre9 mutant strain of C. albicans deficient in beta (1,6) glucans. Conversely, a mutant strain lacking the fibronectin binding protein Als5p showed no defects in induction of high or low affinity fibronectin receptors. Heterozygous mutants of a regulator of white opaque phenotypic switching, HBR1, lacked any detectable high affinity fibronectin receptor expression in response to caspofungin, and re-introduction of the gene restored activity. Therefore, sub-inhibitory dosages of caspofungin induce a high affinity fibronectin receptor that is distinct from the known receptor Als5p and is dependent on beta (1,6) glucans and HBR1. PMID- 17365653 TI - Reduction in false antigenemia in the second generation Histoplasma antigen assay. AB - We have previously reported false Histoplasma antigenemia in solid organ transplant patients who received rabbit antithymocyte globulin (ATG). False antigenemia was caused by human anti-rabbit antibody, produced in response to ATG administration. Those specimens were obtained through a research study to assess the development of anti-rabbit antibodies following ATG administration. Here we compare the likelihood of false antigenemia between the original and second generation assays in clinical specimens obtained specifically for the diagnosis of histoplasmosis. Of 12 serum specimens that were falsely positive in the original assay, four (33%) remained positive in the second generation assay. The sensitivity was 98% in urine was and 80% in serum in patients with AIDS complicated by disseminated histoplasmosis. False-positive results were not observed in serum or urine from healthy subjects. Thus, the second generation assay is less susceptible to false antigenemia caused by anti-rabbit antibodies. PMID- 17365654 TI - Subcutaneous cryptococcosis due to Cryptococcus diffluens in a patient with sporotrichoid lesions case report, features of the case isolate and in vitro antifungal susceptibilities. AB - Environmental fungi, in particular primary pathogens and Cryptococcus spp. can be responsible for skin lesions mimicking sporotrichosis. In this paper, we report a case of subcutaneous cryptococcosis in an apparently healthy, young male patient due to a non-C. neoformans Cryptococcus species, C. diffluens. The isolate showed in vitro phenotypic switching that may affect virulence and host inflammatory and immune responses, and in vitro resistance to amphotericin B and 5-flucytosin. This species shares several phenotypic traits with C. neoformans, and, therefore, decisive diagnosis should be based on biopsy and culturing results followed by molecular identification. PMID- 17365655 TI - Cure of disseminated zygomycosis with cerebral involvement using high dose liposomal amphotericin B and surgery. AB - We present a case of cerebral zygomycosis that did not respond to standard treatment with amphotericin B or amphotericin B lipid complex. The patient was eventually cured through a combination of surgery and the use of high dose liposomal amphotericin B. Since penetration of the central nervous system by amphotericin B is poor the application of high dose therapy may be useful in cases of cerebral zygomycosis. PMID- 17365656 TI - Candida krusei sepsis secondary to oral colonization in a hemopoietic stem cell transplant recipient. AB - Yeasts other than Candida albicans have emerged as important causes of fungal infection in hemopoietic stem cell transplant (HSCT) patients, particularly those receiving fluconazole prophylaxis. We report on an autologous hemopoietic stem cell transplant recipient who developed Candida krusei sepsis from pre-existing oral colonization. PMID- 17365657 TI - Physiology and pathobiology of the pericyte-containing retinal microvasculature: new developments. AB - Evidence is accumulating that pericyte-containing microvessels, which constitute the largest component of the circulatory system, actively regulate capillary perfusion. Because the retinal vasculature is highly specialized for the local control of blood flow, experimental study of its microvessels is proving useful in the quest to elucidate the mechanisms by which local perfusion is regulated. The microcirculation of the retina is also a focus of considerable attention due to its vulnerability to diabetes, which is a leading cause of vision loss. Based on the premise that the transmembrane movement of ions plays a critical role in regulating the function of pericytes, investigators are using the patch-clamp technique to study these contractile mural cells. This review highlights recent progress made in understanding how ion channels and transporters mediate responses of the retinal microvasculature to vasoactive signals. PMID- 17365658 TI - Cellular physiology of retinal and choroidal arteriolar smooth muscle cells. AB - Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 + ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl- channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation. PMID- 17365659 TI - Arteriolar involvement in the microvascular lesions of diabetic retinopathy: implications for pathogenesis. AB - Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term animal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease. PMID- 17365660 TI - Control of retinal arterial tone by a paracrine retinal relaxing factor. AB - Retinal blood flow is regulated by local factors. In vitro bioassay experiments give evidence that retinal tissue from different species (dogs, pigs, sheep, cows, rats, and mice) continuously releases a factor lowering tone of isolated retinal arteries. This factor is a general relaxant as it was effective in relaxing different types of vascular as well as nonvascular smooth muscle preparations. This factor is called the retinal relaxing factor (RRF) and its characteristics do not correspond with those of the many well-known vasorelaxants found in retina (i.e., NO, prostanoids, adenosine, ADP, ATP, lactate, glutamate, GABA, taurine, adrenomedullin, CGRP, ANP, BNP, and CNP). This unknown RRF is transferable, hydrophilic, and heat-stable. Its relaxing effect is independent of the presence of the vascular endothelium and of NO-synthase, adenylyl cyclase, guanylyl cyclase, and cyclooxygenase activity. RRF might have a role in hypoxic vasodilation in retinal arteries since hypoxia induces relaxation only when retinal tissue is present. Thus, the RRF pathway is sensitive to changes in oxygen tension and might be a sensitive mechanism for adjusting vascular diameter to retinal oxygen levels. Diminished RRF release might explain the decreased retinal circulation observed in disease with atrophic retina. PMID- 17365661 TI - Retinal blood flow in diabetes. AB - OBJECTIVE: This is a review of work focused on characterizing retinal blood flow in diabetes. The review describes results on validation of the methodology for retinal blood flow measurements, the mechanisms of action of various factors that contribute to abnormalities in retinal blood flow in diabetic rodent models, and the translation of these results to clinical studies demonstrating the effectiveness of different therapeutic agents in normalizing retinal blood flow abnormalities in patients with diabetes. METHODS: Retinal blood flow measurements were performed using video fluorescein angiography, a methodology that is based on the measurement of fluorescein dye circulation times through the retinal circulation. RESULTS: The results of a number of experiments are summarized, detailing the effects of hyperglycemia and the roles of factors such as protein kinase C activation, endothelin-1 and endothelin-3, angiotensin-II, and nitric oxide in the development of retinal blood flow abnormalities in diabetes. CONCLUSION: The measurement of retinal blood flow both in animals and in clinical trials using the same retinal blood flow measurement methodology can provide a valuable method of quantitation allowing characterization of physiological effects and their association with metabolic alterations in diabetes and their effects on the development and incidence of microvascular complications. PMID- 17365662 TI - Inflammation and breakdown of the blood-retinal barrier during "physiological aging" in the rat retina: a model for CNS aging. AB - OBJECTIVE: To examine the possible contribution of inflammation and breakdown of the blood-brain barrier in the central nervous system (CNS) of physiologically aged rats showing cognitive decline. METHODS: Young (3- to 6-month-old) and aged (24- to 30-month-old) Wistar rats were assessed by the novel object recognition test. Vascular and inflammatory changes in the CNS were investigated in whole mount preparations or sections of retinas from young adult or aged male Wistar rats. RESULTS: Aged rats showed a significant impairment in short-term memory compared with young adults. Deterioration of blood-retinal barrier function in aged rats was evidenced by leakage of intravascular tracer into the retinal parenchyma and reduced immunoreactivity for the tight junctional protein, occludin. Immunohistochemistry revealed the presence of major histocompatibility complex (MHC) class II-positive resident microglia, activated T cells, and monocyte-like cells in the retinal parenchyma of aged rats only. Microglia positive for the ED1 antigen, indicative of phagocytic activity, were also observed in these retinas. CONCLUSION: Breakdown of the blood-retinal barrier, MHC class II expression, microglial activation, and trafficking of activated T cells are associated with physiological aging. Such changes in the CNS may contribute to the pathogenesis of age-related cognitive decline. PMID- 17365663 TI - Host immune competence and local ischemia affects the functionality of engineered vasculature. AB - OBJECTIVE: Localized and sustained delivery of vascular endothelial growth factor (VEGF) is a promising approach to overcome the limited efficacy of bolus delivery. The authors examined the effects of host immune competence and local ischemia on the functionality of new vessel networks formed with this approach. METHODS: Vessel structure and perfusion resulting from implantation of porous 85:15 poly(lactide-co-glycolide) scaffolds releasing VEGF165 were measured in both subcutaneous tissue and ischemic hindlimbs of immune competent C57BL/6 and immune deficient SCID mice. RESULTS: Sustained VEGF delivery resulted in a similar approximately 100% increase in vessel density within scaffolds in both implant sites, and both animal models. However, the resulting perfusion within scaffolds implanted in subcutaneous tissue increased modestly versus control (18 35%), while perfusion increased 52-110% above control when VEGF-releasing scaffolds were placed in ischemic hindlimbs of C57BL/6 or SCID mice. VEGF delivery improved perfusion in the entire ischemic limb (55 +/- 18% of the normal value by week 6; 138% increase over control) in SCID mice. Although C57BL/6 mice demonstrated spontaneous recovery from ischemia, VEGF delivery accelerated recovery as compared to control. CONCLUSIONS: Localized and sustained VEGF delivery can create functional vasculature that amplifies recovery of tissue ischemia. However, increases in local and regional perfusion were highly dependent on the implantation site and the animal model. PMID- 17365664 TI - Proapoptotic nitric oxide production in amyloid beta protein-treated cerebral microvascular endothelial cells. AB - OBJECTIVE: The objective of this study was to investigate the effects of amyloid beta protein (Abeta) on cerebral microvascular endothelium, and their possible involvement in Abeta-induced apoptosis in the neighboring cells. METHODS: Cultured bovine brain microvascular endothelial cells (BBECs) were incubated with Abeta for 24 h. Production of nitric oxide (NO) was assessed by nitric oxide sensitive fluorescent dye, DAF-2, and the expression of NO synthase (NOS) proteins was examined by Western blotting. Effects of Abeta-treated microvascular endothelium on the DNA damage of the neighboring cells were assessed by single cell gel electrophoresis. RESULTS: Abeta increased the expression of iNOS protein, but did not affect eNOS and nNOS expressions in BBECs. Abeta-treated BBECs showed spontaneous NO production in the presence of L-arginine. The neural cell line PC12 showed marked apoptosis after being co-cultured with Abeta-treated BBECs for 48 h, and the apoptosis was as potent as that induced by the inflammatory stimuli lipopolysaccharide and interferon-gamma. The DNA damage of PC12 cells evoked by co-culture with Abeta-treated BBECs was prevented by L-NG nitroarginine methyl ester, an inhibitor of NOS. CONCLUSIONS: These results indicate that Abeta induces the expression of iNOS in BBECs, and that microvascular endothelium-derived NO may induce apoptosis in neighboring neural cells. PMID- 17365665 TI - Blood flow in snake infrared organs: response-induced changes in individual vessels. AB - OBJECTIVE: In the past the microkinetics of blood flow in the infrared pit organs of pit vipers has been studied with Doppler flowmetry using various infrared stimuli such as a human hand or soldering iron at various distances, lasers of various wavelengths, etc. Quick-acting variations in blood flow were recorded, and interpreted as a cooling mechanism for avoiding afterimage in the infrared receptors. However, the Doppler measurements provided only the summation of blood flow in a number of vessels covered by the sensing probe, but did not give data on flow in individual vessels. METHODS: In the present work the authors introduced into the bloodstream of Gloydius and Trimeresurus pit vipers fluorescent microspheres labeled with fluorescein isothiocyanate (FITC) contained in a solution of FITC-dextran in physiological saline. They observed the passage of the microspheres through individual pit organ vessels with a fluorescent microscope to which was attached a high-speed video camera and image intensifier. Output of the camera was recorded before, during, and after stimulus with a 810 nm diode laser. Recording was done at 250 frames/s on high-speed video apparatus and downloaded to a hard disk. Disk files were loaded into proprietary software and particles were tracked and average velocities calculated. The data were then tested for significance by ANOVA with post hoc tests. RESULTS: A significant (p<.05) increase in blood velocity was found at the focal point of the stimulus laser, but not anywhere removed from this point. Proximal severing of the pit sensory nerves caused degeneration of the pit receptor terminals and abolished stimulus-induced blood flow changes, but did not affect normal blood flow. CONCLUSIONS: The authors conclude that the receptors themselves are directly and locally controlling the smooth muscle elements of the blood vessels, in response to heating of the receptors by infrared radiation. They speculate that the heavy vascularization constitutes a cooling system for the radiation-encoding receptors, and further that the agent of control may be a volatile neuromediator such as nitric oxide. PMID- 17365666 TI - Excessive erythrocytosis does not elevate capillary oxygen delivery in subcutaneous mouse tissue. AB - OBJECTIVE: Acclimatization to reduced environmental oxygen includes erythropoietin-regulated increase in erythrocytes enhancing the blood's oxygen content. However, increased hematocrit levels result in elevated blood viscosity that might impair microcirculation and tissue oxygenation. To assess this oxygen supply to the skin, the authors used erythropoietin overexpressing transgenic mice (tg6) that develop excessive erythrocytosis in an oxygen-independent manner. These animals have been previously reported to elevate their blood viscosity 4 fold. METHODS: The partial oxygen pressure (pO2) distribution was evaluated in microvessels as well as in subcutaneous interstitial tissue within a dorsal skinfold chamber of resting conscious mice using automated phosphorescence quenching. RESULTS: Compared to wildtype (wt) animals, transgenic blood viscosity increased 4-fold but microvessel diameter was not altered. Despite sharing similar blood pO2 as the wt siblings, tg6 animals nearly doubled their oxygen content. Moreover, tg6 erythrocytes reduced hemoglobin's oxygen affinity by decreased 2,3-DPG levels and an increased Hill number. Transgenic arterioles and venules showed increased pO2 compared to wt controls whereas capillary and tissue pO2 were not altered. CONCLUSIONS: Excessive erythrocytosis does not elevate capillary oxygen delivery. PMID- 17365667 TI - Abrupt reoxygenation of microvascular endothelial cells after hypoxia activates ERK1/2 and JNK1, leading to NADPH oxidase-dependent oxidant production. AB - OBJECTIVE: Mitogen-activated protein kinases (MAPK) in microvascular endothelial cells (EC) may participate in organ pathophysiology following hypoxia/reoxygenation (H/R). The authors aimed to determine the role of MAPK in H/R-induced reactive oxygen species (ROS) generation in mouse microvascular EC. METHODS: Cultured EC derived from skeletal muscle of male wild-type (WT), gp91phox-/- or p47phox-/- mice were subjected to hypoxia (0.1% O2, 1 h) followed by abrupt reoxygenation, H/RA (hypoxic medium quickly replaced by normoxic medium), or slow reoxygenation, H/RS (O2 diffused to cells through hypoxic medium). Cells were analyzed for ERK, JNK, and p38 MAPK phosphorylation, NADPH oxidase activation, and ROS generation. RESULTS: In WT cells, H/RA but not H/RS rapidly phosphorylated ERK1/2 and JNK1 and subsequently increased ROS production. H/RA did not affect p38. MAPK phosphorylation persisted despite inhibition of NADPH oxidase, mitochondrial respiration, protein tyrosine kinase, or PKC. ROS increase during H/RA was prevented by deletion of gp91phox or p47phox, or MAPK inhibition. CONCLUSIONS: Abrupt reoxygenation after hypoxia activates ERK1/2 and JNK1 in mouse microvascular endothelial cells via a tyrosine kinase-, PKC-, and NADPH oxidase-insensitive mechanism, leading to increased NADPH oxidase-dependent ROS production. The results suggest that MAPK activation in the microvascular endothelium is O2-sensitive, contributing critically to tissue pathophysiology after H/R. PMID- 17365668 TI - Wavelet analysis of skin perfusion in healthy volunteers. AB - OBJECTIVE: Rhythmical changes in microvascular perfusion of the skin depend on various influences, which appear continuously but not in a predictable manner. For identifying and quantifying different physiological influences the authors used wavelet transformation, analyzing continuously and simultaneously measured data. METHODS: A total of 34 healthy volunteers were included in the study. At the dorsum of the left hand, skin perfusion was measured by laser Doppler fluxmetry (LDF) and skin temperature was measured. Simultaneously, the electrocardiogram and the respiration were recorded. The recorded time series were analyzed with wavelet transformation and scale correlation (S-correlation). RESULTS: Semilinear analysis with wavelet transformation allowed a visualization of temporal changes in LDF frequency and amplitude in a color-coded quasi three dimensional diagram. The authors found that tissue perfusion over an observation period of 327.68 s is governed by 6 closely connected, overlying waves with different degrees of freedom. The major determinants are low frequencies in LDF, which correlates with changes in skin temperature, responsible for 68.5% of the influence. Surprisingly, though indispensable for blood flow, respiration and heartbeat contributed to less then 2.5% of the rhythmic changes. CONCLUSIONS: When wavelet transformation is used in analyzing LDF time series, the different rhythms of cutaneous blood flow are made visible and quantifiable and can be assigned to different physiological origins. The application of this novel analysis method allows identifying mechanisms regulating skin perfusion, which will greatly facilitate the diagnosis of a variety of important vascular diseases, such as chronic venous insufficiency, diabetes, or neurotrophic disorders. PMID- 17365669 TI - Angiostatin does not contribute to skeletal muscle microvascular rarefaction with low nitric oxide bioavailability. AB - OBJECTIVE: Ischemic angiogenesis is dependent on vascular nitric oxide (NO) bioavailability, in part by reducing matrix metalloproteinases (MMP)-2 and -9 activity and angiostatin production. In the metabolic syndrome, the authors have demonstrated that reduced skeletal muscle microvessel density (SKMVD) was correlated with chronic reductions in NO bioavailability, but these relationships are complicated by the presence of the multiple pathological states inherent in the metabolic syndrome. Given this, the authors hypothesized that low NO bioavailability could reduce SKMVD in normal rats, independent of any systemic pathologies associated with the metabolic syndrome, and that this would be correlated with increased angiostatin production. METHODS: Rats were separated into 3 groups: (1) control, (2) chronic NOS inhibition (10-4 M L-NAME; drinking water), and (3) NOS inhibition/normotensive (combined L-NAME/hydralazine treatment; 50 mg/kg/d; drinking water). Vessel structure, reactivity, and NO bioavailability were assessed in isolated vessels using standard techniques. SKMVD was determined using established immunohistochemical methods. Established protein analyses were performed for MMP-2 and MMP-9 expression/activity and for angiostatin expression. Alterations in vascular endothelial growth factor (VEGF) levels under the conditions of the study were assessed using ELISA. RESULTS: After 6 weeks, MAP was elevated in L-NAME rats vs. control, although this difference was abolished in L-NAME/hydralazine rats. NOS inhibition abrogated dilation to acetylcholine and arterial eNOS activity. While NOS inhibition reduced SKMVD vs. control, hydralazine treatment did not improve density, suggesting that rarefaction in NOS-inhibited rats was independent of elevated pressure. Skeletal muscle demonstrated reduced active hyperemia and increased minimum vascular resistance in L-NAME rats, which was also associated with increased arteriolar wall stiffness. L-NAME/hydralazine treatment, while still causing an elevated resistance, prevented arteriolar wall stiffening. Protein analysis demonstrated that neither expressions nor activities of MMP-2 or MMP-9 were altered from control in skeletal muscle of rats treated with L-NAME and angiostatin production was not altered in any group. Chronic NOS inhibition was associated with no consistent change in plasma VEGF levels. CONCLUSIONS: These results suggest that a reduced SKMVD develops with low NO bioavailability, although this process was not associated with significant alterations to either VEGF or angiostatin production. PMID- 17365670 TI - Exogenous wild-type p53 gene improved survival of nude mice injected with murine erythroleukemia cell line through amelioration of hemorheological changes. AB - OBJECTIVES: Previous investigations have shown that human wild-type p53 gene (WTp53) inhibits the growth of leukemia and tumor cells in vitro. In the present study, the authors used nude mice and examined the therapeutic role of p53 gene for erythroleukemia in vivo in the absence of MHC effects. METHODS: The nude mice were injected with murine erythroleukemia cells (MEL), MEL cells transfected with wild-type p53 gene (MEL-W), and MEL cells transfected with mutated p53 gene (MEL M). Abnormalities were found in the hemorheological and biophysical properties of red blood cells in all 3 groups of animals, but the abnormalities were lesser in degree and later in appearance in MEL-W group than in MEL and MEL-M groups. Furthermore, the nude mice in MEL-W group lived longer than those in MEL and MEL M groups. RESULTS: The results showed that WTp53 restrained the growth of erythroleukemia cells in vivo and reduced the erythroleukemia tumorigenesis in the microcirculation by improving the hemorheological and biophysical properties of MEL cells, which helped to prolong the life span of nude mice suffering from erythroleukemia. CONCLUSION: These results contribute to our knowledge on the use of wild-type p53 gene for the treatment of erythroleukemia disease. PMID- 17365672 TI - The KTP-(greenlight-) laser--principles and experiences. AB - The most recent advance in laser technology for transurethral prostatectomy is represented by the KTP laser. A potassium-titanyl-phosphate-(KTP-) crystal doubles the frequency of pulsed Neodymium: Yttrium-Aluminum-Garnet (Nd:YAG) laser energy to a 532 nm wavelength, which is in the green electromagnetic spectrum (Greenlight-laser) and is selectively absorbed by hemoglobin and not at all by water. Reducing the wavelength leads to a completely different interaction between laser beam and prostatic tissue. In contrast to the early clinical experiences with the Nd:YAG lasers in which vaporization was observed as a side effect during the procedure, the new KTP laser offers an immediate and efficient vaporization, leading to real tissue ablation. Because of the instant and nearly complete absorption in blood, the depth in vascularized tissue such as prostate is only 0.8 mm. The superficial coagulation prevents the large tissue necrosis that is seen with the Nd:YAG laser, leading to long lasting irritative symptoms due to sloughing of necrotic tissue. Initial experiences, made with a 60W KTP system, demonstrated that the procedure was as effective as conventional transurethral resection of the prostate (TURP) with a lower intraoperative complication rate. In order to speed up vaporization of the prostate laser power has been increased to 80W. The 80W KTP laser combines the tissue debulking properties of TURP and the favourable safety profile of laser surgery. With the new 120W High Performance System, introduced in 2006, vaporization will become more powerful and faster. Initial reports are awaited. PMID- 17365673 TI - Bipolar transurethral resection of the prostate--technical modifications and early clinical experience. AB - The purpose of the study was to update the current modifications of transurethral resection of the prostate (TURP) using bipolar high frequency current and to report on our first own clinical experience. Based on a Medline search covering the period from January 2000 to September 2006 and our clinical experience with three different devices (VISTA-ACMI, Gyrus, Storz), the technical basis of these modifications was described. In addition, an analysis of the actual outcome (handling, complications, morbidity) of bipolar TURP (n = 124) compared to a parallel series of monopolar TURP (N = 148) was carried out. Recently, five different modifications of bipolar resection devices (ACMI, Gyrus, Olympus, Storz, Wolf) have been introduced. Experimental and clinical data were available for four of these modifications (VISTA-ACMI, Gyrus, Olympus, Storz). The devices differ in terms of modification of the passive electrode (two loops, single loop, resectoscope sheath). Bipolar technology allows the use of 0.9% sodium chloride (instead of glycine) as irrigant. In all bipolar devices, a slight prolongation was noted for initiation of the cut, with the VISTA showing the poorest cutting behaviour. Finest apical dissection could be performed with the Storz device. Phase III-studies comparing bipolar and monopolar TURP showed advantages for bipolar concerning the rate of TUR-syndrome/fluid absorption, bleeding, catheter time, whereas the resection speed was similar. In two studies using two different devices (Gyrus, Olympus) a higher rate of urethral strictures was detected. We conclude that TURP still represents the reference standard in the management of benign prostatic hyperplasia. Initial data suggest that bipolar technology is safe and effective. It may offer some advantages with respect to the reduction of TUR-syndrome, less conductive trauma (i.e. tissue charring), cheaper irrigation solution, and a shorter catheter time. In addition to already existing phase III studies, larger randomized mulit-institutional trials will have to substantiate these advantages. PMID- 17365674 TI - HIFU and cryoablation--non or minimal touch techniques for the treatment of prostate cancer. Is there a role for contrast enhanced ultrasound? AB - The incidence of prostate cancer is increasing, and therefore also the need for optimal treatment. Because of the appearance of many different disease stages different treatment modalities are desirable for the treatment of localized prostate cancer. The established therapies, radical prostatectomy and radiation therapy, are associated with a lot of risks, complications and co-morbidity, and not all patients are eligible for these treatments. That is why the need for reliable minimally invasive alternatives has developed. For this paper a literature search was conducted on published studies and review articles to determine the role of HIFU (high intensity focused ultrasound) and cryoablation as minimally invasive treatment modalities for localized prostate cancer. Both therapies are being used as a primary or secondary (salvage) treatment, but can they replace surgery or radiation? And is there a role for contrast enhanced ultrasound (CEUS) of the prostate to improve diagnostics, treatment outcomes and follow-up? To date the outcomes of both therapies are promising but no prospective and comparative randomized studies with a long term follow-up were available for analysis. From this review we can conclude that until those studies are available, HIFU and cryoablation are good alternatives for patients not eligible for prostatectomy or radiation. They should not be used as a first treatment option as long as diagnostics and follow-up have not improved. PMID- 17365675 TI - Haemostasis in laparoscopic partial nephrectomy: current status. AB - Laparoscopic partial nephrectomy (LPN) is increasingly performed all over the world. However, as in its open counterpart, achieving a satisfactory haemostasis may be challenging. Our goal is to describe the different methods employed to control bleeding during LPN. We performed a non-structured review of the literature on the different haemostatic methods used during LPN. The techniques and materials used are divided into two main groups: LPN with ischemia and LPN without ischemia. The techniques to achieve warm, cold and regional ischemia are described. Energy sources and sealants are discussed in the section on LPN without ischemia. Case selection is of capital importance in the choice the appropriate haemostatic tools for LPN. Some refinements, related to the nature of the laparoscopic procedure, are still required to reach an effective cold ischemia. A broad variety of energy sources have been tested in animal models and in human setting. Major disadvantages are tissue scarring, smoke creation and low progression speed. To date none has been demonstrated to be superior to the conventional suturing. Fibrin and thrombin promoters as bio-glues are an important adjuvant method during LPN. Bipolar current devices together with fibrin sealants or coagulation promoters are used in small peripheral tumors. In bigger or central tumors, additionally suturing over Surgicel bolsters, the most popular technique is to secure the suture by means of clips. The level of the recommendations is based on comparative cohorts. We conclude that haemostasis is achieved during LPN adapting the protocols used in open nephron sparing surgery to the laparoscopic approach. Renal ischemia and bolster sutures are still mandatory in complicated LPN while in case of small exophytic tumors a satisfactory haemostasis may be achieved by using only a sealant product. PMID- 17365676 TI - Practical hints for hemostasis in laparoscopic surgery. AB - With the developments achieved in recent years in laparoscopic surgery, the field has acquired a host of new techniques to achieve haemostasis, allowing the surgeon to tackle complex procedures. These techniques include physical modalities (as simple as compression or suturing and as sophisticated as endovascular staples), thermal modalities (such as bipolar coagulation, laser or ultrasonic dissectors), and topical sealants (e.g. Fibrin glue or gelatine matrix). It is up to the laparoscopic surgeon to be familiar with all these different modalities and their proper use and limitations. It should also be kept in mind that the best approach to haemostasis in laparoscopy is prevention by thorough case preparation and meticulous dissection technique. We herein expose an overview of the available techniques to achieve haemostatic control in laparoscopic surgery in the emergency as well as the elective setting. Representative surgeries are used for illustrative purposes to describe special manoeuvres. PMID- 17365677 TI - A review of currently available vessel sealing systems. AB - Laparoscopic surgery is rapidly expanding among urologists as a minimally invasive treatment with surgical procedures becoming increasingly challenging. Accurate haemostatis is of utmost importance in laparoscopy, as bleeding can rapidly impair the working environment conditions. We subsequently reviewed the different haemostatic tools used in laparoscopy with the focus on ultrasonic dissectors and electrothermal bipolar vessel sealer (EBVS). Briefly, there is a wide variety of haemostatic tools currently available in laparoscopy, all with their inherent advantages and limitations. The comparison of ultrasonic dissectors and EBVS shows that both systems are very attractive with similar physical properties concerning thermal spread and bursting pressure of vessels sealed. It has to be noted, however, that EBVS can handle vessels of up to 7 mm. In conclusion, haemostatic tools constitute a rapidly evolving domain with devices being developed which cause less thermal spread, while being more precise and faster. This evolution should finally allow more complex laparoscopic surgical procedures. PMID- 17365678 TI - Principles and initial experience of a new device for dissection and hemostasis. AB - Electrosurgery is a commonly used technology in laparoscopy. Electrosurgical devices are being used in many medical subdisciplines in order to coagulate, cut, and ablate tissue and to produce hemostasis. The latest advance in electrosurgery is the introduction of novel simultaneous hemostatic sealing and cutting bipolar devices that minimize force by delivering energy as high current and low voltage output. One of these systems is the Gyrus Plasma Trissector (GPT), (Gyrus Group PLC, Gyrus International, Ltd.UK), a novel radiofrequency (RF) system based on bipolar technology, which consists of a proprietary PlasmaKinetic (PK) generator and specific instruments, designed as a system. The instrument consists of a 17 mm long gold-coated curved jaw with a ceramic insulated cutting element. The PK system uses high-powered pulsed bipolar energy to produce a plasmakinetic field around the working elements and is designed to operate at temperatures that allow effective tissue dissection but result in minimal collateral damage and adherence to tissue. The GPT was used with the Gyrus G400 WorkStation generator in laparoscopic radical prostatectomies (LRP). Our initial experience with this novel bipolar device demonstrates it to be safe and effective in dissection and hemostasis. The GPT permits us to act quickly when bloody fields are present, improves coagulation, reduces or eliminates sticking, seals large vessels such as dorsal vein complex (DVC) and allows secure grasping and dissecting of tissue. The urologist is familiar with electrosurgery, as we have become comfortable using GPT to dissect, cut, and coagulate tissue. We feel that the GPT can be used in a variety of laparoscopic procedures in urology. PMID- 17365679 TI - Bloodless hepatic resection with automatic bipolar radiofrequency generator and multielectrode device. AB - Liver resection is a standard treatment for liver tumours. Intra-operative blood loss remains a major concern during liver resection due to its association with higher postoperative complications and shorter long-term survival. To perform bloodless hepatic resection we realized an apparatus consisting of an incremental, bipolar radiofrequency generator and a probe with six in-line needles (SURTRON SB). Several ex-vivo and in-vivo pig liver experiments and a first-phase clinical study allowed the realization of a prototype radiofrequency (RF) generator that works at 470 kHz, 150 watts maximum power delivered. The probe consists of six needle electrodes of 1.5 mm diameter, with 4.5 mm free space, 6.0 mm centre to centre, between each. We obtained a coagulation of 35 mm length and 12 mm width. The transection was performed with a common scalpel after coagulation of liver parenchyma. We observed good healing of the liver edge both in animal model and in ongoing pilot clinical study. Coagulation with SURTRON SB allows a feasible, easy and safe bloodless liver resection. This method is tolerated with no systemic complication or adverse reaction. This technique offers a method for a bloodless hepatic transection without the need for sutures, ties, staples or tissue glue. PMID- 17365680 TI - Lignans from Linum species of sections Syllinum and Linum. AB - The aryltetralin lignans 6-methoxypodophyllotoxin, 5'-demethoxy-6 methoxypodophyllotoxin as well as the corresponding 8'-epimers 6 methoxypicropodophyllin, and 5'-demethoxy-6-methoxypicropodophyllin were isolated from suspension cultures of Linum cariense, and 4'-demethyl-6 methoxypodophyllotoxin together with 6-methoxypodophyllotoxin from plants of L. tauricum, which both belong to section Syllinum of the genus Linum. Cell cultures of L. altaicum, L. austriacum ssp. euxinum and L. lewisii belonging to section Linum accumulate the naphthalene lignans justicidin B and isojusticidin B. The different lignans were identified by HPLC and spectroscopic methods. PMID- 17365681 TI - 1H NMR, mass spectroscopic studies and color fastness properties of methyl-4,6 dihydroxy-2-oxo-1-phenyl-5-arylazopyridine-3-carboxylate, part III: new disperse dyes. AB - 1H NMR and mass spectroscopic studies of new disperse dyes synthesized from methyl-4,6-dihydroxy-2-oxo-1-phenyl pyridine-3-carboxylate. Application of the dyes on polyester fabric and color fastness properties are also studied. The dyes are also found to possess DPPH free radical scavenging activity. PMID- 17365682 TI - Cytotoxic kurubasch aldehyde from Trichilia emetica. AB - Kurubasch aldehyde, a sesquiterpenoid with an hydroxylated humulene skeleton, was isolated as free alcohol from Trichilia emetica Vahl. (Meliaceae), belonging to the order Sapindales. Related substances have been previously found in plants as esters of aromatic acids, and these plants were species belonging to the distant order Apiales. This is the first report of humulenes found in the genus Trichilia and only the second of humulenes in the order Sapindales. The aldehyde is a modest inhibitor of the growth of Plasmodium falciparum (IC50 76 microM) and slow proliferating breast cancer cells MCF7 (78 microM), but a potent inhibitor of proliferation of S180 cancer cells (IC50 7.4 microM). PMID- 17365683 TI - Chemical composition and in vitro antimicrobial activity of the essential oils of flower heads and leaves of Santolina rosmarinifolia L. from Romania. AB - The essential oils of the flower heads and leaves of Santolina rosmarinifolia L. (Compositae) cultivated in Romania were obtained through hydrodistillation and analysed by GC-MS. Forty-two components were identified, representing 92.3-94.0% of the whole composition of the samples. Their in vitro antimicrobial activity against gram-positive and gram-negative bacteria strains and the fungus Candida albicans was determined using the agar-diffusion method and the broth dilution method. PMID- 17365684 TI - Chemical composition of the essential oil of Pelargonium quercetorum Agnew. of Iran. AB - The volatile constituents in the essential oil of Pelargonium quercetorum Agnew., growing wild in Kurdistan, Iran were investigated through GC and GC/MS technique. Twenty-six compounds, representing 21 (80.77%) of the total oil were identified. The main components were: alpha-pinene (25.28%), alpha-fenchyl acetate (20.63%), limonene (9.94%), beta-caryophyllene (8.20%), camphene (4.31%), delta-cadinene (3.32%), beta-pinene (3.21%), alpha-amorphene (2.80%), valencene (2.73%), ledene (2.25%) and p-cymene (1.63%). PMID- 17365685 TI - A new aporphine alkaloid from Sabia yunnanensis. AB - A new aporphine alkaloid, 1-hydroxy-2,3-dimethoxy-6-formyl-6a,7-dehydroaporphine, along with 15 known compounds have been isolated from the stems and leaves of Sabia yunnanensis. Their structures were established on the basis of spectral analysis. PMID- 17365686 TI - Extraction of Lantana camara essential oil by supercritical carbon dioxide: influence of the grinding and biological activity. AB - The aim of this study was to produce Lantana camara essential oil by SFE and to study the effect of matrix grinding on the yield and/or composition of the extract. Experiments were carried out on grinding matrices (G) and on not grinding matrices (NG). The extracts were analyzed by GC-MS. A comparison with the oil obtained by hydrodistillation is also given. Finally, the antibacterial and antifungal activity of the various extracts has been assayed. PMID- 17365687 TI - Tambouranolide, a new cytotoxic hydroxybutanolide from a Tambourissa sp. (Monimiaceae). AB - A new cytotoxic hydroxybutanolide, tambouranolide, has been isolated by solid phase extraction from an ethanol extract of the dried roots of a species of Tambourissa (Monimiaceae) from the Madagascar rainforest. The structure was elucidated through the interpretation of spectral data and its comparison to data reported in the literature for related molecules. The compound showed moderate in vitro cytotoxicity with an IC50 of 8 micro g mL(-1) in the A2780 human ovarian cancer cell line assay. PMID- 17365688 TI - Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra. AB - The Sulforodamine B (SRB) assay was used to test cytotoxicity against four human cancer cell lines and one normal cell line of antioxidant constituents isolated from Hypericum triquetrifolium Turra. Methanolic extract and pure compounds were tested against the large cell lung carcinoma cell line COR-L23, the hepatocellular carcinoma cell line HepG-2, renal cell adenocarcinoma ACHN, the amelanotic melanoma cell line C32 and normal human foetal lung MRC5. The results showed that I3-II8-biapigenin exhibited strong cytotoxic activity (IC50 = 5.73 micro g mL(-1)) showing a certain degree of selectivity against the different cell types. PMID- 17365689 TI - In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr. AB - The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3 methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2 enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5 dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7 trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2 hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5 hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1 yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1 yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity. PMID- 17365690 TI - Phenolics of Moringa oleifera leaves. AB - Five flavonol glycosides characterised as kaempferide 3-O-(2'',3'' diacetylglucoside), kaempferide 3-O-(2''-O-galloylrhamnoside), kaempferide 3-O (2''-O-galloylrutinoside)-7-O-alpha-rhamnoside, kaempferol 3-O-[beta-glucosyl-(1 -> 2)]-[alpha-rhamnosyl-(1 --> 6)]-beta-glucoside-7-O-alpha-rhamnoside and kaempferol 3-O-[alpha-rhamnosyl-(1 --> 2)]-[alpha-rhamnosyl-(1 --> 4)]-beta glucoside-7-O-alpha-rhamnoside together with benzoic acid 4-O-beta-glucoside, benzoic acid 4-O-alpha-rhamnosyl-(1 --> 2)-beta-glucoside and benzaldehyde 4-O beta-glucoside have been isolated from methanolic extract of Moringa oleifera leaves. Also obtained from the same extract were known compounds, kaempferol 3-O alpha-rhamnoside, kaempferol, syringic acid, gallic acid, rutin and quercetin 3-O beta-glucoside. Their structures were determined using spectroscopic methods as well as comparison with data from known compounds. PMID- 17365691 TI - Chymotrypsin inhibitory constituents from Haloxylon recurvum. AB - Haloxylase, the triglyceride (1), unsaturated fatty acid (2), and saturated fatty acid methyl ester (3) have been isolated from the chloroform-soluble fraction of Haloxylon recurvum. Their structures have been elucidated through spectroscopic studies and chemical transformation. All these compounds showed significant inhibitory activity against the enzyme chymotrypsin in a concentration dependent fashion. PMID- 17365692 TI - Inhibition of chitin synthase by a series of 7-deoxycasuarine stereoisomers designed as constrained analogues of the potent inhibitor 6-deoxyhomoDMDP. AB - A series of polyhydroxy-pyrrolizidines were designed as constrained analogues of 6-deoxy-homoDMDP, a potent naturally occurring inhibitor of chitin synthase. Enzymatic evaluation revealed that 7-deoxycasuarine was the best inhibitor of the series (IC50 = 820 microM) displaying a noncompetitive inhibition pattern, whereas the other tested compounds had IC50 in the range 4.3-18.9 mM. This is the first report of pyrrolizidine-type iminosugars inhibiting a glycosyltransferase. In addition, the inhibitory potencies towards glycosidases of these synthetic casuarine analogues is also disclosed. PMID- 17365693 TI - Ellagic acid glycosides from Turpinia ternata. AB - Bioassay-guided fractionation of the methanolic extract of Turpinia ternata stems, has led to the isolation of the new ellagic acid derivative 3,4'-di-O methylellagic acid-4-O-alpha-L-arabinofuranoside (1), and the known compounds ellagic acid (2), 3-O-methyl ellagic acid (3), 3-O-methylellagic acid-3'-O-alpha L-rhamnopyranoside (4), and 3,3'-di-O-methylellagic acid-4'-O-alpha-D glucopyranoside (5). Their structures were elucidated by extensive spectroscopic methods. Compounds 1, 3, and 4 showed moderate antioxidant activity against DPPH free radical, whereas compound 1 was found to be moderately cytotoxic against Artemia salina larvae. PMID- 17365695 TI - Isolation of fatty acids and aromatics from cell suspension cultures of Lavandula angustifolia. AB - Cell suspension cultures of Lavandula angustifolia Mill. ssp. angustifolia (syn.: L. officinalis Chaix.) afforded a fatty acid composition, cis and trans p coumaric acids (=p-hydroxy cinnamic acids), and beta-sitosterol. The fatty acid composition was analyzed by GC-MS, and the structures of the isolated three compounds were determined by 1H- and 13C-NMR, and MS spectroscopic techniques. PMID- 17365696 TI - One new triterpenoid saponin from Lysimachia davurica. AB - One new saponin named davuricoside N (1) was isolated from the whole plants of Lysimachia davurica, the structure was determined by 1D and 2D NMR, ESI-MS techniques, and chemical methods. PMID- 17365697 TI - New calamenene sesquiterpenes from Tarenna madagascariensis. AB - Four calamenene sequiterpenes, (+)-(7R,10S)-15-hydroxycalamenene (3), (+) (7R,10S)-2,15-dihydroxycalamenene (4), (+)-(7R,10S)-2-hydroxy-15-calamenal (5), (+)-(7R,10S)-15-calamenal (6), along with the amorphane sesquiterpene (+) (1S,6R,7R,10S)-1-hydroxy-3-oxo-amorph-4-ene (16), have been isolated from the Madagascan shrub Tarenna madagascariensis (Rubiaceae) and their structures determined by spectroscopic methods and chemical correlations. Furthermore, five known related sesquiterpenes [(+)-(7R,10S)-2-hydroxycalamenene (1), (+)-(7R,10S) 3-hydroxycalamenene (2), (-)-alpha-cadinol (13), cadinenal (14), 6-epicadinenal (15)], and three known lignans [(-)-hinokinin, (-)-dihydrocubebin, (-)-cubebin] were also isolated from the same plant. This is the first report of compounds 3, 4, 5, 6, and 16 from a natural source. PMID- 17365698 TI - Constituents of Gardenia volkensii: their brine shrimp lethality and DPPH radical scavenging properties. AB - The seeds and the pulp of Gardenia volkensii yielded one new iridiod, namely 4 (2N-gardenamide)n-butanoic acid, together with the known iridoids genipin and genipin gentiobioside, the pterocarpin medicarpin, coumarins, phenylpropanoids, benzenoids and triterpenes. The structures of these were determined on the basis of spectroscopic data and by comparison of obtained data with those from literature. The fruit extracts of this plant exhibited moderate radical scavenging activity against DPPH radical and moderate lethality against brine shrimps (Artemia salina). PMID- 17365699 TI - Flavonoids and phenol glycosides from Boerhavia diffusa. AB - Four new compounds were isolated from Boerhavia diffusa namely eupalitin 3-O-beta D-galactopyranosyl-(1''' --> 2'')-O-beta-D-galactopyranoside (1), 3,3',5 trihydroxy-7-methoxyflavone (4), 4',7-dihydroxy-3'-methylflavone (5) and 3,4 dimethoxyphenyl-1-O-beta-D-apiofuranosyl-(1'' --> 3')-O-beta-D-glucopyranoside (7) along with eight known compounds. The structures were elucidated by analysis of their spectroscopic data. PMID- 17365700 TI - New diterpenoids from Calceolaria polifolia. AB - Four new and seven known diterpenes have been isolated from the dichloromethane extract of the aerial parts of Calceolaria polifolia. The structures of the new compounds were established by spectroscopic evidence. PMID- 17365701 TI - Diterpenoids from Calceolaria alba. AB - Chemical examination of the petrol ether (60-80) extract of the aerial parts of Calceolaria alba R. et Pav., collected in Santa Juana, VIII Region, Chile, resulted in the isolation of 3 new diterpenoids. Their structures have been elucidated by a study of their physical and spectral data; in particular using 2 NMR spectroscopy (DEPT, 1H-1H, COSY, NOESY, HMQC and HMBC). PMID- 17365702 TI - New terpenoids from two Indonesian marine sponges. AB - A C16 norsesterterpenoid (euplectellodiol, 1) and a norditerpenoid (2) have been isolated from the marine sponges Mycale euplectelloides and Diacarnus megaspinorhabdosa, respectively. Their structures have been determined by spectroscopic methods. Compounds 1 and 2 are new natural products. PMID- 17365703 TI - A new germacranolide-type sesquiterpene lactone from Tanacetum santolinoides. AB - A new germacranolide-type sesquiterpene lactone, 1alpha-hydroxy-3-oxo 7alpha,11betaH-germacra-4Z,9Z-dien-12,6alpha-olide (1), was isolated from the CH2Cl2--MeOH extract of the aerial parts of Tanacetum santolinoides. Its structure was determined by spectroscopic techniques including, IR, high resolution-EIMS, and extensive 400 MHz one- and two-dimensional NMR-analysis (1H, 13C-NMR, DEPT, 1H--1H COSY, HMQC, HMBC, and NOE experiments). PMID- 17365704 TI - A new tricyclic-alpha,beta-unsaturate ketone and a new delta-hexano lactone glycoside from Adenocaulon himalaicum. AB - Two new compounds, a tricyclic-alpha,beta-unsaturate ketone (adenocaulone) (1) and a delta-hexanolactone glycoside (adenocaulolide) (2), along with 10 known compounds 3-12 were isolated from Adenocaulon himalaicum Edgew. Their structures were elucidated by spectroscopic methods (IR, MS, 1H, 13C and 2D NMR). In addition, the antibacterial activity of compounds 2, 3 and 4 were tested. PMID- 17365705 TI - Intra-specific biodiversity of Italian myrtle (Myrtus communis) through chemical markers profile and biological activities of leaf methanolic extracts. AB - Methanolic extracts of Myrtus communis leaves from two Italian regions (Calabria and Sardinia) were processed to determine the content of myrtenol, linalool and eucalyptol. Among the Calabrian and Sardinian myrtle samples, linalool and eucalyptol chemotypes were prevalent. The extracts were also tested for antioxidant, antibacterial and antifungal activities. Myrtle leaves samples were dried and extracted through maceration. Partition chromatography was adopted to separate myrtenol, linalool and eucalyptol fractions. Analyses were performed through GC and GC-MS. Some of the samples showed a good scavenger activity evidenced by DPPH radical scavenging assay and beta-carotene bleaching test. Antibacterial and antifungal activities were generally weak. The phytochemical and biological characterization of all the extracts were determined with an aim to characterize the intra-specific biodiversity of myrtle populations. PMID- 17365706 TI - Phenolic constituents from the rhizomes of Gastrodia elata. AB - Gastrodia elata Bl. (Orchidaceae) is an important traditional medicinal plant as well as a famous foodstuff in China. In the present article, the HPLC chromatograms of different preparation processes were reported, and structures of nine phenolic compounds, isolated from Gastrodia elata, were assigned. The isolated compounds were identified as 1,3-bis(4-hydroxybenzyl)citrate (1), gastrodin (2), 4-hydroxybenzyl alcohol (3), 1-(4-beta-D glucopyranosyloxybenzyl)citrate (4), 4-hydroxybenzaldehyde (5), parishin B (6), 4 hydroxybenzyl methyl ether (7), 4-hydroxybenzyl ethyl ether (8), and 4-(4' hydroxybenzyl)phenol (9). Compounds 1 and 4, named as parishin D and E, were new. Their structures were elucidated on the basis of spectral analyses, including 2D NMR spectroscopy. PMID- 17365707 TI - Antimicrobial activity and pollen composition of honey samples collected from different provinces in Turkey. AB - The antibacterial activity of honey samples from different sources were collected and investigated against Bacillus cereus, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 27736, Morganella morganii, Micrococcus luteus NRRL B-4375, Escherichia coli ATCC 35218, and Candida albicans. Pathogens exhibited different sensitivities towards the honey samples. The results showed that majority of the honey samples (75%) generally inhibitied the bacteria tested. The honey samples which were obtained from Izmir (samples 1 and 2) proved more effective as inhibitors against P. aeruginosa, E. coli, and S. aureus. The honey which was obtained from Mugla (sample 5) exhibited high anticandidal activity on C. albicans. A comparison of the honey samples on the basis of pollen content revealed that they were heterofloral, and samples which had highest antibacterial activity against P. aeruginosa, E. coli, and S. aureus were dominated by pollen from Chenopodiaceae/Amaranthaceae (sample 1), and Trifolium, Trigonella, Cyperaceae, Zea mays and Anthemis taxa (sample 2). The honey proved more effective on bacteria than antibiotics. PMID- 17365708 TI - Preparation of ferulic acid derivatives and evaluation of their xanthine oxidase inhibition activity. AB - Several ferulic acid ethyl esters (3a-h) were synthesized under the Knoevengel reaction condition and they were further reduced to afford the respective allylic alcohol derivatives (4a-g). Some of them were evaluated for the xanthine oxidase (XO) inhibitory activity. Among them, 3h exhibited a significant inhibitory activity with an IC50 value of 1.35 x 10(-5) M, while the IC50 value of allopurinol used as the positive control was 1.49 x 10(-5) M. The study suggested that the higher acidity of the phenolic OH group in the ferulic acid derivatives might result in improved XO inhibitory activity. PMID- 17365709 TI - Antifungal agent and other constituents from Cynanchum otophyllum. AB - Seven constituents were isolated from the ethyl acetate extract of the rhizome of Cynanchum otophyllum Schneid (Asclepiadaceae). Their structures were determined as 1-(4-methoxy-3-(6-methoxy-3-acetylphenylperoxy)phenyl)ethanone (1), 1-(3 hydroxy-7-acetylnaphthalen-2-yl)ethanone (2), 1-(3,4-dihydroxyphenyl)ethanone (3), 1-(2,4-dihydroxyphenyl)ethanone (4), 1-(3-(3,6-dihydroxy-2-methylbenzoyl) 2,4-dihydroxyphenyl)ethanone (beishouwubenzophenone) (5), N,N-dimethylethanamine (6), and 2-oxo-2-phenylacetic acid (7), respectively, by spectral methods. Among them, 1 and 2 were new compounds; 1 had antifungal activity. PMID- 17365710 TI - Antiliperoxidant activity of pomegranate peel extracts on lard. AB - Phenolics were extracted from powdered pomegranate peel using water, methanol, acetone and ethyl acetate (EtOAc), respectively. The antiliperoxidant activity of the extracts on lard was studied by peroxide value method. All the extracts showed enhanced inhibitory effect on lard peroxidation with the increase of phenolic concentrations. Acetone extract exhibited the highest antiliperoxidant activity followed by water, methanol and EtOAc extracts. Acetone extract at 0.1% (w/w) and water extract at 0.2% (w/w) demonstrated an antiliperoxidant effect close to that of tea polyphenols (0.02%, w/w) and higher than that of BHT (0.02%, w/w). At 0.2% (w/w), acetone extract showed a higher inhibitory activity on lard oxidation than that of tea polyphenols and BHT. Owing to the high antiliperoxidant property, acetone extract may have possible application in the food industry. PMID- 17365711 TI - In vivo antitussive potentiality of Lagerstroemia parviflora flower extract using a cough model induced by sulfur dioxide in mice. AB - The methanol extract of the flowers of Lagerstroemia parviflora Roxb (Family: Lythraceae) was investigated for its effect on a cough model induced by sulphur dioxide gas in mice. It exhibited significant antitussive activity when compared with the control in a dose-dependent manner. The extract (100, 200, 300 mg kg( 1)) showed maximum inhibition of cough reflex at 90 min after drug administration and the antitussive activity was comparable to that of codeine phosphate, a standard antitussive agent. PMID- 17365712 TI - Sesquiterpene lactones from Saussurea alata. AB - Two new guaianolides, namely, 3beta,8alpha-dihydroxy-13-methoxyl-4(14),10(15) dien-(1alphaH,5alphaH,6beta H,11betaH)-12,6-olide (1) and 3beta,8alpha-dihydroxy 13-methoxyl-4(14),10(15)-dien-(1alphaH,5alphaH,6beta H,11alphaH)-12,6-olide (2), together with six known guaianolides, 8-hydroxyzaluzanin C, austricin, chlorojanerin, cynaropicrin, chlorohyssopifolin E and chlorohyssopifolin A were isolated from the aerial parts of Saussurea alata. The structures were established mainly based on spectral analysis, especially 2D NMR techniques. PMID- 17365713 TI - Composition and antimicrobial activity of the essential oil of Actinidia macrosperma from China. AB - Actinidia macrosperma is a medicinal plant in China and has been well known for its attraction to cats and activities against leprosy and cancers. The compositions and the antimicrobial activity of its leaf oil were reported for the first time. The oil obtained by hydrodistillation and analyzed by GC and GC-MS, was characterized by the high content of monoterpenes. Linalool (48.14%) is the major component identified, followed by 1,2-dimethyl-lindoline (7.94%), linolenic acid methylester (6.57%) and (E)-phytol (5.29%). The antimicrobial activity of the oil was evaluated against four bacterial and three fungal species. The results showed that it exhibited a mild antibacterial activity against two Gram positive bacteria (Staphylococcus aureus and Bacillus subtilis), a significant activity against Gram-negative bacteria (Escherichia coli), and no activity on Pseudomonas aeruginosa. The test fungi were more sensitive to the oil, with a MIC range of 0.78-1.56 microL mL(-1) than bacteria in the range which were significantly higher from 0.78 to 25.50 microL mL(-1). PMID- 17365714 TI - Callus of Securinega suffruticosa, a cell line accumulates dextro Securinega alkaloids. AB - Investigations on callus cultures of Securinega suffruticosa indicated that the cell line of S. suffruticosa callus was able to accumulate four known Securinega alkaloids with dextro rotation but not levo rotation as reported before: virosecurinine (1), viroallosecurinine (2), 14,15-dihydrovirosecurinine (3) and ent-phyllanthidine (4). Time course studies on the growth of callus cultures were carried out. The effects of different plant growth regulators, sucrose concentrations on callus growth and virosecurinine production were also reported. PMID- 17365715 TI - A new 14-membered cyclopeptide alkaloid from Zizyphus oxyphylla. AB - One new 14-membered frangulanine-type cyclopeptide alkaloid, oxyphyl line-A (1) has been isolated from the stem bark of Zizyphus oxyphylla together with the known 13-membered cyclopeptide, nummularine R (2). The structure was established on the basis of spectral studies particularly 2D NMR. PMID- 17365716 TI - Bioactive constituents from Rollinia emarginata (Annonaceae). AB - From an Argentine collection of the tropical tree Rollinia emarginata (Annonaceae), vomifoliol, dehydrovomifoliol, blumenol C, loliolide, 7 epiloliolide, vanillin, dihydroactinolide, as well as other common plant constituents were obtained, and identified by their NMR and MS features compared with authentic samples. Antifeedant and toxic actions were exerted to the polyphagous moth Spodoptera frugiperda by the ethanol extract of the plant, at 250 ppm in the larval diet. Additionally, in greenhouse studies, a 200 ppm aqueous solution of the extract produced a post-emergency herbicidal effect on the annual weed common lambsquarter (Chenopodium album). PMID- 17365717 TI - (2-Nitro ethyl)phenyl and cyanophenyl glycosides from the fruits of Diploclisia glaucescens. AB - Chemical investigation of polar fractions of the methanol extract of the fruits of Diploclisia glaucescens of the family Menispermaceae furnished two new phenyl glycosides, 4-(2-nitroethyl)phenyl-beta-D-xylopyranosyl-(l approximately 6)-beta D-glucopyranoside, and 4-cyanophenyl-beta-D-xylopyranosyl-(l approximately 6) beta-D-glucopyranoside. PMID- 17365718 TI - Volatile organic compounds of Angelica gigas Nakai, Korean medicinal herb. AB - The study was performed to find out the profile of volatile flavor components from the aromatic medicinal plant, Angelica gigas Nakai. The volatile organic compounds of A. gigas Nakai were extracted by simultaneous steam distillation and extraction (SDE) method, and identified by gas chromatograph/mass spectrometric (GC/MS) analysis. A total of 116 compounds, including 40 hydrocarbons, 37 alcohols, 15 esters, 12 aldehydes, 7 ketones, and 5 miscellaneous were identified and quantified. Among them, 75 volatile organic compounds were detected which make up 90.52% of total volatile content. alpha-Pinene was detected as the prime volatile component which accounted for 30.89% of total volatile content and 2,4,6 trimethyl heptane, camphene, alpha-limonene, beta-eudesmol, vervenol, alpha murrolene, and sphatulenol were detected as the major components of A. gigas Nakai. PMID- 17365719 TI - The effect of citrus flavonoids on the redox state of alimentary-induced fatty liver in rats. AB - Both chronic venous insufficiency (CVI) and fatty liver may develop at the same time. Hesperidin and diosmin are used for the treatment CVI. There is no information, however, on the effect of these flavonoids in the redox state of fatty liver. In this study, male Wistar albino rats were fed a lipid-rich diet with or without 450 mg diosmin-50 mg hesperidin-containing drug (60 mg kg(-1) body weight/day, per os) for 9 days to determine the impact of treatment on antioxidant defence system of the fatty liver. We detected free SH-group concentration (SHC), hydrogen-donating ability (HDA), and natural scavenger capacity were decreased and hepatic malonaldehyde content and dien conjugate (DC) content in rats with fatty liver were increased compared to the control. After treatment in fatty liver, these parameters (except DC) significantly improved and approached the control value. Our results indicate that diosmin-hesperidin containing drug may be a useful agent in improving the antioxidant defensive system in alimentary-induced fatty liver disease. PMID- 17365720 TI - What's new in nicotine & tobacco research? PMID- 17365721 TI - Understanding tobacco use in Minnesota: findings from the ClearWay Minnesota research program. PMID- 17365723 TI - Beliefs and experiences regarding smoking cessation among American Indians. AB - A dearth of information exists about American Indians' views about smoking and cessation. We present results from six focus groups conducted among current and former smokers from American Indian communities in the Minneapolis/St. Paul metropolitan area, as part of a larger qualitative study. Findings indicate that, although smoking is common and acceptable among this population, many would like to quit. The majority of focus group participants attempted cessation without the aid of counseling and pharmacotherapy. Many held negative attitudes toward pharmacotherapy for smoking cessation, including worries about side effects, skepticism about effectiveness, and dislike of medications in general. Negative attitudes were grounded partly in a lack of trust in conventional medicine and, for some, were related to historic and continuing racism. Participants also reported a lack of information about tobacco dependence treatment from health care providers, including information about the functional benefits of such treatment. Nonetheless, participants thought smokers might try pharmacotherapy if it was made more accessible in their community and if community members could offer word-of-mouth testimonials regarding its effectiveness. Results point to the need for community- and peer-based smoking cessation treatment in the American Indian community, including accurate information from trusted sources. PMID- 17365722 TI - Feasibility of Internet health screening to recruit college students to an online smoking cessation intervention. AB - Internet-based cessation programs are promising. However, little information exists on how to recruit college smokers to participate in online interventions. Two studies assessed the feasibility of Internet health screening as a recruitment strategy for college smokers. The Internet Survey Study compared Internet (n = 735), mail (n = 1,490), and phone (n = 550) surveys as means to identify college smokers. The RealU Recruitment Study described the use of an Internet-based general health screening survey (N = 25,000) to recruit for an online cessation trial. The Internet Survey Study showed that, despite large differences in response rates (Internet = 38%, mail = 47%, phone = 90%; p<.001), the rates of past-month tobacco use were similar (Internet = 35%, mail = 38%, phone = 34%; p = .35). Among past-month users, a greater proportion reported daily use on the Internet (33%) and phone (37%) surveys versus the mail survey (23%, p = .007). In the RealU Recruitment Study, 517 college smokers were recruited in 1 week. The Internet survey response rate was 26%, the prevalence of current smoking was 29%, the eligibility rate was 87%, and the enrollment rate was 32% (517/1,618). Internet health screening can be used to quickly identify and enroll large numbers of college smokers in an online smoking cessation intervention. PMID- 17365724 TI - Patterns of tobacco use in a sample of American Indians in Minneapolis-St. Paul. AB - The purpose of this study was to identify patterns of tobacco initiation, current use, and smoking cessation and their correlates in the adult American Indian population in the Twin Cities, using community-based participatory research methods. A total of 300 American Indians aged 18 years or older participated in in-person interviews. Participants were recruited to fill age-gender quotas that reflect the demographic distribution of American Indians in Minnesota. Almost everyone in this sample had smoked cigarettes recreationally: Only 12% had smoked fewer than 100 cigarettes, and nearly two-thirds (62%) reported that they were current smokers. Only 29% of ever-smokers had quit smoking. More than two-thirds (68%) of current smokers would like to quit, and most of them (53% of all smokers) had tried unsuccessfully to quit in the previous 12 months. Our results show a level of current smoking and low cessation rates among American Indians in the Twin Cities area that reflect a crisis for public health and for the Indian community. PMID- 17365725 TI - Secondhand smoke in apartment buildings: renter and owner or manager perspectives. AB - This study explored the views of Minnesota renters and apartment owners or managers about environmental tobacco smoke (ETS) transfer between units in multifamily buildings and about smoke-free housing. A convenience sample of 49 decision makers who manage 27,116 rental units in Minnesota were aware of some ETS transfer in their buildings, but most felt it was rarely or never a significant factor in tenants' decisions to rent or to move. Most of those who had never designated a building smoke free had little or no interest in doing so, due to concerns that it would increase vacancy rates, constitute discrimination, or engender costs for enforcement. Owners who had already designated smoke-free buildings, however, had seen mostly neutral or positive effects on vacancies, turnover, and time required to manage the buildings, and planned to continue offering them. A total of 48% of households in a random sample of 405 reported that at times ETS enters their apartment from elsewhere; 10% said this occurs often or most of the time. Of those experiencing ETS transfer, 37% said it bothered them a lot or so much that they were thinking of moving. Only a small fraction of renters currently live in smoke-free buildings, but nearly half would be extremely or very interested in doing so. Interest is high across ethnicities, income levels, rent levels, and age groups and regardless of whether the household has children. 54% of respondents would be very likely to choose a smoke free building, all other things being equal, and 34% would be willing to pay more to live in one. PMID- 17365726 TI - Minnesota tobacco-free park policies: attitudes of the general public and park officials. AB - A growing number of cities and counties in Minnesota have adopted policies or ordinances that restrict tobacco in outdoor locations. Current policies banning or limiting tobacco use on park and recreation grounds exist in at least 70 communities around Minnesota. However, little is known about the support for such policies. The goal of this project was to learn more about the level of support for tobacco-free park policies in Minnesota. A mail survey was sent to 2,400 randomly selected adult Minnesota residents, and a phone survey was administered to 257 park and recreation directors. Of the 2,400 surveys mailed, 1,501 (68%) were returned. Among the general public, 70% favored tobacco-free park policies. Reasons cited for supporting such policies include to reduce litter (71%), to reduce youth opportunities to smoke (65%), to avoid second-hand smoke (64%), and to establish positive role models for youth (63%). Park and recreation directors also support such policies (75%). Recreation directors in cities without a policy expressed a high level of concern over enforcement issues (91%), but few problems were reported (26%) in communities with a tobacco-free park policy. Broad support for tobacco-free park policies exists among the public at large and among park and recreation directors who work in tobacco-free parks. Fears of policy difficulties among park and recreation directors who work in parks without a tobacco-free policy are much greater than actual problems experienced in Minnesota tobacco-free park areas. PMID- 17365727 TI - Tobacco possession, use, and purchase laws and penalties in Minnesota: enforcement, tobacco diversion programs, and youth awareness. AB - State youth access laws often include restrictions for minor possession, use, or purchase of tobacco (PUP). The Minnesota PUP law allows cited youth to attend a tobacco diversion program in lieu of fines. We surveyed county attorneys in all counties (N = 87), tobacco diversion program coordinators (N = 47), and adolescents (N = 3,377) to assess PUP enforcement level, tobacco diversion program quality, and youth awareness of and experience with PUP laws and penalties. Although almost all county attorneys reported enforcement of the law, mean citation rates were low (9.3/1,000 youth) but somewhat higher in counties with tobacco diversion programs than in counties without such programs. Program coordinators also reported low attendance (Mdn = 30 adolescents per year per program). Almost 70% of classes were 2 h or less, and just 21.3% included multiple sessions; little variation in program approach or materials was observed, nor did programs meet criteria recommended for effective smoking cessation programs in this population. Overall, 59% of adolescents (79% among smokers) reported having heard of adolescents being caught by police or at school for smoking. Smoking prevalence was lower in counties with tobacco diversion programs than in counties without such programs (11.6% vs. 14.6%; adjusted OR = 0.8, 95% CI = 0.6-1.1). Receipt of a citation and attendance in a special class were more commonly reported among past-month smokers who lived in counties with tobacco diversion programs; the association for class attendance reached statistical significance. Our adolescent data provide some support for PUP laws as a potential tobacco control strategy, yet low citation rates and attendance in diversion programs of limited scope reduce the likelihood of detecting any benefit associated with this approach. PMID- 17365728 TI - Lesbian, gay, bisexual, and transgender youths: who smokes, and why? AB - Existing research indicates the rate of smoking among lesbian, gay, bisexual, and transgender (LGBT) youths exceeds the general population's, possibly due to stress, habitual substance abuse, socializing in smoky venues, and tobacco marketing. The study's overall aim was to conduct qualitative research regarding tobacco use and avoidance by LGBT youths. This report focuses on identifying priority subpopulations and corresponding risk and resiliency factors. Purposive and maximum variation sampling were used to select 30 LGBT youths and 30 interactors for face-to-face interviews. Almost a third of participants said that all LGBT youths are at risk for smoking. Other respondents specified a range of high-risk groups, encompassing many subpopulations. Contributing factors for smoking included personal characteristics, interpersonal issues, environmental conditions, and structural issues. More than a third of young smokers were not acquainted with LGBT nonsmokers and could not imagine how they avoid using tobacco. Half of the interactors and four youths ascribed favorable qualities to nonsmokers--such as self-esteem, will power, and concern for personal health, appearance, and well-being. In conclusion, smoking is a pervasive problem among LGBT youths. The findings corroborate prior explanations and implicate new ones. Some risks (e.g., limited opportunities to socialize with LGBT peers outside of smoking venues, the desire to appear more masculine, and sexuality-related stress) and resiliency factors (e.g., positive sexual identity) are unique to LGBT populations, reinforcing the need for culturally specific approaches to prevention and cessation. Highlighting the positive attributes of nonsmokers and nonsmoking might prove useful in prevention campaigns. PMID- 17365729 TI - A comparative study of sociocultural factors and young adults' smoking in two Midwestern communities. AB - Young adults were the only age group to defy the downward trend in cigarette use seen in the 1980s and 1990s. To help explain this phenomenon, we conducted an exploratory study to examine the association between the sociocultural contexts of young adults' everyday lives and their smoking attitudes and behaviors. "Context" was operationalized by (a) including students and nonstudents in the study population, and (b) selecting two distinctly different areas of Minnesota for examination. The study sites were Hibbing and environs (Range), the sparsely populated hub of the state's once-thriving iron ore industry, and the Twin Cities metropolitan area (Metro), center of state government, finance, transportation, education, and industry. This report focuses on the first phase of the study, which consisted of a computer-assisted telephone interview of 995 randomly selected young adults, aged 18-24. Approximately equal numbers of students and nonstudents were selected from each site. Exploratory factor analysis yielded four distinct scales related to alcohol consumption and partying (Drinking Behavior), the social attractiveness and utility of smoking (Social Utility), outdoor recreation (Outdoor Rec), and media use and hours of free time. We decided not to use the media and free time scale, however, because of its low Cronbach alpha (.42). We used polynomial logistic regression to evaluate the association between smoking status, gender, student status, location (Range vs. Metro), and the three retained scales. Results indicated that living on the Iron Range (OR = 2.6), being female (OR = 1.3), and scoring higher on the Social Utility scale (OR = 3.06) increased the risk of smoking, whereas being a student (OR = 0.53) decreased the risk substantially. PMID- 17365730 TI - Feasibility of promoting smoking cessation in small worksites: an exploratory study. AB - The workplace is recognized as an appropriate site for smoking cessation efforts, but little is known about promoting cessation at smaller worksites. The goal of the present study was to identify strategies for promoting smoking cessation in worksites employing 10-100 workers. Qualitative interviews were conducted with 22 employers in small businesses in the manufacturing-labor and hospitality-service sectors; and eight focus groups were conducted with 59 smokers employed in these sectors. Employers mentioned practical barriers to implementing cessation activities and reluctance to intervene in employees' personal health decisions. Nevertheless, both employers and smokers thought it was desirable and appropriate for employers to promote cessation resources to people who want to quit. Discrepancies existed between the worksite activities favored by employers and those endorsed as potentially useful by smokers. Smokers expressed interest in incentive programs, contests, and nicotine replacement products; employers favored providing information. Both groups were generally unaware of smoking cessation resources available through health plans or in the community. Results suggest that interventions should attempt to increase knowledge about available cessation resources and support for cessation at the workplace. Contests, incentives, and free samples of nicotine replacement products might be feasible and effective for promoting cessation. PMID- 17365731 TI - Abstracts of the 12th Annual Meeting of the Society for Research on Nicotine and Tobacco. Orlando, Florida, USA. February 15-18, 2006. PMID- 17365732 TI - Sensitization to nicotine: how the animal literature might inform future human research. AB - Despite a rich neuroscience literature on sensitization, this phenomenon has been neglected in clinical nicotine research. This paper offers a primer on the neuroscience of nicotine sensitization for behavioral scientists, identifying key concepts, potential theoretical and clinical implications, and directions for future research. Sensitization to a drug occurs when repeated exposures to the same dose produce greater responses. In animals, sensitization to nicotine, morphine, alcohol, cocaine, amphetamine, and methamphetamine manifests as increased locomotor activity. In animals, sensitization to nicotine begins with the first dose and is maximal within 5-7 days. It involves multiple neurotransmitters, receptors, and brain structures and cannot be attributed to any single alteration. The processes involved in its induction and expression are not identical. The neurologic changes associated with sensitization are not consistent across drugs, suggesting that sensitization is not an accident of neurophysiology but perhaps an exaggerated adaptive response. Sensitization is incorporated into two theories of addiction: incentive-sensitization and sensitization-homeostasis. Whether sensitization occurs in humans and how it is expressed is unclear, as is its role in human addiction. PMID- 17365733 TI - Spirometry as a motivational tool to improve smoking cessation rates: a systematic review of the literature. AB - Obtaining spirometric testing and providing those results to individuals who smoke has been advocated as a motivational tool to improve smoking cessation. However, its effectiveness is not known. We conducted a systematic review to determine if this approach improves rates of smoking cessation. Data sources included MEDLINE (1966 to October 2005), the Cochrane Library, and experts in the field. Eligible randomized controlled trials (RCTs) enrolled at least 25 smokers per arm, evaluated spirometry with associated counseling or in combination with other treatments, followed subjects at least 6 months, and provided smoking abstinence rates. Results from nonrandomized studies also were summarized. The primary outcome was patient-reported long-term (at least 6 months) sustained abstinence with biological validation. Additional outcomes included self-reported abstinence and point-prevalence abstinence. Seven RCTs (N = 6,052 subjects) met eligibility criteria. Follow-up duration ranged from 9 to 36 months. In six trials, the intervention group received concomitant treatments previously demonstrated to increase cessation independently. The range of abstinence was 3% 14% for control subjects and 7%-39% among intervention groups, statistically significantly in favor of intervention in four studies. The only RCT that assessed the independent contribution of spirometry in combination with counseling demonstrated a nonsignificant 1% improvement in patient-reported point prevalence abstinence at 12 months in the group that received spirometry plus counseling versus counseling alone (6.5% versus 5.5%). Findings from observational studies were mixed, and the lack of controls makes interpretation problematic. Available evidence is insufficient to determine whether obtaining spirometric values and providing that information to patients improves smoking cessation compared with other smoking cessation methods. Spirometric values are of limited benefit as a predictor of smoking cessation or as a tool to "customize" smoking cessation strategies. PMID- 17365734 TI - Assessment of parents' smoking behaviors at a pediatric emergency department. AB - The pediatric emergency department is an important source of treatment for children with complaints related to environmental tobacco smoke (ETS) and may provide a teachable moment to address parent smoking. Parents who smoke were recruited from a pediatric emergency department waiting room and completed an interview assessment used to develop intervention messages. Of the 715 parents in the final sample, 77% were women, 60% White, and 60% low income ( or = 6-month) abstinence rates among smokeless tobacco (ST) users. Available evidence suggests that underdosing may occur with standard-dose nicotine replacement therapy (NRT) in ST users. We investigated the effect of high-dose nicotine therapy on tobacco withdrawal symptoms among ST users in a randomized, controlled clinical pilot study. A total of 42 ST users using at least 3 cans or pouches per week were randomized to nicotine patch doses of 63, 42, or 21 mg/day or placebo for 8 weeks. Multiple daily assessments of tobacco withdrawal and nicotine toxicity were obtained with an electronic diary. During the first week of nicotine patch therapy, we observed a dose-response relationship such that higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.87, p = .009), less negative affect (chi2 = 3.85, p = .05), and less restlessness (chi2 = 3.90, p = .048). During the second week, higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.77, p = .009). Overall, the frequency of nicotine toxicity symptoms did not differ by dose group. Of specific symptoms, nausea was observed to be more frequent in the 63 mg/day dose group compared with placebo (p = .035). In conclusion, high-dose nicotine patch therapy resulted in a greater reduction of tobacco withdrawal symptoms among ST users using at least 3 cans per week. High-dose nicotine patch therapy is safe and well tolerated in this population of tobacco users. PMID- 17365736 TI - The influence of cigarette smoking on adult asthma outcomes. AB - Despite having a chronic respiratory disease, adults with asthma do not appear to selectively avoid smoking. We used data from a prospective cohort study of 865 adults, with asthma recruited from a large managed care organization after hospitalization for asthma. In this study, we analysed the association between cigarette smoking and asthma health outcomes, controlling for age, sex, race, educational attainment, household income, atopic history, and history of childhood asthma onset. Current smoking was associated with increased severity of asthma (mean increment, 1.36 points; 95% CI = 0.36, 2.36), worse asthma-specific quality of life (mean score increment, 5.49 points; 95% CI = 2.19, 8.78), and worse generic mental health status (mean score decrement, -4.57 points; 95% CI = 7.01, -2.12); p<.05 in all cases. Current smoking also was associated with a greater longitudinal risk of hospitalization for asthma (OR = 1.86, 95% CI = 1.03, 3.36). Our results suggest that the pubic health consequences of smoking, in terms of additional asthma morbidity, are considerable. Smoking is a modifiable risk factor for adverse asthma health outcomes. Public health interventions should focus on smoking reduction among adults with asthma. PMID- 17365737 TI - Western media's influence on Egyptian adolescents' smoking behavior: the mediating role of positive beliefs about smoking. AB - Western media has been implicated as an adolescent smoking risk factor in numerous Western studies, but little research has investigated that influence on adolescents from developing Arab countries. One such country is Egypt, which has the highest rate of smoking in the Arab world. An estimated 34% of Egyptians are daily smokers, 4% of whom are under the age 15 years and 0.6% of whom are under the age 10. The present study investigated the association between exposure and receptivity to Western media, positive beliefs about smoking, and Egyptian adolescents' smoking behavior. A school-based cross-sectional survey of 1,930 Egyptian adolescents in 7th, 9th, and 12th grades, from randomly selected schools in Alexandria, Egypt, was conducted in May 2003. Self-reported smoking behaviors, demographics, psychosocial factors, and exposure to Western and pro-tobacco media were assessed. Controlling for demographics, psychosocial smoking risk factors, and pro-tobacco media exposure, we found that Western media exposure was positively associated with ever-smoking across genders and 30-day smoking among adolescent males only. Positive beliefs about smoking partially mediated this association among ever-smokers and completely mediated it among 30-day male smokers. The results indicate that the influence of Western media on Egyptian adolescents' smoking behavior is at least partially mediated by its influence in increasing adolescents' positive beliefs about smoking and consequently their smoking behavior. Regulation of the glamorization of smoking behavior in Western media and correction of the erroneous perception of positive beliefs about smoking among adolescents is necessary to help curb the rising smoking epidemic in Egypt. PMID- 17365738 TI - Nicotine, cotinine, withdrawal, and craving patterns during smoking and nicotine nasal spray use: results from a pilot study with African American men. AB - Nicotine intake via smoking is highly variable. Individualized dosing of nicotine replacement therapy (NRT) may improve product efficacy, but a better understanding of the within-day and within-subject relationships between smoking, NRT use, nicotine and cotinine concentrations in blood, and cravings and withdrawal symptoms is needed to inform dosing algorithms. A pilot study was undertaken to collect data on these relationships and to assess the feasibility of the methods needed for this type of research, including a sophisticated statistical modeling technique (a two-part mixed-effects model with correlated random effects that accounts for clumping at zero). Because nicotine metabolism varies by gender and race, the sample was homogeneous with respect to these characteristics. In a within-subjects study, 27 African American adult male smokers carried a computerized cigarette dispenser for 1 week, capturing the time each cigarette was smoked. Subjects then entered an inpatient setting for 1 day of scheduled smoking (matched to data from the cigarette dispenser to create an ecologically valid schedule) and 4 days of ad libitum nicotine nasal spray use, while tobacco abstinent. Eight times per day, at 2-hour intervals, blood was drawn and ratings of cigarette cravings and withdrawal symptoms were obtained. On average, subjects used less than half of the manufacturer's recommended minimum daily dose of nicotine nasal spray. Large differences in nicotine and cotinine levels were observed between individuals. When predicting nicotine, cotinine, withdrawal, and cravings, we observed significant interactions between route of nicotine intake and a variety of independent variables. PMID- 17365739 TI - The variability of urinary cotinine levels in young children: implications for measuring ETS exposure. AB - This study examined the within-subject variability of urinary cotinine levels in young children (aged = 0.6-7.2 years) of smoking parents to determine the number of urine samples needed to provide accurate estimates of exposure to environmental tobacco smoke (ETS) for different time intervals. Secondary analyses were conducted of five independent studies (N = 376), in which multiple urinary cotinine measures had been collected over time periods up to 13 months. Over measurement periods of 4-15 days, the within-subject cotinine levels varied 3-5 times more than would be expected based on measurement error alone. Over 7-13 months, the within-subject variability was 10-20 times higher than would be expected based on the measurement error. Findings indicated that cotinine measures from single urine samples provided highly accurate estimates of only recent exposure (i.e., 2-3 days; rho = 0.99). To achieve similarly precise estimates of the mean cotinine level of an individual child over 4-15 days, up to nine urine samples may be necessary. Up to 12 urine samples may be required to achieve similarly precise estimates of ETS exposure over a 4- to 13-month period. Epidemiologic and clinical research on ETS exposure in children can benefit from multiple urine samples (a) to accurately measure average exposure at the level of the individual child, (b) to describe temporal patterns, (c) to detect incidences of peak exposure that would remain underrecognized if monitoring is limited to a single time point, and (d) to establish stable baseline levels and endpoints based on urine samples collected over clinically relevant time periods. PMID- 17365740 TI - Decomposing the value of cigarettes using experimental auctions. AB - Using a new brand of cigarettes with less nicotine content than conventional cigarettes, we conducted experimental auctions at two grocery stores to estimate smokers' value of nicotine. Our approach is novel because the brand of cigarettes auctioned was new to the market and the cigarette's nicotine content is reduced using genetic modification, with no effect on the taste of the cigarettes. We found smokers would be willing to pay US$1.25-$1.45 for a pack of cigarettes with no nicotine and $1.59-$1.66 for a pack of cigarettes with low levels of nicotine. PMID- 17365741 TI - Menthol cigarettes and health risks in Lung Health Study data. AB - Whether menthol cigarettes confer a higher risk of death than plain cigarettes is not known. The Lung Health Study (LHS) enrolled 5,887 adult smokers in a clinical trial of smoking cessation and ipratropium in the prevention of chronic obstructive pulmonary disease. LHS participants have been subjected to surveillance for mortality from all causes for 14 years. We examined these data for differences between self-reported smokers of menthol cigarettes versus plain cigarettes. Using proportional hazards regression methods, we found no differences in hazard ratios for coronary heart disease, cardiovascular disease, lung cancer, or death from any cause. Contrary to expectations about nicotine dependence, we found that users of menthol cigarettes had smoked fewer pack-years at baseline. We found no difference in success at smoking cessation with or without menthol. We conclude that our data contain no evidence that mentholation of cigarettes increases the hazards of smoking. PMID- 17365742 TI - The relative contributions of parenting practices in smoking behavior of adolescents with and without asthma. AB - This study tested associations between general parenting dimensions, antismoking socialization practices, and parental smoking status on the one hand and adolescent smoking on the other. These associations were examined within asthmatic adolescents, a group particularly vulnerable to the effects of smoking. Participants were 9,008 young adolescents (aged 11-16 years) from the Netherlands. Associations between factors were tested separately as well as in a combined model using multiple logistic regression analyses. Adolescents with current asthma were more at risk of being current regular smokers. Higher scores on parental involvement and strictness, antismoking socialization, and parental smoking abstinence were associated with lower odds of adolescent smoking. Parents of asthmatic adolescents were more likely to use involvement and strictness. Despite the increased health risks of smoking for people with asthma, parents of asthmatic children were generally not more engaged in antismoking socialization; they just talked more about not smoking. Furthermore, parents of adolescents with asthma were more likely to smoke than were parents of adolescents without asthma. In general, multiple logistic regression analyses showed similar effects for nonasthmatic and asthmatic adolescents. Diagnosis of asthma should be followed by suggestions for parents on how to use antismoking socialization (e.g., setting rules). In addition, the importance of having nonsmoking parents in smoking prevention should be emphasized. PMID- 17365743 TI - Cotinine levels in relation to smoking behavior and addiction in young adolescent smokers. AB - The goal of this study was to identify associations among self-reported nicotine exposure, nicotine addiction, and actual nicotine intake as measured by salivary cotinine levels in adolescent smokers. A total of 170 adolescent smokers with a mean age of 15 years were recruited from seven northern Californian public high schools. Data were collected on smoking behaviors, addiction, craving, and withdrawal. Nicotine dependence was assessed using a modified teen Fagerstrom Tolerance Questionnaire (mtFTQ), a modified Nicotine Dependence Syndrome Scale (mNDSS), and a simple self-rating. Withdrawal was assessed using the Minnesota Withdrawal Questionnaire, and craving was assessed using a survey created by the authors. Salivary cotinine levels were collected from and analysed in participants who self-identified as smokers; data from the 54 participants who smoked in the past 4 days and whose salivary cotinine levels were greater than 0.1 ng/ml were used in the analysis. Among this group of adolescent smokers, the mean number of cigarettes smoked per day was 3.51 (SD = 3.44) and the mean level of salivary cotinine was 44.1 ng/ml (Mdn = 24.2). Even at this low level of nicotine exposure, cotinine was highly correlated with measures of nicotine dependence such as the mtFTQ (r = 0.497, p = .001), NDSS (r = 0.439, p = .002), timing of craving in the morning (r = -0.601, p = .000), and self-rated addiction (r = 0.562, p = .000). Most interesting, cotinine levels reached a plateau at around 4-5 cigarettes/day. PMID- 17365744 TI - Ethnic differences among adolescents seeking smoking cessation treatment: a structural analysis of responses on the Fagerstrom Test for Nicotine Dependence. AB - Features of tobacco dependence vary by ethnicity, which could be partially due to measurement bias inherent in instruments that assess nicotine dependence. This study compared responses on the Fagerstrom Test for Nicotine Dependence (FTND) by African American adolescents (n = 478) with those of White adolescents (n = 661) seeking smoking cessation treatment. We conducted item-by-item comparisons by ethnicity for the six questions composing the FTND and confirmatory factor analyses and multiple indicators-multiple causes (MIMIC) modeling to test the hypothesis of measurement invariance of the FTND by ethnicity. Study participants (N = 1,139) were daily smokers of average age 15.4 years (SD = 1.3); 42.0% were African American and 61.5% female. White adolescents' pattern of responses to the FTND indicated a greater degree of dependence; these differences were statistically significant for five of the six items. The FTND exhibited a unidimensional structure with similar factor loadings in both White and African American adolescents. However, MIMIC modeling indicated differential reporting for three out of six items, suggesting that the FTND may not measure nicotine dependence equivalently for White and African American youth. PMID- 17365745 TI - Cholecystokinin C-45T polymorphism and smoking cessation in women. AB - In view of the effect of cholecystokinin (CCK) on dopaminergic neurons in the mesolimbic "reward" pathway of the brain, its gene has been a focus in studies of dopamine-related conditions and behaviors, including smoking. We assessed the association between the CCK C-45T polymorphism and smoking cessation among women who participated in a randomized clinical trial of d,l-fenfluramine conducted in the Seattle area in 1993-1994. Several years later (Mdn = 3.3 years, range = 2.4 6.9 years), 593 women provided a biological specimen and updated information about smoking habits. We defined short-term quitting as not smoking for at least 7 days immediately preceding the final (12-month) clinical trial visit, and long term quitting as not smoking for at least the 6-month interval before the later recontact. CCK C-45T was not associated with either short-term (relative risk [RR] associated with the presence of T allele = 0.9, 95% CI = 0.6-1.4) or long term (RR = 1.0, 95% CI = 0.6-1.5) smoking cessation. Also, we observed no association of this polymorphism with smoking cessation in subgroups of women defined by age or body mass index. No clear differences were found in smoking cessation rates associated with the presence of the T allele among women treated with d,l-fenfluramine versus those randomized to placebo. Our results fail to support prior evidence of an association of the CCK C-45T polymorphism with the ability to quit smoking. PMID- 17365746 TI - Adolescent risk factors for late-onset smoking among African American young men. AB - This study examined adolescent risk factors for late-onset cigarette smoking among African American males. Data came from the Pittsburgh Youth Study, a longitudinal study of young men followed from age 13 to age 25. Individuals who began smoking at age 17 or older were compared with those who began smoking by age 16 and with those who never smoked in terms of risk factors measured in middle (at age 16) and late adolescence (from age 17 to 19). The study included 281 African American young men. A total of 18 psychological, behavioral, and environmental risk factors were measured at age 16, and 19 risk factors were measured between ages 17 and 19. Several risk factors at age 16 differed between early-onset and late-onset smokers or nonsmokers; however, in multivariate analyses, only peer drug use and truancy were significant. Among the age 16 risk factors, only truancy differentiated late-onset smokers from nonsmokers. Late adolescence behavioral risk factors were significantly related to late-onset smoking. However, only smoking marijuana and highest grade completed differentiated late-onset smokers from nonsmokers in multivariate analyses. Well established predictors of cigarette smoking assessed in middle adolescence could identify individuals who already smoked but could not distinguish between those who would and would not begin smoking later. Late adolescence life transitions were not related to late-onset smoking. More research is needed to examine contextual factors in late adolescence and early adulthood that protect against and precipitate late-onset of smoking for African Americans. PMID- 17365748 TI - Tobacco use and dependence in Asian Americans: a review of the literature. AB - This article reports on an integrative review of literature on Asian American tobacco use and dependence, identifies gaps in the literature, and proposes studies needed in the future. Articles were retrieved from electronic health related databases indexed for permutations of the keywords Asian Americans, smoking, tobacco use, tobacco dependence, and nicotine dependence. A manual search also was done to identify additional literature. A total of 216 articles were identified; the review includes 39 articles reporting gender- and ethnic specific information on subgroups of Asian Americans in the following areas: Smoking prevalence, correlates of smoking, and tobacco dependence treatment. In addition, 13 articles on tobacco and nicotine metabolism were reviewed. Empirical studies have concentrated on Chinese, Korean, and Vietnamese American men. Smoking prevalence is higher among Asian American men with low acculturation than among their counterparts, but the reverse pattern is observed among Asian American women. Asian Americans tend to smoke fewer cigarettes per day than White Americans, and this difference may be explained by differences between the two groups in nicotine metabolism. More research is needed on this diverse population, especially Asian American women of all ethnic subgroups and Asian Indian, Filipino, Pakistani, and Thai American men. A need also exists for the development of specialized tobacco dependence treatments to address the cultural issues of specific Asian American ethnic subgroups, to enhance access to treatment, and to determine how treatment recommendations should reflect differences in acculturation level and tobacco and nicotine metabolism. PMID- 17365749 TI - Expressive writing as a smoking cessation treatment adjunct for young adult smokers. AB - This investigation evaluated the efficacy of expressive writing as a treatment adjunct to a brief office smoking cessation intervention plus nicotine patch therapy in young adults. Participants aged 18-24 years were randomized to a brief office intervention (n=99) or to an expressive writing plus brief office intervention (n=97). Both conditions received four individual visits plus 6 weeks of nicotine patch therapy, which began on the quit date following the week 2 visit. Participants in the expressive writing plus brief intervention condition wrote for 2 consecutive days before and 3 consecutive days after the quit date. The brief office intervention group completed a control writing assignment. At end of treatment (week 8), biochemically confirmed 7-day point-prevalence abstinence for the expressive writing plus brief office intervention condition was significantly greater than for the brief office condition (33% vs. 20%, p=.043, OR=2.0, 95% CI=1.0-3.7, from a logistic regression adjusting for gender). At 24 and 52 weeks, abstinence rates were similar for the brief office intervention versus expressive writing plus brief office intervention (12% vs. 11% at 24 weeks; 11% vs. 11% at 52 weeks). The results suggest that expressive writing has promise as a smoking cessation treatment adjunct for young adults. Lengthier interventions or the use of boosters should be tested to extend treatment effects. However, participants reported a low level of enthusiasm for the expressive writing, which may be a barrier to implementing it over a longer time frame. Therefore, other modes of delivering expressive writing to young adult cigarette smokers should be explored. PMID- 17365750 TI - Smoking practices, risk perception of smoking, and environmental tobacco smoke exposure among 6th-grade students in Ciudad Juarez, Mexico. AB - This study assessed the smoking practices, risk perception of smoking, and environmental tobacco smoke (ETS) exposure among adolescents in Ciudad Juarez, Mexico. We used a cross-sectional method to examine the smoking practices, risk perception of smoking, and ETS exposure of 6th-grade students (N=506), aged 11-13 years, attending six randomly selected middle schools. Schools were classified by school setting (i.e., public vs. private) and socioeconomic status (SES; i.e., low, middle, or high). The results indicated that 6th-grade students attending a public, low-SES school setting in Ciudad Juarez not only exhibited significantly higher rates of ETS exposure at home and in public places (p<.01) but also were more likely to have tried smoking (p<.01) and to be current smokers (p<.01), and were less likely to support a ban on smoking in public places (p<.01), compared with students who attended a private school or a public, middle- or high-SES school setting. These results provide further evidence that public health interventions to prevent initiation of smoking and to assist in smoking cessation among adolescents and to reduce their ETS exposure at home and in public need to target all school-aged students, especially those attending school in a low-SES settings. PMID- 17365751 TI - Physical work-induced oxidative stress is exacerbated in young cigarette smokers. AB - Both cigarette smoking and strenuous physical work are associated with increased oxidative stress, which is implicated in the pathogenesis of cardiovascular disease. No study to date has measured oxidative stress in response to graded exercise in cigarette smokers. We compared oxidative stress biomarkers before and after strenuous exercise (Bruce treadmill protocol) in 14 cigarette smokers and 15 nonsmokers of similar age (24+/-6 years) and fitness status. Plasma protein carbonyls (PC), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were measured pre- and postexercise. Smoking status (p<.01) and time (p<.01) effects were noted for PC with values higher for smokers than nonsmokers and increasing from pre- to postexercise (52% vs. 25%, respectively). The smoking statusxtime interaction for PC approached statistical significance (p=.07). The change in PC from pre- to postexercise was positively correlated with the number of cigarettes smoked per day (r=.5782, p=.03). A smoking statusxtime interaction was noted for MDA (p<.01), with values increasing 37% from pre- (0.6140+/-0.0708 micromol/L) to postexercise (0.8440+/-0.0687 micromol/L) for smokers and remaining relatively unchanged for nonsmokers (from 0.7664+/-0.0901 to 0.7419+/-0.0776 micromol/L). 8 OHdG was unaffected by smoking status (p=.43) or exercise (p=.40). These findings indicate that young cigarette smokers experience an exaggerated oxidative stress response to strenuous physical work, compared with nonsmokers of similar age. These results highlight yet another detrimental impact of cigarette smoking on human health. Future investigations should focus on older, more established smokers. PMID- 17365752 TI - College student involvement in cigarette smoking: the role of psychosocial and behavioral protection and risk. AB - A theory-based protection and risk model was applied to explain variation in college students' cigarette smoking. Key aims were to examine whether psychosocial and behavioral protective and risk factors can account for cross sectional and developmental variation in smoking, and to examine whether protection moderates the impact of risk on smoking involvement. Data for this three-wave longitudinal study were collected in fall 2002, spring 2003, and spring 2004 from 549 male and 427 female first-semester college students at the University of Colorado, Boulder. A 32-page questionnaire was used, with content theoretically derived from the constructs in problem-behavior theory. Cigarette smoking (number of cigarettes smoked on an average day in the past month), three types of psychosocial protection (models protection, controls protection, support protection), three types of psychosocial risk (models risk, opportunity risk, and vulnerability risk), two types of behavioral protection (church involvement, academic achievement), and two types of behavioral risk (problem drinking, marijuana use) were assessed. Psychosocial and behavioral protective and risk factors accounted for significant variation in smoking involvement, and protection moderated the impact of risk. Findings were consistent, for the most part, for both genders and across three separate waves of data. Key predictors of smoking involvement included controls protection, models risk, vulnerability risk, behavioral protection, and behavioral risk. Antecedent protective and risk factors were associated with the initiation of smoking in the college setting. A model of protective and risk factors can be useful in understanding college smoking behavior and suggesting targets for intervention. PMID- 17365753 TI - The serotonin transporter 5-HTTLPR polymorphism and treatment response to nicotine patch: follow-up of a randomized controlled trial. AB - In this follow-up of a randomized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation, 741 smokers of European ancestry who were randomized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region. The study setting was a primary care research network in Oxfordshire, United Kingdom. The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up. The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment (SL: p=.33; SS: p=.81) or 24-week follow-up (SL: p=.05; SS: p=.21), and we found no evidence for a genotypextreatment interaction effect. In summary, despite the theoretically important contribution of serotonin neurotransmission to smoking cessation, the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care based trial. PMID- 17365754 TI - Nicotine lozenges for the treatment of smokeless tobacco use. AB - Nicotine lozenges have been shown to increase tobacco abstinence rates in cigarette smokers, but they have not been evaluated in smokeless tobacco (ST) users. We conducted an open-label, one-arm, phase II clinical trial to evaluate the efficacy of the 4-mg nicotine lozenge for the treatment of withdrawal and craving associated with tobacco abstinence among ST users. Eligible subjects received 4-mg nicotine lozenges for 6 weeks followed by a 6-week taper. Subjects completed daily tobacco withdrawal diaries, and data on lozenge use, adverse events, and lozenge acceptability were collected. Urine anabasine was collected at 3 and 6 months for biochemical confirmation of self-reported tobacco abstinence. Participants were 30 ST users with a mean age of 35.4 years (SD=6.5) using an average of 4.2 cans or pouches (SD=3.2) of ST per week for a mean of 15.1 years (SD=6.5). Among subjects continuously tobacco abstinent for the first 2 weeks, no significant increases in composite withdrawal symptoms were observed, compared with baseline symptoms, whereas craving decreased significantly. Biochemically confirmed 7-day point-prevalence tobacco abstinence was 53% (95% CI=34%-72%) at 12 weeks (end of treatment) and 47% (95% CI=28%-66%) at 6 months. Few adverse events attributable to the nicotine lozenge occurred, and the lozenge was perceived as helpful in assisting subjects quit ST. The use of the 4-mg nicotine lozenge appears promising for the clinical treatment of withdrawal symptoms and craving associated with tobacco abstinence in ST users. Future phase III clinical trials investigating the efficacy of nicotine lozenges are warranted. PMID- 17365755 TI - Cigarette smoking and quitting behaviors among unemployed adults in the United States. AB - Little is known about factors associated with smoking among the unemployed. This study estimated the prevalence of smoking and examined sociodemographic factors associated with current, former, and successful quitting among unemployed adults aged 18-64. Cross-sectional data on 13,480 participants in the 1998-1999 and 2001 2002 Tobacco Use Supplements to the Current Population Surveys were analyzed. Multivariate logistic regression analyses were used to examine factors associated with study outcomes (current vs. never, former vs. current, successful quitter vs. other former smoker). Among the unemployed, 35% were current smokers and 13% were former smokers. Of the former smokers, 81% quit successfully for at least 12 months. Participants with family incomes of less than US$25,000 were more likely than those with incomes of $50,000 or more to currently smoke (OR=2.13, 95% CI=1.85-2.46). Service workers and blue-collar workers were less likely than white-collar workers to report former smoking. Participants unemployed for 6 months or more were twice as likely as those unemployed for less than 6 months to quit successfully (OR=2.05, 95% CI=1.07-3.95). Unemployed blue-collar workers had a greater odds ratio of successfully quitting than white-collar workers (OR=1.83, 95% CI=1.17-2.87). Smoking rates were high among the unemployed, and quitting behaviors varied by sociodemographic factors and length of unemployment. Studies are needed to examine the feasibility of cessation interventions for the unemployed. PMID- 17365756 TI - Design and evaluation of a tobacco-prevention program targeting Chinese American youth in New York City. AB - In 1994 the Centers for Disease Control and Prevention recognized the importance of incorporating tobacco prevention programs into school curricula with the publication of guidelines for such programs. Included in these guidelines are recommendations to provide instruction about the consequences of tobacco use and to provide tobacco prevention programs to all students, with a particularly intensive curriculum in junior high school. Many school-based programs have been developed and tested; however, most have been delivered in English. This paper presents a culturally appropriate tobacco prevention curriculum developed for Chinese American 7th and 8th graders. The curriculum was delivered by a community organizer, in conjunction with lay health advocates, in one junior high school with a large proportion of Chinese immigrant students in New York City. This curriculum, delivered in English and Mandarin, began with 7th graders in four classrooms and consisted of seven sessions during the first year with a booster session the second year. Various presentation methods were used, including lectures, videos, demonstration, and group discussion. Valuable information about components that worked well and parts that need to be improved was gathered from school administrators, teachers, lay health advocates, and the community organizer who delivered the curriculum. This information should be incorporated into future tobacco prevention programs targeting the Chinese American community. PMID- 17365757 TI - Overcoming barriers to recruitment and retention in adolescent smoking cessation. AB - Participant recruitment and retention have been identified as challenging aspects of adolescent smoking cessation interventions. Problems associated with low recruitment and retention include identifying smokers, obtaining active parental consent, protecting participants' privacy, respecting participants' autonomy, and making participation relevant and accessible to adolescents. This paper describes nine strategies for minimizing these recruitment and retention problems via a proactive telephone counseling intervention, and reports on their simultaneous implementation among 1,058 smokers from 25 high schools in Washington state. Results are as follows: (a) 85.9% of parents of minor-age seniors provided active consent for their teen's participation, (b) 89.8% of eligible smokers were successfully contacted by counselors, (c) 86.5% of contacted smokers consented to participate in the cessation counseling, (d) 93.8% of consented smokers participated in smoking cessation counseling calls, and (e) 72.2% of participating smokers completed their full intervention. These results demonstrate that older teens who smoke, and their parents, are receptive to confidential cessation counseling that is personally tailored, supportive of their autonomy, and proactively delivered via the telephone. PMID- 17365758 TI - Anticipating clinical integration of genetically tailored tobacco dependence treatment: perspectives of primary care physicians. AB - Emerging research will likely make it possible to tailor pharmacological treatment for individuals with tobacco dependence by genotype. This study explored primary care physicians' attitudes about the strengths of and barriers to using genetic testing to match patients to optimal nicotine replacement therapy. Four focus groups (n=27) were conducted, and data were analyzed using thematic content analysis. Physicians reported how likely they would be to offer patients a genetic test to tailor smoking treatment in response to three different scenarios that described characteristics of the genetic test based on published research. Respondents were on average 36 years of age; 59% were male and 67% were white. Physicians believed genetically tailored treatment may offer new hope to smokers trying to quit, yet they also noted several potential barriers to clinical integration. Barriers included erroneous assumptions by patients regarding the meaning of genetic test results, possible misinterpretation of information regarding racial differences in the prevalence of certain risk alleles, and potential discrimination against patients undergoing testing. Concerns increased dramatically when physicians were told that the same genotypes that would be identified to tailor smoking treatment also have been associated with increased risk of becoming addicted to nicotine, as well as other addictions and psychiatric disorders. Physicians were interested in the possibility of realizing improved smoking cessation outcomes through pharmacogenetic developments, but they also raised many concerns. Primary care physicians will need additional educational inputs and system support prior to integrating genetic testing for a common trait into their routine clinical practice. PMID- 17365759 TI - Self-help cessation programs for smokeless tobacco users: long-term follow-up of a randomized trial. AB - This paper presents long-term outcomes of the largest clinical trial of smokeless tobacco (SLT) cessation reported to date. SLT users in five northwestern states were recruited to call a toll-free number, and 1,069 users were randomized to one of two self-help conditions: either a manual-only condition or an assisted self help condition, which included the manual, a targeted video, and two support phone calls. Significant between-group differences were not found for either the 12- or 18-month point-prevalence measure of abstinence from either SLT only or all tobacco products using outcomes based on either the responder or intention-to treat outcomes. However, using a repeated point-prevalence measure across all three assessment points, we found that significantly more assisted self-help participants reported abstinence, compared with manual-only participants. Compared with manual-only participants, those in the assisted self-help condition were significantly more likely to use recommended cessation techniques. Results demonstrate that low-cost, minimal interventions delivered by mail and phone can help a sizable proportion of individuals quit using SLT. PMID- 17365760 TI - Gabapentin for smoking cessation: a preliminary investigation of efficacy. AB - Gabapentin affects the glutamate and gamma amino butyric acid (GABA) neurotransmitters through which it may facilitate smoking abstinence. To obtain preliminary estimates of efficacy of gabapentin for smoking cessation, we conducted a single-arm, open-label study of gabapentin, 1,800-mg/day administered in three equal divided doses for 8 weeks. A total of 50 adult smokers were enrolled. All participants received a brief behavioral intervention at each medication visit. A total of 37 participants completed all follow-up assessments. At end-of-treatment the biochemically confirmed point-prevalence and prolonged smoking abstinence rates were 28% (95% CI=16%-42%) and 24% (95% CI=13%-38%), respectively. At 6 months, the biochemically confirmed point-prevalence and prolonged smoking abstinence rates were 20% (95% CI=10%-34%) and 16% (95% CI=7% 29%), respectively. Among subjects who continued to smoke and completed the follow-up assessments, the reported number of cigarettes smoked per day (mean+/ standard deviation) was significantly less than at baseline: -10.0+/-8.2 (p<.001). Adverse effects were minor and well tolerated. Our results suggest that gabapentin may increase smoking abstinence. An adequately powered randomized clinical trial assessing different doses of this drug against a placebo would be the reasonable next step. PMID- 17365761 TI - Support for spirituality in smoking cessation: results of pilot survey. AB - Patient spiritual resources are increasingly included in the treatment of medical conditions such as cancers and alcohol and drug dependence, but use of spiritual resources is usually excluded from tobacco dependence treatment. We hypothesized that this omission may be linked to perceived resistance from smokers. To examine this hypothesis, we conducted a pilot survey to assess whether current smokers would consider spiritual, including religious, resources helpful if they were planning to quit. Smokers at least 18 years of age at Oregon Health & Science University in Portland, Oregon, (N=104) completed a brief survey of smoking behaviors and spiritual beliefs. None were attempting to quit. Of these individuals, 92 (88%) reported some history of spiritual resources (spiritual practice or belief in a Higher Power), and of those respondents, 78% reported that using spiritual resources to quit could be helpful, and 77% reported being open to having their providers encourage use of spiritual resources when quitting. Results of logistic regression analysis indicated that those aged 31-50 years (OR=3.3), those over age 50 years (OR=5.4), and women (OR=3.4) were significantly more likely to have used spiritual resources in the past. Of the 92 smokers with any history of spiritual resources, those smoking more than 15 cigarettes/day were significantly more receptive to provider encouragement of spiritual resources in a quit attempt (OR=5.4). Our data are consistent with overall beliefs in the United States about spirituality and recent trends to include spirituality in health care. We conclude that smokers, especially heavier smokers, may be receptive to using spiritual resources in a quit attempt and that spirituality in tobacco dependence treatment warrants additional investigation and program development. PMID- 17365762 TI - Secondhand smoke exposure and C-reactive protein levels in youth. AB - Using data from the National Health and Nutrition Examination Survey (NHANES, 1999-2002), we examined the association of secondhand tobacco exposure, estimated by serum cotinine, with serum C-reactive protein (CRP) concentrations in nonsmoking participants, aged 6-18 years. The association between serum cotinine and serum CRP was analyzed using multiple linear regression, with adjustment for other study variables. All analyses used weighted data and adjustments for design effects. Multiple regression analysis indicated that a change in serum cotinine of 0.5 ng/ml was associated with a 0.96 mg/dl change in CRP (95% CI=0.93-1.00), even after adjustment for age, white blood cell count, and body mass index percentile. We found a significant association between secondhand smoke exposure, assessed by serum cotinine, and elevated serum CRP among nonsmoking youth. Secondhand smoke exposure may pose an important long-term cardiovascular risk for children and adolescents. PMID- 17365763 TI - What's new in Nicotine & Tobacco Research? PMID- 17365764 TI - Effects of abstinence from tobacco: valid symptoms and time course. AB - This article updates a 1990 review of the effects of tobacco abstinence by reviewing (a) which symptoms are valid indicators of tobacco abstinence and (b) the time course of tobacco abstinence symptoms. The author searched several databases to locate more than 3,500 citations on tobacco abstinence effects between 1990 and 2004; 120 of these were used in this review. Data collection and interpretation were based solely on the author's subjective judgments. For brevity, the review does not evaluate craving, hunger, performance, and several other possible outcomes as withdrawal symptoms. Anger, anxiety, depression, difficulty concentrating, impatience, insomnia, and restlessness are valid withdrawal symptoms that peak within the first week and last 2-4 weeks. Constipation, cough, dizziness, increased dreaming, and mouth ulcers may be abstinence effects. Drowsiness, fatigue, and several physical symptoms are not abstinence effects. In conclusion, no major changes are suggested for DSM-IV criteria for tobacco/nicotine withdrawal, but some deletions are suggested for ICD-10 criteria. Future studies need to investigate several possible new symptoms of withdrawal and to define more clearly the time course of symptoms. PMID- 17365765 TI - Effects of abstinence from tobacco: etiology, animal models, epidemiology, and significance: a subjective review. AB - This article updates a 1990 review of the effects of tobacco abstinence by reviewing (a) the etiology, (b) animal models, (c) the epidemiology, and (d) the clinical significance of tobacco abstinence effects. The author searched several databases to locate more than 3,500 citations on tobacco abstinence effects between 1990 and 2004. For brevity, the review does not evaluate these effects in regard to craving, hunger, or performance. Data collection and study conclusions were based on the author's subjective judgment. The most validated etiological model suggests that withdrawal is related to decreased dopaminergic activity, but how this relates to nicotine receptor changes is unclear. The two most validated animal models describe increases in intracranial self-stimulation thresholds or observable physical signs. Significant withdrawal symptoms occur in at least half of smokers when they try to quit. Withdrawal appears to produce clinically significant distress and impairment. Increases in depression after abstinence, but not other symptoms, prospectively predict relapse. In conclusion, the proposed neurobiological mechanisms by which withdrawal occurs leave several unanswered questions. Although animal models have been developed, how well they mimic withdrawal in humans is unclear. Tobacco withdrawal is common and can be distressing. Withdrawal-induced depression appears to undermine the smoker's ability to remain abstinent. PMID- 17365766 TI - Provider feedback to improve 5A's tobacco cessation in primary care: a cluster randomized clinical trial. AB - The electronic health record (EHR) may be an effective tool to help clinicians address tobacco use more consistently. To evaluate the impact of EHR-generated practice feedback on rates of referral to a state-level tobacco quitline, we conducted a cluster randomized clinical trial (feedback versus no feedback) within 19 primary care clinics in Oregon. Intervention clinics received provider specific monthly feedback reports generated from EHR data. The reports rated provider performance in asking, advising, assessing, and assisting with tobacco cessation compared with a clinic average and an achievable benchmark of care. During 12 months of follow-up, EHR-documented rates of advising, assessing, and assisting were significantly improved in the intervention clinics compared with the control clinics (p<.001). A higher case-mix index and presence of a clinic champion were associated with higher rates of referral to a state-level quitline. EHR-generated provider feedback improved documentation of assistance with tobacco cessation. Connecting physician offices to a state-level quitline was feasible and well accepted. PMID- 17365767 TI - Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets. AB - Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+ hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task related stimuli by modulating somewhat lateralized and task-specific neural networks. PMID- 17365768 TI - Effects of smoking abstinence and alcohol consumption on smoking-related outcome expectancies in heavy smokers and tobacco chippers. AB - Smoking cessation interventions often target expectancies about the consequences of smoking. Yet little is known about the way smoking-related expectancies vary across different contexts. Two internal contexts that are often linked with smoking relapse are states associated with smoking abstinence and alcohol consumption. This report presents a secondary analysis of data from two experiments designed to examine the influence of smoking abstinence, and smoking abstinence combined with alcohol consumption, on smoking-related outcome expectancies among heavy smokers and tobacco chippers (smokers who had consistently smoked no more than 5 cigarettes/day for at least 2 years). Across both experiments, smoking abstinence and alcohol consumption increased expectancies of positive reinforcement from smoking. In addition, alcohol consumption increased negative reinforcement expectancies among tobacco chippers, such that the expectancies became more similar to those of heavy smokers as tobacco chippers' level of subjective alcohol intoxication increased. Findings suggest that these altered states influence the way smokers evaluate the consequences of smoking, and provide insight into the link between smoking abstinence, alcohol consumption, and smoking behavior. PMID- 17365769 TI - Gender differences relative to smoking behavior and emissions of toxins from mainstream cigarette smoke. AB - This study examined whether gender differences exist in the exposure to select mainstream cigarette smoke toxins as a result of differences in smoking behavior or type of cigarettes smoked among 129 female and 128 male smokers. Smoking topography data indicated that, compared with men, women took smaller puffs (37.6 ml/puff vs. 45.8 ml/puff; p = .0001) of shorter duration (1.33 s/puff vs. 1.48 s/puff; p = .002) but drew more puffs per cigarette (13.5 vs. 12.0; p = .001) and left longer butts (36.3 mm or 40.2% of cigarette length vs. 34.3 mm or 39.2% of cigarette length; p = .01). These trends were similar in both African Americans and European Americans. The emissions of select toxins per cigarette, as determined by mimicking human smoking behaviors were greater among the male smokers than the female smokers and correlated significantly with delivered smoke volume per cigarette. The geometric means of emissions of nicotine from cigarettes were 1.92 mg/cigarette (95% CI = 1.80-2.05) for women versus 2.20 (95% CI = 2.04-2.37) for men (p = .005). Cigarettes smoked by women yielded 139.5 ng/cigarette of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 95% CI = 128.8-151.0), compared with 170.3 ng/cigarette (95% CI = 156.3-185.6) for men (p = .0007); benzo(a)pyrene (BaP) emissions were 18.0 ng/cigarette (95% CI = 17.0 19.0) for women and 20.5 ng/cigarette (95% CI = 18.8-22.3) for men (p = .01). The gender differences with regard to cigarette smoke yields of toxins were more profound in European Americans than in African Americans. On average, African American men's smoking habits produced the highest emissions of select toxins from cigarettes, and European American female smokers had the lowest exposure to carcinogens and toxins. Several studies have suggested that women may be more susceptible than men to the ill effects of carcinogens in tobacco and tobacco smoke, whereas other studies have not found differences in lung cancer risk between men and women. The present study suggests that gender differences in exposure to tobacco smoke cannot account for a higher rate of lung cancer in female smokers compared with male smokers. PMID- 17365770 TI - Long-term changes in sleep and depressive symptoms of smokers in abstinence. AB - Few studies have evaluated the impact of smoking cessation on objective measures of sleep. The present study assessed the long-term effects of tobacco smoking abstinence on sleep and depression. A total of 15 chronic smokers with Hamilton Rating Scale for Depression (HAM-D) scores of less than 9 were evaluated. Subjects were screened for baseline data when they were smoking chronically. They underwent a 5-week psychological treatment for tobacco smoking, after which their depressive symptoms and sleep architecture were evaluated at 1, 2, 4, 6, 9, and 12 months of abstinence. We report the results of the seven patients who completed 1 year of evaluations and of those patients who achieved only partial abstinence. Polysomnographic recordings were taken, level of depression was measured with the HAM-D, and urinary cotinine levels also were evaluated. HAM-D scores were analyzed with and without sleep items. Nicotine abstinence reduced latency to rapid eye movement (REM) sleep and increased HAM-D scores, suggesting that chronic smokers have depressive symptoms that may be controlled by nicotine administration. PMID- 17365771 TI - Personality and smoking status: a longitudinal analysis. AB - We attempted to clarify the strength and nature of the association between personality and smoking status in early and middle adulthood, using a longitudinal study design. Data from the Medical Research Council National Survey of Health and Development, based on a stratified sample of all single, legitimate births occurring in England, Wales, and Scotland in one week of March 1946 (N = 5,362), were analyzed using generalized estimating equations methods to account for the correlation between the smoking status variables for the same individual over time. The unadjusted estimates indicated that the odds of being a current smoker increased with higher personality score for both extraversion (p<.0001) and neuroticism (p<.0001) traits. Sex was significantly associated with being a current smoker (p<.0001), with males more likely than females to be current smokers. Current smoking decreased with increasing age (p<.0001). These relationships were maintained in the fully adjusted model. These data indicate that both higher levels of extraversion and higher levels of neuroticism, as measured at age 16, are independently associated with an increased likelihood of subsequently being a current smoker rather than a nonsmoker at all time points, although the observed effect sizes were small. Males also were more likely than females to be current smokers, and increasing age reduced the likelihood of being a current smoker, which is consistent with an attempt by a subset of smokers in the cohort to subsequently stop smoking. PMID- 17365772 TI - Personality and smoking status: a meta-analysis. AB - We used meta-analytic techniques in an attempt to clarify the strength and direction of the association between smoking status and personality, which narrative reviews have indicated remains a largely inconsistent literature. Included were cross-sectional studies that reported personality data for healthy, adult smokers and nonsmokers using measures of personality traits derived from Eysenck's tripartite taxonomy of human personality. Of the 25 studies that contributed to the meta-analysis, 22 reported data on smoking status and extraversion and 22 reported data on smoking status and neuroticism. Meta analysis using a fixed-effects framework indicated a significant difference between smokers and nonsmokers on both extraversion (p<.001) and neuroticism (p<.001) traits, which remained significant when a random-effects framework was used to accommodate significant between-study heterogeneity. These data from cross-sectional observational studies published between 1972 and 2001 indicate that both increased extraversion and increased neuroticism are associated with an increased likelihood of being a smoker rather than a nonsmoker, although in both cases the effect sizes indicated by the meta-analysis were small. We found no evidence that the strength of these associations varied with year of publication. PMID- 17365773 TI - American Cancer Society's QuitLink: randomized trial of Internet assistance. AB - Eligible smokers (N = 6,451) visiting the American Cancer Society's Internet site offering cessation assistance were, with informed consent, randomized to receive access either to a static Internet site with quitting advice or to one of five interactive sites provided by cooperating research partners. Three-month follow up surveys were conducted via online survey with E-mail prompts, or telephone calls, to assess quitting success; 54% of participants provided follow-up data. Results showed no significant overall difference in cessation rates among participants assigned to the interactive or static sites. We found large differences in the utilization of the five interactive sites. When sites were grouped by level of use, a significantly higher reported 3-month cessation rate was observed among participants assigned to the more highly utilized sites than among those assigned to the less utilized sites (12.2% vs. 10.2% of all randomized participants, 26.0% vs. 22.1% of followed participants). These findings show that interactive Internet sites yielding high levels of utilization can increase quitting success among smokers seeking assistance via the Internet. PMID- 17365774 TI - Smoking cessation patterns in methadone-maintained smokers. AB - To determine predictors of smoking cessation duration in a randomized clinical trial, we assigned participants to nicotine patch (8-12 weeks) plus either (a) a baseline tailored brief motivational intervention, a quit date behavioral skills counseling session, and a relapse prevention follow-up session, or (b) brief advice using the National Cancer Institute's 4A's model. A total of 383 smokers from five methadone maintenance treatment centers in Rhode Island were enrolled, of whom 312 (82%) completed 6-month follow-up assessments. The primary outcome was longest period of self-reported abstinence during follow-up. Participants were on average 40.5 years of age; 51.9% were male, and 77.6% were White. In multivariate analysis controlling for demographics, nicotine dependence, depressive symptoms, and smoking-related symptoms, we found longer periods of abstinence in persons reporting at least one 24-hr quit attempt in the year prior to baseline (OR = 1.97, p = .003), in those anticipating success in cessation (OR = 1.33, p = .024), and in those with a greater percentage of nicotine patch use days (OR = 2.78, p<.001). Past quit attempts, self-efficacy, and constant nicotine replacement were associated with duration of abstinence among methadone maintained smokers. Attention to these domains in future intervention studies may improve treatment success. PMID- 17365776 TI - Clinimetrics. Foreword. PMID- 17365775 TI - Prevalence and characteristics of smokers at 30 Pacific Northwest colleges and universities. AB - College is an important transition period during which young adults explore tobacco use. Few large-scale studies have been conducted among college students regarding tobacco use. We initiated a study examining tobacco use in 30 colleges and universities in the Pacific Northwest. We conducted a baseline survey among students. Sample size varied by the school size; for the 14 largest schools, we drew a random sample of all students, oversampling freshmen (n approximately 750) so that we could recruit and follow a cohort to assess smoking onset during the college years. Of the remaining students, we sampled equivalent numbers of sophomores, juniors, and seniors (n = 200 each). For the 16 schools with fewer than 1,350 students, we surveyed all students. We found overall smoking rates of 17.2%. Males (18.6%) were more likely to smoke than females (16.6%; p = .03), and public college students were more likely to smoke (20.5%) than those who attended private independent schools (18.9%; p = .61), whose rates were higher than those of private religious schools (11.6%; p = .001). Overall, college students are light smokers who do not smoke every day of the month. Further, they tend not to be highly dependent on tobacco, do not consider themselves regular smokers, and plan to quit before they graduate (56.8%). School type should be considered when estimating smoking rates among 4-year college students. Data indicate that college smokers wish and plan to quit before graduation, suggesting that efforts to assist smokers in quitting during the college years may be fruitful. PMID- 17365777 TI - Psychiatric outcome studies (POS): does treatment help the patients? A Popperian approach to research in clinical psychiatry. PMID- 17365782 TI - Stigma and humiliation--unfortunately close friends. PMID- 17365783 TI - Mortality in relation to self-reported mixed anxiety and depression symptoms--The HUNT study. AB - Excess mortality in anxiety and depression has mostly been studied for diagnostic categories of each condition separately. The aim of this article is to study the association between self-reported mixed anxiety and depression and mortality in the general population. A population survey of 2624 individuals was defined in three groups according to their total score on Hospital Anxiety and Depression rating Scale (HADS-T): 0-19 points, 19-24 points and 25 points or above; 114 deaths (4.3%) occurred during 4.5 years. Only the highest score group had increased mortality risk after adjustment for all relevant confounding factors (P=0.043). However, trend tests supported a dose-response relationship between increasing HADS-T score and increasing total mortality across the three groups (P for trend = 0.02). All seven suicides occurred in cases detected by HADS-T (>or=19 points) at baseline. Our sample is limited and the findings therefore tentative, yet there seems to a positive correlation between HADS-T symptom level and total mortality risk in a 4.5-year perspective. PMID- 17365784 TI - Depression, e-health and family support. What the Internet offers the relatives of depressed persons. AB - Depression affects the depressed person and her/his closest network, giving rise to needs of support and information. The aim of this study was to examine the presence of information or other useful material for the relatives and significant others of depressed individuals on health-related Web sites and to see whether the possibly found material was addressing relatives' as of today known needs of information and support. A total of 22 Web sites granted with the Health on the Net Foundation's quality logo were examined and analysed according to Grounded Theory methodology. The study showed that a number of studied Web sites contained valuable information and material, thereby partly addressing relatives' known needs, whereas others offered no or little useful material. The study also resulted in a model in part showing the interaction between the depressed individual, the relatives and society. Conclusively, more can be done to help the relatives of depressed individuals cope with a daily life marked by the presence of depression by means of the Internet. PMID- 17365785 TI - Life development for 20 pairs of children with and without psychosocial problems- a 16-year-long study with follow-up. AB - The objective of the study was to describe 20 matched pairs of children born to psychosocial risk mothers who have been followed from early pregnancy through their first 16 years of life. Interviews and standardized behavior measurements with a focus on the children's development were used. When considering the overall data from the different measurements done over the 16-year study period, the study group has significantly more negative results. Nine of the families in the study group had been investigated for abuse, neglect and inadequate parenting during the 16 years. In the rest of the 11 families from the study group, two siblings had been placed in foster care because of maltreatment. The study group mothers' characteristics from the start had a significantly negative impact on the children's behavior and mental health throughout their lives and when they reached 16 years. PMID- 17365786 TI - Suicidal intent and psychiatric symptoms among inpatient suicide attempters. AB - The objective of this study was to investigate associations between suicidal intent and psychiatric symptoms, and to study the usefulness of the Suicidal Intent Scale (SIS) and the Comprehensive Psychopathological Rating Scale (CPRS) for suicide risk assessment in an inpatient population. One hundred and ninety six suicide attempters, of whom 15 eventually committed suicide, were admitted to a psychiatric ward. They were assessed by means of the SIS and the CPRS. Cox regression analyses were performed in order to adjust the relationships between the individual CPRS subscales and suicide for age and gender. The patients who later completed suicide had higher scores on the CPRS than the patients who did not complete suicide. We found no associations between symptoms and suicidal intent. The severity of psychopathology, in terms of high CPRS scores, shows a stronger association with future suicide than the level of suicidal intent (SIS) among inpatient suicide attempters. Suicidal intent is evidently scored regardless of psychiatric symptoms. PMID- 17365787 TI - Point prevalence of neurosis in the Lundby Study 1947-1997. AB - The objective of this article is to report and discuss the changing point prevalence rate of neurosis 1947-1997 in the Lundby cohort. The Lundby Study is a prospective longitudinal study of a geographically defined total population in the south of Sweden. Field investigations were performed in 1947, 1957, 1972 and in 1997, with psychiatrists interviewing the probands in a semi-structured way. Additional information was gathered from registers, case notes and key informants. Throughout the period of 50 years, the Lundby Study used its own diagnostic system with neurosis referring to non-psychotic mental illness in the absence of an organic brain disease. After 1957, no newcomers were included, and therefore only probands 40 years of age or older at the cross-sectional surveys are included in the present paper. For men aged 40-59 and 60 years or older, respectively, the age-specific point prevalence of neurosis increased from 2.5% and 0.5% in 1947, to 8.3% and 8.4% in 1972. The corresponding figures for women were 8.0% and 1.3% in 1947, and 24.2% and 20.1% in 1972. The increase could be seen in all degrees of impairment, but it was most pronounced in the mild and medium impairment groups. Except for a slight decrease in point prevalence in the female group 40-59 years of age, there were no significant changes from 1972 to 1997. A large increase in the point prevalence rate of neurosis could be seen 1947-1972, but not 1972-1997. Because of the many biases inherent in longitudinal psychiatric studies, our results must be interpreted with caution. PMID- 17365788 TI - Mental health problems and healthcare contacts in an urban and a rural area. Comparisons of two Swedish counties. AB - Mental health problems are common in the general population. The aim of this study was to investigate differences in frequencies of self-reported psychiatric symptoms, harmful alcohol use and healthcare contacts, in an urban and a rural area in Sweden. Two samples of 10,441 (urban site) and 3538 (rural site) subjects, aged 20-64, responded to a questionnaire, covering demographic characteristics and self-report psychiatric instruments as well as contact with healthcare during the past 12 months. Psychiatric symptoms and symptoms of substance abuse were reported by 17% of the urban women compared with 13% of the rural women, and by 20% of the urban men compared with 15% of the rural men. This difference is mainly due to an uneven age distribution in the two populations and remains statistically significant only in the oldest age group (50-64 years). Symptoms of anxiety and depression occurred with similar frequencies in both samples. Harmful alcohol use was reported by 3.6% of the urban women, 1.5% of rural women, 11.8% of urban men and 8.6% of rural men. The urban sample had more often been in contact with medical services, 77% vs. 52%. Symptoms of anxiety and depression were equally common in the two samples. Harmful use of alcohol was more common in the urban sample, especially among women. Most obvious was the stronger inclination to seek help in the urban sample. PMID- 17365789 TI - Patients' experience of humiliation in the admission process to acute psychiatric wards. AB - The objective of the study was to investigate the experiences of humiliations by patients in the admission process to acute psychiatric wards. One-hundred-and-two patients were interviewed within 48 h after hospitalization about their experiences of the admission process. The structured Admission Experience Survey questionnaire was used to identify negative events of the admission process. Perceived humiliation was defined by a cut-off on the self-reported Cantrill's Ladder Scale. Six qualitative depth interviews of patients with high and low humiliation scores were performed in order to relate interview information on humiliation experiences to the self-report. Negative events during the admission process were significantly more common among patients with involuntary admission, but were also observed among those voluntary admitted. Humiliation in connection with negative events during the admission process was reported by 48 patients, 24 involuntary and 24 voluntary admitted. In univariate analyses, humiliation was significantly associated with events where the patients were exposed to verbal or physical force, as well as with the conviction that "the admission was not right". In multivariate analyses, the latter conviction was the only significant one, although "use of physical force" also showed a trend (P=0.06). Negative events are common among the routines, procedures, and situations of the admission process to acute psychiatric wards. Some of them can hopefully be modified such as the use of verbal and physical force. In contrast, the conviction that "the admission was not right", which showed the strongest association with humiliation, seems less modifiable in the admission process. PMID- 17365790 TI - On treatment with eye movement desensitization and reprocessing of chronic post traumatic stress disorder in public transportation workers--a randomized controlled trial. AB - Previous studies on post-traumatic stress disorder (PTSD) investigated a variety of treatments and included mostly patients victims of sexual and combat assault. This study aimed to determine the short-term efficacy of eye movement desensitization and reprocessing (EMDR) in occupation-based PTSD. Employees of the public transportation system in Stockholm, who had been experiencing a person under-train accident or had been assaulted at work were recruited. Subjects with trauma exposure since more than 3 months but less than 6 years were included. Twenty-four subjects who fulfilled the DSM-IV criteria for PTSD were randomized to either EMDR therapy (n=13) or waiting list (WL, n=11). They were assessed pre treatment and shortly after completion of treatment or WL period. The pre-defined primary outcome variable was full PTSD diagnosis. Secondary outcome variables were the results of various psychometric scales. Twelve participants began and completed five sessions of EMDR and nine completed the WL. After therapy, eight subjects in the EMDR group (67%) and one (11%) in WL did not fulfil the criteria for PTSD diagnosis (difference, P=0.02). Among the secondary outcome variables, there were significant differences post-treatment between the groups EMDR/WL in Global Assessment of Function (GAF) score and Hamilton Depression (HAM-D) score. This study indicates that EMDR has a short-term effect on PTSD in public transportation workers exposed to occupational traumatic events. Such intensive and brief therapy might be further validated in larger samples of exposed workers with longer periods of follow-up. PMID- 17365791 TI - Seven-year outcome of depression in primary and psychiatric outpatient care: results of the TADEP (Tampere Depression) II Study. AB - The objective of this article was to determine a 7-year naturalistic progression of depression as well as a number of potential prognostic factors among Finnish primary care and psychiatric care patients. Depression-screened patients from primary care and psychiatric care, aged 18-64, were interviewed in 1991-92 with the Present State Examination (PSE) as the diagnostic instrument. The patients were re-contacted in 1998-99, and their depression at final assessment (FinalA) and during the follow-up period (F-up) was assessed by telephone interview using the Composite International Diagnostic Interview--Short Form (CIDI-SF). 250 primary care (58.1%) and 170 (40.2%) psychiatric care patients were successfully followed. Of the primary care patients with severe depression at baseline, 42.4% had had depression during F-up and 21.2% had depression at FinalA. For the patients with mild depression at baseline, the corresponding figures were nearly the same, but for the patients with depressive symptoms clearly lower. Of the psychiatric care patients with severe depression at baseline, 61.0% had had depression during F-up and 26.2% had depression at FinalA. As with primary care patients, the corresponding figures were nearly the same for mild depression at baseline but clearly lower for depressive symptoms. Experienced lifetime mood elevation was associated with having depression during F-up in both primary care and psychiatric care patients. High Depression Scale (DEPS) score at baseline was associated with having depression at FinalA in primary care patients, but in psychiatric care patients, it was the high Hamilton Rating Scale for depression (HAM-D) and drinking problems. Severe depression and mild depression are predictive for subsequent depression at both levels of care. The long-term prognosis for depression is better in primary care. DEPS and HAM-D are useful, prognostic instruments. PMID- 17365792 TI - ICD-10 classification in Danish child and adolescent psychiatry--have diagnoses changed after the introduction of ICD-10? AB - The aim was to test this in a nationwide register study of diagnoses used in child and adolescents psychiatry in Denmark. A larger number of different diagnoses were expected to be applied after the introduction of the 10th version of the International Classification of Diseases (ICD-10). Reflecting the time trend, we particularly expected an increase in the number of neuropsychiatric diagnoses. From the Danish Psychiatric Central Register data were drawn on clinical discharge diagnoses. All patients aged 0-15 years examined at psychiatric hospitals from 1995-2002 were included; 22,469 children and adolescents with a first contact were registered. The most frequent discharge diagnoses were pervasive development disorders (PDD; 11.9%), adjustment disorders (10.6%), conduct disorder (9.5%), emotional and anxiety disorders (7.6%), hyperkinetic disorders (7.3%), and specific developmental disorders (7.3%). We found a significant increase in the number of neuropsychiatric and affective diagnoses and a significant decrease in the number of adjustment, conduct and anxiety diagnoses during the study period. Of the 22,469 diagnoses, 45% were only partly specified according to ICD-10. Thirty-four per cent had diagnoses unspecified on the four-character level (Fxx.9) and 11% had Z-diagnoses. A larger number of different diagnoses and an increase in the use of neuropsychiatric diagnoses were seen after the introduction of ICD-10. Many diagnoses were only partly specified; consequently, a more detailed specification of the ICD-10 is still required. PMID- 17365793 TI - Reaction of glycidamide with 2'-deoxyadenosine and 2'-deoxyguanosine--mechanism for the amide hydrolysis. AB - 2'-Deoxyadenosine (dA) and 2'-deoxyguanosine (dG) were reacted with mutagenic epoxide glycidamide (GA, Scheme 1). The reactions yielded three GA-dA adducts (N1 GA-dA, N6-GA-dA and N1-GA-dI) and two GA-dG adducts (N1-GA-dG I and N1-GA-dG II) (Scheme 2). The structures of the adducts were characterized by spectroscopic and spectrometric methods (1H-, 13C, and 2D NMR, MS, UV). The mechanism of the amide hydrolysis taking place during formation of the adducts N1-GA-dA and N1-GA-dG I was studied. We propose a mechanism where a transamidation is the key step in the hydrolysis of the amide function of GA. PMID- 17365794 TI - N,N'-Bis-(2-(cyano)ethoxycarbonyl)-2-methyl-2-thiopseudourea: a guanylating reagent for synthesis of 2'-O-[2-(Guanidinium)ethyl]-modified oligonucleotides. AB - A guanylating reagent, N,N'-bis-(2-(cyano)ethoxycarbonyl)-2-thiopseudourea, was synthesized and used for synthesis of 2'-O-[2-(guanidinium)ethyl] (2'-O-GE) modified oligonucleotides. A convenient deprotection method for the 2'-O-GE oligonucleotides was developed. PMID- 17365795 TI - Molecular recognition of adenosine deaminase: 15N NMR studies. AB - The elucidation of the molecular recognition of adenosine deaminase (ADA), the interpretation of the catalytic mechanism, and the design of novel inhibitors are based mostly on data obtained for the crystalline state of the enzyme. To obtain evidence for molecular recognition of the physiologically relevant soluble enzyme, we studied its interactions with the in situ formed inhibitor, 6-OH purine riboside (HDPR), by 1D-15N- and 2D-(1H-15N)- NMR using the labeled primary inhibitor [15N4]-PR. We synthesized both [15N4]-PR and an [15N4]-HDPR model, from relatively inexpensive 15N sources. The [15N4]-HDPR model was used to simulate H bonding and possible Zn2+-coordination of HDPR with ADA. We also explored possible ionic interactions between PR and ADA by 15N-NMR monitored pH-titrations of [15N4]-PR. Finally, we investigated the [15N4]-PR-ADA 1:1 complex by 2D-(1H 15N) NMR. We found that HDPR recognition determinants in ADA do not include any ionic-interactions. HDPR N1 H is an H-bond acceptor, and not an H-bond donor. Despite the proximity of N7 to the Zn2+-ion, no coordination occurs; instead, N7 is an H-bond acceptor. We found an overall agreement between the crystallographic data for the crystallized ADA:HDPR complex and the 15N-NMR signals for the corresponding soluble complex. This finding justifies the use of ADA's crystallographic data for the design of novel inhibitors. PMID- 17365796 TI - An alternative advantageous protocol for efficient synthesis of phosphorothioate oligonucleotides utilizing phenylacetyl disulfide (PADS). AB - Phosphorothioate oligonucleotides could be synthesized using a 0.2 M solution of phenylacetyl disulfide (PADS) in a mixture of pyridine and acetonitrile (1:1, v/v) with > 99.9% step-wise efficiency. Unlike most other sulfurizing reagents that need to be stable in solution for performance, PADS needs to degrade and "age" in solution and hence performs efficiently even after storing the solution at room temperature for over a month. High yield and quality of oligonucleotides are produced thereby offering an alternative attractive protocol for use of this efficient sulfurizing reagent. PMID- 17365797 TI - Synthesis of 3',5'-cyclic diguanylic acid (cdiGMP) using 1-(4-chlorophenyl)-4 ethoxypiperidin-4-yl as a protecting group for 2'-hydroxy functions of ribonucleosides. AB - We herein report a convenient synthesis of 3',5'-cyclic diguanylic acid via the modified H-phosphonate approach. The 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) group was used as protecting group for the 2'-hydroxy functions of ribonucleosides. Complete unblocking of the fully protected 3',5'-cyclic diguanylic acid gave cdiGMP as a homogeneous compound in an excellent yield. PMID- 17365798 TI - The chemical and biochemical properties of methylphosphotriester DNA and RNA in comparison with their corresponding methylphosphonates. A dynamic model description. AB - Methylphosphotriester DNA and RNA are of great interest to investigate their hybridization affinity with natural DNA and RNA with respect to their physical and biological properties. The results are compared with related modified oligonucleotides. Specific attention will be given to the development of recent antiretroviral nucleosides focused on their molecular conformation and the mechanistic aspects based on the physical properties of phosphorus in a trigonal bipyramidal configuration corresponding with in vitro and in vivo kinetics. PMID- 17365799 TI - Are intravitreal anti-VEGF antibodies safe? PMID- 17365800 TI - Targeting tissue factor for immunotherapy of choroidal neovascularization by intravitreal delivery of factor VII-Fc chimeric antibody. AB - PURPOSE: ICON is a fusion protein composed of factor VII, the natural ligand for tissue factor, conjugated to the Fc domain of a human IgG1 immunoglobulin. It binds to the tissue factor expressed on neovascular endothelia and initiates a cytolytic immune attack that destroys the neovascular tissue. We previously showed that mouse factor VII-Fc chimeric antibody (mICON) dramatically decreases the frequency of choroidal neovascularization in a laser-induced choroidal neovascularization model in mice. Herein, we determined the safety and efficacy of mICON in destroying subretinal choroidal neovascularization in pig eyes. METHODS: mICON (150-1200 microg) was administered into the midvitreous cavity of the pig eye either before (on Day 0) or after (on Day 10) induction of choroidal neovascularization with laser photocoagulation. On Day 14, the incidence of choroidal neovascularization was determined using confocal microscopy. We also determined the binding specificity (% binding to choroidal neovascularization/% binding to non-choroidal neovascularization areas) of mICON to tissue factor expressed on endothelial cells of laser-induced choroidal neovascularization. RESULTS: We observed that mICON selectively destroyed choroidal neovascularization in a dose-dependent manner (r = -0.93; EDB50B = 571.3 microg). Obliteration of the choroidal neovascular complex was more prominent at doses > 300 microg (p < 0.05). No systemic or local complications (including retinal tear/detachment, inflammation, infection, cataract, or glaucoma) were observed. Binding specificities of hICON (2.2 +/- 0.2) and mICON (3.4 +/- 0.4) were significantly higher than that of anti-von Willebrand antibody (0.1 +/- 0.01, p < 0.001). CONCLUSIONS: Both hICON and mICON bound to the neovascular endothelia of choroidal neovascularization with greater specificity than anti-von Willebrand antibody. Furthermore, mICON can selectively obliterate already established choroidal neovascularization, which suggests that it may be useful for immunotherapy in patients with exudative (wet) macular degeneration. PMID- 17365801 TI - Surgery for hypotony in patients with juvenile idiopathic arthritis-associated uveitis. AB - PURPOSE: To describe the clinical response to cyclitic membrane excision of eyes with juvenile idiopathic arthritis (JIA)-associated uveitis and hypotony. METHODS: The clinical records of patients with JIA-associated uveitis in a tertiary referral center were reviewed. Those patients with JIA-associated uveitis and hypotony who underwent cyclitic membrane excision were included in the study. Patients with hypotony secondary to active inflammation, retinal detachment, and surgical intervention (filtering, cyclo-destructive procedures, and glaucoma valve implantation) were excluded. RESULTS: Two pediatric and two adult patients (4 eyes) were identified. The range of pre-operative intraocular pressure (IOP) was 0-5 mmHg. The two adult patients were noted to have atrophic ciliary processes intra-operatively, while the two pediatric patients had normal ciliary processes. At six months follow-up, the adult patients had IOPs of 5 mmHg, while the two pediatric patients had IOPs of 16 mmHg. At last consultation (mean duration of follow-up: 3.6 years), IOP was normal in all eyes. None of the eyes had a decrease in vision. CONCLUSIONS: Release of traction on the ciliary body by inflammatory membranes may play a role in the management of hypotony in patients with JIA-associated uveitis. However, even though the IOP was successfully elevated, preventing phthisis, vision remained poor due to the long standing complications secondary to chronic uveitis. This emphasizes the critical importance of early diagnosis and appropriate treatment of the inflammation before vision-robbing complications occur. PMID- 17365802 TI - Vitreous hemorrhage in multiple sclerosis-associated uveitis. AB - PURPOSE: To report on six patients who developed vitreous hemorrhage (VH) in the course of intermediate uveitis (IU) associated with multiple sclerosis (MS). METHODS: Observational case series. RESULTS: Six out of 25 patients (24%) with IU and MS seen at two tertiary centers developed VH. Average age at onset of MS was 26 years and average age at the onset of IU was 25 years. IU developed before the onset of MS in four of the six patients (67%). All patients had IU associated with peripheral phlebitis. The average interval between the onset of IU and the occurrence of VH was five years (range: 0-11 years; VH was the initial sign of uveitis in 2 patients). VH cleared spontaneously in all cases; however, subsequent retinal detachment developed in two eyes. All six patients had ischemic retinal areas and four had subretinal neovascularizations. Optimal visual acuity five years after VH varied from no light perception to full visual acuity. The causes of diminished acuity included optic neuritis, cystoid macular edema (CME), and retinal detachment. CONCLUSION: The possibility of MS-associated uveitis should be considered in patients with IU and VH. PMID- 17365803 TI - Photodynamic therapy for subfoveal and juxtafoveal choroidal neovascularization associated with punctate inner choroidopathy. AB - PURPOSE: To evaluate the treatment of subfoveal and juxtafoveal choroidal neovascularization (CNV) using verteporfin photodynamic therapy (vPDT) in patients affected by punctate inner choroidopathy (PIC). METHODS: A chart review of 8 patients with CNV associated with PIC treated with vPDT was done. RESULTS: The 8 patients (8 eyes) included 4 men and 4 women with a mean age of 30.9 years. Six of them presented juxtafoveal CNVs, and two had subfoveal CNVs, at presentation. Mean follow-up time was 22.7 months. The VA improved in five eyes, and three eyes declined. One patient developed a new CNV a few days after vPDT, and one had multiple CNVs at presentation. Two of the 3 patients with longer follow-up period presented late recurrences. CONCLUSIONS: vPDT is a beneficial resource in stabilizing and also improving VA in PIC patients affected with subfoveal and juxtafoveal CNV, although one third of the patients retain poor visual acuity. PMID- 17365804 TI - Treatment of cytomegalovirus anterior uveitis with oral valaciclovir. AB - We report a patient with cytomegalovirus anterior uveitis who was treated with oral valaciclovir preventing recurrence of his uveitis. Valaciclovir appears to be a good alternative to valganciclovir for maintenance therapy in this condition. PMID- 17365805 TI - Necrotising anterior scleritis in a late-onset rheumatoid arthritis (LORA) patient. AB - Late-onset rheumatoid arthritis (LORA) is a clinically distinct entity from rheumatoid arthritis of younger onset (YORA). We present a case of necrotising anterior scleritis in an elderly lady with new-onset LORA that was initially thought to be infective. Oestrogen receptors have been identified on B cells, T cells, and macrophages with oestrogens demonstrated to increase their activation and enhance RA synovial inflammation. The presence of long-term oestrogen supplementation may have contributed to the development and perpetuation of her RA, thereby necessitating awareness of the possible immunomodulatory role of the sex steroids in immune-mediated diseases which affect the eye. PMID- 17365806 TI - Scleritis in a person with stiff-person syndrome. AB - PURPOSE: To describe a case of anterior scleritis in a patient with stiff-person syndrome. METHODS: Case report. RESULTS: A 55-year-old woman with stable stiff person syndrome and off immunomodulatory therapy developed unilateral anterior scleritis, which resolved over three weeks with systemic nonsteroidal anti inflammatory therapy. CONCLUSIONS: The authors are unaware of reports regarding the association of scleritis with stiff-person syndrome. PMID- 17365807 TI - Presumed oculoglandular syndrome from Bartonella quintana. AB - BACKGROUND: To describe a case of clinically diagnosed oculoglandular syndrome in a 17-year-old patient that was presumed to be due to Bartonella quintana, as suggested by a positive serologic titer. METHODS: The patient presented to the Massachusetts Eye and Ear Infirmary emergency room with signs and symptoms suggestive of oculoglandular syndrome. He had a follicular conjunctivitis with a conjunctival granuloma of the right eye and an ipsilateral large, tender submandibular lymph node. He had recently acquired a kitten and a clinical diagnosis of cat-scratch disease was made. A laboratory workup was initiated to determine the cause of this clinical presentation and empirical treatment with antibiotics was started. RESULTS: All laboratory results were negative or normal except for the IgM titer to Bartonella quintana, which was elevated. The patient responded well to treatment and his symptoms resolved within a few weeks. DISCUSSION: Bartonella quintana infection, a pathogen prevalent in HIV-infected, homeless, or alcoholic patients, is a possible etiologic agent of cat-scratch disease and the associated condition of oculoglandular syndrome. PMID- 17365808 TI - Proliferative vascular retinopathy in polymyositis and dermatomyositis with scleroderma (overlap syndrome). AB - AIM: To report the occurrence of proliferative vascular retinopathy in two patients with polymyositis/dermatomyositis. METHOD: Review of case records. RESULTS: One patient presented, six years after the diagnosis of polymyositis, with obliteration of the superior retinal vessels and associated neovascularization of the disc. The second patient with overlap syndrome was detected to have occlusion of the inferotemporal retinal arteriole and venule with early neovascularization of the retina. CONCLUSION: Retinal vascular occlusion with development of proliferative changes can occur in polymyositis/dermatomyositis. To the best of the authors' knowledge, this has not been reported earlier in the literature. PMID- 17365809 TI - Ring keratopathy in a patient with psoriatic arthritis and ulcerative rectocolitis. AB - PURPOSE: To describe a bilateral ring-shaped corneal opacity associated to immunological bowel and skin diseases. METHODS: Ophthalmic examination, tear film evaluation, ultrasound biomicroscopy (UBM), rheumatologic examination, and haematological screening. RESULTS: A 30-year-old man with psoriatic arthritis and ulcerative rectocolitis showed an unusual bilateral ring keratopathy not responding to topical and oral anti-inflammatory treatment. UBM examination revealed the high reflectivity of lesions distributed in the anterior stroma. CONCLUSION: Although association with systemic autoimmune diseases together with the ring aspect could suggest the immunological origin of corneal lesions, degenerative keratopathy cannot be excluded because the poor response to therapy alongside the UBM findings. PMID- 17365811 TI - The value of population-based studies in the genomic era. PMID- 17365812 TI - Survival from uveal melanoma in England and Wales 1986 to 2001. AB - PURPOSE: To analyse survival from uveal melanoma diagnosed in England and Wales between 1986-1999 and followed up to 2001. METHODS: Data from the National Cancer Registry at the Office for National Statistics were analysed. The data were compiled from population-based cancer registries covering all of England and Wales for all adults (aged 15-99) diagnosed with primary ocular malignancy, excluding eyelid tumours. Level of poverty was based on the national classification of area of residence at time of diagnosis. Regression models explored the influence of sex, age, and level of poverty on relative survival for patients diagnosed with uveal melanoma during successive calendar periods. RESULTS: Of 5,519 adults identified with primary ocular malignancy, 4,717 had melanoma, of which 4,308 (91%) were eligible for analysis. Two-thirds (67%) of the ocular melanomas were uveal, 5% conjunctival, and 2% orbital; the subsite was unspecified in 26%. Relative survival from uveal melanoma was 95% at 1 year and 72% at 5 years. There was no statistically significant variation in 1-year or 5 year survival by sex or poverty level and no significant trend over time. Older patients had significantly worse survival (p < 0.001). CONCLUSIONS: This study provides national population-based survival estimates for England and Wales for uveal melanoma, the most common primary intraocular malignancy in adults. Five year relative survival, an important indicator of the quality of cancer care, has not improved since the 1980s. Greater age, but not gender or level of poverty, is associated with a poorer prognosis. A standardised classification of uveal melanoma is required to improve reporting to cancer registries. Further research is required to explore reasons for lower relative survival in older persons. PMID- 17365813 TI - Prevalence and causes of blindness & low vision; before and five years after 'VISION 2020' initiatives in Oman: a review. AB - BACKGROUND: A prevalence survey of blindness and low vision was conducted in Oman in 2005. Here, we present the prevalence and determinants of blindness and low vision among the population >or= 40 years of age. The results are then compared with those of the survey in 1997 and the changes following the 'VISION 2020' initiatives are assessed. METHODS: The survey covered 24 randomly selected clusters (75 houses in each). Teams assessed the distance vision of subjects while wearing glasses. The ophthalmologists examined the anterior segment and fundus to determine the causes of disability. The visual field was tested in those suspected of glaucoma. The prevalence rates of blindness (< 3/60 on presentation), legal blindness (< 6/60) and low vision (< 6/18) were calculated. The data from the 1997 survey was then analyzed to obtain similar rates in the population >or= 40 years of age. RESULTS: The prevalence of blindness was 8.25% (95% CI 7.14-9.36) in the >or= 40 year-old population in 2005. The rate would be 6.95% (95% CI 5.92-7.98) if blindness were defined as vision with best possible correction. The prevalence of legal blindness and low vision were 12% and 45.12%, respectively. In the 1997 survey, the prevalence of blindness in same age group was 7.23% (95% CI 5.91-8.55). Between the two surveys, the prevalence of blindness due to corneal pathology declined from 1.9% to 1.1% but that of blindness due to unoperated cataract increased from 1.8% to 2.3%. CONCLUSIONS: The rate of disability has declined but the number of blind people has increased in Oman. The causes of blindness have changed from communicable/avoidable eye diseases to non-curable/chronic eye diseases, and the number with visual disabilities has increased. An increasing number of operations for cataract and improvements in the care for glaucoma and diabetic retinopathy are recommended. PMID- 17365814 TI - The Persian Wednesday Eve Festival "Charshanbe-Soori" fireworks eye injuries: a case series. AB - PURPOSE: To describe the clinical spectrum and severity of eye injuries sustained during the Persian Wednesday Eve Festival "Charshanbe-Soori" and to identify the fireworks devices involved. METHODS: Prospectively, consecutive patients treated for fireworks-related eye injuries in the emergency room at Farabi Eye Hospital, Tehran, over 3 days around the occasion in 2000, 2001, and 2002 were studied. RESULTS: Four hundred thirty-seven cases of eye injuries with an age range of 2 74 (median 17; SD 11.1) years were studied: 84.6% were male; 18.6% of the injuries were bilateral; 79.9% of the injured were bystanders or passersby. Eleven types of devices were involved, of which seven were explosives and eight were homemade. "Narenjaks," homemade grenades, were involved in 62.2%, firecrackers in 14.8%, and sparklers in 6.2% of the events. Injuries were categorized as severe in 49% of cases, and 45 (10.4%) people were hospitalized. Five eyes with no light perception and/or enucleation, 33 cases of monocular blindness, 54 (12.3%) cases of open globe (including intraocular foreign bodies) were observed. Grenades, bystander and passerby roles, outdoor context, a relatively older age, lower socioeconomic status, and male gender in the subset of passive roles were the determinants of more severe injuries (all p values < 0.05). Lid injuries (67.7%), corneal abrasions (51.6%), hyphema (48.1%), superficial foreign bodies (32.5%), and corneal contusions (13.8%) were the five leading injuries. CONCLUSIONS: In Iran, fireworks cause frequent and diverse injuries during the Wednesday Eve Festival and are a leading cause of severe eye injuries and monocular blindness. PMID- 17365815 TI - Rationale and methodology for a population-based study of eye diseases in Malay people: The Singapore Malay eye study (SiMES). AB - PURPOSE: Although there are approximately 200 million people of Malay ethnicity living in Asia, the burden and risk factors of blinding eye diseases in this ethnic group are unknown. This study summarizes the rationale and study design of a population-based study of eye diseases among adult Malays in Singapore. METHODS: A population-based cross-sectional study of Malays was designed in Singapore. The sampling frame consisted of all Malays aged 40-79 living in designated study areas in southwestern Singapore. From a list of 16,069 names provided by the Ministry of Home Affairs, age-stratified random sampling was used to select 5,600 names (1,400 people from each decade of 40-49, 50-59, 60-69, and 70-79 years). The target sample size for this study was 3,150 persons. Selected individuals were invited to a centralized clinic by letters, telephone calls, and home visits. Participants underwent standardized interview and assessment of blood pressure, anthropometry, presenting and best-corrected visual acuity, subjective refraction, ocular biometry, Goldmann tonometry, slit-lamp biomicroscopy, optic disc imaging, digital lens, and retinal photography. Blood and urine samples were collected for biochemical analyses and further stored for future studies. Selected participants also had gonioscopic examination, visual fields test, and assessment of ankle and brachial blood pressure to detect presence of peripheral vascular disease. CONCLUSIONS: This study provides population-based data on the prevalence of and risk factors for age-related eye diseases in people of Malay ethnicity in Singapore. Data from this study allow further understanding of the etiology and impact of eye diseases in this ethnic group. PMID- 17365816 TI - Use of protective eyewear in U.S. children: results from the National Health Interview Survey. AB - PURPOSE: To study use of protective eyewear in children who participated in activities that can cause eye injury. METHODS: National Health Interview Survey (NHIS) data from 2002 were used to analyze protective eyewear use by children who participated in activities that can cause eye injury. Weighted percentages and 95% confidence intervals (CI) of the sociodemographic characteristics of children who wore protective eyewear were analyzed. Odds ratios (OR) were estimated in logistic regression models. RESULTS: In the 2002 NHIS, 3,901 children aged 6-17 years (51% of interviewed children) participated in activities that can cause eye injury, but while doing so, only 14.5% of children wore protective eyewear. After controlling for potentially confounding effects of study variables, females were less likely to wear protective eyewear than males (OR = 0.61; 95% CI: 0.48-0.76) and children aged 12-17 years were more likely to wear protective eyewear than children aged 6-8 years (12-14 year olds: OR = 1.72, 95% CI: 1.20-2.46; 15-17 year olds: OR = 1.60; 95% CI: 1.11-2.31). Race/ethnicity, parent's education, family structure, poverty status, and region of United States residence did not have significant influence on protective eyewear use. CONCLUSIONS: To achieve the Healthy People 2010 objective of 20% of children using protective eyewear in recreational activities and hazardous situations around the home, intervention/education programs must continue to be improved and implemented. PMID- 17365817 TI - Hazardous drinking among adults with diabetes and related eye disease or visual problems: a population-based cross-sectional survey. AB - PURPOSE: To estimate the prevalence of problem drinking and related risk behaviors among adults with diabetes and eye disease in the United States. METHODS: In a population-based, cross-sectional telephone survey of the noninstitutionalized U.S. adult population (18 years of age or older) conducted in 47 U.S. states in 2002 and 40 U.S. states in 1999, we identified the prevalence of binge drinking (5 or more drinks on an occasion in the last month), drinking and driving in the last month, and binge drinking and concurrent unlocked firearm ownership. We used sample weights to estimate the prevalence and number of individuals reporting each measure in the full U.S. population. RESULTS: In 2002, 130 of 3,670 respondents with diabetes-related eye disease reported binge drinking within the last month (prevalence 4%; 95% confidence interval [CI]: 3%-6%), corresponding to an estimated 116,501 adults in the United States (95% CI: 80,020-152,981). Approximately 0.4% (95% CI: 0.2%-0.9%) of all affected adults, and 0.8% (95% CI: 0.3%-2%) of all affected males, endorsed driving after drinking within the last month, corresponding to an estimated 12,150 Americans with diabetic eye disease who drink and drive (95% CI: 2,414 21,887). An estimated total of 15,356 (95% CI: 2,180-28,533) also reported having a loaded and unlocked firearm at home. Estimates of binge drinking and drinking and driving were at least as high among the 1,854 respondents with diabetes and visual impairment in 1999. CONCLUSIONS: Binge drinking occurs in 4%-5% of adults with diabetes and eye disease. Driving after drinking and unlocked gun ownership, while uncommon, also occur among such individuals, who are apt to be at extraordinarily high risk for injury and other alcohol-related complications. PMID- 17365818 TI - Re: Altangerel et al. 2006, "Assessment of function related, to vision (AFREV)". PMID- 17365820 TI - The rich history of gynaecological pathology: brief notes on some of its personalities and their contributions. AB - The careers and contributions of some of those who have played a major role in the development of knowledge concerning gynaecological pathology are summarised. The emphasis is on workers of prior times beginning with those of the German speaking school: Carl Ruge, Felix Marchand, Hermann Pfannenstiel, Oskar Frankl, Walter Schiller, and Robert Meyer. The two great Scandinavian investigators Lars Santesson and Gunnar Teilum are then considered, followed by those of the British school: John H. Teacher, Elizabeth Hurdon, Magnus Haines, Claud Taylor, Fred Langley, and Harold Fox. North American workers reviewed are: Thomas S. Cullen, Emil Novak, John Albertson Sampson, Arthur Hertig, and Robert E. Scully. The essay concludes with Australasian contributors, those considered in detail being: Hans Frederick Bettinger, Rupert A. Willis, Hazel (Mansell) Gore, Robert Barter, Harold Attwood, Andrew Ostor (the last two also noted historians), Denys Fortune, Alan Ng, and Peter Russell. PMID- 17365821 TI - Molecular targets in gynaecological cancers. AB - The application of high throughput expression profiling and other advanced molecular biology laboratory techniques has revolutionised the management of cancers and is gaining attention in the field of gynaecological cancers. Such new approaches may help to improve our understanding of carcinogenesis and facilitate screening and early detection of gynaecological cancers and their precursors. Individualised prediction of patients' responses to therapy and design of personalised molecular targeted therapy is also possible. The studies of various molecular targets involved in the various signal pathways related to carcinogenesis are particularly relevant to such applications. At the moment, the application of detection and genotyping of human papillomavirus in management of cervical cancer is one of the most well established appliances of molecular targets in gynaecological cancers. Methylation, telomerase and clonality studies are also potentially useful, especially in assisting diagnosis of difficult clinical scenarios. This post-genomic era of clinical medicine will continue to make a significant impact in routine pathology practice. The contribution of pathologists is indispensable in analysis involving tissue microarray. On the other hand, both pathologists and bedside clinicians should be aware of the limitation of these molecular targets. Interpretation must be integrated with clinical and histopathological context to avoid misleading judgement. The importance of quality assurance of all such molecular techniques and their ethical implications cannot be over-emphasised. PMID- 17365822 TI - Molecular genetic changes in epithelial, stromal and mixed neoplasms of the endometrium. AB - Endometrial carcinoma, endometrial stromal tumours and mixed malignant mesodermal tumours (MMMT) develop along distinctive molecular genetic pathways. Two distinctive types of endometrial carcinoma are distinguished, type I and type II, which develop along distinctive pathways and show different clinical behaviour and histological features. Type I carcinomas show endometrioid histology, are oestrogen-related and develop from atypical endometrial hyperplasia. The molecular tumorigenesis is comparable to colorectal carcinoma with a step-like progression and an accumulation of genetic alterations. Alterations of PTEN, K Ras mutations and microsatellite instability are frequent and early events in type I carcinoma, whereas p53 mutations occur during progression to grade 3 carcinoma. Serous and clear cell carcinomas are considered type II carcinomas which are mostly unrelated to oestrogen. p53 mutations occur in almost all serous carcinomas and seem to occur early, leading to massive chromosomal instability and rapid tumour progression. Gene expression profiling has supported this dualistic model of endometrial carcinoma. There is evidence of molecular differences between serous and clear cell carcinomas as well as between endometrioid carcinomas with and without microsatellite instability. A dualistic model of tumorigenesis may be also suggested for endometrial stromal tumours. Endometrial stromal sarcomas (ESS; type I endometrial sarcoma) are oestrogen related and seem to develop from endometrial stromal nodules (ESN). They are histologically and genetically distinct from undifferentiated endometrial sarcoma (UES) which seem to be mostly unrelated to oestrogen (type II endometrial sarcoma). ESS and ESN share the fusion gene JAZF1/JJAZ1 caused by a t(7;17)(p15;q21) translocation, whereas UES lacks a distinctive molecular alteration so far. In MMMT, which is considered a metaplastic carcinoma, p53 alteration occurs early, before clonal expansion and acquisition of genetic diversity during progression. PMID- 17365823 TI - Uterine sarcomas. AB - A wide variety of sarcomas occur in the uterus but two subtypes - leiomyosarcoma and endometrial stromal sarcoma - account for a majority of those more routinely encountered. Using the 2003 World Health Organization classification, this review focuses on six uterine sarcomas: endometrial stromal sarcoma, undifferentiated endometrial sarcoma, leiomyosarcoma, rhabomyosarcoma, angiosarcoma and liposarcoma. The epidemiological, clinical, pathological and molecular features are presented along with therapeutic approaches. Familiarity with molecular aspects of these tumors and application of novel technologies in their assessment should be encouraged as they may provide alternate therapies resulting in improved survival for the patient. Clinical information necessary for accurate diagnosis of these lesions is emphasised. A multidisciplinary approach to management of patients with uterine sarcomas is essential for optimal management. PMID- 17365824 TI - Endometrial carcinoma: pathology and genetics. AB - In the Western world, endometrial carcinoma is the most common malignant tumour of the female genital tract and the fourth most common cancer in women after carcinomas of breast, colorectum, and lung. The annual incidence has been estimated at 10-20 per 100 000 women. In the United States, endometrial carcinoma accounts for approximately 6000 deaths per year. Two different clinicopathological subtypes are recognised: the oestrogen-related (type I, endometrioid) and the non-oestrogen related (type II, non-endometrioid). The clinicopathological differences are parallelled by specific genetic alterations, with type I showing microsatellite instability and mutations in PTEN, PIK3CA, K Ras, and CTNNB1 (beta-catenin), and type II exhibiting p53 mutations and chromosomal instability. This article reviews the genetic changes of endometrial carcinogenesis in the light of morphological features of the tumours and their precursors. PMID- 17365825 TI - The pathology of gestational trophoblastic disease: recent advances. AB - When inundated with numerous specimens of products of conception as the consequence of miscarriage, it is all too easy for histopathologists to forget that the biology of trophoblast and the events of early placental implantation continue to fascinate because of the inherently invasive properties of the non villous (extravillous) trophoblast. However, unlike the invasion of a malignant tumour, the invasion of trophoblast is controlled. The failure of adequate conversion of maternal uteroplacental arteries is a major pathogenetic phenomenon of important disorders of pregnancy including pre-eclampsia. However, it is in the field of gestational trophoblastic disease that diagnostic acumen is most called for. There are several problematic areas that give rise to diagnostic error; e.g., the diagnosis of early complete mole as partial mole, the over diagnosis of hydatidiform mole in tubal pregnancy and the diagnosis of placental site non-villous trophoblast as placental site trophoblastic tumour or choriocarcinoma, particularly if associated with atypia, as frequently observed in complete mole. The chorionic villi of early diploid complete mole show characteristic features of villous profile, stromal mucin and stromal nuclear debris. The distinction between complete mole and triploid partial mole can be facilitated by ploidy analysis and immunohistochemistry for the product of the paternally imprinted, maternally expressed gene, p57kip2. Persistent trophoblastic disease (PTD) is a clinical not a histopathological diagnosis and the role of the histopathologist once a diagnosis of PTD has been made is limited. Invasive mole and choriocarcinoma are encompassed by PTD. Tumours of the non-villous trophoblast are placental site trophoblastic tumour and the more recently recognised epithelioid trophoblastic tumour. The role of immunohistochemistry in the elucidation of trophoblastic lesions is discussed pragmatically. PMID- 17365826 TI - Immunohistochemistry as a diagnostic aid in cervical pathology. AB - As with biopsies from other sites in the female genital tract, immunohistochemistry is now being increasingly used in cervical pathology as an aid to diagnosis. In this review, I discuss applications of immunohistochemistry in diagnostic cervical pathology with a particular focus on recent developments. It is emphasised that immunohistochemistry is to be used as an adjunct to routine morphological examination and that no marker is totally specific or sensitive for a given lesion. Although much of this review focuses on glandular lesions, the value of markers, such as MIB1 and p16, in the assessment of pre-invasive cervical squamous lesions is discussed. In the broad field of cervical glandular lesions, topics covered include: the value of markers such as MIB1, p16 and bcl-2 in distinguishing adenocarcinoma in situ and glandular dysplasia from benign mimics; markers of mesonephric lesions, including CD10; markers of value in the diagnosis of minimal deviation adenocarcinoma, such as HIK1083; markers of value in distinguishing metastatic cervical adenocarcinoma in the ovary from primary ovarian endometrioid or mucinous adenocarcinoma. Rarely ectopic prostatic tissue occurs in the cervix, which can be confirmed by positive staining with prostatic markers. A panel of markers, comprising oestrogen receptor, vimentin, monoclonal carcinoembryonic antigen and p16, is of value in distinguishing between a cervical adenocarcinoma and an endometrial adenocarcinoma of endometrioid type. Markers of use in the diagnosis of cervical neuroendocrine neoplasms, including small cell and large cell neuroendocrine carcinoma, are discussed. It is stressed that small cell neuroendocrine carcinomas may be negative with most of the commonly used neuroendocrine markers and this does not preclude the diagnosis. p63, a useful marker of squamous neoplasms within the cervix, is of value in distinguishing small cell neuroendocrine carcinoma (p63 negative) from small cell squamous carcinoma (p63 positive) and in confirming that a poorly differentiated carcinoma is squamous in type. PMID- 17365827 TI - Neoplasms of the fallopian tube and broad ligament: a selective survey including historical perspective and emphasising recent developments. AB - Recent contributions on selected aspects of the pathology of tubal and paratubal neoplasms are reviewed after a brief historical perspective. The most important, considering both frequency and clinical importance, are those pertaining to tubal carcinoma. These can be grouped as follows: (1) recognition that endometrioid carcinoma is the second most common carcinoma of the tube, after serous, and other variants of mullerian carcinoma are rare; (2) expansion of knowledge about the morphological spectrum of tubal endometrioid carcinoma; (3) modifications of the FIGO staging system; (4) heightened appreciation of the occasional origin of tubal carcinomas from the tubal fimbriae; (5) increased awareness of early carcinoma arising in patients with the BRCA mutation; (6) greater recognition of the propensity for non-tuberculous salpingitis with reactive atypia to mimic carcinoma. Brief consideration then follows of certain other tubal and paratubal neoplasms including those of the broad ligament, emphasising issues in differential diagnosis. PMID- 17365828 TI - Minimal uterine serous carcinoma: current concepts in diagnosis and prognosis. AB - Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer with a propensity to have extra-uterine spread at diagnosis, in some cases despite limited involvement of the uterus. Serous endometrial intra-epithelial carcinoma (EIC) is a recently recognised entity with the same cytological features and p53 mutations as USC, but it does not demonstrate stromal or myometrial invasion. In addition to representing the putative precursor to USC, the pure form of serous EIC may also be associated with extra-uterine tumour at the time of diagnosis and with risk for recurrence, spread, and eventual death from tumour. Current evidence indicates that serous EIC is a form of minimal USC with behaviour that is stage dependent, thereby necessitating complete surgical staging despite limited disease in the uterus. We review the diagnostic criteria for minimal USC, pitfalls in the differential diagnosis, and discuss a practical approach to evaluating biopsies, polypectomies, or hysterectomies containing minimal USC. PMID- 17365830 TI - The enigma of struma ovarii. AB - Since its first description in the early part of the twentieth century, struma ovarii has elicited considerable interest because of its many unique features; however, at present a number of aspects remain enigmatic. Although the typical presentation is that of a pelvic mass, unusual clinical manifestations such as hyperthyroidism, ascites, and Meigs' syndrome have been recognised. Uncommon macroscopic and especially histological patterns in struma can cause difficulties in diagnosis. Cystic strumas are challenging to diagnose both macroscopically and histologically. Proliferative changes within struma can be misdiagnosed as cancer. In regard to the occurrence of thyroid-type carcinoma in struma ovarii, precise terminology should be utilised, and the term 'malignant struma ovarii' should be avoided because it has been used for several different pathological entities. Papillary carcinoma is the most commonly occurring thyroid-type carcinoma in ovarian struma; however, cases of follicular carcinoma are not infrequent. Histological malignancy in struma does not necessarily equate with biological malignancy, and the majority of thyroid-type carcinomas do not spread beyond the ovary. Strumal carcinoid, a neoplasm apparently unique to the ovary containing elements of both struma and carcinoid, has been misdiagnosed as 'malignant struma ovarii' in the past. The differential diagnosis of extra ovarian spread of struma includes the usual types of thyroid cancer, minimal deviation follicular carcinoma, and peritoneal strumosis. This review emphasises articles both recent and past that have significantly advanced our knowledge of struma ovarii and related neoplasms. PMID- 17365829 TI - Undifferentiated carcinoma of the endometrium: a review. AB - Undifferentiated carcinoma of the endometrium is a high grade carcinoma and under recognised, frequently diagnosed as grade 3 endometrioid carcinoma. We have found that undifferentiated carcinoma represents 9% of all endometrial carcinomas; it is composed of solid sheets of epithelial cells and in most cases only 5-10% of the cells are positive for keratin. The recognition of undifferentiated carcinoma is extremely important when this neoplasm is associated with a grade 1 or grade 2 endometrioid adenocarcinoma. In this situation it is important to diagnose the solid areas of carcinoma as undifferentiated and avoid evaluating them as the solid component of endometrioid carcinoma because there is significant difference between the excellent prognosis of grade 2 endometrioid carcinoma, the intermediate prognosis of grade 3 carcinoma, and the poor prognosis of undifferentiated carcinoma, which in cases of association with differentiated areas should be diagnosed as dedifferentiated endometrioid carcinoma. PMID- 17365831 TI - Neoplasms and pathology of sexual developmental disorders (intersex). AB - Continuing new insights into the biology of sexual development and advances in chromosome analysis have led to early identification and prompt treatment of the intersexual patient, the results of which facilitate a more normal life for affected individuals. Based on these advances, a classification of abnormal sexual development has been developed and refined that correlates the gonadal and genital anatomy with the chromosomal findings and specific genetic or metabolic defects. In a shift from a classification anchored on whether the intersex revolves about a specific gene or whole chromosomal abnormality, the current classification is organised by broader categories into which the intersexual disorders are divided into 'abnormalities of genital differentiation', due largely to the abnormal production or sensitivity of a single hormone, or 'abnormalities in sex determination', due to abnormal gonadal differentiation, usually testicular, with or without chromosomal aberration. The current classification is an integrated approach to this complex group of disorders and is organised according to the manner by which patients present as well as on the pathophysiological basis of the defect. The classification also groups patients who are at high risk for development of gonadal neoplasia. PMID- 17365832 TI - Test and teach. 53. Diagnosis: An interesting retroperitoneal mass. PMID- 17365833 TI - Carcinoma of the cervix with incisional skin metastasis: a rare event. PMID- 17365834 TI - Appendiceal mixed endocrine-exocrine neoplasm presenting as bilateral solid tubular and classical Krukenberg tumour. PMID- 17365835 TI - Fine needle aspiration cytology of stromal sarcoma of the breast. PMID- 17365836 TI - Expression of 15-hydroxyprostaglandin dehydrogenase, a COX-2 antagonist and tumour suppressor, is not altered in gastric carcinomas. PMID- 17365837 TI - First reported case of ileal malignant paraganglioma. PMID- 17365838 TI - F-18 FDG-avid sclerosing angiomatoid nodular transformation (SANT) of the spleen: case study and literature review. PMID- 17365839 TI - Lethal metatropic dysplasia: a case report. PMID- 17365840 TI - Splenosis mimicking lymphoma. PMID- 17365841 TI - Acute haemoperitoneum: a surgical emergency due to a rare cause of ruptured splenic artery aneurysm. PMID- 17365842 TI - Kawasaki's disease: morphology of coronary artery aneurysms. PMID- 17365843 TI - Fulminant toxoplasmosis following heart transplantation. PMID- 17365844 TI - Isolation of an extended spectrum beta-lactamase producing Pseudomonas aeruginosa from a patient in a Sydney hospital. PMID- 17365847 TI - Alpha-delta platelet storage pool deficiency in three generations. AB - Alpha-Delta platelet storage pool deficiency (alphadelta SPD) is a rare inherited bleeding disorder affecting both males and females, occurring in families, as well as sporadically. Patient platelets in most cases are moderately deficient in both alpha granules and dense bodies. Only one patient has been severely deficient in both organelles. The present study is the first to document a severe decrease in both platelet alpha granules and dense bodies in four members in three generations of the same family. Efforts to differentiate this disorder from other hypogranular platelets syndromes in the present investigation suggested that the alpha granules and dense bodies become connected to channels of the open canalicular system (OCS) and lose their contents to the exterior without prior activation of the cells. In contrast, alpha granule formation in the white platelet syndrome is too slow, and cells leave the bone marrow still in the process of producing organelles. Gray platelet syndrome platelets can make alpha granules, but their enclosing membranes are unable to retain stored products. As a result, the organelles lose their contents to surrounding cytoplasm in megakaryocytes and platelets, not selectively through the demarcation system channels and OCS channels. Thus, the pathogenesis of alphadelta SPD is unique. PMID- 17365848 TI - Doppler velocimetry alterations related to platelet changes in third trimester pregnancies. AB - The aim of this study was to evaluate the correlations between the haematological parameter mean platelet volume and Doppler velocimetry parameters in order to improve clinical management in third trimester complicated pregnancies (pre eclampsia, PE, and IUGR) affected by altered uterine resistances. Fifty-one patients were included in the abnormal uterine arteries Doppler velocimetry group (25 pregnancies were complicated by PE, 26 pregnancies were complicated by IUGR). Ninety-nine normotensive pregnant women taking no drugs for at least 2 weeks prior to testing and with no difference in gestational age at evaluation, with normal Doppler velocimetry profiles at routine screen, were used as controls. From all pregnant women, 20 mL of whole blood were obtained into citrate tubes after Doppler velocimetry evaluation and analysed for red blood cell counts (RBC), mean corpuscular volume (MCV), haemoglobin (HGB), haematocrit level (HCT), white blood cells count (WBC), platelet counts (PLT), mean platelets volume (MPV) and other biochemical parameters. From all blood parameters studied, MPV was significantly higher in women with altered uterine artery Doppler velocimetry compared with those with normal Doppler profiles (9.4 +/- 1.0 vs. 8.05 +/- 1.2 fL, P<0.001). In the group with altered uterine artery Doppler velocimetry, pregnancies complicated by PE showed a MPV value higher than pregnancies affected by IUGR (9.5 +/- 1.6 vs. 8.9 +/- 1.1, P<0.001). Finally, mean uterine arteries RI values were significantly related to MPV (fL) in both PE and IUGR groups (P<0.01, r=0.37 and P<0.01, r=0.38, respectively). Our study shows that a periodical monitoring of haematological parameters such as MPV can be associated to Doppler velocimetry in order to improve the management of pregnancies with uterine arteries Doppler velocimetry alterations. PMID- 17365849 TI - Platelets and white blood cell subpopulations among patients with myocardial infarction and unstable angina. AB - Platelet (PLT)-endothelial cell and PLT-leukocyte interactions at lesion-prone sites might trigger a local inflammatory response early in the genesis of atherosclerosis and contribute to plaque destabilization leading to acute coronary syndromes (ACS). The aim of this study was to assess the PLT count, mean PLT volume (MPV), PLT mass, white blood cell (WBC; including eosinophils) and plasma interleukin (IL)-5, in patients with ACS and controls. PLT count, MPV, PLT mass, WBC and eosinophil percentage were determined in 167 consecutive patients with ACS (86 with acute myocardial infarction, AMI, and 81 unstable angina, UA) and 83 controls. Plasma IL-5 was measured in some patients and controls. Patients were considered in subgroups depending on smoking status and if they had or did not have diabetes mellitus (DM). The PLT count was lower in the UA and AMI groups although this did not always achieve significance. The MPV was significantly raised in all patient groups except in DM non-smokers with UA or AMI. All AMI patients had significantly higher WBC counts compared with controls. The percentage of eosinophils was lower in the UA and AMI groups although this did not always achieve significance. Plasma IL-5 levels were significantly increased in the UA and AMI groups. In conclusion, patients with ACS present with changes in the count of several cell types. These cells may become therapeutic targets and these changes may also act as markers of myocardial damage or prognosis. PMID- 17365850 TI - Effects of beta2-glycoprotein-I on platelet aggregation in cord versus adult whole blood. AB - We present a peculiarity of the neonatal hemostatic system that might contribute to establish a procoagulant readiness in neonatal blood by sensitizing neonatal platelets for ADP stimulation. beta2-glycoprotein-I (beta2-GP-I) is a plasma constituent capable of suppressing ADP-induced platelet aggregation. We found significant lower levels of beta2-GP-I in cord vs. adult plasma (120 +/- 27 vs. 180 +/- 37 microg/mL, P<0.001). We demonstrate dose-dependent inhibition of ADP induced platelet aggregation in cord whole blood (WB) in the presence of increasing amounts of beta2-GP-I, evaluated by means of WB aggregometry employing the impedance method. Particularly, raising the beta2-GP-I concentration in cord WB from neonatal level up to the respective adult value caused significant reduction of amplitude (from 9.5 +/- 2.7 to 2.8 +/- 0.9 Omega, P<0.001) and of slope (from 5.9 +/- 2.4 to 1.89 +/- 0.9 Omega/min, P<0.001), and a significant prolongation of the aggregation time (from 51.8 +/- 22.9 to 110.8 +/- 60.3 s, P<0.001). In conclusion, physiological low levels of beta2-GP-I in cord WB cause enhanced responsiveness of neonatal platelets to ADP stimulation. This mechanism might help to explain the clinically observed well-functioning hemostasis in neonates. PMID- 17365851 TI - Effects of garlic oil on platelet aggregation: a double-blind placebo-controlled crossover study. AB - The use of antiplatelet therapies decreases the incidence of mortality in persons prone to cardiovascular events. Several in vitro studies suggest that garlic may decrease platelet aggregation. We aimed to test the acute effects of garlic on platelet aggregation in 14 healthy volunteers using a randomised, double-blind, placebo-controlled, crossover research method. The active agent tested was solvent-extracted garlic oil incubated in ethanol to obtain organosulphur compounds that demonstrate the highest antiplatelet activity when tested in vitro. Platelet aggregation was induced ex vivo by adrenaline, collagen or adenosine diphosphate (ADP). Four hours after consuming one large dose of oil derived from 9.9 g garlic, there was little or no effect in the reduction of platelet aggregation. Platelet aggregation induced by adrenaline was reduced slightly but significantly (P<0.05; 12% reduction). The oil had no effect on collagen- or ADP-induced aggregation. The results of this controlled trial indicate that this type of garlic oil should not be relied on in persons with conditions in which reductions in platelet aggregation are desired or necessary. PMID- 17365852 TI - Platelets possess functional TGF-beta receptors and Smad2 protein. AB - TGF-beta1 plays a main role in tissue repair by regulating extracellular matrix production and tissue granulation. Platelets are one of the main sources of this cytokine in the circulation. The aim of this study was to evaluate the presence of the TGF-beta receptors on platelets, the effect of TGF-beta1 on platelet aggregation and the underlying intracellular mechanisms. TGF-beta receptors on platelets were studied by flow cytometry and their mRNA by PCR. Platelet aggregation was assessed by turbidimetric methods and intracellular pathways by Western blot. TGF-beta receptor type II and mRNA codifying for TbetaRI and TbetaRII were found in platelets. We demonstrated that TGF-beta1 did not trigger platelet aggregation by itself but had a modulating effect on ADP-induced platelet aggregation. Either inhibition or increase in platelet aggregation, depending on the exposure time to TGF-beta1 and the ADP concentration used, were shown. We found that platelets possess Smad2 protein and that its phosphorylation state is increased after exposure to TGF-beta1. Besides, TGF-beta1 modified the pattern of ADP-induced tyrosine phosphorylation. Increased phosphorylation levels of 64-, 80- and 125-kDa proteins during short time incubation with TGF-beta1 and increased phosphorylation of 64- and 125-kDa proteins after longer incubation were observed. The modulating effect of TGF-beta1 on platelet aggregation could play a role during pathological states in which circulating TGF-beta1 levels are increased and intravascular platelet activation is present, such as myeloproliferative disorders. In vascular injury, in which platelet activation followed by granule release generates high local ADP concentrations, it could function as a physiological mechanism of platelet activation control. PMID- 17365853 TI - Comparison of changes in erythrocyte and platelet phospholipid and fatty acid composition and protein oxidation in chronic obstructive pulmonary disease and asthma. AB - OBJECTIVE: To analyse and compare the phospholipid and fatty acid composition of total lipids and the occurrence of lipid peroxidation and protein oxidation directly in erythrocytes or platelets from chronic obstructive pulmonary disease (COPD) and asthma patients. PATIENTS: Fifteen consecutive outpatients with COPD (all smokers) and asthma (non-smokers) recruited during a moderate-to-severe (COPD) or moderate (asthma) exacerbation. Fifteen subjects with smoking habits similar to those of COPD patients were studied as a control group. METHODS: Phospholipid and total fatty acid compositions were analysed by two-dimensional thin layer chromatography or gas chromatography-mass spectrometry, respectively. The lipid fluorescence of lipid extracts was measured by spectrofluorimetry. Protein carbonyl contents and profiles were measured by immunoblot detection. RESULTS: No differences were found either in erythrocyte or platelet cholesterol or phospholipid levels. Only a decrease in the content of phosphatidylserine + phosphatidylinositol (P<0.003) was detected in platelets from the asthma patients. In erythrocytes, the fatty acid profile changed in both lung pathologies, especially as regards polyunsaturated fatty acids (decreases in arachidonic and 22:4 fatty acid contents). Other observed changes were: COPD, an increase in palmitic fatty acid; asthma, an increase in oleic and decreases in eicosapentaenoic and 22:6 + 24:1 fatty acids. In platelets, the fatty acid profiles revealed many differences between both lung pathologies: COPD, a decrease in 18:1 and increases in 20:5 and 22:5 + 24:0; asthma, a decrease in 20:4 and increase in 22:6 + 24:1. In COPD vs. asthma patients, fatty acid changes were mainly detected in platelets, especially in 18-carbon species, with decreases in stearic and 18:1 fatty acids in the COPD patients. Protein oxidation levels were increased in both lung pathologies in both erythrocytes and platelets. CONCLUSIONS: COPD and asthma are associated with common or specific changes in the lipid composition of erythrocytes and/or platelets. The data point to lipid peroxidation and protein oxidation phenomena in both types of blood cell, although platelets would be more susceptible to stress. PMID- 17365854 TI - Helicobacter pylori eradication reduces platelet count in patients without idiopathic thrombocytopenic purpura. AB - Discrepant outcomes of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura have been reported. Here patients with dyspepsia and no other complications underwent gastroendoscopic examination and evaluation for Helicobacter pylori infection. Helicobacter pylori-infected patients with gastritis and gastric ulcer received eradication therapy: lansoprazole (60 mg/day), clarithromycin (400 mg/day), and amoxicillin (1500 mg/day) for 1 week. Lansoprazole 30 mg/day was administrated additional 7 weeks. Peripheral platelets were counted before treatment, 8 weeks after initiation of therapy, and at follow-up periods. Platelet counts in patients with both gastritis and gastric ulcer were evaluated with reference to the presence of Helicobacter pylori infection. Eighty-seven patients with gastritis and 35 of those with gastric ulcer underwent successful eradication therapy. Peripheral platelet counts in patients with gastritis decreased from 235+/-55 to 228+/-58 (10(3)/microL) (p=0.0337), and those with gastric ulcer decreased from 248+/-60 to 232+/-48 (10(3)/microL) (p=0.020) 8 weeks after initiation of therapy. Non eradicated patients did not show such a tendency. Helicobacter pylori eradication reduced peripheral platelet counts in patients with gastritis and gastric ulcer. Amelioration of thrombocytopenia by eradicating Helicobacter pylori appears to involve mechanisms specific to idiopathic thrombocytopenic purpura. PMID- 17365856 TI - Microparticle-associated P-selectin reflects platelet activation in preeclampsia. AB - Platelet activation in preeclampsia is reflected by elevated levels of platelets exposing P-selectin. In plasma, a non-cell bound (soluble) form of P-selectin is present. Elevated levels of this soluble form have been reported in preeclampsia. Plasma P-selectin may consist of two fractions: microparticle (MP)--associated P selectin and non-MP--associated P-selectin. In the present cross-sectional study, we investigated to which extent plasma P-selectin is MP--associated and whether such MP are elevated in preeclamptic patients. Preeclamptic patients (n=10) were matched with normotensive pregnant women (n=10) and non-pregnant controls (n=10). Plasma P-selectin was measured by ELISA. MP were isolated, double labelled with anti-CD61 (GPIIIa) and anti-CD62P (P-selectin) and subsequently analyzed with flowcytometry. Plasma P-selectin concentration was elevated in preeclamptic patients compared to non-pregnant controls (p=0.007), but not compared to normotensive pregnant women (p=0.210). Plasma P-selectin is partially MP- associated (3-5%). In pregnancy, the fraction of P-selectin exposing platelet derived MP (PMP) (10.9%) was increased compared to non-pregnant controls (8%). This fraction further increased in preeclamptic patients (15.4%), and significantly differed from normotensive pregnant women (p=0.02). A minor fraction of plasma P-selectin is associated with PMP. The fraction of PMP exposing P-selectin is increased in preeclamptic patients and to a lesser extent in normotensive pregnancy. Because MP associated P-selectin exclusively originates from platelets, this fraction indicates platelet activation. Platelet activation is prominent in preeclampsia and this study proves that at least a part of the plasma P-selectin originates from platelets. PMID- 17365855 TI - Minimal regulation of platelet activity by PECAM-1. AB - PECAM-1 is a member of the superfamily of immunoglobulins (Ig) and is expressed on platelets at moderate level. PECAM-1 has been reported to have contrasting effects on platelet activation by the collagen receptor GPVI and the integrin, alphaIIbbeta3, even though both receptors signal through Src-kinase regulation of PLCgamma2. The present study compares the role of PECAM-1 on platelet activation by these two receptors and by the lectin receptor, CLEC-2, which also signals via PLCgamma2. Studies using PECAM-1 knockout-mice and cross-linking of PECAM-1 using specific antibodies demonstrated a minor inhibitory role on platelet responses to the above three receptors and also under some conditions to the G-protein agonist thrombin. The degree of inhibition was considerably less than that produced by PGI2, which elevates cAMP. There was no significant difference in thrombus formation on collagen in PECAM-1-/- platelets relative to litter-matched controls. The very weak inhibitory effect of PECAM-1 on platelet activation relative to that of PGI2 indicate that the Ig-receptor is not a major regulator of platelet activation. PECAM-1 has been reported to have contrasting effects on platelet activation. The present study demonstrates a very mild or negligible effect on platelet activation in response to stimulation by a variety of agonists, thereby questioning the physiological role of the immunoglobulin receptor as a major regulator of platelet activation. PMID- 17365858 TI - Hypoglycaemia predisposes platelets to death by affecting calcium homeostasis and mitochondrial integrity. AB - Factors affecting platelet survival are poorly understood. To explore the hypothesis that platelet lifespan correlates with the lifespan of a key housekeeping process we subjected human platelets to in vitro incubation at 37 degrees C for 24 h to several days under hypoglycaemic conditions. Viability was assessed both by microscopy and flow cytometry using calcein-AM and/or FM4-64. In keeping with previous data we found that, under control conditions platelets died at a linear rate during 120 h of incubation. Hypoglycaemia did not affect the death rate but did lead to an increase in the frequency of platelets unable to accumulate the mitochondrial potentiometric dye 10-Nonyl Acridine Orange (NAO) and promoted platelet death in response to the pro-apoptotic molecule BH3I-2'. Hypoglycaemia led to an increase in intraplatelet calcium that could be prevented 2-aminoethoxydiphenylborate (2-APB), a store operated calcium channel (SOCC) blocker. However, this agent was unable to rescue the platelets' ability to accumulate NAO. These data suggest that extracellular glucose is utilised by platelets for calcium homeostasis and maintenance of mitochondrial integrity and that hypoglycaemia primes platelets for death. PMID- 17365859 TI - Variation of pH in lysed platelet concentrates influence proliferation and alkaline phosphatase activity in human osteoblast-like cells. AB - Activated platelets release a multifaceted blend of growth factors that has stimulatory effects on mesenchymal cells, both in vitro and in vivo, which imply beneficial effects on wound repair and tissue regeneration. Previous studies on fibroblast cultures have revealed that more potent growth factors, with respect to cell proliferation, are released in acidic preparations of lysed platelet concentrates in comparison with neutral and alkaline preparations. The current study was intended to investigate the influence of pH on lysed platelet concentrates with respect to release of growth factors, cell proliferation and alkaline phosphatase (ALP) activity in human osteoblast-like cells (hFOB 1.19). Cell proliferation was assessed with the MTT kit, ALP activity by conventional enzymatic reaction kinetics and growth factors platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) by enzyme-linked immunosorbent assays. Osteoblast-like cells were stimulated with lysed platelet concentrates preincubated at pH 4.4, 5.4, 7.4, and 7.6. A 3-13-fold increase of cell proliferation was found in comparison with controls and the most evident increase was observed with platelets activated at pH 5.4. The highest ALP activity was observed in preparations at pH 7.6. Platelets incubated in an acidic environment (pH 5.4) induced a higher proliferation compared with preincubation at neutral or alkaline pH and the level of PDGF was also found to be higher in acidic preincubations. The level of TGF-beta was, in contrast, lowest at pH 4.4. We suggest, based on these experimental findings, that acidic milieu influence platelets to release growth factors more potent to stimulate osteoblast proliferation than neutral and alkaline platelet preparations. Lysed platelet concentrates prepared at an alkaline pH might release additional components with stimulating effects resulting in other features than cell proliferation. This is the first report, to our knowledge, about a pH dependent stimulatory effect of lysed platelet concentrates on human osteoblast-like cell proliferation. Lysed platelet concentrates, preincubated in acidic or alkaline buffers, may benefit fracture healing, implant fixation and might also be advantageous in the treatment of wounds with platelet constituents; however, this has to be investigated in extended experimental and clinical settings. PMID- 17365860 TI - Thrombin-induced interleukin 1beta synthesis in platelet suspensions: impact of contaminating leukocytes. AB - A controversial discussion as to whether human platelets are capable of regulated protein synthesis has been ongoing for over half a century. A previous study has suggested that human platelets synthesize large amounts of interleukin 1beta (IL 1beta) in response to external cues and in a physiologically significant manner. However, cytokines such as IL-1beta are generally considered to be products of leukocytes and it could not be completely excluded that contaminating leukocytes may have contributed to the IL-1beta results in platelet preparations. It was therefore our intention to investigate whether residual leukocytes had an impact on thrombin-induced IL-1beta synthesis. Using various methods to reduce the level of contaminating leukocytes, we found that IL-1beta production in platelet-rich suspensions is dependent on the presence of leukocytes, as it was decreased by reducing the number of leukocytes. In addition, we found that thrombin-induced IL 1beta synthesis was completely eliminated in leukocyte-free platelet preparations and could be restored by adding leukocytes. IL-1beta synthesis could be detected in platelet suspensions contaminated with at least 1 leukocyte per 10(5) platelets. This study demonstrated that platelets are incapable of synthesizing detectable amounts of IL-1beta on their own. We suggest that any IL-1beta synthesis detected is a by-product of leukocytes contaminating the platelet preparations. Thus, the hypothesis that platelets producing IL-1beta, provide a new link between thrombosis and inflammation needs to be reconsidered. PMID- 17365861 TI - Platelet aggregation in obese and diabetic subjects: association with leptin level. AB - To clarify the relationship between serum leptin concentration and platelet aggregation mechanism, we investigated serum leptin concentration and agonist induced platelet aggregation in eight obese subjects and eight non-obese and non diabetic controls. In addition we also measured them in 15 type 2 diabetic subjects and 17 control subjects. Maximum platelets aggregation rate (MPAR) in control and diabetic subjects by adenosine diphosphate (ADP), collagen and thrombin were measured by aggregometer after pretreatment with 100 ng/ml leptin for 60 min. The MPAR by 0.15 U/ml thrombin stimulation in leptin-treated platelet in the controls was significantly increased compared with that in non-treated platelets, but not by ADP and collagen stimulation. Despite a significantly higher concentration of leptin in obese subjects, agonist-induced platelet aggregation in obese subjects was not different from that in controls. There were no significant differences in serum leptin concentration and MPAR by various agonists between diabetic and control subjects. When MPAR by ADP in the diabetic subjects was divided into two groups (high group: >50%, low group: <50%), the serum leptin concentration in the high group was significantly increased, compared with that in the low group. These results suggest that ADP-induced platelet aggregation may be associated with serum leptin concentration in diabetic subjects, and that leptin-associated platelet aggregation may affect the development of cardiovascular complications in obese and diabetic subjects. PMID- 17365862 TI - Epinephrine induces intracellular Ca2+ mobilization in thrombin-desensitized platelets: a role for GPIb-IX-V. AB - In this work we have investigated the ability of epinephrine to trigger the release of intracellular Ca2+ in thrombin-desensitized platelets. Addition of thrombin to platelets in the presence of extracellular EGTA caused a rapid and transient release of Ca2+ from intracellular stores and rendered platelets unresponsive to a second addition of the same agonist. Although epinephrine alone had no effect on intracellular Ca2+ mobilization, its addition to thrombin desensitized platelets was associated to a rapid and evident secondary release of intracellular Ca2+. This effect of epinephrine was not observed when platelets were desensitized with other agonists able to induce phospholipase C activation, including convulxin, U46619, and ADP. Although the platelet receptor for epinephrine is coupled to the Gi family member Gz, no secondary Ca2+ release was seen in thrombin-desensitized platelets upon stimulation of other Gi-coupled receptors, including the P2Y12 receptor and the CXCR4. Addition of hirudin to thrombin-desensitized platelets prevented epinephrine-promoted secondary release of Ca2+, indicating that thrombin, rather than epinephrine itself, is actually responsible for this event as a consequence of thrombin receptors resensitization. Studies with platelets stimulated with specific PAR1- and PAR4- activating peptides proved that neither one of these thrombin receptors were involved in the secondary epinephrine-assisted Ca2+ release. Moreover, we found that thrombin was still able to induce a reduced, but evident release of Ca2+ from internal stores in PAR1- and PAR4-desensitized platelets, which could be followed by a secondary Ca2+ release upon subsequent addition of epinephrine. Importantly, both the primary and the secondary Ca2+ release induced by thrombin and epinephrine in PAR1- and PAR4-desensitized platelets were abrogated upon cleavage of GPIbalpha by the metalloproteinase mocarhagin. These results demonstrate a direct role of thrombin binding to GPIb-IX-V in the mobilization of Ca2+ from intracellular stores, and reveal that epinephrine can restore this process in desensitized platelets, thus prolonging the effect of thrombin stimulation. PMID- 17365863 TI - Thrombus formation without platelets under inflammatory condition: an in vitro study. AB - Platelet derived microvesicles, which are shed from platelets upon platelet activation, interact with monocytes in the blood. In this study the nature of this interaction was characterized in a model system with the monocytic cell line MM6 and isolated platelet derived microvesicles (PMV). The interaction of PMV with MM6 is separated in two consecutive steps, which are partially overlapped in time. In a first step there is an immediate conjugate formation with single MM6 and PMV, which was proved microscopically and by cytometry measurements. This process is dependent on CD62P, determined by an inhibition after pre-incubation with anti-CD62P. After a lag time of 4 min this process is supplemented by an aggregate formation of single conjugates, which leads finally to one macroscopic visible aggregate. The Nature of this aggregate was characterized by immunohistochemistry and laser aggregatometry. An addition of GPRP blocks the formation of a fibrin network and also the aggregate formation, proving the necessity of fibrin network formation. This was also shown by diminishing the aggregate formation by addition of hirudin. Finally fluorescent microscopic images proved the necessity of a fibrin network holding MM6 cell/PMV aggregates together. Even pure PMV can form such an aggregate only visible as thin film and less stable as the cell PMV aggregate. The described process might be important in vivo causing thrombotic events without direct involvement of platelets. Especially in situations with extreme PMV levels, such as acute coronary heart disease, trauma and sepsis, these events could lead to the appearance of haemostatic complications. PMID- 17365864 TI - Platelet alpha granules in BLOC-2 and BLOC-3 subtypes of Hermansky-Pudlak syndrome. AB - Hermansky-Pudlak syndrome (HPS) is a disorder of lysosome-related organelle biogenesis that displays genetic locus heterogeneity. The eight known HPS proteins combine in functional complexes, two of which are called BLOC-2 and BLOC 3; a BLOC is a Biogenesis of Lysosome-related Organelles Complex. Organelles affected in HPS include the melanosome, resulting in hypopigmentation, and the platelet delta (dense) granule, resulting in prolonged bleeding times. Whole mount electron microscopy (EM) detects the absence of platelet delta granules and confirms the diagnosis of HPS. To date, the status of other organelles and granules in HPS platelets has not been documented. We performed ultrastructural studies on platelets of patients with different genetic forms of HPS, specifically those comprising the BLOC-2 and BLOC-3 subtypes. No differences in distribution, size or quantity of other platelet organelles and membrane structures could be detected in our patients. Since alpha and delta granules are formed from multivesicular bodies in the megakaryocyte, and since only delta granules are defective in HPS, we conclude that HPS genes function within the portion of delta granule biogenesis that has diverged from that of alpha granules. Thus, it is unlikely that the generalized bleeding diathesis of HPS is attributed to a deficiency of alpha granules. PMID- 17365865 TI - Potentiation of platelet responsiveness to nitric oxide by angiotensin-(1-7) is associated with suppression of superoxide release. AB - Recently we showed that angiotensin (Ang) II potentiates platelet aggregation, while Ang-(1-7) potentiates the anti-aggregatory action of the nitric oxide (NO) donor sodium nitroprusside (SNP), and may therefore counteract platelet NO resistance that accompanies cardiovascular disease and is associated with increased levels of superoxide (O(2)(-)). In the current study, we investigated whether the effect of Ang-(1-7) on platelet NO responsiveness is associated with the modulation of O(2)(-) release and is mediated by a specific Ang-(1-7) receptor. In whole blood, SNP (10 micromol/L) inhibited ADP (2.5 micromol/L) induced platelet aggregation by 21 +/- 8% (p < 0.02), measured via extent of aggregation. Ang-(1-7) did not directly affect platelet aggregation, but potentiated the inhibitory action of SNP. This effect of Ang-(1-7) was bimodal, with maximal increase in SNP-induced inhibition of aggregation by incremental 18 +/- 2% (2-fold, on average; p<0.01) at 10-100 nmol/L Ang-(1-7) (Cmax), and was abolished at higher concentrations of Ang-(1-7). The Ang-(1-7) receptor antagonist D-ala7-Ang-(1-7) (1 micromol/L) completely eliminated the potentiating effects of Ang-(1-7). Platelet aggregation was accompanied by O(2)(-) release (assessed via lucigenin-derived chemiluminescence). SNP suppressed this O(2)(-) release, and Ang-(1-7) at Cmax augmented (by incremental 23 +/- 8%, p<0.03) the effect of SNP. In order to examine possible association of Ang-(1-7) receptor with platelets, we performed aggregation experiments in platelet-rich plasma. However, in these experiments Ang-(1-7) did not potentiate the anti-aggregatory action of SNP. Furthermore, in isolated polymorphonuclear leukocytes (PMN), a major cellular source of O(2)(-) in blood, Ang-(1-7) did not modify O(2)(-) release (after stimulation with fMLP, PMA or ADP), either in the absence or presence of SNP. Hence, Ang-(1-7) effects occurred only in whole blood. In conclusion, Ang-(1-7) potentiates the anti-aggregatory effects of NO donor, presumably via a specific Ang-(1-7) receptor. This potentiation is associated with the suppression of O(2)(-) release during aggregation and arises via an interaction between platelets and PMN. PMID- 17365866 TI - Effect of oral contraceptives and ovarian cycle on platelet function. AB - In past decades, numerous epidemiological and clinical studies in women taking oral contraceptives revealed the impact of sex steroids on coagulation factors and the incidence of venous thrombosis. To date, only scarce data regarding the impact of oral contraceptives on platelet function are available. The aim of this study was to further elucidate the impact of sex steroids on platelet function. We conducted an observational study in young women using different types and dosages of monophasic oral contraceptives (OCs) compared to women not taking OCs. During the follicular phase, the mean closure time (CT) in Col/Epi was 168.0 +/- 64.9 s compared to 131.5 +/- 28.9 s during the luteal phase (p=0.012). In Col/Epi cartridges, no difference was detected between women taking second/third generation OCs and low-dose OCs (145.2 +/- 44.3 vs. 169.4 +/- 63.5, p=0.34). In contrast, mean Col/Epi values of women using anti-androgen-containing OCs were less (110.3 +/- 15.6 s) than in both other OC groups (p=0.03 for both comparisons). The same holds for Col/Epi values from women during the follicular- and luteal phases compared to women using anti-androgen-containing OCs (p=0.0002, p=0.013). Significant correlations between progesterone and platelet function in women not using OCs (p=0.02) could be found. In conclusion, the results of the study show that platelet function might be modulated by OCs and the female cycle. As for OCs, the main factor seems to be the progestagen. During the female cycle, the main impact on platelet function might be mediated by progesterone. PMID- 17365867 TI - Platelet count and platelet activation: impact of a fat meal and day time. PMID- 17365870 TI - A response to criticism of our estimates of under-5 mortality in Iraq, 1980-98. AB - According to estimates published in this journal, the number of deaths of children under 5 in Iraq in the period 1991-98 resulting from the Gulf War of 1991 and the subsequent imposition of sanctions by the United Nations was between 400,000 and 500,000. These estimates have since been held to be implausibly high by a working group set up by an Independent Inquiry Committee appointed by the United Nations Secretary-General. We believe the working group's own estimates are seriously flawed and cannot be regarded as a credible challenge to our own. To obtain their estimates, they reject as unreliable the evidence of the 1999 Iraq Child and Maternal Mortality Survey--despite clear evidence of its internal coherence and supporting evidence from another, independent survey. They prefer to rely on the 1987 and 1997 censuses and on data obtained in a format that had elsewhere been rejected as unreliable 30 years earlier. PMID- 17365871 TI - Socio-economic status, permanent income, and fertility: a latent-variable approach. AB - This paper examines how permanent income and other components of socio-economic status (SES) are related to fertility in less developed countries. Because permanent income cannot be measured directly, we employ a latent-variable method. We compare our results with those of the more common proxy-variable method and investigate the consequences of not accounting for measurement error. Using data from Ghana and Peru, we find that permanent income has a large, negative influence on fertility and that research must take the latent nature of permanent income into account to uncover its influence. Controlling for measurement error in the proxies for permanent income can also lead to substantial changes in the estimated effects of control variables. Finally, we examine which of the common proxies for permanent income most closely capture the concept. The results have implications beyond this specific dependent variable, providing evidence on the sensitivity of microanalyses to the treatment of long-term economic status. PMID- 17365872 TI - Measuring housing quality in the absence of a monetized real estate market. AB - Measuring housing quality or value or both has been a weak component of demographic and development research in less developed countries that lack an active real estate (housing) market. We describe a new method based on a standardized subjective rating process. It is designed to be used in settings that do not have an active, monetized housing market. The method is applied in an ongoing longitudinal study in north-east Thailand and could be straightforwardly used in many other settings. We develop a conceptual model of the process whereby households come to reside in high-quality or low-quality housing units. We use this theoretical model in conjunction with longitudinal data to show that the new method of measuring housing quality behaves as theoretically expected, thus providing evidence of face validity. PMID- 17365873 TI - The effects of siblings on the migration of women in two rural areas of Belgium and the Netherlands, 1829-1940. AB - This study explores the extent to which the presence and activities of siblings shaped the chances of women migrating to rural and urban areas in two rural areas of Belgium and the Netherlands during the second half of the nineteenth and first decades of the twentieth century. Shared-frailty Cox proportional hazard analyses of longitudinal data from historical population registers show that siblings exerted an additive impact on women's migration, independently of temporal and household characteristics. Just how siblings influenced women's migration depended on regional modes of production and on employment opportunities. In the Zeeland region, sisters channelled each other into service positions. In the Pays de Herve, where men and women found industrial work in the Walloon cities, women were as much influenced by their brothers' activities. Evidence is found for two mechanisms explaining the effects of siblings: micro-economic notions of joint household decision-making and social capital theory. PMID- 17365874 TI - Late marriage and the HIV epidemic in sub-Saharan Africa. AB - The causes of large variation in the sizes of HIV epidemics among countries in sub-Saharan Africa are not well understood. Here we assess the potential roles of late age at marriage and a long period of premarital sexual activity as population risk factors, using ecological data from 33 sub-Saharan African countries and with individual-level data from Demographic and Health Surveys (DHS) in Kenya and Ghana in 2003. The ecological analysis finds a significant positive correlation between HIV prevalence and median age at first marriage, and between HIV prevalence and interval between first sexual intercourse and first marriage. The individual-level analysis shows that HIV infection per year of exposure is higher before than after first marriage. These findings support the hypothesis of a link between a high average age at marriage and a long period of premarital intercourse during which partner changes are relatively common and facilitate the spread of HIV. PMID- 17365875 TI - Increase in common longevity and the compression of mortality: the case of Japan. AB - This study shows a strong increase in the modal age at death (M) in Japan over a period of 50 calendar years, accompanied by a clear decrease in the standard deviation of ages at death above M (SD(M+)) until the 1990s for men and the mid 1980s for women. For the most recent periods SD(M+) appears to have stopped decreasing, even though M has continued to increase linearly. This stagnation in SD(M+) has been accompanied by stagnation in q(M). The number of deaths at M (d(M)) and the number of deaths at and above M (d(M+)) have increased, but significantly more slowly since the period 1975-79. Since the 1980s an acceleration in the increase of M+kSD(M+), our indicator of the longest life durations, has been essentially due to the pause in SD(M+). Our data do not suggest that we are approaching an upper limit in human longevity. PMID- 17365876 TI - Correcting missing-data bias in historical demography. AB - Studies on population history are often based on incomplete records of life histories. For instance, in studies using data obtained from family reconstitution, the date of death is right censored (by migration) and the censoring time is never observed. Several methods for the correction of mortality estimates are proposed in the literature, most of which first estimate the number of individuals at risk and then use standard techniques to estimate mortality. Other methods are based on statistical models. In this paper all methods are reviewed, and their merits are compared by applying them to simulated and to seventeenth-century data from the English parish of Reigate. An ad hoc method proposed by Ruggles performs reasonably well. Methods based on statistical models, provided they are sufficiently realistic, give comparable accuracy and allow the estimation of several other quantities of interest, such as the distribution of migration times. PMID- 17365881 TI - Development and analysis of modular uniaxial leg adapter. AB - The adapters of modular prostheses are the structural components mostly likely to fail during the use of prostheses because of the high forces and moments occurring during the human gait. In this study, structural performance of a modular uniaxial leg adapter during gait is analysed utilizing computer software. By analysing the results, the relevant product was redesigned in order to prevent possible failures. Subsequently, the developed modular uniaxial leg adapter was tested in accordance with ISO 10328 in order to ensure the safety of the design. Further, the test results are compared with a finite element analysis to evaluate the performance of the numerical analysis. PMID- 17365882 TI - Comparison of the results of four users of a contemporary CAD/CAM system. AB - The objective of this study was to investigate the variation of measurements recorded when four different users of the TracerCAD system trace a model of known dimensions and volume. This complements a previous study where the accuracy and consistency of a single user was measured. Landmarks were added to indicate proximal, distal, anterior, medial and lateral regions of a specially manufactured cylindrical nylon 6.6 model. Four circumferential lines were added at regular intervals along the length of the cylinder with a view to calculating diameters and volumes relative to these landmarks. The model was measured using a comparator with guaranteed accuracy to one hundredth of a millimetre, and was traced using the TracerCAD system by four different users. The difference in mean volume between measured results and TracerCAD scans of differing users ranged to 3%. Individual trace volumes varied by up to -7.85%. In all volumes measured, 11 out of 12 maximum volume percentage differences measured greater than 2%, and of these, seven results showed maximum volume percentage difference to measure greater than 4%. PMID- 17365883 TI - Locating the axis of rotation when fitting an elbow orthosis: a comparison of measurement and palpation. AB - No other previously published studies consider the relative motion of orthotic components positioned on the upper arm and the forearm. This study therefore measured the location and direction of the axis of rotation of an orthotic component fixed to the forearm in relation to an orthotic component fixed to the upper arm, and compared the results with those obtained by palpation. A plane flexion or extension motion of the forearm component in relation to the component on the upper arm can be described as a pure rotation about a fixed centre. However, activation of the biceps or triceps shifts that centre by around 2 cm, due to a displacement of the humerus within the orthotic component on the upper arm. Within a range of approximately 1 cm, the location of the axis of rotation was similar to that obtained by palpation. Neither custom-made plastic/foam orthoses with their hinges aligned to the measured axis, nor orthoses with their hinges aligned to the palpated axis, exhibited any difference in the wearer's comfort. It is concluded that the best choice for the location of the axis of a hinge-type orthosis for the elbow constitutes a compromise between the axes for active flexion and active extension. In view of the large influence that muscle activation has on axis location, errors in the order of 1 cm seem to be negligible when adjusting the hinge of an orthosis in individual cases. PMID- 17365884 TI - Trans-femoral amputation in elderly dysvascular patients: reliable results with a technique of myodesis. AB - The clinical and functional results of traditional techniques for trans-femoral amputation are often poor. The ISPO consensus conference on amputation surgery in 1990 at Glasgow recommended myodesis as an important integral part of surgical procedure and should be carried out as much as possible. Muscle stabilization provides a stable functional amputation stump. This improves the prosthetic management and walking ability. A technique of myodesis for trans-femoral amputation has been developed in Dundee, especially for elderly dysvascular patients. The functional and clinical results of this technique were studied in 33 patients, who underwent the surgical procedure. Data regarding patient demographics, postoperative morbidity, mortality and functional status were obtained from a prospectively recorded pro forma. Fourteen patients out of 33, who were operated using this technique, were fitted with artificial limbs. Of these, 11 (78.5%) were still using the prosthesis at a mean follow-up of 40 months. There was 100% primary wound healing. Two patients underwent further revision surgery for delayed stump problems. Good clinical and functional results were obtained using this technique. It is particularly suited for the elderly dysvascular patients, whose stumps are shorter and bone quality poor. The low rate of stump problems and consequent revision surgery enables a more comfortable stump for non-prosthetic users. PMID- 17365885 TI - Comparison between the C-leg microprocessor-controlled prosthetic knee and non microprocessor control prosthetic knees: a preliminary study of energy expenditure, obstacle course performance, and quality of life survey. AB - This study investigated energy expenditure and obstacle course negotiation between the C-leg and various non-microprocessor control (NMC) prosthetic knees and compared a quality of life survey (SF-36v2) of use of the C-leg to national norms. Thirteen subjects with unilateral limb loss (12 with trans-femoral and one with a knee disarticulation amputation) participated in the study. The mean age was 46 years, range 30-75. Energy expenditure using both the NMC and C-leg prostheses was measured at self-selected typical and fast walking paces on a motorized treadmill. Subjects were also asked to walk through a standardized walking obstacle course carrying a 4.5 kg (10 lb) basket and with hands free. Finally, the SF-36v2 was completed for subjects while using the C-leg. Statistically significant differences were found in oxygen consumption between prostheses at both typical and fast paces with the C-leg showing decreased values. Use of the C-leg resulted in a statistically significant decrease in the number of steps and time to complete the obstacle course. Scores on a quality of life index for subjects using the C-leg were above the mean for norms for limitation in the use of an arm or leg, equal to the mean for the general United States population for the physical component score and were above this mean for the mental component score. Based on oxygen consumption and obstacle course findings, the C-leg when compared to the NMC prostheses may provide increased functional mobility and ease of performance in the home and community environment. Questionnaire results suggest a minimal quality of life impairment when using a C-leg for this cohort of individuals with amputation. PMID- 17365886 TI - Clinical applications of sensors for human posture and movement analysis: a review. AB - Measurement of human posture and movement is an important area of research in the bioengineering and rehabilitation fields. Various attempts have been initiated for different clinical application goals, such as diagnosis of pathological posture and movements, assessment of pre- and post-treatment efficacy and comparison of different treatment protocols. Image-based methods for measurements of human posture and movements have been developed, such as the photogrammetry, optoelectric technique and video analysis. However, it is found that these methods are complicated to set up, time-consuming to operate and could only be applied in laboratory environments. Electronic sensors and systems with advanced technology, namely accelerometer, gyroscope, flexible angular sensor, electromagnetic tracking system and sensing fabrics, have been developed and applied to solve the relevant application problems of the image-based methods. Nonetheless, other problems for using these electronic sensors emerged, including the environment influence and signal extraction difficulties. Further development of these electronic sensors and measurement methods could enhance their clinical applications in institutional as well as community levels. This article reviews the possible applications of these electronic sensors and systems, and precautions of their applications in analysis of human posture and movement. Such information would help researchers and clinicians in selecting and developing the most appropriate measurement techniques of using the electronic sensors for clinical applications of human posture and movement analysis. PMID- 17365887 TI - A model to predict the effect of ankle joint misalignment on calf band movement in ankle-foot orthoses. AB - Accurate alignment of anatomical and mechanical joint axes is one of the major biomechanical principles pertaining to articulated orthoses, yet knowledge of the potential effects of axis misalignment is limited. The purpose of this project was to model the effects of systematic linear (proximal-distal and anterior posterior) misalignments of single axis mechanical ankle joints in an ankle-foot orthosis (AFO) in order to determine the degree and direction of calf band travel that would occur over a functional range of motion. Sagittal plane misalignments of the ankle joint centres of an AFO were simulated using a simple two dimensional model for both a range of ankle angles and a typical able-bodied ankle kinematic curve for self-selected normal walking speed. The model assumed that no movement occurred between the foot and the foot-plate of the AFO. The model predicted that for anterior (positive horizontal) misalignments, dorsiflexion movements would cause the calf band to travel proximally (i.e., up the leg) and plantar flexion movements would cause the calf band to travel distally (i.e., down the leg). The opposite was predicted for posterior (negative horizontal) misalignments. Proximal (positive vertical) misalignments would cause only distal movements of the calf band while distal (negative vertical) misalignments would cause only proximal movements of the calf band. Anterior posterior misalignments were found to have a much larger effect on the amount of calf band travel than proximal-distal misalignments. PMID- 17365888 TI - Advanced trans-tibial socket fabrication using selective laser sintering. AB - There have been a variety of efforts demonstrating the use of solid freeform fabrication (SFF) for prosthetic socket fabrication though there has been little effort in leveraging the strengths of the technology. SFF encompasses a class of technologies that can create three dimensional objects directly from a geometric database without specific tooling or human intervention. A real strength of SFF is that cost of fabrication is related to the volume of the part, not the part's complexity. For prosthetic socket fabrication this means that a sophisticated socket can be fabricated at essentially the same cost as a simple socket. Adding new features to a socket design becomes a function of software. The work at The University of Texas Health Science Center at San Antonio (UTHSCSA) and University of Texas at Austin (UTA) has concentrated on developing advanced sockets that incorporate structural features to increase comfort as well as built in fixtures to accommodate industry standard hardware. Selective laser sintering (SLS) was chosen as the SFF technology to use for socket fabrication as it was capable of fabricating sockets using materials appropriate for prosthetics. This paper details the development of SLS prosthetic socket fabrication techniques at UTHSCSA/UTA over a six-year period. PMID- 17365889 TI - Andre-R. Bahler (10 march 1925--13 september 2006). PMID- 17365890 TI - Gerhard Fitzlaff 20 april 1936--6 october 2006. PMID- 17365891 TI - Clinical field testing of vulcanized Jaipur rubber feet for trans-tibial amputees in low-income countries. AB - The purpose of this study was to check out the performance and durability of vulcanized Jaipur rubber feet in tropical areas of the developing world. Forty one MUKTI and 40 NISHA feet were followed for 16 (8-17) months. The user compliance was high and nearly all were satisfied. Failure of the prosthetic foot with the need for exchange at the end of the study amounted to 27% (22/81), which is equivalent to a mixed series of rubber feet previously reported (Jansen et al. 2006b). Failures were mostly related to skin fracture and gliding between sponge rubber layers of the heel block. PMID- 17365892 TI - Associated factors of post-stroke depression among Hong Kong Chinese: a longitudinal study. AB - The aim of this study was to explore associated factors of post-stroke depression (PSD) among Chinese first-time stroke patients. A 6-month prospective design was adopted with data collected by face-to-face interviews and physical assessment at two observation time points: T1, within 48 h of admission to the rehabilitation hospitals and T2, 6 months after the first interview in the subject's current place of residence. The prevalence of PSD at T1 and T2 was found to be 69% and 48% respectively. Backward linear regression showed that five variables explained 55% of the variance of PSD at T2. Participants who had a higher level of depression at T2 tended to have a higher level of functional disability, less social companionship and poorer informational support. Those who had been homemaker at pre-morbid state and those who exhibited a higher level of depressive symptoms at T1 showed a higher level of depression at T2. The results of this study suggest that PSD could be a psychological condition arising from the disabling consequences and altered family roles caused by a stroke. PMID- 17365893 TI - Factor structure of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4). AB - The Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4) appears to offer excellent potential as an easily administered and patient acceptable assessment and monitoring measure of quality of life (QoL). However, a principle psychometric criterion crucial to the use and validity of the instrument concerns the underlying factor structure. The SQLS-R4 comprises two sub-scales, these being cognition and vitality QoL and psychosocial feelings QoL. However, the factor structure of the SQLS-R4 has yet to be established in a patient group in the UK. Confirmatory factor analysis was conducted on the SQLS-R4 to determine its psychometric properties in 100 patients with a primary ICD-10 diagnosis of schizophrenia. Internal reliability of the SQLS-R4 cognition and vitality QoL and psychosocial feelings QoL sub-scales was found to be excellent. Consistent with the original validation of the SQLS-R4, two correlated factors comprising cognition and vitality QoL and psychosocial feelings QoL were observed to offer the best fit to the data. In conclusion, the SQLS-R4 would appear to be suitable for use in patients with a primary diagnosis of schizophrenia in the UK. Potential clinical uses and the direction of future research with the SQLS-R4 are indicated. PMID- 17365894 TI - Objective risk, subjective risk, and colorectal cancer screening among a clinic sample. AB - Among cancers, colorectal (CRC) is the third most incident and the second most lethal. Although screening for the disease has been shown to be effective in reducing morbidity and mortality, screening rates remain low. Risk of disease has been shown to increase screening uptake, but different types of risk may influence intent to screen, screening in a timely manner, or participating in screening at all. A cross-sectional design was used to select a diverse sample of CRC asymptomatic patients 50 or more years of age (N=104) visiting one of three Midwestern medical clinics. Results showed a positive relationship between receipt of CRC screening and planning to screen for CRC in the future. Objective risk factors (personal/family history and having a primary care physician) were associated with CRC screening uptake and screening within the time intervals recommended by professional screening guidelines, but subjective risk did not obtain significance for screening participation. Both objective (primary care physician) and subjective risk (long-term comparative risk, knowledge) were associated with future plans to screen. Findings suggest that CRC screening behaviors may be differentially influenced by type of risk. PMID- 17365895 TI - Motivational antecedent beliefs of endurance, strength, and flexibility activities. AB - Research into the correlates of physical activity has focused almost exclusively on physical activity as an omnibus construct. Health Canada and the American College of Sports Medicine, however, advocate physical activity in terms of performing regular endurance, strength, and flexibility activities. The purpose of this study was to investigate the absolute and relative contributions of behavioral, normative, and control beliefs associated with endurance, strength, and flexibility activities within a theory of planned behavior (TPB) structure. Participants were 185 undergraduates who completed measures of the TPB and a 2 week follow-up of endurance, strength, and flexibility behavior. Results using structural equation modeling and Hotelling's t-tests for dependent correlations identified different motivational antecedents for each type of physical activity (p < .05). Endurance behavior was influenced exclusively by behavioral beliefs, flexibility behavior was influenced by normative and control beliefs, and strength behavior was influenced by key behavioral, normative, and control beliefs. The different motivational profiles for each physical activity allude to the importance of tailoring interventions by physical activity type. PMID- 17365896 TI - Nursing specialty and burnout. AB - We examined the relationship between perceived control and burnout among three nursing specialties: nurse practitioners, nurse managers, and emergency nurses. Survey data were collected from 228 nurses from 30 states. Findings indicated that emergency nurses had the least control and the highest burnout, whereas nurse practitioners had the most control and the least burnout. Mediational analyses showed that expected control, hostility, and stressor frequency explained differences between specialties in burnout. The implications of these findings for interventions that reduce burnout and promote nursing retention are discussed. PMID- 17365897 TI - Psychological adaptation to ICDs and the influence of anxiety sensitivity. AB - Forty-nine patients scheduled for implantable cardioverter defibrillator (ICD) implantation completed self-report psychological questionnaires prior to surgery and at 2, 4 and 6 months after surgery. The most common psychological problem identified was anxiety, with clinically significant cases based on the Depression Anxiety and Stress Scale (DASS) ranging between 26% and 34%. Clinically significant depression ranged between 8% and 20%. Anxiety sensitivity was associated with high levels of anxiety, depression and stress at baseline, but not at follow-up assessments. It is possible that within this population anxiety sensitivity is associated with distress during high-threat situations, but the relationship diminishes once the threat has passed. In addition, the reassurance provided by the ICD may reduce negative perceptions of symptoms, promoting psychological adaptation. PMID- 17365898 TI - Depression, constructive thinking and patient satisfaction in cardiac treatment adherence. AB - Many patients fail to adhere to prescribed treatment regimens, particularly patients who are depressed. This study examined the link between depression and adherence among 92 patients undergoing post-operative cardiac rehabilitation. Self-reported adherence was measured in terms of both general recommendations and specific health behaviours. Greater depression was associated with general - but not specific - adherence, and this relationship was mediated by lower satisfaction with their doctor - patient interactions. The link between depression and patient satisfaction was itself mediated by less constructive thinking among patients. These results suggest that adherence among cardiac rehabilitation patients may be enhanced by addressing patients' cognitive coping, and by improving the quality of their doctor - patient interactions. PMID- 17365899 TI - The nature of benefit finding in multiple sclerosis (MS). AB - This study examined the nature of benefit finding in MS and the adequacy of the Benefit Finding Scale (BFS; Mohr et al., 1999) as a comprehensive measure of perceived benefits in MS. A total of 502 people with MS completed questionnaires at Time 1 and 3 months later, Time 2 (n=404). Data on demographics and illness were collected at Time 1 and qualitative data on benefit finding was obtained at Time 2. Content analyses revealed seven benefit finding themes (personal growth, strengthening of relationships, appreciation of life, new opportunities, health gains, change in life priorities/goals and spiritual growth). Two of the themes were represented by several items on the BFS (personal, relationship growth), three were not reflected by items on the BFS (health, new opportunities, life priorities) and two were represented by one item each (spiritual, life appreciation). PMID- 17365900 TI - Chronic pain and head injury following motor vehicle collisions: a double whammy or different sides of a coin. AB - Chronic pain and head injury are common and burdensome sequelae of motor vehicle collisions. The aim of this study was to compare differences in physical injury and functional impairment, psychological distress and pain coping in head injured and non-head injured chronic pain persons subsequent to motor vehicle collisions. Two groups of 54 participants matched in terms of age, gender, and years of formal education underwent a psychological-legal assessment. As part of the assessment, participants completed the Multidimensional Pain Inventory, Sickness Impact Profile, Minnesota Multiphasic Personality Inventory-2, and Coping Strategies Questionnaires. Select scales from questionnaires were combined and underwent multivariate analyses of covariance to test the effects of pain sites at the time of psychological-legal assessment (low, high) and head injury status (head injured and non-head injured chronic pain). Overall, some differences between the two groups were noted but the results did not strongly support the hypothesis that head injured chronic pain participants have a greater physical or psychological burden than non-head injured chronic pain participants. The results suggest the import of assessing and managing pain sites and pain severity in persons injured in motor vehicle collisions. PMID- 17365901 TI - Can the theory of planned behaviour predict maintenance of a frequently repeated behaviour? AB - The present study used the theory of planned behaviour to predict self-monitoring of blood glucose in patients with type 1 diabetes. Sixty-four adult patients with type 1 diabetes completed a questionnaire assessing the variables of the TPB in addition to demographic variables and a measure of conscientiousness. Self-report measures of daily self-monitoring behaviour were obtained for a two-week period. The extended model predicted 46% of the variance in behavioural intention and 57% of variance in self-monitoring behaviour, suggesting that the TPB is able to predict useful levels of variance, comparable to initiation, even in familiar and frequently repeated maintenance behaviours. Implications of these results are discussed. PMID- 17365902 TI - Validation study of a Portuguese version of the Hospital Anxiety and Depression Scale. AB - The study aims to develop and assess metric proprieties of the Portuguese version of the Hospital Anxiety and Depression Scale. A sequential sample includes 1322 participants diagnosed with cancer, stroke, epilepsy, coronary heart disease, diabetes, myotonic dystrophy, obstructive sleep apnoea, depression and a non disease group, which completed the HADS. The first step includes translation, retroversion, inspection for lexical equivalence and content validity, and cognitive debriefing. Then we reproduce oblique exploratory factor analysis and use confirmatory factor analysis. We explore the sensibility of the questionnaire. The validation process of the Portuguese HADS version shows metric properties similar to those in international studies, suggesting that it measures the same constructs, in the same way, as the original HADS form. PMID- 17365903 TI - The link between judgments of comparative risk and own risk: further evidence. AB - Individuals typically believe that they are less likely than the average person to experience negative events, a phenomenon termed "unrealistic optimism". The direct method of assessing unrealistic optimism employs a question of the form, "Compared with the average person, what is the chance that X will occur to you?". However, it has been proposed that responses to such a question (direct estimates) are based essentially just on estimates that X will occur to the self (self-estimates). If this is so, any factors that affect one of these estimates should also affect the other. This prediction was tested in two experiments. In each, direct- and self-estimates for an unfamiliar health threat - homocysteine related heart problems - were recorded. It was found that both types of estimate were affected in the same way by varying the stated probability of having unsafe levels of homocysteine (Study 1, N=149) and varying the stated probability that unsafe levels of homocysteine will lead to heart problems (Study 2, N=111). The results are consistent with the proposal that direct-estimates are constructed just from self-estimates. PMID- 17365904 TI - Role of dietary phosphorus and degree of uremia in the development of renal bone disease in rats. AB - The remnant kidney rat model has been extensively used for the evaluation of bone changes due to uremia. The present study aimed to assess the effect of the dietary phosphorus availability and of the severity of renal failure on bone histomorphometric changes and various biochemical markers over time in this model. Chronic renal failure (CRF) was induced in male Wistar rats by 5/6th nephrectomy. Half of the number of animals received a standard rat diet (STD) (0.67% P, containing low bioavailable phosphorus of plant origin); the other animals were fed a high phosphorus diet (HPD) (0.93% P, containing inorganic phosphorus with high bioavailability). Every two weeks, blood and urine samples were collected. At sacrifice after 6 or 12 weeks, bone samples were taken for the measurement of histological and histodynamic parameters. Serum creatinine measurements indicated the development of mild to moderate renal failure in both diet groups. Phosphaturia was unexpectedly low in all animals that received the STD, indicating relative phosphorus depletion despite the normal dietary phosphorus content. In the HPD CRF group, a decrease in calcemia and a rise in phosphatemia were seen after 12 weeks of CRF, which were more pronounced in animals with higher serum creatinine. Serum iPTH levels were distinctly increased in CRF rats fed a HPD, especially those with more pronounced renal failure. Serum osteocalcin and to a lesser extend tartrate-resistant acid phosphatase and urinary pyridinoline and deoxypyridinoline crosslinks were higher in the CRF animals compared to the shams, particularly in the animals of the HPD group with more pronounced CRF. In both diet groups, the CRF animals had significantly higher amounts of osteoid compared to shams. Only the animals that received a HPD developed distinct histological signs of secondary hyperparathyroidism (sHPTH), that is, an increased bone formation rate, mineral apposition rate, osteoblast perimeter, and eroded perimeter. Again, this effect was most prominent in rats with more severe CRF. In conclusion, data of the present study indicate that in experimental studies using the remnant kidney rat model, both the dietary phosphorus bioavailability and the degree of renal failure in the development of hyperparathyroidism should be considered. PMID- 17365905 TI - Mechanisms of PKC-dependent Na+ K+ ATPase phosphorylation in the rat kidney with chronic renal failure. AB - The present work was designed to study Na+ K+ ATPase alpha1-subunit phosphorylation in rats with chronic renal failure (CRF) in comparison with normal rats. Na+ K+ ATPase alpha1-subunit phosphorylation degree was measured by binding the McK-1 antibody to dephosphorylated Ser-23 in microdissected medullary thick ascending limb of Henle (mTAL) segments. In addition, the total Na+ K+ ATPase alpha1-subunit expression and activity were also measured in the outer renal medulla homogenates and membranes. CRF rats showed a higher Na+ K+ ATPase activity, as compared with control rats (18.95 +/- 2.4 vs. 11.21 +/- 1.5 micromol Pi/mg prot/h, p < 0.05), accompanied by a higher total Na+ K+ ATPase expression (0.54 +/- 0.04 vs. 0.27 +/- 0.02 normalized arbitrary units (NU), p < 0.05). When McK-1 antibody was used, a higher immunosignal in mTAL of CRF rats was observed, as compared with controls (6.3 +/- 0.35 vs. 4.1 +/- 0.33 NU, p < 0.05). The ratio Na+ K+ ATPase alpha1-subunit phosphorylation/total Na+ K+ ATPase alpha1-subunit expression per microg protein showed a non-significant difference between CRF and control rats in microdissected mTAL segments (2.11 +/- 0.12 vs. 2.26 +/- 0.18 NU, p = NS). The PKC inhibitor RO-318220 10(-6) M increased immunosignal (lower phosphorylation degree) in mTAL of CRF rats to 128.43 +/- 7.08% (p < 0.05) but did not alter McK1 binding in control rats. Both phorbol 12-myristate 13-acetate (PMA) 10(-6) M and dopamine 10(-6) M decreased immunosignal in CRF rats, corresponding to a higher Na+ K+ ATPase alpha1-subunit phosphorylation degree at Ser-23 (55.26 +/- 11.17% and 53.27 +/- 7.12% compared with basal, p < 0.05). In mTAL of CRF rats, the calcineurin inhibitor FK-506 10(-6) M did not modify phosphorylation degree at Ser-23 of Na+ K+ ATPase alpha1-subunit (100.21 +/- 3.00% compared with basal CRF). In control rats, FK 506 10(-6) M decreased the immunosignal, which corresponds to a higher Na+ K+ ATPase alpha1-subunit phosphorylation degree at Ser-23. The data suggest that the regulation of basal Na+ K+ ATPase alpha1-subunit phosphorylation degree at Ser-23 in mTAL segments of CRF rats was primarily dependent on PKC activation rather than calcineurin dependent mechanisms. PMID- 17365906 TI - Amikacin-induced nephropathy: is there any protective way? AB - Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2 g/kg intraperitoneally), N acetylcysteine (150 mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150 mg/kg intraperitoneally). Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment. The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects. PMID- 17365907 TI - In situ expression of mononuclear cell markers and interleukin-2 receptor in renal allograft biopsies of acute rejection and borderline cases. AB - The correct diagnosis of renal allograft rejection may be difficult using only clinical and/or histopathological criteria. Immunological assays should be considered in order to evaluate the phenotype of inflammatory infiltrate in renal allograft biopsies. Immunohistochemical studies were performed to detect mononuclear cells, CD4 and CD8 T lymphocytes, B lymphocytes, macrophages, null cells, and positive cells for interleukin-2 receptors. A total of 41 allograft biopsies classified into three groups were studied: acute cellular rejection (28 biopsies/22 patients), borderline (7 biopsies/5 patients) and control (6 biopsies/6 patients). In the rejection group (RG), increased cellularity was found mainly at the tubulo-interstitial level. Expression of CD8 positive cells was higher in RG when compared to borderline (BG) and control (CG) groups, respectively (0.9 vs. 0.0 vs. 0.35 cells/mm2; p < 0.001). Expression of macrophages was not statistically significant among the three groups (RG = 0.6 vs. BG = 0.2 vs. CG = 0.0 cells/mm2; p < 0.02). In the BG, CD4 + cells predominated (BG = 0.2 vs. RG = 0.05 vs. CG = 0.0 cells/mm2; p < 0.05). Clinically these patients were treated as cases of acute rejection. The numbers and different types of infiltrating cells did not correlate with patient's clinical outcome. PMID- 17365908 TI - Evaluation of the heart and great vessel calcification by conventional computed tomography in hemodialysis patients. AB - Heart diseases are responsible for death in hemodialysis patients. The aim of this study was to determine whether we can assess the degree of calcification of the heart and great vessels in hemodialysis patients by non-gated conventional computed tomography (CT) without contrast media. Thirty patients were included in the present study. The hemodialysis group comprised 15 patients and the age matched control group comprised 15 patients without hemodialysis or cardiac diseases who underwent CT scanning. Axial cross-sectional images were taken from the aortic arch to the diaphragm to detect calcification of the aorta and coronary arteries. Eleven patients in the hemodialysis group showed calcification in 1.9 +/- 1.4 coronary vessels, a frequency significantly greater than that of the 0.3 +/- 0.2 coronary vessels in the control group (p < 0.01). Fourteen patients in the hemodialysis group showed calcification of the aorta with a mean score 9.7 +/- 7.2, significantly greater than mean score in the control group (3.5 +/- 2.2; p < 0.01). These results suggest that we can assess an increase in the incidence of calcification of the coronary arteries and the aorta by conventional CT scanning without contrast media in patients undergoing hemodialysis. PMID- 17365909 TI - Predictive factors of clinical outcome in patients with diffuse proliferative lupus nephritis treated early by intravenous methylprednisolone pulse therapy. AB - BACKGROUND: Diffuse proliferative lupus nephritis (DPLN) is associated with significant morbidity and mortality unless aggressive immunosuppressive therapy is initiated early in the course of the disease. It has been observed that with steroid pulse therapy, some patients with DPLN enter clinical remission while others do not. The factors predictive of clinical remission with steroid pulse therapy in these patients has not yet been elucidated. METHODS: The authors retrospectively reviewed the records of 52 consecutive patients of DPLN treated by steroid pulse therapy in order to compare the characteristics of patients in the clinical remission group and those in the non-remission group. Clinical remission was defined as a serum creatinine level of < or = 1.2 mg/dL, negative or trace proteinuria, and the observation of < or = 1-4 red blood cells/high power field in a routine urine examination. The 52 patients were divided into the clinical remission group (n = 29) and the non-remission group (n = 23), and also into subcategories of DPLN, namely, the IV-G group (n = 28) and the IV-S (n = 24). The characteristics of the patients were then compared between the two respective groups to identify factors that might be significantly related to clinical remission using Mann-Whitney's U test and the Cox proportional hazards model. RESULTS: In regard to the clinical and immunological characteristics of the patients, except for a significant difference in the serum albumin level, there were no significant differences in any of the parameters examined, including blood pressure, degree of proteinuria, and serum creatinine, between the remission group and non-remission group. Added to that, in the non-remission group, the pretreatment period was significantly longer than in the remission group. In relation to the histological characteristics, the Chronicity Index (CI) and severity of interstitial fibrosis were significantly higher (p = 0.021) in the non-remission group than in the remission group. The result of the Cox proportional hazards analysis revealed that the serum albumin, pretreatment period, CI, and severity of interstitial fibrosis were strongly related to the clinical outcome, whereas the results of the multivariate Cox proportional hazards analysis revealed only a weak correlation between the CI and the outcome. CONCLUSION: It was concluded that the diagnosis should be performed early and the pretreatment period should be shortened before treatment. Also, an aggressive therapeutic intervention should be initiated early, before chronic renal injury becomes established, to increase the likelihood of remission in patients with DPLN. PMID- 17365910 TI - Improvement of endothelial dysfunction with simvastatin in patients with autosomal dominant polycystic kidney disease. AB - Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. Statins have a beneficial effect in the reversal of ED. The aim of this study was to investigate the effects of a statin, simvastatin, on ED in patients with ADPKD. Sixteen patients with ADPKD having well-preserved renal function were included in the study. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. After the baseline evaluations of EDDs, patients were started treatment with simvastatin at a dose of 40 mg/day and were treated for six months. EDDs were recalculated after one and six months of therapy. Interleukin-6 (IL-6) and high-sensitivity C reactive protein were also measured as markers of inflammation. Baseline EDD was 11.3 +/- 6.9% in patients with ADPKD. After one month of simvastatin treatment, EDD increased significantly to 14.6 +/- 4.6 % (P = 0.016 versus baseline). Endothelial-dependent dilatation further increased significantly to 18.9 +/- 7.5 % (P = 0.011 versus baseline, P = 0.048 versus first month) after six months of therapy. There was also a significant decrease in the level of IL-6 from 21.6 +/- 21.7 pg/mL to 9.1 +/- 3.5 pg/mL (P= 0.002). Six months of simvastatin therapy resulted in a significant improvement of ED in patients with ADPKD. This finding may be in part related to the pleiotropic effects of simvastatin. PMID- 17365911 TI - Ultrastructural examination of glomerular and tubular changes in renal allografts with acute rejection. AB - Acute rejection is the most important threat to transplanted kidneys in the early phase after transplantation. With the advances in renal transplant surgery and immunosuppressive therapies, one-year graft survival rates reached 90%, but long term graft survival did not improve to a similar degree. To prevent acute rejection more effectively and decrease the risk of chronic nephropathy development, the pathogenesis and effects of acute rejection on renal grafts should be further explored. This study aimed to examine the glomerular and tubular changes ultrastructurally. Tissues were obtained from 11 renal allografts with acute rejection, fixed in 1% Osmium tetra oxide embedded in Epon. The changes in glomerular basement membrane, podocyte, mesangium, and proximal tubules were examined by electron microscope. Tubular changes such as tubular basement membrane multi-lamellation, MN and PMN cells in peritubular capillaries, tubular vacuolization, mitochondrial changes (increase in number, alterations in cristae organization, or cristae effacement), and infiltration of tubular epithelium by MN cells (mainly lymphocytes) were found statistically significant (p < 0.01) when compared to those of control group. Some forms of endothelial injury (swelling of endothelial cells or fenestrae loss) were also statistically significant (p < 0.01). Acute rejection is an important predictor of long-term graft survival, and there may be no clinical clue to make diagnosis easier. Therefore ultrastructural changes may help solve this problem together with molecular studies. PMID- 17365912 TI - Determinants of coronary artery disease in nondiabetic hemodialysis patients: a matched case-control study. AB - BACKGROUND/AIMS: The aim of this matched case-control study was to evaluate the determinants of coronary artery disease (CAD) other than conventional risk factors in nondiabetic hemodialysis (HD) patients. METHODS: Among 312 consecutive patients on regular HD, 26 nondiabetic patients with angiographically defined coronary artery disease (20 men, 6 women; mean age 57.0 +/- 13 years) constituted the case group (group 1). A subject group of the same gender, smoking status, and hypertension with similar ages and body mass indexes who had normal electrocardiography and myocardial perfusion scintigraphy served as controls (20 men, 6 women; mean age 54.1+/-12 years, group 2). Demographics, high sensitivity C-reactive protein (hs-CRP), erythrocytes dimentation rate (ESR), hematocrit corrected ESR, beta-2 microglobulin, cardiac troponin I, parathyroid hormone, albumin, calcium (Ca), phosphorus (P), Ca x P, and lipid profiles were compared between the groups. RESULTS: Patients in group 1 had higher hs-CRP and troponin I (18.0+/-12 vs. 7.2+/-5 mg/L, p < 0.001; 0.36+/-0.16 vs. 0.22+/-0.05 ng/mL, p < 0.001, respectively) and lower HDL cholesterol levels than group 2 (37.0+/-10 mg/dL vs. 46.3+/-17 mg/dL, p = 0.02). Backwards stepwise logistic regression analysis revealed that high hs-CRP and troponin I levels (p = 0.03 and p = 0.01) and low HDL cholesterol levels (p = 0.02) were independently related with CAD. CONCLUSION: According to these results, in nondiabetic patients on regular hemodialysis, high hs-CRP, troponin I levels and low HDL-cholesterol were the determinants of CAD. PMID- 17365913 TI - Urinary glycosaminoglycan levels as a marker of renal amyloidosis in patients with familial Mediterranean fever. AB - INTRODUCTION AND AIM: Familial Mediterranean Fever (FMF) is an autosomal recessive disease with a defect in the pyrine gene and is manifested with short attacks of inflammatory serositis, fever, and erysipelas-like skin lesions. Secondary amyloidosis is the most serious complication of the disease, in which extracellular deposits of amyloid (an amorphous and eosinophilic protein) are seen in tissues. Glycosaminoglycans are mucopolysaccharide molecules that take place in amyloid deposits with fibrillar links to amyloid. They form glycoproteins by linking to proteins, and their free forms are excreted in the urine in the form of polysaccharides. The aims of this study were to evaluate if the urinary levels of glycosaminoglycans have a predictive value in the diagnosis of amyloidosis secondary to FMF and if these levels are affected by treatment with colchicine. MATERIALS AND METHODS: The study included 55 volunteer patients (age range: 18-36 years) with FMF (15 with amyloidosis) of the same socio economic circumstances without other concomitant inflammatory, malignant, or chronic diseases, along with 20 healthy subjects as control. Urinary glycosaminoglycan levels were determined twice, once when the patients were on medication and once after they have stopped treatment for two weeks. RESULTS: Initial mean urinary GAG levels were significantly lower in amyloidosis patients. Mean urinary GAG levels determined two weeks after the cessation of colchicine was also significantly lower than controls in both amyloidosis and non amyloidosis FMF patients. Likewise, in patients with a disease duration longer than ten years, urinary GAG levels were also lower than those with a disease duration of less than three years. CONCLUSION: Urinary GAG level can have a predictive value for amyloidosis in patients with FMF, and it can also be used as a non-invasive marker for screening the effects of colchicine on fibrillogenesis as well as for the follow-up of the patients. PMID- 17365914 TI - Nitric oxide synthase gene polymorphisms in children with primary nocturnal enuresis: a preliminary study. AB - AIMS: Recent studies demonstrated some differences in urinary electrolytes of enuretic children. Intrarenal nitric oxide (NO) serves as a major regulator of renal sodium and water excretion like an endogenous diuretic. This study aimed to investigate endothelial (eNOS), and neuronal (nNOS) NO synthase gene polymorphisms in children with primary nocturnal enuresis (PNE). MATERIALS AND METHODS: The eNOS gene polymorphism was investigated in 171 Turkish children (57 PNE cases and 114 healthy, non-enuretic controls), and nNOS gene polymorphism was determined in 158 Turkish children (83 PNE cases and 75 healthy, non-enuretic controls). The glu298asp (G/T) polymorphism of the eNOS and C276T (C/T) polymorphism of nNOS genes were genotyped using PCR. RESULTS: The distribution of GG, TG, and TT genotypes for eNOS gene was 48%, 33%, and 19% in PNE, compared with 61%, 26%, and 13% in the controls (p > 0.05). The distribution of CC, TC, TT and genotypes for nNOS gene was 31%, 29%, and 40% in PNE compared with 10%, 43%, and 47% in the controls. CC genotype was found higher in enuretic children (p = 0.002). The eNOS and nNOS gene polymorphisms were not associated with positive family history, frequency of enuresis, and clinical response to desmopressin. CONCLUSIONS: This study is the first to search the NOS gene polymorphisms in children with PNE. It was determined that eNOS gene polymorphism may not be associated with PNE, while nNOS gene polymorphism, a predominantly CC genotype, may be associated with PNE in Turkish children. Further studies with larger samples together with the detection of enuresis gene may help determine the exact role of nNOS gene polymorphism in enuresis. PMID- 17365915 TI - Effect of anti-HCV positivity on markers of malnutrition and inflammation in hemodialysis patients. AB - AIM: To investigate the influence of anti-HCV positivity on markers of malnutrition and inflammation in hemodialysis (HD) patients. METHODS: Stable HD patients who had persistently negative or positive HCV antibodies (at least three) and without elevated aminotransferase levels in routine periodical tests with a duration of more than 12 months were included. Patients with conditions known to be associated with acute-phase responses or clinically active (HCV RNA positive) or advanced liver failure were excluded. Thirty-six anti-HCV-positive patients (22 male, 14 female, mean age 47.3 +/- 14.5 years, mean time on HD 72.0 +/- 39.0 months), were compared with 36 anti-HCV negative patients with similar age and HD duration (25 male, 11 female, mean age 49.2 +/- 13.8 years, mean time on HD 59.7 +/- 27.1 months). Malnutrition-Inflammation Score (MIS), a fully quantitative score adopted from subjective global assessment, was recorded for each patient (ranges from 0 to 30). High sensitivity serum C-reactive protein (hs CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and hematocrit corrected ESR were compared as indices of the degree of inflammation beyond anthropometric evaluation and routine laboratory tests. RESULTS: There was no significant difference in MIS of two groups (6.1 +/- 3.2 vs. 5.6 +/- 3.2, p > 0.05). In the comparison of components of MIS, co-morbidity including number of years on dialysis was higher in anti-HCV-positive patients (p = 0.04). Anthropometric values and serum levels of hs-CRP, IL-6, ESR, and hematocrit corrected ESR of two groups were not statistically different from each other (p > 0.05 for all). ALT (p = 0.0001) and AST (p = 0.001) levels were higher in anti HCV-positive patients. CONCLUSION: Anti-HCV positivity without active infection seems to have no additional negative effect on malnutrition and inflammation in maintenance HD patients. PMID- 17365916 TI - Non-insertion-related complications of central venous catheterization--temporary vascular access for hemodialysis. AB - The authors analyzed 309 central venous catheters (CVC) inserted in 147 hemodialysis patients before the maturation of the first or new arteriovenous fistula. One clinical manifestations of sepsis after CVC insertion was found. In all, 33.7% of the catheters were removed because of early minor complications: CVC occlusion, inadequate blood flow in CVC, shattered suture and malposition of CVC, fever, signs of infection at the site of CVC insertion, and bleeding at the site of CVC insertion. The most frequently isolated pathogenic bacteria at the tips of the catheters were coagulase-negative staphylococci highly sensitive to vancomycin and gentamicin. PMID- 17365917 TI - Eradication of Helicobacter pylori in hemodialysis patients. AB - BACKGROUND: Helicobacter pylori (H. pylori) are a causative agent of digestive disease. Although a proton pump inhibitor combined with amoxicillin clarithromycin is the accepted drug treatment for H. pylori eradication in Japan, there is no consensus treatment for hemodialysis patients. STUDY: Seventy-seven hemodialysis patients underwent upper digestive tract endoscopy. Biopsy specimens were taken, and histological findings, culture, and rapid urease tests were performed to confirm the presence of H. pylori. H. pylori-positive patients were then administered at random either a seven-day lansoprazole (60 mg a day) amoxicillin (750 mg a day)-clarithromycin (400 mg a day) (LAC) regimen or a seven day lansoprazole (60 mg a day)-clarithromycin (400 mg a day) (LC) regimen. The success of H. pylori eradication was determined from histological findings, culture, and rapid urease tests. RESULTS: In 13 of 77 patients (13.6%), ulcers and/or ulcer scars were seen by endoscopy. Thirty-one patients (40.3%) were positive for H. pylori, and 20 patients among them were randomized to one of two regimens: one is seven-day LAC regimen (eleven patients) and the other is seven day LC regimen (nine patients). Eradication was successful in nine of the eleven patients (72.7%) receiving the LAC regimen, but in only three of the nine patients (33.3%) who underwent the LC regimen. No serious adverse effects were observed with either regimen, and 95% of the patients reported complete compliance. CONCLUSION: A seven-day low dose LAC regimen is safe and effective and recommended for treatment of H. pylori infection in hemodialysis patients. PMID- 17365918 TI - A novel immunosuppressive agent, sirolimus, in the treatment of Kaposi's sarcoma in a renal transplant recipient. AB - Renal transplant recipients are susceptible to Kaposi's sarcoma (KS) because of treatment with immunosuppressive drugs. Sirolimus, a new immunosuppressive agent, has been successfully used for immune-suppression in kidney transplant recipients. Several studies have shown the potential role of sirolimus to inhibit progression of KS in kidney-transplant recipients. This report details a kidney transplant recipient with cutaneous KS who had a complete remission in response to sirolimus therapy. PMID- 17365919 TI - A case of Kaposi's sarcoma following treatment of membranoproliferative glomerulonephritis and a review of the literature. AB - Kaposi's sarcoma (KS) is an unusual tumor principally affecting the skin of the lower extremities. Although the association between KS and renal transplant has been well documented, there are a few KS cases in the literature associated with membranoproliferative glomerulonephritis or other glomerular diseases. This report presents a patient with membranoproliferative glomerulonephritis (MPGN) who developed KS following treatment with long-term medium dose glucocorticoid and short-term additional immunosuppressives. The KS cases associated with glomerulonephritis are also reviewed. KS is a rare complication in glomerular diseases that may (or may not) be related to immunosuppression. Hence, immunosuppression treatment should be carefully planned in glomerulonephritis treatment and avoided if they are not essentially necessary. PMID- 17365920 TI - Acute renal failure and hypercalcaemia: sarcoidosis may be the culprit. PMID- 17365921 TI - Insulin resistance, the renin-angiotensin system, and associated renal injury: is insulin resistance the culprit? PMID- 17365922 TI - Burkitt lymphoma in renal transplant recipient. PMID- 17365923 TI - Renal amyloidosis in a patient with Kartagener syndrome. PMID- 17365925 TI - Reactive oxygen species independent cytotoxicity induced by radiocontrast agents in tubular cells (LLC-PK1 and MDCK). AB - PURPOSE: Radiocontrast agents (RAs) cause renal tubular damage by hemodynamic imbalance, which could cause hypoxic stimulus and direct cytotoxicity. However, reactive oxygen species (ROS) could be an important factor in RAs' direct cytotoxicity. This study investigated the involvement of ROS in deleterious effects produced by RAs on normoxic and hypoxic renal tubular cells. MATERIALS AND METHODS: LLC-PK1 and MDCK were exposed to diatrizoate and ioxaglate in normoxic and hypoxic conditions. Apoptotic and necrotic cell death were assessed by acridine orange/ethidium bromide and annexin V methods. Hydrogen peroxide, superoxide anion, and malondialdehyde levels were analyzed by, respectively, 2',7'-dichlorofluorescein, luminal, and thiobarbituric acid. Antioxidant agents were used to prevent cellular RAs damage. RESULTS: Diatrizoate and ioxaglate decreased cellular viability in both cells, and this effect was enhanced by hypoxic conditions. Diatrizoate induced more injury than ioxaglate to both cell lines. LLC-PK1 underwent necrosis, while MDCK cells underwent apoptosis when exposed to diatrizoate. These results could not be attributed to an increase in osmolality. RAs did not increase hydrogen peroxide, superoxide anion or malondialdehyde levels in both cells. Additionally, N-acetyl-L-cysteine (NAC), ascorbic acid, alpha-tocopherol, glutathione, beta-carotene, allopurinol, cimetidine, and citric acid did not protect cells against RAs damage. Surprising, NAC increased the cellular damage induced by ioxaglate in the both cell lines. CONCLUSION: The present study shows that RAs induce damage in cultured tubular cells, especially in hypoxic conditions. ROS were not involved in the observed RAs' cytotoxicity, and NAC increased ioxaglate-induced tubular damage. PMID- 17365926 TI - Association of cigarette smoking with albuminuria in the United States: the third National Health and Nutrition Examination Survey. AB - BACKGROUND: The association of cigarette smoking with albuminuria has been reported but not examined in a representative U.S. population. No study has evaluated the association between serum cotinine (a biological marker for tobacco exposure) and kidney damage. METHODS: A cross-sectional analysis was conducted among 15,719 adult participants of the third National Health and Nutrition Examination Survey to assess the association between smoking exposure and kidney damage. Smoking was assessed by self-reported lifetime cigarette use and serum cotinine. Kidney damage was assessed by urine albumin-to-creatinine ratio (ACR), with albuminuria defined as ACR of > or =17 microg/mg in males and > or =25 microg/mg in females. RESULTS: The analysis included 13,121 with normal albumin (mean ACR 6.3 microg/mg) and 2,414 with albuminuria (mean ACR 143 microg/mg); hypertension was prevalent in 27% and 59%, respectively. Former smoking was similar between groups (21%), while current smoking was more common in persons with albuminuria (26%) compared to normal ACR (21%). Adjusted for other risk factors, among hypertensives, current smokers were 1.85 (95% CI: 1.29, 2.64) times more likely to have albuminuria than never smokers. Current smokers with a > or =40 pack-year history were at highest risk for albuminuria. Among non smoking hypertensives, those exposed to passive smoke (highest versus lowest quartile of serum cotinine) were 1.41 (95% CI: 1.04, 1.90) times more likely to have albuminuria. Former smoking with cessation of > or =1 year among hypertensives was not associated with albuminuria. Among non-hypertensives, smoking and albuminuria were not consistently associated. CONCLUSION: Current and passive smoking, but not former smoking, were associated with the presence of albuminuria in the general U.S. population with hypertension, indicating a benefit to the kidney from smoking cessation. PMID- 17365927 TI - Effects of low sodium dialysate in chronic hemodialysis patients: an echocardiographic study. AB - BACKGROUND: Chronic kidney disease (CKD) and hemodialysis (HD) patients who cannot restrict sodium consumption in their diets sometimes develop significant saline excess and hypertension between dialyses. This study assessed the effect of relatively low sodium dialysate dialysis on changes of echocardiography in hemodialysis patients. METHODS AND RESULTS: Eighteen patients with end stage renal failure on chronic HD were studied (8 females, 10 males) with a mean age 48.3 +/- 14.6 (24-70) years. The mean time on HD was 30.8 +/- 14.0 (12-60) months. Patients with hematocrit levels under 24% were excluded from the study. In all patients, echocardiography was performed thrice weekly before and after eight-week HD treatment with low sodium dialysate hemodialysis by the same operator (135 mEq/L for patients with sodium levels less than 137, 137 for patients with sodium levels over 137). Left atrium (LA) and left ventricle (LV) volumes and ejection fractions were measured, specifically: LV systolic diameter (LVSD), LV diastolic diameter (LVDD), interventricular septum (IVS), tricuspid regurgitation (TR), mitral regurgitation (MR), pulmonary artery pressure (PAP), and inferior vein cava diameter (IVCD). RESULTS: In terms of echocardiographic parameters, LVSD, TR, PAP, and IVCD were statistically decreased after low-sodium dialysate treatments (p = 0.002, 0.04, 0.013, and 0.00, respectively). Predialysis systolic and diastolic blood pressure (BP), post-dialysis systolic blood pressure, and interdialytic weight gain was statistically decreased when compared to basal levels (p = 0.00, p = 0.011, p = 0.022, p = 0.001, respectively). CONCLUSION: A reduction of the dialysate sodium concentration based on the predialysis sodium levels of the patients could reduce the systolic BP and decrease the volume load on the heart as assessed by echocardiography. Within this short period, postdialysis diastolic BP could not be lowered. The effect of this approach should be studied in broad and lengthy series. PMID- 17365928 TI - Serum leptin, resistin, and lipid levels in patients with end stage renal failure with regard to dialysis modality. AB - Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities. METHODS: This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) alpha levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance. RESULTS: Serum resistin, adiponectin, IL-6, TNF-alpha, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied. CONCLUSION: Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients. PMID- 17365929 TI - Improvement of renal function in type 2 diabetic nephropathy. AB - BACKGROUND: Therapeutic failure in preventing renal disease progression in type 2 diabetic nephropathy (DN) is due to a failure in the early detection of DN by microalbuminuria and the inappropriate correction of renal hemodynamic maladjustment secondary to glomerular endothelial dysfunction. METHODS: Thirty patients associated with normoalbuminuric type 2 DN were subject to the following studies: tubular function by means of fractional excretion of magnesium (FE Mg), vascular function by means of determining the circulating endothelial cell, VEGF, VEGF/TGF B ratio, and intrarenal hemodynamic studies. RESULTS: FE Mg, circulating endothelial cells, and TGF B were abnormally elevated, and VEGF/TGF B ratio was decreased in these normoalbuminuric patients. The intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by a preferential constriction at the efferent arteriole and a reduction in peritubular capillary flow. Following treatment with vasodilators, a decrease in efferent arteriolar resistance and increase in peritubular capillary flow as well as glomerular clearance were observed. CONCLUSION: FE Mg appears to be a more sensitive marker than microalbuminuria for the early detection of DN. Increased endothelial cell injury is reflected by enhanced circulating endothelial cell loss in conjunction with the increased TGF B and the decreased ratio between VEGF and TGF B. This is further supported by the dysfunctioning glomerular endothelium, which is characterized by hemodynamic maladjustment and a reduction in the peritubular capillary flow. A correction of such hemodynamic maladjustment by multidrug vasodilators effectively improves renal perfusion and restores renal function in type 2 DN. PMID- 17365930 TI - Leptospiral acute renal failure: effects of dopamine and furosemide. AB - From unpublished experience of clinicians in the rural tropics, the combination of furosemide and dopamine is beneficial in the management of mild acute renal failure in tropical disease. We studied two groups of patients with leptospirosis and mild acute renal failure whose serum creatinine ranged from 2.4 to 5 mg/dL and fractional excretion of sodium varied from 1.21 to 2.08%. Group 1, consisting of 9 patients with the serum creatinine ranging from 2.4 to 5 mg/dL, served as the control. They received only penicillin G sodium and supportive treatment. Group 2, consisting of 8 patients with the serum creatinine ranging from 2.8 to 5 mg/dL, received, in addition to penicillin, dopamine (renal dose) and furosemide along with fluid and electrolyte replacement. The control group ran the usual clinical course of acute renal failure, and 3 patients required dialysis. There was profuse diuresis, and the recovery of renal function was faster in group 2 patients. Dopamine and furosemide are therefore useful in mild acute renal failure in leptospirosis. It is felt that this combination could be beneficial in the management of mild acute ischemic renal failure due to a clean single insult. PMID- 17365931 TI - Hospital-acquired and community-acquired acute renal failure in hospitalized Chinese: a ten-year review. AB - OBJECTIVES: To investigate the difference between hospital-acquired acute renal failure (HA-ARF) and community-acquired acute renal failure (CA-ARF) in hospitalized Chinese. METHODS: The diagnosis of ARF in Peking University Third Hospital from January 1994 to December 2003 was reconfirmed and subdivided into AC-ARF and HA-ARF. Data of epidemiology, etiology, prognosis, and associated factors were analyzed. Single-variable analysis and multivariate logistic regression analyses were performed to investigate the correlation between clinical features and prognosis respectively. Results among 205 reconfirmed CA ARF had a predominance of 59.5%, but HA-ARF demonstrated an increase by 1.06 during the last five years (p = 0.003). In all, 70.5% CA-ARF was diagnosed in internal medicine with 45.9% in department of nephrology, whereas 59.1% HA-ARF was diagnosed in surgical department with 51.8% in ICU. Distribution difference among departments was significant (p < 0.01). Further, 90.2% CA-ARF was associated with a single factor, while 36.1% of HA-ARF had two or more causes (p < 0.01). Also, 26.5% HA-ARF and 18.9% CA-ARF was drug-associated (p > 0.05) while 24.1% HA-ARF and 12.3% CA-ARF was infection-associated (p < 0.01). HA-ARF vs. CA ARF was 62.7% vs. 23.0% in mortality (p < 0.01), 0.54 +/- 0.24 vs. 0.27 +/- 0.18 in ATI-ISS index (p < 0.01) and 19.6 +/- 4.9 vs. 15.7 +/- 5.6 in APACHE II scores (p < 0.01). MODS and SIRS were common independent predictors with oliguria for HA ARF and advanced age for CA-ARF, respectively. CONCLUSIONS: In hospitalized Chinese during the last ten years, CA-ARF was still predominant with simpler cause and lower mortality, whereas HA-ARF was increasing with more complicated cause and higher mortality. PMID- 17365932 TI - Comparison of higher dose of losartan treatment with losartan plus carvedilol and losartan plus ramipril in patients with glomerulonephritis and proteinuria. AB - BACKGROUND: Proteinuria may cause a worsening of accompanying renal disease or even lead to glomerulosclerosis. There is no data about the effect of carvedilol on patients with proteinuric (>0.5 g/day) glomerulonephritis. This study aimed to compare the effects of carvedilol with ramipril and losartan in patients with proteinuric glomerulonephritis. METHODS: Twenty-one glomerulonephritis patients were followed for 12 months. Patients were divided into three groups. All patients were treated with losartan 50 mg once daily for two weeks. After two weeks (baseline), patients were given additional medications: 50 mg losartan, 5 mg ramipril, and 25 mg carvedilol were given additionally to the patients in groups 1, 2, and 3 respectively. RESULTS: Baseline mean proteinuria values of patients in groups 1, 2 and 3 were 1.6 +/- 1.1 g/day, 2.1 +/- 1.3 g/day, and 1.4 +/- 1.2 g/day, respectively. These values decreased to 0.5 +/- 0.7 g/day, 0.6 +/- 0.7 g/day, and 0.9 +/- 0.9 g/day, respectively, at the end of the 12th month. These results were statistically significant only in group 1 (p = 0.04). The rational variation of proteinuria between the first and 12th month of losartan, ramipril, and carvedilol were -61%, -62%, and -27%, respectively. The decreases in blood pressures between baseline and the first, sixth, and twelfth-month measurements were significant in all groups. CONCLUSIONS: Thee results showed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (AT1ras) provide marked decreases in proteinuria, making their use indisputable in patients with glomerulonephritis. Carvedilol was not found to be as effective as ACEIs and AT1ras in decreasing proteinuria and preserving renal function. PMID- 17365933 TI - Culture-negative peritonitis: a fifteen-year review. AB - Peritonitis is a serious complication in peritoneal dialysis (PD) patients; however, the clinical outcome of culture-negative peritonitis (CNP) is controversial. This retrospective study of CNP attempts to resolve this controversy. In 813 episodes of peritonitis, 202 episodes of CNP in 152 PD patients were reviewed. Two different methods of effluent culture were utilized during the study period. The incidence of CNP was lower with 50 ml centrifugation culture than 10 ml direct inoculation culture (20.7% vs. 35.7%; p < 0.05). The overall cure rate of CNP was greater than 80% of patients receiving cefamezine and gentamicin as initial therapy. Relapse within 30 days after completion of treatment happened in 9.6% of cases, and antibiotic therapy failed in 8.1% of CNP cases. In comparison with cured patients, patients with relapse or treatment failure are older (62.0 +/- 15.0 years vs. 54.3 +/- 15.3 years; p = 0.007) and have a higher rate of abdominal pain (91.4% vs. 69.3%; p = 0.007) and greater need for salvage therapy (54.3 % vs. 11.0%; p < 0.001). A history of antibiotic use or peritonitis within 30 days before onset of CNP was noted in 23.3% and 12.5% of cases, respectively, but was not associated with clinical outcome. The clinical outcome of CNP was benign in this study. Older age, abdominal pain, and need for salvage therapy were associated with an increased risk for relapse and treatment failure in CNP cases. Moreover, 50 ml centrifugation culture method was better than 10 ml direct inoculation culture in reducing the incidence of CNP. PMID- 17365934 TI - Differences between myeloperoxidase-specific and -nonspecific P-ANCA-associated renal disease. AB - BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) are classified into perinuclear (P)-ANCA and cytoplasmic-ANCA by an indirect immunofluorescence (IIF) test with ethanol-fixed neutrophils. Circulating P-ANCA with specificity for myeloperoxidase (MPO) are frequently found in patients with pauci-immune necrotizing glomerulonephritis. P-ANCA without a specificity for MPO are also found in a minority of patients with this form of glomerulonephritis, but their clinicopathological features remain poorly delineated. METHODS: The clinical data, the renal pathology, and the outcome were compared between 48 patients with MPO-specific P-ANCA-associated glomerulonephritis (MPO-specific group) and five patients with MPO-nonspecific P-ANCA-associated glomerulonephritis (MPO nonspecific group). In the MPO-nonspecific group, antibodies against bactericidal/permeability-increasing protein were detected in one patient, but the other known antibodies that can produce a P-ANCA pattern on the IIF test were not detected in the remaining patients. All patients in the two groups were treated with steroids with or without cyclophosphamide. RESULTS: There were no remarkable differences in the degree of hematuria and serum levels of C-reactive protein and creatinine between the two groups. In contrast, proteinuria levels and the rate of glomerular crescent formation were higher in the MPO-nonspecific group than in the MPO-specific group. While the patient survival rate was similar between the two groups, the renal survival rate was lower in the MPO-nonspecific group. CONCLUSIONS: This pilot analysis suggests that there are clinicopathological differences between patients with MPO-specific and nonspecific P-ANCA-associated pauci-immune necrotizing glomerulonephritis. Renal lesions appear to be more active in patients with MPO-nonspecific P-ANCA than in patients with MPO-specific P-ANCA. PMID- 17365935 TI - Quality of life in CAPD, transplant, and chronic renal failure patients with diabetes. AB - Although quality of life (QoL) is an important outcome measure, there are few studies of QoL in diabetic patients. We performed a cross-sectional study to assess QoL in such patients comparable for age, sex, and co-morbidity. PATIENTS: Group CAPD: DM (n = 19, 12 males), diabetic CAPD patients; group CAPD: no DM (n = 26, 15 males) CAPD patients without diabetes; group TXP (n = 20, 10 males), diabetic transplant patients; and group CKD: DM (n = 20, 11 males), diabetics with chronic kidney disease. Two valid QoL instruments were used: a generic one (SF-36) and one that is disease-specific (RQLP). RESULTS: As a whole, CAPD patients scored badly as far as concerned the physical domain, but with a good mental adaptation. Diabetic CAPD patients exhibited worse QoL for physical functioning, energy, vitality, leisure activity, and eating/drinking limitations. Diabetic transplant patients exhibited the best QoL. The RQLP instrument had better discriminative power for domains such as eating/drinking, treatment effects, and psychosocial aspects. Using analysis of co-variance and adjusting for age, sex, and co-morbidity, QoL differences disappeared. In conclusion, diabetic CAPD patients exhibited the worst QoL though with a satisfactory mental adaptation, a renal-specific instrument had better discriminative power, and the prevention of co-morbidity is likely to improve QoL in such patients. PMID- 17365936 TI - Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients. AB - Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise. PMID- 17365937 TI - The influence of the amount of ultrafiltration in chronic hemodialysis on P wave dispersion. AB - OBJECTIVE: Paroxysmal atrial fibrillation (AF) observed in patients undergoing chronic hemodialysis program with higher rates is an important morbidity and mortality cause that negatively influences the hemodynamics and leads to thromboembolic complications. It is known that P wave dispersion (PWD) facilitating the development of paroxysmal atrial fibrillation is increasing during intradialytic process. This study researched the influence of various amounts of ultrafiltration that applied in the various hemodialysis sessions in the same patient cohort on PWD. MATERIALS AND METHODS: 25 patients in a chronic hemodialysis program undergoing four hours bicarbonate hemodialysis three times a week were included in the study. The patient cohort was divided into four groups regarding the amount of ultrafiltration (UF) performed during a four-hour standard hemodialysis session as following: UF up to 1 liter, UF of 1-2 liters, UF of 2-3 liters, and UF of 3-4 liters. Notes were kept until each patient had been included once into each group regarding the amount of ultrafiltration performed parallel to intradialytic weight gain in different hemodialysis session. A 12-lead ECG was taken from the patients immediately before the hemodialysis and within 20 minutes after completion of the session, and maximum P wave duration (Pmax), minimum P wave duration (Pmin) and PWD values (i.e., the difference between Pmax and Pmin) were measured. The inter-group data was assessed with a one-way ANOVA, and the within-group assessments were performed with paired samples test. Mann Whitney U test was used for the evaluations performed according to the presence of diabetes. FINDINGS: The mean age of 25 patients (15 male and 10 female) was 62.7 +/- 20.2 (range: 21-89). PWD after UF was decreased significantly in group 1 (56.12 +/- 15.26 vs. 46.60 +/- 18.45 ms, p = 0.018) and were increased in groups with UF more than 1 liter: group 2 (39.68 +/- 21.26 vs. 47.12 +/- 21.20 ms, p = 0.020), group 3 (41.60 +/- 23.99 vs. 65.92 +/- 31.04 ms, p = 0.001), and group 4 (17.52 +/- 14.67 vs. 26.80 +/- 15.52 ms, p = 0.007). Furthermore, while PWD before UF was significantly higher in a diabetic group compared to a nondiabetic group (68.85 +/- 10.44 vs. 51.16 +/- 14.06 ms, p = 0.007), it was seen that PWD difference had disappeared after UF application (57.14 +/- 17.99 vs. 42.50 +/- 17.40 ms, p = 0.065). CONCLUSION: UF application of more than 1 liter during hemodialysis session increases the PWD value significantly. Hypervolemia exceeding 1 liter between two dialysis sessions should be avoided in all patient groups, especially in diabetics, and an effective UF planning should be arranged because of a decrease in PWD values with UF observed in diabetics. PMID- 17365938 TI - Correlation of dietary intakes and biochemical determinates of nutrition in hemodialysis patients. AB - OBJECTIVE: The purpose of this study was to determine the effect of dietary intakes on nutritional indicators of patients on hemodialysis. METHOD: This study was carried out at the hemodialysis unit at the Ministry of Health, Ankara Hospital, from 2003-2004. Sixty-seven patients on regular hemodialysis were enrolled in the study. Nutritional status was assessed by biochemical parameters (urea, uric acid, creatinine, Na, K, Cl, Ca, P, alkaline phosphatase, SGOT, SGPT, cholesterol, total protein, albumin, hemoglobin, hematocrit) and anthropometric measurements (height, dry weight, body mass index), and dietary intakes were calculated. RESULTS: In this study, the mean age of the patients was 45.3 +/- 13.49, and the duration of hemodialysis was 4.9 +/- 3.64 year. Dialysis time was 12.4 +/- 2.7 h/week. The ratio of individuals with BMI of 20 kg/m2 or below this value was 19.4%. Blood hemoglobin and hematocrit levels were below than the recommended level. Mean serum urea (148.0 +/- 27.76 mg/dL) and creatinine (8.8 +/ 2.13 mg/dL) were found to be high, while a significant negative correlation was found between blood urea level and dietary fat (p < 0.01, r = -0.31). A significant positive correlation was found between vitamin B1, vitamin B6, folate, potassium, iron, and magnesium; between uric acid and vitamin D; between blood creatinine level and dietary vitamin B1, vitamin B6, folate, vitamin C, potassium, iron, magnesium; between blood potassium level and dietary vitamin C only; and between blood cholesterol level and dietary vitamin D only (p < 0.01). PMID- 17365939 TI - Renal function parameters of Thai vegans compared with non-vegans. AB - In Asia, vegetarianism is a well-established eating behavior. It appears that the adoption of a vegan diet leads to a lessening of several health risk factors. Although vegetarianism has some notable effects on the hematological system, the effect on the nephrological system has not been well clarified. The pattern of renal function parameters was studied in 25 Thai vegans compared with 25 non vegetarians. Of the studied parameters, it was found that urine protein was significantly different (p < 0.05) in vegans and controls. Vegans had significantly lower urine protein level. PMID- 17365940 TI - Relationships between brain natriuretic peptide, troponin I and QT dispersion in asymptomatic dialysis patients. AB - OBJECTIVES: The relationships between increased wall stress, myocyte death, and ventricular repolarization instability in patients with heart failure were reported. DESIGN AND METHODS: The relationships between brain natriuretic peptide (BNP), a predictor of increased wall stress of hearth; troponin I (cTnI), a predictor of myocyte death; and QT dispersion (QTd), a reflection of ventricular repolarization instability were evaluated in age- and sex-matched asymptomatic 29 hemodialysis (HD) patients and 26 peritoneal dialysis (PD) patients, and the finding were compared. RESULTS: Serum BNP and cTnI levels in HD patients (722.9 +/- 907.9 pg/mL, 0.05 +/- 0.07 microg/L, respectively), just before HD, were significantly higher than those of PD patients (255.4 +/- 463.7 pg/mL, 0.02 +/- 0.02 microg/L, respectively; p < 0.05). There was no significant difference between groups with regard to corrected QTd and maximum and minimum QT intervals (p > 0.05). Serum cTnI levels were significantly and positively correlated with serum BNP levels in both dialysis groups (r = 0.447, p = 0.048). No relationship was found between plasma BNP and ECG parameters studied in both groups (p > 0.05). CONCLUSION: Increased serum cTnI levels were associated with elevated BNP levels in both dialysis groups. The increases in BNP and troponin I are more likely to reflect hypervolemia. Although CAPD patients were receiving dialysis daily and HD patients were more hypervolemic, CAPD patients have similar QTdc and accordingly a similar tendency toward arrhythmias. This suggests that factors other than electromechanical interaction may be important in determining the QT interval length in patients on dialysis. PMID- 17365941 TI - Nephrotic syndrome as a complication of intravesical BCG treatment of transitional cell carcinoma of urinary bladder. AB - Nephrotic syndrome can be associated with various neoplasms, especially solid tumors and lymphomas. This patient presented with painless hematuria of transitional cell carcinoma of urinary bladder, underwent transurethral resection, but developed recurrence 16 months later. Repeat resection was done and intravesical Bacillus Calmette-Guerin (BCG) injections were started. After six months, the patient developed hypertension and nephrotic syndrome with a biopsy revealing membranous glomerulonephritis, though there was no radiological evidence of tumor. This is the first case of nephrotic syndrome with intravesical BCG instillation in a bladder carcinoma patient. PMID- 17365942 TI - Renal cortical nephrocalcinosis following acute renal failure due to polytrauma. AB - Renal cortical nephrocalcinosis is a rare condition in which there is calcification within the renal parenchyma. This article reports a 33-year-old patient who developed acute renal failure following multiple injuries leading to hemorrhagic shock. His renal failure improved gradually, though he required dialysis support for two months. Serial ultrasounds showed a progressive decrease in renal size, and a radiograph of the abdomen showed speckled calcification in both renal areas. A CT scan of abdomen showed diffuse cortical calcification involving the entire right kidney and upper half of the left kidney. PMID- 17365943 TI - Propylthiouracil-induced vasculitis associated with ANCA: a case report. AB - Propylthiouracil is a drug used in the treatment of hyperthyroidism for more than 60 years. Adverse side effects are seen in 1-5% of patients. Renal complications of the drug including glomerulonephritis and vasculitis are rarely seen. Cases of propylthiouracil-induced rapidly progressive glomerulonephritis and vasculitis are reported in association with antineutrophil cytoplasmic autoantibodies. Here we report a case of positive antineutrophil cytoplasmic autoantibodies rapidly progressive glomerulonephritis (RPGN) associated with propylthiouracil treatment. PMID- 17365944 TI - A young female with Spitzer-Weinstein syndrome diagnosed by thiazide test. AB - Spitzer-Weinstein syndrome is a rare disorder characterized by thiazide responsive hyperkalemia and normal anion gap metabolic acidosis, similar to Gordon syndrome. The hyperfunction of thiazide-sensitive Na+-Cl- cotransporter (TSC) is the main pathophysiological mechanism. We presented a 19-year-old female with short stature, normal blood pressure, persistently elevated serum potassium, and metabolic acidosis. The diagnosis of Spitzer-Weinstein Syndrome was made by clinical pictures and thiazide test. After taking 4 mg hydrochlorothiazide, her daily urine potassium excretion increased from 18.1 mmol to 41.8 mmol, urine pH decreased from 7.32 to 6.50, and urinary net charge decreased from 65.7 to 54.4. This patient then took hydrochlorothiazide 4 mg daily. The persistent hyperkalemia and metabolic acidosis were corrected. Thiazide, a powerful inhibitor of TSC, proved to be a useful tool for the diagnosis and treatment of Spitzer-Weinstein syndrome. PMID- 17365945 TI - Occult donor malignancy in pancreas transplantation. AB - Tumor of the pancreas allograft is extremely rare. We report a case of an occult donor malignant undifferentiated tumor arising in a pancreas allograft. A 42-year old female with Type 1 diabetes received a macroscopically normal pancreas allograft. The donor was a 22-year-old male who died of spontaneous intracerebral hemorrhage. She underwent transplant pancreatectomy, the histology of the pancreas allograft demonstrated a tumor measuring 5 mm in diameter, and a diagnosis of malignant undifferentiated tumor was made. In a different transplant center, the recipient of the left kidney transplant from the same donor had a nephrectomy, and the recipient of the liver transplant died of metastatic disease. Microscopic examination of the liver and kidney allografts subsequently revealed histological features identical to the pancreas tumor. Tumor transmission in transplantation may occur from an organ that contains metastatic cells or, less commonly, from the transmission of an unrecognized or occult primary tumor. A report from the United Network for Organs Sharing transplant data 1997-2002 is illustrated and discussed. This case illustrates the difficulties associated with identifying donors with occult primary tumor or metastases. PMID- 17365946 TI - Is there any benefit from oral a-tocopherol administration in hemodialysis patients? PMID- 17365947 TI - Consistency of refrigerated pathological urine sediment. AB - Urinalysis is a routine medical laboratory investigation, as examination of the urine plays a vital role in the diagnosis of kidney diseases. Sometimes the identification of urine sediment needs confirmation by expertise in clinical microscopy, and this is difficult in the far rural area in the developing countries. Here, the author evaluated a feasibility to use refrigerated urine sediment for repeated analysis. In this work, the author found that it is feasible to use refrigerated urine sediment for repeated analysis. The good correlation (> 0.9) can be seen for the epithelium, red blood cell, and cast but not for the white blood cell. The consistency of the repeat analysis results are an orderly decrease from epithelium (4 days), red blood cell (3 days), white blood cell (3 days), and cast (2 days). However, as time passes, reliability decreases. PMID- 17365948 TI - Metabolic consequences of resistive force selection during cycle ergometry exercise. AB - The purpose of this study was to compare power outputs and blood lactate concentrations ([La-]B) following 30 s of maximal cycle ergometry when resistive forces were derived from total-body mass (TBM) or fat-free mass (FFM). Differences (P < 0.05) in peak power output (PPO), pedal velocity (PV) and resistive forces (RF) were observed when the TBM and FFM protocols were compared (953 +/- 114 W vs. 1020 +/- 134 W; 134 +/- 8 rpm vs. 141 +/- 7 rpm; 6 +/- 1 kg vs. 5 +/- 1 kg, respectively). Blood lactate values ([La-]B) increased (P < 0.01) postexercise for both protocols and were significantly greater for TBM (10.6 +/- 1.2 mmol.l-1 vs 11.6 +/- 1.1 mmol.l-1, P < 0.05). These findings indicate that the FFM resistive force protocol may maximise adenosinotriphosphate phosphocreatine (ATP-PC) utilisation with smaller contributions from anaerobic glycolysis when compared with TBM. These results may have important implications in the assessment of high intensity exercise performance. PMID- 17365949 TI - Psychological intervention programs for reduction of injury in ballet dancers. AB - The purpose of this study was to examine the effects of two psychological interventions designed to reduce injury among dancers by enhancing coping skills. Participants were 35 ballet dancers. They were assigned to three conditions: control (n = 12), autogenic training (n = 12), and a broad-based coping skills condition, including autogenic training, imagery, and self-talk (n = 11). The 12 week interventions were designed on the basis of results from previous studies. For the 12 weeks following the intervention, participants were asked to practice their respective interventions three times a week. During the 24-week period (12 weeks training plus 12 weeks practice), training staff at the dance academies recorded injuries on a record sheet each day. Participants wrote injury records by themselves for another 24 weeks. Multivariate analysis of variance (MANOVA) and univariate tests for each dependent variable showed that the broad-based coping skills condition enhanced coping skills, in particular, peaking under pressure, coping with adversity, having confidence and achievement motivation, and concentrating. Separate analyses of covariance (ANCOVA), one using preintervention injury frequency as the covariate and one using preintervention injury duration as the covariate, revealed that participants in the broad-based coping skills condition spent less time injured than participants in the control condition. PMID- 17365950 TI - Maternal physiological responses to swimming training during the second trimester of pregnancy. AB - Maternal submaximal aerobic fitness (PWC170) was measured before, during, and after 12 weeks of swimming training during the second trimester of pregnancy in 23 sedentary women. For comparison, 11 women maintained their normal activities, but did not swim. Training sessions were 3 times per week for 40 min, producing heart rate (HR) responses of 65%-70% of estimated maximum HR and increases in rectal temperature (n = 8) of approximately 0.4 degrees C. Distance swum per session almost doubled over the training period (581 +/- 177 m to 1110 +/- 263 m). PWC170 of the nonswimming group remained stable over time; that of the swimming group increased significantly by 13.8% after 8 weeks of training (790 +/ 145 to 909 +/- 137 kpm/min; p = 0.026). The results indicate that a significant aerobic training effect can be achieved by light-moderate-intensity swimming during pregnancy in previously sedentary women. Further, all women remained healthy, with no adverse outcomes for mother or baby. PMID- 17365951 TI - Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome. AB - The purpose of this study was to determine whether chronic fatigue syndrome (CFS) subjects would produce greater force production in their matching limb during a fatiguing contralateral limb-matching task of the elbow flexors, compared with healthy, matched controls. Eight CFS subjects and 8 healthy, matched control subjects participated in a fatiguing task that consisted of intermittent submaximal contractions (30% maximal voluntary contraction) of the nondominant arm performed over a 45 min duration. Each minute, the subject attempted to match the force of the nondominant arm with their dominant arm (without visual feedback for the dominant arm). Results showed that average matching force and ratings of perceived effort values were significantly higher in the CFS group during the fatiguing task (P = 0.04, P = 0.02, respectively). This study demonstrated objectively that CFS subjects experienced a greater sense of effort in the elbow flexors while performing a fatiguing task. PMID- 17365952 TI - Noninvasive profiling of exercise-induced hypoxemia in competitive cyclists. AB - The purpose of this case study was to profile maximal exercise and the incidence of exercise-induced arterial hypoxemia (EIAH) at three different altitudes within a group of competitive cyclists residing and training at 1,500 m. Ten male cyclists (category I or II professional road cyclists: ages, 27.7 +/- 6.1; weight, 69.9 +/- 6.9 kg) participated in three randomly assigned VO2max tests at sea level (SL), 1,500 m and 3000 m. Arterial saturation (pulse oximetry), ventilation, and power output (PO) were recorded continuously throughout the test. The SaO2 percentages at VO2max were significantly higher at SL when compared with 1500 m (p < 0.001); however, no difference was observed between VO2max values at either altitude (SL: 72.3 +/- 2.5 mL.kg-1.min-1, 1,500 m: 70.6 +/- 2.3 mL.kg-1.min-1), only when compared with 3,000 m: 63.9 +/- 2.1 mL.kg-1.min 1, p < 0.021. Percent SaO2 did correspond with maximal PO, and there was an overall main effect observed between POs as they continually declined from SL to 3,000 m (SL: 403.3 +/- 10.6 W; 1,500 m: 376.1 +/- 9.8 W; 3,000 m: 353.9 +/- 7.8 W; p < 0.0001). The results of this case study revealed that training and residing at 1,500 m did not reduce the incidence of EIAH during maximal exercise at 1,500 m for this selected group of cyclists. PMID- 17365954 TI - Proceedings of the 12th International Workshop on Quantitative Structure-Activity Relationships in Environmental Toxicology, Lyon, France, 8-12 May 2006. PMID- 17365953 TI - Validation of Cosmed's FitMate in measuring exercise metabolism. AB - The purpose of this study was to assess the validity of the FitMate metabolic system (Cosmed, Rome, Italy) in measuring oxygen consumption during graded exercise. The FitMate is a new, small (20 x 24 cm) metabolic analyzer designed for measurement of oxygen consumption during rest and exercise. Subjects included 40 healthy adults (N = 20 males, N = 20 females) ranging in age from 18 to 37 kg/m2 (mean +/- SD age, 22.5 +/- 3.6 years) and body mass index (BMI) from 18.3 to 32.5 kg/m2 (23.2 +/- 3.3 years). One-minute FitMate and Douglas bag measurements were made during steady state conditions at the end of each 3-minute stage of the Bruce treadmill graded exercise test, and subjects continued until they could not attain steady state exercise during a stage. Oxygen consumption difference scores (Douglas bag minus FitMate measurements) did not differ between males and females, so data were combined and analyzed for the entire group. During the first three stages, mean oxygen consumption did not differ significantly between the Douglas bag and FitMate systems (26.5 +/- 1.1 and 26.7 +/- 1.3 ml.kg-1.min-1, respectively, P = 0.140) with a mean absolute difference of 0.23 +/- 0.91 ml.kg-1.min-1 or 14.2 +/- 67.5 ml.min-1. In conclusion, the FitMate metabolic system accurately measures oxygen consumption during graded treadmill exercise when compared with the Douglas bag system in male and female adults. PMID- 17365955 TI - Evolution of the international workshops on quantitative structure-activity relationships (QSARs) in environmental toxicology. AB - This presentation will review the evolution of the workshops from a scientific and personal perspective. From their modest beginning in 1983, the workshops have developed into larger international meetings, regularly held every two years. Their initial focus on the aquatic sphere soon expanded to include properties and effects on atmospheric and terrestrial species, including man. Concurrent with this broadening of their scientific scope, the workshops have become an important forum for the early dissemination of all aspects of qualitative and quantitative structure-activity research in ecotoxicology and human health effects. Over the last few decades, the field of quantitative structure/activity relationships (QSARs) has quickly emerged as a major scientific method in understanding the properties and effects of chemicals on the environment and human health. From substances that only affect cell membranes to those that bind strongly to a specific enzyme, QSARs provides insight into the biological effects and chemical and physical properties of substances. QSARs are useful for delineating the quantitative changes in biological effects resulting from minor but systematic variations of the structure of a compound with a specific mode of action. In addition, more holistic approaches are being devised that result in our ability to predict the effects of structurally unrelated compounds with (potentially) different modes of action. Research in QSAR environmental toxicology has led to many improvements in the manufacturing, use, and disposal of chemicals. Furthermore, it has led to national policies and international agreements, from use restrictions or outright bans of compounds, such as polychlorinated biphenyls (PCBs), mirex, and highly chlorinated pesticides (e.g. DDT, dieldrin) for the protection of avian predators, to alternatives for ozone-depleting compounds, to better waste treatment systems, to more powerful and specific acting drugs. Most of the recent advances in drug development could not have been achieved without the use of QSARs in one form or another. The pace of such developments is rapid and QSARs are the keystone to that progress. These workshops have contributed to this progress and will continue to do so in the future. PMID- 17365956 TI - Structure-activity relationships for abiotic thiol reactivity and aquatic toxicity of halo-substituted carbonyl compounds. AB - Using abiotic thiol reactivity (EC50) and Tetrahymena pyriformis toxicity (IGC50) data for a group of halo-substituted ketones, esters and amides (i.e. SN2 electrophiles) and related compounds a series of structure-activity relationships are illustrated. Only the alpha-halo-carbonyl-containing compounds are observed to be thiol reactive with the order I > Br > Cl > F. Further comparisons disclose alpha-halo-carbonyl compounds to be more reactive than non-alpha-halo-carbonyl compounds; in addition, the reactivity is reduced when the number of C atoms between the carbonyl and halogen is greater than one. Comparing reactivity among alpha-halo-carbonyl-containing compounds with different beta-alkyl groups shows the greater the size of the beta-alkyl group the lesser the reactivity. A comparison of reactivity data for 2-bromoacetyl-containing compounds of differing dimensions reveals little difference in reactivity. Regression analysis demonstrates a linear relationship between toxicity and thiol reactivity: log (IGC(50)(-1)) = 0.848 log (EC(50)(-1)) + 1.40; n=19, s=0.250, r2=0.926, r2(pred)=0.905, F=199, Pr > F=0.0001. PMID- 17365957 TI - Prediction of dermal absorption from complex chemical mixtures: incorporation of vehicle effects and interactions into a QSPR framework. AB - Significant progress has been made on predicting dermal absorption/penetration of topically applied compounds by developing QSPR models based on linear free energy relations (LFER). However, all of these efforts have employed compounds applied to the skin in aqueous or single solvent systems, a dosing scenario that does not mimic occupational, environmental or pharmaceutical exposure. We have explored using hybrid QSPR equations describing individual compound penetration based on the molecular descriptors for the compound modified by a mixture factor (MF) which accounts for the physicochemical properties of the vehicle/mixture components. The MF is calculated based on percentage composition of the vehicle/mixture components and physical chemical properties selected using principal components analysis. This model has been applied to 12 different compounds in 24 mixtures for a total of 288 treatment combinations obtained from flow-through porcine skin diffusion cells and in an additional dataset of 10 of the same compounds in five mixtures for a total of 50 treatment combinations in the ex vivo isolated perfused porcine skin flap. The use of the MF in combination with a classic LFER based on penetrant properties significantly improved the ability to predict dermal absorption of compounds dosed in complex chemical mixtures. PMID- 17365958 TI - A quantitative structure-activity relationship (QSAR) study of dermal absorption using theoretical molecular descriptors. AB - Quantitative structure-activity relationship (QSAR) models were developed for the prediction of dermal absorption based on experimental log Kp data for a diverse set of 101 chemicals obtained from the literature. Molecular descriptors including topostructural (TS), topochemical (TC), shape or three-dimensional (3D) and quantum chemical (QC) indices were calculated. Based on this information, a generic predictive model was created using the diverse set of 101 compounds. In addition, two submodels were prepared for subsets of 79 cyclic and 22 acyclic chemicals. A modified Gram-Schmidt variable reduction algorithm for descriptor thinning was followed by regression analyses using ridge regression (RR), principal components regression (PCR) and partial least squares regression (PLS). The RR results were found to be superior to PLS and PCR regressions. The cross validated correlation coefficients for the full set and subsets were 0.67-0.87. Computational methods such as QSAR modelling can be used to augment existing data to prioritise chemicals that need to be studied further for toxicological evaluation and risk assessment. PMID- 17365959 TI - Structure-based modelling in reproductive toxicology: (Q)SARs for the placental barrier. AB - The replacement of animal testing for endpoints such as reproductive toxicity is a long-term goal. This study describes the possibilities of using simple (quantitative) structure-activity relationships ((Q)SARs) to predict whether a molecule may cross the placental membrane. The concept is straightforward, if a molecule is not able to cross the placental barrier, then it will not be a reproductive toxicant. Such a model could be placed at the start of any integrated testing strategy. To develop these models the literature was reviewed to obtain data relating to the transfer of molecules across the placenta. A reasonable number of data were obtained and are suitable for the modelling of the ability of a molecule to cross the placenta. Clearance or transfer indices data were sought due to their ability to eliminate inter-placental variation by standardising drug clearance to the reference compound antipyrine. Modelling of the permeability data indicates that (Q)SARs with reasonable statistical fit can be developed for the ability of molecules to cross the placental barrier membrane. Analysis of the models indicates that molecular size, hydrophobicity and hydrogen-bonding ability are molecular properties that may govern the ability of a molecule to cross the placental barrier. PMID- 17365960 TI - QSAR and mode of action studies of insecticidal ecdysone agonists. AB - A series of our SAR and QSAR studies of synthetic moulting hormone agonists, dibenzoylhydrazines (DBH), exhibiting insecticidal/larvicidal activity are reviewed in this article. We prepared a number of analogues where various substituents are introduced into the two benzene rings of DBH and measured their biological activity using various biological systems. Larvicidal activity was against larvae of the rice stem borer Chilo suppressalis and the moulting hormone activity was in terms of the stimulation of N-acetylglucosamine incorporation in a cultured integument system of the same insect species. Binding affinity to the ecdysone receptor was assayed with intact Sf-9 cell lines in which the ADME processes are negligible as well as using receptor proteins obtained by in vitro translation of the responsible cDNA cloned from cell-free preparation of integumentary tissue of C. suppressalis. Variations in the biological activity indices were either correlated between two types of activity or correlated using physicochemical molecular and substituent parameters in terms of the classical QSAR. Comparisons among correlations and with recently revealed X-ray crystallographic findings clearly indicate the physicochemical meaning of parameters significant in the correlation equations to help understanding molecular mechanism of the moulting hormonal action. PMID- 17365961 TI - The quality of QSAR models: problems and solutions. AB - Assessment of the quality of goodness-of-fit and the confidence in predictivity (prediction power) are the main terms used to define the statistical quality of QSAR models. Three parts of this assessment can be defined as: (1) Measure of goodness-of-fit. (2) Validation of model stability. (3) Predictivity analysis. Currently there are no mandatory requirements for the validation methods to be used and rules for the quantitative confidence estimates. To compare the statistical quality of QSAR models it is necessary to have an overall statistical quality index which will depend on the goodness-of-fit, validation and predictivity results together. To do so it is necessary to define the set of mandatory parameters for all three parts of assessment listed above and develop the approach for overall quality estimates based on these parameters. It is also necessary to include into the overall index the penalty mechanism for parameter absence. The goal of the present study is to analyse parameters for all three parts of the QSAR model statistical quality assessment and investigate the flexible weighting approach for the overall statistical quality index development. Due the different statistical parameters traditionally used for assessment of goodness-of-fit it is necessary to create the mechanism, which allows flexible set of parameters to be used for the overall statistical quality index. Only after approval by scientific community and regulatory boards the final set of mandatory parameters can be selected. PMID- 17365962 TI - PASS: identification of probable targets and mechanisms of toxicity. AB - Toxicity of chemical compound is a complex phenomenon that may be caused by its interaction with different targets in the organism. Two distinct types of toxicity can be broadly specified: the first one is caused by the strong compound's interaction with a single target (e.g. AChE inhibition); while the second one is caused by the moderate compound's interaction with many various targets. Computer program PASS predicts about 2500 kinds of biological activities based on the structural formula of chemical compounds. Prediction is based on the robust analysis of structure-activity relationships for about 60,000 biologically active compounds. Mean accuracy exceeds 90% in leave-one-out cross-validation. In addition to some kinds of adverse effects and specific toxicity (e.g. carcinogenicity, mutagenicity, etc.), PASS predicts approximately 2000 kinds of biological activities at the molecular level, that providing an estimated profile of compound's action in biological space. Such profiles can be used to recognize the most probable targets, interaction with which might be a reason of compound's toxicity. Applications of PASS predictions for analysis of probable targets and mechanisms of toxicity are discussed. PMID- 17365963 TI - The role of the European Chemicals Bureau in promoting the regulatory use of (Q)SAR methods. AB - Under the proposed REACH (Registration, Evaluation and Authorisation of CHemicals) legislation, (Q)SAR models and grouping methods (chemical categories and read across approaches) are expected to play a significant role in prioritising industrial chemicals for further assessment, and for filling information gaps for the purposes of classification and labelling, risk assessment and the assessment of persistent, bioaccumulative and toxic (PBT) chemicals. The European Chemicals Bureau (ECB), which is part of the European Commission's Joint Research Centre (JRC), has a well-established role in providing independent scientific and technical advice to European policy makers. The ECB also promotes consensus and capacity building on scientific and technical matters among stakeholders in the Member State authorities and industry. To promote the availability and use of (Q)SARs and related estimation methods, the ECB is carrying out a range of activities, including applied research in computational toxicology, the assessment of (Q)SAR models and methods, the development of technical guidance documents and computational tools, and the organisation of training courses. This article provides an overview of ECB activities on computational toxicology, which are intended to promote the development, validation, acceptance and use of (Q)SARs and related estimation methods, both at the European and international levels. PMID- 17365964 TI - A general structure-property relationship to predict the enthalpy of vaporisation at ambient temperatures. AB - The vapour pressure is the most important property of an anthropogenic organic compound in determining its partitioning between the atmosphere and the other environmental media. The enthalpy of vaporisation quantifies the temperature dependence of the vapour pressure and its value around 298 K is needed for environmental modelling. The enthalpy of vaporisation can be determined by different experimental methods, but estimation methods are needed to extend the current database and several approaches are available from the literature. However, these methods have limitations, such as a need for other experimental results as input data, a limited applicability domain, a lack of domain definition, and a lack of predictive validation. Here we have attempted to develop a quantitative structure-property relationship (QSPR) that has general applicability and is thoroughly validated. Enthalpies of vaporisation at 298 K were collected from the literature for 1835 pure compounds. The three-dimensional (3D) structures were optimised and each compound was described by a set of computationally derived descriptors. The compounds were randomly assigned into a calibration set and a prediction set. Partial least squares regression (PLSR) was used to estimate a low-dimensional QSPR model with 12 latent variables. The predictive performance of this model, within the domain of application, was estimated at n=560, q2Ext=0.968 and s=0.028 (log transformed values). The QSPR model was subsequently applied to a database of 100,000+ structures, after a similar 3D optimisation and descriptor generation. Reliable predictions can be reported for compounds within the previously defined applicability domain. PMID- 17365965 TI - Predicting activities without computing descriptors: graph machines for QSAR. AB - We describe graph machines, an alternative approach to traditional machine learning-based QSAR, which circumvents the problem of designing, computing and selecting molecular descriptors. In that approach, which is similar in spirit to recursive networks, molecules are considered as structured data, represented as graphs. For each example of the data set, a mathematical function (graph machine) is built, whose structure reflects the structure of the molecule under consideration; it is the combination of identical parameterised functions, called "node functions" (e.g. a feedforward neural network). The parameters of the node functions, shared both within and across the graph machines, are adjusted during training with the "shared weights" technique. Model selection is then performed by traditional cross-validation. Therefore, the designer's main task consists in finding the optimal complexity for the node function. The efficiency of this new approach has been demonstrated in many QSAR or QSPR tasks, as well as in modelling the activities of complex chemicals (e.g. the toxicity of a family of phenols or the anti-HIV activities of HEPT derivatives). It generally outperforms traditional techniques without requiring the selection and computation of descriptors. PMID- 17365966 TI - Discriminating toxicant classes by mode of action: 3. Substructure indicators. AB - Decision support for selecting suitable QSARs for predictive purposes is suggested by a stepwise procedure: The first tier pre-filters the compounds based on substructure indicators for baseline versus excess toxicity. This step, if sufficiently conservative, discriminates chemicals, whose toxicity can be reliably estimated from their log KOW from those, that require further classification by biological and chemical domain. A test set of 115 chemicals from 9 different MOA classes was used to compare the discriminatory power of several classification schemes based on substructure indicators. Performance, evaluated by contingency table statistics, is varied and no single scheme provides sufficient applicability and reliability for pre-filtering chemical inventories. Major improvements are feasible with combined use of three classification schemes: assignments of baseline toxicants are protective, recognition of excess toxicants is acceptable and applicability range increases favourably. PMID- 17365967 TI - Approaches for externally validated QSAR modelling of Nitrated Polycyclic Aromatic Hydrocarbon mutagenicity. AB - Nitrated Polycyclic Aromatic Hydrocarbons (nitro-PAHs), ubiquitous environmental pollutants, are recognized mutagens and carcinogens. A set of mutagenicity data (TA100) for 48 nitro-PAHs was modeled by the Quantitative Structure-Activity Relationships (QSAR) regression method, and OECD principles for QSAR model validation were applied. The proposed Multiple Linear Regression (MLR) models are based on two topological molecular descriptors. The models were validated for predictivity by both internal and external validation. For the external validation, three different splitting approaches, D-optimal Experimental Design, Self Organizing Maps (SOM) and Random Selection by activity sampling, were applied to the original data set in order to compare these methodologies and to select the best descriptors able to model each prediction set chemicals independently of the splitting method applied. The applicability domain was verified by the leverage approach. PMID- 17365969 TI - The accurate timing of surgery in aortic stenosis. PMID- 17365970 TI - Do the benefits outweigh the risks with drug-eluting stents? PMID- 17365971 TI - Comment to text by Leif Thuesen, "PCI-the ugly duckling". PMID- 17365972 TI - Diagnostic and referral delay in patients with aortic stenosis is common and negatively affects outcome. AB - OBJECTIVE: Aortic stenosis (AS) patients are often severely symptomatic at the time of aortic valve replacement (AVR). We wanted to investigate doctors' delay and its impact on outcome. DESIGN: AS patients undergoing AVR (n = 422) were included. Clinical and echocardiographic data at the time of diagnosis and preoperatively were noted. The risk of death after AVR was estimated using Poisson regression, incorporating age, gender, coronary artery disease, NYHA III/IV and time on the waiting list for AVR. RESULTS: The age (mean+/-SD) was 71+/-8.6 years, 45% were women, and 48% were in NYHA III/IV. 55% underwent AVR within one year of diagnosis, indicating late diagnosis. The time from referral to AVR (median, range) was 112 (1-803) days. NYHA III/IV independently predicted mortality (hazard ratio 1.76, 95% CI 1.28-2.43, p = 0.0005). The time from referral to AVR influenced the risk of death immediately after operation (p = 0.0083). CONCLUSION: Late diagnosis and late referral for AVR are common, and negatively influence outcome in patients with AS. Delay in surgery after referral increase the mortality immediately after AVR. PMID- 17365973 TI - Short and long-term outcome in diabetic patients with acute myocardial infarction in the invasive era. AB - OBJECTIVES: To investigate the outcome after acute myocardial infarction in diabetic patients compared with non-diabetic patients in a period with invasive treatment as the preferred treatment for acute myocardial infarction (MI). DESIGN: Patient records for all patients admitted with an acute MI in a two-year period from July 1, 2001 to June 30, 2003 were reviewed. RESULTS: A total of 334 patients entered the study: 48 with diabetes mellitus (DM) and 286 without diabetes. ST-elevation infarction occurred in 49% of non-diabetic patients and 36% of diabetic patients. In-hospital mortality was 23% among diabetic patients compared to 5% among non-diabetic patients (p < 0.001). Long-term mortality (median 2 years and 10 months) was 44% in diabetic-patients and 23% in non diabetic patients (p = 0.001). Diabetic patients were older, more frequently had hypertension and three-vessel disease, but DM was found to be an independent risk factor for death after MI (p = 0.005). CONCLUSIONS: In an era of invasive therapy as the preferred therapy for acute MI, DM is still associated with considerably increased mortality after an acute MI. PMID- 17365974 TI - The electrocardiographic reperfusion peak in patients with ST-elevation myocardial infarction. AB - OBJECTIVES: To analyse the incidence and the prognostic value of the reperfusion peak in a population of patients with AMI treated with thrombolysis. DESIGN: Two hundred and sixty-nine patients with ST-elevation myocardial infarction treated with thrombolysis were monitored with continuous on-line vectorcardiography. RESULTS: A reperfusion peak defined as a transiently increased ST-VM of >50 microV followed by an immediate decrease to a level lower than the starting point was seen in 112 of all 269 (42%) patients and in 111 of 149 (75%) of the patients with successful ST-resolution. A reperfusion peak was an independent predictor of better prognosis both in the short- and the long term but had no implications on the prognosis in the subgroup with successful ST-resolution. CONCLUSION: A reperfusion peak was equally common in patients treated with thrombolysis having a successful ST-resolution as observed in studies of patients with successful primary coronary angioplasty. The reperfusion peak was associated with better prognosis and should be recognised as a possible marker of successful reperfusion but can mimic aggravated ischemia. PMID- 17365975 TI - The NORwegian study on DIstrict treatment of ST-elevation myocardial infarction (NORDISTEMI). AB - OBJECTIVES: Thrombolysis is the treatment of choice for patients with ST elevation myocardial infarction (STEMI) living in rural areas with long transfer delays to percutaneous coronary intervention (PCI). This trial compares two different strategies following thrombolysis: to transfer all patients for immediate coronary angiography and intervention, or to manage the patients more conservatively. DESIGN: The NORwegian study on DIstrict treatment of STEMI (NORDISTEMI) is an open, prospective, randomized controlled trial in patients with STEMI of less than 6 hours of duration and more than 90 minutes expected time delay to PCI. A total of 266 patients will receive full-dose thrombolysis, preferably pre-hospital, and then be randomized to either strategy. Our primary endpoint is the one year combined incidence of death, reinfarction, stroke or new myocardial ischaemia. The study is registered with ClinicalTrials.gov, number NCT00161005. RESULTS: By April 2006, 109 patients have been randomized. Thrombolysis has been given pre-hospital to 52% of patients. The median transport distance from first medical contact to catheterization laboratory was 155 km (range 90-396 km). Results of the study are expected in 2008. PMID- 17365976 TI - Off-pump CABG in diabetic patients: does insulin dependency matter? AB - BACKGROUND: We aimed to analyze influence of insulin dependency on short-term outcomes after OPCAB in patients with diabetes. METHODS: Retrospective cohort study was planned based on chart review. Study population consisted of 148 diabetic cases (63 insulin-dependent diabetics in group I and 85 non-insulin dependent diabetics in group II). Patients' preoperative data and risk factors for adverse outcomes are analysed. The primary endpoint was all causes of mortality during the in-hospital course. Preestablished secondary endpoints included all major postoperative complications, including non-fatal acute myocardial infarction, non-fatal stroke, sepsis, shock, mediastinitis, respiratory insufficiency, and renal insufficiency, and minor postoperative complications, including mechanical ventilation for more than 24 hours, inotropic support, reoperation for bleeding, and necessity of blood transfusion. Additional analysis was performed on the duration of stay in the intensive care unit and overall hospital stay. RESULTS: Group I patients were significantly more likely to have hypertension (87.3% versus 82.5%, p=0.023), they also had a trend toward higher prevalence of hypercholesterolemia (71.4% versus 68.6%, p=0.092) and body mass index (28.1+/-4.2 versus 26.9+/-3.7, p=0.085). Angiographic characteristics and number of distal anastomosis were similar in the two groups. There was no significant difference in mortality during the in-hospital course as the primary endpoint. However, analysis in secondary endpoints revealed that group I patients were significantly more likely to have stroke (3.1% versus 2.3%, p=0.027), sternal wound infection (4.7% versus 3.4%, p=0.036) and atrial arrhythmia (28.3% versus 20.9%, p=0.021). Moreover, group I patients were significantly more likely to stay longer than 2 days in ICU (14.2% versus 11.6%, p=0.038). Higher prevalence of renal dysfunction was also observed in group I patients (7.9% versus 6.9%, p=0.069). CONCLUSION: Similar to insulin dependent diabetes who had on-pump CABG, insulin dependent diabetes develop higher rate of major postoperative complications and stay longer in ICU after off-pump CABG. PMID- 17365977 TI - Peak CKMB and cTnT accurately estimates myocardial infarct size after reperfusion. AB - OBJECTIVES: To find the time-to-peak for creatine kinase MB(mass) (CKMB) and cardiac troponin T (cTnT) after acute reperfusion, to compare peak and cumulative values to estimate infarct size (IS), and to evaluate clinical routine sampling for assessment of IS. DESIGN: Acute primary percutaneous coronary intervention (PCI) was performed in 38 patients with first-time myocardial infarction. In 21 patients, CKMB and cTnT were acquired before PCI and at 1.5, 3, 6, 12, 18, 24, and 48 hours thereafter. In 17 patients, clinical routine samples were acquired at arrival, and at 10 and 20 h. IS was assessed by delayed contrast-enhanced MRI (DE-MRI). RESULTS: Time-to-peak was 7.6+/-3.6 h for CKMB and 8.1+/-3.4 h for cTnT. Peak values correlated strongly to cumulative values (r(s)=0.97-0.98) as well as to DE-MRI (r(s)=0.8-0.82). Clinical routine sampling showed lower rs values (0.47-0.60). CONCLUSIONS: Peak values are likely captured if CKMB and cTnT are acquired at 3, 6, and 12 h after acute PCI. These peak values can be used to estimate myocardial infarct size after acute PCI. PMID- 17365978 TI - ALCAPA, a possible reason for mitral insufficiency and heart failure in young patients. AB - OBJECTIVES: ALCAPA, anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease. We have from 1990 to 2003 operated on seven patients in our clinic. The objective of this study was to describe our experience of treating the condition and to remind other doctors of it as a possible diagnosis. DESIGN: The patients were identified by a retrospective review of our clinical records. RESULTS: Symptoms and signs varied from discomfort and pathologic heart murmur to ventricular fibrillation. All patients were operated on by use of cardiopulmonal bypass. Two died postoperatively within one week, two were reoperated later on because of pulmonary artery stenosis. CONCLUSION: ALCAPA should be suspected if a young patient with no previous history of heart failure presents with dyspnoe, chest pain or dysrhythmia. ALCAPA must be excluded by coronary angiography in younger patients with mitral insufficiency and no other morphological findings. Patients diagnosed early and operated on have a good prognosis. PMID- 17365979 TI - Functional and phenotypic changes in polymorphonuclear neutrophils induced by catecholamines. AB - PURPOSE: To elucidate differential functional and phenotypic changes in response to relevant catecholamines, the generation of oxidative free radicals by PMN, and changes in the expression of L-selectin and Mac-1 on the surface of PMN were examined in the presence of epinephrine, norepinephrine and dopamine in physiological and pharmacological concentrations. MATERIALS AND METHODS: Human polymorphonuclear neutrophils were obtained from healthy donors and pretreated with 0.5 nM or 500 nM epinephrine; 1.18 nM or 1 180 nM norepinephrine; or 0.26 nM or 261 nM dopamine, followed by stimulation with FMLP. Stimulated neutrophils were incubated with antibodies against CD 11 b or CD 62 l and assessed by flow cytometry. Additional probes were assessed by flow cytometry for the generation of oxidative free radicals. RESULTS: All catecholamines in high concentration inhibited the suppression of CD 62 l expression and CD 11 b upregulation following stimulation with FMLP. A high concentration of epinephrine suppresses generation of oxidative free radicals. CONCLUSIONS: The effect of catecholamines on the expression of CD 62 l explains the increased expression of L-selection on PMN observed after trauma. The suppression of CD 11 b reduces leukocyte adherence and consecutive abnormalities in microvascular flow. Epinephrine inhibits the generation of oxidative free radicals by PMN with potentially detrimental effects with respect to bacterial clearance. PMID- 17365980 TI - Current trends in the diagnosis and management of haemoglobinopathies. PMID- 17365981 TI - Haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in a Scandinavian perspective. AB - Haemoglobinopathies (mainly thalassaemia and sickle-cell anaemia syndromes) and glucose-6-phosphate dehydrogenase deficiency (G6PD) are globally among the most prevalent single-genomic diseases. About 3% of the world's population are heterozygotic for beta-thalassaemia and about 1-2% for sickle-cell anaemia, and it is estimated that more than 400 million people are affected by G6PD deficiency worldwide. The disorders are most prevalent in the Mediterranean area, in Asia and Africa. The Scandinavian countries, among others, have seen a boom in immigration during the past 20 years, and therefore migration makes haemoglobinopathies as well as G6PD deficiency increasingly more important from a differential diagnostic perspective in most countries. The purpose of the present special issue of the Journal is to summarize current epidemiological data and elucidate trends and practices in the laboratory diagnosis of these disorders. PMID- 17365982 TI - The thalassaemia syndromes. AB - The thalassaemia syndromes, endemic in the Mediterranean area, the Middle East, the Indian subcontinent, the Far East and in tropical Africa, are the most common hereditary disorders in humans, and millions of people are affected by diseases. Due to a widespread population flow between continents in recent past centuries, the thalassaemias are now occurring with relatively high frequency in many non endemic areas. In the Nordic countries, homozygous thalassaemia is still relatively rare, and most health-care personnel are not familiar with these diseases. This article focuses on two important issues, namely the biological and the clinical aspects of thalassaemia. PMID- 17365983 TI - Sickle cell disease in North Europe. AB - The numbers of patients with sickle cell disease in Northern Europe are steadily increasing due to migration, leading to a need for improved healthcare services for these patients. We outline the role of neonatal and antenatal screening programmes in the diagnosis of sickle cell disease, clinical aspects of care and the therapeutic options available. The clinical areas discussed in detail are pain management, the management of stroke and other neurological complications and the management of pulmonary and splenic complications. The role of hydroxyurea, blood transfusion and bone marrow transplantation are also discussed. PMID- 17365984 TI - Epidemiology of haemoglobin disorders in Europe: an overview. AB - OBJECTIVE: As a result of global population movements, haemoglobin disorders (thalassaemias and sickle cell disorders) are increasingly common in the formerly non-indigenous countries of Northern and Western Europe and in the indigenous countries of Southern Europe. This article presents an overview of the changing picture and a method for assessing service needs. METHOD: Data on country of birth or ethnic origin of residents are adjusted to obtain the estimated proportions of residents and births in non-indigenous groups at risk for haemoglobin disorders in European countries. The results are combined with prevalence data in each country of origin to obtain country prevalence estimates. Service indicators (annual tests or other interventions required to ensure equitable delivery of treatment and prevention) are then derived by country. RESULTS: Haemoglobin disorders now occur at comparable frequency throughout Northern, Western and Southern Europe. Annually, there are more affected conceptions in Northern and Western than in Southern Europe, and sickle cell disorders are more common than thalassaemias. There is growing need for health policy-makers to support motivated professionals working to develop optimal patient care, carrier diagnosis, genetic counselling and access to prenatal diagnosis throughout the Region. CONCLUSION: There is a strong case for pan European collaboration on haemoglobin disorders to share policies, standards and the instruments required to support them. These include methods for needs assessment, service standards, education and information strategies and materials, and methods for evaluating service delivery. PMID- 17365985 TI - Screening and genetic diagnosis of haemoglobinopathies. AB - The haemoglobin disorders are a group of autosomal recessive disorders characterized by either the reduced synthesis of one or more normal globin chains (the thalassaemias), the synthesis of a structurally abnormal globin chain (the haemoglobin variants) or in a few cases by both phenotypes (the reduced synthesis of a Hb variant, e.g. Hb E). They are the commonest single-gene disorders known and approximately 1000 different mutant alleles have now been characterized at the molecular level. The mutations are regionally specific, with each country having its own unique spectrum of abnormal haemoglobins and thalassaemia mutations, and can occur at high gene frequencies in some ethnic groups 1. Although haemoglobinopathy mutations are rarely found in individuals of North European origin, the number of immigrants in the North European countries is steadily increasing and the variety of their ethnic origins poses a problem for screening and accurate diagnosis. PMID- 17365986 TI - Microcytosis, iron deficiency and thalassaemia in a multi-ethnic community: a pilot study. AB - The high prevalence of microcytosis (defined here as mean cell haemoglobin<27 pg) with no other abnormality is a principal cause of confusion in screening for haemoglobin disorders. Here we report the results of a small pilot study aiming to resolve this confusion by routinely proceeding to plasma ferritin and HPLC assay, using the original sequestrene blood sample, when microcytosis is detected. Participants comprised a random sample of 1,302 people referred for a full blood count by their General Practitioner (GP) to the laboratory of a North London district general hospital serving a multi-ethnic inner-city population. Ethnicity was established by questionnaire. In North Europeans, microcytosis was present in 3% of males (half were iron-deficient) and 11% of females (most were iron-deficient). Among ethnic minorities, microcytosis was present in 35% of males (one tenth were iron-deficient), and 45% of females (less than half were iron-deficient): an exclusion diagnosis of "probable alpha thalassaemia" could be made in the remainder. We conclude that when microcytosis is present, routine further analysis of the original sequestrene sample by plasma ferritin assay and haemoglobinopathy screening could lead to a more efficient and cost-effective laboratory service for primary care and maternity services. PMID- 17365987 TI - Phenotypic presentation and underlying mutations in carriers of beta-thalassaemia and alpha-thalassaemia in the Danish immigrant population. AB - OBJECTIVE: The thalassaemia syndromes are the most common hereditary diseases in the world and now appear with relatively high frequency in non-endemic regions. Guidelines recommend the use of mean corpuscular haemoglobin (MCH) alone or in combination with mean corpuscular volume (MCV) in screening for alpha- and beta thalassaemia. This article deals with the viability of MCV<78 fL alone as screening parameter for thalassaemia in non-endemic regions. MATERIAL AND METHODS: Data from the Center for Haemoglobinopathies, Herlev University Hospital, consist of MCV measurements from 438 patients with alpha-thalassaemia and 450 patients with beta-thalassaemia referred between 1996 and 2005, and simultaneously measured MCV and MCH measurements in 86 patients referred between November 2004 and November 2005. RESULTS: In 450 beta-thalassaemia patients and 117 alpha0-thalassaemia patients diagnosed between 1996 and 2005, only two beta thalassaemia patients had MCV>or=78 fL. All alpha0-thalassaemia patients had MCV<78 fL. In contrast, 38% of patients with alpha+-thalassaemia had MCV>78 fL. When MCV and MCH were measured simultaneously, one patient with beta-thalassaemia was missed if MCV was used as a screening tool and one patient was missed if MCH was used. Forty-four different beta-thalassaemic mutations were found. CONCLUSIONS: Our data support the notion that the use of MCV<78 fL instead of MCH<27 pg is acceptable as a screening criterion in a non-endemic population. Only 0.5% of the beta-thalassaemia patients were missed and all the patients with alpha0-thalassaemia were diagnosed. Since the racial heterogeneity of the immigrant population in non-endemic regions creates a scenario with a broad spectrum of mutations and haemoglobinopathy, laboratories should be equipped to detect a large variety of mutations. PMID- 17365988 TI - Inherited, non-spherocytic haemolysis due to deficiency of glucose-6-phosphate dehydrogenase. AB - The about 400 million individuals worldwide suffering from a hereditary deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) may experience different degrees of haemolytic anaemia. Haemoglobin is present in very high concentrations in the erythrocyte cytoplasm, at risk of falling out of solution if the internal environment or the haemoglobin itself is changed. G6PD is a crucial enzyme producing reduced glutathione in the erythrocyte cytoplasm for the purpose of protecting haemoglobin against oxidative damage. The presence of unopposed oxidizing agents leading to oxidation of the sulfhydryl bridges between parts of the haemoglobin molecule decrease the solubility of haemoglobin, leading to precipitations called Heinz bodies. The laboratory investigation of G6PD deficiency is commonly done by a quantitative spectrophotometric analysis or by a rapid fluorescent spot test detecting the generation of NADPH from NADP. Genetic tests based on polymerase chain reaction detect specific mutations and may be used for population screening, family studies, or prenatal diagnosis. PMID- 17365990 TI - CD40: a new marker in coronary heart disease. PMID- 17365991 TI - High plasma levels of CD40 are associated with low coenzyme Q and vitamin E content of low-density lipoprotein in healthy men. AB - OBJECTIVE: There is a growing body of evidence to suggest that low-density lipoprotein (LDL) cholesterol, inflammation and oxidative stress are pivotal in the development of cardiovascular disease, but their interconnections are not well known. The objective of this study was to determine whether immunological activation, reflected by the plasma levels of soluble CD40 (sCD40), interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6 are associated with the antioxidant potential of LDL particles or with common lipid, immunological or thrombotic markers in 51 young healthy men. MATERIAL AND METHODS: We determined the coenzyme Q level from an oxidized LDL fraction, obtaining the concentration for ubiquinone, which indicates total coenzyme Q levels. RESULTS: The plasma level of sCD40 was negatively correlated with LDL ubiquinone (r=-0.45, p=0.001) and E vitamin (r=-0.37, p=0.008) and positively correlated with plasma concentration of plasminogen activator inhibitor-1 (PAI-1, r=0.52, p=0.002) and caspase-1 (r=0.40, p=0.004). No correlation was detected between sCD40 and plasma lipid or C-reactive protein concentrations. As sCD40 was strongly correlated with the content of LDL ubiquinone and vitamin E, their values were compared according to groups formed by sCD40 tertiles. Analysis of variance showed that there were significant differences in LDL ubiquinone (p<0.0001) and vitamin E (p=0.004) concentrations between sCD40 tertiles. CONCLUSIONS: The data indicate that increased activation of the CD40 system is related to low levels of LDL ubiquinone and vitamin E. This suggests that chronic or increased immunological activation may consume the antioxidant potential of LDL particles. PMID- 17365992 TI - Human intestinal P-glycoprotein activity estimated by the model substrate digoxin. AB - OBJECTIVE: P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (MDR1) gene single nucleotide polymorphisms (SNPs) G2677T and C3435T using the model drug digoxin. MATERIAL AND METHODS: Pgp activity was estimated from the pharmacokinetics of orally administered digoxin in blood samples from 32 healthy subjects. MDR1 gene expression in duodenal biopsies was monitored by real-time quantitative RT-PCR (RQ-PCR) and Western blot analyses. MDR1 SNPs were determined by PCR-restriction fragment length polymorphism (PCR-RFLP). The effect of medical treatment was tested by open, randomized, cross-over treatment with rifampicin and ketoconazole. RESULTS: Rifampicin treatment resulted in increased Pgp activity, duodenal MDR1 mRNA expression and Pgp detection compared with that in the control group (p<0.05 for all), Pgp activity being associated with duodenal MDR1 mRNA level (p<0.05). Individuals homozygous for the 3435 wild-type allele (CC) showed higher Pgp activity (p<0.05), whereas SNP 2677 apparently did not affect Pgp activity. No variation in Pgp in relation to age or gender was found. CONCLUSIONS: Our data confirm that rifampicin increases Pgp activity, by increasing MDR1 mRNA and Pgp levels. Moreover, we found that the wild-type allele of the synonymous polymorphism of MDR1 position 3435 confers a higher Pgp activity. These data support other findings suggesting an effect of Pgp on treatment response and disease susceptibility. PMID- 17365993 TI - Plasma concentrations of osteoprotegerin during normo- and hyperglycaemic clamping. AB - OBJECTIVE: Plasma levels of osteoprotegerin (OPG) are elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. In previous studies a positive correlation was found between plasma levels of OPG and markers of glycaemic control in diabetic subjects. The aim of the present study was to examine the effect of acute hyperglycaemia on plasma levels of OPG in non-diabetic subjects. MATERIAL AND METHODS: Nine healthy, lean, male subjects were examined in a randomized, blinded, cross-over study design during hyperglycaemic (plasma glucose = 15 mmol/L, study H) as well as during euglycaemic (plasma glucose = 5 mmol/L, study E) conditions. Blood samples were collected at baseline and at t=240 min. RESULTS: Plasma OPG decreased slightly during study H (1.26+/-0.39 versus 1.19+/-0.35 ng/mL, p<0.05), whereas the level did not change significantly during study E (1.40+/-0.46 ng/mL versus 1.57+/-0.50 ng/mL, NS). The decrease in plasma OPG during hyperglycaemia did not correlate with the change in plasma glucose but correlated significantly with changes in serum insulin (r=-0.70, p=0.038). CONCLUSIONS: Acute hyperglycaemia does not seem to increase plasma levels of OPG in non-diabetic subjects, whereas hyperinsulinaemia may suppress plasma levels of OPG. This finding indicates that the elevated plasma levels of OPG observed in diabetic subjects with poor metabolic control cannot be ascribed to hyperglycaemia per se. PMID- 17365994 TI - Capacity of glycine to modulate early inflammatory disturbances after serious gunshot injuries in the pig. AB - OBJECTIVE: Perturbation of immune homeostasis is an important determinant for organ dysfunction following multiple injuries. The aim of this study was to investigate the ability of glycine to influence the immediate post-traumatic inflammatory environment and altered reactivity of circulating leucocytes. MATERIAL AND METHODS: Twenty pigs were subjected to two standardized gunshots to the abdomen and thigh. Treatment was started immediately. The animals were randomized to receive either glycine 180 mg/kg i.v. over 30 min (n=10) or normal saline (n=10). Blood samples were drawn at baseline and 75 min after injury. In a follow-up study 12 pigs were exposed to an identical trauma. Blood was drawn at the same time-points and stimulated with lipopolysaccharide (LPS) or LPS plus glycine for 2 h in an ex vivo whole blood model. RESULTS: Selected physiologic variables and organ injury did not differ between groups 75 min after trauma. Reactive oxygen species decreased to 82.7+/-5.5 % of baseline (p<0.05) in the glycine group (unaltered in the controls). Liver glutathione concentrations decreased in parallel in both groups. In vivo production of TNF-alpha and IL-1 beta increased to the same extent regardless of treatment. Trauma induced a strong LPS tolerance. In whole blood challenged with LPS, glycine inhibited cytokine synthesis, but only in samples drawn at baseline. CONCLUSIONS: Post traumatic infusion of glycine only modestly influenced the early post-traumatic inflammatory environment. Our ex vivo results confirm previous reports on the anti-inflammatory potential of glycine, but restricted to pre-trauma conditions. PMID- 17365995 TI - Glucose metabolism in human adipose tissue studied by 13C-glucose and microdialysis. AB - OBJECTIVE: Microdialysis can be used to monitor carbohydrate metabolism and lipolysis in adipose tissue. This method, however, does not discriminate between local metabolite production and delivery from other tissues. Our aim was to study glucose metabolism by direct delivery of 13C-labelled glucose into adipose tissue by microdialysis. MATERIAL AND METHODS: Seven healthy adults were studied after an overnight fast. In three of them the effect of physical activity on glucose metabolism was tested. Microdialysis catheters were introduced into abdominal adipose tissue and 25 mM 13C-labelled glucose was added to the perfusion fluid. An extraction procedure for separating lactic acid from glucose and glycerol in the microdialysate samples was developed. After derivatization, the 13C enrichment of the compounds was analysed by gas chromatography-mass spectrometry. RESULTS: 13C-labelled lactate was detected in the first 15-min eluate fraction following that in which 13C-glucose had reached the microdialysis probe. In the different subjects, 22-35 % of adipose tissue lactate was produced locally. During exercise there was an increase in the lactate concentration and a decrease in 13C enrichment of lactate. Although lactate production in the adipose tissue increased during exercise, most adipose tissue lactate resulted from inflow. The administered 13C-labelled glucose also rapidly converted to 13C-glycerol. The 13C enrichment of glycerol was lower than that of lactate. During exercise the 13C enrichment of glycerol increased, indicating that newly synthesized depot fat was preferentially hydrolysed during physical activity. CONCLUSIONS: Metabolism of glucose to lactate and glycerol in subcutaneous adipose tissue is a rapid process that can be monitored in vivo by administration of stable isotope labelled glucose into the microdialysis probe. In adults at rest about one-fourth of adipose tissue lactate is produced locally. PMID- 17365996 TI - Quantification of Staphylococcus aureus and Staphylococcus epidermidis on the hands of health-care workers using a real-time polymerase chain reaction method. AB - OBJECTIVE: The objective of this study was to test a polymerase chain reaction (PCR) assay intended as a tool for monitoring hand hygiene in hospital wards. METHODS: The hands of 20 health-care workers were sampled for 10 days using real time PCR for quantification of Staphylococcus aureus and S. epidermidis. Reference intervals (CI) and biological variation were evaluated using index of individuality (II) and critical difference (CD). RESULTS: 45% of the participants were positive for S. aureus on all 10 days. Intra-individual biological variation (CVI) was 129% for S. aureus and 62% for S. epidermidis. Inter-individual biological variation (CVG) was 245% for S. aureus and 107% for S. epidermidis. II was 0.55 for S. aureus and 0.71 for S. epidermidis, indicating a high degree of individuality and limited use of the reference values. A significant individual change was determined at 374% for S. aureus and 211% for S. epidermidis. In an intervention study aimed at better hand hygiene in a ward with n participants, the difference before and after intervention is significant at CDI/sqrt[n] per cent. CONCLUSIONS: The PCR assay can be used to detect change in a group mean of S. aureus and S. epidermidis in a hospital ward, i.e. before and after an intervention to improve hand hygiene. For the individual, the change in bacteria levels needed for significance is compromised by high intra-individual variation. PMID- 17365997 TI - Cystatin C reduces the in vitro formation of soluble Abeta1-42 oligomers and protofibrils. AB - There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (Abeta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric Abeta1-42 significantly attenuated the in vitro formation of Abeta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed Abeta oligomers. Direct binding of cystatin C to Abeta was demonstrated with the formation of an initial 1:1 molar high-affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric Abeta to larger and perhaps more toxic molecular species in vivo. PMID- 17365998 TI - Carbohydrate-deficient transferrin determined in blood microsamples from healthy newborns by using capillary zone electrophoresis. AB - OBJECTIVE: There is a paucity of studies on quantitative determination of carbohydrate-deficient transferrin (CDT) in newborns. The aim of our study was therefore to determine CDT concentrations in newborns by using capillary zone electrophoresis (CZE). MATERIAL AND METHODS: Capillary blood was collected from the heels of 28 at-term healthy newborns, simultaneously with the Guthrie card screening. Forty-seven adults were examined as controls. CZE separations were performed with a P/ACE MDQ capillary electropherograph in uncoated fused-silica capillaries using a commercial reagent kit. After iron saturation, the samples were loaded by application of 0.5 psi for 15 s, and separated under 28kV with UV detection. All relevant transferrin (Tf) glycoforms were separated within 7 min. CDT quantification (%CDT) was carried out by calculating the percentage ratio between the sum of the peak areas of CDT-related glycoforms and the sum of peak areas of all Tf glycoforms. RESULTS: In most cases, good separations of Tf glycoforms were obtained. In the newborns the %CDT was 0.51 versus 0.66 in adults (difference not statistically significant). Trisialo-Tf concentration was significantly lower in newborns (3.20) than in adults (4.11). Furthermore, pentasialo-Tf appeared to be lower in newborns (7.30) than in adults (14.00), but because complete separation of the peaks of tetrasialo- and pentasialo-Tf was not always possible, this finding could not be confirmed statistically. CONCLUSIONS: CZE showed definite advantages in terms of volume of blood to be collected, simplicity and standardization of analysis and, because of the direct detection of the separated zones, accuracy of quantification. The present study provides the basic information in the search for glycosylation defects in newborns. PMID- 17365999 TI - Interleukin-6 and lipopolysaccharide-binding protein in acute appendicitis in children. AB - The aim of the study was to evaluate the diagnostic accuracy of interleukin-6 (IL 6) and lipopolysaccharide-binding protein (LBP) in children with acute appendicitis (AA) and to compare this with the diagnostic accuracy of routinely used C-reactive protein (CRP) and white blood cell (WBC) count. Eighty-two consecutive children admitted to our Department because of suspected AA were enrolled in this prospective study and classified into two groups: group 1 (49 children who underwent surgery for AA) and group 2 (33 children with no surgery with diagnosis of non-specific abdominal pain or sonographic mesenteric lymphadenitis). There were no negative appendectomies during the time of the study. The patients were further classified into three subgroups: subgroup 1A (43 patients with advanced AA), subgroup 2A (11 patients with mesenteric lymphadenitis) and subgroup 2B (10 patients with non-specific abdominal pain). The perforation rate was 32.7 %. WBC count and serum CRP, IL-6 and LBP were measured on admission. Area under receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity and predictive values were evaluated. Serum IL-6 and LBP were significantly higher in group 1 than in group 2. The highest AUC for AA was that for IL-6 (0.776), followed by WBC count (0.684), CRP (0.637) and LBP (0.635). In conclusion, only IL-6, determined on admission, showed medium diagnostic accuracy, while other laboratory markers showed low diagnostic accuracy for AA in children. The new laboratory markers therefore do not significantly improve the diagnosis of AA. PMID- 17366000 TI - Systemic immune response after open versus laparoscopic cholecystectomy in acute cholecystitis: a prospective randomized study. AB - OBJECTIVE: Laparoscopic surgery is thought to reduce the postoperative immunologic effects of surgical trauma. The aim of this study is to evaluate the influence of surgical trauma on systemic inflammation and the immune response in acute cholecystitis. MATERIAL AND METHODS: Thirty-three patients with acute calculous cholecystitis were assigned to laparoscopic cholecystectomy (LC, n=18) or open cholecystectomy (OC, n=15). Blood samples were obtained preoperatively and on postoperative day 1 (24 h after surgery) and day 3 (72 h after surgery), and blood concentration of C-reactive protein (CRP), leukocyte subpopulations, as well as levels of tumor necrosis factor-alpha (TNF-alpha) ex vivo secretion by peripheral blood mononuclear cells (PBMCs) were measured in both groups. RESULTS: Hospitalization was significantly shorter in the LC group than in the OC group (LC group: 3.7+/-1.2 days versus OC group: 6.3+/-2.7 days, p=0.010). There was no postoperative morbidity in the LC group, but two patients in the OC group had postoperative complications. Postoperative TNF-alpha ex vivo secretion by PBMCs and PBMC counts in the OC group were significantly lower than those in the LC group (p=0.002). The CRP level declined by postoperative day 3, but was significantly less in the OC group than in the LC group (p<0.001). Postoperative monocyte counts significantly decreased in the OC group compared with those in the LC group (p=0.001). CONCLUSIONS: A laparoscopic approach appears to cause less surgical trauma and immunosuppression than open surgery in patients with acute cholecystitis. PMID- 17366001 TI - Associations of resistin with inflammation and insulin resistance in patients with type 2 diabetes mellitus. AB - OBJECTIVE: Resistin has been linked to obesity, type 2 diabetes, inflammation and atherosclerosis but the results of animal and human studies have been at variance. The purpose of this study was to investigate the potential roles of resistin in patients with type 2 diabetes and to evaluate the correlation between resistin and markers of obesity, inflammation, insulin resistance, metabolic parameters, diabetes control and complications. MATERIAL AND METHODS: Fasting resistin, leptin, insulin, glucose, HbA1c, full lipid profile, C-reactive protein (CRP) (high sensitivity assay) and complete blood count were determined in 135 patients with type 2 diabetes. Univariate regression and multivariate logistic regression analyses were used to relate resistin with indices of obesity, inflammation, insulin resistance (homeostasis model, HOMA), insulin sensitivity, diabetic control, coronary heart disease (CHD) and degree of microalbuminuria. RESULTS: Resistin showed significant (p<0.05) correlations with body mass index (BMI) "(Spearman r=0.67), waist circumference (r=0.54), fasting insulin (0.51), insulin sensitivity (r=-0.29), HOMA (r=0.30), leptin (r=0.39), CRP (r=0.29), white cell count (r=0.25) and lipid parameters but showed no significant correlation with glucose and HbA1c. Partial correlation analysis, with correction for BMI, abolished the correlation of resistin with insulin sensitivity and HOMA but not with the white cell count. When confounding factors were fixed using multiple logistic regression, resistin was not independently associated with CHD (odds ratio=1.05, p=0.08) and degree of microalbuminuria (odds ratio=1.06, p=0.24). CONCLUSIONS: Resistin showed significant BMI-dependent associations with insulin resistance and factors linked with obesity and inflammation in patients with type 2 diabetes. Resistin may represent a link between obesity and insulin resistance via pro-inflammatory pathways. PMID- 17366002 TI - Decentralized glomerular filtration rate (GFR) estimates in healthy kidney donors show poor correlation and demonstrate the need for improvement in quality and standardization of GFR measurements in Sweden. AB - OBJECTIVE: Glomerular filtration rate (GFR) is generally accepted as the best overall index of renal function. Thus, all potential live kidney donors are tested to ensure that they have a normal GFR before they are eligible for kidney transplantation. The choice of GFR test is very much dependent on local traditions and may include iohexol, 51Cr-EDTA, inulin, or creatinine clearance based on urine collection, and creatinine clearance calculated from the Cockcroft Gault or Modification of Diet in Renal Disease (MDRD) equation as well as cystatin C. The aim of this study was to compare the results of GFR measurements performed in all actual live kidney donors who have undergone live donor nephrectomy at the University Hospital in Uppsala, Sweden, between the years 2000 and 2004. MATERIAL AND METHODS: The patients were selected from all parts of Sweden and the measurements were performed at their local hospital. RESULTS: We found large discrepancies between repeated iohexol measurements in these presumably healthy individuals. There was also a poor correlation between iohexol clearance and calculated creatinine clearance using the Cockcroft-Gault (R2=0.046) or MDRD formula (R2=0.045). CONCLUSIONS: The study shows that the standardization and quality of GFR measurements in Sweden have to be improved. PMID- 17366003 TI - Ophthalmic timolol: plasma concentration and systemic cardiopulmonary effects. AB - Timolol maleate is a non-selective beta-adrenoceptor antagonist currently used mainly as an ocular preparation for the treatment of glaucoma and ocular hypertension. Despite the topical administration, ophthalmic timolol causes systemic adrenergic beta-blocking because of absorption from the eye into the systemic circulation. Gel formulations of ophthalmic timolol have been developed to reduce systemic absorption and adverse effects in comparison with conventional aqueous solution formulations. Timolol is metabolized by the polymorphic cytochrome P450 2D6 enzyme (CYP2D6). The changes in heart rate (HR) are the most striking effects of the systematically absorbed fraction of ophthalmic timolol, with 0.5 % aqueous formulations presenting larger effects than 0.1 % hydrogel formulations, especially during exercise. Plasma levels of ophthalmic timolol correlate with the changes in HR. Neither 0.5 % aqueous nor 0.1 % hydrogel formulations of timolol have exerted noteworthy effects on systolic (SAP) or diastolic (DAP) arterial pressures, probably because of a compensatory increase in systemic vascular resistance due to the attenuation of HR. Ophthalmic timolol does not exert remarkable effects on pulmonary parameter peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) in non-asthmatic patients. CYP2D6 activity is clearly associated with the pharmacokinetic parameters, particularly when 0.5 % aqueous solution of timolol is used: peak plasma concentration, elimination half-life and area-under-the-curve are highest in CYP2D6 poor metabolizers. Finally, since there is a correlation between the plasma level of timolol and several haemodynamic effects - especially HR in the state of elevated beta-adrenergic tonus - the CYP2D6 poor metabolizers may be more prone to bradycardia during treatment with (aqueous) ophthalmic timolol. PMID- 17366004 TI - Pyrosequencing assay for genotyping of the Transcobalamin II 776C>G polymorphism. AB - The 776C>G polymorphism of the Transcobalamin II gene is located in a GC-rich region and TaqMan real-time polymerase chain reaction (PCR) does not yield satisfactory genotyping results. We therefore hypothesized that a method based on DNA sequencing would be needed for this single nucleotide polymorphism (SNP) analysis; Pyrosequencing technology was tested for this purpose. A Pyrosequencing protocol was developed, optimized and applied to a sample of 389 Swedish senior citizens. The three genotypes CC, CG, and GG consistently yielded typical programs that were readily distinguishable from each other. The prevalence of the mutated allele in the studied Swedish population was q=0.445. It is concluded that the TC II 776C>G polymorphism can be reliably genotyped by Pyrosequencing technology. PMID- 17366005 TI - Lack of randomness of internal quality control data: an alert for the in vitro diagnostic industry. PMID- 17366006 TI - The epidemiology of and risk factors for invasive Staphylococcus aureus infections in western Sweden. AB - We conducted a prospective study of all cases of invasive Staphylococcus aureus infections (ISA) in the catchment area of Skaraborg Hospital (population 255,109) in western Sweden from March 2003 to February 2005. The annual incidence was 33.9 cases/100,000 population. Of these, 49% were classified as community-acquired, 32% as nosocomial and 19% as health care-associated. The mean age was 65 y. We registered children (age < or = 18 y) in 13 episodes. The most common predisposing illnesses/conditions were persons undergoing haemodialysis (relative risk 291), peritoneal dialysis (relative risk 204), persons with rheumatoid arthritis (relative risk 9), diabetes mellitus (relative risk 8), and cancer (relative risk 7). The patients were treated at various departments; only 18% of the episodes were primarily cared for at a department of infectious diseases. The most common diagnosis was soft tissue infection (27% of the episodes), bacteraemia without focus (19%), arthritis (15%), and line-associated infection (14%). A total of 197 invasive isolates was obtained, the vast majority from blood, in 141 of 170 episodes. We documented the wide spectrum of signs and symptoms. One- quarter of the patients had no history of fever, and one-third of the bacteraemia patients had normal white blood cell count (<10 x 10(9)/l) at presentation. All cases were of MSSA (methicillin-sensitive Staphylococcus aureus). PMID- 17366007 TI - Pertussis seroprevalence in different age groups in Greece. AB - In order to target the appropriate age population for booster vaccination, we examined the antibody titres against pertussis toxin (PT) in different age groups in immunized and non-immunized individuals. In the immunized population, the highest anti-PT levels were observed in the 0- to 2-y age group and the lowest in the teenager and young adult groups. In contrast, in the control group, anti-PT levels were minimal in infants and young children, increasing in adolescence and early adulthood, and waning after 30 y of age. Antibody levels >30 U/ml were observed with higher frequency in children <2 y of age, in individuals with complete vaccination history and in non-immunized individuals. These findings may have important implications in optimizing vaccination policies. PMID- 17366008 TI - Antimicrobial susceptibility of invasive pneumococcal isolates from a region in south-west Sweden 1998-2001. AB - Invasive disease caused by antibiotic resistant pneumococci is a worldwide problem. All invasive pneumococcal strains in an area of south-west Sweden with 1.7 million inhabitants were collected prospectively during 1998-2001. Minimum inhibitory concentrations (MICs) were determined by E-test and correlated to serotypes and clinical characteristics. Of 827 strains, 744 (90%) were susceptible (S) to all agents tested and 83 (10%) were indeterminate (I) or resistant (R) to at least 1 agent. 22 isolates (2.7%) were I to penicillin (MIC >0.06 to < or = 1.0 mg/l), but none were R (MIC >1.0 mg/l). Numbers and proportions of decreased susceptibility against other agents tested were as follows: erythromycin R: 30 (3.6%), clindamycin R: 6 (0.7%), tetracycline R: 16 (1.9%), moxifloxacin R: 1 (0.1%), cotrimoxazole I: 17 (2%) and R: 31(4%). Non susceptibility to at least 1 agent was not correlated with age, clinical manifestation, underlying diseases and outcome. The serotype distribution differed between non-susceptible and susceptible strains. The serotypes in the 7 valent pneumococcal conjugate vaccine covered 42% of all infections and 73% of those caused by non-susceptible strains. In conclusion, the impact of antibiotic resistance in invasive pneumococcal disease remains limited in south-west Sweden. PMID- 17366009 TI - Diagnosis of meningococcal meningitis in Brazil by use of PCR. AB - Fever and a petechial rash are strongly associated with meningococcal disease in the city of Rio de Janeiro. Early antibiotic therapy is indicated and, consequently, a reduction of confirmed cases by culture, Gram stain, and latex agglutination test is expected. We evaluated a multiplex PCR assay to identify Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae in biological samples from cases of non-culture proven meningitis with a petechial rash at presentation. To detect DNA in cerebrospinal fluid (n = 71) or blood (n = 5), a PCR screen was performed, based on the crgA, ply and bexA targets, respectively. Of the total, 70 CSF and 3 blood samples (96%) were positive by PCR for the presence of N. meningitidis DNA. Another PCR assay predicted in 82% of these samples N. meningitidis serogroups A (2%), B (60%), C (7%), X (3%), Y (2%), 29E (2%) or W135 (24%). In non-culture proven meningitis, PCR was found to be a valuable adjunct for the demonstration of meningococcal aetiology. PMID- 17366010 TI - Chest X-ray findings in relation to gender and symptoms: a study of patients with smear positive tuberculosis in Vietnam. AB - The aim of the study was to analyse chest X-ray (CXR) findings among men and women with smear positive pulmonary tuberculosis (TB). All new cases of smear positive pulmonary TB diagnosed during 6 months in 23 districts in Vietnam were included in a cross-sectional study. 366 cases fulfilled the inclusion criteria. Pleuritis was demonstrated in 17% of the men's CXR versus 3% of the women's, p = 0.002. A miliary pattern was seen in 11% of the men's CXR versus 3% of the women's, p = 0.04. Hilar adenopathy was common and equally distributed among men and women (65% vs 61%). Dyspnoea was common among patients with pleuritis (67%) and a miliary pattern (65%). The radiological findings were more advanced in men than women, despite a similar time from symptom onset to diagnosis. The primary manifestations of TB found among men were unexpected in this setting with an HIV prevalence <0.1% at the time. The association with other risk factors for TB in men needs further investigation. The less advanced CXR findings in women may correspond to a slower rate of progression to smear positive disease, which would have implications for the possibilities of women to obtain a timely TB diagnosis. PMID- 17366011 TI - High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multidrug-resistant Acinetobacter baumannii. AB - The increased incidence of multidrug-resistant (MDR) Acinetobacter baumannii ventilator-associated pneumonia in critically ill patients poses a severe therapeutic problem. The aim of this study was to evaluate the efficacy and safety of 2 high-dose treatment regimens of ampicillin-sulbactam (A/S) for MDR Acinetobacter baumannii VAP. We undertook a randomized, prospective trial of critically ill patents with (MDR) Acinetobacter baumannii VAP. Patients were randomly assigned to 1 of 2 treatment regimens of A/S (at a rate 2:1 every 8 h): 1) group A, 18/9 g daily dose (n = 14); and 2) group B, 24/12 g daily dose (n = 13). The duration of therapy was 8+/-2 d for both groups. A total of 27 patients were enrolled in the study. Clinical improvement was seen in 66.7% of the study population in 9/14 (64.3%) of group A patients and 9/13 (69.2%) of group B patients, respectively. Bacteriological success was achieved in 77.8% of the study population (12/14, 85.7% of group A) and in 9/13 (69.2%) of group B patients. The 14-d mortality rate was 25.9% and the all cause 30-d mortality was 48.1%. Both mortality rates did not differ significantly between the 2 groups. No major adverse reactions were recorded. We concluded that clinical and bacteriological results of the study support the use of high-dose regimen of ampicillin-sulbactam for MDR Acinetobacter baumannii VAP. PMID- 17366012 TI - Immunoglobulin prophylaxis in 350 adults with IgG subclass deficiency and recurrent respiratory tract infections: a long-term follow-up. AB - 350 adult patients in Sweden were included in a retrospective study covering more than 2000 patient-y, to evaluate the efficacy of immunoglobulin (Ig) prophylaxis. All patients had selective or combined IgG subclass deficiency, without IgA deficiency, and suffered from recurrent respiratory tract infections (RTIs). The patients had been given Ig prophylaxis for 0.5-21 y (mean 5.5 y). In total, 164/350 of the patients had a concomitant lung disease. Because of the heterogeneity of this retrospective material we evaluated only those patients with 4 or more antibiotic-demanding (i.e. presumably bacterial) episodes of RTI per y treated with an Ig dose of about 100 mg/kg/week (132/350). The frequency of antibiotic treated RTIs prior to and during latest y/s of Ig prophylaxis was compared. No difference in response could be found between patients with and without chronic lung diseases. In 92/132 a > or = 50% reduction of the rate of episodes of antibiotic-demanding RTIs was recorded (p < 0.001). The overall reduction of the RTI frequency was for IgG1 57%, IgG2 59%, IgG3 63% and for the combinations 61% (all p<0.001). PMID- 17366013 TI - HIV related and non-HIV related mortality before and after the introduction of highly active antiretroviral therapy (HAART) in Norway compared to the general population. AB - The objective of the study was to compare the mortality in HIV infected individuals to the general population, and to explore the relative contribution of HIV to mortality before and after the introduction of highly active antiretroviral therapy (HAART). All HIV patients attending Ulleval University Hospital, Oslo, Norway before (cohort 1) and after (cohort 2) the introduction of HAART were included. Causes of deaths were classified as HIV related or not. Mortality in the Norwegian general population was standardized according to the distribution of age and gender in our cohorts. Ratios between mortality in our cohorts and the standardized mortality were calculated. The risk ratio (RR) for 5 y mortality compared to the general population was 22.6 (95% confidence interval (CI), 19.5-26.4) in cohort 1 (n = 782), and 3.96 (95% CI 2.25-6.97) in cohort 2 (n = 398). The non-HIV related mortality RR was 4.42 (95% CI 3.18-6.13) in cohort1 and 0.89 (95% CI 0.29-2.76) in cohort 2. Higher age and low CD4 cell count were associated with increased mortality. Thus, in the HAART era the mortality in HIV patients was reduced by 80%. However, the mortality in the HAART era was still 4 times higher than in the general population. PMID- 17366014 TI - Frequency of human papillomavirus infection in oesophageal squamous cell carcinoma in Iranian patients. AB - Human papillomavirus (HPV) is 1 of the possible aetiological factors in the development of oesophageal squamous cell carcinoma (ESCC). We aimed to study the role of HPV in ESCC. 140 cases of ESCC were analysed for the HPV DNA by polymerase chain reaction (PCR) using GP5+/GP6+ primers for L1 open reading frame (ORF) to amplify a 150 bp segment of HPV L1 ORF. This region was subsequently sequenced to identify the type of HPV. Of the 140 patients enrolled to our study 50.7% were female and 49.3% were male, aged between 20 and 81 y. 33 tumour specimens (23.6%) and 12 (8.6%) non-involved tumour margins were HPV positive. From HPV positive tumour cases 36% were positive in tumour margins. The HPV positive cases were 21.7% male and 25.3% female. There is no correlation between presence and types of HPV with patients' gender and age. The frequency of HPV subtypes in tumoural regions was as follows: HPV-16, 60.6%; HPV-18, 30.3%; HPV 33, 6.1%; and HPV-31, 3%. We found only HPV-16 in tumour margins. Our results are consistent with HPV studies conducted in other high-risk areas for ESCC and provided further evidence to support a causal association of HPV infection with ESCC. PMID- 17366015 TI - Prescription of antibiotic agents in Swedish intensive care units is empiric and precise. AB - Since the prescription of antibiotics in the hospital setting is often empiric, particularly in the critically ill, and therefore fraught with potential error, we analysed the use of antibiotic agents in Swedish intensive care units (ICUs). We examined indications for antibiotic treatment, agents and dosage prescribed among 393 patients admitted to 23 ICUs at 7 tertiary care centres, 11 secondary hospitals and 5 primary hospitals over a 2-week period in November 2000. Antibiotic consumption was higher among ICU patients in tertiary care centres with a median of 84% (range 58-87%) of patients on antibiotics compared to patients in secondary hospitals (67%, range 35-93%) and in primary hospitals (38%, range 24-80%). Altogether 68% of the patients received antibiotics during the ICU stay compared to 65% on admission. Cefuroxime was the most commonly prescribed antibiotic before and during admission (28% and 24% of prescriptions, respectively). A date for decision to continue or discontinue antibiotic therapy was set in 21% (6/29) of patients receiving prophylaxis, in 8% (16/205) receiving empirical treatment and in 3% (3/88) when culture-based therapy was given. No correlation between antibiotic prescription and laboratory parameters such as CRP levels, leukocyte and thrombocyte counts, was found. The treatment was empirical in 64% and prophylactic in 9% of cases. Microbiological data guided prescription more often in severe sepsis (median 50%, range 40-60% of prescriptions) than in other specified forms of infection (median 32%, range 21-50%). The empirically chosen antibiotic was found to be active in vitro against the pathogens found in 55 of 58 patients (95%) with a positive blood culture. This study showed that a high proportion of ICU patients receive antimicrobial agents and, as expected, empirical-based therapy is more common than culture-based therapy. Antibiotics given were usually active in vitro against the pathogen found in blood cultures. We ascribe this to a relatively modest antibiotic resistance problem in Swedish hospitals. PMID- 17366016 TI - West Nile virus in Spain: report of the first diagnosed case (in Spain) in a human with aseptic meningitis. AB - We report the first case of illness caused by West Nile virus (WNV) so far diagnosed in Spain. A 21-y-old male presented with clinical and biological signs compatible with viral meningitis. Acute and convalescent serum samples showed IgM and IgG positivity for WNV. These results were confirmed by microneutralization assays. PMID- 17366017 TI - Successful treatment of Pasteurella multocida meningitis with aztreonam. AB - This is the first reported case of the successful treatment of Pasteurella multocida meningitis with aztreonam in a patient with multiple antibiotic allergies. PMID- 17366018 TI - Infective endocarditis caused by daptomycin-resistant Enterococcus faecalis: a case report. AB - Daptomycin is a first-in-class antibiotic with efficacy against Gram-positive bacteria. We document the second report of daptomycin resistance in a clinical isolate of Enterococcus faecalis. PMID- 17366019 TI - Fatal myocarditis due to Clostridium novyi type B in a previously healthy woman: case report and literature review. AB - Clostridium novyi is a Gram-positive anaerobe, which is commonly a pathogen of domestic and wild animals. Disease in humans typically presents as myonecrosis. C. novyi has not previously been reported as a cause of myocarditis. We report a fatal case with infection of the myocardium by C. novyi type B. PMID- 17366020 TI - Fatal Salmonella enteritidis septicaemia in a rheumatoid arthritis patient treated with a TNF-alpha antagonist. AB - We report a patient with a rare presentation of extra-intestinal salmonellosis after infliximab therapy for rheumatoid arthritis. We discuss the increasing incidence of primary infections and reactivation of intracellular microorganisms after treatment with TNF-alpha blockage, with emphasis on salmonellosis. PMID- 17366021 TI - Neurological morbidity and the pertussis vaccine: an old story revisited. AB - We describe 3 children with neurological disorders that developed in association with their receipt of the whole-cell pertussis vaccine. Newer studies supported the ability of the wP vaccine to adversely affect the CNS. The possibility that it worsened their clinical course in infancy by causing additional damage should not be disregarded. PMID- 17366022 TI - Scedosporium prolificans brain abscess in a patient with chronic granulomatous disease: successful combination therapy with voriconazole and terbinafine. AB - A patient with chronic granulomatous disease developed brain abscesses with Scedosporium prolificans. In vitro susceptibility revealed a synergistic effect of terbinafine and voriconazole. He received therapy with both these antifungals which resulted in disappearance of the brain abscesses. This is the first reported cure of a CNS S. prolificans infection in an immunocompromised host. PMID- 17366023 TI - Unusual onset of varicella zoster reactivation with meningoencephalitis, followed by rhabdomyolysis and renal failure in a young, immunocompetent patient. AB - We present an unusual onset of meningoencephalitis due to VZV reactivation, with increased intrathecal production of IgG VZV antibodies and negative PCR, in a young, immunocompetent adult. Herpes zoster erupted 5 d later. Rare complication of VZV-related rhabdomyolysis occurred, with subsequent ARF, in combination with acyclovir and ceftriaxone. The patient recovered fully and remained healthy. PMID- 17366024 TI - Acute renal failure caused by intravenous acyclovir for disseminated varicella zoster virus infection. PMID- 17366025 TI - Gender differences in infective endocarditis: pre- and co-morbid conditions lead to different management and outcomes in female patients. AB - The impact of gender on the presenting characteristics, management, and outcomes in infective endocarditis (IE) has not been adequately studied. The goal of our study was to better understand differences in management and outcome of IE between genders. Data were obtained prospectively from 439 patients in the Duke Endocarditis Database from 1996 to 2004. Baseline characteristics of patients were examined using univariable analysis. Variables associated with gender, in hospital surgery and long-term mortality in patients with IE were considered for multivariable analysis. Hemodialysis, diabetes mellitus, and immunosuppression were more frequent in female patients with IE. Intracardiac abscesses and new conduction abnormalities were more common in male patients. The following factors were predictive of short-term mortality through univariable analysis: female gender, age, diabetes mellitus, septic pulmonary infarcts, intracranial hemorrhage, infection with Staphylococcus aureus, and persistently positive blood cultures. Female gender was not associated with mortality in an adjusted analysis of short-term outcome. Age, diabetes mellitus, renal failure requiring hemodialysis, cancer, pulmonary edema, systemic embolization, persistently positive blood cultures, and chronic indwelling central catheters but not female gender were associated with long-term mortality using univariable and an adjusted analysis. In both analyses, surgery was associated with improved mortality. Female gender, a history of diabetes mellitus, hemodialysis, and immunosuppression therapy were predictive of a medical management without the use of surgery, although in the adjusted analysis there was no association between surgery and gender. In conclusion, differences between genders in treatment and outcomes frequently reported in patients with IE most likely result from pre- and co-existing conditions such as diabetes mellitus, renal failure requiring hemodialysis, and chronic immunosuppression. PMID- 17366026 TI - An outbreak of botulism in a family in Eastern Anatolia associated with eating suzme yoghurt buried under soil. AB - Cases of botulism in a family in eastern Anatolia were studied. In late September 2005, an outbreak of botulism developed in our region, first in 2 patients, a teenage boy and his mother, in whom the disease culminated in respiratory insufficiency and death. An additional 8 cases of botulism were identified later; most of them presented to our medical centre the next d. These patients with milder symptoms recovered gradually. All the patients received anti-botulinum toxin. The investigation of the source of the outbreak showed an unexpected vehicle for botulism infection in the these patients, suzme (condensed) yoghurt buried under soil. Type A botulinal toxin was detected in the yoghurt sample. The clinical diagnosis was also confirmed by a mouse bioassay performed with the serum samples of the patients. The most common symptoms were dry mouth, difficulty in speaking and swallowing, and change in voice quality. The 10 identified patients with botulism constitutes the largest-ever outbreak of botulism reported in Turkey to date. The present study shows the importance of considering a diagnosis of botulism soon after patients present with acute cranial nerve dysfunction and of promptly treating suspected cases with antitoxin. PMID- 17366027 TI - Efficacy of humanlike Augmentin SR (2000/125 mg) twice daily treatment on Haemophilus influenzae experimental pneumonia in rabbits. AB - We investigated the efficacy of 2 formulations of Augmentin on experimental pneumonia due to Haemophilus influenzae (HI) in rabbits. Two strains were used (H128 and 401285) with amoxicillin/clavulanic acid MICs of 1/0.5 mg/l and 4/2 mg/l. Pneumonia was induced in immunocompetent rabbits by inoculation of 10 log(10) CFU HI. The treatments were infused by using computer controlled pumps in order to mimic the human pharmacokinetic (PK) profile of either conventional Augmentin treatment (875/125 mg twice daily) or the sustained release formulation (SR: 2000/125 mg twice daily). After 2 d of treatment, the bacterial concentrations in the lungs were similar for both strains and both treatments: isolate H128, conventional Augmentin reduced bacterial numbers to 3.8+/-2.1 log(10) CFU/g and Augmentin SR to 3.1+/-2.4 log(10) CFU/g; isolate 401285, conventional Augmentin to 3.5+/-2. Thus, both treatments demonstrated similar efficacy against H. influenzae pneumonia in this model, even when induced by a strain with an amoxicillin/clavulanic acid MIC of 4/2 mg/l. These results support current breakpoints for conventional Augmentin against H. influenzae and suggest that Augmentin SR is at least as effective against these isolates. PMID- 17366028 TI - Streptococcus pneumoniae and Legionella pneumophila pneumonia in HIV-infected patients. AB - We compared the epidemiological data, clinical features and mortality of community-acquired pneumonia (CAP) by Streptococcus pneumoniae and Legionella in HIV-infected patients and determined discriminative features. An observational, comparative study was performed (January 1994 to December 2004) in 15 HIV patients with CAP by Legionella and 46 by S. pneumoniae. No significant differences were observed in delay until initiation of appropriate antibiotic therapy. Smoking, cancer and chemotherapy were more frequent in patients with Legionella pneumonia (p=0.03, p=0.00009 and p=0.01). Patients with Legionella pneumonia had a higher mean CD4 count (p=0.04), undetectable viral load (p=0.01) and received highly active antiretroviral therapy more frequently (p=0.004). AIDS was more frequent in patients with S. pneumoniae pneumonia (p=0.03). Legionella pneumonia was more severe (p=0.007). Extrarespiratory symptoms, hyponatraemia and increased creatine phosphokinase were more frequent in Legionella pneumonia (p=0.02, p=0.002 and p=0.006). Respiratory failure, need for ventilation and bilateral chest X-ray involvement were of note in the Legionella group (p=0.003, p=0.002 and p=0.002). Mortality tended to be higher in the Legionella group (6.7 vs 2.2%). In conclusion, CAP by Legionella has a higher morbimortality than CAP by S. pneumoniae in HIV-infected patients. Detailed analysis of CAP presentation features allows suspicion of Legionnaires' disease in this subset. PMID- 17366029 TI - Efficacy of serum procalcitonin in evaluating severity of community-acquired pneumonia in childhood. AB - Microbe-specific diagnosis of community-acquired pneumonia (CAP) in childhood is difficult in clinical practice. Chest radiographs and non-specific inflammatory markers have been used to separate presumably bacterial from viral infection but the results have been inconsistent. The aim of the present study was to evaluate the usefulness of procalcitonin (PCT) in assessing the severity as well as the bacterial or viral aetiology of CAP. Serum PCT was measured by an immunoluminometric assay in 100 patients with CAP; 26 were treated as inpatients and 74 as outpatients. The pulmonary infiltrate was considered to be alveolar in 62 and interstitial in 38 cases, according to the radiological diagnosis. The bacterial and viral aetiology of pneumonia was studied by an extensive serological test panel. No differences were found in PCT concentrations between the 4 aetiological (pneumococcal, atypical bacterial, viral, unknown) and the 3 age (< 2, 2-4 and > or = 5 y) groups. Serum PCT was >0.5 ng/ml in 69%, >1.0 ng/ml in 54% and >2.0 ng/ml in 47% of all patients. PCT was higher in patients that were admitted than as outpatients (medians 17.81 vs 0.72 ng/ml, respectively, p<0.01) and higher in alveolar than in interstitial pneumonia (medians 9.43 vs 0.53 ng/ml, respectively, p<0.01). In conclusion, serum PCT values were found to be related to the severity of CAP in children even though they were not capable, at any level of serum concentration, to differentiate between bacterial and viral aetiology. PMID- 17366030 TI - Non-tuberculous mycobacteria in China. AB - Infection with non-tuberculous mycobacteria (NTM) is relatively rare in areas that are high-endemic for tuberculosis. We identified 126 strains of NTM in respiratory specimens collected by the Chinese Nationwide Survey in 2000, the Beijing Tuberculosis and Thoracic Tumour Institution, and the Guangzhou Thoracic Hospital. Species diagnosis was attained by sequencing of 16S-rDNA complemented by phenotypic characterization when necessary. Mycobacterium avium-intracellulare complex - well known as a potential pulmonary pathogen - was diagnosed in all 3 surveys. Potentially pathogenic rapid growing strains of M. abscessus, M. chelonae and M. fortuitum were also detected. Moreover, species non-pathogenic in the airways such as M. nonchromogenicum, M. terrae and M. gordonae were encountered. Also, single strains of rare NTM species were isolated. Thus, several potentially pathogenic species of NTM were isolated from pulmonary specimens in China, and molecular techniques made possible exact species diagnosis. PMID- 17366031 TI - Drug resistance of Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. AB - Spread of drug-resistant tuberculosis (TB) threatens TB-control programmes, and all countries need to monitor the patterns and trends of anti-TB drug resistance. Such data assess the quality of control programmes and help forecast future trends of drug resistance. It will also help to establish guidelines for TB therapy. The aim of the current study was to describe the rate of drug-resistant Mycobacterium tuberculosis in the Sunamganj District of Bangladesh. Bacterial isolates were collected from sputum smear positive (ss+) patients who attended the National TB Programme from November 2003 to December 2004. A total of 95 isolates was tested for susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) at the National Reference Laboratory for Mycobacteria at the Norwegian Institute of Public Health (NIPH), Oslo. The total resistance among new cases to any drug was 31%. For SM it was 18%, INH 23%, RMP 2%, EMB 10% and 2% were multidrug-resistant (MDR). The National Tuberculosis Programme (NTP) in Sunamganj is still effective, although the high resistance to INH is alarming. An increased risk of treatment failure has been demonstrated in areas with high levels of INH resistance, and a high proportion of INH resistant cases may develop resistance to RMP during treatment. PMID- 17366032 TI - Clinical experience of urine D-arabinitol/L-arabinitol ratio in the early diagnosis of invasive candidiasis in paediatric high risk populations. AB - In 2 prospective studies, we previously reported on the early and accurate diagnosis of invasive candidiasis by determining the D-arabinitol/L-arabinitol (DA/LA) ratio in urine in neutropenic children with cancer at the paediatric oncology unit (POU) and in premature infants at the neonatal intensive care unit (NICU) at our hospital. In this retrospective study at the same units, we report how the DA/LA assay was implemented in clinical practice immediately after the prospective study periods. We found that, in the POU, the recommendation of regularly monitoring urine DA/LA ratios in patients at risk and considering antifungal therapy in the case of elevated ratios had been followed. A significant decrease in the incidence of culture positive invasive candidiasis may have been attributed to the introduction of the DA/LA assay. At the NICU, where the DA/LA assay was recommended only as an adjunct to other diagnostic tools, morbidity in invasive candidiasis remained unchanged. While regular monitoring of the urine DA/LA ratio probably facilitates the early detection of invasive candidiasis in paediatric oncology, it remains to be determined if the test can be used in a similar way in neonatal intensive care. PMID- 17366033 TI - Positive rate of serum SARS-CoV immunoglobulin G antibody among healthcare workers. AB - We evaluated the positive rate for severe acute respiratory syndrome (SARS) -CoV IgG antibody among Taiwanese healthcare workers (HCWs). A retrospective cohort research was performed in 2 teaching hospitals and 2 non-teaching hospitals. SARS CoV IgG antibodies were checked and a structured questionnaire was prepared. A total of 2512 sets of questionnaires was distributed with a return rate of 87.5% (2197 sets). 882 of the respondents had contact with SARS patients. Among 2197 subjects studied, a total of 9 subjects (0.4%) displayed positive findings for SARS-CoV IgG antibody. The relative risk (RR) of contracting SARS for HCWs in the emergency room (ER) was estimated to be 25.94 times greater than the corresponding risk for those HCWs who worked in the ordinary ward (95% CI 7.07 95.14, p<0.001). If we estimated the HCWs who came into contact with SARS patients, the RR for positive serum IgG antibody titer among HCWs from the ER was significantly greater than it was for those working in the ordinary ward (RR 9.45, 95% CI 2.58-34.64, p=0.001). In conclusion, HCWs from the ER faced a relatively high risk for potential infection by the SARS virus when caring for patients who had not been diagnosed with SARS. PMID- 17366034 TI - Contribution of procalcitonin to occult bacteraemia detection in children. AB - We conducted a prospective study in 215 children, 3 to 36 months of age, presenting with fever > or = 39 degrees C without obvious origin, in order to evaluate the diagnostic value of procalcitonin (PCT) in detection of occult bacteraemia. PCT associated with white blood cell count constitutes an efficient screening method with sensitivity 100%, specificity 61.9% and positive and negative likelihoods ratios of 2.62 and 0, respectively. PMID- 17366035 TI - Campylobacter, polyneuropathy, and Guillain-Barre syndrome in Denmark, 1994-2003. AB - We examined the incidence of Campylobacter infections, Guillain-Barre syndrome and unspecified polyneuropathies in an ecological study from 1994 to 2003. The increase in Campylobacter cases in Denmark in the 1990s was comparable to an increase in cases of unspecified polyneuropathies; however, the incidence of Guillain-Barre syndrome cases remained stable during the period. PMID- 17366036 TI - Serum myeloperoxidase in cystic fibrosis patients receiving systemic antibiotics. AB - Serial serum myeloperoxidase was determined in 27 cystic fibrosis patients with chronic endobronchial Pseudomonas aeruginosa infection over the course of 1 y. The effect of repeated courses of antibiotic therapy on mean serum myeloperoxidase levels was significant (p = 0.034). Serial serum myeloperoxidase may help to guide therapy for pulmonary exacerbations. PMID- 17366037 TI - Fatal Pasteurella multocida septicemia and necrotizing fasciitis related with wound licked by a domestic dog. AB - A 68-y-old male had necrotizing fasciitis and bacteremia due to Pasteurella multocida. Saliva culture from his dog grew P. multocida and Pseudomonas aeruginosa. The human and dog P. multocida strains were of the same antibiogram but not identical tested with ribotyping. The wound licked by his dog was the only risk factor. PMID- 17366038 TI - Shigella sonnei bacteremia: two adult cases and review of the literature. AB - Shigella sonnei bacteremia in adult patients is rare. We present 2 cases from our center, and 7 others from the literature are reviewed in detail. Diabetes mellitus and malignancy are frequent predisposing conditions. Despite severe illness at presentation, our patients achieved good outcomes with prompt initiation of antimicrobial therapy. PMID- 17366039 TI - A haemophagocytic lymphohistiocytosis (HLH)-like picture following breastmilk transmitted cytomegalovirus infection in a preterm infant. AB - Due to septic illness, neutro- and thrombocytopenia, blocked myelopoiesis, CMV positive breast milk and CMV-pp65 antigen in bone marrow mononuclear cells, CMV related HLH was presumed in a breast fed neonate (gestational age 24 weeks). Treatment was successful with foscarnet and methylprednisolone. HLH may be a complication of post-natal CMV-infection acquired from breast milk. PMID- 17366040 TI - Portal hypertension caused by acute cytomegalovirus infection with liver involvement in an immunocompetent patient. AB - Primary infection by cytomegalovirus in immunocompetent patients is usually unapparent. We report a case of severe acute cytomegalovirus infection in a young immunocompetent male with pulmonary and hepatic involvement and portal hypertension who recovered without specific antiviral therapy with complete resolution of sonographic signs of portal hypertension after 6 months. PMID- 17366041 TI - Infectious tenosynovitis and osteomyelitis caused by Mycobacterium nonchromogenicum. AB - Infections due to Mycobacterium terrae complex are rare. We report a severe case of chronic tenosynovitis and osteomyelitis of the hand caused by Mycobacterium nonchromogenicum requiring second ray finger amputation. PMID- 17366042 TI - Infective endocarditis due to Actinomyces neuii. AB - Actinomyces endocarditis is very rare. At present the only Actinomyces species identified causing endocarditis are A. israelii, A. bovis, A. viscosus, A. pyogenes, A. meyeri and A. funkei. We here report the first case of endocarditis caused by Actinomyces neuii. PMID- 17366043 TI - Fatal Staphylococcus aureus haemorrhagic pneumonia producing Panton-Valentine leucocidin. AB - We present 2 cases of community acquired S. aureus pneumonia carrying Panton Valentine leucocidin (PVL). These cases illustrate this clinical entity characterized by a younger and healthier population than usual staphylococcal pneumonias and complicated by a 75% mortality rate. We also discuss the diagnosis and therapeutic difficulties. PMID- 17366044 TI - Myalgia and swelling of interphalangeal joints as side-effect of prolonged azithromycin therapy in patient with pelvic actinomycosis: case report. PMID- 17366045 TI - Myasthenia and neuroborreliosis with excessively high acetylcholine-receptor antibodies. AB - In a 29-y-old male with neuroborreliosis, partially responsive to ceftriaxone, myasthenia gravis with acetylcholine-receptor antibodies elevated almost 1000 times the upper reference limit was diagnosed. Pyridostigmine resolved all remaining neurological deficits. During a 1-y follow-up the patient remained symptom free, despite persistently high acetylcholine-receptor antibodies. They were attributed to epitope homology of the acetylcholine receptors and Borrelia surface antigens. PMID- 17366046 TI - A rare case of hepatitis associated with cefprozil therapy. AB - Cefprozil is a novel third generation, broad-spectrum oral cephalosporin. Serum sickness-like reaction and rash caused by cefprozil have been previously reported, but liver damage has not been documented. We report on a 15 years-old female with tonsillopharyngitis who developed hepatitis after treatment with cefprozil. Following discontinuation of cefprozil therapy, her liver functions returned to normal limits within four weeks. We suggest that for patients presenting with hepatitis associated with drugs, Cefprozil should be considered in the differential diagnosis of hepatitis. PMID- 17366047 TI - In-hospital and long-term mortality in infective endocarditis in injecting drug users compared to non-drug users: a retrospective study of 192 episodes. AB - In a retrospective study, in-hospital and long-term mortality for patients with infective endocarditis (IE) was analysed. The study was conducted at a department of infectious diseases in Stockholm, Sweden. Mortality was compared between injecting drug users (IDUs) and patients without drug abuse (non-IDUs). 192 episodes of IE from 1995 to 2000 were analysed, 60 in IDUs and 135 in non-IDUs, median follow-up 4.4 y. Episodes were classified using the Duke criteria: 145 definite and 47 possible. Of 53 definite episodes in IDUs, 55% were right-sided IE and 43% left-sided IE (including combined left- and right-sided). Surgical treatment was used in 34/145 definite episodes, all being left-sided IE. The in hospital mortality was 14/145 (9.6%). There was no difference in in-hospital mortality between patient groups with left-sided IE. The IDU patients with left sided IE had a higher long-term mortality with the increased mortality rate explained by late deaths in the surgically treated IDUs. Treatment results for IDUs with right-sided IE were good with no in-hospital mortality, no relapses and no increase in long-term mortality. This difference in prognosis between left sided and right-sided IE in IDUs makes high quality echocardiography important to identify patients with left-sided IE and worse prognosis. PMID- 17366048 TI - Asymptomatic Brucella bacteraemia and isolation of Brucella melitensis biovar 3 from human breast milk. AB - Brucellosis is a zoonotic disease and virtually all infections derived from exposure to animals or ingestion of unpasteurized dairy products. Brucellosis among family members has been reported. However, screening household members of an index case of acute brucellosis is not a routine procedure. A 10-y-old boy was diagnosed with acute brucellosis. Unpasteurized goat cheese commonly consumed within the family was thought to be the possible source of the bacteria. The family (parents, sister and brother) was screened with physical examination, serum tube agglutination test, blood cultures and routine laboratory tests. Three additional cases (parents and sister) of serological and culture proven brucellosis were detected. Two of them (mother and sister) were asymptomatic and had no clinical findings. Brucella melitensis biovar 3 was isolated from breast milk culture and from all blood cultures of 4 brucellosis cases. In conclusion, brucellosis, even with bacteraemia, can be completely asymptomatic. Consumption of raw milk products by household members is a common risk factor for brucellosis outbreak among family members. Thus, screening household members of an index case of brucellosis can expose new brucellosis cases. PMID- 17366049 TI - Pooling of urine specimens allows accurate and cost-effective genetic detection of Chlamydia trachomatis in Lithuania and other low-resource countries. AB - The aims of this study were to compare performance characteristics and cost effectiveness of pooling urine samples for screening and diagnosis of Chlamydia trachomatis using Digene Hybrid Capture II CT/NG Test (HCII), and to examine the prevalence of C. trachomatis in male military recruits in Lithuania. A total of 410 urine samples were individually tested and pooled by 5 and 10 samples, respectively. The sensitivity and specificity of diagnosis were not affected by either pooling strategy. The estimated population prevalence of C. trachomatis infection was nearly identical, i.e. 4.4%, 4.4% and 4.1% based on individually tested samples, and samples pooled by 5 and 10, respectively. For this estimation of the population prevalence, pooling 5 samples reduced the costs by 80% and pooling 10 samples reduced the costs by 90%. For diagnosis of each individual sample, the pooling strategies resulted in cost savings of 60% (5 samples per pool) and 56% (10 samples per pool). The present pooling strategies were sensitive, specific and cost-efficient for screening and diagnosis of C. trachomatis infection in male military recruits in Lithuania. The strategies would be most useful for reasonably inexpensive large-scale screening, prevalence studies and even diagnostics in Lithuania and many other low-resource countries. PMID- 17366050 TI - Nosocomial Legionnaires' disease caused by Legionella pneumophila serogroup 6: implication of the sequence-based typing method (SBT). AB - Sequence-based typing (SBT) was used to determine the allelic profiles of 3 sporadic clinical isolates as well as 7 environmental isolates of Legionella pneumophila serogroup 6, isolated at the Karolinska Hospital during 2004. The clinical isolates were cultured from patients with nosocomial Legionnaires' disease (LD), while the environmental isolates were cultured from potable water sources of the hospital wards in the close vicinity of the 3 patients being investigated. The genes sequenced for the construction of the SBT profile included flaA, pilE, asd, mip, mompS and proA, in this pre-determined order and the allelic profile of the 10 isolates was identical (3, 13, 1, 28, 14, 9). Furthermore, 2 of the isolates, 1 clinical and 1 environmental, were analysed using the amplified fragment length polymorphism analysis (AFLP). The AFLP genotype of both isolates was congruent. Eight of 9 control L. pneumophila serogroup 6 isolates had the same SBT profile as the study isolates. We conclude that the environmental strain isolated from our hospital's drinking water is indistinguishable genotypically from the 3 clinical isolates of Legionella. However, this genotype of L. pneumophila is geographically widespread. Thus, results of genotyping must be evaluated in conjunction with the clinical and epidemiological data. PMID- 17366051 TI - A community outbreak of Legionnaires' disease from an industrial cooling tower: assessment of clinical features and diagnostic procedures. AB - An outbreak of Legionnaires' disease (LD) occurred in Lidkoping, Sweden, in August 2004. A cooling tower was identified as the probable source of infection. During the outbreak period an unexpected 3-6-fold increase in pneumonia patients was noted at the local hospital. During 7 weeks LD was diagnosed in 15 patients by urinary antigen and/or sputum culture. Additionally, 15 LD patients were diagnosed later by serology. Patients with LD were generally younger, more healthy, and more often smokers compared to other pneumonia patients. On admittance they had more severe symptoms with high fever and raised CRP levels, and more often hyponatraemia, gastrointestinal and CNS symptoms. A causative agent besides Legionella was found in 2 patients only. A significant titre rise for Mycoplasma and/or Chlamydophila pneumoniae was found in 13 of 29 tested patients with confirmed LD. We conclude that the clinical diagnosis of LD is difficult and that available diagnostic methods detect only a minority of patients in the acute phase. Therefore in severe pneumonia, empirically targeted therapy should be instituted on clinical grounds irrespective of the results of diagnostic tests. The observation of increased antibody levels for M. and C. pneumoniae suggests an unspecific immune reaction and merits further study. PMID- 17366052 TI - Endogenous ocular candidiasis: changes in epidemiology and factors associated with poor functional outcome. AB - The evolution of the incidence and the epidemiology of ocular candidiasis in our hospital during the past 12 y, as well as the factors associated with poor functional outcome were analysed. A retrospective study of all cases of ocular candidiasis admitted to a university hospital between 1993 and 2004 was performed. Epidemiological, clinical and final outcome data were recorded. 37 episodes of ocular candidiasis in 36 patients were studied. 28 (75%) episodes occurred between 1993 and 1998 (13.09 episodes/100,000 admissions/y), and all of these patients were intravenous drug users. In contrast, only 9 episodes of ocular candidiasis were recorded between 1999 and 2004 (4.42 episodes/100,000 admissions/y; p<.0001) and 3 (33%) patients were not drug users (p<0.01). 19 (57%) cases had final visual acuity <0.1. Treatment with conventional amphotericin B instead of other newer antifungal drugs was associated with poor visual prognosis in the univariate (p = 0.03) and multivariate (p = 0.03) analysis. In conclusion, the incidence of ocular candidiasis has decreased significantly in recent y and the epidemiology has changed. Currently, one-third of patients are immunocompromised non-drug users. Therapy with conventional amphotericin B instead of newer antifungal drugs appears to be associated with a poorer functional outcome. PMID- 17366053 TI - Seroprevalence of Toxoplasma gondii, rubella and cytomegalovirus among pregnant women in southern Turkey. AB - Primary infections caused by Toxoplasma gondii, rubella and cytomegalovirus (CMV) can lead to serious complications in pregnant women. The aim of this study was to determine the seroprevalence of Toxoplasma, rubella and CMV infections through antenatal screening. In this study, the consecutive records of 1652 pregnant women examined between the period March 2004 to January 2006 were included. The results of the antenatal screening for Toxoplasma, rubella and CMV during the first trimester of pregnancy were evaluated. Anti-Toxoplasma, anti-rubella and anti-CMV IgG and IgM antibodies were assayed using an enzyme linked immunosorbent assay method. Of the 1652 pregnant women tested, anti-Toxoplasma IgG antibody was found in 860 (52.1%) of the cases, while 9 (0.54%) of the subjects tested positive for anti-Toxoplasma IgM. Anti-rubella IgG and IgM antibodies were reactive in 1570 (95.0%), and in 9 (0.54%) of the tested women, respectively. Moreover, 1568 (94.9%) of them were found to be positive for anti-CMV IgG, while 7 (0.4%) tested positive for anti-CMV IgM. Consequently, because of the high seropositivity of T. gondii, rubella and CMV in the pregnant women, the country's health authorities should be alerted, and preventive measures should be taken. PMID- 17366054 TI - Post-transplant lymphoproliferative disease and other Epstein-Barr virus diseases in allogeneic haematopoietic stem cell transplantation after introduction of monitoring of viral load by polymerase chain reaction. AB - The clinical value of monitoring of Epstein-Barr virus (EBV) viraemia by quantitative polymerase chain reaction during 1 y was evaluated. 39 recipients of allogeneic hematopoietic stem cell transplantation (SCT) were followed. More than 100 EBV genome equivalents (gEq)/ml in blood or plasma were found in 16/39 patients (41%) at 34 d (range 1-139) post-transplant. Seven of these 16 patients developed EBV disease; 3 post-transplant lymphoproliferative disease (PTLD), 1 myelitis, 1 encephalitis and 2 reactivations with fever. EBV diseases were only found in the high-risk group among recipients of mismatched related or unrelated donor grafts or in patients who underwent reduced-intensity conditioning. In this group, 3/20 (15%) developed PTLD. Conditioning with antithymocyte globulin was significantly associated with EBV disease (p<0.01). EBV load in plasma was more strongly associated with EBV disease than viral load in blood. A cut-off level of 1000 gEq/ml plasma distinguished EBV disease from asymptomatic viraemia, but not PTLD from other EBV diseases. Weekly monitoring of EBV load in plasma in high risk patients in the first 3 months following SCT seems to be of value for prediction of EBV disease. Therapy for PTLD including rituximab was evaluated during 2 y and showed response in 4/6 cases. PMID- 17366055 TI - Liver biopsy performance and histological findings among patients with chronic viral hepatitis: a Danish database study. AB - We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis (> or =F2) and 13.9% had cirrhosis (F4). The frequency of cirrhosis varied from 8.3 to 18.6% among centres, and was independently associated with age, male gender, elevated alanine aminotransferase (ALT) and non-Danish origin. Among 141 patients with hepatitis C and known duration of infection, cirrhosis had developed in 23% after 20 y of infection. Age above 40 y was a better predictor of cirrhosis than elevated ALT. National database comparison may identify factors of importance for improved management of patients with chronic viral hepatitis. PMID- 17366056 TI - Respiratory picornavirus infections in Korean children with lower respiratory tract infections. AB - Recently, human rhinoviruses (RVs) and enteroviruses have been suggested as important etiological agents in young children with lower respiratory tract infections (LRTIs). We investigated the role of respiratory picornaviruses in hospitalized children with LRTI. A total of 233 nasopharyngeal samples were collected from hospitalized children with LRTIs from July 2004 to January 2006. All specimens were tested for the presence of human respiratory syncytial virus (hRSV), influenza virus A, influenza B, parainfluenzavirus, and adenovirus using direct immunofluorescent assay, and for human metapneumovirus (HMPV) by RT-PCR. Detection of RV was performed in nasopharyngeal samples by a RT-PCR assay that incorporated a BglI restriction enzyme digestion of the picornavirus RT-PCR amplicon, and detection of enterovirus was accomplished by hemi-nested RT-PCR using specific primers. Viral agents were detected in 70.4% (164/233) of the study population. The most frequently detected viruses were RV (64/233, 27.4%), hRSV (48/233, 20.6%), and enterovirus (43/233, 18.4%). Picornaviruses were detected as the sole viral agents in 27.0% (63/233) of children, whereas mixed viral infection was detected in 12.0%. These results suggest that picronavirus infection is an important etiological cause of LRTIs in Korean children. PMID- 17366057 TI - P. vivax malaria complicated by shock and ARDS. AB - We report a case of Plasmodium vivax malaria complicated by shock and ARDS. The patient responded to oral chloroquine and primaquine and PCR was positive for P. vivax DNA and negative for P. falciparum DNA. P. vivax may cause severe complications and where the possibility of mixed infections exists, blood should be sent for PCR analysis so that mixed infections can reliably be excluded. PMID- 17366058 TI - Cutaneous Salmonella infection. AB - Pustular dermatitis caused by Salmonella stanley developed on the arm of a veterinary surgeon after the delivery of a dead bovine calf. The vet did not develop any systemic symptoms and made a full recovery. This is the only report of cutaneous infection caused by this organism. PMID- 17366059 TI - Cerebral abscesses complicating tularemia meningitis. AB - Tularemia meningitis is a distinctly rare entity with only 14 cases reported in the literature, half of which occurred prior to 1950. In this case we provide the first description of cerebral microabscesses which occurred as a complication of tularemia meningitis. PMID- 17366060 TI - Visceral leishmaniasis with aplastic bonemarrow: coincidental or causal. AB - Acquired aplastic anaemia (AAA) is caused by aetiologies ranging from infectious agents, chemical toxins, drugs, and autoimmune disorders. Few reports exist which establish a causal association of parasites in AAA. Causal association of Leishmania donavani infection in AAA has not been reported to date. PMID- 17366061 TI - Case of bacteraemic cellulitis by a non-haemolytic strain of Streptococcus pyogenes. AB - Erysipelas and bacteraemia with what initially was diagnosed as a non-haemolytic streptococcus is reported. As neither colony morphology nor clinical picture was characteristic of non-haemolytic streptococci, the isolate was sent to a reference laboratory. 16S rRNA sequencing and phenotypic characterization identified the strain as a streptolysin S-deficient S. pyogenes.. PMID- 17366062 TI - First detection of a VIM-1 metallo-beta-lactamase in a carbapenem-resistant Citrobacter freundii clinical isolate in an acute hospital in Germany. AB - We report the first detection of a carbapenem-resistant Citrobacter freundii clinical strain in Germany. It was isolated from an abscess of a patient with acute necrotic pancreatitis in an acute hospital. PCR and sequencing experiments revealed that the carbapenem resistance was mediated by a VIM-1 metallo-beta lactamase, located on a plasmid encoded class 1 integron. Carbapenem resistance in Enterobacteriaceae is so far a rare event and 1 of the major therapeutic concerns in the future. PMID- 17366063 TI - Infective endocarditis of the tricuspid valve caused by Staphylococcus aureus after ear piercing. AB - Right-sided endocarditis usually involves the tricuspid valve, predominantly in intravenous drug abusers, in patients with anti-arrhythmic devices or central venous lines, and in patients with skin or genitourinary infection and with congenital heart disease 1. We describe a case of a 15-y-old patient, who had tricuspid valve endocarditis in a morphologically normal valve after having his ear pierced, without history of parenteral drug addiction and vascular catheter use. Progression of vegetation size and development of tricuspid valve regurgitation in spite of the intensive antibiotic treatment eventually required surgical intervention. PMID- 17366064 TI - Endovascular repair of mycotic aneurysms of the aorta: an alternative to conventional bypass surgery in patients with acute sepsis. AB - Treatment of mycotic aneurysms of the aorta includes excision of infected tissue followed by anatomic or extra-anatomic bypass. However, operative mortality remains high particularly in elderly patients with comorbidities. We describe here 2 patients with mycotic aneurysms of the descending aorta in whom endovascular repair was successfully performed. In 1 of these patients, stent grafting was attained during the acute, bacteraemic phase of infection. After 12 and 20 months, respectively, of diagnosis, both patients are doing well. PMID- 17366065 TI - Fatal subarachnoidal haemorrhage in a Norwegian traveller with dengue virus infection. AB - We present a Norwegian female in her thirties who acquired dengue fever caused by dengue virus serotype 2 while travelling to Mexico. When hospitalised 3 days after symptom onset, the patient had severe headache, fever, rash and a positive tourniquet test, but did not fulfil the criteria of dengue haemorrhagic fever (DHF). Five days later she developed a fatal subarachnoidal haemorrhage. A post mortem examination failed to reveal any intracranial arterial aneurysm. Our case was consistent with so called 'dengue fever with haemorrhages', a recently described entity that mainly affects adults and may cause severe bleedings also in the absence of DHF. PMID- 17366066 TI - A forgotten but important risk factor for infective endocarditis in patients with prosthetic valve: pedicure. AB - We report a case of infective endocarditis developing after pedicure in a 36-y old female. Methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis was diagnosed. Even aggressive therapy was ineffective. To our knowledge, we report the first case of infective endocarditis secondary to pedicure in the literature. PMID- 17366068 TI - A case of osteomyelitis due to Leuconostoc lactis. AB - A baby case of haematogenous rib osteomyelitis that was caused by Leuconostoc lactis was presented. The patient had high fever and an abscess formation on the right scapula. Diagnosis was made with the results of blood, bone and abscess cultures, pathological findings of the involved rib and direct bone graphies. The patient was treated succesfully with cefotaxime for 6 weeks. PMID- 17366067 TI - Myelitis associated with human herpes virus 6 (HHV-6) after allogeneic cord blood transplantation. AB - Human herpes virus 6 (HHV-6) has been recognized as 1 of the pathogens causing central nervous system diseases such as encephalitis after hematopoietic stem cell transplantation. We here report 2 patients who developed HHV-6-associated myelitis soon after allogeneic cord blood transplantation. PMID- 17366069 TI - Fatal bacterial meningitis after spinal anaesthesia. AB - A 37-y-old male was admitted to the ICU because of meningitis and respiratory failure with epileptic seizures. Spinal fluid grew Streptococcus salivarius. Prior to presentation the patient underwent surgical excision of a chronic toe ulcer, performed under spinal anaesthesia, which raised the suspicion of iatrogenic origin of the disease. The clinical situation deteriorated over the following d and the patient died from multi-organ failure. Careful hygiene measures are needed to prevent such a severe complication. PMID- 17366070 TI - Catastrophic aortic thrombosis due to Toxocara infection. AB - Toxocariasis, a common helminthozoonosis with a worldwide prevalence, usually manifests as 'visceral larva migrans' (VLM). Among its wide range of clinical presentations, large vessel thrombosis has never been described before. We report a case of aortic thrombosis caused by Toxocara canis infection in a young male who was successfully treated with albendazole. PMID- 17366071 TI - Voriconazole resistant Candida spp. and Saccharomyces spp. isolates from oropharyngeal candidiasis from Cambodian children with AIDS not pretreated with azoles (letter). PMID- 17366073 TI - Housing matters in very old age - yet differently due to ADL dependence level differences. AB - In order to support the development of optimal housing options for older people, we need to increase our understanding of relations between aspects of housing and aspects of health in old and very old age. The objective of this cross-sectional study was to explore whether and how aspects of housing are related to life satisfaction and perceived health among very old, single-living Swedish people. Based on survey study data from the ENABLE-AGE Project (n = 397), correlation and regression analyses were performed with sub-groups of participants defined according to different levels of ADL dependence. The results showed that the aspects of housing related to life satisfaction and perceived health were different in the three ADL sub-groups. Among objective aspects of housing, accessibility problems influenced life satisfaction as well as perceived health, yet differently among the sub-groups. As concerns perceived aspects of housing, aspects of meaning of home (MOH) were influential on perceived health in several sub-groups, while only among persons dependent in I-ADL were social aspects of MOH related to life satisfaction. Among persons dependent in I-ADL, external housing-related control beliefs also played a role. In conclusion, the results indicate that housing matters in very old age, yet differently due to ADL dependence-level differences. Most importantly, different aspects of housing seem to play a role in different phases of the trajectory of disability in very old age, while longitudinal studies are needed to verify these indicative results. PMID- 17366074 TI - Home as a signification of independence and autonomy: experiences among very old Swedish people. AB - The aim of this study was to explore independence in the home as experienced by very old single-living people in Sweden. A grounded theory approach was used and interviews were conducted with 40 men and women aged 80-89. Data analysis revealed the core category "Home as a signification of independence" with two main categories: "Struggle for independence" and "Governing daily life". The findings showed that home is strongly linked to independence, and being independent is extremely valued. Explicit descriptions of the ageing process as an individual process of changing living conditions within the home emerged from the findings. Hence, the ageing process influences the participants' perception of themselves as independent persons. Along the ageing process the participants' view of independence changed from being independent in activity performance without help from others to experiencing independence in being able to make autonomous decisions concerning daily life at home. Consequently, there is a need to develop strategies to support very old people in staying as active and independent as possible in their own homes. In addition, since the findings highlight that independence is a complex construct, there is a need for conceptual differentiation between independence and a construct often used synonymously, namely autonomy. PMID- 17366075 TI - The multiple meaning of home as experienced by very old Swedish people. AB - The aim of this study was to explore aspects of the meaning of home as experienced by very old single-living people in Sweden. A grounded theory approach was used, and interviews were conducted with 40 men and women aged 80 89. The findings indicate that home has a central place in the lives of very old people because it is where they live and spend so much time. The significance of the home is based on the fact that it means so many different things to the participants. The theme comprises two key categories: home means security and home means freedom. Each of these has three sub-categories. In home means security, these are: living in a familiar neighborhood, everything functions, and having memories to live on. Home means freedom comprises a place for reflection, a social meeting-point, and leaving your own mark. Home is part of the environment and influences the meaning and selection of activities that very old people decide to engage in. When occupational therapists prescribe assistive devices or recommend changes in the home environment, they must be very well aware of and reflect on what home means to their clients and base their measures on that. PMID- 17366076 TI - Housing-related control beliefs and independence in activities of daily living in very old age. AB - Control beliefs, i.e. a person's perceived control over his or her own behaviour, are important predictors of psychological functioning in old age. The aim of this study is to examine the mediating effect of housing-related control beliefs on the relationship between housing accessibility and independence in activities of daily living (ADL). Moreover, cross-national differences in five European countries were analysed, based on data from the ENABLE-AGE Project. Data were collected at home visits with 1 918 very old people aged 75-89 years, living alone at home in Swedish, German, British, Hungarian, and Latvian urban areas. Assessments were based on standardized instruments with good psychometric properties. Correlations showed small to medium relationships between accessibility, housing-related control beliefs, and ADL independence. Further, multi-group structural equation modelling revealed that not only housing accessibility but housing-related control beliefs explain unique portions of variation in the independent performance of daily activities. In particular, participants with lower external control beliefs performed more independently in ADL. Though some differences among countries were observed, cross-national similarity in correlative patterns existed regarding control beliefs and independence in ADL. Introducing the concept of housing-related control beliefs into occupational therapy, comprehensively and cross-nationally, has the potential to increase our professional understanding of older people's housing situation. PMID- 17366077 TI - Performance of activities of daily living in a sample of applicants for home modification services. AB - Home modification services are provided to support persons with functional limitations to live independently at home. It is not well known what causes individuals to apply for home modifications, or in what kind of life situation this need appears. The aim of this study was to examine the relationship between performance of activities of daily living, housing and living situation, and the home modification applied for in a sample of home modification applicants. Further, the aim was to examine differences in performance of activities of daily living between subgroups with different social support. A total of 102 participants were included in the study. Data on performance of activities of daily living was collected through interviews in the participants' homes, using structured instruments. The participants reported high levels of independence in activities of daily living, and were using assistive devices to a large extent. However, the applicants clearly experienced difficulties in performing activities related to the applied home modification. The study indicates that the main reason for applying for Home Modification Grants was perceived difficulties in performance of activities of daily living. This stresses the importance of including other aspects besides independence when trying to understand persons' activity performance and planning for occupational therapy interventions. PMID- 17366078 TI - Challenges in implementation of research methodology in community-based occupational therapy: the Housing Enabler example. AB - This paper focuses on challenges in implementation of research in community-based occupational therapy practice. Based on a two-year project in a south Swedish municipality aiming at studying implementation of structured assessment procedures in the housing adaptation process, the first purpose is to provide a detailed project description, and the second is to report on first results identifying challenges in implementation of research in practice. The project was managed following a non-profit marketing model involving activities based on user needs, e.g. assessment training, support visits, and seminars with the users, i.e. occupational therapists. In order to collect data on implementation challenges, a multidimensional approach was utilized. Involving all occupational therapists in the municipality under study, 422 housing adaptation cases were assessed by means of the Housing Enabler. Good inter-rater reliability was demonstrated (kappa=0.62), but large differences between districts in the municipality were seen. Qualitative analyses of diaries, e-mail correspondence and minutes from workshops and seminars elucidated three categories reflecting research implementation challenges: Utilizing research in practice is not straightforward; Utilizing information technology is demanding; and Establishing cooperation and communication is challenging. The results can be utilized for planning of research implementation projects in practice not used to scientific work. PMID- 17366079 TI - Influences of the social environment on engagement in occupations: the experience of persons with rheumatoid arthritis. AB - The aim of this explorative study was to describe and enhance the understanding of how persons with rheumatoid arthritis (RA) experience the influence of the social environment on their engagement in occupations. Nine persons were interviewed and the data obtained were analysed using a comparative method. The findings revealed that other persons in the social environment influenced informants' experiences of engaging in occupations in two ways, which formed the categories: "Constructive collaboration" and "Insufficient collaboration". These categories had certain properties related to the actions the others undertook to assist the informants during their collaboration. These assisting actions influenced the informants' possibilities to engage in occupations, and also their experience of engagement. The findings also showed that the "Conditions for collaboration" varied and influenced their collaboration, which thereby constituted a third category. The findings may contribute to a deeper understanding of how other persons can facilitate and restrict meaningful occupational experiences. This provides knowledge that can be used by occupational therapists when empowering their clients and those close to them to reflect on their actions and the consequences of these actions to enhance occupational engagement. PMID- 17366080 TI - Public health ethics in times of global environmental change: time to look beyond human interests. PMID- 17366081 TI - Predictiveness of body mass index for fatal coronary heart disease in men according to length of follow-up: a 21-year prospective cohort study. AB - AIMS: To test the association between body mass index (BMI) and other coronary risk factors and the risk of a fatal coronary heart disease (CHD) event in different time periods during follow-up. METHODS: Prospective cohort study with a 21 year follow-up period. A screened sample of 14,403 men aged 40-49 years initially free of CHD. Risk of fatal CHD was calculated for 21 years' cumulative follow-up and for four consecutive 5-year periods. RESULTS: After adjustment for age and the other risk factors, total cholesterol and systolic blood pressure retained their predictive strength for CHD mortality throughout follow-up. Though cigarette smoking remained a significant predictor, the relative risk decreased with time (test of trend: p=0.01). Intermediate to vigorous physical activity at leisure was protective for 10 years of follow-up and a question on mental stress for 5 years. The test of trend indicated that the risk associated with BMI increased with the duration of follow-up (p=0.002). CONCLUSIONS: Our data show that coronary risk factors predicted CHD mortality differently according to the length of follow-up, and suggest that the harm associated with obesity may take more than a decade to become evident, in contrast to the classical CHD risk factors. PMID- 17366082 TI - Hip fractures among the elderly in a Swedish urban setting: different perspectives on the significance of country of birth. AB - OBJECTIVES: The study investigates the significance of country of birth for hip fractures among the elderly in a Swedish urban setting. DESIGN: Cross-sectional register-based study. METHODS: All people aged 65 or above hospitalized because of hip fracture in Stockholm County over the years 1993-95 were identified in the County's Hospital Discharge Register. Information was obtained from Sweden's National Population Register on the countries of birth of the people affected (reference year: 1994). The foreign-born were grouped in two ways: according to the geographic location of their country of birth, and to the level of development of that country (as measured by the UN's Human Development Index). Age-standardized odds ratios were computed for men and women separately, with the Swedish-born elderly as reference group. RESULTS: Many of the foreign-born groups registered significantly lower odds of hip fracture than their Swedish-born counterparts, regardless of whether countries of birth were grouped geographically or according to level of development. This applied to both men and women. CONCLUSIONS: As a whole, the Swedish elderly population has one of the highest prevalences of hip fracture in the world. When country of origin is accounted for, the foreign-born elderly are significantly less vulnerable than native Swedes. This contrasts remarkably with other health outcomes. PMID- 17366083 TI - Misclassification of occupation-based socioeconomic position and gender comparisons of socioeconomic risk. AB - AIMS: Because occupational classification systems tend to be less precise in the female sector of the working market there has been concern that this might imply more misclassification of socioeconomic position among women, biasing comparisons of gender-specific socioeconomic differences in risk. METHODS: The Stockholm Heart Epidemiology Program (SHEEP) is a population-based case-control study of risk factors for incident myocardial infarction. The study base included all Swedish citizens aged 45-70 in Stockholm County during 1992-94, 550 female and 1201 male cases, and 776 female and 1538 male controls. The use of an occupational classification as the base for categorizing socioeconomic position was compared with socioeconomic position based on detailed self-reported information on job titles and work tasks. RESULTS: Women are categorized into fewer occupational categories than men and the socioeconomic heterogeneity within occupational categories is substantial for women as has been reported by others. However, despite more occupational categories for male types of jobs the socioeconomic heterogeneity within occupational categories is actually larger for men, implying larger misclassification among men. In simulations with different levels of socioeconomic misclassification among women, the effects on the gender comparison of socioeconomic differences in disease risk were small and they were mostly compensated for by less misclassification among men. CONCLUSIONS: The findings do not support the assumption that misclassification of socioeconomic position among women due to a restricted working market and a crude occupational classification for female jobs is an important issue when comparing measures of socioeconomic inequalities in health between men and women. PMID- 17366084 TI - Influence of health, lifestyle, working conditions, and sociodemography on early retirement among nurses: the Danish Nurse Cohort Study. AB - AIMS: The aim of the study was to analyze the relationship between health, lifestyle, work-related and sociodemographic factors, and older nurses' exit from the labor market to Post-Employment Wage (PEW). PEW is an early retirement scheme to make it possible for workers to retire at the age of 60. METHODS: The study was based on 5,538 nurses in the age of 51-59 who in 1993 completed a questionnaire on health, lifestyle, working environment, and sociodemographic factors. The survey information was combined with longitudinal data from the Danish Integrated Database for Labor Market Research compiled by Statistics Denmark. The follow-up period was from 1993 to 2002. RESULTS: Nurses who had poor self-rated health were more likely to join PEW compared with nurses who considered their health as good (HR 1.28, 95% CI 1.16-1.41). Low job influence, high workload, and physical job demands only marginally increased the probability of retiring. Nurses who have relatively low gross incomes had an increased probability of entering PEW compared with nurses with relatively high gross incomes (HR 1.60, CI 1.43-1.79). Having a spouse increased the probability of joining PEW, especially having a spouse who had retired or was unemployed. CONCLUSIONS: The retirement age among nurses is influenced by a number of sociodemographic, work-related, and health-related factors. Poor health, low income, living outside the Copenhagen area, being married, having a spouse who is outside the labor force, and working in the daytime are all predictors of early retirement among nurses. Poor working environment only marginally increased the probability of retiring early. PMID- 17366085 TI - Tobacco images and texts in Norwegian magazines and newspapers. AB - BACKGROUND: Print media may influence smoking behaviour through tobacco advertisements and editorial use of tobacco pictures and texts. In Norway tobacco advertising has been banned for many years. The authors studied the coverage of tobacco promotion and tobacco and health in some general Norwegian magazines and newspapers. The findings were related to the publications' policy as stated by their editors. METHODS: During three months in 1998-99 all pictures of tobacco and smoking situations were registered, plus the coverage on health aspects of tobacco in all consecutive issues of 7 newspapers and 19 magazines. The editors were asked about their attitudes regarding indirect tobacco advertisement and editorial use of people smoking. RESULTS: All editors for men's magazines and the majority of newspaper editors had no restrictions on displaying both indirect tobacco advertisements and images of people smoking. In total, 610 texts or pictures on tobacco were found in the 624 issues of magazines and newspapers. Only 26 items were indirect tobacco advertisements. Items promoting smoking were more common than coverage of tobacco and health (71% vs 29%), and occurred most frequently in men's magazines (2.1 per issue) and least frequently in local newspapers (0.3 per issue). The proportion of tobacco and health coverage compared with the total tobacco coverage was significantly lower in men's than in family magazines and local newspapers. CONCLUSION: Editors should be encouraged to increase the coverage of tobacco and health in print media. This may be an important factor in helping their readers to give up or not to take up smoking. PMID- 17366086 TI - Self-rated health and indicators of SES among the ageing in three types of communities. AB - AIMS: This paper examines associations between self-rated health, three indicators of SES (self-reported education, disposable household income, adequacy of income) and three types of communities (urban, densely or sparsely populated rural areas) among ageing men and women in the Province of Paijat-Hame, Southern Finland. There is a lack of knowledge regarding the magnitude of community type when examining the relation between subjective health and SES. METHODS: Cross sectional questionnaire data gathered in the spring of 2002 for a prospective follow-up of community interventions were used. These data, together with a number of clinical and laboratory measurements, yielded the baseline for a 10 year community intervention study. A representative stratified (age, gender, area) sample of men and women living in the province and belonging to the birth cohorts 1926-1930, 1936-1940, and 1946-1950 was obtained from the National Population Registry. The target sample was 4,272, with 2,815 persons responding (66% response rate). RESULTS: Positive associations between indicators of SES and self-rated health were observed in all three community types. After adjusting for other factors, adequacy of income showed the strongest (positive) association with self-rated health in urban areas in all age groups. A similar pattern of associations, with varying statistical significance, though, was found in the two rural areas. CONCLUSIONS: This study supports the view that while actual income is positively correlated to health, adequacy of income is an even stronger predictor of it. Thus, there was a significant link between better financial standing and good health among ageing people, especially in urban areas. PMID- 17366087 TI - Obesity in young adulthood and later disability pension: a population-based cohort study of 366,929 Swedish men. AB - BACKGROUND: The prevalence of obesity has increased threefold among Swedish men during recent decades. Knowledge from Sweden on how obese men manage in working life and become disability pensioners is sparse. The aim of this nationwide and population-based cohort study was to investigate to what extent body mass index (BMI) in young adulthood predicts later disability pension. METHOD: All Swedish men born 1952-59, who had their weight and height measured at age 18 years in the compulsory military conscription examinations, were followed up longitudinally from 1990 to 2001 with regard to receiving disability pension. Data on own socioeconomic position (1985), education and marital status (1990), parental socioeconomic position (1960), and education (1970) were obtained from censuses. For 366,929 men (81% of the eligible men) the hazard ratio for receiving disability pension was calculated with Cox regression controlling for own education, parental education, childhood and adult socioeconomic position, marital status, morbidity, and type of municipality. RESULTS: Obesity in young adulthood increased the risk for disability pension later in life (1.35, 95% CI 1.19, 1.52) compared with men of normal weight. The relationship between BMI and disability pension was J-shaped with higher risks for underweight (1.14, 95% CI 1.09, 1.20) and obese men. CONCLUSIONS: Obese men in Sweden are at higher risk of receiving disability pension. The relationship between BMI and disability pension is J-shaped. An important future task is to estimate the societal costs due to disability pension of obese people. PMID- 17366088 TI - "Eyes Wide Shut"--sexuality and risk in HIV-positive youth in Sweden: a qualitative study. AB - AIMS: This study explores the perception of sexual risk-taking behaviour in young HIV+ women and men in Sweden and their understanding of why they caught HIV. METHOD: In-depth interviews were conducted with 10 HIV+ women and men aged 17-24 years, 7 born in Sweden and 3 immigrants. Interviews were tape-recorded, transcribed verbatim, and analysed according to the stages of grounded theory. RESULTS: The core category varying agency in the gendered sexual arena illustrated a spectrum of power available to these informants during sexual encounters. Two subcategories contextualized sexual practice: sociocultural blinds and from consensual to forced sex. Lack of adult supervision as a child, naive views, being in love, alcohol and drugs, the macho ideal, and cultures of silence surrounding sexuality both individually and structurally all blinded them to the risks, making them vulnerable. Grouping narratives according to degree of consensus in sexual encounters demonstrated that sexual risks happened in a context of gendered power relations. CONCLUSION: This pioneering study reveals mechanisms that contribute to vulnerability and varied agency that may help in understanding why and how young people are at risk of contracting HIV. Public health strategies, which consider the role of gender and social background in the context of risky behaviours, could be developed from these findings. PMID- 17366089 TI - The impact of moderate and major workplace expansion and downsizing on the psychosocial and physical work environment and income in Sweden. AB - AIMS: To describe the effect of organizational change (moderate and major expansion and downsizing) on psychosocial work characteristics, physical hazards, and income in a representative sample of larger workplaces in Sweden. METHODS: Annual changes in workforce size for the years 1991-1996 were derived from tax registry data. Work environment characteristics were measured in a sub-set of participants from the biennial Swedish Work Environment Surveys for 1991, 1993, and 1995. Income data were derived from national registries. RESULTS: Not all organizational change resulted in a poorer work environment. The number of beneficial outcomes associated with moderate downsizing and moderate expansion in the public sector outweighed the number of adverse outcomes. However, in the private sector the overall effect of moderate organizational change was a poorer work environment. Major downsizing was associated with a better psychosocial work environment for private-sector men and major expansion with a poorer environment for public-sector women and private-sector men. Otherwise, associations between major organizational change and the psychosocial work environment were mixed across sex and sector, although major organizational change was consistently associated with a greater risk of physical hazards. Low income was associated exclusively with organizational downsizing in the private sector. CONCLUSIONS: More research is needed to determine whether the work environment can explain observed associations between organizational change and health. Data limitations prevented the authors from examining this in the present study. Their findings indicate that future research on the work environment should pay more attention to physical hazards. PMID- 17366090 TI - Patient experiences in relation to respondent and health service delivery characteristics: a survey of 26,938 patients attending 62 hospitals throughout Norway. AB - AIMS: To assess the association between patient experiences, aspects of healthcare delivery, and patient characteristics for adult somatic inpatients attending hospitals throughout Norway. METHODS: The Patient Experiences Questionnaire (PEQ) was mailed to 26,938 patients attending inpatient clinics at 62 Norwegian hospitals during 2002 and 2003 within a six-week period. Reminders were mailed at four weeks. Scores for the PEQ were regressed on whether the patient felt that he/she had received incorrect treatment, had spent the night in a corridor bed, had been an emergency or routine admission, his/her number of previous admissions, hospital teaching status, hospital size and location, health status, and sociodemographic variables. RESULTS: A total of 13,700 (50.9%) patients responded. Patients who felt that they had received incorrect treatment had significantly poorer scores for all 10 PEQ dimensions. Those spending the night in a corridor bed had significantly poorer scores for six dimensions. Emergency admissions and the previous number of inpatient stays were significantly associated with poorer experiences for 10 and 7 dimensions respectively. Hospital size and university status had negative relationships with scores for six and four dimensions respectively. CONCLUSIONS: Whether the patient felt that he/she had received the incorrect treatment had by far the strongest association with patient experiences. Future studies of patient experiences and satisfaction should include this variable. As found in previous research, patient experiences were significantly associated with age and health status. PMID- 17366091 TI - Predictors of disability pension over a 10-year period for men and women. AB - AIMS: The number of people leaving the labour market with a disability pension is high and knowledge regarding risk factors is limited. The aim of this study was to explore work- and non-work-related predictors of disability pension among men and women and to estimate to what extent the gender difference in retirement rate could be explained by factors in and outside work. METHODS: A random sample of 5,940 employees registered in the Danish National Work Environment Cohort Study in 1995 was followed up with regard to labour market status in 2005 using the DREAM register, which contains data on all social transfer payments in the Danish population. Associations between disability pension and measures of ergonomic and psychosocial work environment, public employment, family status, and lifestyle were analysed by Cox regression and the difference in retirement rates adjusted separately for each group of variables. RESULTS: The results showed (a) that both men and women had a higher risk of disability pension when they had work that involved standing or if they smoked; (b) that women in addition had a higher likelihood if they were public employees, had low job security, or low social support at work; (c) that the higher rate of disability pension among women compared with men could not be explained by work environmental factors, lifestyle, or family situation. Public employment was the single factor that explained most of the difference. CONCLUSIONS: Gender differences in exposures and predictors of disability pension were found, but few explanations of the higher rate of disability pension among women. PMID- 17366092 TI - Improving motivation and goal setting for return to work in a population on sick leave: a controlled study. AB - AIM: Limited knowledge precludes evidence-based interventions targeting return to work among employees on sick leave. The objective of this study was to examine the vocational effect of an intervention focused on motivation, goal setting, and planning of return to work. DESIGN AND METHODS: A total of 2,795 people, across 6 municipalities, on sick leave for at least 21 days received a questionnaire; 1,256 with a self-assessed poor prognosis for fast return to work were eligible for the study. An examination by a specialist in social medicine, followed by additional counselling by a social worker, was offered to 510 residents in two municipalities and accepted by 264 (52%). The goal was to enhance motivation, goal setting, and planning of return to work. Residents in the remaining municipalities (n=746) received the standard case management offered by the municipalities; 845 (67%) persons completed a follow-up questionnaire gathering data on general health and employment status. The duration of the sick leave was analysed by Cox regression, and the chance of being gainfully employed was analysed by logistic regression analysis, both adjusted for several covariates. RESULTS: The intervention neither shortened sick leave periods nor increased the likelihood of gainful employment after one year (OR 0.76; 95% CI 0.45-1.28). CONCLUSIONS: A low-cost counselling programme addressing motivation, goal setting, and planning of return to work did not improve vocational outcomes or reduce the duration of sick leave. PMID- 17366093 TI - Orientations in adolescent use of information and communication technology: a digital divide by sociodemographic background, educational career, and health. AB - AIMS: The role of information and communication technology (ICT) in adolescents' lives was studied, with emphasis on whether there exists a digital divide based on sociodemographic background, educational career, and health. The assumption was that some groups of adolescents use ICT more so that their information utilization skills improve (computer use), while others use it primarily for entertainment (digital gaming, contacting friends by mobile phone). METHODS: Data were collected by mailed survey from a nationally representative sample of 12- to 18-year-olds (n=7,292; response 70%) in 2001 and analysed using ANOVA. RESULTS: Computer use was most frequent among adolescents whose fathers had higher education or socioeconomic status, who came from nuclear families, and who continued studies after compulsory education. Digital gaming was associated with poor school achievement and attending vocational rather than upper secondary school. Mobile phone use was frequent among adolescents whose fathers had lower education or socioeconomic status, who came from non-nuclear families, and whose educational prospects were poor. Intensive use of each ICT form, especially of mobile phones, was associated with health problems. High social position, nuclear family, and a successful educational career signified good health in general, independently of the diverse usage of ICT. CONCLUSIONS: There exists a digital divide among adolescents: orientation to computer use is more common in educated well-off families while digital gaming and mobile phone use accumulate at the opposite end of the spectrum. Poorest health was reported by mobile phone users. High social background and success at school signify better health, independently of the ways of using ICT. PMID- 17366094 TI - Stockholm Birth Cohort Study 1953-2003: a new tool for life-course studies. AB - AIMS: To create a new tool for life-course studies of health outcomes as well as social outcomes. METHODS: Two anonymous data sets, one a local birth cohort and the other a nationwide registry, covering information from early and middle life, respectively, were matched using a "key for probability matching" based on a large number of variables, common to both data sets. The first data set provides social and health information from birth, childhood, and adolescence on boys and girls, born in Stockholm in 1953. The second data set provides information on income, work, and education as well as any inpatient visits and any mortality from mid-life for the entire Swedish population. RESULTS: For 96% of the original cohort it was possible to add data from mid-life. Thus, a new database has been created, referred to as the Stockholm Birth Cohort Study, which provides rich and unique life-course data from birth to age 50 for 14,294 individuals: 7,305 men and 6,989 women. Comparison of matched and unmatched cases in the original cohort suggests that those individuals that could not be matched had slightly more favourable social and intellectual circumstances and had often moved away from Sweden in the 1980s. CONCLUSION: The new database provides excellent opportunities for life-course studies on health and social outcomes. It allows for studies that have not previously been possible in Sweden or elsewhere. Further, it provides an opportunity for collaborative work with similar databases in Copenhagen and Aberdeen. PMID- 17366095 TI - Angiogenesis and other markers for prediction of survival in metastatic renal cell carcinoma. AB - OBJECTIVE: The treatment of metastatic renal cell carcinoma (RCC) remains a clinical challenge. Factors predicting any benefit of different therapies would therefore be useful. Angiogenesis is important in tumor progression and the development of metastases. The aim of this study in patients with distant metastases at diagnosis was to evaluate possible outcome information obtained with a number of soluble angiogenic variables in serum. MATERIAL AND METHODS: Serum samples were taken at diagnosis from 120 consecutive patients with metastatic RCC who were operated on with radical nephrectomy. Different clinicopathological variables and vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-1 (VEGFR-1), basic fibroblast growth factor (bFGF) and erythropoietin levels in serum were compared with the clinical course. RESULTS: The median survival time for all patients was 9 months. Six patients (5%) died during the postoperative period, all of whom had a performance status (PS) of 2 or 3. None of the angiogenic factors (VEGF, VEGFR-1, bFGF, erythropoietin) gave any prognostic information, except that VEGF was associated with survival (p = 0.0234) in patients with a good PS. A number of other variables gave prognostic information in univariate analysis but, after multivariate analysis, only PS (p = 0.002), the number of metastatic sites (p = 0.003) and capsule invasion (p = 0.017) remained as independent predictive factors. CONCLUSIONS: Among predictive factors, only PS, the number of metastatic sites and capsule invasion independently predicted survival in patients with metastatic RCC, while soluble angiogenic factors in serum gave no prognostic information. Nephrectomy in patients with metastatic RCC remains controversial but long-term survival can be achieved in selected patients, especially those with a good PS. PMID- 17366096 TI - Nephron-sparing surgery for renal cell carcinoma in the solitary kidney. AB - OBJECTIVE: Partial nephrectomy in solitary kidneys carries the risk of tumour progression as well as loss of renal function. We evaluated complications and outcome in patients with renal cell cancer in solitary kidneys who were treated by means of nephron-sparing surgery. MATERIAL AND METHODS: Between 1993 and 2003, 38 patients with renal cell carcinoma in a solitary kidney underwent nephron sparing surgery (partial nephrectomy, n = 37; work-bench resection, n = 1). Of these patients, 21 had asynchronous and eight had synchronous bilateral tumours and underwent contralateral radical nephrectomy. The variables examined were tumour size, disease progression, pre- and postoperative renal function and early (within 30 days of nephron-sparing surgery) and late complications. RESULTS: After a mean follow-up period of 41.7 months (range 8-93 months) the mean serum creatinine level had increased from 1.25 mg/dl preoperatively to 1.62 mg/dl postoperatively. Seventeen patients retained normal renal function and 21 developed some degree of renal insufficiency. New-onset chronic renal insufficiency after nephron-sparing surgery with creatinine levels >2 mg/dl was the only late complication observed, occurring in 10 cases. None of the patients required dialysis. Transient urinary leakage was the most frequent early complication, occurring in four cases. Recurrence and/or progression were seen in six patients: four with local recurrence (three of whom also had distant metastases) and two with pure metastatic progression. Nephron-sparing surgery was repeated for the patient with isolated local tumour recurrence. The mean tumour size was 3.8 cm (range 0.7-9.9 cm). Tumour size was markedly greater in patients who developed disease progression (6.2 vs 3.5 cm) and in those who developed renal insufficiency (5.2 vs 3.3 cm). CONCLUSIONS: Nephron-sparing surgery for renal cell carcinoma involving a solitary kidney provides effective curative treatment for small tumours, with preservation of renal function. However, patients who undergo partial nephrectomy for locally extensive tumours are at high risk of disease progression. PMID- 17366098 TI - Men's perception of fatigue when newly diagnosed with localized prostate cancer. AB - OBJECTIVES: Cancer is a complicated issue both medically and psychosocially, and the process of the disease affects the whole human being. Fatigue is the commonest symptom associated with cancer and its treatment. Prostate cancer is the third commonest male cancer worldwide and the leading cause of male cancer death. The aims of this study were: (i) to identify whether fatigue is found in men with newly diagnosed localized prostate cancer (predominantly early-stage, very low tumour burden asymptomatic patients); and (ii) to gain a perception of whether fatigue has an influence on these men and to try to find out what the cause of this fatigue was. MATERIAL AND METHODS: Sixteen men who had been newly diagnosed with localized prostate cancer were interviewed to determine whether fatigue is experienced by such men and whether it has an effect on them. Verbal transcripts were analyzed using hermeneutical interpretation. RESULTS: Five equivalent fusions were identified according to the time when the participants received their diagnosis of early-stage prostate cancer. These fusions occurred successively, in three steps. The first step was Enclosing Intrapersonal Emotions and Enclosing Interpersonal Attachments, when the men were living in a kind of vacuum. Moving onto step two, another two fusions were triggered and contributed to a positive attitude: Reopening Intrapersonal Emotions and Reopening Interpersonal Attachments. Finally, at step three, a unifying fusion was identified: Living with a New Perspective. This study provides insights and new knowledge indicating that prostate cancer does not in itself cause fatigue. CONCLUSIONS: The clinical implications of these findings are that it is not possible to handle new and detailed information about prostate cancer at the first visit. The need for information occurs, however, relatively soon afterwards and it would seem appropriate to offer a new appointment within 1 week of the first visit. PMID- 17366097 TI - Gastrointestinal function and metabolic control after construction of an orthotopic ileal neobladder in bladder cancer. AB - OBJECTIVE: To investigate the effects of ileum resection in orthotopic neobladder construction on gastrointestinal function and metabolic control. MATERIAL AND METHODS: We included 28 patients who underwent radical cystectomy and construction of an orthotopic neobladder or continent ileal reservoir for bladder cancer. As controls, 10 patients endoscopically treated for non-invasive bladder cancer (TaG2) were enrolled. Gastrointestinal symptoms, enterohepatic bile salt circulation, gastric emptying and gastrointestinal hormones involved in metabolic control were monitored. RESULTS: Of the cystectomy patients, 25% experienced daily diarrhoea and faecal urgency due to bile acid malabsorption, compared to 0% of the controls (p = 0.013). The cystectomy patients experienced faster gastric emptying and had higher levels of peptide YY. Plasma concentrations of insulin, glucagon-like peptide-1 and glucose were unchanged. CONCLUSIONS: Using the distal ileum for orthotopic neobladder construction causes bowel disorders in a quarter of cystectomy patients. Diarrhoea and faecal urgency are probably caused by decreased reabsorption of bile and are not due to changes in gastrointestinal hormones. A sizeable proportion of patients develop bile salt-induced diarrhoea, which can be relieved by treatment with cholestyramine. PMID- 17366099 TI - Uric acid as inducer of calcium oxalate crystal development. AB - OBJECTIVE: This paper deals with the mechanism by which uric acid affects calcium oxalate crystallization and the role of crystallization inhibitors in this process. MATERIAL AND METHODS: Pure uric acid crystals and fragments of uric acid renal calculi were used to induce calcium oxalate crystal formation and development. These studies were performed in flow systems, using synthetic urine and similar conditions to those found in real renal situations. The type and size of the developed crystals were evaluated by scanning electron microscopy and the amount of calcium oxalate crystallized was quantitated by means of inductively coupled plasma atomic emission spectroscopy. RESULTS: The presence of uric acid crystals in a flow system provoked calcium oxalate monohydrate (COM) crystallization at a rate of 3.3 microg/h/mg uric acid. When uric acid renal calculi fragments were used, the amount of COM crystallized varied between 0.048 and 0.161 microg/h/mg of renal calculi depending on the porosity of the calculus. At particular concentrations (3.03 microM phytate, 28.75 microM pyrophosphate, 40 mg/l chondroitin sulphate) the crystallization inhibitors assayed produced a maximum decrease of approximately 50% in the amount of COM crystallized on uric acid crystals. Mucin (a glycoprotein) caused only slight effects. CONCLUSION: Uric acid crystals can clearly induce the development of COM crystals on them through a heterogeneous nucleation process and some crystallization inhibitors can notably delay such a process. PMID- 17366100 TI - Bothersome urinary symptoms and disease-specific quality of life in patients with benign prostatic obstruction. AB - OBJECTIVES: Firstly, to describe self-reported urinary symptoms and bothersomeness, including disease-specific quality of life (QOL), in patients with symptomatic benign prostatic obstruction (BPO) before and 6 months after intervention. Secondly, to identify factors which predict disease-specific QOL. Thirdly, to develop and test the reliability of an instrument to evaluate incontinence, the Linkoping Incontinence Questionnaire (LIQ). Finally, to translate and test the reliability of Swedish versions of the International Prostate Symptom Score, including the bother question, the American Urological Association Symptom Problem Index (SPI) and the Benign Prostatic Hyperplasia Impact Index. MATERIAL AND METHODS: Disease-specific QOL was studied in 572/720 consecutively treated patients using structured questionnaires. The reliability of the instruments was tested in 122 patients with lower urinary tract symptoms (LUTS) or BPO. RESULTS: The frequency and weak stream items of the SPI were among those that best explained the patients' disease-specific QOL both before and after intervention. Before and after intervention the prevalence of urinary incontinence, assessed using the LIQ instrument, was 46% and 16%, respectively. Symptoms and disease-specific QOL improved most in the surgery group, intermediately in the transurethral incision of the prostate/transurethral microwave thermotherapy group and least in the drug therapy group. CONCLUSIONS: The frequency and weak stream items of the SPI were the factors that best explained disease-specific QOL. The prevalence of incontinence before and after intervention was higher than that previously reported. PMID- 17366101 TI - Anatomic and hemodynamic evaluation of renal venous flow in varicocele formation using color Doppler sonography with emphasis on renal vein entrapment syndrome. AB - OBJECTIVE: To investigate the anatomic and hemodynamic properties of testicular venous drainage and its effects on varicocele formation and reflux using color Doppler ultrasound (US) with emphasis on renal vein entrapment syndrome. MATERIAL AND METHODS: Upper abdominal and scrotal US examinations of 35 varicocele patients and 35 healthy male subjects were performed in the supine position during rest, during a Valsalva maneuver and in the erect position. The aortomesenteric angle and distance (AMA and AMD, respectively), peak mean velocities (PVs) and diameters of different segments of renal veins, testicular vein diameters and duration of flow inversion were measured. RESULTS: In the varicocele group, the lateral segment of the left renal vein (LRV) had a larger diameter and slower PV, and the medial segment of the LRV had a smaller diameter and faster PV. The diameter of the dominant draining vein correlated with the PV of the medial and lateral segments of the LRV, whereas there was no correlation between the diameter of the dominant draining vein and the diameters of the right renal vein (RRV) and the lateral segment of the LRV or the PV of the RRV. The duration of flow inversion correlated with the diameter and PV of the medial segment of the LRV. No correlation between the diameters and PVs of the RRV and the lateral segment of the LRV was detected. CONCLUSIONS: The decreases in the AMA, AMD, diameter of the medial segment of the LRV and PV of the lateral segment of the LRV, and the increases in the PV of the medial segment of the LRV and the diameter of the lateral segment of the LRV in varicocele patients in all positions suggest the entrapment or impingement of the left renal vein between the aorta and the superior mesenteric artery. This has been defined as the "nutcracker phenomenon", which is known to affect varicocele formation. PMID- 17366102 TI - Regional changes in renal cortical glucose, lactate and urea during acute unilateral ureteral obstruction. AB - OBJECTIVE: Acute unilateral ureteral obstruction (UUO) leads to changes in kidney function and metabolism. Microdialysis offers the possibility of topical analysis of changes in kidney metabolism. We applied microdialysis to the porcine kidney and evaluated its impact on gross kidney function. Furthermore, we investigated regional variations in renal interstitial fluid (RIF) glucose, lactate and urea during acute UUO. MATERIAL AND METHODS: Eight anesthetized pigs were used. Microdialysis probes were inserted in the upper, middle and lower thirds of the left renal cortex and perfused with Ringer's chloride at a rate of 0.3 microl/min. Dialysates were fractionated for 30-min periods. Bilateral intrapelvic pressure, urinary output, urinary osmolality, the excretion fractions of sodium and potassium, renal blood flow and the glomerular filtration rate were measured. Subsequently, left-sided graded ureteral obstruction was initiated, using the kidney's own urine production as a counter-pressure. RESULTS: The application of three microdialysis probes did not have any impact on kidney function. Ureteral obstruction decreased RIF glucose in the upper and lower thirds of the kidney, but not in the middle third. RIF lactate did not change. Interstitial urea increased in all regions of the kidney, but most markedly in the upper and lower poles. CONCLUSIONS: Microdialysis is of potential value for assessing the renal interstitial milieu under different pathophysiological conditions. Ureteral obstruction resulted in regional differences in cortical metabolites, predominantly affecting the upper and lower poles. PMID- 17366103 TI - Varicocelectomy by means of subinguinal cremasteric compartment disruption and venous ligation. AB - OBJECTIVE: To evaluate the efficacy of addition of disruption of the cremasteric compartment to venous ligation in infertile men with varicocele and abnormal semen parameters. MATERIAL AND METHODS: A prospective non-randomized study was undertaken in 380 infertile men with varicocele and abnormal semen parameters. They were operated on using subinguinal venous ligation with the addition of cremasteric compartment disruption on an outpatient basis. RESULTS: Following surgery, the median values for each semen parameter were compared preoperatively and 1-year postoperatively using the Wilcoxon signed rank test. The difference in the median values was significant for all the parameters. Over a minimum 2-year follow-up period, 304 men (80%) contributed to pregnancies leading to live births. CONCLUSIONS: The results suggest that subinguinal venous ligation with the addition of cremasteric compartment disruption is a physiological, economic and safe option for varicocele repair in men with abnormal sperm parameters. A high rate of unassisted pregnancy compared to conventional isolated venous obliteration is achievable, with minimal morbidity and recurrence. PMID- 17366104 TI - Use of collagen for endoscopic correction in complicated vesicoureteral reflux. AB - OBJECTIVE: Endoscopic treatment of children with primary vesicoureteral reflux (VUR) has become an alternative to long-term antibiotic prophylaxis and open surgery. The purpose of this study was to assess the efficiency and safety of endoscopic subureteral injections of collagen (STING) as a treatment for complicated VUR in children. MATERIAL AND METHODS: Twenty-five patients (41 ureteral units) underwent a modified STING procedure for the correction of complicated VUR. Of these patients, five (nine refluxing units) had Hutch's diverticulum, 10 (17 refluxing units) had a duplex system, eight (10 refluxing units) had ureterocele, one (three refluxing units) had a unilateral triple ureter and one (two refluxing units) had a bilateral single ectopic ureter. Of these 41 ureteral units, 14 had grade III VUR, 17 grade IV and 10 grade V. Fourteen refluxing units (30%) received one session of STING, which was successful, and 27 (70%) needed a second session. A follow-up voiding cystourethrogram was performed 3 months after each session of STING. RESULTS: The mean follow-up period was 24 months (range 3-36 months). Of these 41 refluxing units, 34 were treated successfully and regression or downgrading occurred in seven. Follow-up i.v. pyelography or sonography did not reveal any urinary tract obstruction. CONCLUSIONS: The results of this study showed that endoscopic correction of these complicated refluxing ureters may be the first choice of treatment, but the technique must be modified to suit each individual case. PMID- 17366105 TI - Comparison of three disease-specific quality-of-life questionnaires (Bristol Female Lower Urinary Tract Symptoms, Incontinence Quality of Life and King's Health Questionnaire) in women with stress urinary incontinence. AB - OBJECTIVES: To examine the impact of stress urinary incontinence (UI) on quality of life (QOL) using three disease-specific QOL instruments and compare the results obtained with these instruments. MATERIAL AND METHODS: A total of 28 women (age range 36-74 years) with stress UI were included in the study. To obtain QOL assessments, patients were asked to complete the Bristol Female Lower Urinary Tract Symptoms (BFLUTS), Incontinence Quality of Life (I-QoL) and King's Health Questionnaire (KHQ) instruments. RESULTS: One domain in the BFLUTS (Incontinence symptoms) and one in the KHQ (Severity measures) correlated inversely with the Valsalva leak point pressure and the cough leak point pressure, respectively; however, other domains in the three questionnaires did not correlate with objective data. Two BFLUTS domains (Incontinence symptoms and QOL) correlated weakly or moderately with six KHQ domains; however, other BFLUTS domains did not correlate with most KHQ domains. Significant negative correlations were noted between two BFLUTS domains (Incontinence symptoms and QOL) and most I-QoL domains; however, other BFLUTS domains did not correlate with the I-QoL. Role limitations, Emotional problems and Severity measures in the KHQ correlated weakly or moderately with the I-QoL; however, General health and Personal relationships did not correlate significantly with the I-QoL. CONCLUSIONS: Subjective QOL results of stress UI using condition-specific QOL questionnaires may differ because there are a plethora of measurement instruments that vary in terms of their scope and content. Our findings suggest that, before deciding on an instrument, its contents should be thoroughly reviewed to ensure that a particular aspect of QOL does not need additional assessment. PMID- 17366106 TI - Gil-vernet anti-reflux surgery and primary vesicoureteral reflux in women. AB - OBJECTIVE: To review the results of Gil-vernet anti-reflux surgery in adult female patients suffering from primary vesicoureteral reflux. MATERIAL AND METHODS: A total of 39 women with a diagnosis of primary vesicoureteral reflux who were surgically treated at our medical center using the Gil-vernet anti reflux method between 1995 and 2004 were included in the study. Data concerning gender, age, pre- and postoperative symptoms, reflux grading and the outcome of surgery were reviewed. RESULTS: Thirty-nine females (mean+/-SD age 29.19+/-10 years; range 18-65 years) with a total of 49 refluxing renal units were studied. The Gil-vernet technique was effective in eliminating reflux in 48/49 renal units (97.95% success rate) and 38/39 patients (97.43% success rate). The chief complaints of the patients were resolved after surgery in 87.17% of cases. CONCLUSION: Gil-vernet anti-reflux surgery had a high success rate in adult female patients. PMID- 17366107 TI - Primitive neuroectodermal tumor of the kidney confirmed by fluorescence in situ hybridization. AB - We report a rare case of primitive neuroectodermal tumor of the kidney. The diagnosis was confirmed by the immunohistochemical profile and fluorescence in situ hybridization in formalin-fixed, paraffin-embedded tissues. The patient received intensive chemoradiotherapy after radical surgery and remains alive without recurrence 1 year after initial presentation. PMID- 17366108 TI - Unilateral asymptomatic adrenal tuberculoma: the role of percutaneous biopsy. AB - We report the case of a 55-year-old male with a large left adrenal mass that conformed to the normal shape of the adrenal gland. Percutaneous biopsy revealed tuberculosis and, following anti-tuberculosis therapy, there was a >75% decrease in the size of the mass. In large tumefactions of the adrenal glands in which a normal adrenal contour is maintained, a percutaneous biopsy may obviate the need for major intervention. PMID- 17366110 TI - Traumatic bitemporal hemianopia. AB - A 45-year-old male pedestrian was struck by a motor vehicle moving at high speed. Upon initial assessment, the patient scored a 3T on the Glasgow Coma Scale. The patient suffered multiple facial and sinus fractures, a right orbital wall fracture, and a depressed open frontal skull fracture with visible brain parenchyma. Due to the nature of the brain injury, the patient was taken to the operating room emergently for a right frontal craniectomy. The patient required prolonged hospitalization followed by transfer to a rehabilitation facility. Six weeks after the accident, the patient underwent an extensive neuro-ophthalmologic evaluation. At that time, visual acuity was 20/200 in both eyes. On visual field testing, a bitemporal hemianopia was noted. Ophthalmoscopic examination revealed bilateral temporal disc pallor, right greater than left. Neuroimaging demonstrated damage to the optic chiasm. Although rare, head trauma may cause a bitemporal hemianopia secondary to optic chiasmal injury. PMID- 17366111 TI - Resolution of Chiari I malformation following acetazolamide therapy. AB - A 25-year-old obese woman developed headaches and visual blurring. Examination showed papilledema and cranial MRI showed a large Chiari I malformation. Acetazolamide was initiated and a repeat cranial MRI surprisingly showed resolution of the Chiari I malformation. Chiari I malformation associated with papilledema has never been shown to resolve with acetazolamide therapy. PMID- 17366112 TI - Visual loss due to Wernicke syndrome following gastric bypass. AB - PURPOSE: To report a case of Wernicke encephalopathy after gastric bypass surgery resulting in vision loss, ophthalmoplegia, and ataxia, all of which reversed with a single dose of IV thiamine. METHODS: Observational case report. RESULTS: A 34 year-old woman presented with decreased vision and intermittent diplopia after gastric bypass surgery. She was found to have bilateral limitation of horizontal gaze, decreased vision with bilateral central scotoma and mild disc edema OU. Her cranial magnetic resonance imaging (MRI) was normal. A presumptive diagnosis of Wernicke encephalopathy was made. The patient was admitted, and a single dose of IV thiamine reversed the ophthalmoplegia and vision loss within 24 hours. CONCLUSION: Wernicke encephalopathy should be considered in patients with vision loss after gastric bypass surgery. The classic triad of confusion, ataxia, and ophthalmoplegia may not be present and, although uncommon, the findings of optic disc edema and vision loss should not deter the clinician from making the diagnosis. Replacement thiamine if given promptly may rapidly reverse the findings. PMID- 17366113 TI - Isolated bilateral abducens nerve palsy associated with traumatic prepontine hematoma. AB - We describe a 15-year-old boy who developed isolated bilateral abducens nerve palsies immediately following a motor vehicle accident and who was found to have a pre-pontine extra-axial hematoma. We review the literature on isolated bilateral traumatic abducens palsies and discuss the alternate mechanisms for this injury. PMID- 17366115 TI - Spasm of the near reflex in a patient with multiple sclerosis. AB - A 33-year-old woman with a history of relapsing-remitting multiple sclerosis presented with complaints of episodic horizontal diplopia and blurred vision over the past two months. The patient gave a past history of similar episodes of diplopia that had occurred with previous clinical relapses of her multiple sclerosis. On eye movement examination, the patient exhibited intermittent spasms of convergence coupled with miosis. On upward gaze, the convergence and miosis became more marked. An auto-refraction revealed variable measurements in both eyes, consistent with accommodative spasms. A cycloplegic auto-refraction revealed significantly lower myopia present in both eyes than the initial pre cycloplegic auto-refraction with minimal variability in readings. Symptomatic relief was achieved by cycloplegia and spectacle correction. PMID- 17366114 TI - Optic disc edema with adjacent cilioretinal artery occlusion in a male with ulcerative colitis. AB - OBJECTIVE: To report a case of optic disc edema with adjacent retinal ischemia in ulcerative colitis. DESIGN: Photo essay. CASE REPORT: A 36-year-old white man presented with visual loss OD. Past medical history was significant for ulcerative colitis. The patient had suffered presumed non-arteritic anterior ischemic optic neuropathy OS one year prior to the episode OD. Ophthalmoscopic exam showed optic disc edema associated with an area of adjacent retinal ischemia that was confirmed on fluorescein angiography OD. An extensive evaluation for infectious, inflammatory, vasculitic, and hypercoagulable etiologies was negative. The presumptive diagnosis of ulcerative colitis-related ischemic optic neuropathy with simultaneous retinal ischemia was made. The patient was treated with antiplatelet therapy and the vision stabilized but did not recover. CONCLUSION: To our knowledge, this is the first report in the English language literature of a simultaneous ischemic event involving the optic nerve and the adjacent retina in a patient with ulcerative colitis. PMID- 17366116 TI - Asaccadia and ataxia after repair of ascending aortic aneurysm. AB - Absent saccades is a rare complication of cardiovascular procedures. We present a patient who developed absent volitional saccades and reflex fast eye movements, low gain pursuit, and intact oculocephalic slow phases, dysphagia, dysarthria and progressive gait instability following repair of an ascending aortic aneurysm. Postulated pathophysiologies and prognosis for this syndrome are discussed. PMID- 17366117 TI - Rapid regression of retinochoroidal venous collaterals following optic nerve sheath fenestration in idiopathic intracranial hypertension. AB - A woman with idiopathic intracranial hypertension (IIH) experienced rapid regression of retinochoroidal venous collaterals ("optociliary shunt vessels") following optic nerve sheath fenestration. The presence of these vessels is a nonspecific sign of chronic retinal venous compression in patients with optic disc edema including IIH. PMID- 17366118 TI - Spontaneous closure of macular holes developed after pars plana vitrectomy. AB - PURPOSE: To report a small, retrospective, noncomparative case series (3 patients) of idiopathic macular holes with spontaneous closure in previously vitrectomized eyes. METHODS: The first patient developed a macular hole 14 months after vitrectomy for penetrating ocular trauma. In the rest of the patients, the macular holes were documented ten days and two months after vitrectomies for retinal detachment. RESULTS: In all cases the macular holes resolved spontaneously 2 years, 6 and 9 months after their documentation, respectively. CONCLUSIONS: Despite the limitations placed by the small sample of studied patients, it seems that spontaneous closure of macular holes developed after vitrectomy can happen as part of their natural course. Both pathogenetic and repair factors involved in macular hole can act spontaneously in a vitrectomized eye. PMID- 17366119 TI - Ultrawide-angle retinal imaging and retinal detachment. AB - PURPOSE: To illustrate the utility of ultrawide-angle fundus imaging in documenting the clinical course of a retinal detachment. DESIGN: Observational case report. METHOD: A 20-year-old man with high myopia and a blind fellow eye noted symptoms of retinal detachment and was imaged with an ultrawide-angle fundus imaging device (Optos P200). Imaging was performed after scleral buckling and before and after additional vitreoretinal surgery. RESULTS: Ultrawide-angle images were useful in delineating the extent of retinal detachment even in the presence of intraocular gas. CONCLUSION: The ability to rapidly image the ocular fundus well anterior to the equator facilitates clinical management and may prove particularly useful in electronic record keeping. PMID- 17366120 TI - Cotton wool spots associated with interferon beta-1 alpha therapy. AB - PURPOSE: To describe a case of cotton wool spots associated with interferon beta 1a treatment. METHODS: Observational case report. RESULTS: A 40-year-old man with a history of multiple sclerosis was on interferon beta-1a. He presented with cotton wool spots on fundus exam, which resolved and then recurred all while on therapy. Interferon was discontinued after the second episode and again the cotton wool spots resolved. Upon restarting the interferon, no further cotton wool spots have recurred. CONCLUSION: To our knowledge this represents only the third case of interferon beta-1a associated cotton wool patches and the first in the English-language ophthalmic literature. Unlike interferon alpha therapy, interferon beta 1-a retinopathy is presumed to be extremely rare and more common etiologies for cotton wool spots should be excluded in these patients. Given this limited number of cases versus the relatively frequent use of interferon beta-1a in the management of multiple sclerosis, no conclusions regarding causality or screening can be made but the issue probably deserves further study. PMID- 17366121 TI - Occlusion therapy of unilateral amblyopia with botulinum toxin induced ptosis. AB - In order to evaluate the role of botulinum toxin induced ptosis as an occlusion method to treat unilateral deep strabismic amblyopia in two uncooperative children, we injected 0.2 ml of diluted botulinum toxin in the levator palpaebrae; low sedation was necessary in one of the two children. In both cases a marked ptosis was achieved, which lasted about four weeks and then gradually resolved completely. The visual acuity of the ablyopic eye increased in both children, making patching easy thereafter. One child developed amblyopia in the injected eye, which was handled successfully using part-time occlusion. No other side effects were noted. Whether this new method could be a simple, safe and effective alternative method of occlusion for the treatment of deep amblyopia in uncooperative children needs to be proven with a larger series of children. PMID- 17366122 TI - Photorefractive keratectomy in a patient with epithelial basement membrane dystrophy. AB - PURPOSE: To report a case of excimer laser photorefractive keratectomy (PRK) in a patient with epithelial basement membrane dystrophy (EBMD). METHODS: Interventional case report. RESULTS: A 36-year-old male with clinical manifestations of EBMD underwent bilateral, simultaneous PRK for low myopia correction. A delay (up to 17 days) in the epithelial healing process with unstable epithelium was observed. During the first three postoperative months a visually significant subepithelial haze was developed in both eyes. One year postoperative, an improvement in haze formation and visual acuity in both eyes was found. CONCLUSIONS: PRK in patients with EBMD could result in favorable refractive and clinical outcome. PMID- 17366123 TI - Relapse among substance-abusing women: components and processes. AB - This article is based on part of a project in which 32 women who experienced substance use-related problems were interviewed. The purpose of the article is to explore factors related to the women's relapse so that practitioners can better understand the nature of women's relapse and more effectively help them. Qualitative in-depth interviews were conducted, audiotaped (with the exception of three women), and transcribed. The interview was guided by open-ended questions - exploring factors that led to the women's initial substance use, abstinence, and relapse; factors that prompted them to come for treatment; and their experience with the treatment. These open-ended questions were supplemented with follow-up questions probing further critical elements shared by participants initially. The mean age of the sample was 34 years old, with over half being white, followed by Latina/Hispanic, African American, and Native American. Most women reported being poly-drug users, followed by methamphetamine/amphetamines, heroine, cocaine, and alcohol. The average number of years of education was 11 years. Four major themes representing factors contributing to the women's relapse were identified: (1) low self-worth and its connection to intimate relationships with men; (2) interpersonal conflicts and/or negative emotion; (3) less ability to sever the tie with the using network and to establish a tie with the non-using network; and (4) a lack of AOD-related knowledge and relapse prevention coping skills. The qualitative approach enables the study to report not only the four general themes but also the multiple dimensions and building blocks underlying each theme so that the pertinent contexts and specific meanings of women's relapses can be understood. Many of the factors appeared to be related to women's socialization and the gender-role formation process as well as their disadvantageous social reality. The study suggests several topics for inclusion in women's relapse prevention curriculum and program. It also suggests a holistic life approach that combines both the environment and the individual and emphasizes both habilitation and rehabilitation to help women prevent relapse. Suggestions for future research are also discussed. PMID- 17366124 TI - Development and validation of transtheoretical model measures for Bulgarian adolescent non-smokers. AB - The goal of this study was to develop, translate, and evaluate measures for decisional balance and situational temptations for Bulgarian adolescent nonsmokers and to test the predicted relationships with stages of change. Students in the last grades of high school (15-19 years old) recruited in 12 randomly selected schools participated in the study. Data from the 369 nonsmokers (61.8% female, mean age 16.4 years, 97.1% Bulgarian) were used in the measurement development. A two-factor model for decisional balance (CFI=.94) and a hierarchical three-factor model for temptations (CFI=.90) demonstrated the best fit. The predicted crossover pattern for decisional balance and decreasing trend for temptations across the stages of change was verified. Both measures demonstrated tau-equivalent invariance across gender, in addition to good psychometric properties. These results, with the caveat of the noted limitations, support the cross-cultural validity of these transtheoretical model (TTM) constructs and indicate that they can be used as a basis for development of smoking prevention interventions. PMID- 17366125 TI - Self-perceptions of dispositional luck: relationship to DSM gambling symptoms, subjective enjoyment of gambling and treatment readiness. AB - In the present study, we examined whether having a gambling disorder is related to: (a) the personality trait of perceived personal luck and (b) subjective enjoyment associated with placing bets. We also examined whether the presence or absence of disordered gambling and wagering enjoyment are related to probability of treatment entry. In 2001, we surveyed 82 young adults at the University of Windsor who gambled, but were not in treatment. They completed measures assessing symptoms of pathological gambling (American Psychiatric Association [APA], 1994), dispositional luck (Steenbergh, Meyers, May, and Whelan, 2002), enjoyment of gambling (Ben-Tovim, Esterman, Tolchard, and Battersby, 2001), and attitudes toward treatment (adapted from Fisher and Turner, 1970). Results showed elevated perceptions of personal luck, enjoyment of gambling, and more negative attitudes toward seeking treatment among those who exhibited sub-clinical levels of disordered gambling (n = 41) compared to recreational gamblers (n = 41). Other results showed that, after controlling for the effects of personal luck, the strength of the positive relationship between level of disordered gambling and subjective pleasure of wagering was diminished. Removing the effects of personal luck also weakened the positive association between having a gambling problem and having a negative attitude toward seeking treatment. In light of these results, we suggest cognitive interventions that seek to prevent and treat problematic wagering in early stage gamblers might be efficacious to the extent to which they can modify these young people's belief that they are charmed by high levels of dispositional luck. PMID- 17366126 TI - Neighborhood effects on the efficacy of a program to prevent youth alcohol use. AB - This study examines how neighborhood characteristics affect program efficacy. Data come from a randomized trial of a substance use prevention program called keepin' it REAL, which was administered to a predominantly Mexican American sample of 4,622 middle school students in Phoenix, Arizona, beginning in 1998. Multilevel models and multiple imputation techniques address clustered data and attrition. Among less linguistically acculturated Latinos, living in poorer neighborhoods and those with many single-mother families decreased program effectiveness in combating alcohol use. High neighborhood immigrant composition increased program effectiveness. Unexpectedly, the program was also more effective in neighborhoods with higher rates of crime. There were no significant effects on program efficacy for the more linguistically acculturated Latinos and non-Hispanic White students. Findings are discussed in light of theories of neighborhood social disorganization, immigrant adaptation, and social isolation. PMID- 17366127 TI - Indicators of adolescent alcohol use: a composite risk factor approach. AB - A self-reported alcohol inventory measured prevalence and frequency of lifetime, recent, and current alcohol use by an opportunity sample of 3226 young people aged 11-18 in Welsh secondary schools in 2005 comparing findings to extant U.K. and European levels. A risk factor-based questionnaire enabled comprehensive, sensitive sample profiling by gender and age, combining factor analysis with logistic regression to identify composite risk factors influential upon alcohol use by young people in Wales and salient to policy makers and practitioners, notably the endogenous factors: anti-social behaviour/attitudes, inadequate relationships/activities in school, negative experiences in school, lack of commitment to school, and impulsivity. Overlap with composite risk factors for youth offending was identified, but not with drug use, suggesting that the commonly cited "gateway" relationship between elements of "substance use" requires further examination. The study's limitations and implications are discussed. PMID- 17366128 TI - Services to patients with dual diagnoses: findings from Washington's mental health service system. AB - This study examined how Washington State's (WA) mental health treatment system provided services to patients with substance use disorders or dual diagnoses at several stages of care: crisis commitment, hospitalization, and outpatient treatment. A total of 30 key informants from urban and rural areas were surveyed between February and July 2004 using semi-structured interviews. Key informants represented direct service providers to chief operating officers. Themes, consensus, and disagreements were summarized. Results indicated that best practices are not consistently implemented and administrative and provider barriers hinder provision of more effective care. Findings highlight that work on how to best implement evidence-based practices is critical to improving care of dual diagnosis patients. Limitations of the study are noted as well as future research directions. PMID- 17366129 TI - "Heavy users," "controlled users," and "quitters": understanding patterns of crack use among women in a midwestern city. AB - Over the past two decades, the use of crack cocaine has become an enduring part of the social ecology of many cities across the United States. The purpose of this exploratory study is to describe patterns of crack use drawing on life history interviews conducted with 18 women in Dayton, Ohio, between 1998 and 2000. Ten of the women were African American, and eight were white. Age ranged between 23 and 47. The women were at very different stages of their crack-cocaine careers. We focus on understanding the social factors, life history, and everyday circumstances that participants related to their current patterns and levels of crack use. Implications for intervention are discussed. PMID- 17366130 TI - Rurality and criminal history as predictors of HIV risk among drug-involved offenders. AB - The current study examined rurality and criminality as predictors of the lifetime HIV risk behaviors of 661 male, drug-abusing state prisoners. HIV risk behaviors included the number of lifetime sex partners, the number of lifetime drug injections, the number of times had sex with an injection drug user, and the frequency with which a condom was used. Regression analyses showed that criminality was related to the number of lifetime injections, whereas rurality was related to fewer lifetime sex partners and less frequent condom use. A rurality by criminality interaction for sex with an injection drug user was found. Specifically, those from rural areas who had more extensive criminal histories reported relatively high numbers of sex partners who were IDUs. Results are discussed in the context of rural and criminal justice interventions for HIV risk behavior. PMID- 17366131 TI - Do specialized services exist for LGBT individuals seeking treatment for substance misuse? A study of available treatment programs. AB - Substance abuse research has demonstrated that client sexual orientation influences treatment outcomes. Consequently, many substance user treatment programs offer services for lesbian, gay, bisexual, and transgender (LGBT) individuals. In a recent search of SAMHSA treatment listings, 11.8% (N=911) of substance user treatment programs (including residential, outpatient, and partial hospitalization) in the United States and Puerto Rico indicated that they offer specialized services for LGBT clients. However, a telephone survey we conducted in 2003-2004 revealed that 70.8% of these "LGBT" programs were no different from services offered to the general population, and only 7.4% could identify a service specifically tailored to the needs of LGBT clients. Implications for LGBT individuals seeking services are discussed, the study's limitations are noted, and future research directions are identified. PMID- 17366132 TI - From the first drug to crack: the sequence of drugs taken in a group of users in the city of Sao Paulo. AB - To identify a progression in drug use and influencing factors among crack users, a qualitative methodology was used for a more in-depth investigation, taking into consideration the view that the interviewee has of the problem. A long duration and a semi-structured interview was used; a purposeful sampling was outlined and a criterion sampling was achieved. Thirty-one crack users or ex-users were interviewed in order to reach theoretical saturation. Two distinct phases of drug use were detected. The first, with licit drugs, where alcohol and tobacco were the most frequent, the relatives and friends were the ones who encouraged use, and the need for self-assurance was the reason most often reported. The early start and the "heavy use" of one or both drugs were determinant for the beginning of a progression towards illicit drugs. Marijuana was the first drug of the second phase. A stronger attitude for the search of a drug as a source of pleasure replaced the reason previously stated. The study reveals that the progression in drug use seems to be associated more with external decisions (e.g., peer pressure, dealing influence, etc.) than to the preference of the user. Two different progressions were identified: among the younger (<30): tobacco and/or alcohol, marijuana, snorted cocaine, and crack, and among the older (>30): tobacco and/or alcohol, marijuana, intravenous medication, snorted cocaine, intravenous cocaine, and crack. This pilot study's findings are limited in generalizability to its sample. Further research is needed. PMID- 17366133 TI - From phylogenetics to phylogenomics: the evolutionary relationships of insect endosymbiotic gamma-Proteobacteria as a test case. AB - The increasing availability of complete genome sequences and the development of new, faster methods for phylogenetic reconstruction allow the exploration of the set of evolutionary trees for each gene in the genome of any species. This has led to the development of new phylogenomic methods. Here, we have compared different phylogenetic and phylogenomic methods in the analysis of the monophyletic origin of insect endosymbionts from the gamma-Proteobacteria, a hotly debated issue with several recent, conflicting reports. We have obtained the phylogenetic tree for each of the 579 identified protein-coding genes in the genome of the primary endosymbiont of carpenter ants, Blochmannia floridanus, after determining their presumed orthologs in 20 additional Proteobacteria genomes. A reference phylogeny reflecting the monophyletic origin of insect endosymbionts was further confirmed with different approaches, which led us to consider it as the presumed species tree. Remarkably, only 43 individual genes produced exactly the same topology as this presumed species tree. Most discrepancies between this tree and those obtained from individual genes or by concatenation of different genes were due to the grouping of Xanthomonadales with beta-Proteobacteria and not to uncertainties over the monophyly of insect endosymbionts. As previously noted, operational genes were more prone to reject the presumed species tree than those included in information-processing categories, but caution should be exerted when selecting genes for phylogenetic inference on the basis of their functional category assignment. We have obtained strong evidence in support of the monophyletic origin of gamma-Proteobacteria insect endosymbionts by a combination of phylogenetic and phylogenomic methods. In our analysis, the use of concatenated genes has shown to be a valuable tool for analyzing primary phylogenetic signals coded in the genomes. Nevertheless, other phylogenomic methods such as supertree approaches were useful in revealing alternative phylogenetic signals and should be included in comprehensive phylogenomic studies. PMID- 17366134 TI - Inconsistency of phylogenetic estimates from concatenated data under coalescence. AB - Although multiple gene sequences are becoming increasingly available for molecular phylogenetic inference, the analysis of such data has largely relied on inference methods designed for single genes. One of the common approaches to analyzing data from multiple genes is concatenation of the individual gene data to form a single supergene to which traditional phylogenetic inference procedures - e.g., maximum parsimony (MP) or maximum likelihood (ML) - are applied. Recent empirical studies have demonstrated that concatenation of sequences from multiple genes prior to phylogenetic analysis often results in inference of a single, well supported phylogeny. Theoretical work, however, has shown that the coalescent can produce substantial variation in single-gene histories. Using simulation, we combine these ideas to examine the performance of the concatenation approach under conditions in which the coalescent produces a high level of discord among individual gene trees and show that it leads to statistically inconsistent estimation in this setting. Furthermore, use of the bootstrap to measure support for the inferred phylogeny can result in moderate to strong support for an incorrect tree under these conditions. These results highlight the importance of incorporating variation in gene histories into multilocus phylogenetics. PMID- 17366135 TI - Conditioned genome reconstruction: how to avoid choosing the conditioning genome. AB - Genome phylogenies can be inferred from data on the presence and absence of genes across taxa. Logdet distances may be a good method, because they allow expected genome size to vary across the tree. Recently, Lake and Rivera proposed conditioned genome reconstruction (calculation of logdet distances using only those genes present in a conditioning genome) to deal with unobservable genes that are absent from every taxon of interest. We prove that their method can consistently estimate the topology for almost any choice of conditioning genome. Nevertheless, the choice of conditioning genome is important for small samples. For real bacterial genome data, different choices of conditioning genome can result in strong bootstrap support for different tree topologies. To overcome this problem, we developed supertree methods that combine information from all choices of conditioning genome. One of these methods, based on the BIONJ algorithm, performs well on simulated data and may have applications to other supertree problems. However, an analysis of 40 bacterial genomes using this method supports an incorrect clade of parasites. This is a common feature of model-based gene content methods and is due to parallel gene loss. PMID- 17366136 TI - A step toward barcoding life: a model-based, decision-theoretic method to assign genes to preexisting species groups. AB - A major part of the barcoding of life problem is assigning newly sequenced or sampled individuals to existing groups that are preidentified externally (by a taxonomist, for example). This problem involves evaluating the statistical evidence towards associating a sequence from a new individual with one group or another. The main concern of our current research is to perform this task in a fast and accurate manner. To accomplish this we have developed a model-based, decision-theoretic framework based on the coalescent theory. Under this framework, we utilized both distance and the posterior probability of a group, given the sequences from members of this group and the sequence from a newly sampled individual to assign this new individual. We believe that this approach makes efficient use of the available information in the data. Our preliminary results indicated that this approach is more accurate than using a simple measure of distance for assignment. PMID- 17366137 TI - Imputing supertrees and supernetworks from quartets. AB - Inferring species phylogenies is an important part of understanding molecular evolution. Even so, it is well known that an accurate phylogenetic tree reconstruction for a single gene does not always necessarily correspond to the species phylogeny. One commonly accepted strategy to cope with this problem is to sequence many genes; the way in which to analyze the resulting collection of genes is somewhat more contentious. Supermatrix and supertree methods can be used, although these can suppress conflicts arising from true differences in the gene trees caused by processes such as lineage sorting, horizontal gene transfer, or gene duplication and loss. In 2004, Huson et al. (IEEE/ACM Trans. Comput. Biol. Bioinformatics 1:151-158) presented the Z-closure method that can circumvent this problem by generating a supernetwork as opposed to a supertree. Here we present an alternative way for generating supernetworks called Q imputation. In particular, we describe a method that uses quartet information to add missing taxa into gene trees. The resulting trees are subsequently used to generate consensus networks, networks that generalize strict and majority-rule consensus trees. Through simulations and application to real data sets, we compare Q-imputation to the matrix representation with parsimony (MRP) supertree method and Z-closure, and demonstrate that it provides a useful complementary tool. PMID- 17366138 TI - Artifactual phylogenies caused by correlated distribution of substitution rates among sites and lineages: the good, the bad, and the ugly. AB - Despite the advances in understanding molecular evolution, current phylogenetic methods barely take account of a fraction of the complexity of evolution. We are chiefly constrained by our incomplete knowledge of molecular evolutionary processes and the limits of computational power. These limitations lead to the establishment of either biologically simplistic models that rarely account for a fraction of the complexity involved or overfitting models that add little resolution to the problem. Such oversimplified models may lead us to assign high confidence to an incorrect tree (inconsistency). Rate-across-site (RAS) models are commonly used evolutionary models in phylogenetic studies. These account for heterogeneity in the evolutionary rates among sites but do not account for changing within-site rates across lineages (heterotachy). If heterotachy is common, using RAS models may lead to systematic errors in tree inference. In this work we show possible misleading effects in tree inference when the assumption of constant within-site rates across lineages is violated using maximum likelihood. Using a simulation study, we explore the ways in which gamma stationary models can lead to wrong topology or to deceptive bootstrap support values when the within-site rates change across lineages. More precisely, we show that different degrees of heterotachy mislead phylogenetic inference when the model assumed is stationary. Finally, we propose a geometry-based approach to visualize and to test for the possible existence of bias due to heterotachy. PMID- 17366139 TI - Base-compositional heterogeneity in the RAG1 locus among didelphid marsupials: implications for phylogenetic inference and the evolution of GC content. AB - Although theoretical studies have suggested that base-compositional heterogeneity can adversely affect phylogenetic reconstruction, only a few empirical examples of this phenomenon, mostly among ancient lineages (with divergence dates > 100 Mya), have been reported. In the course of our phylogenetic research on the New World marsupial family Didelphidae, we sequenced 2790 bp of the RAG1 exon from exemplar species of most extant genera. Phylogenetic analysis of these sequences recovered an anomalous node consisting of two clades previously shown to be distantly related based on analyses of other molecular data. These two clades show significantly increased GC content at RAG1 third codon positions, and the resulting convergence in base composition is strong enough to overwhelm phylogenetic signal from other genes (and morphology) in most analyses of concatenated datasets. This base-compositional convergence occurred relatively recently (over tens rather than hundreds of millions of years), and the affected gene region is still in a state of evolutionary disequilibrium. Both mutation rate and substitution rate are higher in GC-rich didelphid taxa, observations consistent with RAG1 sequences having experienced a higher rate of recombination in the convergent lineages. PMID- 17366140 TI - Multistate characters and diet shifts: evolution of Erotylidae (Coleoptera). AB - The dominance of angiosperms has played a direct role in the diversification of insects, especially Coleoptera. The shift to angiosperm feeding from other diets is likely to have increased the rate of speciation in Phytophaga. However, Phytophaga is only one of many hyperdiverse lineages of beetles and studies of host-shift proliferation have been somewhat limited to groups that primitively feed on plants. We have studied the diet-diverse beetle family Erotylidae (Cucujoidea) to determine if diet is correlated with high diversification rates and morphological evolution by first reconstructing ancestral diets and then testing for associations between diet and species number and diet and ovipositor type. A Bayesian phylogenetic analysis of morphological data that was previously published in Leschen (2003, Pages 1-108 in Fauna of New Zealand, 47; 53 terminal taxa and 1 outgroup, 120 adult characters and 1 diet character) yielded results that are similar to the parsimony analyses of Leschen (2003). Ancestral state reconstructions based on Bayesian and parsimony inference were largely congruent and both reconstructed microfungal feeding (the diet of the outgroup Biphyllidae) at the root of the Erotylidae tree. Shifts among microfungal, saprophagous, and phytophagous diets were most frequent. The largest numbers of species are contained in lineages that are macrofungal feeders (subfamily Erotylinae) and phytophagous (derived Languriinae), although the Bayesian posterior predictive tests of character state correlation were unable to detect any significant associations. Ovipositor morphology correlated with diet (i.e., acute forms were associated with phytophagy and unspecialized forms were associated with a mixture of diets). Although there is a general trend to increased species number associated with the shift from microfungal feeding to phytophagy (based on character mapping and mainly restricted to shifts in Languriinae), there is a large radiation of taxa feeding on macrofungi. Cycad feeding is scattered in more deeply diverged taxa and may have preceded the evolution of angiosperm feeding in some groups. Preliminary analysis of diet mapped onto higher beetle phylogenies suggests that about half of the major Coleoptera lineages may have had fungus feeding ancestors. We discuss the roles of stochastic models and prior distributions of the reconstruction of ancestral character states in the context of the current data. PMID- 17366141 TI - Pitfalls of heterogeneous processes for phylogenetic reconstruction. AB - Different genes often have different phylogenetic histories. Even within regions having the same phylogenetic history, the mutation rates often vary. We investigate the prospects of phylogenetic reconstruction when all the characters are generated from the same tree topology, but the branch lengths vary (with possibly different tree shapes). Furthering work of Kolaczkowski and Thornton (2004, Nature 431: 980-984) and Chang (1996, Math. Biosci. 134: 189-216), we show examples where maximum likelihood (under a homogeneous model) is an inconsistent estimator of the tree. We then explore the prospects of phylogenetic inference under a heterogeneous model. In some models, there are examples where phylogenetic inference under any method is impossible - despite the fact that there is a common tree topology. In particular, there are nonidentifiable mixture distributions, i.e., multiple topologies generate identical mixture distributions. We address which evolutionary models have nonidentifiable mixture distributions and prove that the following duality theorem holds for most DNA substitution models. The model has either: (i) nonidentifiability - two different tree topologies can produce identical mixture distributions, and hence distinguishing between the two topologies is impossible; or (ii) linear tests - there exist linear tests which identify the common tree topology for character data generated by a mixture distribution. The theorem holds for models whose transition matrices can be parameterized by open sets, which includes most of the popular models, such as Tamura-Nei and Kimura's 2-parameter model. The duality theorem relies on our notion of linear tests, which are related to Lake's linear invariants. PMID- 17366142 TI - Investigating stagnation in morphological phylogenetics using consensus data. PMID- 17366143 TI - Time to standardize taxonomies. PMID- 17366144 TI - Opinions on multiple sequence alignment, and an empirical comparison of repeatability and accuracy between POY and structural alignment. PMID- 17366148 TI - Ipsa Scientia Potestas Est (knowledge is power). PMID- 17366150 TI - Neuroscience and ethics: intersections. PMID- 17366151 TI - The neurobiology of addiction: implications for voluntary control of behavior. AB - There continues to be a debate on whether addiction is best understood as a brain disease or a moral condition. This debate, which may influence both the stigma attached to addiction and access to treatment, is often motivated by the question of whether and to what extent we can justly hold addicted individuals responsible for their actions. In fact, there is substantial evidence for a disease model, but the disease model per se does not resolve the question of voluntary control. Recent research at the intersection of neuroscience and psychology suggests that addicted individuals have substantial impairments in cognitive control of behavior, but this "loss of control" is not complete or simple. Possible mechanisms and implications are briefly reviewed. PMID- 17366152 TI - Voluntary control of behavior and responsibility. PMID- 17366153 TI - Wrestling Satan and conquering dopamine: addiction and free will. PMID- 17366154 TI - The social implications of neurobiological explanations of resistible compulsions. PMID- 17366155 TI - Addiction, responsibility and moral psychology. PMID- 17366156 TI - Affective neuroscience and addiction. PMID- 17366157 TI - Addiction, molecules and morality: disease does not obviate responsibility. PMID- 17366158 TI - Brain disease or moral condition? Wrong question. PMID- 17366159 TI - Addiction as an amoral condition? The case remains unproven. PMID- 17366160 TI - Normative judgments, responsibility and executive function. PMID- 17366161 TI - Addiction is not an affliction: addictive desires are merely pleasure-oriented desires. PMID- 17366162 TI - Ameliorating and exacerbating: surgical "prosthesis" in addiction. PMID- 17366163 TI - The social: a missing term in the debate over addiction and voluntary control. PMID- 17366164 TI - Personhood and neuroscience: naturalizing or nihilating? AB - Personhood is a foundational concept in ethics, yet defining criteria have been elusive. In this article we summarize attempts to define personhood in psychological and neurological terms and conclude that none manage to be both specific and non-arbitrary. We propose that this is because the concept does not correspond to any real category of objects in the world. Rather, it is the product of an evolved brain system that develops innately and projects itself automatically and irrepressibly onto the world whenever triggered by stimulus features such as a human-like face, body, or contingent patterns of behavior. We review the evidence for the existence of an autonomous person network in the brain and discuss its implications for the field of ethics and for the implicit morality of everyday behavior. PMID- 17366165 TI - The neuroscience of a person network. PMID- 17366166 TI - Border zones of consciousness: another immigration debate? PMID- 17366167 TI - The necessary-and-sufficient boondoggle. PMID- 17366168 TI - The illusion of personhood. PMID- 17366169 TI - Persons and personification. PMID- 17366170 TI - Neuroscience and metaphysics (redux). PMID- 17366171 TI - Personhood: elusive but not illusory. PMID- 17366172 TI - Is personhood an illusion? PMID- 17366173 TI - Personhood: empirical thing or rational concept? PMID- 17366174 TI - Illusions about persons. PMID- 17366175 TI - Against scientism, for personhood. PMID- 17366176 TI - Persons, metaphysics and ethics. PMID- 17366177 TI - Differing vulnerabilities: the moral significance of Lockean personhood. PMID- 17366178 TI - A transcendental argument for the concept of personhood in neuroscience. PMID- 17366179 TI - Identifying challenges and conditions for the use of neuroscience in bioethics. PMID- 17366181 TI - Ethics and public health emergencies: restrictions on liberty. AB - Responses to public health emergencies can entail difficult decisions about restricting individual liberties to prevent the spread of disease. The quintessential example is quarantine. While isolating sick patients tends not to provoke much concern, quarantine of healthy people who only might be infected often is controversial. In fact, as the experience with severe acute respiratory syndrome (SARS) shows, the vast majority of those placed under quarantine typically don't become ill. Efforts to enforce involuntary quarantine through military or police powers also can backfire, stoking both panic and disease spread. Yet quarantine is part of a limited arsenal of options when effective treatment or prophylaxis is not available, and some evidence suggests it can be effective, especially when it is voluntary, home-based and accompanied by extensive outreach, communication and education efforts. Even assuming that quarantine is medically effective, however, it still must be ethically justified because it creates harms for many of those affected. Moreover, ethical principles of reciprocity, transparency, non-discrimination and accountability should guide any implementation of quarantine. PMID- 17366182 TI - Response to open peer commentaries on "Ethics consultation in U.S. hospitals: a national survey". PMID- 17366183 TI - Why bioethics cannot figure out what to do with race. AB - Race and religion are integral parts of bioethics. Harm and oppression, with the aim of social and political control, have been wrought in the name of religion against Blacks and people of color as embodied in the Ten Commandments, the Inquisition, and in the history of the Holy Crusades. Missionaries came armed with Judeo/Christian beliefs went to nations of people of color who had their own belief systems and forced change and caused untold harms because the indigenous belief systems were incompatible with their own. The indigenous people were denounced as ungodly, pagan, uncivilized, and savage. Hence, laws were enacted because of their perceived need to structure a sense of morality and to create and build a culture for these indigenous people of color. To date bioethics continues to be informed by a Western worldview that is Judeo/Christian in belief and orientation. However, missing from bioethical discourse in America is the historical influence of the Black Church as a cultural repository, which continues to influence the culture of Africans and Blacks. Cultural aspects of peoples of color are still largely ignored today. In attempting to deal with issues of race while steering clear of the religious and cultural impact of the Black Church, bioethics finds itself in the middle of a distressing situation: it simply cannot figure out what to do with race. PMID- 17366184 TI - Ethics consultation in United States hospitals: a national survey. AB - CONTEXT: Although ethics consultation is commonplace in United States (U.S.) hospitals, descriptive data about this health service are lacking. OBJECTIVE: To describe the prevalence, practitioners, and processes of ethics consultation in U.S. hospitals. DESIGN: A 56-item phone or questionnaire survey of the "best informant" within each hospital. PARTICIPANTS: Random sample of 600 U.S. general hospitals, stratified by bed size. RESULTS: The response rate was 87.4%. Ethics consultation services (ECSs) were found in 81% of all general hospitals in the U.S., and in 100% of hospitals with more than 400 beds. The median number of consults performed by ECSs in the year prior to survey was 3. Most individuals performing ethics consultation were physicians (34%), nurses (31%), social workers (11%), or chaplains (10%). Only 41% had formal supervised training in ethics consultation. Consultation practices varied widely both within and between ECSs. For example, 65% of ECSs always made recommendations, whereas 6% never did. These findings highlight a need to clarify standards for ethics consultation practices. PMID- 17366185 TI - A better way to evaluate clinical ethics consultations? An ecological approach. PMID- 17366186 TI - A comment on community consultation. PMID- 17366187 TI - The failure of the consult model: why "mediation" should replace "consultation". PMID- 17366188 TI - Pride and prejudice: how might ethics consultation services minimize bias? PMID- 17366189 TI - Credentialing ethics consultants: an invitation to collaboration. PMID- 17366190 TI - Failure to thrive: can education save the life of ethics consultation? PMID- 17366191 TI - Education to dispel the myth. PMID- 17366192 TI - Ethics consultation: whose ethics? PMID- 17366193 TI - The goals of ethics consultation: rejecting the role of "ethics police". PMID- 17366194 TI - The war on error. PMID- 17366195 TI - Different questions, different goals. PMID- 17366196 TI - Additional implications of a national survey on ethics consultation in United States hospitals. PMID- 17366197 TI - Who's guarding the henhouse? Ramifications of the Fox study. PMID- 17366198 TI - Why a criminal ban? Analyzing the arguments against somatic cell nuclear transfer in the Canadian parliamentary debate. AB - Somatic cell nuclear transfer (SCNT) remains a controversial technique, one that has elicited a variety of regulatory responses throughout the world. On March 29, 2005, Canada's Assisted Human Reproduction Act came into force. This law prohibits a number of research activities, including SCNT. Given the pluralistic nature of Canadian society, the creation of this law stands as an interesting case study of the policy-making process and how and why a liberal democracy ends up making the relatively rare decision to use a statutory prohibition, backed by severe penalties, to stop a particular scientific activity. In this article, we provide a comprehensive and systematic legal analysis of the legislative process and parliamentary debates associated with the passage of this law. PMID- 17366199 TI - An Islamic view to stem cell research and cloning: Iran's experience. PMID- 17366200 TI - Slippery slopes to slippery slopes: therapeutic cloning and the criminal law. PMID- 17366201 TI - Overstating the ban, ignoring the compromise. PMID- 17366202 TI - Professionalism in biomedical science. PMID- 17366203 TI - Canada's Assisted Human Reproduction Act: a chimera of religion and politics. PMID- 17366204 TI - The Canadian Assisted Human Reproduction Act: protecting women's health while potentially allowing human somatic cell nuclear transfer into non-human oocytes. PMID- 17366205 TI - Criminal law in the regulation of somatic cell nuclear transfer. PMID- 17366206 TI - Money and distorted ethical judgments about research: ethical assessment of the TeGenero TGN1412 trial. AB - The recent TeGenero phase I trial of a novel monoclonal antibody in healthy volunteers produced a drastic inflammatory reaction in participants receiving the experimental agent. Commentators on the ethics of the research have focused considerable attention on the role of financial considerations: the for-profit status of the biotechnology company and Contract Research Organization responsible respectively for sponsoring and conducting the trial and the amount of monetary compensation to participants. We argue that these financial considerations are largely irrelevant and distort ethical appraisal of this tragic research. Except for administering the antibody to all 6 participants nearly simultaneously, the trial appears to fulfill all of the critical ethical requirements for clinical research--social value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, informed consent, and respect for enrolled participants. PMID- 17366207 TI - Risk, judgment and fairness in research incentives. PMID- 17366208 TI - Evaluation of research design by research ethics committees: misleading reassurance and the need for substantive reforms. PMID- 17366209 TI - Money matters. PMID- 17366210 TI - Money, advertising and seduction in human subjects research. PMID- 17366211 TI - Ethical flaws in the TeGenero trial. PMID- 17366212 TI - Faulty premise, premature conclusion: that money was extraneous to the research ethics of the TGN1412 study. PMID- 17366216 TI - Playing it safe. PMID- 17366217 TI - Response to open peer commentaries on "Compelled authorizations for disclosure of health records: magnitude and implications". PMID- 17366218 TI - What vaccination programs mean for research. PMID- 17366219 TI - Determining risk in pediatric research with no prospect of direct benefit: time for a national consensus on the interpretation of federal regulations. AB - United States federal regulations for pediatric research with no prospect of direct benefit restrict institutional review board (IRB) approval to procedures presenting: 1) no more than "minimal risk" ( section sign 45CFR46.404); or 2) no more than a "minor increase over minimal risk" if the research is commensurate with the subjects' previous or expected experiences and intended to gain vitally important information about the child's disorder or condition ( section sign 45CFR46.406) (DHHS 2001). During the 25 years since their adoption, these regulations have helped IRBs balance subject protections with the pursuit of scientific knowledge to advance children's welfare. At the same time, inconsistency in IRB application of these regulations to pediatric protocols has been widespread, in part because of the ambiguity of the regulatory language. During the past decade, three federally-charged committees have addressed these ambiguities: 1) the National Human Research Protections Advisory Committee (NHRPAC) (Washington, DC), 2) the Institute of Medicine (IOM) Committee on the Ethical Conduct of Clinical Research Involving Children (Washington, DC); and 3) the United States Department of Health and Human Services Secretary's Advisory Committee for Human Research Protections (SACHRP) (Washington, DC). The committees have reached similar conclusions on interpretation of language within regulations section sign section sign 45CFR46.404 and 406; these conclusions are remarkably consistent with recent international recommendations and those of the original National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) report from which current regulations are based. Drawing on the committees' public reports, this article identifies the ethical issues posed by ambiguities in regulatory language, summarizes the committees' deliberations, and calls for a national consensus on recommended criteria. PMID- 17366220 TI - Research in wonderland: does "minimal risk" mean whatever an institutional review board says it means? PMID- 17366221 TI - Is risky pediatric research without prospect of direct benefit ever justified? PMID- 17366222 TI - When can children with conditions be in no-benefit, higher-hazard pediatric studies? PMID- 17366223 TI - When "risk" and "benefit" are open to interpretation--as is generally the case. PMID- 17366224 TI - Instead of revising half the story, why not rewrite the whole thing? PMID- 17366225 TI - The risky business of assessing research risk. PMID- 17366226 TI - Difficult hospital inpatient discharge decisions: ethical, legal and clinical practice issues. PMID- 17366227 TI - Discharge dilemmas as system failures. PMID- 17366228 TI - Difficult discharge: lessons from the oncology setting. PMID- 17366229 TI - Changing policy to reflect a concern for patients who sign out against medical advice. PMID- 17366230 TI - When cure entails care. PMID- 17366231 TI - Holding the hospital hostage. PMID- 17366232 TI - Compelled authorizations for disclosure of health records: magnitude and implications. AB - Each year individuals are required to execute millions of authorizations for the release of their health records as a condition of employment, applying for various types of insurance, and submitting claims for benefits. Generally, there are no restrictions on the scope of information released pursuant to these compelled authorizations, and the development of a nationwide system of interoperable electronic health records will increase the amount of health information released. After quantifying the extent of these disclosures, this article discusses why it is important to limit disclosures of health information for nonmedical purposes as well as how it may be possible to do so. PMID- 17366233 TI - Practical, state, and federal limits on the scope of compelled disclosure of health records. PMID- 17366234 TI - Addressing privacy concerns through the health insurance portability and accountability act privacy rule. PMID- 17366235 TI - Physicians, patients and confidentiality: the role of physicians in electronic health records. PMID- 17366236 TI - The flaw of informed consent. PMID- 17366241 TI - A new gender-based model for women's recovery from substance abuse: results of a pilot outcome study. AB - Despite repeated calls for gender-based recovery models for women, there has been a lack of empirical research on this topic. We thus sought to evaluate a women's manual-based substance use disorder recovery model in a pilot study. Participants were opioid-dependent women in a methadone maintenance treatment program who received 12 sessions of the gender-based model in group format over two months. Assessment was conducted before and after the intervention, with results indicating significant improvements in drug use (verified by urinalysis), impulsive-addictive behavior, global improvement, and knowledge of the treatment concepts. Patients' high attendance rate (87% of available sessions) and strong treatment satisfaction additionally support the potential use of this treatment model. Future research would benefit from larger samples and enhanced scientific methodology. PMID- 17366242 TI - Decreased perfusion in young alcohol-dependent women as compared with age-matched controls. AB - AIM: To use the superior spatial resolution of magnetic resonance imaging (MRI) to examine differences in cerebral perfusion between young alcohol dependent and normal women. METHODS: Eight alcohol dependent women and 8 controls (all ages 18 25) received single-slice resting perfusion-weighted MRI (directly proportional to brain blood flow), with slices located above the corpus callosum. RESULTS: Alcohol-dependent women had decreased perfusion in prefrontal and left parietal regions. CONCLUSIONS: Reduced perfusion has not previously been reported in young, physically healthy alcohol dependent females, yet is consistent with previously reported decreased cerebral activity in alcohol dependence. PMID- 17366243 TI - Gender differences in the relationship between heavy episodic drinking, social roles, and alcohol-related aggression in a U.S. sample of late adolescent and young adult drinkers. AB - To better understand alcohol-related aggression among late adolescent and young adult drinkers, the present research aimed to examine whether: 1) the relationship between heavy episodic drinking and alcohol-related aggression was different for males and females; and 2) social roles (marital and employment status, living arrangement, student status) influenced alcohol-related aggression. Secondary analyses of the National Longitudinal Survey of Youth were conducted using a composite sample of drinkers aged 17 to 21 in 1994, 1996 and 1998 (n = 808). A stronger relationship was found between heavy episodic drinking and fights after drinking for females than for males. In terms of social roles, males who lived with their parents were more likely to fight after drinking than those living in their own dwelling, while females who dropped out of high school were significantly more likely to fight after drinking compared with college students. A gender focus is required in future research on alcohol-related aggression. PMID- 17366244 TI - Sexual aggression among White, Black, and Hispanic couples in the U.S.: alcohol use, physical assault and psychological aggression as its correlates. AB - This article examines the prevalence of sexual aggression and its association with alcohol and other forms of violence, such as physical abuse and psychological aggression, in a national sample of married and cohabiting couples. These couples were part of a longitudinal study conducted in 1995 and 2000. The analyses include 406 White, 232 Black, and 387 Hispanic couples interviewed in 2000. Male-to-female sexual aggression rates ranged from 11% to 23% and female-to male aggression rates ranged from 5.5% to 13.5%. Insisting on having sex without use of physical force and having sex without a condom are the two most frequently reported types of sexual aggression across all ethnic groups. Male and female perpetrated sexual aggression rates among Black couples were over 2 times the rate of White couples. Male perpetrated severe psychological aggression is a significant predictor of male sexual aggression. Female perpetrated severe psychological aggression predicted female sexual aggression. The study findings underscore the importance of addressing alcohol use and the presence of psychological abuse in the light of preventing other forms of violence including sexual aggression among couples. PMID- 17366245 TI - Maternal depression and cognitive features of 9-year-old children prenatally exposed to cocaine. AB - This study evaluated cocaine exposure and maternal characteristics as competing predictors of school-age cognitive, achievement, and language performance. One group of 47 exposed 9-year-old children were first studied in an earlier prenatal study. A non-exposed contrast group (n = 46) served as a reference. Maternal measures included: IQ, psychopathology, drugs, demographics, and environment. Child intelligence, language, and achievement scores were inversely related to maternal IQ and depression scores, with cocaine exposure significant secondary or tertiary predictors for many children. Verbal IQ scores of exposed children strongly reflected maternal depression (r = .54) but no such relationship was found among the non-exposed cohort (r = .00). PMID- 17366246 TI - Characteristics, drug use, and sex partners of a sample of male sex workers. AB - Some male sex workers (MSWs) are also engaging in a significant amount of illicit drug use and other high risk behavior. The purpose of this study was to examine demographic characteristics, HIV risk behaviors, and sex partner characteristics in a sample of MSW. Data were collected from 179 men who were trading sex for money in Houston, TX. In the past 30 days they reported an average of 56 male partners and 5 female partners. Of the 179 men, 152 had been tested for HIV and knew their status. Twenty-six percent of those tested had tested positive. PMID- 17366247 TI - Adherence and retention of female injection drug users in a phase III clinical trial in inner city Baltimore. AB - Adherence and retention of female injection drug users (IDUs) in clinical trials are not well known and were evaluated among 458 female IDUs in a clinical trial in Baltimore. Of all, 62.9% were adherent to visits (attended > or = 80% of visits). Of women with > or = 1 visit after enrollment, 76% were adherent to treatment (took > or = 80% of pills); 27.7% were lost to follow-up (missed > or = 3 consecutive visits). Women nonadherent to visits were younger and less likely to be on methadone. Women lost to follow-up were younger, more often white, not on methadone, and injecting drugs daily. Fair-moderate adherence to visits and treatment occurs among female IDUs in a clinical trial. PMID- 17366248 TI - Predictors of cannabis dependence recovery among epidemiological survey respondents in the United States. AB - Cannabis Dependence remains a highly prevalent disorder in the United States. Though longitudinal studies have accumulated data regarding risk factors and psychosocial correlates of habitual cannabis use, the field lacks knowledge regarding predictors of recovery in community samples. Thus we conducted a secondary data analysis of The National Epidemiological Survey on Alcohol and Related Conditions to address this issue. Recovery was defined as the absence of Cannabis Dependence and Cannabis Abuse during the past year. Logistic Regression analysis revealed that older age, marriage, and non-daily cannabis use were positively associated with recovery. PMID- 17366249 TI - An example of activity based costing of treatment programs. AB - We introduce a new tool that can be used for estimating number, length of time, and nature of services patient receive in drug treatment programs. While the field has made significant progress in standardizing the collection of expenditure data, little progress has been made on creating a standard measure for estimating program activities and census. We report on a method of estimating program activities. PMID- 17366250 TI - Correlates of injury among ED visits: effects of alcohol, risk perception, impulsivity, and sensation seeking behaviors. AB - This cross-sectional study used a random sample of 412 Emergency Department (ED) patients to test the following hypothesizes: 1) injury would be positively associated with problem drinking and recent drinking; 2) impulsivity and sensation seeking would be positively associated with injury, while risk perception would be negatively associated with injury. Results show recent drinking is associated with 2-fold increase in the odds of injury [OR and 95%; CI = 2.34 (1.07-5.10)] while problem drinking and personality factors were unrelated to injury. Other significant predictors were gender and age. Findings suggest a need for alcohol screening for patients who check themselves into the ED due to injury. PMID- 17366251 TI - Successfully integrating an HIV risk reduction intervention into a community based substance abuse treatment program. AB - A number of evidence-based HIV risk reduction interventions are now widely available to clinicians. However, difficulties with intervention transportability have historically impeded the integration of evidence-based interventions into clinical settings. In this article, we discuss one successful approach to transportability through appropriate intervention selection, adaptation, placement, and evaluation. Our intervention adaptation process required substantially reducing the content and duration of an evidence-based intervention. Findings from 226 assessed participants suggested significant drug- and sex-related risk reduction outcomes, particularly among participants at greatest risk. Results point to a need to examine the relative costs/benefits of comprehensive, evidence-based interventions vs. shortened, adapted versions thereof. PMID- 17366252 TI - Treatment entry and predictors among opiate-using injection drug users. AB - This study examines entry into drug treatment among 491 street-recruited injection drug users in Denver, Colorado. The primary outcome was treatment entry within 6 months. Univariate tests were run using chi-square t-test analyses. Significant variables were included in a multiple logistic regression. Results showed that having more outreach contacts, not being homeless, having fewer problems with alcohol but more problems with drugs, and the contemplation or determination stage of change were associated with entering treatment. The identification of predictors of treatment entry may be useful for treatment centers in engaging certain populations of drug users. Behavioral interventions are an important tool in recruiting drug injectors into treatment. PMID- 17366253 TI - Effectiveness of motivational incentives in stimulant abusing outpatients with different treatment histories. AB - OBJECTIVE: To determine if prize-based abstinence incentives will differentially affect substance abuse outcomes in patients with different treatment histories. DESIGN: Treatment seeking outpatients with more or less prior treatment episodes were randomized to receive either prize-based incentives plus treatment as usual (TAU) or TAU alone. Outcome variables included longest sustained period of abstinence, number of negative urine drug screens (UDS), and retention in treatment. RESULTS: Treatment experienced participants were older, more likely to be female, African American, unemployed, and with more severe cocaine and psychiatric problems. The effectiveness of incentives did not differ significantly between the two treatment history groups with regard to the outcome measures. PMID- 17366254 TI - The impact of childhood maltreatment on young adults' substance abuse. AB - Designed to establish a causal relationship between childhood victimization and young adults' substance abuse, this study also examined depression's role as mediator in that causal relationship. The study employs child-abuse measures that weigh both the type (sexual, physical) and the persistence of abuse. The study took as its substance-abuse measures the DSM-IV criteria for current alcohol abuse, current marijuana abuse, and current drug abuse. Data from the first 5 waves of the National Youth Survey (NYS) was employed, along with data from its 7th wave, to establish the temporal order needed to determine causal relationship. Childhood physical abuse proved a strong predictor of young adults' current substance abuse, although sexual abuse did not. Depression was shown to mediate the relationship of physical abuse to current alcohol abuse and current drug abuse, but not to current marijuana abuse. PMID- 17366255 TI - The impact of a brief induction on short-term continuation in a therapeutic community. AB - Continuation in substance abuse treatment is one of the strongest predictors of successful post-treatment outcomes across all major treatment modalities. However, since rates of attrition are highest within the first month of treatment, many clients drop out before these positive outcomes are realized. The impact of organizational and therapeutic factors on treatment continuation in therapeutic communities has received little attention in the literature. This study was conducted to determine whether a brief induction to treatment was associated with improved treatment continuation in a therapeutic community. Multivariable logistic regression analysis indicated that induction was associated with 30-day continuation. Prior treatment and court-mandated treatment were also associated with continuation. PMID- 17366256 TI - Substance use behaviors of young people with a moderate learning disability: a longitudinal analysis. AB - Substance use behaviors of young people attending a special school are reported over a 4-year period from the age of 12-16 years. The article investigated these behaviors by surveying a cohort of young people with a statement for moderate learning disabilities annually during the last 4 years of compulsory schooling. The findings show that these young people consistently reported lower levels of tobacco, alcohol, and cannabis use compared with those attending mainstream school. No other illicit drug use was reported. The potential implications of these findings are discussed in relation to the context and timing of targeted substance education and prevention initiatives for young people with moderate learning disability attending a special school. PMID- 17366257 TI - Providing live supervision via teleconferencing improves acquisition of motivational interviewing skills after workshop attendance. AB - Teleconferencing Supervision is a method for training community-based substance abuse clinicians in Motivational Interviewing (MI). Following a 2-day workshop, 13 clinicians received live supervision via telephone during 5 counseling sessions conducted at their community treatment facilities. Clinicians were assessed for skill level at post-workshop, at post-training, and 3 months later; learning was assessed using the MI Treatment Integrity instrument. All summary scores and therapist behavior frequency counts improved by post-training or by the 3 month follow-up, although some gains were not statistically significant. Teleconferencing Supervision may help facilitate the proficient use of MI community clinicians following workshop instruction. PMID- 17366258 TI - Associations between alcohol, heroin, and cocaine use and high risk sexual behaviors among detoxification patients. AB - The purpose of this study was to assess associations between substance use (alcohol to intoxication, heroin, and cocaine) and sexual activity, high risk sexual behaviors, and STD among detoxification inpatients (n = 470). Participants were surveyed on past 30 day substance use, past 6 month sexual behaviors, and STD in the past 6 months and/or over 24 months of follow-up. Logistic regression models adjusted for demographics found that cocaine use was significantly associated with being sexually active (OR(adj) = 2.3, 95% CI = 1.1-4.8) and selling sex (OR(adj) = 2.6, 95% CI = 1.3-5.3). Alcohol and heroin were not significantly associated with sexual activity, high risk sexual behaviors or STD in this sample. PMID- 17366259 TI - Screening for alcohol use patterns among methadone maintenance patients. AB - Alcohol use among Methadone Maintenance Treatment (MMT) patients poses a major health risk, exacerbates psychopathology, and increases the risk of death by accidental overdose. Despite these factors, screening for alcohol use remains underutilized in the methadone community. Utilizing a self-report screening measure - the Michigan Alcohol Screening Test (MAST) - and consistent with the literature, we found high rates of alcohol problems among MMT patients. Benefits and limitations of using the MAST to screen for alcohol use patterns are discussed. PMID- 17366260 TI - Influence of religious affiliation in alcohol use among adolescents in Trinidad, Tobago, and St. Lucia: a follow-up study. AB - OBJECTIVE: This study examined the effects of religious affiliation and other demographic variables in alcohol use and attitudes among adolescents in Trinidad, Tobago and St. Lucia. METHOD: The study used a stratified random sample design of 380 male and 455 female students belonging to the 3 major ethnic groups in Trinidad, Tobago and St. Lucia (Afro-Trinidadian, Indo-Trinidadian, and Mixed group). RESULTS: MANOVA showed an effect for religion, with Hindu adolescents having higher levels of regular alcohol use. CONCLUSIONS: This finding supports the existing research in Trinidad and developed countries on the effect of various religious denominations of alcohol use and attitudes. PMID- 17366262 TI - The role of the cerebellum for predictive control of grasping. AB - Predictive control of grasping forces when manipulating objects in the environment is suggested to reflect internal models that capture the causal relationship between actions and their consequences. The anatomical correlate of predictive control of grasping within the central nervous system is not completely understood. One structure which has been related to the neural representation of internal models is the cerebellum. Given its stereotyped cytoarchitecture, the widespread connections with cortical and subcortical sensory-motor structures and the neural activity of cerebellar Purkinje cells during sensory-motor tasks, the cerebellum has long been considered to play a major role in the establishment and maintenance of sensory-motor representations related to voluntary movement. Such representations are necessary to predict the consequences of our own movements. Here we review theoretical concepts, electrophysiological, imaging and behavioural data suggesting the cerebellum to be the anatomical and functional correlate of internal models relevant for predictive control of grasping. PMID- 17366263 TI - The cerebellum and neural networks for rhythmic sensorimotor synchronization in the human brain. AB - Sensorimotor synchronization (SMS) is the rhythmic synchronization between a timed sensory stimulus and a motor response. This rather simple function requires complex cerebral processing whose basic mechanisms are far from clear. The importance of SMS is related to its hypothesized relevance in motor recovery following brain lesions. This is witnessed by the large number of studies in different disciplines addressing this issue. In the present review we will focus on the role of the cerebellum by referring to the general modeling of SMS functioning. Although at present no consensus exists on cerebellar timekeeping function it is generally accepted that cerebellar input and output flow process time information. Reviewed data are considered within the framework of the 'sensory coordination' hypothesis of cerebellar functioning. The idea that timing might be within the parameters that are under cerebellar control to optimize cerebral cortical functioning is advanced. PMID- 17366264 TI - The cerebellum and sensorimotor coupling: looking at the problem from the perspective of vestibular reflexes. AB - Cerebellar modules process afferent information and deliver outputs relevant for both reflex and voluntary movements. The response of cerebellar modules to a given input depends on the whole array of signals impinging on them. Studies on vestibular reflexes indicate that the response of the cerebellar circuits to the vestibular input is modified by the integration of multiple visual, vestibular and somatosensory afferent signals. In this way the cerebellum slowly adapts these reflexes when they are not adequate to the behavioural condition and allows their fast modifications when the relative position of the body segments and that of the body in space are changed. Studies on voluntary movements indicate that the cerebellum is responsible for motor learning that consists of the development of new input-output associations. Several theoretical, anatomical and clinical studies are consistent with the hypothesis that the cerebellum allows the delivery of motor commands which vary according to the condition of the motor apparatus. Finally, the cerebellum could change the relation between visual information and aimed reaching movements according to the position of the eyes in the orbit and of the neck over the body. We propose that, due to the large expansion of its cortex, an important function of the cerebellum could be that of expanding the range of sensorimotor associations according to all the factors characterizing the behavioural condition. Indeed, following cerebellar lesion, learning is often lost, the movement results impaired and requires an increased attention. In the light of the recently discovered connections of the cerebellum with the rostral regions of the frontal lobe, it can be suggested that the ability of cerebellar circuits to modify the rules of input-output coupling according to a general context is a fundamental property allowing the cerebellum to control not only motor but also cognitive functions. PMID- 17366265 TI - The involvement of the human cerebellum in eyeblink conditioning. AB - Besides its known importance for motor coordination, the cerebellum plays a major role in associative learning. The form of cerebellum-dependent associative learning, which has been examined in greatest detail, is classical conditioning of eyeblink responses. The much advanced knowledge of anatomical correlates, as well as cellular and molecular mechanisms involved in eyeblink conditioning in animal models are of particular importance because there is general acceptance that findings in humans parallel the animal data. The aim of the present review is to give an update of findings in humans. Emphasis is put on human lesion studies, which take advantage of the advances of high-resolution structural magnetic resonance imaging (MRI). In addition, findings of functional brain imaging in healthy human subjects are reviewed. The former helped to localize areas involved in eyeblink conditioning within the cerebellum, the latter was in particular helpful in delineating extracerebellar neural substrates, which may contribute to eyeblink conditioning. Human lesion studies support the importance of cortical areas of the ipsilateral superior cerebellum both in the acquisition and timing of conditioned eyeblink responses (CR). Furthermore, the ipsilateral cerebellar cortex seems to be also important in extinction of CRs. Cortical areas, which are important for CR acquisition, overlap with areas related to the control of the unconditioned eyeblink response. Likewise, cortical lesions are followed by increased amplitudes of unconditioned eyeblinks. These findings are in good accordance with the animal literature. Knowledge about contributions of the cerebellar nuclei in humans, however, is sparse. Due to methodological limitations both of human lesion and functional MRI studies, at present no clear conclusions can be drawn on the relative contributions of the cerebellar cortex and nuclei. PMID- 17366266 TI - The neural basis of ataxic dysarthria. AB - Lesions to the cerebellum often give rise to ataxic dysarthria which is characterized by a primary disruption to articulation and prosody. Converging evidence supports the likelihood of speech motor programming abnormalities in addition to speech execution deficits. The understanding of ataxic dysarthria has been further refined by the development of neural network models and neuroimaging studies. A critical role of feedforward processing by the cerebellum has been established and linked to speech motor control and to aspects of ataxic dysarthria. Moreover, this research has helped to define models of the cerebellar contributions to speech processing and production, and to posit possible regions of speech localization within the cerebellum. Bilateral, superior areas of the cerebellum appear to mediate speech motor control while a putative role of the right cerebellar hemispheres in the planning and processing of speech has been suggested. PMID- 17366267 TI - Rodent models of tremor. AB - This review focuses on rodent models of tremor, particularly those induced by pharmacological agents. Harmaline is one of the most frequently used tremor generating drugs and harmaline-induced tremor is regarded as a model of essential tremor. Harmaline acts on inferior olive neurons, causing enhanced neuronal synchrony and rhythmicity in the olivocerebellar system. In addition, it selectively induces cerebellar Purkinje cell death, speculatively because of excessive glutamate release from nerve terminals of the olivocerebellar system onto Purkinje cells. Systemic administration of cholinomimetics can also produce generalized tremor, and muscarinic receptors on striatal neurons are thought to be the best candidate for the tremor-generating mechanism. On the other hand, dopaminergic neurotoxins, which are used in models of parkinsonism, have yet to be used for experimental analysis of tremor, because tremors induced by dopamine depletion in rodents are less remarkable than those induced by harmaline or cholinomimetics. Recently developed gamma-aminobutyric acid (GABA)(A) receptor alpha-1 subunit knockout mice exhibit postural and kinetic tremors, and clearly reproduce the features of essential tremors. Although from a phenomenological point of view, rodent models of tremor cannot entirely mimic human tremor disorders, they have useful advantages in the analysis of pathophysiological mechanisms underlying tremor. Development of convenient and reproducible methods for evaluating rodent tremor is therefore recommended. PMID- 17366268 TI - Mechanical suppression of essential tremor. AB - This paper describes a new treatment for essential tremor. A wearable orthosis, which can be adapted to each configuration of each joint of the upper limb, is able to apply effective dynamic force between consecutive segments of the upper limb and change its biomechanical characteristics. The orthosis is controlled by a computer with a dedicated software application that distinguishes between real time tremor and voluntary movement. The wearable orthosis is able to detect position, rate and acceleration of rotation of the joint by means of a chip gyroscope. This technology was evaluated in six patients suffering from essential tremor. The technique is non invasive and represents an alternative to medication and deep brain stimulation. PMID- 17366269 TI - Mechanisms of cerebellar gait ataxia. AB - The cerebellum is important for movement control and plays a critical role in balance and locomotion. As such, one of the most characteristic and sensitive signs of cerebellar damage is gait ataxia. How the cerebellum normally contributes to locomotor behavior is unknown, though recent work suggests that it helps generate appropriate patterns of limb movements, dynamically regulate upright posture and balance, and adjust the feedforward control of locomotor output through error-feedback learning. The purpose of this review is to examine mechanisms of cerebellar control of locomotion, emphasizing studies of humans and other animals. Implications for rehabilitation are also considered. PMID- 17366270 TI - Role of cerebellum in learning postural tasks. AB - For a long time, the cerebellum has been known to be a structure related to posture and equilibrium control. According to the anatomic structure of inputs and internal structure of the cerebellum, its role in learning was theoretically reasoned and experimentally proved. The hypothesis of an inverse internal model based on feedback-error learning mechanism combines feedforward control by the cerebellum and feedback control by the cerebral motor cortex. The cerebellar cortex is suggested to acquire internal models of the body and objects in the external world. During learning of a new tool the motor cortex receives feedback from the realized movement while the cerebellum produces only feedforward command. To realize a desired movement without feedback of the realized movement, the cerebellum needs to form an inverse model of the hand/arm system. This suggestion was supported by FMRi data. The role of cerebellum in learning new postural tasks mainly concerns reorganization of natural synergies. A learned postural pattern in dogs has been shown to be disturbed after lesions of the cerebral motor cortex or cerebellar nuclei. In humans, learning voluntary control of center of pressure position is greatly disturbed after cerebellar lesions. However, motor cortex and basal ganglia are also involved in the feedback learning postural tasks. PMID- 17366272 TI - An introduction to the section. PMID- 17366271 TI - The role of transcranial magnetic stimulation in the study of cerebellar cognitive function. AB - Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of brain structures. This technique can be used either for stimulating the motor cortex, recording motor evoked potentials from peripheral muscles, or for modulating the excitability of other non-motor areas in order to establish their necessity for a given task. TMS of the cerebellum can give interesting insights on the cerebellar functions. Paired-TMS techniques, delivering stimuli over the cerebellum followed at various interstimulus intervals by stimuli over the motor cortex, allow studying the pattern of connectivity between the cerebellum and the contralateral motor cortex in physiological as well as in pathological conditions. Repetitive TMS, delivering trains of stimuli at different frequencies, allows interfering with the function of cerebellar circuits during the execution of cognitive tasks. This application complements neuropsychological and neuroimaging studies in the study of the cerebellar involvement in a number of cognitive operations, ranging from procedural memory, working memory and learning through observation. PMID- 17366273 TI - President's Annual State Of The Academy Report. PMID- 17366276 TI - Functional near infrared spectroscopy (fNIRS): an emerging neuroimaging technology with important applications for the study of brain disorders. AB - Functional near-infrared spectroscopy (fNIRS) is an emerging functional neuroimaging technology offering a relatively non-invasive, safe, portable, and low-cost method of indirect and direct monitoring of brain activity. Most exciting is its potential to allow more ecologically valid investigations that can translate laboratory work into more realistic everyday settings and clinical environments. Our aim is to acquaint clinicians and researchers with the unique and beneficial characteristics of fNIRS by reviewing its relative merits and limitations vis-a-vis other brain-imaging technologies such as functional magnetic resonance imaging (fMRI). We review cross-validation work between fMRI and fNIRS, and discuss possible reservations about its deployment in clinical research and practice. Finally, because there is no comprehensive review of applications of fNIRS to brain disorders, we also review findings from the few studies utilizing fNIRS to investigate neurocognitive processes associated with neurological (Alzheimer's disease, Parkinson's disease, epilepsy, traumatic brain injury) and psychiatric disorders (schizophrenia, mood disorders, anxiety disorders). PMID- 17366277 TI - Applications of functional near-infrared spectroscopy (fNIRS) to Neurorehabilitation of cognitive disabilities. AB - Functional Near-Infrared Spectroscopy (fNIRS) is a neuroimaging technique that utilizes light in the near-infrared spectrum (between 700 and 1000 nm) to detect hemodynamic changes within the cortex when sensory, motor, or cognitive activation occurs. FNIRS principles have been used to study brain oxygenation for several decades, but have more recently been applied to study cognitive processes. This paper provides a description of basic fNIRS techniques, and provides a review of the rehabilitation-related literature. The authors discuss strengths and weaknesses of this technique, assert that fNIRS may be particularly beneficial to neurorehabilitation of cognitive disabilities, and suggest future applications. PMID- 17366278 TI - The influence of neuropathology on the FMRI signal: a measurement of brain or vein? AB - There is a rapidly growing literature using fMRI technology to investigate the various forms of behavioral impairment associated with brain injury and disease. Given this, surprisingly little work has been conducted to examine the influence of neuropathophysiological processes on the fMRI signal. This paper reviews the literature examining baseline alteration in cerebrovascular parameters associated with normal aging, brain injury, and brain disease. In addition, findings from three cases of individuals with severe brain trauma will be presented to show the influence of brain trauma on baseline cerebrovascular parameters measured by fMRI. The methods used here can be implemented by other investigators to accurately isolate specific hemodynamic changes that can influence the BOLD fMRI signal. PMID- 17366279 TI - Neuroimaging of white matter in aging and dementia. AB - Clinical neuroscientists have focused increasing attention on white matter connections in the brain and on the effects of aging and disease on these connections. Recent advances in magnetic resonance imaging (MRI) analysis have given researchers new tools for quantifying and visualizing white matter to better relate white matter structure and function. The goals of this article are (a) to acquaint the reader with both established and newer methods for imaging and quantifying white matter anatomy and pathology; and (b) to review recent findings on white matter pathology in aging and dementia. Computer-assisted quantification appears to offer better statistical power than visual rating scales for detecting these relationships. New MR modalities such as diffusion imaging can detect white matter abnormalities not shown with conventional acquisition sequences. These newer techniques hold promise for early detection of disease and for delineating functional connections between brain areas. PMID- 17366280 TI - EEG neurofeedback: a brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly. AB - Neurofeedback (NF) is an electroencephalographic (EEG) biofeedback technique for training individuals to alter their brain activity via operant conditioning. Research has shown that NF helps reduce symptoms of several neurological and psychiatric disorders, with ongoing research currently investigating applications to other disorders and to the enhancement of non-disordered cognition. The present article briefly reviews the fundamentals and current status of NF therapy and research and illustrates the basic approach with an interim report on a pilot study aimed at developing a new NF protocol for improving cognitive function in the elderly. EEG peak alpha frequency (PAF) has been shown to correlate positively with cognitive performance and to correlate negatively with age after childhood. The present pilot study used a double-blind controlled design to investigate whether training older individuals to increase PAF would result in improved cognitive performance. The results suggested that PAF NF improved cognitive processing speed and executive function, but that it had no clear effect on memory. In sum, the results suggest that the PAF NF protocol is a promising technique for improving selected cognitive functions. PMID- 17366282 TI - Is learning and memory different in a virtual environment? AB - It has been suggested that virtual reality may provide a medium for producing neuropsychological measures with greater ecological validity. The present study examined the usefulness of virtual reality (VR) to assess learning and memory in individuals with traumatic brain injury (TBI). A total of 20 TBI participants were compared with 20 healthy controls on their ability to learn and recall 16 target items presented within a VR-based generic office environment. The results indicated that VR memory testing accurately distinguished the TBI group from controls. Additionally, non-memory-impaired TBI participants acquired targets at the same rate as HC participants. Finally, there was a significant relationship between the VR Office and a standard neuropsychological measure of memory, suggesting the construct validity of the task. These findings suggest that the VR Office provides a viable medium for measuring learning and memory. The present results provide preliminary support for the ecological validity of the VR Office, which ultimately can improve assessment of real-world functioning following TBI. PMID- 17366281 TI - Hippocampal volume and shape analysis in an older adult population. AB - This report presents a manual segmentation protocol for the hippocampus that yields a reliable and comprehensive measure of volume, a goal that has proven difficult with prior methods. Key features of this method include alignment of the images in the long axis of the hippocampus and the use of a three-dimensional image visualization function to disambiguate anterior and posterior hippocampal boundaries. We describe procedures for hippocampal volumetry and shape analysis, provide inter- and intra-rater reliability data, and examine correlates of hippocampal volume in a sample of healthy older adults. Participants were 40 healthy older adults with no significant cognitive complaints, no evidence of mild cognitive impairment or dementia, and no other neurological or psychiatric disorder. Using a 1.5 T GE Signa scanner, three-dimensional spoiled gradient recalled acquisition in a steady state (SPGR) sequences were acquired for each participant. Images were resampled into 1 mm isotropic voxels, and realigned along the interhemispheric fissure in the axial and coronal planes, and the long axis of the hippocampus in the sagittal plane. Using the BRAINS program (Andreasen et al., 1993), the boundaries of the hippocampus were visualized in the three orthogonal views, and boundary demarcations were transferred to the coronal plane for tracing. Hippocampal volumes were calculated after adjusting for intracranial volume (ICV). Intra- and inter-rater reliabilities, measured using the intraclass correlation coefficient, exceeded .94 for both the left and right hippocampus. Total ICV-adjusted volumes were 3.48 (+/-0.43) cc for the left hippocampus and 3.68 (+/-0.42) for the right. There were no significant hippocampal volume differences between males and females (p > .05). In addition to providing a comprehensive volumetric measurement of the hippocampus, the refinements included in our tracing protocol permit analysis of changes in hippocampal shape. Shape analyses may yield novel information about structural brain changes in aging and dementia that are not reflected in volumetric measurements alone. These and other novel directions in research on hippocampal function and dysfunction will be facilitated by the use of reliable, comprehensive, and consistent segmentation and measurement methods. PMID- 17366283 TI - Deep brain stimulation and the role of the neuropsychologist. AB - Deep brain stimulation (DBS) now plays an important role in the treatment of Parkinson's disease, tremor, and dystonia. DBS may also have a role in the treatment of other disorders such as obsessive-compulsive disorder, Tourette's syndrome, and depression. The neuropsychologist plays a crucial role in patient selection, follow-up, and management of intra-operative and post-operative effects (Pillon, 2002; Saint-Cyr & Trepanier, 2000). There is now emerging evidence that DBS can induce mood, cognitive, and behavioral changes. These changes can have dramatic effects on patient outcome. There have been methodological problems with many of the studies of DBS on mood, cognition, and behavior. The neuropsychologist needs to be aware of these issues when following up patients, and constructing future studies. Additionally, this article will review all aspects of the DBS procedure that can result in mood, cognitive, and behavioral effects and what role(s) the neuropsychologist should play in screening and follow-up. PMID- 17366284 TI - Why consider impaired social language usage in a case of corticobasal degeneration? AB - The purpose of this case study was to examine the integrity of cognitive skills, language usage, and language structure components in a patient with corticobasal degeneration (CBD). CBD is a levadopa-nonresponsive, degenerative neurologic movement disorder that is generally accompanied by cognitive (frontal executive dysfunction, dementia) and linguistic (aphasia) disorders. However, no one has reported on social language usage deficits in cases of CBD. The reported frontal executive dysfunction found in CBD led us to expect social language usage deficits in the present case study. Consistent with the literature, the patient demonstrated motor, cognitive (severe apraxia, frontal executive deficits, dementia), and linguistic deficits (aphasia). However she also demonstrated significantly abnormal social language usage previously unreported in the literature. PMID- 17366286 TI - Unconventional therapies and general practice: implications for academic medicine. PMID- 17366287 TI - Management of hepatitis C among drug users attending general practice in Ireland: baseline data from the Dublin area hepatitis C in general practice initiative. AB - OBJECTIVE: In Ireland, general practice is increasingly providing long-term care for injecting drug users, 62-81% of whom are infected with hepatitis C (HCV). Clinical guidelines for the management of HCV among drug users have recently been developed in Ireland, and this study aimed to describe HCV care among drug users attending general practice in the greater Dublin area, prior to the implementation of the clinical practice guidelines. METHODS: The clinical records of 196 patients attending 25 general practices in the Eastern Regional Health Authority area of Ireland for methadone maintenance treatment were examined on site and anonymized data collected on HCV care processes. RESULTS: Patients had been attending general practice for methadone maintenance treatment for a mean of 30.7 months, 72% were male and 51% had provided a urine sample testing positive for metabolites of drugs of abuse other than methadone in the previous 3 months. There was evidence that 77%, 69% and 60% had been screened for HCV, human immunodeficiency virus (HIV) and hepatitis B (HBV), respectively. Among those who had been tested, the prevalence of HCV, HIV and HBV infection was 69%, 10% and 11%, respectively. Of those known to be HCV positive, 36 (35%) had been tested for HCV-RNA (29 testing positive), 31 (30%) had been referred to a hepatology clinic, 24 (23%) had attended a clinic, 13 (13%) had a liver biopsy performed and three (3%) had started treatment for HCV. CONCLUSION: While the majority of patients have been screened for blood-borne viruses, a minority of those infected with HCV have had subsequent investigations or treatment. New interventions to facilitate optimum care in this regard need to be considered. PMID- 17366288 TI - Use of the bacteriology laboratory to decrease general practitioners' antibiotic prescribing. AB - OBJECTIVE: Use of the bacteriology laboratory to guide antibiotic prescribing in primary care is often considered inappropriate due to difficulties of access in a relevant time scale. The overnight analysis offered to general practitioners in the Grampian area of Scotland for the past 6 years (ABLE), and which had previously been shown to reduce antibiotic prescribing by two-thirds in a randomized controlled trial, was audited to see if it was being used correctly in general practice, that is to reduce unnecessary antibiotic prescribing. METHODS: 699 consultations were audited. Of these, 357 were ABLE patients. The other 342 were chosen because an antibiotic had been prescribed. RESULTS: Only 36.7% (140) of the ABLE patients were prescribed an antibiotic, 65.7% being given a delayed action script. All but 10 were culture positive. ABLE patients had a greater proportion of urinary tract infections than the non-ABLE patients, but less lower respiratory and skin or soft-tissue infection. The antibiotics prescribed reflected the differences in infection type. The repeat visit rate and repeat antibiotic prescription rate were almost identical between the two groups. CONCLUSION: While the overall use of ABLE in Grampian is low, its use seems to be appropriate in that it is successfully being used to identify bacterial infection and reduce unnecessary antibiotic prescribing. PMID- 17366289 TI - General practitioners' needs for ongoing support for the interpretation of spirometry tests. AB - BACKGROUND: Although one out of three general practitioners (GPs) carries out spirometry, the diagnostic interpretation of spirometric test results appears to be a common barrier for GPs towards its routine application. METHODS: Multivariate cross-sectional analysis of a questionnaire survey among 137 GPs who participated in a spirometry evaluation programme in the Netherlands. We identified characteristics of GPs and their practice settings associated with GPs' need for ongoing support for spirometry interpretation. RESULTS: Response rate on the survey questionnaire was 98%. The need for ongoing support among the participating GPs was 69%. GPs' recent spirometry training showed a statistically significant association with the need for ongoing support for the interpretation of spirometry (odds ratio 0.43, 95% CI 0.20-0.92). CONCLUSION: There is a need for ongoing support for spirometry interpretation among GPs. Recent spirometry training partially diminished this need. PMID- 17366290 TI - The role of general practitioners in the initial management of women with urinary incontinence in France, Germany, Spain and the UK. AB - OBJECTIVE: To describe the role of general practitioners (GPs) in the initial management of women with urinary incontinence (UI) in four European countries with different healthcare systems. METHODS: Cross-sectional community postal survey of 2953 women with UI in France, Germany, Spain and the UK. RESULTS: Forty eight per cent of community-dwelling women with UI had discussed their UI with a doctor. More women discussed UI in France and Germany than in the UK and Spain. The patient usually raised the issue during consultations for some other reason. Fear of or actual deterioration in UI was the most important reason for discussing UI. Overall, 52% of incontinent women first discussed their UI with a GP, and almost a third of women reported having all their UI discussions in a GP setting. Twenty-nine per cent of women reported that GPs had either recommended treatment or monitoring of their condition before beginning treatment, and 24% reported that the GP had referred them to another doctor for evaluation and treatment. Most women in the UK first discussed UI with a GP, whereas in Germany most discussed UI with a specialist. In Spain and France, about half the women first discussed their UI with a GP. CONCLUSION: GPs are involved to varying degrees in the initial management of UI in France, Germany, Spain and the UK. Even in countries where women have a choice of whether to see a GP or specialist about UI, many choose to have their first contact with a GP. PMID- 17366291 TI - Primary prevention of cardiovascular diseases by lipid-lowering treatment in German general practice: results from GPs ignoring guidelines and risk calculators. AB - OBJECTIVE: Guidelines/risk calculators for the primary prevention of cardiovascular disease have been developed, which could make decisions for or against therapy easier. However, it has been shown for different countries that there is still quite a discrepancy between what is done and what should be done according to guidelines/risk calculators. Usually, in Germany, neither guidelines nor risk calculators are used. On what basis, then, and with what result do German general practitioners decide for or against a treatment? METHODS: 26 GPs agreed to participate in the study. From their surgeries, data from a random sample of 401 patients diagnosed with hyperlipidaemia were taken, of which 290 were eligible for the study on primary prevention. Patient risk factors were taken from their files to analyse their need for treatment using risk calculators for ERCP III (US guideline) and the European guideline. These results were compared with the treatment they received from their GPs. In semi-structured interviews, GPs were asked about their decision-making process (in four randomly chosen patients from each surgery) concerning the chosen treatment. Additionally, GPs were asked about their attitude towards guidelines/risk calculators. RESULTS: 89% of the patients who received treatment would also have received it according to ERCP III. According to European guidelines, only 38% of those receiving treatment need it. Concerning those not receiving treatment, 54% would not receive it according to NCEP III and 89% would not according to the European guideline. In interviews, around 75% of doctors demonstrated that they follow a multifactorial approach and a high-risk strategy. However, about 50% and 70% explicitly stated not using guidelines or risk calculators, respectively, and even among those stating that they used them, the majority were unaware of names/sources. Patient values or wishes as well as the healthcare system influenced their decisions. CONCLUSION: German GPs seem to follow quite effectively a high-risk strategy in primary prevention, usually using a multifactorial approach, even without using risk calculators/guidelines. This kind of personalized care is also reflected in the considered importance of patient wishes and values. It is difficult to judge GPs concerning their quality of care having as a "gold standard" different risk calculators/guidelines that define whether such different populations receive treatment or not. PMID- 17366292 TI - Attitudes to antibiotic prescribing, resistance and bacteriology investigations amongst practitioners and patients in the Grampian region of Scotland. PMID- 17366293 TI - Urgent referrals to a specialist by family physicians--is the "urgency" real: a prospective study. PMID- 17366294 TI - What do smokers really fear? A survey of behavior, knowledge, and attitudes toward cigarette smoking among visitors to a primary care clinic in Israel. PMID- 17366297 TI - News from Italy. PMID- 17366300 TI - European general practice research network and its mission for strong research in primary health care. PMID- 17366302 TI - Associationism and cognition: human contingency learning at 25. AB - A major topic within human learning, the field of contingency judgement, began to emerge about 25 years ago following publication of an article on depressive realism by Alloy and Abramson (1979). Subsequently, associationism has been the dominant theoretical framework for understanding contingency learning but this has been challenged in recent years by an alternative cognitive or inferential approach. This article outlines the key conceptual differences between these approaches and summarizes some of the main methods that have been employed to distinguish between them. PMID- 17366304 TI - Inferences about unobserved causes in human contingency learning. AB - Estimates of the causal efficacy of an event need to take into account the possible presence and influence of other unobserved causes that might have contributed to the occurrence of the effect. Current theoretical approaches deal differently with this problem. Associative theories assume that at least one unobserved cause is always present. In contrast, causal Bayes net theories (including Power PC theory) hypothesize that unobserved causes may be present or absent. These theories generally assume independence of different causes of the same event, which greatly simplifies modelling learning and inference. In two experiments participants were requested to learn about the causal relation between a single cause and an effect by observing their co-occurrence (Experiment 1) or by actively intervening in the cause (Experiment 2). Participants' assumptions about the presence of an unobserved cause were assessed either after each learning trial or at the end of the learning phase. The results show an interesting dissociation. Whereas there was a tendency to assume interdependence of the causes in the online judgements during learning, the final judgements tended to be more in the direction of an independence assumption. Possible explanations and implications of these findings are discussed. PMID- 17366303 TI - Comparing associative, statistical, and inferential reasoning accounts of human contingency learning. AB - For more than two decades, researchers have contrasted the relative merits of associative and statistical theories as accounts of human contingency learning. This debate, still far from resolution, has led to further refinement of models within each family of theories. More recently, a third theoretical view has joined the debate: the inferential reasoning account. The explanations of these three accounts differ critically in many aspects, such as level of analysis and their emphasis on different steps within the information-processing sequence. Also, each account has important advantages (as well as critical flaws) and emphasizes experimental evidence that poses problems to the others. Some hybrid models of human contingency learning have attempted to reconcile certain features of these accounts, thereby benefiting from some of the unique advantages of different families of accounts. A comparison of these families of accounts will help us appreciate the challenges that research on human contingency learning will face over the coming years. PMID- 17366305 TI - Outcome maximality and additivity training also influence cue competition in causal learning when learning involves many cues and events. AB - Recent evidence shows that outcome maximality (e.g., De Houwer, Beckers, & Glautier, 2002) and additivity training (e.g., Lovibond, Been, Mitchell, Bouton, & Frohard, 2003) have an influence on cue competition in human causal learning. This evidence supports the idea that cue competition is based on controlled reasoning processes rather than on automatic associative processes. Until now, however, all the evidence for controlled reasoning processes comes from studies with rather simple designs that involved only few cues and events. We conducted two experiments with a complex design involving 24 different cues. The results showed that outcome maximality and additivity training had an influence on cue competition but that this influence was more pronounced for forward cue competition than for retrospective cue competition. PMID- 17366306 TI - Interference between cues of the same outcome depends on the causal interpretation of the events. AB - In an interference-between-cues design, the expression of a learned Cue A --> Outcome 1 association has been shown to be impaired if another cue, B, is separately paired with the same outcome in a second learning phase. In the present study, we assessed whether this interference effect is mediated by participants' previous causal knowledge. This was achieved by having participants learn in a diagnostic situation in Experiment 1a, and then by manipulating the causal order of the learning task in Experiments 1b and 2. If participants use their previous causal knowledge during the learning process, interference should only be observed in the diagnostic situation because only there we have a common cause (Outcome 1) of two disjoint effects, namely cues A and B. Consistent with this prediction, interference between cues was only found in Experiment 1a and in the diagnostic conditions of Experiments 1b and 2. PMID- 17366307 TI - Asymmetries in cue competition in forward and backward blocking designs: Further evidence for causal model theory. AB - A hallmark feature of elemental associative learning theories is that multiple cues compete for associative strength when presented with an outcome. Cue competition effects have been observed in humans, both in forward and in backward blocking procedures (e.g., Shanks, 1985) and are often interpreted as evidence for an associative account of human causal learning (e.g., Shanks & Dickinson, 1987). Waldmann and Holyoak (1992), however, demonstrated that cue competition only occurs in predictive, and not diagnostic, learning paradigms. While unexplainable from an associative perspective, this asymmetry readily follows from structural considerations of causal model theory. In this paper, we show that causal models determine the extent of cue competition not only in forward but also in backward blocking designs. Implications for associative and inferential accounts of causal learning are discussed. PMID- 17366308 TI - A dissociation between causal judgement and the ease with which a cause is categorized with its effect. AB - The associative view of human causal learning argues that causation is attributed to the extent that the putative cause activates, via an association, a mental representation of the effect. That is, causal learning is a human analogue of animal conditioning. We tested this associative theory using a task in which a fictitious character suffered from two allergic reactions, rash (O1) and headache (O2). In a conditioned inhibition design with each of these two outcomes (A-O1/AX and B-O2/BY-), participants were trained that one herbal remedy (X) prevented O1 and that the other (Y) prevented O2. These inhibitory properties were revealed in a causal judgement summation test. In a subsequent categorization task, X was most easily categorized with O1, and Y with O2. Thus, the categorization data indicated an excitatory X-O1 and Y-O2 association, the reverse of the inhibitory relationship observed on the causal judgement measure. A second experiment showed that this pattern of excitation and inhibition is dependent on intermixed A-O1 and AX- trials. These results are problematic for the standard application of associative activation theories to causal judgement. We argue instead that the inhibition revealed in the causal judgement task reflects inferential reasoning, which relies, in part, on the ability of the cue in question to excite a representation of the outcome, as revealed in the categorization test. PMID- 17366309 TI - Statistical contingency has a different impact on preparation judgements than on causal judgements. AB - Previous studies on causal learning showed that judgements about the causal effect of a cue on an outcome depend on the statistical contingency between the presence of the cue and the outcome. We demonstrate that statistical contingency has a different impact on preparation judgements (i.e., judgements about the usefulness of responses that allow one to prepare for the outcome). Our results suggest that preparation judgements primarily reflect information about the outcome in prior situations that are identical to the test situation. These findings also add to previous evidence showing that people can use contingency information in a flexible manner depending on the type of test question. PMID- 17366310 TI - Predictions and causal estimations are not supported by the same associative structure. AB - Studies performed by different researchers have shown that judgements about cue outcome relationships are systematically influenced by the type of question used to request those judgements. It is now recognized that judgements about the strength of the causal link between a cue and an outcome are mostly determined by the cue-outcome contingency, whereas predictions of the outcome are more influenced by the probability of the outcome given the cue. Although these results make clear that those different types of judgement are mediated by some knowledge of the normative differences between causal estimations and outcome predictions, they do not speak to the underlying processes of these effects. The experiment presented here reveals an interaction between the type of question and the order of trials that challenges standard models of causal and predictive learning that are framed exclusively in associative terms or exclusively in higher order reasoning terms. However, this evidence could be easily explained by assuming the combined intervention of both types of process. PMID- 17366311 TI - Second-order conditioning in human predictive judgements when there is little time to think. AB - Associative accounts uniquely predict that second-order conditioning might be observed in human predictive judgements. Such an effect was found for cue X in two experiments in which participants were required to predict the outcomes of a series of training trials that included P + and PX-, but only when training was paced by requiring participants to make a prediction within 3 s on each trial. In Experiment 1 training on P + ended before training was given on PX - . In Experiment 2 trials with P+, PX-, T + and other cues were intermixed. In the unpaced group inhibitory learning was revealed by a summation test, TX versus TM, where M was a control stimulus. These results suggest either that pacing interferes with learning successive associations more than with learning simultaneous associations or that lack of time to think interferes with inferential processes required for this type of inhibitory learning. PMID- 17366312 TI - Depressive realism and the effect of intertrial interval on judgements of zero, positive, and negative contingencies. AB - In three experiments we tested how the spacing of trials during acquisition of zero, positive, and negative response-outcome contingencies differentially affected depressed and nondepressed students' judgements. Experiment 1 found that nondepressed participants' judgements of zero contingencies increased with longer intertrial intervals (ITIs) but not simply longer procedure durations. Depressed groups' judgements were not sensitive to either manipulation, producing an effect known as depressive realism only with long ITIs. Experiments 2 and 3 tested predictions of Cheng's (1997) Power PC theory and the Rescorla-Wagner (1972) model, that the increase in context exposure experienced during the ITI might influence judgements most with negative contingencies and least with positive contingencies. Results suggested that depressed people were less sensitive to differences in contingency and contextual exposure. We propose that a context processing difference between depressed and nondepressed people removes any objective notion of "realism" that was originally employed to explain the depressive realism effect (Alloy & Abramson, 1979). PMID- 17366313 TI - The sad truth about depressive realism. AB - In one form of a contingency judgement task individuals must judge the relationship between an action and an outcome. There are reports that depressed individuals are more accurate than are non-depressed individuals in this task. In particular, nondepressed individuals are influenced by manipulations that affect the salience of the outcome, especially outcome probability. They overestimate a contingency if the probability of an outcome is high--the "outcome-density effect". In contrast, depressed individuals display little or no outcome-density effect. This apparent knack for depressives not to be misled by outcome density in their contingency judgements has been termed "depressive realism", and the absence of an outcome-density effect has led to the characterization of depressives as "sadder but wiser". We present a critical summary of the depressive realism literature and provide a novel interpretation of the phenomenon. We suggest that depressive realism may be understood from a psychophysical analysis of contingency judgements. PMID- 17366314 TI - The rat mammary gland: morphologic changes as an indicator of systemic hormonal perturbations induced by xenobiotics. AB - The development and morphology of the rat mammary gland are dependent upon several hormones including estrogens, androgens, progesterone, growth hormone and prolactin. In toxicology studies, treatment with xenobiotics may alter these hormones resulting in changes in the morphology of reproductive tissues such as the mammary gland. In the rat, male and female mammary glands exhibit striking morphologic differences that can be altered secondary to hormonal perturbations. Recognizing these morphologic changes can help the pathologist predict potential xenobiotic-induced perturbations in the systemic hormonal milieu. This review examines the development of the rat mammary gland and the influence of sex hormones on the morphology of the adult male and female rat mammary gland. Specific case examples from the literature and data from our laboratory highlight the dynamic nature of the rat mammary gland in response to hormonal changes. PMID- 17366315 TI - Drug-induced thrombosis--experimental, clinical, and mechanistic considerations. AB - Awareness of the dangers of drug-induced thrombosis has recently been heightened and led to demand for improved testing methodology. For example, reports indicating that some selective inhibitors of cyclooxygenase-2 (COX-2) increase the risk of myocardial infarction and atherothrombotic events caused the withdrawal of rofecoxib from global markets and the issuance of warnings concerning the usage of other COX-2 inhibitors. Drugs may exert a prothrombotic state by a variety of mechanisms--those affecting the vessel wall, the blood flow, and/or different blood constituents. Our review serves as an update to that of Gerhard Zbinden published in 1976 by presenting recently acquired data that more fully elucidate the different mechanisms by which drugs are believed to induce thrombogenic effects and discussing new methods used to detect these without losing sight of the classical pathology of thrombosis. We offer correlations between experimental findings and clinical data and conclude that, because drugs may induce a prothrombotic state by a variety of mechanisms, they should be tested for these using appropriate experimental methods and animal models. PMID- 17366316 TI - Effects of cyclosporin A and cyclophosphamide on Peyer's patches in rat, exposed in utero and neonatally or during adult age. AB - The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies, animals were exposed at young adult age: female rats received orally 5 or 20 mg/kg/day CY or 5 or 10 mg/kg bw CPS for 4 weeks; males received orally 5 mg/kg bw CPS for 4 weeks, or a single i.v. injection of 50 mg/kg bw CPS. Upon in utero and neonatal exposure, the numbers of grossly observed PP were increased in male pups from the high-dose CY dams at 70 days of age. Exposure to high-dose CY at adult age only tended to decrease the numbers of PP; germinal center development was reduced in the PP from the middle segment of the small intestines, as examined microscopically. Exposure to both doses CPS at adult age reduced the numbers of PP and reduced germinal centre development and the number of lymphocytes in all compartments of PP. It was concluded that the effects of CPS and CY could be established by counting the number of grossly visible PP and by microscopic observation of PP, provided that regional differences of PP were taken into account. Moreover, the type of effects of an immunotoxic agent may vary with age of exposure. PMID- 17366317 TI - Spontaneous renal tubular hyperplastic and neoplastic lesions in three Sprague Dawley rats from a 90-day toxicity study. AB - Multiple renal tubular cell adenomas and atypical tubular hyperplasia were diagnosed in 2 high-dose and 1 mid-dose female Sprague-Dawley (Crl:CD (SD)IGS BR) rats from a 90-day toxicity study of an amino acid found in green tea. The tumors were bilateral multicentric adenomas accompanied by atypical foci of renal tubular hyperplasia in both kidneys of the 3 animals. Toxic tubular changes that typically accompany renal carcinogenesis were not seen in any of the other animals of the study, suggesting rather, an underlying germline mutation of a tumor suppressor gene in these three rats. The histological appearance of these tumors and short latency was reminiscent of the spontaneous lesions reported to arise in Sprague-Dawley rats in the Nihon rat model. Nihon rats develop kidney tumors as a result of a spontaneous mutation in the rat homologue of the Birt Hogg-Dube gene (Bhd). Frozen samples of liver from two tumor-bearing rats were assayed for germline alterations in the Bhd gene. The entire coding region (exons 3-13) of the Bhd gene was sequenced, and a guanine (nt106G) to adenine (nt106A) polymorphism was detected resulting in a glycine to arginine (G36R) substitution in both tumor-bearing animals. In the study animals, the frequency of the A allele (adenine) was determined to be 27% (19/70). Interestingly, rats obtained from two other sources (n = 17) only carried the nt106G-allele, consistent with the published rat sequence for this gene. Genetic fingerprinting of microsatellite loci indicated that the rats had a shared genetic background. Laser capture microdissection (LCM) of the tumor cells demonstrated a loss of heterozygosity in the Bhd gene in neoplastic cells of one of the two animals. Taken together, these data suggest that the tumors observed in these animals arose spontaneously as a result of a shared genetic susceptibility leading to the development of renal tubular neoplasms. PMID- 17366318 TI - Hepatic transcript levels for genes coding for enzymes associated with xenobiotic metabolism are altered with age. AB - Metabolism studies are crucial for data interpretation from rodent toxicity and carcinogenicity studies. Metabolism studies are usually conducted in 6 to 8 week old rodents. Long-term studies often continue beyond 100 weeks of age. The potential for age-related changes in transcript levels of genes encoding for enzymes associated with metabolism was evaluated in the liver of male F344/N rats at 32, 58, and 84 weeks of age. Differential expression was found between the young and old rats for genes whose products are involved in both phase I and phase II metabolic pathways. Thirteen cytochrome P450 genes from CYP families 1-3 showed alterations in expression in the older rats. A marked age-related decrease in expression was found for 4 members of the Cyp3a family that are critical for drug metabolism in the rat. Immunohistochemical results confirmed a significant decrease in Cyp3a2 and Cyp2c11 protein levels with age. This indicates that the metabolic capacity of male rats changes throughout a long-term study. Conducting multiple hepatic microarray analyses during the conduct of a long-term study can provide a global view of potential metabolic changes that might occur. Alterations that are considered crucial to the interpretation of long-term study results could then be confirmed by subsequent metabolic studies. PMID- 17366319 TI - An overview on the toxic morphological changes in the retinal pigment epithelium after systemic compound administration. AB - Many medications that are administered systemically for nonocular conditions may evoke ocular toxicological complications. Therefore, the eye is routinely investigated histopathologically in preclinical in vivo toxicity studies. The retinal pigment epithelium is a likely target for systemically administered compounds, since the underlying choroid is highly vascularized. The specialized pigment epithelium has numerous functions that all maintain the integrity and function of photoreceptors. Consequently, toxic effects on the pigment epithelium will eventually affect the neural retina. The potential of pigment epithelial cells to respond to toxic injury is limited, but a standardized terminology to describe its morphological changes does not exist in the scientific literature. Detailed morphologic analysis, however, might allow early detection of retinotoxicity and may provide evidence on the underlying pathomechanism. We here review toxic effects on the pigment epithelium focusing in particular on the morphology of toxic cell injury. Morphological changes comprise hypertrophy, intracytoplasmic accumulation of cellular components, loss of cell polarity, degeneration, metaplasia, and formation of subretinal membranes. Some of these changes are reversible whereas others are permanent, leading to impaired function of the pigment epithelium and eventually to photoreceptor loss and retinal atrophy. PMID- 17366320 TI - A correlative study on red blood cell parameters and urine trans, trans-muconic acid in subjects with occupational benzene exposure. AB - Benzene is of particular concern because of recent research indicating that benzene exposure can result in toxicity. The hematotoxic effect of benzene is mentioned. However, there is little knowledge about the correlation between the biomarker of benzene exposure and changes in red blood cell parameters. Here, the correlation between the urine trans, trans-muconic acid (ttMA) level and red blood cell parameters were studied in 30 Thai subjects at risk. The regression analysis shows no significant correlation between urine ttMA and any studied red cell parameters (Hb, MCV or MCH). Based on our hematologic data, we proposed that only investigation for the urine ttMA might be not sufficient in detection of alteration in red blood cell parameters in the exposed population. Combinations between biomarker and hematological test are recommended. PMID- 17366321 TI - Renal proximal tubule segment-specific nephrotoxicity: an overview on biomarkers and histopathology. AB - The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with segment-specific nephrotoxicants. Male Wistar rats were treated with a single injection of K2Cr2O7 (25 mg/kg s.c. in saline), cis-Pt (10 mg/kg i.p. in buffered MSO) or HCBD (100 mg/kg i.p. in corn oil). Twenty-four and 48 hours after treatment, the rats were sacrificed and the kidneys were drawn for histopathological and biochemical evaluation, i.e., GS activity in renal cortex and PAH uptake in renal cortical slices. Histopathological findings show that cis-Pt and HCBD cause diffuse necrosis of S3 segment of proximal tubules in the outer stripe of outer medulla, respectively. On the contrary, K2Cr2O7 damages exclusively S1-S2 segments, inducing vacuolization at 24 hr and diffuse necrosis at 48 hr after treatment. GS activity in renal tissue is significantly decreased after HCBD and cis-Pt, but not K2Cr2O7 treatment. In contrast, PAH uptake is significantly reduced by K2Cr2O7, but not by cis-Pt or HCBD treatment (even if HCBD causes a slight decrease 48 hr after treatment). The evidence of this study confirms the high specificity of GS activity as marker of S3 segment injury, that PAH uptake is prevalently active in the S1-S2 segments, and that there is complete correspondence among segment-specific nephrotoxicants, biomarkers of segment specific damage, and histopathological findings. PMID- 17366322 TI - Gene expression analysis offers unique advantages to histopathology in liver biopsy evaluations. AB - Liver diseases that induce nonuniform lesions often give rise to greatly varying histopathology results in needle biopsy samples from the same patient. This study examines whether gene expression analysis of such biopsies could provide a more representative picture of the overall condition of the liver. We utilized acetaminophen (APAP) as a model hepatotoxicant that gives a multifocal pattern of necrosis following toxic doses. Rats were treated with a single toxic or subtoxic dose of APAP and sacrificed 6, 24, or 48 hours after exposure. Left liver lobes were harvested, and both gene expression and histopathological analysis were performed on biopsy-sized samples. While histopathological evaluation of such small samples revealed significant sample to sample differences after toxic doses of APAP, gene expression analysis provided a very homogeneous picture and allowed clear distinction between subtoxic and toxic doses. The main biological function differentiating animals that received sub-toxic from those that had received toxic doses was an acute stress response at 6 hours and signs of energy depletion at later time points. Our results suggest that the use of genomic analysis of biopsy samples together with histopathological analysis could provide a more precise representation of the overall condition of a patient's liver than histopathological evaluation alone. PMID- 17366323 TI - Inhibition of ALK5 signaling induces physeal dysplasia in rats. AB - TGF-beta, and its type 1 (ALK5) receptor, are critical to the pathogenesis of fibrosis. In toxicologic studies of 4 or more days in 10-week-old Sprague-Dawley rats, using an ALK5 inhibitor (GW788388), expansion of hypertrophic and proliferation zones of femoral physes were noted. Subphyseal hyperostosis, chondrocyte hypertrophy/hyperplasia, and increased matrix were present. Physeal zones were laser microdissected from ALK5 inhibitor-treated and control rats sacrificed after 3 days of treatment. Transcripts for TGF-beta1, TGF-beta2, ALK5, IHH, VEGF, BMP-7, IGF-1, bFGF, and PTHrP were amplified by real-time PCR. IGF and IHH increased in all physis zones with treatment, but were most prominent in prehypertrophic zones. TGF-beta2, bFGF and BMP7 expression increased in proliferative, pre-and hypertrophic zones. PTHrP expression was elevated in proliferative zones but decreased in hypertrophic zones. VEGF expression was increased after treatment in pre- and hypertrophic zones. ALK5 expression was elevated in prehypertrophic zones. Zymography demonstrated gelatinolytic activity was reduced after treatment. Apoptotic markers (TUNEL and caspase-3) were decreased in hypertrophic zones. Proliferation assessed by Topoisomerase II and Ki67 was increased in multiple zones. Movat stains demonstrated that proteoglycan deposition was altered. Physeal changes occurred at doses well above those resulting in fibrosis. Interactions of factors is important in producing the physeal dysplasia phenotype. PMID- 17366324 TI - Chronic lymphocytic thyroiditis in a cynomolgus macaque (Macaca fascicularis). AB - Chronic lymphocytic thyroiditis characterized by multifocal follicular lymphoid cell infiltrates with germinal centers, thyroid acinar atrophy and pituitary cell hyperplasia/hypertrophy of the adenohypophysis was detected in a vehicle control, 4-year-old female Cynomolgus macaque in a routine toxicology study. Lymphoid cells of germinal centers were positive for the B-cell marker CD20 by immunohistochemistry (IHC), while remaining lymphocytes were positive for the T cell marker CD3. Hypertrophied/hyperplastic pituitary cells were positive for thyroid stimulating hormone (TSH) by IHC, consistent with an adaptive response due to removal of hormonal negative feedback from the diseased thyroid gland. Features of this case are similar to chronic lymphocytic thyroiditis in humans, an autoimmune disorder also known as Hashimoto's disease. Chronic lymphocytic thyroiditis with compensatory pituitary changes may occur spontaneously in young, clinically normal cynomolgus macaques and its presence in drug treated animals should be interpreted with caution. PMID- 17366325 TI - Aurintricarboxylic acid inhibits protein synthesis independent, sanguinarine induced apoptosis and oncosis. AB - Sanguinarine, a benzophenanthridine alkaloid, has anticancer potential through induction of cell death. We previously demonstrated that sanguinarine treatment at a low concentration (1.5 microg/ml) induced apoptosis in K562 human erythroleukemia cells, and a high concentration (12.5 microg/ml) induced the morphology of blister formation or oncosis-blister cell death (BCD). Treatment of cells at an intermediate sanguinarine concentration (6.25 microg/ml) induced diffuse swelling or oncosis-diffuse cell swelling (DCS). To assess the underlying mechanism of sanguinarine-induced apoptosis and oncosis-BCD in K562 cells, we studied their response to pre-treatment with two chemical compounds: aurintricarboxylic acid (ATA) and cycloheximide (CHX). The pretreatment effects of both chemical compounds on apoptosis and oncosis-BCD were evaluated by measuring multiple parameters using quantitative morphology, electron microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling and annexin-V-binding. ATA, a DNA endonuclease inhibitor, efficiently prevented DNA nicking and inhibited apoptosis almost completely and oncosis-BCD by about 40%, while CHX, a protein synthesis inhibitor, failed to inhibit both apoptosis and oncosis-BCD. These results demonstrate, first, the importance of endonuclease in sanguinarine induced apoptosis and to some extent in oncosis-BCD and, second, that this inhibition does not require de novo protein synthesis. PMID- 17366326 TI - Administration of an antagonist of neurokinin receptors 1, 2, and 3 results in reproductive tract changes in beagle dogs, but not rats. AB - SCH 206272, an antagonist of neurokinin receptors 1, 2, and 3, was administered orally by gavage for 1 month to 8- to 10-month-old dogs at doses of 0, 15, 30, or 60 mg/kg, and to 6-week-old rats at doses of 0, 30, 100, or 300 mg/kg. The most important changes occurred in the reproductive tract of the dogs at all doses. Absolute and relative group mean organ weights for the testes, prostate gland, epididymides, ovaries, and uterus were 33-86% lower than concurrent controls in groups receiving SCH 206272. Organ weight changes were not dose-related. Microscopic changes that correlated with the organ weight changes occurred in all groups receiving SCH 206272. For males, they included minimal to severe atrophy of the testes, epididymides, and prostate gland. In addition, the epididymides exhibited severe oligospermia or aspermia, minimal epithelial apoptosis and mild epithelial vacuolation. In female dogs, the ovaries and uteri appeared immature. Microscopic changes were similar in incidence and severity in dogs receiving 30 or 60 mg/kg, but were slightly less in dogs receiving 15 mg/kg. In contrast, similar findings were not observed in the reproductive tract of male or female rats, despite overlapping systemic, hypothalamic, and pituitary gland concentrations of SCH 206272. PMID- 17366328 TI - Phospholipidosis in nonclinical toxicity studies. PMID- 17366329 TI - Industry and academia forge strong links to train veterinary pathologists. PMID- 17366330 TI - Hardcore drinking drivers and other contributors to the alcohol-impaired driving problem: need for a comprehensive approach. AB - OBJECTIVE: Understanding the hardcore drinking driver concept in the context of the alcohol-impaired driving problem. METHOD: Review of the relevant literature. RESULTS: As progress against alcohol-impaired driving slowed in the early 1990s, public and political attention turned to "hardcore" drinking drivers, and they have been a priority for the past 15 years. Though intuitive, the hardcore concept has been difficult to conceptualize. Its definition of hard-to-change chronic heavy drinking drivers focuses on a group that is not easily identifiable and ignores many who account for a large portion of alcohol-impaired driving crashes. These include drivers who drink heavily on occasion and drivers who drink at more moderate levels that elevate crash risk. Emphasis on the hardcore has focused attention on the small proportion of drinking drivers who have been detected and arrested, whereas the vast majority of drinking drivers go undetected. Some countermeasures aimed at the hardcore group have been effective in reducing recidivism, but attention and resources also need to be given to general deterrent initiatives (e.g., 0.08 g/dL, sobriety checkpoints, administrative license suspension). There has been no reduction in the overall alcohol-impaired driving problem since the mid-1990s. CONCLUSION: Reductions in the alcohol-impaired driving problem require that attention be focused on all relevant target groups. Some benefits could accrue by recognizing that countermeasures developed for hardcore drinking drivers, such as alcohol ignition interlocks and vehicle or plate impoundment, might also be effective with more numerous first-time offenders. However, such strategies are likely to be most effective against recidivism (specific deterrence). Greater gains could be achieved through general deterrent efforts (increasing the real and perceived risk of arrest and punishment to all drinking drivers), along with application of public health measures designed to reduce overall consumption. Additional ways need to be found to separate drinking and driving, either through cultural changes in drinking and/or driving behavior or, in the future, with the use of technology that can make vehicles inoperable by drivers with illegal blood alcohol concentrations. PMID- 17366331 TI - Perceptions and experiences of random breath testing in Queensland and the self reported deterrent impact on drunk driving. AB - OBJECTIVE: The present study explored the impact of random breath testing (RBT) on the attitudes, perceptions, and self-reported behavior of motorists in the Australian state of Queensland. Particular attention was given to how exposure to RBT impacted motorists' perceived risk of apprehension and self-reported behavior, relative to other variables of interest such as alcohol consumption. METHODS: The study involved a telephone survey of 780 motorists drawn from throughout the state of Queensland. Participants were volunteers recruited from a random sample of all listed telephone numbers in the state, adjusted according to district population figures. The survey questionnaire collected information relating to the participants' socio-demographic characteristics, drinking and drunk driving behaviors, attitudes toward drunk driving and RBT, and experiences and perceptions of RBT. RESULTS: The analysis indicated that a large proportion of the sample had both observed RBT and been breath tested within the last six months and believed the practice served an important role in improving road safety. However, a considerable percentage also reported drunk driving at least once in the last six months without being detected, with further analysis indicating that the threat of apprehension associated with RBT did not appear to greatly influence their offending behavior. Rather, a higher frequency of alcohol consumption, combined with more favorable attitudes to drunk driving and lower levels of support for RBT, appeared to be associated with offending behavior. CONCLUSIONS: While the results confirm the high levels of exposure to RBT achieved in Queensland, the direct impact of recent exposure on drunk driving behavior appears less important than other factors such as alcohol consumption and attitudes to drunk driving and RBT. Further research is required to better understand how recent and lifetime exposure to RBT impacts on motorists' perceived risk of apprehension and subsequent drunk driving behavior. PMID- 17366332 TI - Mandating interlocks for fully revoked offenders: the New Mexico experience. AB - OBJECTIVE: In New Mexico, between July 1999 and December 2002, the installation of an ignition interlock was an optional judicial sanction for second and third driving-while-impaired (DWI) offenders. This is a study of the recidivism of 437 offenders who were convicted and installed interlocks for an average of 322 days during that period. METHODS: The comparison group was a stratified random sample (N = 12,554) of the 20,949 offenders who were convicted during the same period but did not install interlocks. DWI arrest and conviction data for all study participants were received from the Motor Vehicle Department's Citation Tracking System. RESULTS: Only 11 (2.5%) of the interlock offender group were rearrested for DWI while interlocks were installed, whereas 1,017 (8.1%) of the comparison group were rearrested during an equivalent 322-day period. Survival graphs and Cox proportional hazard regression analyses were used to compare the interlock and noninterlock groups during installation, after installation, and for the entire period up to December 2004. Results indicate a reduction in recidivism of 65% during installation. After removal, there was no significant difference in recidivism rates in a 3-year follow-up period. Following all offenders for 4 years, including both the period while the interlock was installed and the period after its removal, indicates that the difference in recidivism achieved during installation, though not increased, is maintained, so at the end of 4 years, interlock users still have lower total recidivism than nonusers. CONCLUSIONS: The magnitude of interlock effectiveness reported here is similar to those in other published studies with comparable samples. PMID- 17366333 TI - Do speeding tickets reduce the likelihood of receiving subsequent speeding tickets? A longitudinal study of speeding violators in Maryland. AB - OBJECTIVE: Speeding tickets are the most commonly used tool to deter speeders, yet little is known about how speeding citations affect individual drivers' behavior over time. This study examined the effects of being cited for speeding and types of legal consequences on drivers' subsequent speeding citations, which are an indicator of speeding behavior. METHODS: A cohort of 3,739,951 Maryland licensed drivers were identified and followed for one year. Drivers were categorized by whether or not they received a speeding citation in May 2002. Among those cited for speeding in May 2002, drivers were grouped by type of penalty (fines and points; probation before judgment [PBJ, which results in fines but no points]; or no legal consequences). The relative risks (RR) and 95 percent confidence intervals (CI) of receiving a speeding citation during follow-up were compared between drivers ticketed and not ticketed in May 2002, as well as among different penalty groups. Cox proportional hazards regression modeling was used to adjust for potential confounders, including age, gender, alcohol-impaired driving, and residence. Kaplan-Meier survival functions were used to examine timing of violations. RESULTS: Young drivers and male drivers were more likely to receive a speeding citation. Drivers who received a speeding citation in May 2002 had almost twice the risk of receiving a speeding citation during follow-up, compared with those not cited for speeding that month (RR 1.6, 95% CI 1.52-1.68). Overall legal consequences had no significant effect on the risk of receiving a repeat speeding citation relative to ticketed drivers who escaped those consequences (RR 0.98, 95% CI 0.84-1.15); however, stratified analyses showed a significant decrease in repeat citations among females (RR 0.75, 95% CI 0.63 0.90) and drivers who received PBJ (RR 0.81, 95% CI 0.67-0.96). Kaplan-Meier curves showed that the study group of speeders had a significantly shorter time between May 2002 until receipt of a speeding citation than controls. Among penalty groups, significantly shorter times until receipt of another citation were observed among drivers escaping consequences or receiving fines/points compared with drivers receiving fines/PBJ. CONCLUSIONS: Drivers who receive speeding citations are at increased risk of receiving subsequent speeding citations, suggesting that speeding citations have limited effects on deterrence in the context of the current traffic enforcement system. When comparing different penalties, PBJ is associated with a reduced rate of recidivism more than stronger penalties; however, it is unclear whether the reduction primarily is attributable to the penalty itself or to characteristics of drivers receiving PBJ. Increasing drivers' perceptions that they are at risk of being caught speeding may improve the effectiveness of speeding law enforcement. PMID- 17366334 TI - The effects of graduated driver licensing on hospitalization rates and charges for 16-and 17-year-olds in North Carolina. AB - OBJECTIVE: To mitigate the high risk of motor vehicle crashes for young beginning drivers, over 40 states and the District of Columbia have implemented graduated driver licensing (GDL) systems that gradually and systematically ease teen drivers into higher risk driving conditions. Evaluations of GDL programs using motor vehicle crash data have demonstrated marked declines in crashes. The objective of this study is to examine the association between the implementation of the North Carolina GDL program and the rate of hospitalization, as well as hospital charges, for 16-and 17-year-old drivers. METHODS: Data were obtained from the North Carolina Hospital Discharge Database for the 26 months before and 46 months after the December 1, 1997, implementation of the GDL program. ARIMA interrupted time series analyses were used to model monthly hospitalization rates, controlling for the hospitalization rates of 25-to 54-year-old drivers. ARIMA analyses were also used to determine whether changes occurred in monthly total hospital charges. RESULTS: Among the 568 16-year-old hospitalized drivers, GDL was associated with a 36.5% decline in the hospitalization rate per population and a 31.2% decline in the total monthly driver hospitalization charges. Although a 12% reduction in the rate of hospitalizations was observed among the 615 17-year-old drivers, the analysis lacked sufficient power to be statistically reliable. No consistent change was observed in the 16-year-old driver total monthly hospital charges. CONCLUSIONS: The North Carolina GDL program was associated with a marked decline in the rate of hospitalizations and hospital charges for 16-year-old drivers. Following the implementation of GDL, over $650,000 in hospital charges have been averted each year for 16-year-old drivers. Analyses suggest these reductions were primarily the result of reduced exposure rather than an improvement in teen driving. PMID- 17366335 TI - Persuasion and licensure: a randomized controlled intervention trial to increase licensure rates among Maryland motorcycle owners. AB - OBJECTIVE: This study aimed to determine whether a persuasive educational intervention could increase licensure among motorcycle owners. Unlicensed motorcycle operators appear to be disproportionately involved in police-reported motorcycle crashes in Maryland, accounting for about 27% of motorcycle operators in police-reported crashes, although unlicensed owners comprise 17% of primary motorcycle owners. METHODS: A randomized controlled trial was conducted among unlicensed owners. Linking Maryland records of registered motorcycles with license files, 8,499 unlicensed owners who had no licensed co-owners were identified. Half were randomized to receive a persuasive educational mailing in early June 2005 from Maryland Motor Vehicle Administration (MVA). Motorcycle licenses can be attained by passing an accredited motorcycle training class or passing knowledge and skills tests administered by the state driver licensing agency. Licensure rates and motorcycle class enrollment were followed for 6 months post-intervention. RESULTS: As of December 16, 2005, 280 intervention group owners had obtained Class M motorcycle licenses and 158 had obtained Class R motorcycle learner's permits. The comparison group obtained 209 M licenses and 122 R permits. The overall success rate in the intervention group, defined as obtaining Class M or R, was 10.4% compared with 7.9% in the comparison group (licensure ratio (LR) = 1.33; 95% confidence interval (CI) = 1.16-1.52). The intervention was most successful among men, whose LR for obtaining M licenses was 1.45 (95% CI = 1.21-1.75). LRs were higher among owners ages 40-48 and 49+ receiving the intervention compared with younger groups. Motorcycle training class enrollment rates were higher in the intervention group, particularly among those taking a course for riders with intermediate skills (enrollment ratio = 2.24; 95% CI = 1.41-3.55). CONCLUSION: The intervention appeared to increase licensure, yet the licensure rate remained low among the intervention group. Potential risks and benefits of increasing the percentage of motorcyclists who are licensed need to be studied. PMID- 17366336 TI - Reconstruction of crashes involving injured child occupants: the risk of serious injuries associated with sub-optimal restraint use may be reduced by better controlling occupant kinematics. AB - OBJECTIVE: To determine whether injuries to sub-optimally restrained child occupants in real-world crashes were likely to be preventable by alternative restraint usage practices and to assess the usefulness of crash reconstruction for exploring injury mechanisms in child occupants. METHODS: Real-world crashes in which child occupants sustained significant injuries were reconstructed on a laboratory crash sled using the Hybrid III family of child dummies. Alternative restraint scenarios and cases in which children were not seriously injured were also simulated to compare dummy kinematics and dynamic responses in optimal restraint configurations. RESULTS: Restraint misuse was associated with greater motion of the dummy torso and head during crashes, often allowing contact between the child and the vehicle interior, resulting in injury. Poor pre-crash posture for a child inappropriately restrained in an adult belt appeared to worsen the geometry of the sash (shoulder) belt, resulting in a cervical injury due to direct interaction with the belt. Dynamic dummy data did not appear to discriminate between injury and non-injury cases. CONCLUSIONS: Dummy kinematics suggest that injuries in which inappropriate use and misuse were a factor were less likely if the most appropriate restraint was used correctly. Adequately controlling the head and upper body of the child occupant was seen to prevent undesirable interactions with the vehicle interior and restraint system, which were associated with injury in the real world. Neck forces and moments and injury criteria calculated from these did not predict injury reliably. PMID- 17366337 TI - Exploring motorcyclist injury severity resulting from various crash configurations at T-junctions in the United Kingdom--an application of the ordered probit models. AB - OBJECTIVES: The fact that motorcycle users tend to be more vulnerable to injuries than those using other motorized vehicles may act synergistically with the complexity of conflicting movements between vehicles and motorcycles to increase injury severity in a junction-type accident. A junction-type collision tends to be more severe than a non-junction case due to the fact that some of the injurious crashes such as angle-collision commonly occur. Existing studies have applied several statistical modeling techniques to examine influential factors on the occurrences of different crashes among motorized vehicles but surprisingly very little has empirically explored whether a particular crash type, resulting from a junction-type accident, is more injurious to motorcyclists. This article attempts to investigate whether a particular collision is more deadly to motorcyclists conditioned on crash occurrence at T-junctions in the U.K., while controlling for environment, vehicle, and demographic factors. METHODS: The statistical modeling technique employed is the ordered probit models using the data extracted from the STATS19 accident injury database (1999-2004). RESULTS: The modeling found determinants of injury severity among motorcyclists at T junctions in the U.K. For example, an approach-turn/head-on collision is much more injurious to motorcyclists; and, those riding in early morning (i.e., 0000 0659) are more likely to be severely injured. CONCLUSIONS: This study offers a guideline for future research, as well as insight into potential prevention strategies that might help moderate motorcyclist injuries. PMID- 17366338 TI - The impact of roadway intersection design on driving performance of young and senior adults. AB - OBJECTIVE: To test the effectiveness of the FHWA guidelines for intersection design. METHODS: In an experimental design we used kinematics measures from an instrumented vehicle and behavioral (error) data collected during on-road evaluations to quantify the effects of improved versus unimproved intersections (turn phase) and to determine if these intersections were safer (vehicular stability and driver confidence) for both older (65-85 years) and younger (25 45) drivers. We analyzed kinematics data with a 2 x 2 repeated measures ANOVA and behavioral data (driving errors yes, no) with Wilcoxon sign rank test (within subject variable: intersection improved vs. unimproved) and Wilcoxon rank sum test (between subject variable: age, younger vs. older driver). RESULTS: Kinematics measures (turn phase), showed three maneuvers had statistically significantly lesser side forces (measured by lateral acceleration and combined acceleration) for the improved conditions, and four maneuvers had statistically significantly greater, yet appropriate, speeds for the improved conditions. Lesser side forces indicated improved lateral stability and increased speed indicated greater confidence. Drivers made fewer errors on two of the improved intersections; but across all maneuvers, older drivers appeared to make fewer errors on the improved intersections. CONCLUSIONS: This study brings empirical intersection design and safety information for engineers and city planners to consider as they plan and develop intersections. Future researchers may want to use the conceptual and analytical framework of this study to determine the effectiveness of other FHWA guidelines. Given that these intersection design guidelines benefit younger and older drivers alike, plausible policy-making opportunities are opened in the design of safe roadway systems, to benefit the broad spectrum of adult drivers. PMID- 17366339 TI - The impact of intersection design on simulated driving performance of young and senior adults. AB - PURPOSE: The Federal Highway Administration (FHWA) proposed guidelines for highway design to increase the safe driving ability of older drivers; however, little empirical evidence exists to support the effectiveness of these guidelines. The purpose of this study was to investigate the effects of implementing these guidelines (in 4 pairs of intersections) on safe driving performance of older and younger drivers using a high-fidelity driving simulator. DESIGN AND METHODS: We replicated four intersection pairs (improved versus unimproved) in a high-fidelity, virtual reality driving simulator. Simulator scenarios were created from actual road locations, replicating road geometrics and traffic control devices. The simulator's controls were integrated with an actual vehicle to make the driving experience as realistic as possible. Kinematic measures were obtained from the simulator in conjunction with driving errors recorded by trained driving evaluators sitting in the cab of the car. Thirty-nine subjects, 19 younger and 20 older adults, participated in the study. RESULTS: For the kinematic data we found greater lateral control, as indicated by significantly smaller maximum yaw during the turn phase, at all of the improved intersections when compared to the unimproved intersections. We found some significant age differences, but mostly in only one of the intersection-pairs. For the behavioral data, there were significant differences in driving errors between improved and unimproved intersections in two intersection-pairs; however, there were no significant differences in driving errors between the older and younger drivers. IMPLICATIONS: The findings suggest that both young and older drivers may benefit from roadways with safety features recommended by the FHWA guidelines as indicated by the increased lateral control of the vehicle when negotiating these intersections. These findings generate critical information for those involved in the design of roadway systems. PMID- 17366340 TI - Backset and cervical retraction capacity among occupants in a modern car. AB - OBJECTIVES: The horizontal distance between the back of the head and the frontal of the head restraint (backset) and rearward head movement relative to the torso (cervical retraction) were studied in different occupant postures and positions in a modern car. METHODS: A stratified randomized population of 154 test subjects was studied in a Volvo V70 year model 2003 car, in driver, front passenger, and rear passenger position. In each position, the subjects adopted (i) a self selected posture, (ii) a sagging posture, and (iii) an erect posture. Cervical retraction, backset, and vertical distance from the top of the head restraint to the occipital protuberance in the back of the head of the test subject were measured. These data were analyzed using repeated measures ANOVA and linear regression analysis with a significance level set to p < 0.05. RESULTS: In the self-selected posture, the average backset was 61 mm for drivers, 29 mm for front passengers, and 103 mm for rear passengers (p < 0.001). Women had lower mean backset (40 mm) than men (81 mm), particularly in the self-selected driving position. Backset was larger and cervical retraction capacity lower in the sagging posture than in the self-selected posture for occupants in all three occupant positions. Rear passengers had the largest backset values. Backset values decreased with increased age. The average cervical retraction capacity in self-selected posture was 35 mm for drivers, 30 mm for front passengers, and 33 mm for rear passengers (p < 0.001). CONCLUSIONS: Future design of rear-end impact protection may take these study results into account when trying to reduce backset before impact. Our results might be used for future development and use of BioRID manikins and rear-end tests in consumer rating test programs such as Euro-NCAP. PMID- 17366341 TI - Head injuries in child pedestrian accidents--in-depth case analysis and reconstructions. AB - OBJECTIVE: The aim of this study was to investigate head injuries, injury risks, and corresponding tolerance levels of children in car-to--child pedestrian collisions. METHODS: An in-depth accident analysis was carried out based on 23 accident cases involving child pedestrians. These cases were collected with detailed information about pedestrians, cars, and road environments. All 23 accidents were reconstructed using the MADYMO program with mathematical models of passenger cars and child pedestrians developed at Chalmers University of Technology. The contact properties of the car models were derived from the European New Car Assessment Program (EuroNCAP) subsystem tests. RESULTS: The accident analysis demonstrated that the head was the most frequently and severely injured body part of child pedestrians. Most accidents occurred at impact speeds lower than 40 km/h and 98% of the child pedestrians were impacted from the lateral direction. The initial postures of children at the moment of impact were identified. Nearly half (47%) of the children were running, which was remarkable compared with the situation of adult pedestrians. From accident reconstructions it was found that head impact conditions and injury severities were dependent on the shape and stiffness of the car front, impact velocity, and stature of the child pedestrian. Head injury criteria and corresponding tolerance levels were analyzed and discussed by correlating the calculated injury parameters with the injury outcomes in the accidents. CONCLUSIONS: Reducing head injuries should be set as a priority in the protection of child pedestrians. HIC is an important injury criterion for predicting the risks of head injuries in child pedestrian accidents. The tolerance level of head injuries can have a considerable variation due to individual differences of the child pedestrians. By setting a suitable speed limit and improving the design of car front, the head injury severities of child pedestrians can be reduced. PMID- 17366342 TI - Reducing primary and secondary impact loads on the pelvis during side impact. AB - OBJECTIVE: The objective of the study was to determine which vehicle factors are significantly related to pelvic injury in side impact collisions. Identification of relevant parameters could aid in the reduction of these injuries. METHOD: Side impact crashes from the CIREN database were separated into those in which the occupant sustained a pelvic fracture and those in which no pelvic fracture occurred, although all occupants had serious injuries. A multibody MADYMO model was created of a USDOT SINCAP (U.S. Department of Transportation Side Impact New Car Assessment Program) test of a vehicle with a large center console. RESULTS: From a study of 113 side impact crashes in the ciren database, nearside occupants with pelvic fractures (n = 78) had (i) more door intrusion (mean, 37 vs. 32 cm, p = 0.02) than those who had serious injuries, but not pelvic fractures (ii) a greater likelihood that the lower border of the door intruded more than the upper part (40% vs. 18%, p < 0.025); and (iii) a greater likelihood that their vehicle had a center console (47 vs. 17%, p < 0.005). Other parameters such as occupant age, weight, gender, vehicle weight, and struck vehicle speed change were not significantly different. MADYMO modeling showed that with a center console, an initial positive pelvic acceleration occurred at about 30 msec, followed at about 45 msec by a second acceleration peak in the opposite direction. Reducing console stiffness reduced the second acceleration but not the initial peak. Allowing the seat to translate laterally when contacted by the door reduced the initial pelvic acceleration by 50% and eliminated the second acceleration peak. CONCLUSIONS: Redesigning the center console using less stiff materials and allowing some lateral translation of the seat could aid in reducing pelvic injuries in side impact collisions. PMID- 17366343 TI - Could pharmacogenetics play a role as predictor in treatment of depressive disorders? PMID- 17366344 TI - Evolving trends in the long-term treatment of bipolar disorder. AB - The episodic and chronic nature of bipolar disorder usually requires long-term treatment in all patients, yet there is an unmet need for well-tolerated and clinically effective maintenance therapy with enhanced patient adherence. Few well-tolerated treatment options are currently available that are both effective in all phases of bipolar disorder and prevent recurrence of episodes. Lithium has well-established efficacy in the prevention of further manic episodes and may also be effective in the prevention of depression and suicide, but safety is a concern due to narrow therapeutic window. For valproate and carbamazepine, data appear much less compelling. Lamotrigine has shown to be effective for long-term prevention of depressive episodes. Controlled studies suggest that atypical antipsychotics may also have mood-stabilizing properties and might become standard for long-term therapy in the new future. The role of psychoeducation in improving adherence to medication in long-term treatment and overall patient outcomes is also crucial. PMID- 17366345 TI - Potential genetic variants in schizophrenia: a Bayesian analysis. AB - A number of different gene polymorphisms have been found to dispose for the development of schizophrenia. However, no single gene polymorphism is sufficient for the precipitation of schizophrenia. Swedish psychosis patients (n=103) and control subjects (n=89) were analyzed for 36 single nucleotide polymorphisms in 30 candidate genes for schizophrenia. Evidence of association was analyzed with Bayesian statistical methods. Variants in the genes coding for dopamine-D2 receptor, brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), neuregulin 1, reelin and synapsin 3 showed association with schizophrenia, although few subjects were found in the minority allele for the two latter variants. The six gene variants, all with suspected connection to schizophrenia, were found to be risk factors when considered in combination, but not separately. The results indicate that the Bayesian statistical method gives additional possibilities in the search for risk factors for schizophrenia or other complex disorders. PMID- 17366346 TI - Brain activation in elderly people with and without dementia: Influences of gender and medication. AB - Patients suffering from dementia show altered functional brain activation patterns especially in prefrontal brain regions, as research suggests. The present study follows three aims: to replicate these findings, to investigate treatment effects when administering galantamine, and to put gender differences in focus. We compared 12 patients with dementia to 12 age- and gender-matched healthy subjects regarding changes in haemoglobin concentration in brain tissue while performing a verbal fluency task (VFT). Concentration changes of oxygenated (O(2)Hb) and deoxygenated (HHb) haemoglobin were measured by multi-channel near infrared spectroscopy (NIRS), an easily applicable and non-invasive method of optical topography. In the patient group, measurement was repeated 4 and 8 weeks after starting treatment with galantamine. The results showed a reduced increase in O(2)Hb during task performance for patients compared to healthy controls. Furthermore, female subjects showed more pronounced activation in O(2)Hb as well as HHb compared to male subjects. Regarding treatment effects, no clear results could be obtained. In HHb, evidence for an entrainment effect was found. In the light of existing literature, the present study suggests an interaction of gender and age regarding brain activation patterns which should be aimed at in future investigations. PMID- 17366347 TI - The ultrastructure of lymphocytes in schizophrenia. AB - OBJECTIVE: Replicated abnormalities in schizophrenia include decreased cellular immunity. The aim of the study was to verify whether there are some abnormalities in the ultrastructure of lymphocytes in drug-free schizophrenic patients. METHOD: Fifty-nine in-patients with paranoid schizophrenia (DSM-IV 295.30) and 31 normal controls were used. Psychosis severity was assessed by the PANSS psychotic cluster. Electron microscopy and morphometric methods were applied to estimate the frequency and ultrastructural parameters of small, large, large activated lymphocytes (LAL) (containing 10 and more mitochondria) and of atypical lymphocytes (lymphoblasts, LB). RESULTS: The frequency of small lymphocytes in schizophrenic patients was lower and that of large lymphocytes, LAL and LB was higher than in controls (all p= < 0.01). The volume density (Vv) of mitochondria in LAL in individuals with schizophrenia was lower than in controls (p<0.05), correlated negatively with the frequency of LB, Vv and number of lysosomes in LB (all p<0.01) and with the psychosis severity (p<0.05). In schizophrenic patients a trend towards positive correlations between the frequency of LB and psychosis severity were found (p<0.07). CONCLUSION: The data suggest that the excess of LB in schizophrenic patients is associated with the dysfunction of energy metabolism in LAL, and these abnormalities are related to schizophrenia. PMID- 17366348 TI - Quetiapine in the treatment of psychotic adolescents: a case series of 23 patients with severe early onset psychosis. AB - Clinical efficacy, safety and tolerability of quetiapine in the treatment of 23 hospitalized psychotic adolescents were evaluated retrospectively. Twelve patients were changed to quetiapine from another antipsychotic medication during their hospital stay. In these patients, CGI-S improved from 4.75+/-0.87 to 2.92+/ 0.67 (observation period 3.7+/-1.6 months). The most common adverse events were transient tachycardia and sedation. Mild EPS occurred only in one patient under quetiapine monotherapy. Transaminase increases more than threefold above norm were observed in two patients. fT4 values were slightly below the norm in 67% of the cases. In 11 patients, quetiapine was initiated using a rapid titration schedule with high dosages in the acute phase. Receiving a mean maximum daily dose of 927+/-300 mg, CGI-S improved from 6.00+/-0.63 to 3.18+/-1.25 (observation period 2.9+/-1.8 months). Severe adverse events did not occur. Besides applying lorazepam temporarily in nine of the 11 patients, antipsychotic co-medication was not necessary in this group. In line with other studies, quetiapine may be considered as an effective treatment for adolescents with a severe psychotic disorder showing a favourable side-effect profile. Our preliminary data suggest that a rapid initiation with high doses could be a promising approach in acute psychotic adolescents. PMID- 17366349 TI - Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment. AB - Neuroleptic malignant syndrome (NMS) is the rarest and most serious of the neuroleptic-induced movement disorders. We describe a case of neuroleptic malignant syndrome (NMS) associated with the use of ziprasidone. Although conventional neuroleptics are more frequently associated with NMS, atypical antipsychotic drugs like ziprasidone may also be a cause. The patient is a 24 year-old male with a history of schizophrenia who developed signs and symptoms of NMS after 2 days of treatment with an 80-mg/day dose of orally administrated ziprasidone. This case is the earliest (second day of treatment) NMS due to ziprasidone reported in the literature. PMID- 17366350 TI - Risperidone-induced priapism. AB - A 31-year-old patient suffering from schizophrenic psychosis was treated with risperidone, and developed priapism which required surgical intervention and resulted in long-term erectile dysfunction. PMID- 17366351 TI - Second run of transcranial magnetic stimulation has no effects on persistent auditory hallucinations. AB - We report the case of a 30-year-old male schizophrenic patient with persistent auditory hallucinations (AHs) who had received two 1-Hz transcranial magnetic stimulations (TMS) to the left temporoparietal cortex. The patient had suffered from severe persistent AHs for more than 5 years with little improvement in response to various types of combination pharmacotherapy of antipsychotics. Upon commencement of TMS, however, the patient reported substantial improvement by the end of the third week of the treatment. The patient was discharged, but readmitted 6 months later because his AHs returned to their initial severity. A second run of TMS had no therapeutic effect. Further research is needed to establish the therapeutic duration of TMS treatment and to assess whether the second run of TMS after AH re-occurrence has therapeutic benefits. PMID- 17366352 TI - Hyponatremia-induced seizure during carbamazepine treatment. AB - We report the case of a 54-year-old woman who was admitted for benzodiazepine withdrawal. After 6 weeks of carbamazepine treatment (600, then 200 mg) the patient suddenly suffered from a grand mal seizure. Laboratory findings revealed a clinical significant hyponatremia of Na 125 mmol/l (baseline: 143 mmol/l). CCT and ECG were normal. To our knowledge, this is the first description of a seizure related to hyponatremia in an adult carbamazepine-treated patient. PMID- 17366353 TI - Butterfly glioma of corpus callosum presenting as catatonia. AB - Catatonia can occur with functional psychiatric disorders as well as organic conditions. In this case report, catatonia occurred with a butterfly glioma originating from the corpus callosum with bilateral medial frontal extensions. Medial frontal lobe structures have been implicated in the pathophysiology of catatonia. PMID- 17366354 TI - Depression as a manifestation of latent chronic hypoparathyroidism. AB - The exact cause of depression in cases of hypoparathyroidism is not known. We report the first case of an elderly patient with a long history of major depression as a complication of an undiagnosed chronic hypoparathyroidism following surgery on a parathyroid adenoma. Her depression was completely eliminated by calcium supplementation therapy to restore the calcium homeostasis in serum. As it is well known that disturbances in the endocrine hypothalamus pituitary-thyroid system might be consistent findings of depressive disorders concerning neuroendocrinological alterations, this case report and review of literature strongly supports our claim that also parathyroid diseases like chronic hypoparathyroidism, even in its latent form, might be a relevant factor in the development of depressive symptoms. PMID- 17366355 TI - Effects of pathogenic factors on prognosis in patients with prosthetic valve endocarditis. AB - INTRODUCTION: Despite progress in medicine, the prevalence of infective endocarditis (IE) in patients with prosthetic valves (PVE) has not decreased. Positive blood and valve cultures are one of the most important diagnostic criteria of IE. There are no unambiguous data regarding the influence of pathogenic factors on prognosis. AIM: To analyse blood and valve cultures in patients with PVE and assess their impact on the risk of early and late deaths as well as IE relapse. METHODS: The study group consisted of 71 PVE patients. Infective endocarditis was diagnosed based on the Polish Cardiac Society guidelines. Early and late mortality as well as IE relapse were analysed in patients hospitalised between 1988 and 1998. RESULTS: Positive blood cultures were found in 55 (77.5%) patients. Early mortality was 15.5% (11 deaths). Coagulase-negative Staphylococcus infection was an independent risk factor of early death (p=0.02). During long-term follow-up 8 (13.3%) patients died. The risk of late death increased with positive valve culture (p=0.04). Recurrence of IE was diagnosed in 6 (10%) patients. Staphylococcus epidermidis was a risk factor of disease relapse (p=0.03). Six-year survival was 73%. CONCLUSIONS: 1. Coagulase-negative Staphylococcus aetiology increases the risk of early death in patients with PVE. 2. Pathogenic factors did not influence the risk of late death. 3. The risk of late death was increased with positive valve culture with negative blood cultures. 4. Staphylococcus epidermidis aetiology increases the risk of PVE relapse. PMID- 17366356 TI - Percutaneous closure of recanalised ductus arteriosus--a single-centre experience. AB - INTRODUCTION: Restoration of blood flow through a previously occluded ductus arteriosus may occur in some patients. Treatment strategy in patients with such residual shunts has not yet been uniformly established. AIM: To present single centre experience and to attempt to establish a strategy of management of patients with residual ductus arteriosus shunts following percutaneous closure. METHODS: Of 352 patients who underwent percutaneous closure of ductus arteriosus, in 13 subjects complete closure failed (coils and Rashkind occluders were used in 10 and 3 patients, respectively). In these patients other percutaneous interventions aiming at total closure of residual shunt were attempted. RESULTS: In 12 patients coils were inserted (one patient received two coils). Introduction of implant in one patient failed, but total occlusion of the shunt was confirmed one day after the procedure. Trivial residual shunt was observed in one patient after one-year follow-up. CONCLUSIONS: Percutaneous treatment of residual shunts within the ductus arteriosus is an effective and safe procedure. In our opinion identifying and treating such leaks is important, as it prevents complications and long-term need for antibiotic prevention of infective endocarditis. In the case of a small residual shunt, insertion of a coil seems to be the optimal therapy due to the low cost of the device, favourable design and high effectiveness. For patients in whom anatomy of the ductus arteriosus has been significantly changed, particularly in previously treated subjects, techniques using vascular loops or insertion using a catheter wedge may be helpful. PMID- 17366357 TI - Characteristics of patients with coronary artery disease managed on an outpatient basis in the population of Poland. Results of the multicentre RECENT trial. AB - INTRODUCTION: Comprehension of clinical characteristics and therapeutic methods in patients with coronary artery disease (CAD) is mandatory for the introduction of successful prevention. AIM: The aim of the multicentre RECENT trial carried out in Poland in 2005 was to gather comprehensive information regarding individuals with CAD treated by specialists as well as by general practitioners on an outpatient basis. In this report, clinical characteristics of the Polish patient population with confirmed CAD are presented. METHODS: A representative group of 215 general practitioners and 67 specialists participated in this study. They collected information about 2593 patients with CAD and filled-in a specially designed questionnaire. RESULTS: Coronary artery disease was confirmed predominantly based on a history of myocardial infarction (50.1%), followed by positive electrocardiographic stress test (38.8%), history of typical angina in subjects at the age of >60 years (36.4%), history of previous acute coronary syndrome (29.0%), PCI (22.1%) or CABG (14.3%) or positive coronary angiography (17.6%). In patients with diagnosed stable CAD, 44.6% were women and the mean age was 65.0+/-9.8 years. Among patients with a history of hypertension (78.0%), only 34.0% had blood pressure within the normal range. History of dyslipidaemia was positive in 57.6% of patients. Normal LDL cholesterol concentrations (<3.36 mmol/L) were found in 56.7% of patients. A family history of CAD had 17.3% of subjects, 23.5% had previously detected diabetes mellitus and 11.0% were active smokers at the time of study enrolment. Overweight or obesity both in men and women was found in 79.3% of patients while metabolic syndrome (diagnosed according to NCEP ATP III criteria) was found in 31.3%. The following comorbidities were detected: 34.3% presented symptoms of congestive heart failure, 32.1% had rhythm or conduction disturbances (most commonly atrial fibrillation--in 19.0% of cases). Previous stroke was noted in 4.7% of patients with CAD and transient ischaemic attack in 5.5%. Peripheral artery disease was observed in 9.9% of CAD patients, whereas asthma or COPD--in 9.0%. CONCLUSIONS: The results of the RECENT trial are representative for the CAD patient population managed on an outpatient basis in our country. They suggest that CAD in the Polish population is rather advanced, and indicate still insufficient use of imaging modalities (particularly coronary angiography) and significant prevalence of risk factors throughout this population. PMID- 17366358 TI - The myocardial performance index in children after surgical correction of congenital malformations with intracardiac shunt. AB - BACKGROUND: The lack of a simple and clinically useful method of myocardial function assessment makes it difficult to monitor patients after repair of congenital cardiac malformations. The myocardial performance index (MPI) introduced in 1995 by Chuwa Tei may help to precisely follow the course of postoperative myocardial function disturbances. AIM: To assess the usefulness of MPI for cardiac function evaluation following surgical correction of congenital defects performed in cardiopulmonary bypass and to evaluate it's prognostic value. METHODS: This prospective study involved 73 children who underwent surgery for simple defects with intracardiac shunt--34 children with atrial septal defect (ASD) and 39 with ventricular septal defect (VSD). In the examined patient group, MPI and the parameters of cardiac index were measured in the early postoperative period. Then the results were correlated with congenital defect severity and postoperative course. The control group consisted of 77 healthy children. RESULTS: In the control group of healthy children, mean values of the right (RVMPI) and the left ventricular MPI (LVMPI) were 0.32+/-0.06 and 0.33+/-0.05, respectively. In children after ASD correction, MPI was elevated only for the right ventricle (mean value of 0.41+/-0.07). Meanwhile in children operated on for VSD, both the RVMPI and LVMPI values increased postoperatively. RVMPI reached a peak value on the 2nd postoperative day (0.48+/-0.20) while LVMPI reached a peak value between the 3rd and 5th day after surgery (0.49+/-0.10). A significant and strong correlation between severity of VSD and MPI values was observed. A marked correlation between MPI calculated on the 1st postoperative day and the course after surgery was also noted. CONCLUSIONS: The MPI is a precise tool assessing both systolic and diastolic ventricular performance in the early postoperative period following surgical correction of a congenital defect with intracardiac shunt and is also a useful predictive factor of the postoperative course. PMID- 17366359 TI - Early and long-term outcomes after surgical treatment in patients with aortic stenosis and severe left ventricular heart failure without concomitant coronary artery disease with respect to preoperative mean transvalvular pressure gradient. AB - INTRODUCTION: There are limited data on early and long-term prognosis in patients after aortic valve replacement who have left ventricular dysfunction, reduced ejection fraction (EF) < or =35% and no concomitant coronary artery disease. AIM: To assess the prognosis in this group of patients depending on the mean aortic gradient (MAG) value. METHODS: This study involved 60 patients with severe aortic stenosis and EF < or =35%. Patients with coronary artery disease, more than moderate aortic regurgitation and any other valvular lesion were excluded. Patients were divided into two groups based on the MAG values: group I included patients with MAG < or =35 mmHg, and group II included patients with MAG >35 mmHg. RESULTS: Early mortality after aortic valve replacement was 14.2% in group I, and 5.1% in group II. During a mean follow-up of 48 months mortality in groups I and II was 16.6% and 2.6%, respectively. In the follow-up period, a significant functional improvement according to NYHA scale as well as significant decrease of left ventricular dimensions and increase of EF was observed in both groups of patients. CONCLUSIONS: Patients with severe aortic stenosis, left ventricular ejection fraction <35% and MAG < or =35 mmHg constitute a group of the highest early and long-term mortality risk after valve replacement. In turn, patients with MAG >35 mmHg should be classified as the group of slightly increased risk. PMID- 17366360 TI - Totally epicardial cardiac re-synchronization therapy system implantation in patients with heart failure undergoing CABG--description of 3 cases. AB - INTRODUCTION: Systolic dyssynchrony as an indication for cardiac re synchronization therapy is present in a considerable subset of patients with congestive heart failure undergoing surgical coronary revascularisation. Coronary artery bypass grafting offers an optimal setting for totally epicardial cardiac re-synchronization system implantation. AIM: To assess the feasibility and safety of totally epicardial cardiac re-synchronization system implantation in patients with ischaemic heart disease and heart failure undergoing coronary artery bypass grafting. METHODS: Three male patients with coronary artery disease and postinfarction functional class III congestive heart failure underwent a combined procedure of on-pump surgical coronary revascularisation and totally epicardial cardiac re-synchronization system implantation (all three leads implanted epicardially). In all patients intraventricular dyssynchrony was revealed in preoperative echocardiography. RESULTS: There was no perioperative morbidity or mortality. The mean total time required for cardiac re-synchronization system implantation was 17.3+/-2.3 minutes. We obtained excellent pacing and sensing parameters at implant (left ventricular pacing thresholds: 0.8, 0.5, 0.5 V at 0.5 ms; left ventricular sensing thresholds: 17, 15, 20 mV, respectively in consecutive patients). After 12 months pacing and sensing parameters remained stable. Significant improvement in 6-minute walk test distance, functional class and echocardiographic parameters (left ventricular ejection fraction, intraventricular dyssynchrony) was observed in all patients. CONCLUSIONS: Totally epicardial cardiac re-synchronization system implantation is safe and can be regarded as an important supplement to surgical coronary revascularisation in the still growing population of patients with severe heart failure and systolic dyssynchrony, which can be used for the optimisation of treatment results. PMID- 17366361 TI - [Transient left ventricular apical ballooning syndrome--a case report]. AB - We present a case of a 78-year-old female who was admitted to the hospital due to clinical and electrographic features of ST-elevation acute myocardial infarction. Coronary angiography revealed normal coronary arteries and severe left ventricular contractility abnormalities, detected initially by echocardiography, which resolved within 20 days from hospital admission. Because of these findings and typical echocardiographic picture, a transient left ventricular apical ballooning syndrome (the tako-tsubo syndrome) was diagnosed. PMID- 17366362 TI - [Right atrial thrombus following surgical closure of atrial septal defect--a case report]. AB - A case of an 11-year-old girl with atrial septal defect is described. The patient underwent surgical closure of the defect, which was complicated by asymptomatic thrombus formation in the right atrium. Anticoagulant therapy was initially successful, but thrombus recurred. Surgical thrombus removal was successful. PMID- 17366363 TI - [Spontaneous recanalisation of the superficial femoral artery following angioplasty of the femoral artery in a patient with disseminated atherosclerosis- a case report]. AB - We present a case of a 51-year-old male with multivessel coronary artery disease and disseminated peripheral arterial disease (PAD) who underwent coronary angioplasty, followed by angioplasty with stent implantation of the left superficial iliac artery and right femoral artery. Thirty days later the patient was admitted for elective angioplasty of the previously closed superficial right femoral artery; however, angiography showed that the artery was patent with a residual stenosis which narrowed the vessel lumen by 10%. We believe that spontaneous recanalisation of this artery was caused by multiple factors, including cessation of smoking, physical training, pharmacological therapy and previous angioplasty of the right femoral artery. PMID- 17366364 TI - [Clinical significance of muscle bridge narrowing coronary artery lumen- description of three cases]. AB - The muscle bridge is an anomaly which is found in 0.5-2.5% of coronary angiography examinations and may lead to impairment of coronary blood flow. The clinical course of the disease may be heterogeneous--from completely asymptomatic to the development of myocardial infarction or severe ventricular arrhythmia. We present three patients with muscle bridge in the left anterior descending artery. The clinical course of the disease was different in each patient--from mild symptoms to cardiac arrest during exercise test. PMID- 17366365 TI - [Clinical significance and prognostic value of anemia in heart failure patients]. PMID- 17366366 TI - [Erythropoietin in the treatment of heart failure and ischemia]. PMID- 17366367 TI - [Complete heart block?]. PMID- 17366368 TI - [Successful thrombectomy with Diver aspirator in the treatment of acute myocardial infarct of the lower heart wall]. PMID- 17366369 TI - [Atrial tachycardia ablated from the non-coronary aortic cusp]. AB - We present a case of a patient with drug resistant atrial tachycardia which was ablated from the noncoronary aortic cusp. Tachycardia was adenosine-sensitive and was characterized by a long RP' interval and low amplitude P waves (biphasic in II, III, aVF and V1-V2 leads, and positive in aVL). The earliest atrial activation during tachycardia was recorded at His region and from non-coronary aortic sinus of Valsalva. RF ablation at this area terminated tachycardia and did not impair atrio-ventricular conduction. PMID- 17366370 TI - [Large, asymptomatic left atrial myxoma--a case report]. AB - We report a patient with a large, asymptomatic left atrial myxoma detected by transoesophageal echocardiography. The tumour filled the great part of the left atrium cave and led to mitral valve obstruction. Surgical management gave an excellent result. PMID- 17366371 TI - [Commentary to the article: Kahn SE, Haffner SM, Heise MA, et al. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-43]. PMID- 17366372 TI - Cytotoxic triterpene and sesquiterpene lactones from Elephantopus mollis and induction of apoptosis in neuroblastoma cells. AB - Activity-guided fractionation of root and leaf extracts from Elephantopus mollis led to the isolation of a new triterpene (1) and a new sesquiterpene lactone (2) together with five known sesquiterpene lactones (3-7). The structures of compounds 1 and 2 were determined based on their spectroscopic data. The cytotoxic activity of the isolated compounds was evaluated against neuroblastoma B104 cells. The sesquiterpene lactone-type compounds 2-7 were highly cytotoxic. Among these, compound (5) was the most cytotoxic and induced apoptosis of neuroblastoma B104 cells in a dose- and time-dependent manner. No significant difference was observed for cytotoxicity of compound 5 towards all 3 cell lines tested. PMID- 17366373 TI - Antiproliferative cardenolides from Periploca graeca. AB - Nine cardiotonic steroids, six 17beta-cardenolides (2, 4, 6-9) and three 17alpha cardenolides (1, 3, 5) have been identified from the chloroform and chloroform methanol extracts of Periploca graeca L. (Asclepiadaceae) stems. Among these, compound 5, the 17alpha-isomer of periplocin 6, was identified as a new compound. The antiproliferative effects of these compounds were tested in vitro in the hormone-independent prostate cancer cell line PC-3. Five of these compounds, all 17beta-isomers with a 14beta-OH group and at least one sugar molecule (4, 6-9), showed a very strong antiproliferative effect, with IC50 values between 18 and 50 nM. Compound 2, the only 17beta-cardenolide aglycone, had an IC50 value of 0.6 microM, which is 13 to 16 times higher than the values found for the corresponding cardenolides with one or two sugars. The IC50 values found for the three 17alpha-isomers were significantly higher (5.4 and 7.3 microM), with IC50 ratios (17alpha-cardenolide/17beta-cardenolide) of up to 192. In the 17alpha cardenolide series, the presence of a sugar unit does not seem to have a significant effect on the IC50 values. This is the first report showing a markedly different cytotoxicities between the 17alpha- and 17beta-isomers in the cardenolide series. PMID- 17366374 TI - [Sonographic diagnosis of hilar cholangiocarcinomas by the use of contrast agents]. AB - PURPOSE: Imaging of hilar cholangiocarcinomas (Klatskin tumour) is very difficult as these tumours spread along the bile ducts and are hardly distinguishable from the surrounding liver parenchyma. Improved imaging techniques are useful for diagnosis and monitoring of new treatment strategies like photodynamic therapy. In a prospective study, we investigated whether contrast-enhanced sonography is useful in the imaging of Klatskin tumours. MATERIALS AND METHODS: Between 1997 and 2004, 72 patients with suspected Klatskin tumour were admitted to our clinic. 47 patients with histologically confirmed hilar cholangiocarcinomas (Bismuth III/IV) were included in the study and investigated by standard B-mode sonography. Consecutively, patients were investigated by the use of an echo enhancer. 27 patients were investigated by Levovist (power-Doppler sonography, 2nd harmonic imaging, high MI), 20 patients were investigated by Sonovue (CPS, low MI). RESULTS: By use of baseline sonography, visualisation of a tumour and differentiation from normal liver parenchyma was possible in 17 of 47 (36%) patients. After application of contrast agents, tumours showed defects in comparison to the intense flow signal of the surrounding liver tissue during the portalvenous phase and could be discriminated from normal liver tissue allowing determination of tumour size and infiltration of liver parenchyma in all patients (100%). During the arterial phase, 42/47 (89%) of neoplasms showed hypovascularisation compared to surrounding liver tissue, 5/47 (11%) tumours were hypervascularised. During follow-up, metastatic tumour spread was observed in (20/47) 43% of patients, 25/47 (53%) patients developed ascites. CONCLUSION: Contrast agents allow improved imaging of hilar cholangiocarcinomas. The majority of hilar cholangiocarcinomas are hypovascularised. PMID- 17366375 TI - Reliability of modeling evoked flow responses. AB - PURPOSE: Visually evoked flow characterises the relative changes of blood flow velocity in the posterior cerebral artery in response to visual stimulation. The present study is the first to address the reliability of model fitting to evoked flow responses, rigorously defined by Cronbach's alpha. MATERIALS AND METHODS: We fitted two models to the evoked flow responses recorded from 19 subjects on two different days. Model 1 characterises a harmonic oscillator with frequency omega and damping coefficient xi which (after a delay DeltaT) is driven from zero towards a new equilibrium K by an impulse with magnitude T. Model 2 is the sum of a first order system subjected to a step and a transient smoothed pulse, both again delayed by DeltaT. RESULTS: Model 1 exhibited slightly smaller fit errors and convergence was less dependent on starting values for the parameters. As judged from the residual noise in the evoked flow response, there was no clear indication of sustained oscillations characterising model 1 exclusively. Both models showed considerable retest errors. Nonetheless, Cronbach's alpha was significant for K and omega, and highest for K. CONCLUSION: Retest errors were considerable, particularly so for the damping coefficient xi and impulse magnitude T. A physiological interpretation of these parameters is limited by our findings. PMID- 17366376 TI - Aneurysm of the extracranial carotid artery with spontaneous echo contrast revealed by duplex sonography. AB - A 56-year old male patient without cerebrovascular disease or risk factors presented with a painless, pulsatile right-sided cervical swelling. Ultrasonography showed a large aneurysm of the right common and internal carotid artery with homogeneous thickening of the vessel wall as well as a parietal thrombus and a dilation of the left common and internal carotid artery with markedly reduced blood flow velocities. In the enlarged lumen of the right internal carotid artery spontaneous echo contrast was apparent with slow, ineffective but orthograde blood flow motions. Ensuing diagnostic procedures revealed multiple aneurysms involving the aorta and its branches. Despite surgical removal of the aneurysm and glucocorticoid therapy, the patient died from a ruptured aneurysm of a coronary artery a few weeks later. Post-mortem examination showed panarteritis consistent with Takayasu's disease. Spontaneous echo contrast is a frequent echocardiographic finding in patients with atrial fibrillation and mitral stenosis, indicating decreased blood flow. This is associated with an increased risk of embolism. In our patient, spontaneous echo contrast indicated severely disturbed haemodynamics due to a large aneurysm of the carotid artery. In the rare case of multiple aneurysms, differential diagnosis should include dissections, infections, and connective tissue diseases. Takayasu's arteritis, however, should also be considered, which usually presents with stenoses, but may be associated with multiple aneurysms of the aorta or its branches. If the diagnostic criteria are present, immunosuppressive treatment should be initiated. PMID- 17366377 TI - [Effective acute stroke treatment beyond approval limitations: intravenous thrombolysis within an extended time window (3-6 h) and in old patients (aged 80 or older)]. AB - Intravenous thrombolysis with tPA is the only approved and effective treatment for acute ischemic stroke. The approval, however, is restricted to treatment within 3 hours of stroke onset, and it is not recommended to treat patients beyond 80 years of age. Due to these restrictions, thrombolysis is only given to a small number of acute stroke patients. At the same time there is growing evidence that patients can be treated with thrombolysis safely and effectively even beyond these restrictions. We give an overview over the published data regarding thrombolysis beyond the 3 hour time window and in patients aged 80 or over. Based on these data we conclude that (1.) intravenous thrombolysis in MRI selected patients is safe and effective within an extended time window of up to 6 hours, and (2.) there is no increase in mortality or symptomatic intracerebral bleeding complications in patients aged 80 or over treated with thrombolysis. A great number of acute stroke patients reaches the hospital beyond the 3 hour time window, and there is a growing number of old and very old stroke patients in the western world. Treating patients up to a 6 hour time window and beyond the age of 80 years would clearly increase the number of patients, which might benefit from this effective treatment. To summarize, we recommend experienced stroke centres to treat acute stroke patients with thrombolysis up to 6 hours using MRI criteria for patient selection, and to treat also patients aged 80 years or older. PMID- 17366378 TI - [Treatment prevalence in pathological gambling]. AB - Based on American studies lifetime prevalence of 'Pathological Gambling' (ICD-10, F 63.0) in Germany can be estimated at 0.5 %. That means about 400,000 gamblers requiring treatment. Epidemiological studies showed that only a little proportion is actually seeking treatment. Reliable knowledge about treatment prevalence does not exist for Germany. The study at hand using secondary data was performed to validate the estimation of the 'Deutsche Suchthilfestatistik' regarding inpatient and outpatient treatment prevalence in 'Pathological Gambling' with data from service providers (cost unit). The analysis proves the estimation of the German Addiction Statistics ('Deutsche Suchthilfestatistik') that the inpatient treatment prevalence has considerably risen. In spite of the consideration that treatment of pathological gambling is not limited to specialized hospitals there is still a considerable gap between estimated prevalence and treatment prevalence. PMID- 17366379 TI - [New options in the treatment of depression]. AB - Despite the advances in the psychopharmacology, the treatment of depressive disorder is still not satisfactory. All current pharmacological substances are affecting the monoamines in the central nervous system. The present review discusses advances in the field of monoaminergic antidepressants as well as new treatment alternatives. The new monoaminergic substances include metabolites of known antidepressants, direct serotonin-agonists, and triple-reuptake inhibitors, blocking the transport of serotonin, norepinephrine, and dopamine. Non monoaminergic strategies include substances affecting melatonin or neuropeptides. Glutamate modulating agents such as ketamine or riluzole are another promising approach in the treatment of depression. Some advances have also been achieved in the field of HPA-axis modulation. PMID- 17366380 TI - [Obsessive-compulsive disorders and religion in contemporary perspective]. AB - After a retrospect on former viewpoints about the relationship between psychiatry and religion, especially concerning obsessive-compulsive disorders (S. Freud; "Ekklesiogenic Neurosis") a contemporary perspective shows: religion is hardly mentioned in German-speaking psychiatry textbooks. Pathogenic interaction between religion and psychological disorders is discussed in plurifactorial perspective. Religious views can be distorted by psychic disorders and adapted to the disorders. Starting from an anthropological definition of religion (C. Geertz), the paper presents three functions of religion and explains the relationship of Christian faith and obsessions/compulsions. Teaching programs for students and psychiatrists seem indicated for a better understanding of religion (and its absence) in the context of psychological disorders. PMID- 17366381 TI - Breast cancer metastatic to the colon 20 years after bilateral mastectomy. PMID- 17366382 TI - Video capsule diagnosis of intestinal duplication in a 15-year-old patient. PMID- 17366383 TI - Epiphrenic diverticulum. PMID- 17366384 TI - Endoscopic mucosal resection of a gastric bronchogenic cyst that was mimicking a solid tumor. PMID- 17366385 TI - Hemorrhagic bullous colitis as a primary manifestation of AL amyloidosis. PMID- 17366386 TI - Endoscopic ultrasound-guided drainage of an intra-abdominal abscess: a new therapeutic window to the left subphrenic space. PMID- 17366387 TI - Malignant melanoma metastasis to the colon. PMID- 17366388 TI - Pyogenic granuloma presenting as a rectal polyp at the site of a previous polypectomy. PMID- 17366389 TI - Esophageal small-cell cancer mimicking stromal tumor. PMID- 17366390 TI - Aluminum phosphide-induced esophageal stricture: an unusual complication. PMID- 17366391 TI - Two cases of cystic lymphangioma of the pancreas: a rare finding in endoscopic ultrasonography. PMID- 17366392 TI - Congenital defect of the hard palate. PMID- 17366393 TI - Esophageal tuberculosis in a patient with acquired immune deficiency syndrome: a rare presentation. PMID- 17366394 TI - Esophageal hematoma: a masquerade of rare occurrence. PMID- 17366395 TI - Esophageal duplication cyst presenting as a submucosal tumor: diagnosis by endoscopic ultrasound-guided fine-needle aspiration. PMID- 17366396 TI - Two cases of solitary Peutz-Jeghers-type hamartoma of the duodenum. PMID- 17366397 TI - Vegetable bezoar simulating a malignant mass in the colon. PMID- 17366398 TI - Incidental video-capsule diagnosis of small-bowel Taenia saginata in a patient with recurrent hemorrhage due to angiodysplasias. PMID- 17366399 TI - Ovarian teratoma presenting as a pedunculated polyp at colonoscopy. PMID- 17366400 TI - An esophageal ulcer mimicking advanced esophageal cancer in a patient on alendronate sodium treatment for osteoporosis. PMID- 17366401 TI - Life-threatening delayed-onset bleeding after endoscopic ultrasound-guided 19 gauge Trucut needle biopsy of a gastric stromal tumor. PMID- 17366402 TI - Leiomyoma of the jejunum diagnosed by capsule endoscopy in a pediatric patient. PMID- 17366403 TI - A case of buried bumper syndrome in a patient with a balloon-tipped percutaneous endoscopic gastrostomy tube. PMID- 17366404 TI - Acute appendicitis diagnosed with high-resolution endoscopy plus narrow-band imaging. PMID- 17366405 TI - Capsule endoscopy in a child with a jejunal hemangioma. PMID- 17366406 TI - Removal technique for grapefruit-sized BioEnterics intragastric balloon. PMID- 17366407 TI - Rectal endometriosis mimicking a large polypoid rectal cancer. PMID- 17366408 TI - A rare case of hemobilia associated with aneurysms of the celiac trunk, the hepatic artery, and the splenic artery. PMID- 17366409 TI - Hemorrhage into the gallbladder caused by pseudoaneurysm of the cystic artery. PMID- 17366410 TI - Perforation of a Dacron vascular endoprosthesis into the duodenum. PMID- 17366411 TI - Giant diaphragmatic hernia with intrathoracic gastric volvulus. PMID- 17366412 TI - An unusual cause of intractable vomiting after cisplatin chemotherapy. PMID- 17366413 TI - An inverted hyperplastic polyp with a characteristic colonoscopic appearance. PMID- 17366414 TI - Home-made vacuum syringe for endoscopic ultrasound-guided fine-needle aspiration. PMID- 17366415 TI - Placement of a percutaneous endoscopic gastrostomy feeding tube via a cervical pharyngocutaneous fistula. PMID- 17366416 TI - Metastatic thymic neuroendocrine carcinoma presenting as a pancreatic tumor. PMID- 17366417 TI - Is the fluoroscopic image always a true representation of the position of an endoscopically placed device? PMID- 17366418 TI - An unusual cause of azathioprine inefficacy. PMID- 17366419 TI - A composite adenoma and carcinoid tumor in a single rectal polyp. PMID- 17366420 TI - A patient with protein-losing colon cancer with massive ascites who was successfully treated by surgical resection of the tumor. PMID- 17366421 TI - Sarcoidosis mimicking cholangiocarcinoma. PMID- 17366422 TI - Sigmoidorectal intussusception caused by a malignant tumor of the sigmoid colon: computed tomography with three-dimensional reconstruction. PMID- 17366423 TI - Diagnosis of multinodular goiter by endoscopic ultrasound-guided fine-needle aspiration. PMID- 17366424 TI - A seminal vesicle cyst palpable in the rectum. PMID- 17366425 TI - Sucralfate-formed esophageal bezoar detected following sudden vomiting. PMID- 17366426 TI - Endoscopic sealing of a pancreatic fistula using ethyl-2-cyanoacrylate. PMID- 17366427 TI - Endoscopic ultrasound-assisted transpapillary stent placement. PMID- 17366428 TI - Ascending venous thrombosis from the middle hepatic vein to the left pulmonary artery as a complication of endoscopic Histoacryl sealing of a bile leak after blunt liver injury. PMID- 17366429 TI - Infectious gastritis caused by a mixed fungal and bacterial infection. PMID- 17366430 TI - Inverted Meckel's diverticulum presenting as iron deficiency anemia. PMID- 17366431 TI - A newly developed bipolar-current needle-knife for endoscopic submucosal dissection of large colorectal tumors. PMID- 17366432 TI - Delayed colonic perforation after metal stent placement for malignant colorectal obstruction. PMID- 17366433 TI - Symptomatic esophageal ulceration caused by a Bravo wireless pH probe and subsequent endoscopic removal of the probe using a retrieval net. PMID- 17366434 TI - Glutaraldehyde colitis. PMID- 17366435 TI - Endoscopic ultrasound-guided fine-needle aspiration for diagnosis of an infectious mediastinal mass and/or lymphadenopathy. PMID- 17366436 TI - [Anaesthesia for patients with adrenal gland diseases]. AB - Perioperative management of patients with adrenal gland diseases requires detailed information on the individual endocrine status and the potential complications. Typical signs of primary hyperaldosteronism (Conn's syndrome) comprise arterial hypertension, hypokalaemia and metabolic alkalosis. In such cases preoperative treatment with spironolactone is highly recommended. In patients with hypercortisolism (Cushing's syndrome) the following concomitant disorders must be considered particularly: arterial hypertension, osteoporosis, vulnerable skin, diabetes mellitus, and increased risk for infection and thromboembolism. In all patients with proven or suspected adrenocortical insufficiency (i.e. Addison's disease, after removal of a cortisol producing tumour or as the result of long-term therapy with glucocorticoids) consequent perioperative supplementation of hydrocortisone is mandatory. In patients with phaeochromcytoma hypertensive crisis and tachyarrhythmias may occur intraoperatively resulting from massive catecholamine release. Thus, preoperative treatment with the beta-antagonist phenoxybenzamine is obligatory. In contrast, nitroprusside is the substance of choice for intraoperative control of blood pressure. beta-blocking agents may be used in phaeochromocytoma but only under sufficient beta-blockade. Removal of a malignant tumour of the adrenal gland may induce massive haemorrhage, and thus anaesthetic management has to be modified. PMID- 17366437 TI - [Psychiatric disorders in intensive care--part three: psychic reactions, affective and anxiety disorders]. AB - Perpetual noise, pain, disturbed day-night-cycle, the inability to talk and the difficulty, especially during weaning, to differentiate alertness from sleep and dream from reality are some of the burdens ICU patients are suffering from. Additional sedation and potential sedation gaps plus the medical treatment itself put strain on critically ill humans. Those external stimuli partly cannot be handled well by the patients. Some of these factors or a combination of them, combined with a predisposition and/or insufficient coping mechanisms can result in a wide range of psychiatric disorders. Often psychiatric symptoms appear unspecific and difficult to categorize. Firstly some psychopathological cardinal symptoms are described and potential differential diagnoses are mentioned. After that the following article focuses on sleep, adjustment, depressive and the spectrum of anxiety disorders (especially generalized anxiety disorders, panic disorders, acute stress disorder (ASD) and posttraumatic stress disorder (PTSD)). The article provides prevalences, etiology and risk factors as well as symptomatology, diagnostics and therapeutic options. Those disorders can be diagnosed in ICU but also after transferring to general ward. In our own experience the transfer period is a vulnerable phase for psychopathologic symptoms. As apart from the individual suffering the course of the somatic disease as well as the rehabilitation process are impaired and the disorders have a tendency to have a chronic course, close and early collaboration of ICU physicians and psychiatrists is mandatory. PMID- 17366438 TI - [Pharmacotherapy--physostigmine administered post-operatively]. AB - The central anticholinergic syndrome should be considered in patients with altered mental status following anaesthesia. Physostigmine, a reversible acetylcholinesterase inhibitor, is a first-line medicament for the therapy of the central anticholinergic syndrome. Physostigmine crosses the blood-brain barrier and elevates acetylcholine levels in the brain. For prevention of postanaesthetic shivering, for treatment of intoxications and postoperative pain, and for patients suspected of having antimuscarinic delirium physostigmine is also indicated. PMID- 17366439 TI - [Anesthesia and analgesia in childbirth--introduction and survey]. PMID- 17366440 TI - [Preoperative fasting in labour]. AB - Numerous scientific case reports and observational studies, including that of Curtis Mendelson with its great historical relevance, have reported the problem of aspiration pneumonitis during labour. Because of this, strict fasting prior to delivery to reduce pulmonary aspiration has been doctrine since the 1940s. However, maternal mortality from anaesthesia, particularly from aspiration, has dropped dramatically over recent decades. This is due both to far-reaching improved quality of care as well as technical progress in anaesthesia, which increasingly challenge the scientific basis for fasting in obstetric anaesthesia. Strict fasting has never been proven to reduce morbidity or mortality in labouring women. Because of the physiological and anatomical changes of pregnancy, gastric emptying is theoretically prolonged, and therefore the risk of aspiration is assumed to be increased. However, the available data with patients receiving clear fluids run contrary to this assumption, or at least dispute its clinical relevance. Recent studies report positive influence of reduced fasting time on both maternal comfort and maternal/fetal metabolism without increased risk. This has already led to meaningful discussion regarding a corresponding change in official recommendations. PMID- 17366441 TI - [Spinal and epidural anaesthesia for caesarean section in patients with pre eclampsia]. AB - Neuraxial regional anaesthesia is now widely used in obstetric anaesthesia. Specifically, the rate of spinal anaesthesia increased considerably and is favoured for scheduled caesarean section. Former concerns to use regional anaesthetic techniques in non scheduled cases, e.g. spinal anaesthesia for pre eclampsia are not supported by recent study data. Spinal and epidural anaesthesia are both safe in patients presenting with pre-eclampsia, if contraindications for neuraxial anaesthesia are taken into account. PMID- 17366442 TI - [Prevention and treatment of hypotension during Caesarean delivery]. AB - Regional anesthesia for Caesarean delivery is often accompanied by a reduction in maternal blood pressure. Maternal hypotension may lead to a reduction in uteroplacental blood flow with consecutive fetal acidosis. In order to avoid reductions in uteroplacental blood flow, tremendous research has been performed, showing that the avoidance of aortocaval compression, compression of the lower extremities, and prehydration with colloids are effective in reducing maternal hypotension. Further means include the recent introduction of low dose spinal anesthesia with a combination of small amounts of local anesthetics and opioids. Nevertheless, maternal hypotension is not always preventable and the use of vasopressors is still frequently required. Although ephedrine has been considered the vasopressor of choice over the last decades, current studies show that fetal acidosis is less frequently encountered with the use of phenylephrine, which should thus be considered as a first-line agent. PMID- 17366443 TI - Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? AB - BACKGROUND: Most documented "superspreading events" of severe acute respiratory syndrome (SARS) occurred in hospitals, but the underlying causes remain unclear. We systematically analyzed the risk factors for nosocomial outbreaks of SARS among hospital wards in Guangzhou and Hong Kong, China. METHODS: A case-control study was conducted. Case wards were hospital wards in which superspreading events of SARS occurred, and control wards were wards in which patients with SARS were admitted, but no subsequent nosocomial outbreaks occurred. Information on environmental and administrative factors was obtained through visits to the wards and interviews with ward managers or nursing officers. Relevant information about host factors was abstracted from the medical records. Logistic regression analyses were used to identify the major risk factors for superspreading events. RESULTS: Eighty-six wards in 21 hospitals in Guangzhou and 38 wards in 5 hospitals in Hong Kong were included in the study. Six risk factors were significant in the final multiple-logistic regression model: minimum distance between beds of < or = 1 m (odds ratio [OR], 6.94; 95% confidence interval [CI], 1.68-28.75), availability of washing or changing facilities for staff (OR, 0.12; 95% CI, 0.02-0.97), whether resuscitation was ever performed in the ward (OR, 3.81; 95% CI, 1.04-13.87), whether staff members worked while experiencing symptoms (OR, 10.55; 95% CI, 2.28-48.87), whether any host patients (index patient or the first patient with SARS admitted to a ward) required oxygen therapy (OR, 4.30; 95% CI, 1.00-18.43), and whether any host patients required bi level positive airway pressure ventilation (OR, 11.82; 95% CI, 1.97-70.80). CONCLUSIONS: Our results revealed that factors that were associated with the ward environment and administration were important in nosocomial outbreaks of SARS. The lessons learned from this study remain very important and highly relevant to the daily operation of hospital wards if we are to prevent nosocomial outbreaks of other respiratory infections in the future. PMID- 17366444 TI - Internationally distributed frozen oyster meat causing multiple outbreaks of norovirus infection in Australia. AB - BACKGROUND: Between November 2003 and January 2004, outbreaks of norovirus in 3 Australian jurisdictions involving 83 cases of illness were associated with imported oyster meat. METHODS: Cohort studies were conducted in 2 jurisdictions to identify relative risks of illness for the consumption of oysters. A case series was conducted in the third jurisdiction. RESULTS: The cohort studies conducted in the first 2 jurisdictions identified relative risks of illness of 17 (95% confidence interval, 5-51) and 35 (95% confidence interval, 5-243), respectively, for the consumption of oysters. Multiple strains of norovirus were detected in fecal specimens from 8 of 14 patients and in 1 of the 3 batches of implicated oyster meat using seminested reverse-transcriptase polymerase chain reaction methods. Traceback investigations revealed that all oyster meat was harvested from the same estuary system in Japan within the same month. CONCLUSIONS: These outbreaks demonstrate the potential of foodborne disease to spread internationally and the need for national and international collaboration to investigate such outbreaks. Foodborne illness related to norovirus is underestimated because of underreporting of human cases and challenges in laboratory detection of viruses in foods, both of which can delay public health action. PMID- 17366445 TI - Widespread outbreak of norovirus gastroenteritis among evacuees of Hurricane Katrina residing in a large "megashelter" in Houston, Texas: lessons learned for prevention. AB - BACKGROUND: After Hurricane Katrina, an estimated 200,000 persons were evacuated to the Houston metropolitan area, >27,000 of whom were housed in 1 large "megashelter," the Reliant Park Complex. We investigated an outbreak of gastroenteritis reported among the evacuees who resided in the Reliant Park Complex to assess the spread of the infectious agent, norovirus, and to implement and evaluate the effectiveness of interventions used for control. METHODS: Public health authorities conducted surveillance of gastroenteritis among evacuees treated at the Reliant Park Medical Clinic during 2-12 September 2005. Basic demographic and clinical data were recorded. Specimens of stool and vomitus were collected and tested for bacteria, parasites, and viruses. Shelter census data were used to estimate the daily incidence of disease. RESULTS: During a period of 11 days, >1000 patients were treated at the clinic for gastroenteritis, which accounted for 17% of all clinic visits. Norovirus was the sole enteric pathogen identified, but multiple different strains were involved. Among the evacuees residing in the Reliant Park Complex, the incidence of gastroenteritis was estimated to be 4.6 visits per 1000 persons per day, and among the evacuees who resided there for 9 days, 1 (4%) of 24 persons would have been ill. Intensive public health measures were promptly instituted but did not definitively slow the progression of the outbreak of norovirus gastroenteritis. CONCLUSIONS: Our investigation underscores the difficulties in managing such outbreaks in crowded settings and the need for rapid, sensitive laboratory assays to detect norovirus. Additional research is needed to establish more effective measures to control and prevent this highly contagious gastrointestinal illness. PMID- 17366446 TI - Strategies to prevent varicella among newly arrived adult immigrants and refugees: a cost-effectiveness analysis. PMID- 17366447 TI - Varicella vaccination in adults: is it cost-effective? PMID- 17366448 TI - Perinatal and crowding-related risk factors for invasive pneumococcal disease in infants and young children: a population-based case-control study. AB - BACKGROUND: Denmark's systems of registry-based data offer a unique opportunity to examine, on a population basis, risk factors for invasive pneumococcal disease (IPD) relating to perinatal and crowding exposures among children. The main objective of this study was to identify the role of familial and day care factors in the risk of IPD among unvaccinated infants and children. METHODS: A total of 1381 children aged 0-5 years old who experienced IPD were identified from a national surveillance program of IPD in Denmark. Risk factors were assessed in a matched, nested, case-control study that assigned 10 population control subjects to every case patient. Exposure information was obtained from several population based, person-identifiable Danish registries. RESULTS: Preterm birth and low birth weight significantly increased the risk of IPD among infants. In infants 0 5 months of age, the risk of IPD was high among infants who had older siblings, compared with infants of the same age who had no older siblings (adjusted rate ratio [aRR], 3.38; 95% confidence interval, 2.11-5.42), whereas the aRR was low (aRR, 0.56; 95% confidence interval, 0.47-0.65) in children aged 6-23 months. Day care attendance, compared with home care, increased the aRR of IPD 0-2 months after enrollment in a day care program (aRR, 2.28; 95% confidence interval, 1.73 3.00), whereas the aRR was 0.70; (95% confidence interval, 0.46-1.06) > or = 6 months after enrollment in children aged 6-23 months. CONCLUSIONS: During infancy (age, 0-6 months), risk of IPD is associated with low birth weight, presumably because of lower levels of passively acquired maternal antibody. During early childhood, exposure to other young children (either siblings or through day care attendance) is clearly associated with IPD, but natural exposure appears to occur rapidly and confer durable immunity. PMID- 17366449 TI - Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial. AB - BACKGROUND: The optimal treatment of nontuberculosis mycobacterial cervical lymphadenitis in children has not been established. Until recently, surgical excision was the standard treatment, but the number of reports of successful antibiotic treatment is increasing, which questions whether surgery is the preferred treatment. In this randomized, multicenter trial, we compared surgical excision with antibiotic treatment. METHODS: One hundred children with microbiologically proven nontuberculous mycobacterial cervicofacial lymphadenitis were randomly assigned to undergo surgical excision of the involved lymph nodes or to receive antibiotic therapy with clarithromycin and rifabutin for at least 12 weeks. The primary end point was cure, defined as regression of the lymph node enlargement by at least 75%, with cure of the fistula and total skin closure without local recurrence or de novo lesions after 6 months, as assessed by clinical and ultrasound evaluation. Secondary end points included complications of surgery and adverse effects of antibiotic therapy. RESULTS: Intention-to-treat analysis revealed that surgical excision was more effective than antibiotic therapy (cure rates, 96% and 66%, respectively; 95% confidence interval for the difference, 16%-44%). Treatment failures were explained neither by noncompliance nor by baseline or acquired in vitro resistance to clarithromycin or rifabutin. Surgical complications were seen in 14 (28%) of 50 patients; staphylococcal wound infection occurred in 6 patients, and a permanent grade 2 facial marginal branch dysfunction occurred in 1 patient. The vast majority of patients who were allocated to antibiotic therapy reported adverse effects (39 [78%] of 50 patients), including 4 patients who had to discontinue treatment. CONCLUSIONS: Surgical excision is more effective than antibiotic treatment for children with nontuberculous mycobacterial cervicofacial lymphadenitis. PMID- 17366450 TI - Evidence guiding the treatment of children with mycobacterial diseases. PMID- 17366452 TI - Combination therapy for malaria: mission accomplished? PMID- 17366451 TI - Dihydroartemisinin-piperaquine versus artesunate-amodiaquine: superior efficacy and posttreatment prophylaxis against multidrug-resistant Plasmodium falciparum and Plasmodium vivax malaria. AB - BACKGROUND: Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies. METHODS: We conducted a randomized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine (DHP) with artesunate-amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42. RESULTS: Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45% (95% confidence interval [CI], 36% 53%) for AAQ and 13% (95% CI, 7.2%-19%) for DHP (hazard ratio [HR], 4.3; 95% CI, 2.5-7.2; P<.001). Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95% CI, 1.2-9.4] and 4.3 [95% CI, 2.2-8.2], respectively; P<.001). By the end of the study, AAQ recipients were 2.95-fold (95% CI, 1.2- to 4.9-fold) more likely to be anemic and 14.5-fold (95% CI, 3.4- to 61-fold) more likely to have carried P. vivax gametocytes. CONCLUSIONS: DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia. PMID- 17366453 TI - Comparison of histopathological analysis, culture, and polymerase chain reaction assays to detect invasive mold infections from biopsy specimens. AB - BACKGROUND: With the advent of new antifungal agents, the identification of a causative pathogen is crucial to guide the antifungal treatment of invasive mold infection. However, tissue cultures often fail to grow a fungal pathogen in cases of suspected mold infection. METHODS: In a prospective multicenter study, we compared the results of histopathological analysis, culture, and 2 seminested polymerase chain reaction assays identifying Aspergillus species and Zygomycetes as causative agents of invasive mold infections using respiratory tract biopsy samples obtained from 56 immunocompromised patients who had suspected mold infection. RESULTS: Mold hyphae were detected histopathologically in 27 (48%) of the tissue specimens. Hyphae corresponded to either aspergillosis (n=18) or zygomycosis (n=6) or could not be further specified (n=3). A mold was cultured from 14 of 18 samples with aspergillus hyphae, 2 of 6 samples with Zygomycetes hyphae, and 1 of 3 samples with unspecified hyphae. Polymerase chain reaction was superior to culture in detecting the infecting mold (26 of 27 samples vs. 17 of 27 samples, respectively; P=.006) from histopathologically positive samples. Genus or species identification by sequencing of the polymerase chain reaction products were in accordance with culture results in 16 of 18 culture-positive samples. Both polymerase chain reaction assays failed to detect fungal DNA in 1 sample that had unspecified hyphae and negative culture results. CONCLUSION: The PCR assays offer a reliable etiologic diagnosis that is superior to culture in patients with proven invasive mold infection. This may improve patient management through tailored antifungal therapy when cultures fail to grow a pathogen. PMID- 17366454 TI - Cases of swine influenza in humans: a review of the literature. AB - As the threat of a pandemic looms, improvement in our understanding of interspecies transmission of influenza is necessary. Using the search terms "swine," "influenza," and "human," we searched the PubMed database in April 2006 to identify publications describing symptomatic infections of humans with influenza viruses of swine origin. From these reports, we extracted data regarding demographic characteristics, epidemiological investigations, and laboratory results. We found 50 cases of apparent zoonotic swine influenza virus infection, 37 of which involved civilians and 13 of which involved military personnel, with a case-fatality rate of 14% (7 of 50 persons). Most civilian subjects (61%) reported exposure to swine. Although sporadic clinical cases of swine influenza occur in humans, the true incidence of zoonotic swine influenza virus infection is unknown. Because prior studies have shown that persons who work with swine are at increased risk of zoonotic influenza virus infection, it is prudent to include them in pandemic planning efforts. PMID- 17366455 TI - Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. AB - The number of reported cases of zygomycosis in patients with diabetes mellitus in developed countries has decreased since the 1990s, despite the rapid increase in the prevalence of diabetic patients in the Western world. Although prospective population-based studies need to better document this phenomenon, which may have a complex explanation, here I propose the hypothesis that widespread use of statins in patients with diabetes underlies such a trend. Statins have been shown to direct inhibitory activity against a range of Zygomycetes molds, both in vitro and in vivo. PMID- 17366456 TI - Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries. AB - The European Surveillance of Antimicrobial Consumption (ESAC) project collects data on antibacterial use in Europe, applying the Anatomic Therapeutic Chemical classification system and defined daily dose methodology, as recommended by the World Health Organization. Comparable data for the United States have been collected from IMS Health. The IMS Health sales data, processed according to ESAC methodology, suggest that outpatient antibacterial use in the United States is high (only 3 of 27 European countries used more) and is mainly characterized by a shift towards newer antibiotics. PMID- 17366457 TI - Methods for the classification of leprosy for treatment purposes. AB - The World Health Organization advocates 2 leprosy treatment regimens on the basis of disease classification (as multibacillary or paucibacillary) by skin lesion count. This method, which, in the Philippines, results in a high prevalence (78%) of patients with multibacillary leprosy, was directly compared with classification using standard histopathological and microbiological criteria in 264 currently untreated patients with leprosy. Of those whose leprosy was classified as paucibacillary, 38%-51% of patients had multibacillary leprosy according to classic criteria and were thus at risk of undertreatment according to World Health Organization recommendations. PMID- 17366458 TI - Woman with diarrhea and a worm. PMID- 17366459 TI - Look before you leap: active surveillance for multidrug-resistant organisms. AB - Hospitals in the United States are under increasing pressure to perform active surveillance cultures for detection of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) among newly admitted patients. Results of such cultures can then be used to direct contact precautions to prevent transmission of MRSA and VRE in the health care setting. However, using active surveillance cultures to expand contact precautions is a complicated and resource-intensive intervention that has the potential for several unintended adverse consequences. Therefore, careful forethought and preparation should precede the institution of any active surveillance culture program. We review the following important steps that should be performed when planning any such intervention: preparing the laboratory and reducing the turnaround time for screening tests, monitoring and optimizing the intervention of instituting contact precautions, monitoring and ameliorating the known adverse effects of contact precautions, and measuring important outcomes to evaluate the effectiveness of a program of active surveillance cultures and contact precautions. PMID- 17366460 TI - Detection and identification of microorganisms by gene amplification and sequencing. AB - Gene amplification and sequencing have led to the discovery of new pathogens as agents of disease and have enabled us to better classify microorganisms from culture. Sequence-based identification of bacteria and fungi using culture is more objective and accurate than conventional methods, especially for classifying unusual microorganisms that are emerging pathogens in immunocompromised hosts. Although a powerful tool, the interpretation of sequence-based classification can be challenging as microbial taxonomy grows more complex, without known clinical correlatives. Additionally, broad-range gene polymerase chain reaction and sequencing have emerged as alternative, culture-independent methods for detecting pathogens from clinical material. The promise of this technique has remained strong, limited mainly by contamination and inadequate sensitivity issues. This review explains sequence-based microbial classification, with emphasis on relating the complex world of microbial taxonomy to a clinical context. Additionally, this review discusses a rational approach to broad-range bacterial polymerase chain reaction and gene sequencing when applied directly to clinical samples. PMID- 17366462 TI - Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis. AB - BACKGROUND: Observational studies suggest that maternal human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection is associated with increased odds of vertical HCV transmission. We performed a meta-analysis to summarize current evidence. METHODS: We systematically searched for relevant articles published during the period from January 1992 through July 2006 and independently abstracted articles that met our inclusion criteria. Under a random effects model, we calculated the pooled odds ratio for vertical HCV transmission according to maternal HIV-HCV coinfection status and performed sensitivity analyses. RESULTS: Ten articles met our inclusion criteria. Study quality varied widely, and study estimates displayed high statistical heterogeneity. Restriction of the analysis to studies that included >50 HIV-HCV-coinfected women provided our most reliable estimate: maternal HIV-HCV coinfection increases the odds of vertical HCV transmission by approximately 90% (odds ratio, 1.9; 95% confidence interval, 1.36-2.67), compared with maternal HCV infection alone. When we restricted analyses to HIV-infected mothers with HCV viremia, the odds of vertical HCV transmission were 2.82-fold (95% confidence interval, 1.17-fold to 6.81-fold) greater than the odds for HIV-infected mothers without HCV viremia. CONCLUSIONS: HIV-HCV-coinfected women have significantly higher odds of transmitting HCV to their infants than do women who are infected with HCV alone. PMID- 17366461 TI - The effect of antiretroviral therapy on secondary transmission of HIV among men who have sex with men. AB - BACKGROUND: Antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) RNA load and the probability of transmitting HIV to an HIV-uninfected partner. However, the potential reduction in secondary transmission associated with ART may be offset by the longer duration of infectiousness. METHODS: To estimate the effects of ART on the secondary transmission of HIV among men who have sex with men, we used a previously published state-transition model of HIV disease to simulate the clinical and virologic course of HIV infection among 2 cohorts of men who have sex with men: (1) a cohort of individuals who were not receiving ART and (2) a cohort of individuals treated with US guideline concordant ART. The model tracked the number of acts of unprotected insertive anal intercourse, transmission risk per act as determined by HIV RNA level, and the number of secondary cases generated in each cohort. RESULTS: The estimated mean number of secondary transmissions from an HIV-infected individual after 10, 20, and 30 years of infection were 1.9, 2.5, and 2.5, respectively, in the untreated cohort, compared with 1.4, 1.8, and 2.3, respectively, in the treated cohort. The total number of transmissions for the treated cohort began to exceed the total number of transmissions for the untreated cohort 33 years after infection; over the entire course of infection, treatment with ART led to a 23% increase in secondary infections. All estimates of the impact of ART on secondary transmission were sensitive to changes in risk behaviors. CONCLUSIONS: These results suggest that ART must be accompanied by effective HIV-related risk reduction interventions. Programs that target prevention to decrease further HIV transmission are crucial to epidemic control. PMID- 17366464 TI - Antibiotic treatment of children with erythema migrans. PMID- 17366465 TI - Lyme disease guidelines--it's time to move forward. PMID- 17366466 TI - Concerns regarding the Infectious Diseases Society of America Lyme disease clinical practice guidelines. PMID- 17366467 TI - Accuracy of recommendations in the Infectious Diseases Society of America clinical practice guidelines for Lyme disease. PMID- 17366469 TI - Effect of pneumococcal polysaccharide vaccine on nonbacteremic pneumococcal pneumonia. PMID- 17366471 TI - Streptococcus agalactiae in relapsing cellulitis. PMID- 17366472 TI - Does the nose know? The odiferous diagnosis of Clostridium difficile-associated diarrhea. PMID- 17366473 TI - Discovering robust protein biomarkers for disease from relative expression reversals in 2-D DIGE data. AB - This study assesses the ability of a novel family of machine learning algorithms to identify changes in relative protein expression levels, measured using 2-D DIGE data, which support accurate class prediction. The analysis was done using a training set of 36 total cellular lysates comprised of six normal and three cancer biological replicates (the remaining are technical replicates) and a validation set of four normal and two cancer samples. Protein samples were separated by 2-D DIGE and expression was quantified using DeCyder-2D Differential Analysis Software. The relative expression reversal (RER) classifier correctly classified 9/9 training biological samples (p<0.022) as estimated using a modified version of leave one out cross validation and 6/6 validation samples. The classification rule involved comparison of expression levels for a single pair of protein spots, tropomyosin isoforms and alpha-enolase, both of which have prior association as potential biomarkers in cancer. The data was also analyzed using algorithms similar to those found in the extended data analysis package of DeCyder software. We propose that by accounting for sources of within- and between-gel variation, RER classifiers applied to 2-D DIGE data provide a useful approach for identifying biomarkers that discriminate among protein samples of interest. PMID- 17366474 TI - Phanerochaete chrysosporium soluble proteome as a prelude for the analysis of heavy metal stress response. AB - A 2-D reference map in pI range 3-10 was constructed for the soluble protein fraction of Phanerochaete chrysosporium growing vegetatively under standard conditions. Functional annotation could be made for 517 spots out of 720 that were subjected to MALDI-TOF-MS analysis, according to the specific accession numbers from the P. chrysosporium genomic database. Further analysis of the data revealed 314 distinct ORFs, 118 of which yielded multiple spots on the master gel. Functional classification of the proteins was made according to the eukaryote orthologous groups defined in the organism's genome website. The functional class of PTMs, protein turnover and chaperones was represented with the highest number (63) of the identified ORFs. Six proteins were assigned to the hypothetical proteins and 29 were predicted to have a signal peptide sequence. Subcellular localization predictions were also made for the identified proteins. Of the protein spots detected on the master gel, 380 were found to be probably phosphorylated and 96 of these matched to the identified proteins. The reference map was efficiently used in the identification of the proteins differentially expressed under cadmium and copper stress. Three new ribosomal proteins as well as zinc-containing alcohol dehydrogenase, glucose-6-phosphate isomerase, flavonol/cinnamoyl-CoA reductase, H+-transporting two-sector ATPase, ribosomal protein S7, ribosomal protein S21e, elongation factor EF-1 alpha subunit were demonstrated as the most strongly induced. PMID- 17366475 TI - From the genome sequence to the proteome and back: evaluation of E. coli genome annotation with a 2-D gel-based proteomics approach. AB - The ambition of systems biology to understand complex biological systems at the molecular level implies that we need to have a concrete and correct understanding of each molecular entity and its function. However, even for the best-studied organism, Escherichia coli, a large number of proteins have never been identified and characterised from wild-type cells, and/or await unravelling of their biological role. Instead, the ORF models for these proteins have been predicted by suitable algorithms and/or through comparison with known, homologous proteins from other organisms, approaches which may be prone to error. In the present study, we used a combination of 2-DE, MALDI-TOF-MS and PMF to identify 1151 different proteins in E. coli K12 JM109. Comparison of the experimental with the theoretical Mr and pI values (4000 experimental values each) allowed the identification of numerous proteins with incorrect or incomplete ORF annotations in the current E. coli genome databases. Several inconsistencies in genome annotation were verified experimentally, and up to 55 candidates await further investigation. Our findings demonstrate how an up-to-date 2-D gel-based proteomics approach can be used for improving the annotation of prokaryotic genomes. They also highlight the need for harmonization among the different E. coli genome databases. PMID- 17366476 TI - 2-DE analysis of a new human cell line EM-G3 derived from breast cancer progenitor cells and comparison with normal mammary epithelial cells. AB - We performed a 2-DE analysis of proteins of the newly established spontaneously immortalized clonal cell line EM-G3 derived from a primary lesion of infiltrating ductal breast carcinoma. EM-G3 cells may represent progenitors of the mammary epithelial cells spontaneously immortalized in early phase of cancerogenesis. We compared the protein profile of EM-G3 line with proteins from populations of normal mammary epithelial cells (NME), and determined the phenotype of both types of cells. NME cells are a mixture of both main cell types in breast epithelia, myoepithelial and luminal cells. The EM-G3 breast cancer cell line has a unique basal-like phenotype. We identified proteins that are differently expressed in these cells. Cytokeratin 16, cytokeratin 19, squamous cell carcinoma antigen 1, caphepsin B and caspase 14 were predominantly expressed by NME cells. Cytokeratin 13, isoelectric variant of annexin 5, isoelectric variant of chloride intracellular channel protein 1, glyoxalase 1 and glutamine synthetase were predominantly expressed by EM-G3 cells. The proteins up-regulated in EM-G3 cells may represent potential protein markers of mammary epithelial cells progenitors and may be important in early phase of carcinogenesis. PMID- 17366477 TI - Antigen discovery: a postgenomic approach to paratuberculosis diagnosis. AB - Paratuberculosis is a chronic enteritis caused in domestic and wild ruminant species by Mycobacterium avium subsp. paratuberculosis (MAP) that is responsible for major economic losses to the agricultural industry. To date, no satisfactory therapeutic, vaccine, or diagnostic tools are available, globally impairing all control programs. In this study, we have undertaken a large-scale postgenomic analysis of MAP proteins, to identify specific antigens that could potentially improve the diagnosis of paratuberculosis. Two complementary approaches were implemented, the first one consisting in the systematic proteomic identification of proteins present in MAP culture filtrates (CFs), followed by the selection of MAP-specific proteins by BLAST query on available mycobacterial genomes. The resulting database represents the first established secretome of MAP and a useful source of potentially specific antigens. The second approach consisted in the immunoproteomic analysis of both MAP extracts and CFs, using sera from MAP infected and uninfected cattle. Combining results obtained with both approaches resulted in the identification of 25 candidate diagnostic antigens. Five of these were tested in an ELISA assay for their diagnostic potential, on a limited panel of field sera, and the combination of three of them competed in performance with available commercial assays, reaching a test sensitivity of 94.74% and specificity of 97.92%. PMID- 17366478 TI - Proteome changes associated with hippocampal MRI abnormalities in the lithium pilocarpine-induced model of convulsive status epilepticus. AB - Convulsive status epilepticus is associated with subsequent hippocampal damage and development of mesial temporal sclerosis in a subset of individuals. The lithium pilocarpine model of status epilepticus (SE) in the rat provides a model in which to investigate the molecular and pathogenic process leading to hippocampal damage. In this study, a 2-DE-based approach was used to detect proteome changes in the hippocampus, at an early stage (2 days) after SE, when increased T2 values were detectable by magnetic resonance imaging. Gel image analysis was followed by LC-MS/MS identification of protein species that differed in abundance between pilocarpine-treated and control rats. The most significantly up-regulated species in the experimental animals was identified as heat shock 27 kDa protein, in line with findings in humans and in other experimental models of epilepsy. Additional up-regulated species included dihydropyrimidinase-related protein-2, cytoskeletal proteins (alpha-tubulin and ezrin) and dihydropteridine reductase. In summary, the hippocampus of rats subject to pilocarpine-induced SE exhibits specific changes in protein abundance, which likely relate to pathogenic, neuroprotective and neurogenic responses. PMID- 17366479 TI - Semipermanent capillary coatings in mixed organic-water solvents for CE. AB - This report describes the creation of semipermanent capillary coatings that are compatible with organic-water solvent systems in CE. The coatings are created by simply rinsing the fused-silica capillary with long double-chain cationic surfactants, such as dimethyl-ditetradecyl ammonium bromide (2C(14)DAB), dihexadecyldimethyl ammonium bromide (2C(16)DAB), and dimethyldioctadecyl ammonium bromide (2C(18)DAB). These surfactants generate semipermanent bilayer coatings on the capillary surface, which display a high degree of stability in buffers containing up to 60% v/v of organic solvents, such as methanol and ACN. The coating stability increases with increasing hydrophobicity of the surfactant, i.e., with increasing chain length. For instance, the EOF changes by only 1.2% in a 2C(18)DAB-coated capillary after 130 capillary volumes of rinsing with 60% v/v methanol containing buffer. The bilayer coatings allow separations to be performed without the need to regenerate the coating between runs or to maintain the EOF modifier in the run buffer. Rapid separations (<2 min) of anions and basic drugs with migration time reproducibility of less than 0.5% RSD and efficiencies of 0.4-0.6 million plates/m are obtained. In addition, selectivity changes for small anions and cationic drugs are also observed when the organic solvent content is adjusted. PMID- 17366480 TI - Simultaneous identification of natural dyes in the collection of drawings and maps from The Royal Chancellery Archives in Granada (Spain) by CE. AB - A simple and rapid capillary electrophoretic method with UV detection (CE-UV) has been developed for the identification of five natural dyes namely, carmine, indigo, saffron, gamboge and Rubia tinctoria root. The separation was performed in a fused-silica capillary of 64.5 cm length and 50 microm id. The running buffer was 40 mM sodium tetraborate buffer solution (pH 9.25). The applied potential was 30 kV, the temperature was 25 degrees C and detections were performed at 196, 232, 252, 300 and 356 nm. The injections were under pressure of 50 mbar during 13 s. The method was applied to the identification of carminic acid, gambogic acid, crocetin, indigotin, alizarin and purpurin in the collection of drawings and maps at the Royal Chancellery Archives in Granada (Spain). The method was validated by using HPLC as a reference method. PMID- 17366481 TI - CIEF with hydrodynamic and chemical mobilization for the separation of forms of alpha-1-acid glycoprotein. AB - Alpha-1-acid glycoprotein (AGP) is a protein that exists in different forms, which is due to variations in the amino acid sequence and/or in the glycosidic part of the protein. These differences confer to these forms, among other characteristics, diverse pIs. Changes in these forms of AGP have been correlated to modifications of the pathophysiological conditions of the individuals. One of the analytical techniques employed for their study has been IEF performed in slab gels. CIEF method with hydrodynamic and chemical mobilization, involving an isotachophoretic process, is developed in this work to separate up to 12 bands of forms of standard AGP, which is proposed as a more reproducible, quantitative, less sample-consuming, and more automated one than conventional IEF. The challenge of this work has been the development of a CIEF method for the separation of bands of a very acidic protein (pI range: 1.8-3.8) in a capillary. Intraday RSD values < or = 1.7% have been achieved for the relative migration time of the AGP bands to that of an internal standard. For intraday area precision, RSD (%) in the range of 2.70-22.71% for AGP zones accounting for more than 10% of total area of AGP sample has been obtained. As a proof of the potential of the methodology proposed, an AGP sample purified from a pool of sera of patients suffering from ovary cancer is analyzed by CIEF. PMID- 17366482 TI - Electrophoretic separation of environmentally important phenolic compounds using montomorillonite-coated fused-silica capillaries. AB - This paper reports a simple procedure for coating fused-silica capillaries with poly(diallyldimethyl ammonium chloride) and montmorillonite. The coated capillaries were characterized by performing EOF measurements as a function of buffer pH, number of layers of coating, and number of runs (stability). The coated capillaries showed a highly stable mu(EOF) (run-to-run RSD less than 1.5%, n = 20), allowing continuous use for several days without conditioning. The coated capillaries were then used for the effective separation of nine environmentally important phenolic compounds showing a significant improvement in the resolution, when compared to bare fused-silica capillaries. The EOF of the coated capillaries was constant in alkaline solutions (pH > or = 7), allowing the optimization of the separation conditions of phenolic compounds without significantly affecting the mu(EOF). PMID- 17366483 TI - Short-column CE coupled with inductively coupled plasma MS for high-throughput speciation analysis of chromium. AB - A method was developed for high-throughput speciation analysis of chromium by on line coupling of short-column capillary electrophoresis (SC-CE) and inductively coupled plasma mass spectrometry (ICP-MS). Baseline separation of Cr(III) and Cr(VI) was achieved within 1 min by SC-CE in a 15 cm x 75 microm id fused-silica capillary at 6 kV using 15 mM HNO(3) as running electrolyte. The precisions (RSD, n = 5) of migration time and peak area for Cr(III) and Cr(VI) were in the range of 1.8-2.4% and 2.2-5.7%, respectively. The limits of detection (3sigma) of Cr(III) and Cr(VI) were 1.8 and 1.9 microg/L, respectively. The synthesized samples containing Cr(III) and Cr(VI) species were determined by the developed SC CE-ICP-MS hyphenated technique, and the recoveries of Cr(III) and Cr(VI) in the synthesized samples were in the range of 103-110% and 90-108%, respectively. PMID- 17366484 TI - A sheathless poly(methyl methacrylate) chip-CE/MS interface fabricated using a wire-assisted epoxy-fixing method. AB - Using a wire-assisted epoxy-fixing method, a sheathless CE/MS interface on a poly (methyl methacrylate) (PMMA) CE chip has been developed. The sheathless chip CE/MS interface utilized a tapered fused-silica tip and the electrical connection was achieved through a layered coating of conductive rubber. The wire-assisted method provided facile alignment of channels between the PMMA CE chip and an external capillary sprayer without the need for micromachining. Because the wire was in the channel during fixing, the risk of channel blockage by the epoxy was avoided. This chip CE device has minimal dead volume because the interstitial spaces were filled by a fast-fixing epoxy resin. The performance of the chip-CE ESI-MS device was demonstrated with the analysis of peptide mixtures. PMID- 17366485 TI - Parallel separation of multiple samples with negative pressure sample injection on a 3-D microfluidic array chip. AB - A simple and powerful microfluidic array chip-based electrophoresis system, which is composed of a 3-D microfluidic array chip, a microvacuum pump-based negative pressure sampling device, a high-voltage supply and an LIF detector, was developed. The 3-D microfluidic array chip was fabricated with three glass plates, in which a common sample waste bus (SW(bus)) was etched in the bottom layer plate to avoid intersecting with the separation channel array. The negative pressure sampling device consists of a microvacuum air pump, a buffer vessel, a 3 way electromagnet valve, and a vacuum gauge. In the sample loading step, all the six samples and buffer solutions were drawn from their reservoirs across the injection intersections through the SW(bus) toward the common sample waste reservoir (SW(T)) by negative pressure. Only 0.5 s was required to obtain six pinched sample plugs at the channel crossings. By switching the three-way electromagnetic valve to release the vacuum in the reservoir SW(T), six sample plugs were simultaneously injected into the separation channels by EOF and electrophoretic separation was activated. Parallel separations of different analytes are presented on the 3-D array chip by using the newly developed sampling device. PMID- 17366486 TI - On-line preparation of microsamples prior to CE. AB - An experimental setup is presented here for the automated analysis of microsamples, based on the on-line coupling of a capillary SPE module and a CE unit using a two-position six-port valve, an open-closed valve to isolate electrically the sample preparation from the CE unit and a "T" interface. A C18 trapping microcolumn (dimensions 2.5 cm x 100 microm id x 360 microm od) was used for the SPE step. The utility of the proposed experimental setup was demonstrated by applying it to the determination of quinolone antibiotics in serum microsamples, which was efficiently carried out in less than 20 min (4 min for protein denaturation and 15 min for analytes preconcentration and CE-UV separation-determination). A complete optimization study was performed for preconcentration and cleanup of quinolones, the coupling of sample preparation module to the CE unit and electrophoretic separation of quinolones. A preconcentration factor of 10.4 was achieved. The volume injected with the proposed method was 125 nL versus 160 nL introduced by hydrodynamic injection. The volume required for the analysis was 2 microL, which makes the proposed experimental setup very useful for the analysis of microsamples in fields of current interest such as metabolomics or proteomics. PMID- 17366487 TI - Separation of fluorescent phosphatidyl inositol phosphates by CE. AB - Phosphatidyl inositol 4,5-bisphosphate (PIP2) and phosphatidyl inositol 3,4,5 trisphosphate (PIP3) labeled with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s indacene-3-propionic acid (BODIPY FL) on the acyl chain or a phosphatidyl ethanolamine head group were separated by CE with LIF detection. Several methods and capillary-coating procedures were tested for the separation of these phosphatidyl inositol phosphates (PIPs) at 20 degrees C. Separation of the PIPs in less than 20 min with excellent resolution was achieved using a buffer containing sodium deoxycholate (SDC), 1-propanol, MgCl2 and the polymer coating reagent, EOTrol LR. The efficiency of the optimized method was as high as 1.3x10(5) plates. The dependence of the separation on the concentration of 1 propanol, SDC, and MgCl2 was determined. The separation of PIP2 and PIP3 was primarily due to differential binding of the lipids to Mg2+ rather than to different solubilities in the micellar phase. The role of the SDC was to prevent adsorption of the hydrophobic lipids to the capillary wall and thus enhance the efficiency. The fluorescent PIPs are of value for both in vitro and in vivo assays of phospholipid metabolism. In particular, the use of these lipids with the optimized capillary-based separation will be of utility for drug screening as well as cell-based assays. PMID- 17366488 TI - Carbon nanotube detectors for microchip CE: comparative study of single-wall and multiwall carbon nanotube, and graphite powder films on glassy carbon, gold, and platinum electrode surfaces. AB - The performance of microchip electrophoresis/electrochemistry system with carbon nanotube (CNT) film electrodes was studied. Electrocatalytic activities of different carbon materials (single-wall CNT (SWCNT), multiwall CNT (MWCNT), carbon powder) cast on different electrode substrates (glassy carbon (GC), gold, and platinum) were compared in a microfluidic setup and their performance as microchip electrochemical detectors was assessed. An MWCNT film on a GC electrode shows electrocatalytic effect toward oxidation of dopamine (E(1/2) shift of 0.09 V) and catechol (E(1/2) shift of 0.19 V) when compared to a bare GC electrode, while other CNT/carbon powder films on the GC electrode display negligible effects. Modification of a gold electrode by graphite powder results in a strong electrocatalytic effect toward oxidation of dopamine and catechol (E(1/2) shift of 0.14 and 0.11 V, respectively). A significant shift of the half-wave potentials to lower values also provide the MWCNT film (E(1/2) shift of 0.08 and 0.08 V for dopamine and catechol, respectively) and the SWCNT film (E(1/2) shift of 0.10 V for catechol) when compared to a bare gold electrode. A microfluidic device with a CNT film-modified detection electrode displays greatly improved separation resolution (R(s)) by a factor of two compared to a bare electrode, reflecting the electrocatalytic activity of CNT. PMID- 17366489 TI - The primary structure of a low-Mr multiphosphorylated variant of beta-casein in equine milk. AB - Highly phosphorylated casein with a low molecular mass was isolated from Haflinger mare's milk by RP-HPLC. It accounts for 4.0% of the casein content. Its mass was determined by LC-ESI-MS before and after treatment by alkaline phosphatase. The molecular mass found for the apo-form (10,591 +/- 2 Da) is in agreement with its primary structure, which was established by ESI-MS/MS from tryptic peptides. It appeared that this short protein (94 amino acid residues) is an internally truncated form of the full-length equine beta-casein (226 residues). This low-Mr variant of equine beta-casein displays a large deletion (residues 50-181), due to a cryptic splice site usage occurring within exon 7 during the course of primary transcripts processing. The phosphorylation pattern of this equine beta-casein variant was investigated by LC-ESI-MS and 2-DE. Seven phosphorylation forms were identified with one to seven phosphate groups with pIs ranging between 4.67 and 4.01. The major isoforms carry five and six phosphate groups. PMID- 17366490 TI - Comprehensive yeast proteome analysis using a capillary isoelectric focusing based multidimensional separation platform coupled with ESI-MS/MS. AB - As demonstrated in this study, a CIEF-based multidimensional separation platform not only is compatible with the detergent-based membrane protein preparation protocol, but also achieves both the largest yeast membrane proteome coverage and the most comprehensive analysis of the yeast proteome to date. By using a 1% false discovery rate for total peptide identifications, a total of 2513 distinct yeast proteins are identified from the SDS-solubilized fraction with an average of 5.4 peptides leading to each protein identification. Among proteins identified from the SDS-solubilized fraction, 407 proteins are predicted to contain at least two or more transmembrane domains using TMHMM (www.cbs.dtu.dk/services/TMHMM 2.0/), corresponding to 46% yeast membrane proteome coverage. Only four additional membrane proteins are identified in the soluble and urea-solubilized fractions, affirming the utility of SDS extraction for enriching the membrane proteome. By combining proteome results obtained from the soluble, urea solubilized, and SDS-solubilized fractions, a single yeast proteome analysis yields the identification of 3632 distinct yeast proteins, corresponding to 55% theoretical yeast proteome coverage or 70% of proteins predicted to be expressed during log-phase growth in rich media. PMID- 17366491 TI - Aminoborylene complexes of group 6 elements and iron: a synthetic, structural, and quantum chemical study. AB - Transition-metal-borylene complexes of the type [(OC)(5)M=BR] {M=Cr, Mo, W; R=N(SiMe(3))(2), 1a-3a, Si(SiMe(3))(3), 4a} and [(OC)(4)Fe=B=N(SiMe(3))(2)] (8) were prepared by salt elimination reactions. Synthesis of the latter complex was accompanied by the formation of substantial amounts of an unusual dinuclear iron complex [Fe(2){mu-C(2)O(2)(BN(SiMe(3))(2))}(2)(CO)(6)] (9). The aminoborylene complexes of Group 6 metals were converted to trans [(Cy(3)P)(CO)(4)M=B=N(SiMe(3))(2)] (5a-7a) by irradiation in the presence of PCy(3). Structural and spectroscopic parameters were discussed with respect to the trans-effect of the borylene ligand and the degree of M-B d(pi)-p(pi) backbonding. Computational studies were performed on Group 6-borylene complexes. The population and topological analyses as well as the molecular orbital composition are consistent with the presence of both sigma-and pi-type interactions. There are, however, indications that the d(pi)-p(pi)-backbonding in the silylborylene complex is significantly more pronounced than in the aminoborylene complexes. PMID- 17366492 TI - Synthesis of metal-(pentadentate-salen) complexes: asymmetric epoxidation with aqueous hydrogen peroxide and asymmetric cyclopropanation (salenH2: N,N' bis(salicylidene)ethylene-1,2-diamine). AB - It is known that the rates and stereochemical outcomes of epoxidations and cyclopropanations using a metallosalen (salenH(2): N,N'-bis(salicylidene)ethylene 1,2-diamine) complex as catalyst are affected by a trans effect of the apical ligand of the complex. By taking into consideration this trans effect, we have synthesized optically active pentadentate salen ligands bearing an imidazole or pyridine derivative as the fifth coordinating group, and have prepared the corresponding manganese(III) and cobalt(II) complexes, in which the fifth ligand is expected to intramolecularly coordinate to the metal center and exert a trans effect. Indeed, high enantioselectivity has been achieved in epoxidations using aqueous hydrogen peroxide as the terminal oxidant and in cyclopropanations with these complexes as catalysts. In general, metallosalen-catalyzed reactions have been carried out in the presence of an excess of a donor ligand; however, the present reactions do not need the addition of any extra donor ligand. PMID- 17366493 TI - "Chiral amnesia" as a driving force for solid-phase homochirality. AB - The formation of a single homochiral solid phase from crystallization of achiral compounds has recently been under discussion. We show that the state of single solid-phase homochirality does not represent a more stable thermodynamic state than that of a racemate consisting of two separate homochiral solids. We introduce the term "chiral amnesia" as a more appropriate molecular-level description than "chiral recognition" to describe the driving force for establishing solid-phase homochirality in the case of achiral molecules that form chiral solids as well as in the case of rapidly racemizing enantiomers. PMID- 17366494 TI - Ytterbocenes as one- and two-electron reductants in their reactions with diazadienes: YbIII mixed-ligand bent-sandwich complexes containing a dianion of diazabutadiene. AB - Ytterbocene [Yb(C(5)MeH(4))(2)(thf)(2)] reacts with diazabutadiene 2,6 iPr(2)C(6)H(3)-N=CH-CH=N-C(6)H(3)iPr(2)-2,6 (DAD) as a one-electron reductant to afford a bis(cyclopentadienyl) Yb(III) derivative containing a DAD radical anion [Yb(C(5)MeH(4))(2)(dad(-.))]. However, ytterbocenes [YbCp*(2)(thf)(2)] (Cp*=C(5)Me(5), C(5)Me(4)H) coordinated by sterically demanding cyclopentadienyl ligands act as two-electron reductants in their reactions with DAD. These reactions occur by abstraction of one Cp* ring and result in the formation of novel Yb(III) mixed-ligand bent-sandwich complexes, [YbCp*(dad)(thf)], in which the dianion of DAD has an uncommon terminal eta(4)-coordination to the ytterbium atom. The variable-temperature magnetic measurements of complex [Yb(C(5)Me(5))(dad)(thf)] suggest the existence of redox tautomerism for this compound. PMID- 17366495 TI - The low-barrier hydrogen bond of deuterated benzoylacetone probed by very low temperature neutron and X-ray diffraction studies and theoretical calculations. AB - Low-temperature neutron diffraction data is used to show that the enol deuteron in deuterated benzoylacetone has a bimodal probability density distribution. In a previous study of normal benzoylacetone we showed that the enol hydrogen atom has a broad unimodal probability density distribution. Deuteration gives hardly any change to the molecular framework other than a small lengthening of the O...O distance. We solve the vibrational Hamiltonian for a series of model hydrogen potentials and show how the proton/deuteron probability density function can become strongly perturbed by small changes to the potential. The potentials are used to show that the deuteron in benzoylacetone can be interpreted as an atom tunnelling between two possible localised positions, while the proton in benzoylacetone can be viewed as having sufficient energy to shuttle over the low energy barrier, even at 15 K. We underline the necessity of accounting for the dynamic nature of the hydrogen bond and not relying on a description of the proton/deuteron by a single atomic coordinate, and compare our results to structure correlation studies. PMID- 17366496 TI - Increased Lewis acidity in hafnium-substituted polyoxotungstates. AB - Monolacunary polyoxotungstates [alpha(1)-P(2)W(17)O(61)](10-) and [alpha PW(11)O(39)](7-) react with HfCl(4) to yield [alpha(1)-HfP(2)W(17)O(61)](6-) and [alpha-Hf(OH)PW(11)O(39)](4-), isolated as organo-soluble tetrabutylammonium (TBA) salts. Subsequent analyses, including mass spectrometry, show that they are stronger Lewis acids than (TBA)(5)H(2)[alpha(1)-YbP(2)W(17)O(61)]. The new polyoxotungstates catalyze Lewis acid mediated organic reactions, such as Mukaiyama aldol and Mannich-type additions. In particular, reactions with aldehydes, which were impossible with lanthanide polyoxotungstates, are made possible. Thus these modifications of the polyoxometalate composition allowed fine tuning of the Lewis acidity. The catalysts could be easily recovered and reused. PMID- 17366497 TI - Dynamic protonation equilibrium of solvated acetic acid. PMID- 17366498 TI - Evolving a thermostable DNA polymerase that amplifies from highly damaged templates. PMID- 17366499 TI - closo-[B21H18]-: a face-fused diicosahedral borate ion. PMID- 17366500 TI - 1-alkyl-2,3,5,6,7,8-hexasilabicyclo[2.2.2]octanes: unconventional class of mesomorphic columnar compounds. PMID- 17366501 TI - Dynamic hydrogels: translating a protein conformational change into macroscopic motion. PMID- 17366502 TI - Molecular recognition drives oligonucleotide binding to nucleolipid self assemblies. PMID- 17366503 TI - Highly efficient and versatile synthesis of proteoglycan core structures from 1,6 anhydro-beta-lactose as a key starting material. PMID- 17366504 TI - Auxiliary-mediated site-specific peptide ubiquitylation. PMID- 17366505 TI - Enantioselective total synthesis of the osteoclastogenesis inhibitor (+) symbioimine. PMID- 17366506 TI - A highly enantioselective intramolecular Michael reaction catalyzed by N heterocyclic carbenes. PMID- 17366507 TI - Dinitrogen activation by group 4 metal complexes. PMID- 17366508 TI - Excited-state relaxation of protonated adenine. AB - The excited state dynamics of protonated adenine in the gas phase were investigated by femtosecond pump-probe transient mass spectroscopy. Adenine was protonated in an electrospray ionization source and transferred to a Paul trap. Two femtosecond laser pulses at 266 nm and 800 nm excited the lowest electronic pipi* state and probed the excited-state dynamics by monitoring ion fragment formation. The measured excited state decay is monoexponential with a lifetime shorter than 161 fs. This agrees with a theoretical prediction of very fast internal conversion via a conical intersection with the ground state. PMID- 17366509 TI - Atmospheric plasma treatment of porous polymer constructs for tissue engineering applications. AB - Porous 3D polymer scaffolds prepared by TIPS from PLGA (53:47) and PS are intrinsically hydrophobic which prohibits the wetting of such porous media by water. This limits the application of these materials for the fabrication of scaffolds as supports for cell adhesion/spreading. Here we demonstrate that the interior surfaces of polymer scaffolds can be effectively modified using atmospheric air plasma (AP). Polymer films (2D) were also modified as control. The surface properties of wet 2D and 3D scaffolds were characterised using zeta potential and wettability measurements. These techniques were used as the primary screening methods to assess surface chemistry and the wettability of wet polymer constructs prior and after the surface treatment. The surfaces of the original polymers are rather hydrophobic as highlighted but contain acidic functional groups. Increased exposure to AP improved the water wetting of the treated surfaces because of the formation of a variety of oxygen and nitrogen containing functions. The morphology and pore structure was assessed using SEM and a liquid displacement test. The PLGA and PS foam samples have central regions which are open porous interconnected networks with maximum pore diameters of 49 microm for PLGA and 73 microm for PS foams. PMID- 17366510 TI - Long-range self-governing motion of polymer gel on a gradiently charged insulating substrate. AB - Herein, we report a special poly(vinyl alcohol)/dimethylsulfoxide (PVA/DMSO) gel electromechanical system with great self-governed capability. The system is operated in air by applying a noncontacted DC electric field. When the applied electric field exceeds a certain critical value, the gel exhibits fast and self governing locomotion on the gradiently charged glass substrate. In contrast to field-controlled gel systems developed earlier, the crawling direction of the gel is independent of the direction of the applied electric field and can be actively controlled. The maximum crawling velocity can reach 3.22 mm s(-1), which is much larger than that of the actuators described earlier. Furthermore, some factors that influence the critical driving electric field and the average crawling speed of the gel were studied. The mechanism analysis indicates that, the self governing linear motion of the gel is due to the spatially and temporally varying electrostatic interaction between the gel and the applied electric field in response to the gradient change of the charge density and the charge polarity on the substrate. PMID- 17366511 TI - In situ ESR and UV/vis spectroelectrochemical study of eosin Y upon reduction with and without Zn(II) ions. AB - The electroreduction of eosin Y on a platinum electrode in deaerated slightly acidic aqueous 0.1 mol L(-1) potassium chloride medium is followed in situ by electron spin resonance (ESR) spectroscopy and UV/Vis spectroscopy. The electrochemical formation of a semiquinone radical is proved by both the appearance of an absorbing band at 408 nm, and a strong ESR signal observed during a negative-going scan. The system is also studied in the presence of Zn(II) ions due to its importance for understanding the growth mechanism of nanostructured ZnO/Eosin Y hybrid films by electrodeposition; under such conditions the ESR and UV/Vis response of the semiquinone radical is not observed. Zinc (II) ions form a complex with the dye, which is reduced by a fast two-electron process. PMID- 17366512 TI - Chemical space travel. PMID- 17366513 TI - An abnormal resonance light scattering arising from ionic-liquid/DNA/ethidium interactions. AB - In the aqueous phase, ethidium bromide (EB) intercalates into the double helix structure of dsDNA (ds=double-stranded) with a notable enhancement in fluorescence and resonance light scattering (RLS). However, when dsDNA was extracted into an ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF(6)), an abnormal RLS arising from the interactions of IL-DNA-EB was observed, with a substantial decrease of the recorded RLS. The cationic Bmim(+) groups of BmimPF(6) intercalate into the DNA helix structure, in which they interact with the P-O bonds of phosphate groups in DNA strands and result in a reduction of the base-pair interstice along with transformation of DNA conformations that consequently prohibits the intercalation of EB with DNA. Thus, in the IL phase, the interactions between ethidium and DNA were dominated by electrostatic interactions and hydrogen bonding, leading to a congregation of EB entities around the DNA strands that results in an increase of absorption by ethidium, and consequently the inner filter effect leads to a reduction of the RLS. The present observation has been applied to the direct quantification of DNA in an ionic-liquid phase after DNA from human whole blood was extracted into BmimPF(6). PMID- 17366514 TI - Theoretical evidence for pyramidalized bicyclic serine enolates in highly diastereoselective alkylations. AB - A new chiral serine equivalent and its enantiomer have been synthesized from (S)- and (R)-N-Boc-serine methyl esters (Boc: tert-butyloxycarbonyl). The use of these compounds as chiral building blocks has been demonstrated in the synthesis of alpha-alkyl alpha-amino acids by diastereoselective potassium enolate alkylation reactions and subsequent acid hydrolyses. Theoretical studies were performed to elucidate the stereochemical outcome of both the formation of five-membered cyclic N,O-acetals and the subsequent alkylation process, which occurs with total retention of configuration. This feature could be explained in terms of the high degree of pyramidalization of enolate intermediates. PMID- 17366515 TI - Redox-driven intramolecular anion translocation between a metal centre and a hydrogen-bond-donating compartment. AB - Dicationic ligands incorporating two 2,2'-bipyridine units and two imidazolium moieties, [1](2+) and [2](2+), form stable chelate complexes with Cu(II) and Cu(I) in acetonitrile solution. Each Cu(II) complex binds two X(-) ions according to two stepwise equilibria, the first involving the Cu(II) centre and the second involving the bis-imidazolium compartment. Cu(I) complexes are able to host only one NO(3)(-) ion in the bis-imidazolium cavity, while other anions induce demetallation. Thus, in the presence of one equivalent of NO(3)(-), the Cu(II)/Cu(I) redox change makes the anion translocate quickly and reversibly from one binding site to the other within the [Cu(II,I)(1)](4+/3+) system, as demonstrated by cyclic voltammetry and controlled-potential electrolysis experiments. PMID- 17366516 TI - Structure design of multifunctional furoate and pyroglutamate esters of dextran by polymer-analogous reactions. AB - Well-defined multifunctionalized dextran esters bearing photo-crosslinkable and chiral groups as well as small alkyl moieties for the adjustment of the solubility were prepared from two dextran samples with different origin and molecular weight. The examination of side structures of the starting dextran was carried out by different one- and two-dimensional NMR techniques. The main synthesis path via in situ activation of furan-2-carboxylic- and pyroglutamic acid with CDI under mild conditions gives highly functionalized dextran derivatives possessing a degree of polymerization in the range of the starting polysaccharide. The subsequent reaction with propionic anhydride leads to completely substituted, CHCl(3) soluble derivatives useful for the determination of the particular degree of substitution. By variation of the molar ratios of polymer to reagent with photo-crosslinkable- and chiral moieties during the reaction and even by subsequent peracylation, multifunctional dextran derivatives with adjustable properties like the hydrophilic/hydrophobic balance were obtained that may form biocompatible spherical nanoparticles. PMID- 17366517 TI - New solvents for cellulose: dimethyl sulfoxide/ammonium fluorides. AB - New solvents based on DMSO in combination with alkylammonium fluorides, in particular TBAF . 3H(2)O and BTMAF . H(2)O, were established as media for homogeneous functionalization of cellulose. Even DMSO in combination with freshly prepared, anhydrous TBAF, obtained by the reaction of tetrabutylammonium cyanide and hexafluorobenzene, dissolves cellulose. In contrast, a mixture of DMSO and tetramethylammonium fluoride does not dissolve cellulose. The solvents were characterized by capillary viscosity, which showed that a cellulose solution of DMSO/BTMAF . H(2)O possesses a lower viscosity at comparable cellulose concentrations compared with DMSO/TBAF . 3H(2)O. The determination of the degree of polymerization of the starting cellulose (microcrystalline cellulose, spruce sulfite pulp, and cotton linters), and of the regenerated samples, shows that degradation of the polymer depends on the dissolution time, temperature and on the ammonium fluoride used. The results of different homogeneous reactions including acylation and carbanilation of cellulose in the solvents were compared with those of the most-commonly-applied solvent N,N-dimethylacetamide/LiCl. The products were characterized by elemental analysis, (1)H- and (13)C NMR spectroscopy (additionally after perpropionylation) and FTIR spectroscopy. PMID- 17366519 TI - Factors that influence VSV-G pseudotyping and transduction efficiency of lentiviral vectors-in vitro and in vivo implications. AB - Pseudotyping viral vectors with vesicular stomatitis virus glycoprotein (VSV-G) enables the transduction of an extensive range of cell types from different species. We have discovered two important parameters of the VSV-G-pseudotyping phenomenon that relate directly to the transduction potential of lentiviral vectors: (1) the glycosylation status of VSV-G, and (2) the quantity of glycoprotein associated with virions. We measured production-cell and virion associated quantities of two isoform variants of VSV-G, which differ in their glycosylation status, VSV-G1 and VSV-G2, and assessed the impact of this difference on the efficiency of mammalian cell transduction by lentiviral vectors. The glycosylation of VSV-G at N336 allowed greater maximal expression of VSV-G in HEK293T cells, thus facilitating vector pseudotyping. The transduction of primate cell lines was substantially affected (up to 50-fold) by the degree of VSV-G1 or VSV-G2 incorporation, whereas other cell lines, such as D17 (canine), were less sensitive to virion-associated VSV-G1/2 quantities. These data indicate that the minimum required concentration of virion-associated VSV-G differs substantially between cell species/types. The implications of these data with regard to VSV-G-pseudotyped vector production, titration, and use in host-cell restriction studies, are discussed. PMID- 17366520 TI - Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents. AB - The use of cholesterol-based cationic lipids and the ability of glucocorticoids to reduce local inflammatory response to lipoplexes motivated an investigation of structure-activity relationships for cationic steroids. A one-step synthetic scheme using iminothiolane was developed to link spermine to the 21-OH position of steroids via an amidine linkage. Five steroids (cortisol, dexamethasone, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone) with increasing hydrophobicity of the parent steroid (Log P(ster) from 1.51 to 3.01) were conjugated with spermine, formulated with dioleoylphosphatidylethanolamine (DOPE) at DOPE : steroid mole ratios (R) of R = 0.5 to 2, and then complexed with 1 microg enhanced green fluorescent protein (EGFP) plasmid DNA at charge ratios (CR) = 2 to 24 amines per phosphate (0.5 to 6 steroids per phosphate). The resulting 105 different formulations of the cationic steroid series were used to lipofect bovine aortic endothelial cells. Transgene expression data at either 24 or 48 h post-lipofection for all formulations was collapsed onto master curves when plotted against a single empirical dimensionless parameter, the lipofection index (LI) = CR (Log P(liposome))(Log P(ster)/|DeltaLog P|) [R/(R + 1)] where DeltaLog P = Log P(DOPE)- Log P(ster) and Log P(liposome) is a mole-weighted average of the DOPE/cationic steroid liposome hydrophobicity. For 7 < LI < 29, the EGFP expression at 24 or 48 h post-lipofection increased linearly with LI (EGFP approximately 0 for LI < 7), but did not increase further for LI > 29, thus providing a predictive design rule based on Log P of the hydrophobic moiety of the cationic steroid lipid. PMID- 17366518 TI - Pleural and pericardial effusion: a potential ultrasonographic marker for the prenatal differential diagnosis between congenital diaphragmatic eventration and congenital diaphragmatic hernia. AB - OBJECTIVES: To determine whether or not the presence of pleural and/or pericardial effusion can be used prenatally as an ultrasonographic marker for the differential diagnosis between diaphragmatic eventration and diaphragmatic hernia. METHODS: We present two case reports of non-isolated diaphragmatic eventration associated with pleural and/or pericardial effusion. Additionally, we reviewed the literature for all cases of congenital diaphragmatic hernia (CDH) and diaphragmatic eventration that met the following criteria: (1) prenatal diagnosis of a diaphragmatic defect and (2) definitive diagnosis by autopsy or surgery. The frequencies of pleural effusion, pericardial effusion and hydrops were compared between the two conditions using Fisher's exact test. A subanalysis was conducted of cases with isolated diaphragmatic defects (i.e. diaphragmatic defects not associated with hydrops and other major structural or chromosomal anomalies). RESULTS: A higher proportion of fetuses with diaphragmatic eventration had associated pleural and pericardial effusions compared with fetuses with diaphragmatic hernia (58% (7/12) vs. 3.7% (14/382), respectively, P < 0.001). This observation remained true when only cases of diaphragmatic defects not associated with hydrops and other major structural or chromosomal anomalies were compared (29% (2/7) with eventration vs. 2.2% (4/178) with CDH, P < 0.02). CONCLUSIONS: The presence of pleural and/or pericardial effusion in patients with diaphragmatic defects should raise the possibility of a congenital diaphragmatic eventration. This information is clinically important for management and counseling because the prognosis and treatment for CDH and congenital diaphragmatic eventration are different. Published by John Wiley & Sons, Ltd. PMID- 17366521 TI - A new putative Zygosaccharomyces yeast species isolated from traditional balsamic vinegar. AB - The taxonomic status and species number of the genus Zygosaccharomyces have rapidly changed in the last years. In this study, two new osmotolerant Zygosaccharomyces strains isolated from traditional balsamic vinegar, viz. ABT301 and ABT601, were investigated to elucidate their taxonomic relationships with Zygosaccharomyces rouxii species. A multi-gene sequence approach was employed, including regions of the rDNA repeat [5.8S, two internal transcribed spacers (ITS) and the 26S D1/D2 domain], COX2 mitochondrial gene and two nuclear genes (SOD2 and HIS3). Cloning and sequence analysis of 5.8S-ITS rDNA revealed that these strains bear an unusual polymorphism for this region. Three highly divergent 5.8S-ITS sequences were detected, one identical to Z. rouxii, the other two showing some relatedness to Z. mellis. Sequence and gene number polymorphism was also observed for the protein-encoding nuclear genes SOD2 and HIS3, as two copies for each gene different from those found in Z. rouxii were detected. Analysis of the D1/D2 26S domain showed that ABT301 and ABT601 have only one type of D1/D2 sequence statistically different from that of Z. rouxii. The findings obtained in this work suggest that the genomic background of strains ABT301 and ABT601 is different from the other Zygosaccharomyces species. We speculated that they could belong to a new putative species related to Z. rouxii. PMID- 17366522 TI - Delayed accumulation of the yeast G1 cyclins Cln1 and Cln2 and the F-box protein Grr1 in response to glucose. AB - The ability to integrate nutrient availability into cell cycle regulation is critical for the viability of organisms. The Saccharomyces cerevisiae ubiquitin ligase SCF(Grr1) regulates the stability of several proteins that participate in cell division or nutrient sensing. Two of its targets, the cyclins Cln1 and Cln2, accumulate in the presence of glucose. When glucose is added to cells growing asynchronously, we show that the accumulation of the cyclins is a very slow response. We report that the F-box protein Grr1 also accumulates at higher levels in the presence of glucose, and that the response to glucose follows a delayed pattern strikingly similar to that described for Cln1 and Cln2. A model for the regulation of F-box proteins predicts that substrate accumulation could stabilize Grr1. While we found that Grr1 is more stable in cells growing with glucose, we show that the delayed responses to glucose occur independently: Grr1 accumulates in the absence of the cyclins, and vice versa. Thus, our results indicate that this model might not apply to the cyclins and Grr1. Glucose is known to strengthen the interaction of Grr1 with Skp1 in the SCF complex. We hypothesize that glucose could promote the accumulation of Grr1 and its assembly into a SCF complex as a feedback regulation that helps compensate for higher cyclins levels. PMID- 17366523 TI - Immune response to conjugated meningococcal C vaccine in pediatric oncology patients. AB - BACKGROUND: Following outbreaks of meningococcal disease in Quebec in 1991-1993 and 2000-2001, a mass vaccination campaign was performed. In 2001-2002, children aged 2 months to 20 years were immunized with the Meningococcal CRM197 vaccine (Menjugate). We examined the response of pediatric oncology patients during or following maintenance chemotherapy and post-bone-marrow transplantation to Meningococcal C vaccine. PROCEDURE: This was an open label descriptive study of a cohort of patients from the oncology clinic at the Montreal Children's Hospital. A positive vaccine response was defined as a fourfold increase in specific IgG from baseline and a bactericidal assay using human complement (hBCA) titer >1:4. RESULTS: Of the 25 patients with ALL, 13 had a serologic response (average 60 fold increase). The serologic responders had a higher mean B cell count (0.262) compared to non-responders 0.068 x 10.9/L [t(23) = 2.843 (P < 0.05)]. Eleven of the 12 non-responders and 4 of the responders were on maintenance chemotherapy. In addition, two of the five patients post-bone-marrow transplant, responded. Fifteen of the 34 patients (44%) had an adequate hBCA response (mean titer 61). The group included 14/18 serologic responders with hBCA response (P < 0.001) and 16/17 non-serologic responders with no hBCA response (P < 0.001). CONCLUSIONS: Meningococcal C-conjugate vaccine produced variable responses in children with common cancers. Proximity to chemotherapy and total B cell number may help predict likelihood of response. PMID- 17366524 TI - Carotid cavernous fistula in CNS choriocarcinoma. AB - Carotid artery-cavernous sinus fistulas (CCFs) are infrequently reported in the pediatric population, and are rarely reported in conjunction with CNS neoplasms. The authors present a 7-year-old girl with CNS choriocarcinoma who acutely developed left eye proptosis and conjunctival injection. Computed tomography angiography revealed a CCF, which was endovascularly embolized with detachable coils. There may be a direct cause-and-effect relationship between choriocarcinoma and development of CCFs. PMID- 17366525 TI - Evidence of population mixing based on the geographical distribution of childhood leukemia in Ohio. AB - BACKGROUND: This ecologic study examined the geographic distribution of childhood leukemias in Ohio, 1996-2000, among children aged 0-19 for evidence that population mixing may be a factor. PROCEDURE: (1) State incidence rates were compared to Surveillance, Epidemiology and End Results (SEER) rates for each year and for the 5-year period, 1996-2000; (2) incidence rates for each of Ohio's 88 counties were compared to statewide rates; and (3) county incidence rates were compared based on population density, population growth, and rural/urban locale. SEER*Stat version 5.0 was used to derive age-specific and 0-19 age-adjusted rates. Expected values, standardized incidence ratios (SIRs), and Poisson P values were calculated with Excel using the indirect method of standardization. RESULTS: Of the 585 cases, 73.3% were acute lymphocytic leukemia (ALL), 16.6% acute myelogenous leukemia (AML), 3.2% acute monocytic leukemia (AMoL), and 2.6% chronic myelogenous leukemia (CML). Rates for total leukemia burden were significantly below national levels for all races (P = 0.00001), likely due to poor ascertainment of cases. Yearly incidence rates for 1996-2000 were stable for ALL and AML; CML rates declined over the period. Based on 2000 Census and intercensal population estimates for 1996-2000, statistically higher rates for ALL were noted for counties experiencing >10% population change 1990-2000 (P < 0.05), especially for ages 1-4 (P < 0.03) in counties with 10-20% growth. Counties 67.9-99.2% urban experienced fewer than expected cases of AML + AMoL (P < 0.06). CONCLUSION: Data support Kinlen's theory of population mixing and warrant further studies in Ohio, the US and other countries. PMID- 17366526 TI - Randomized clinical trial of efficacy of self-monitoring techniques to treat urinary incontinence in women. AB - AIM: To assess the efficacy of self-monitoring techniques to reduce urine loss and increase quality of life for women with urinary incontinence. METHODS: The design was a two arm, randomized, clinical trial with a wait list control group and 3-week intervention. Participants were 224 community-dwelling women 18 and older with UI. Self-monitoring was individualized counseling about fluid and caffeine intake, quick pelvic floor muscle contraction, voiding frequency, and management of constipation. The primary outcome measure was grams of urine loss. Secondary outcomes included episodes of urine loss, quality of life, and caffeine and fluid consumption. RESULTS: The main effect of self-monitoring on grams of urine loss was significant. After adjusting for baseline urine loss, time in the intervention or in wait list group, age, hormone status, and race the self- monitoring group lost an average of 13.3 g less urine and had improved 26.1 points in quality of life compared to the wait list group. The effect of self monitoring on episodes of urine loss was not significant in the total sample but was more effective for women who had 9 or more episodes of urine loss, were 65 years or older, and were premenopausal or taking hormone replacement therapy. Participants in the self-monitoring group reduced their caffeine intake, but did not increase their fluid intake compared to the wait list control group. CONCLUSIONS: Since self-monitoring techniques are simple, safe, inexpensive, and within the scope of practice for most health professionals, they should be considered as first steps to treat women with UI. PMID- 17366527 TI - Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study. AB - BACKGROUND: Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care. PROCEDURE: Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control). Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization, and cost between both groups. RESULTS: A prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated on an outpatient basis. We found a statistically significant difference between the duration of hospitalization of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P < 0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications. CONCLUSIONS: We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization. PMID- 17366529 TI - Galactosamine-induced hepatotoxic effect and hepatoprotective role of a protein isolated from the herb Cajanus indicus L in vivo. AB - dd(+)-Galactosamine is a well-known experimental hepatotoxin. The present study was conducted to determine the protective role of a 43-kD protein isolated from the leaves of the herb Cajanus indicus L against D(+)-galactosamine (GalN) induced liver damage in mice. Both preventive and curative effects of the protein have been investigated in the study. The protein was administered intraperitoneally at a dose of 2 mg/kg body weight for 4 days before and after GalN intoxication at a dose of 800 mg/kg body weight for 3 days. The increased activities of serum marker enzymes, alanine aminotransferase, and alkaline phosphatase because of GalN administration, were significantly reduced by the protein treatment. The protein also normalized the altered activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione-S-transferase as well as the levels of cellular metabolites, reduced glutathione, glutathione disulfide, and total thiols. In addition, the enhanced hepatic lipid peroxidation because of GalN intoxication was also effectively inhibited by the protein treatment. Results suggest that GalN caused hepatic damages via oxidative insult and that the protein provided protection through its antioxidant mechanism. PMID- 17366530 TI - High resolution protein-DNA binding energy landscapes via a novel high throughput method. PMID- 17366531 TI - Treatment of pediatric non-Hodgkin lymphoma in Hungary: 15 years experience with NHL-BFM 90 and 95 protocols. AB - Retrospective analysis was performed to assess the survival-rates of children with non-Hodgkin lymphoma (NHL), treated according to the NHL-BFM (Berlin Frankfurt-Munster)-90 and -95 protocols between 1990 and 2004 in Hungary, and to compare our data with the international results. Ninety-one patients had non-B NHL, 108 B-NHL, and 31 ALCL. Complete remission rate was 89%, while 12% relapsed later. The 5-year-overall-survival was 78% and the event-free survival was 75%. These results are lower than those reported by the BFM study group, but comparable from other European centers. In the last 5 years, the results showed 10% improvement and death during induction was reduced from 10 to 3%. PMID- 17366532 TI - Chronic myelomonocytic leukemia (CMML) as a second malignancy following Ewing sarcoma. PMID- 17366533 TI - Complementary and alternative therapy use in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. AB - BACKGROUND: Little information is available on the use of complementary and alternative medicine (CAM) in long-term survivors of childhood and adolescent cancer. PROCEDURE: The Childhood Cancer Survivor Study (CCSS) is a resource evaluating the long-term effects of cancer and associated therapies in 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986 before the age of 21 years. A survey of CAM use during the previous year was distributed in 2000-2001 and completed by 9,984 survivors and 2,474 sibling controls. RESULTS: CAM use reporting was similar in cases (39.4%) and siblings (41.1%). Compared to female siblings, female survivors were more likely to use biofeedback (odds ratio (OR) = 3.3; 95% CI = 1.0-10.8) and hypnosis/guided imagery (OR = 3.2; 95% CI = 1.6-6.8); male survivors were more likely than male siblings to use herbal remedies (OR = 1.3; 95% CI = 1.1-1.6). Factors associated with CAM use in survivors included elevated scores on the brief symptom inventory (BSI)-18 (OR = 1.6; 95% CI = 1.3-1.9), prolonged pain (OR = 1.5; 95% CI = 1.3 1.7), and having seen a physician in the past 2 years (OR = 1.6; 95% CI = 1.4 1.8). Survivors reporting low alcohol intake and excellent or good general health reported lower levels of CAM use (OR = 0.7; 95% CI = 0.7-0.8 and OR = 0.8; 95% CI = 0.7-0.9, respectively). CONCLUSIONS: Survivors have a similar reported use of CAM compared to a sibling cohort. However, our data suggest that survivors turn to CAM for specific symptoms related to previous diagnosis and treatment. Future research is needed to determine whether CAM use reflects unmet health needs in this population. PMID- 17366537 TI - Nutrient mixture including vitamin C, L-lysine, L-proline, and epigallocatechin is ineffective against tumor growth and metastasis in a syngeneic neuroblastoma model. AB - BACKGROUND: The replacement of established evidence-based cancer therapy protocols (mainstream therapy) by unevaluated complementary and alternative medicine (CAM) is a challenge in pediatric oncology. We tested the hypothesis that oral application of L-lysine and ascorbic acid (Lysin C Drink) in combination with epigallocatechin-gallate (EGCG) and amino-acids (Epican forte) is effective in a preclinical model of neuroblastoma. METHODS: Primary tumors and spontaneous metastases were induced in A/J mice by injection of NXS2 neuroblastoma cells. Mice were treated by daily oral gavage with L-lysine and ascorbic acid (Lysin C Drink) (equivalent to 150 mg ascorbic acid/day/mouse) (treatment A) or with EGCG plus ascorbic- and amino-acids (Epican forte) (9.2 mg/mouse) (treatment B). Treatment A was started in the prophylactic setting (7 days before tumor cell injection) as well as in the therapeutic setting (1 day after tumor cell inoculation). Finally, treatment B was evaluated alone and in combination with treatment A in the therapeutic setting. The effect on primary tumor growth and the development of spontaneous liver metastases was evaluated. RESULTS: L-lysine and ascorbic acid (Lysin C Drink) and EGCG plus ascorbic- and amino-acids (Epican forte) are ineffective in reduction of primary tumor growth and prevention of spontaneous liver metastases in this model. CONCLUSIONS: Neither a formal clinical development nor the use of these substances can be recommended for neuroblastoma. PMID- 17366538 TI - Early-onset sarcoidosis mimicking refractory cutaneous histiocytosis. AB - A 10-year-old female was diagnosed as having early-onset sarcoidosis (EOS) after a prolonged skin disease. A granuloma emerged on the face at age 2 and massive lesions extended to the rest of the body. Repeated biopsies indicated histiocytic proliferation. At age 7, fever, disseminated macular eruptions, and multinucleated giant cells in the bone marrow prompted vinblastine and prednisolone therapy. Five months after stopping therapy, hypercalcemic crisis occurred along with fever, cytopenias, and interferon-gamma-nemia indicating a macrophage activation syndrome. A biopsy of nodules confirmed the diagnosis of sarcoidosis. The atypical EOS should be differentiated from histiocytosis. PMID- 17366539 TI - Substrate activation of butyrylcholinesterase and substrate inhibition of acetylcholinesterase by 3,3-dimethylbutyl-N-n-butylcarbamate and 2-trimethylsilyl ethyl-N-n-butylcarbamate. AB - Carbamates are used to treat Alzheimer's disease. These compounds inhibit acetylcholinesterase and butyrylcholinesterase. The goal of this work is to use the substrate analogs of butyrylcholinesterase, 3,3-dimethylbutyl-N-n butylcarbamate (1) and 2-trimethylsilyl-ethyl-N-n-butylcarbamate (2) to probe the substrate activation mechanism of butyrylcholinesterase. Compounds 1 and 2 are characterized as the pseudo substrate inhibitors of acetylcholinesterase; however, compounds 1 and 2 are characterized as the essential activators of butyrylcholinesterase. Therefore, compounds 1 and 2 mimic the substrate in the acetylcholinesterase-catalyzed reactions, but the behavior of compounds 1 and 2 mimics the substrate activation in the butyrylcholinesterase-catalyzed reactions. PMID- 17366540 TI - Ontogeny of hepatic CYP1A2 and CYP2E1 expression in rat. AB - We report a comprehensive examination of rat hepatic CYP1A2 and CYP2E1 ontogeny. We compare the data to human data to determine the rat's capacity as a model to identify CYP-mediated mechanisms underlying age-dependent differences in susceptibility to toxicity. We evaluated CYP expression using real-time RT-PCR, immunoblot and immunohistochemistry, and specific probe activity in male rat livers (n = 4) at critical developmental life stages. CYP2E1 mRNA expression was low at birth, then increased rapidly to peak prior to weaning. CYP1A2 transcript levels remained very low postnatally and then increased dramatically to reach peak expression during weaning. Immunoreactive CYP1A2 and CYP2E1 was first detected at postnatal day 3 (PD3), and reached 50% of adult levels after weaning, and adult levels by puberty. CYP1A2 and CYP2E1 probe activity (pmol/(min mg)) was detected at PD3 and peaked during weaning and late neonatal period, respectively. CYP activity fell to adult values by puberty, a pattern that closely mirrored the temporal changes in mRNA but not protein. An increasing preferential localization of CYP1A2 and CYP2E1 immunoreactivity in perivenous hepatocytes was observed with maturation to adulthood. Although differences in CYP1A2 and CYP2E1 ontogeny between rats and humans exist, knowledge of these differences will aid interspecies extrapolation of developmental toxicokinetic data. PMID- 17366541 TI - Preventive effect of rutin on lipids, lipoproteins, and ATPases in normal and isoproterenol-induced myocardial infarction in rats. AB - The present study was designed to evaluate the preventive role of rutin on lipids, lipoproteins, and ATPases in normal and isoproterenol (ISO)-induced myocardial infarction in rats. Rutin (40 and 80 mg/kg) was orally administered to rats for a period of 42 days. After that period, isoproterenol (150 mg/kg) was injected subcutaneously to male wistar rats at an interval of 24 h for 2 days. The weight of heart and the concentrations of total cholesterol, triglycerides, and free fatty acids were increased significantly (p < 0.05), and the concentration of phospholipids was decreased significantly (p < 0.05) in the heart of ISO-treated rats. ISO-treated rats also showed a significant increase (p < 0.05) in the levels of total cholesterol, triglycerides, phospholipids, low density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) with a significant decrease (p < 0.05) in high-density lipoprotein cholesterol (HDL-C) level in serum. The activities of sodium potassium dependent adenosine triphosphatase (Na(+)/K(+) ATPase) and magnesium dependent adenosine triphosphatase (Mg(2+) ATPase) were decreased significantly (p < 0.05), and the activity of calcium-dependent adenosine triphosphatase (Ca(2+)ATPase) was increased significantly (p < 0.05) in the heart in ISO-treated rats. Pretreatment with rutin at doses of 40 or 80 mg/kg to ISO-treated rats showed a significant (p < 0.05) effect in all the parameters studied. Oral administration of rutin to normal rats did not show any significant effect. Thus, the results of our study show that pretreatment with rutin maintained the levels of lipids, lipoproteins, and ATPases in ISO-induced myocardial infarcted rats. The observed effects might be due to the antioxidant potential of rutin. PMID- 17366542 TI - Cloning, tissue expression, and inducibility of CYP 3A79 from sea bass (Dicentrarchus labrax). AB - Multiple members of the CYP3A subfamily have been identified and intensively studied in mammals as they represent prominent CYP enzymes involved in drug metabolism. Also in fish, some CYP3A genes have been identified by cDNA cloning and immunological techniques, but relatively little is known about their function, distribution, and inducibility. In this study, a novel CYP3A, designated as CYP3A79 was isolated from adult male sea bass, an economically valuable species in fisheries. The sea bass CYP3A79 that was cloned contained an open-reading frame of 1512 bp that encoded a 504 amino acid protein and shared a high-sequence identity with medaka, killifish, and trout CYP3As. Interestingly, CYP3A79 also shares five of six substrate recognition sites (SRS) with the SRS of other fish CYP3As, suggesting an evolutionary conservation of the function of these enzymes. In this fish, we also investigated the expression of CYP3A79 and its susceptibility to induction by various compounds including clotrimazole and dehydroepiandrosterone, two strong ligands of zebrafish PXR. The expression of CYP3A79 mRNA was detected by RT-PCR only in the intestine and liver. The immunoblot analysis by antitrout CYP3A27 confirmed the presence of a CYP3A-like protein in the microsomes of these tissues, but, in addition, a immunoreactive protein with this antibody was also observed in the heart microsomes, suggesting the presence of other CYP3A isoforms in this fish. Accordingly, the southern blot analysis of genomic DNA indicated that multiple CYP 3As may be present in sea bass. All attempts to induce 6beta-testosterone hydroxylase, as a marker of CYP3A79, by dexametasone, 17beta-estradiol, pregnenolone 16alpha-carbonitrile, corticosterone, clotrimazole, and dehydroepiandrosterone failed. On the contrary, the administration of 17beta-estradiol, pregnenolone 16alpha-carbonitrile, and corticosterone strongly inhibited this activity and, in parallel, reduced the expression of CYP3A79 transcript. Thus, the sea bass CYP3A79 appears to be resistant to induction, suggesting that this enzyme and likely other CYP3As are regulated differently compared to those of mammals. PMID- 17366544 TI - Inactivation of phospholipase A2 and metalloproteinase from Crotalus atrox venom by direct current. AB - To achieve our aim of understanding the interactions between direct current and enzymes in solution, we exposed reconstituted Crotalus atrox venom to direct electric current by immersing two platinum thread electrodes connected to a voltage generator (between 0 and 8 V) into a reaction mixture for a few seconds. Then, we assayed the residual activity of phospholipases A(2) (PLA(2)),metalloproteinases, and phosphodiesterases, abundant in crotaline snake venoms and relevant in the pathophysiology of envenomation, characterized by hemorrhage, pain, and tissue damage. C. atrox venom phospholipase A(2) and metalloproteinases were consistently and irreversibly inactivated by direct current (between 0 and 0.7 mA) exposure. In contrast, C. atrox venom phosphodiesterases were not affected. Total protein content and temperature of the sample remained the same. Secretory pancreatic phospholipase A(2), homologue to snake venom phospholipases A(2), was also inactivated by direct current treatment. In order to understand the structural reasoning behind PLA(2) inactivation, circular dichroism measurements were conducted on homogeneous commercial pancreatic phospholipase A(2), and it was found that the enzyme undergoes structural alterations upon direct current exposure. PMID- 17366546 TI - Retracted and replaced: Sodium cromoglicate: an ineffective drug or meta-analysis misused? AB - The following article from Pharmaceutical Statistics, Sodium cromoglicate: an ineffective drug or meta-analysis misused? by M. T. Stevens, A. M. Edwards, J. B. L. Howell published online on 15 March 2007 in Wiley InterScience (www.interscience.wiley.com), has been retracted by agreement between the author, the journal Editor in Chief, Steven Julious, and John Wiley & Sons, Ltd. The retraction has been agreed because the article is not yet ready for publication and an early version without revisions was published in error. Replacement article pending. Copyright (c) 2007 John Wiley & Sons, Ltd. PMID- 17366547 TI - Development and calcium level changes in pre-implantation porcine nuclear transfer embryos activated with 6-DMAP after fusion. AB - This study investigated the effect of treatment with 6-dimethylaminopurine (6 DMAP) following fusion on in vitro development of porcine nuclear transfer (NT) embryos. Frozen thawed ear skin cells were transferred into the perivitelline space of enucleated oocytes. Reconstructed oocytes were fused and activated with electric pulse in 0.3 M mannitol supplemented with either 0.1 or 1.0 mM CaCl(2). In each calcium concentration, activated oocytes were divided into three groups. Two groups of them were exposed to either ionomycin (I + 6-DMAP or 6-DMAP alone. In experiment 2, fused NT embryos in 0.3 M mannitol containing 1.0 mM CaCl(2) were exposed to 6-DMAP either immediately or 20 min after fusion/activation. For 0.1 mM CaCl(2), oocytes activated with either I + 6-DMAP or 6-DMAP alone showed a higher (P < 0.05) developmental rate to the blastocyst stage than those activated with an electric pulse alone (26.7 and 22.5 vs. 12.5%). For 1.0 mM CaCl(2), oocytes activated with either I + 6-DMAP or 6-DMAP alone showed significantly higher (P < 0.05) developmental rate to the blastocyst stage (35.6 and 28.3 vs. 19.8%). Developmental rate to the blastocyst stage was (P < 0.05) increased in NT embryos activated with 6-DMAP 20 min after fusion. 6-DMAP made a higher and wider Ca(2+) transient compared to that induced by electric pulses (Fig. 3). The fluctuation lasted during the time that oocytes were cultured in 6-DMAP. Regardless of Ca(2+) concentration in fusion medium, activation with 6-DMAP following electric pulses supported more development of porcine NT embryos. Activation of NT embryos with 6-DMAP after fusion in the presence of 1.0 mM CaCl(2) could support better developmental rate to the blastocyst stage. PMID- 17366548 TI - A fifteen-year cytogenetic remission following interferon treatment in a patient with an indolent ETV6-ABL positive myeloproliferative syndrome. PMID- 17366549 TI - Hepatitis B virus reactivation in a case of Waldenstrom's macroglobulinemia treated with chemotherapy and rituximab despite adefovir prophylaxis. PMID- 17366550 TI - A normal radial glial scaffold is necessary for migration of interneurons during neocortical development. AB - The relationship between radial glia and neurons migrating tangentially from the ganglionic eminence (GE) has been suggested but not firmly established. To study this relationship we used a ferret model of cortical dysplasia where radial glia are highly disorganized. To produce this, an antimitotic, methylazoxy methanol (MAM) is injected on the 24th day of gestation (E24 MAM). Neurons migrating away from the GE in MAM-treated animals tend to remain in the intermediate zone (IZ) and do not reach the cortical plate (CP) as they do in normal ferret slices. We recently observed that the disrupted radial glia after MAM treatment could be restored toward their normal morphology by exogenous application of neuregulin1 (NRG1). We demonstrate here that when E24 MAM slices are treated with NRG1, the distribution of cells arising from the GE was similar to normal slices. In a second paradigm, we disrupted radial glia by adding ciliary neurotrophic factor (CNTF) to the culture media of normal ferret slices; CNTF induces acute differentiation of radial glia into astrocytes. After CNTF exposure, few tangentially migrating cells reach the CP compared to untreated slices. These results show that interneurons fail to reach the CP by disrupted normal radial glia and restoring the normal radial glial scaffold is sufficient to allow migrating cells to invade the CP. Our results suggest an important role for radial glia by controlling directly or indirectly the migration of interneurons to the CP, their main target. PMID- 17366551 TI - In vitro synthesis of 1,N6-etheno-2'-deoxyadenosine and 1,N2-etheno-2' deoxyguanosine by 2,4-dinitrophenol and 1,3-dinitropyrene in presence of a bacterial nitroreductase. AB - The formation of covalent nitro-PAH DNA adducts and nitro-PAH mediated oxidative lesions are two possible mechanisms for the initiation of nitro-PAH carcinogenesis. Sixty-minute incubation of 1,3-dinitropyrene (100 microM) or 1,4 dinitrophenol (100 microM) with a mixture of 150 microM NADH, 0.5 units of E. coli nitroreductase, 100 microM linoleic acid, 0.5 mM ferrous iron, and 100 microM 2'-deoxyadenosine (2'-dA) or 100 microM 2'-deoxyguanosine (2'-dG) were analyzed by liquid chromatography multistage mass spectrometry. Mixtures of 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) plus 4-oxo-2-nonenal (4-ONE) and 1,N(2)-etheno-2'-deoxyguanosine (epsilondG) plus 4-ONE could be detected from 2' dA and 2'-dG, respectively. Addition of 2% propanol inhibited the formation of etheno adducts. Analyses of disappearance kinetics of dA and dG showed that dG was more rapidly eliminated than does dA (t[1/2] = 23.3 min and 98.3 min for dG and dA, respectively). Curves of formation kinetics revealed that the peak of epsilondG was at 55.6 min while that of epsilondA was at 186.9 min. These peaks represented 1.43% and 1.25% of the original dG and dA, respectively. In both cases, the peaks were followed by rapid degradations of etheno adducts. The results, obtained in this system, do not allow any extrapolation to realistic cellular responses; nevertheless, these data questioned the validity of the use of unsubstituted etheno adducts as reliable oxidative stress and nitro-PAH exposure biomarkers. PMID- 17366553 TI - Intraductal sonography of biliary varices associated with extrahepatic portal vein obstruction. AB - We report a case of biliary varices associated with extrahepatic portal vein obstruction (EHPVO) that were identified via intraductal sonography during endoscopic retrograde cholangiography. A 35-year-old man was admitted to our hospital because of jaundice that had developed during an episode of EHPVO. Laboratory data showed obstructive jaundice. Endoscopic retrograde cholangiography showed some bile duct stenosis with smooth stricture along the extrahepatic biliary duct. Intraductal sonographic examination revealed numerous vessels around the lower and upper parts of the bile duct. Compression by these vessels was suspected as the cause of the biliary stricture. PMID- 17366555 TI - Solitary necrotic nodule of the liver: contrast-enhanced sonography. AB - PURPOSE: To report contrast-enhanced sonography (CEUS) for solitary necrotic nodule (SNN) of the liver and to assess its clinical value. METHODS: CEUS was performed in 17 patients with pathologically proven SNN. Contrast pulse sequencing and the contrast agent SonoVue were used to depict lesion vascularity at a low mechanical index. The enhancement patterns were evaluated in real time. RESULTS: Lesions were depicted as perfusion defects throughout all phases on CEUS. CONCLUSIONS: CEUS can be a convenient imaging modality for the differential diagnosis of SNN and may obviate the need for further imaging studies. PMID- 17366556 TI - Acute binocular blindness. AB - BACKGROUND: Acute binocular blindness is an uncommon cause for neurologic consultation. METHODS: Over the last 20 months 10 patients with acute onset blindness were seen at a tertiary cancer center. Probable cause was identified in all patients. RESULTS: Treatment varied and was determined by etiology of visual loss. CONCLUSIONS: Six patients made a complete or near complete recovery. PMID- 17366558 TI - Resistance and pulsatility index increase in capsular branches of testicular artery: indicator of impaired testicular microcirculation in varicocele? AB - PURPOSE: To evaluate the effect of clinical varicocele on testicular microcirculation using spectral Doppler analysis. METHODS: Forty-nine young and healthy volunteers were enrolled in this prospective study. Varicocele grades were determined according to sonographic parameters. Patients with left-sided clinical varicocele were classified as the patient group (n = 15), while the remaining patients served as controls (n = 34). Spectral Doppler measurements of testicular arteries (peak systolic/end diastolic velocity, resistance index, pulsatility index) were measured from capsular and intratesticular branches. RESULTS: No statistically significant difference was found between the Doppler parameters obtained from the intratesticular branches of both testes and the capsular branches of the right testis. On the other hand, in left-sided clinical varicocele cases, the average resistance index (RI) and pulsatility index (PI) of capsular branches of the left testes (RI, 0.68 +/- 0.04; PI, 1.22 +/- 0.15) were significantly greater than in the control group (RI, 0.64 +/- 0.06; PI, 1.07 +/- 0.18) (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: Increased RI and PI of capsular branches of testicular arteries on spectral Doppler examination may be an indicator of impaired testicular microcirculation in patients with clinical varicocele. Further studies addressing the correlations with sperm counts are needed to determine the cut-off values for these indices. PMID- 17366557 TI - A genome-wide linkage scan for cleft lip and cleft palate identifies a novel locus on 8p11-23. AB - Isolated or nonsyndromic cleft lip and palate (NS CLP) is a complex disorder resulting from multiple genetic and environmental factors. NS CLP has a birth prevalence of 1 per 500 in the Philippines where large families provide an opportunity for gene localization. Genotyping of 392 microsatellite repeat markers at 10 cM intervals over the genome was performed by the Center for Inherited Disease Research (CIDR) on 220 Filipino families with 567 affected and 1,109 unaffected family members genotyped. Among the most statistically significant results from analysis of the genome-wide scan data was a 20 cM region at 8p11-23 in which markers had LODs > or =1.0. This region on 8p11-23 has not been found in any previous genome wide scan nor does it contain any of the candidate genes widely studied in CLP. Fine mapping in 8p11-23 was done in the 220 families plus an additional 51 families, using SNP markers from 10 known genes (FGFR1, NRG1, FZD3, SLC8A1, PPP3CC, EPHX2, BNIP3L, EGR3, PPP2R2A, and NAT1) within the 20 cM region of 8p11-23. Linkage and association analyses of these SNPs yield suggestive results for markers in FGFR1 (recessive multipoint HLOD 1.07) and BAG4 (recessive multipoint HLOD 1.31). PMID- 17366559 TI - Sonographic diagnosis of cesarean scar pregnancy at 16 weeks. AB - Cesarean scar pregnancy is rare. However, there has been a rapid increase in the reporting of such cases in recent years. Most of the cases reported in the literature were diagnosed early in the first trimester. Possible management options proposed are pertinent to an early diagnosis. We present a case of a cesarean scar pregnancy diagnosed at 16 weeks that posed a dilemma with regard to management. The patient subsequently suffered a ruptured uterus, which was preserved at surgery. PMID- 17366560 TI - Hemoperitoneum from ruptured cyst in a hyperstimulated ovary: a sonographic mimic of ovarian hyperstimulation syndrome. AB - We report a case of a ruptured cyst in a hyperstimulated ovary that was initially misinterpreted as ovarian hyperstimulation syndrome (OHSS). A 22-year-old woman who was on oral clomiphene citrate for primary infertility presented with pain in the lower abdomen, hypotension, and tachycardia. Sonographic examination revealed multiple cysts in both ovaries and free fluid in the abdomen, and the initial diagnosis was OHSS. However, sonographically guided aspiration of free fluid revealed a hemoperitoneum, and the patient underwent emergent surgery. At laparotomy, an actively bleeding ruptured cyst in a hyperstimulated ovary was found to be the cause of the hemoperitoneum. Radiologists must be familiar with the imaging features of this condition to avoid misdiagnosing it as OHSS, because this could potentially delay urgently required surgery. PMID- 17366561 TI - Cutaneous metastasis of esophageal adenocarcinoma with an unusual presentation. AB - We describe an unusual presentation of a cutaneous metastasis of esophageal adenocarcinoma in the left tempero-parietal skull and the sonographic features that helped establish the diagnosis. The patient had a primary tumor surgically resected 4 years earlier and was in clinical remission at the time of presentation. The patient presented to our radiology department with a lump on the head after a fall, and sonographic examination was recommended to assess the presumed posttraumatic hematoma. The examination revealed typical features of malignancy: a superficial solid mass invading the skull surrounded by an irregular network of blood vessels. This was confirmed on CT, and a definitive diagnosis was obtained on histologic analysis following sonographically guided biopsy. PMID- 17366562 TI - Effect of dibutyltin on ATP levels in human natural killer cells. AB - This study investigates the role that decreased ATP levels may play in dibutyltin (DBT)-induced decreases in the tumor-cell-lysing (lytic) function of natural killer (NK) cells. NK cells are a subset of lymphocytes capable of killing tumor cells, virally infected cells, and antibody coated cells. DBT is used as stabilizer in PVC plastics and has also been used as a deworming product in poultry. NK cells were exposed to various concentrations of DBT for 1 h, 24 h, 48 h, and 6 days before determining ATP levels and lytic function. ATP levels and lytic function were also determined in NK cells that were exposed to DBT for 1 h followed by 24 h, 48 h, and 6 days in DBT-free media. The results indicated that exposure of NK cells to 10 muM DBT for 1 h did not cause any significant decrease in NK cell ATP levels but did cause a very significant loss in lytic function. NK cells exposed to 500 nM DBT for 24 h showed significant loss of lytic function but showed no decrease in ATP levels. However, 48 h and 6 days exposures to those concentrations of DBT that caused decreases in tumor lysing function also caused significant decreases in ATP levels. Exposures of NK cells to varying DBT concentrations for 1 h followed by 24 h, 48 h, and 6 days in DBT free media produced effects on lytic function and ATP levels that were similar to those seen with continuous DBT exposures. The results indicate that DBT exposures decrease ATP levels in NK cells but that tumor lysing function can be reduced independent of any decreases in ATP levels. Additionally the results show that the effects of a range of DBT concentrations on ATP levels and tumor lysing function are irreversible. PMID- 17366563 TI - Sampling and analysis of microcystins: Implications for the development of standardized methods. AB - Microcystins (MC), a group of cyanotoxins, have been found in lakes and rivers worldwide. One goal of MC research is to develop models which predict MC concentrations, but these efforts have been hampered by a lack of standardized methods necessary for comparing data across studies. Here, we investigate the effect of chemical analysis (HPLC-PDA and ELISA), sample collection (whole water, plankton tow and surface scum), and choice of normalizing parameter (volume, dry weight, and chlorophyll a) on reported MC concentrations. Samples were collected over three years from a temperate mesotrophic, shallow lake with episodic blooms of cyanobacteria. We found that microcystins were up to four times higher in lake samples when analyzed by ELISA relative to HPLC-PDA and that MC concentration measured by HPLC explained less than half of the variation in MC concentrations measured by ELISA. Also, samples collected by plankton tow gave consistently higher concentrations than whole water samples. An additional HPLC analysis of two chlorophyte cultures revealed the presence of compounds with a similar UV absorbance spectrum to MC-LR, suggesting that identifying MC based solely on UV absorbance is not valid. Our results document the discrepancy in MC concentrations that can arise by using different methods throughout all stages of sampling, analysis, and reporting of MC concentrations. PMID- 17366564 TI - Protective effects of insulin on polychlorinated biphenyls-induced disruption of actin cytoskeleton in hippocampal neurons. AB - Insulin receptors are widely distributed in the brain, and insulin improves learning and memory in some brain injury. Insulin elevates LIM kinase 1 (LIMK-1) activity and induces actin polymerization in some cells, while actin cytoskeleton dynamics mediated via LIMK-1/cofilin signal pathway is considered important to learning and memory formation. Our previous studies have shown that polychlorinated biphenyls (PCBs) disrupt the actin cytoskeleton by inhibiting LIMK-1/cofilin signaling pathway in the cultured hippocampal neurons. To determine potential neuronal protective effects by insulin, we administered insulin to the cultured hippocampal neurons after exposure to PCBs mixture Aroclor 1254 (A 1254). We found that insulin antagonized a loss of filamentous actin and the cytotoxicity induced by A 1254. Similarly, insulin restored the decrease of LIMK-1 and cofilin phosphorylation induced by A 1254. We concluded that insulin could protect neurons, probably partly by ameliorating filamentous actin cytoskeleton disruption mediated via the activation of LIMK-1/cofilin signal pathway in cultured hippocampal neurons after exposure to A 1254. The above protective effects in hippocampal neuron may have important implications in the treatment of PCBs-induced neurotoxicity and the mechanism by which insulin improves learning and memory. (c) 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 152-158, 2007. PMID- 17366565 TI - Contact hypersensitivity to stainless steel cages (chromium metal) in hairless descendants of mexican hairless dogs. AB - Canine allergic contact hypersensitivity is an uncommon skin disease as compared with human beings because hair coat is a good natural barrier to environmental contactants. In our colony of hairless dogs housed in stainless steel cages, we have encountered spontaneously occurring contact hypersensitivity. The author has attempted to study the toxicological effects of environmental sensitizing substances on the canine skin. The purpose of this study is to elucidate dermatological characteristics in canine species with contact hypersensitivity. This skin lesion was investigated by patch tests, macroscopic observations, and histopathological examinations. Patch tests exhibited positive reactions to potassium dichromate. Macroscopically, early lesions were macules and/or papules and they gradually progressed to severe inflammatory dermatitis over the dorsum. In the chronic phase, lichenification, kyperkeratosis, hyperpigmentation, dryness, scaliness, and fissuring were observed in the skin. Avoidance of contact with the stainless steel cages resulted in clinical improvement. Histopathologically, the epidermis apparently showed hyperkeratosis, thickening, hyperplasia, and rete ridge formation. Lichenified lesions had clumps of melanin granules in the stratum basale and spinosum. In the dermis, there was marked edema and dense mononuclear cell infiltration. Vasodilation, hemorrhage, and hyperplasia of sebaceous glands were also found. Both dermal mast cells and epidermal Langerhans cells significantly increased in the skin lesions, as compared with nonlesional sites. The present results revealed that constant contact with stainless steel cages (chromium metal) caused contact hypersensitivity in hairless dogs with very sparse hairs. PMID- 17366566 TI - Short-term effects of Quirlan (chlorfenvinphos) on the behavior and acetylcholinesterase activity of Gambusia holbrooki. AB - Chlorfenvinphos is a widespread organophosphorous (OP) insecticide and it is a reported hazardous chemical for aquatic nontarget organisms. This study intended to evaluate the effects of sublethal concentrations of Quirlan(R) (commercial formulation of chlorfenvinphos) on several behavioral parameters of the mosquitofish, Gambusia holbrooki. The insecticide showed high toxicity to G. holbrooki by significantly impairing all the behavioral responses (location in the test vessel, activity/excitability, swimming, and feeding), exhibiting a time dependent pattern. Behavioral EC50s, after a 96-h exposure, ranged from 5.2 to 9.0 microg L(-1). As OP pesticides are acutely neurotoxic, acetylcholinesterase (AChE) activity was also selected for use as a biomarker in this study for the establishment of a relationship with the observed behavior abnormalities. A strong inhibition of AChE was observed in fish exposed to chlorfenvinphos (IC50 = 3.55 microg L(-1)). Behavioral impairment was registered in fish with >40% AChE inhibition levels, while mortality was only observable in fish exhibiting AChE inhibition levels >80%. Additionally, significant correlations were found between behavioral impairment and AChE inhibition, suggesting a mechanistic link. These results show the usefulness of integrating biochemical and individual endpoints in a small-sized model species, and confirm a potential hazard of chlorfenvinphos to nontarget aquatic organisms. PMID- 17366567 TI - Relationship between clinical features and blood levels of pentachlorodibenzofuran in patients with Yusho. AB - BACKGROUND: Yusho is a form of food poisoning that occurred in 1968, as a result of consuming rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins such as polychlorinated dibenzofurans (PCDFs). The victims of Yusho suffered from various dermatological, ophthalmological, and mucosal symptoms in addition to general fatigue, weight loss, anorexia, headache, paresthesia of the extremities, abdominal pain, cough and sputa, dysmenorrhea, and growth retardation in infants and children. We measured the blood levels of dioxins in the annual medical check-up of Yusho patients from 2001 to 2003. PURPOSE: To analyze the relationship between the concentrations of PCDFs/PCBs and the subjective/objective/laboratory findings of patients with Yusho. We also compared the present clinical findings with those collected in 1988. RESULTS AND DISCUSSION: The mean blood level of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) in 359 patients with Yusho was 177.50 pg/g lipids, which was much higher than that of normal controls (15.2 +/- 8.9 pg/g lipids). The blood levels of PeCDF were significantly correlated with total PCB levels, hexachlorobiphenyl levels, urinary sugar, 2-h erythrocyte sedimentation rate, thymol turbidity test, and sodium levels. A significant correlation was also noted with dermatological findings (acneform eruption and comedones), mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. The incidence and severity of most of the dermatological and ophthalmological symptoms decreased from 1988 to 2001-2003. In conclusion, high amounts of PCBs and PeCDF are still present in a number of patients with Yusho. The patients still suffer from various mucocutaneous and subjective symptoms. PMID- 17366568 TI - Mechanism of DNA damage by cadmium and interplay of antioxidant enzymes and agents. AB - Cadmium is an environmental toxicant, which causes cancer in different organs. It was found that it damages DNA in the various tissues and cultured cell lines. To investigate the mechanism of DNA damage, we have studied the effect of cadmium induced DNA damage in plasmid pBR322 DNA, and the possible ameliorative effects of antioxidative agents under in vitro conditions. It was observed that cadmium alone did not cause DNA damage. However, it caused DNA damage in the presence of hydrogen peroxide, in a dose dependent manner, because of production of hydroxyl radicals. Findings from this study show the conversion of covalently closed circular double-stranded pBR 322 DNA to the open circular and linear forms of DNA when treated with 10 muM cadmium and various concentrations of H(2)O(2). The conversion was due to nicking in DNA strands. The observed rate of DNA strand breakage was dependent on H(2)O(2) concentration, temperature, and time. Metallothionein I failed to prevent cadmium-induced DNA nicking in the presence of H(2)O(2). Of the two antioxidant enzymes (catalase and superoxide dismutase) studied, only catalase conferred significant (50-60%) protection. EDTA and DMSO exhibited protection similar to catalase, while mannitol showed only about 20% protection against DNA damage. Ethyl alcohol failed to ameliorate cadmium-induced DNA strands break. From this study, it is plausible to infer that cadmium in the presence of hydrogen peroxide causes DNA damage probably by the formation of hydroxyl ions. These results may indicate that cadmium in vivo could play a major role in the DNA damage induced by oxidative stress. PMID- 17366569 TI - Activation of transcription factor IL-6 (NF-IL-6) and nuclear factor-kappaB (NF kappaB) by lipid ozonation products is crucial to interleukin-8 gene expression in human airway epithelial cells. AB - Ozone (O(3)) is a major component of smog and an inhaled toxicant to the lung. O(3) rapidly reacts with the airway epithelial cell membrane phospholipids to generate lipid ozonation products (LOP). 1-Hydroxy-1-hydroperoxynonane (HHP-C9) is an important LOP, produced from the ozonation of 1-palmitoyl-2-oleoyl-sn glycerol-3-phosphatidylcholine. This LOP, at a biologically relevant concentration (100 microM), increases the activity of phospholipase C, nuclear factors-kappaB (NF-kappaB), and interleukin-6 (NF-IL-6) and the expression of the inflammatory gene, interleukin-8 (IL-8) in a cultured human bronchial epithelial cell line (BEAS-2B). The signaling pathways of ozone and its biologically-active products are as yet undefined. In the present study, we report that the HHP LOP, HHP-C9 (100 microM x 4 h), activated the expression of IL-8 (218 +/- 26% increase over control, n = 4, P < 0.01) through an apparent interaction between the two transcription factors, NF-kappaB and NF-IL-6. Transfection studies using luciferase reporter assays demonstrated that HHP-C9 induced a significant increase in NF-kappaB-DNA binding activity (37 +/- 7% increase over control, n = 6, P < 0.05). Inhibition of NF-kappaB showed a statistically significant but modest decrease in IL-8 release, which suggested a role for another transcription factor, NF-IL-6. Exposure of BEAS-2B cells to HHP-C9 induced a significant increase in the DNA binding activity of NF-IL-6 (45 +/- 11% increase over control, n = 6, P < 0.05). The results of the present study indicate that NF-IL-6 interacts with NF-kappaB in regulating the expression of IL-8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung. PMID- 17366570 TI - Infrasound-induced hemodynamics, ultrastructure, and molecular changes in the rat myocardium. AB - Recent interest in adverse effects of infrasound on organisms arises from health concerns. We assessed the association between infrasound exposure of 5 Hz at 130 dB and changes of cardiac ultrastructure and function in rats. Thirty-two Sprague Dawley rats were randomized into control, 1, 7, and 14 days groups for 2 h of infrasound once daily according to planned schedules. Changes of cardiac ultrastructure, hemodynamics indices, intracellular Ca(2+) concentrations ([Ca(2+)](i)), and sarcoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) were detected. Heart rates in 1 day group were significantly increased compared with control group and no significant changes in other groups. Left ventricular systolic pressures were significantly increased with time. Left ventricular diastolic end pressure and maximum rising rates of left ventricular pressure (+dl/dt) were significantly increased in 7 and 14 days groups and not changed in 1 day group, compared with control group. Maximum dropping rates of left ventricular pressure (-dl/dt) were significantly decreased in 7 and 14 days groups and not changed in 1 day group, compared with control group. In heart cells, there were several swelled mitochondria in 1 day group, more swelled mitochondria in 7 days group, platelet aggregation in the intercellular substance in 14 days group. [Ca(2+)](i) were significantly increased with time. There was a significant increase in SERCA2 in 1 day group, while a significant decrease in 7 and 14 days groups, compared with control group. Infrasound of 5 Hz at 130 dB can damage cardiac ultrastructure and function. Changes of [Ca(2+)](i) and SERCA2 play an important role in the secondary cardiac damage. PMID- 17366571 TI - Testing estrogenicity of known and novel (xeno-)estrogens in the MolDarT using developing zebrafish (Danio rerio). AB - The MolDarT is a novel short-term assay for testing mechanism-based molecular effects in developing zebrafish embryos. The objective of this study was to evaluate the inducibility of vitellogenin1 mRNA (Vtg1) by the estrogenically active compounds 17beta-Estradiol (E2), 17alpha-Ethinylestradiol (EE2), Nonylphenol (NP), Bisphenol A (BPA), Cyproconazol, and the suspected xeno estrogen Atrazin in the MolDarT. Freshly fertilized zebrafish eggs were exposed semistatically for 120 h. Using reverse transcription real-time PCR, the relative abundance of Vtg1 was measured. For EE2 a dose-response relationship was established with EC50 = 60.7 ng/L (205 pM). Induction of Vtg1 was significant at concentrations of 84 pM EE2 (25 ng EE2/L) and above, 10 nM E2 (2.7 microg E2/L), 100 nM E2 (27 microg E2/L), 10 microM BPA (2280 microg BPA/L), and 15 microM BPA (3420 microg BPA/L). At NP concentrations of 0.75 microM (165 microg NP/L) and 1.5 microM (330 microg NP/L) Vtg1 was significantly down-regulated. Both atrazine and cyproconazol showed no effect on relative Vtg1 abundance. With this study we further characterize the MolDarT assay and show its applicability for effect screening of compounds. PMID- 17366572 TI - Oxidative stress in the clam Ruditapes decussatus (Linnaeus, 1758) in relation to polycyclic aromatic hydrocarbon body burden. AB - Seasonal variation of antioxidant enzymes activities (superoxide dismutase, catalase, and glutathione peroxidases) and lipid peroxidation (LPO) were studied in the clam Ruditapes decussatus in relation to body burdens of polycyclic aromatic hydrocarbons (PAHs). Clams were sampled in eight sites from the Ria Formosa lagoon. PAH concentrations were seasonally rather than spatially dependent, being higher in summer (August). Antioxidant enzymes activities and LPO levels in the clam digestive gland were also seasonally dependent. Antioxidant enzymes presented distinct seasonal variations: Mit SOD (superoxide dismutase activity measured in the mitochondrial fraction) was induced in the summer and down-regulated in winter and spring, while Cyt SOD activity (measured in the cytosolic fraction) was highest in autumn and lower in the summer. Neither Mit nor Cyt SOD were related to the clam PAH body burden, suggesting that cells are using other antioxidant systems to eliminate oxyradicals. Catalase (CAT), however, was induced in spring and down-regulated in summer, the inverse of the PAH concentrations in clam tissues. CAT induction in spring appears to be related to the excess of oxyradicals arising from the metabolic activity associated with the reproductive cycle. Conversely, the decrease in CAT activity in the summer may be related to the high water temperatures reached in the Ria Formosa (up to 30 degrees C). Glutathione peroxidases (total fraction - T-GPx and dependent on selenium - Se-GPx) presented a similar seasonal pattern, and were negatively related to PAH concentrations, which may indicate a precarious state of the clams, associated with PAH toxicity. Similarly, LPO was also inversely correlated to the PAH concentrations indicating that increases in PAH concentrations were not causing membrane oxidative damage in R. decussatus digestive gland. The results suggest that antioxidant enzymes in R. decussatus digestive gland are strongly affected by seasonal factors stressing the need of other experiments to clarify the PAHs effect on this clam species. PMID- 17366573 TI - Oscillator mechanism of Notch pathway in the segmentation clock. AB - Somites are formed by periodic segmentation of the presomitic mesoderm (PSM). This periodic event is controlled by the segmentation clock, where Notch signaling plays an essential role. The basic helix-loop-helix factor Hes7, a Notch effector, is cyclically expressed by negative feedback and regulates cyclic expression of Lunatic fringe (Lfng), a Notch modulator. Lfng then seems to periodically inhibit Notch, leading to oscillation in Notch activity. It is thought that these coupled negative feedback loops by Hes7 and Lfng are important for sustained and synchronized oscillations in the PSM. Of interest, another Notch effector, Hes1, is cyclically expressed by many cell types such as neuroblasts, suggesting that this clock is widely distributed and regulates many biological events. This review summarizes the recent finding about roles and mechanism of Notch signaling in the segmentation clock and discusses the significance of Hes1 oscillation in non-PSM cells. PMID- 17366574 TI - Postplasmic/PEM RNAs: a class of localized maternal mRNAs with multiple roles in cell polarity and development in ascidian embryos. AB - Ascidian is a good model to understand the cellular and molecular mechanisms responsible for mRNA localization with the discovery of a large family of localized maternal mRNAs, called postplasmic/PEM RNAs, which includes more than 40 members in three different ascidian species (Halocynthia roretzi, Ciona intestinalis, and C. savignyi). Among these mRNAs, two types (Type I and Type II) have been identified and show two different localization patterns from fertilization to the eight-cell stage. At the eight-cell stage, both types concentrate to a macromolecular cortical structure called CAB (for Centrosome Attracting Body) in the posterior-vegetal B4.1 blastomeres. The CAB is responsible for unequal cleavages and the partitioning of postplasmic/PEM RNAs at the posterior pole of embryos during cleavage stages. It has also been suggested that the CAB region could contain putative germ granules. In this review, we discuss recent data obtained on the distribution of Type I postplasmic/PEM RNAs from oogenesis to late development, in relation to their localization and translational control. We have first regrouped localization patterns for Type I and Type II into a comparative diagram and included all important definitions in the field. We also have made an exhaustive classification of their embryonic expression profiles (Type I or Type II), and analyzed their functions after knockdown and/or overexpression experiments and the role of the 3'-untranslated region (3'UTR) controlling both their localization and translation. Finally, we propose a speculative model integrating recent data, and we also discuss the relationship between postplasmic/PEM RNAs, posterior specification, and germ cell formation in ascidians. PMID- 17366575 TI - Ascidian embryonic development: an emerging model system for the study of cell fate specification in chordates. AB - The ascidian tadpole larva represents the basic body plan of all chordates in a relatively small number of cells and tissue types. Although it had been considered that ascidians develop largely in a determinative way, whereas vertebrates develop in an inductive way, recent studies at the molecular and cellular levels have uncovered several similarities in the way developmental fates are specified. In this review, we describe ascidian embryogenesis and its cell lineages, introduce several characteristics of ascidian embryos, describe recent advances in understanding of the mechanisms of cell fate specification, and discuss them in the context of what is known in vertebrates and other organisms. PMID- 17366576 TI - An oligonucleotide based array-CGH system for detection of genome wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation. AB - Developmental delay (DD) and mental retardation (MR) are important child heath issues with a one percent prevalence. Karyotyping with or without subtelomeric FISH (fluorescent in situ hybridization), unless the phenotype of the patient suggests a specific aberration for a specific FISH assay, is the most common procedure in cytogenetic evaluation of MR/DD. In addition, there are several platforms utilizing microarray based comparative genomic hybridization technology (array-CGH) for genetic testing. Array-CGH can detect deletions or duplications in very small segments of chromosomes and the use of this technology is expected to increase the diagnostic yield. The major limitation of the current BAC based array technologies is the low resolution ( approximately 1 Mb) of the chip and suboptimal coverage particularly in the subtelomeric regions. Our aim was to design a novel array-CGH chip with high-density of probes in the subtelomeric regions as well as to maintain sufficient density in other regions of the genome to provide comprehensive coverage for DD/MR. For this purpose, we used Human Genome CGH Microarray 44B chip (Agilent) as the template for the novel design. Using e-array 4.0 (Agilent), one third of the probes were randomly removed from the array and replaced by 14,000 subtelomeric probes. The average density of the probe coverage is 125 kb and 250-400 probes interrogate subtelomeric regions. To evaluate the array, we tested 15 samples (including subtelomeric aberrations and other microdeletion syndromes), which were previously analyzed by karyotyping and/or FISH. The concordance rate between array results and previous results is 100%. In addition we detected two novel aberrations that were not detected by karyotyping. These results demonstrate the utility of this format of array-CGH in detecting genome wide submicroscopic copy number changes as well as providing comprehensive coverage of all subteleomeric regions. PMID- 17366578 TI - Double paternal nondisjunction in an infant with transient neonatal diabetes mellitus and Klinefelter syndrome. PMID- 17366577 TI - Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome. AB - Cardio-facio-cutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by heart defects, a distinctive facial appearance, ectodermal abnormalities and mental retardation. Clinically, it overlaps with both Noonan syndrome and Costello syndrome, which are caused by mutations in two genes, PTPN11 and HRAS, respectively. Recently, we identified mutations in KRAS and BRAF in 19 of 43 individuals with CFC syndrome, suggesting that dysregulation of the RAS/RAF/MEK/ERK pathway is a molecular basis for CFC syndrome. The purpose of this study was to perform comprehensive mutation analysis in 56 patients with CFC syndrome and to investigate genotype-phenotype correlation. We analyzed KRAS, BRAF, and MAP2K1/2 (MEK1/2) in 13 new CFC patients and identified five BRAF and one MAP2K1 mutations in nine patients. We detected one MAP2K1 mutation in three patients and four new MAP2K2 mutations in four patients out of 24 patients without KRAS or BRAF mutations in the previous study [Niihori et al., 2006]. No mutations were identified in MAPK3/1 (ERK1/2) in 21 patients without any mutations. In total, 35 of 56 (62.5%) patients with CFC syndrome had mutations (3 in KRAS, 24 in BRAF, and 8 in MAP2K1/2). No significant differences in clinical manifestations were found among 3 KRAS-positive patients, 16 BRAF-positive patients, and 6 MAP2K1/2-positive patients. Wrinkled palms and soles, hyperpigmentation and joint hyperextension, which have been commonly reported in Costello syndrome but not in CFC syndrome, were observed in 30-40% of the mutation-positive CFC patients, suggesting a significant clinical overlap between these two syndromes. PMID- 17366579 TI - Familial neonatal Marfan syndrome due to parental mosaicism of a missense mutation in the FBN1 gene. AB - We present a family in which three siblings were born with neonatal Marfan syndrome (MFS) to unaffected parents. The clinical findings included joint contractures, large ears, loose skin, ectopia lentis, muscular hypoplasia, aortic root dilatation, mitral and tricuspid valve insufficiency, and pulmonary emphysema. All three siblings died due to cardiorespiratory insufficiency by 2-4 months of age. Screening of the FBN1 gene showed the heterozygous c.3257G > A (p.Cys1086Tyr) mutation in the proband. Mosaicism of the mutation was demonstrated in the somatic cells and in the germ line of the father. Although three examples of parental mosaicism for classical MFS were demonstrated previously, this is the first report of familial occurrence of neonatal MFS due to a heterozygous mutation in FBN1. In conclusion, the p.Cys1086Tyr mutation in FBN1 is consistently associated with neonatal MFS. Parental mosaicism should always be kept in mind when counseling families with MFS. PMID- 17366580 TI - Novel oral findings in Schimmelpenning syndrome. AB - We report a patient with Schimmelpenning syndrome with two previously unreported oral manifestations: multiple pigmented malformed teeth and an adenomatoid odontogenic tumor of the anterior mandible. Also found were multiple complex odontomas, bilateral maxillary fibro-osseous lesions and recurrent central giant cell granulomas of the jaws. PMID- 17366581 TI - Spondylothoracic dysplasia: prenatal diagnosis and the problems of nosologic overlap. PMID- 17366582 TI - Clinical lumping and molecular splitting of LEOPARD and NF1/NF1-Noonan syndromes. PMID- 17366583 TI - Spinal extradural arachnoid cysts associated with distichiasis and lymphedema. AB - Spinal extradural arachnoid cysts (SEDAC) are lesions communicating to the subarachnoid space of the spinal canal via a dural defect. SEDAC occupies intraspinal space and sometimes causes neurological disturbances. Although most reported cases are sporadic, several familial cases have been described, suggesting a genetic etiology. Here we report on a family with SEDAC inherited in an autosomal dominant mode. Detailed study showed that the family has the lymphedema-distichiasis syndrome. Among family members examined, a total of ten in two generations manifested all or some of the following features: SEDAC, distichiasis and lymphedema. Seven had spinal cysts, four had both SEDAC and distichiasis, and one had SEDAC distichiasis and lymphedema; three did not have SEDAC. These findings, together with rarity of both distichiasis and lymphedema in the general population, support that all of the ten members were affected with one clinical entity, the lymphedema-distichiasis syndrome. The distribution of features illustrates the variable expressivity of clinical manifestations. Although FOXC2 mutation analysis was not performed in our family, it is likely that SEDAC is a component manifestation of lymphedema-distichiasis syndrome and more consistent in our family than those reported. PMID- 17366584 TI - What to call a syndrome. PMID- 17366585 TI - Risk factors for poor bone health in adolescents and adults with CHARGE syndrome. AB - CHARGE syndrome, is associated with genital hypoplasia, feeding difficulties and delayed puberty. In this study we examined the prevalence of risk factors for poor bone health in adolescents and adults with CHARGE. Questionnaires assessing fracture history, dietary intake of calcium and vitamin D, pubertal status and activity level using the Habitual Activity Estimation Scale (HAES) were completed by caregivers. Control data were collected for the HAES. When available, reports from dual-energy X-ray absorptiometry (DEXA) were obtained. Thirty individuals with CHARGE syndrome (n = 15 males; n = 15 females; age range 13 to 34 years; mean age 19.6 years) were recruited. Traumatic bony fractures were identified in 30% of the population. The recommended nutritional intake (RNI) for calcium and vitamin D were not met by 41% and 87% of the population, respectively, and 53% required past tube feeding. Delayed puberty was experienced by 87% with only 4 individuals (2 female, 2 males) having experienced normal puberty. Hormone replacement therapy (HRT) was taken by 33% of females and 60% of males. According to the HAES, adolescents with CHARGE syndrome (13-18 years) were significantly less active than controls. Individuals with CHARGE syndrome age 19 and older were also less active than controls, although this difference was not significant. DEXA scan data was obtained, however, due to small sample size (n = 10) and confounding variables (i.e., short stature, pubertal stage, height, weight), it was difficult to draw meaningful conclusions. Feeding difficulties, inactivity and hypogonadism are predisposing factors for the development of poor bone health among individuals with CHARGE syndrome. Education is necessary to raise awareness regarding the importance of HRT, proper nutrition and weight-bearing activity for healthy bone development and maintenance in individuals with CHARGE syndrome. PMID- 17366586 TI - Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. PMID- 17366587 TI - Abstracts from the 28th Annual Meeting of the American Society for Apheresis. April 18-21, 2007. Nashville, Tennessee, USA. PMID- 17366588 TI - Soft tissue sarcomas. PMID- 17366589 TI - Phase II trial of irinotecan and cisplatin with early concurrent radiotherapy in limited-disease small-cell lung cancer. AB - BACKGROUND: A Phase II trial of irinotecan and cisplatin (IP) with early concurrent radiotherapy was performed in limited-disease small-cell lung cancer (LD-SCLC) to evaluate the efficacy and toxicity. METHODS: For untreated LD-SCLC patients, irinotecan (60 mg/m2, Days 1, 8, and 15) and cisplatin (40 mg/m2, Days 1 and 8) were repeated every 4 weeks for a maximum of 6 cycles. Thoracic radiotherapy of 1.8 Gy/day was begun on Day 1 of the second chemotherapy cycle, up to a total of 45 to 54 Gy. Prophylactic cranial irradiation (30 Gy in 10 fractions) was performed on patients with a complete response (CR). RESULTS: Thirty-three LD-SCLC patients were enrolled. The median age was 60 years and 31 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Twelve (36.4%) patients had N3 disease. The response rate was 87.9%, with a CR rate of 45.5%. At a median follow-up period of 27 months the median progression-free survival (PFS) and overall survival (OS) were 14.4 and 26.1 months, respectively, with 2-year PFS and OS rates of 26.8% and 54.9%. The dominating toxicity was neutropenia, with grade 3-5 of 81.8%. The most common grade 3-5 nonhematologic toxicities were diarrhea (21.2%), anorexia (21.2%), and fatigue (21.2%). Grade 3-5 radiation esophagitis and pneumonitis occurred in 18.2% and 9.1% of patients, respectively. There were 2 treatment-related deaths from sepsis and radiation pneumonitis. CONCLUSIONS: IP with early concurrent radiotherapy was effective and tolerable in untreated LD-SCLC. PMID- 17366590 TI - Modulation of muscle activity and force fluctuations in the plantarflexors after bedrest depends on knee position. AB - Force fluctuations in leg muscles increase after bedrest, perhaps due to modulation of the neural strategy that is specific to a muscle or common to agonist muscles. The purpose of this study was to examine the modulation of muscle activity and force fluctuations during steady contractions with variable involvement of plantarflexor muscles after bedrest at knee-flexed (FLX) and extended (EXT) positions. Before and after 20-day bedrest, plantarflexion force and surface electromyogram (EMG) in the medial gastrocnemius (MG), lateral gastrocnemius, and soleus muscles were measured during steady isometric contractions in five young men. In EXT, power 16% aromatic amino acids), PxAry1 and PxAry2 belong to the arylphorin-like protein genes. Analysis using Northern hybridization and RT-PCR showed varying levels of genes expression in the developmental stages with a small difference between sexes. Expression of both genes in fourth instar larvae was suppressed after treatment with a JH analog. Southern hybridization revealed the presence of multiple arylphorin genes in the genome. PMID- 17366600 TI - Identification of a putative azadirachtin-binding complex from Drosophila Kc167 cells. AB - Cell-proliferation in Drosophila Kc167 cells was inhibited by 50% when cell cultures contained 1.7 x 10(-7) M azadirachtin for 48 h (a tertranortriterpenoid from the neem tree Azadirachta indica). Drosophila Kc167 cells exhibited direct nuclear damage within 6-h exposure to azadirachtin (5 x 10(-7) M and above) or within 24 h when lower concentrations were used (1 x 10(-9) M). Fractionation of an extract of Drosophila Kc167 cells combined with ligand overlay technique resulted in the identification of a putative azadirachtin binding complex. Identification of the members of this complex by Peptide Mass Fingerprinting (PMF) and N-terminal sequencing identified heat shock protein 60 (hsp60) as one of its components. PMID- 17366601 TI - Expression and function of cathepsin B-like proteinase in larval hemocytes of Helicoverpa armigera during metamorphosis. AB - Previous work has revealed that Helicoverpa armigera cathepsin B-like proteinase (HCB) is expressed in oocytes as well as fat bodies of pupae and adults. It plays key roles in the degradation of yolk proteins during embryogenesis and the decomposition of adult fat bodies of H. armigera. This study investigated the expression and function of HCB in larval hemocytes during larva-pupa metamorphosis. Results showed that the expression of HCB in hemocytes exhibited developmental stage specificity. No HCB was found in hemocytes from 5th-molting larvae. On the contrary, HCB was highly transcribed in the hemocytes from 6th-48 h larvae. Besides, it was abundantly translated in 6th-96-h larvae (prepupation). HCB is mainly expressed in plasmatocytes and granulocytes at both transcriptional and translational levels. The number of plasmatocytes and granulocytes markedly increased before pupation. In addition, hemocytes distributed in hematopoietic organs at early larval stage, then migrated to midgut and fat bodies that would undergo histolysis at later larval stage. These findings suggested that HCB is expressed in H. armigera larval hemocytes and involved in larva-pupa metamorphosis. PMID- 17366602 TI - COPS3 amplification and clinical outcome in osteosarcoma. AB - BACKGROUND: Amplification of several genes that map to a region of chromosome 17p11.2, including COPS3, was observed in high-grade osteosarcoma. These genes were also shown to be overexpressed and may be involved in osteosarcoma tumorigenesis. COPS3 encodes a subunit of the COP9 signalosome implicated in the ubiquitination and ultimately degradation of the P53 tumor suppressor. To determine the relation between COPS3 amplification, P53 mutation, and patient outcome in osteosarcoma, tumors from a large cohort of patients with high-grade osteosarcoma and long-term clinical follow-up were examined. METHODS: Quantitative real-time polymerase chain reaction (PCR) was performed to detect copy number changes for COPS3, as well as additional genes (NCOR1, TOM1L2, and PMP22) from the 17p11.2 amplicon, in 155 osteosarcomas from a prospective collection of tumors with corresponding clinical data. Univariate and multivariate analyses were performed to assess differences in survival between groups. RESULTS: Amplification of COPS3, detected in 31% of the osteosarcomas, was strongly associated with large tumor size (P=.0009), but was not associated with age at diagnosis, site, sex, and tumor necrosis. COPS3 amplification was significantly correlated with a shorter time to metastasis with an estimated hazard ratio (HR) of 1.61 (95% confidence interval [CI], 1.02-2.55) in univariate analysis (log-rank test, P=.042). However, in an a priori multivariate Cox model including the other clinical parameters, the HR for COPS3 amplification decreased to 1.32 (95% CI, 0.82-2.13, P=.25), mainly due to the strong correlation with tumor size. COPS3 amplification and P53 mutation frequently occurred in the same tumors, suggesting that these are not mutually exclusive events in osteosarcoma. Although not statistically significant, patients whose tumors exhibited both molecular alterations tended to be more likely to develop metastasis compared with patients with either COPS3 amplification or P53 mutation alone. CONCLUSIONS: COPS3 is the likely target of the 17p11.2 amplicon. COPS3 may function as an oncogene in osteosarcoma, and an increased copy number may lead to an unfavorable prognosis. PMID- 17366603 TI - Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival. AB - BACKGROUND: The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival. METHODS: ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients. RESULTS: In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR]=0.46, 95% confidence interval [CI]: 0.30-0.73 and HR=0.52, 95% CI: 0.33-0.81, respectively) and overall survival (HR=0.56, 95% CI: 0.35-0.92 and HR=0.70, 95% CI: 0.43-1.13, respectively). CONCLUSIONS: The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis. PMID- 17366604 TI - Area map of mouse visual cortex. AB - It is controversial whether mouse extrastriate cortex has a "simple" organization in which lateral primary visual cortex (V1) is adjoined by a single area V2 or has a "complex" organization, in which lateral V1 is adjoined by multiple distinct areas, all of which share the vertical meridian with V1. Resolving this issue is important for understanding the evolution and development of cortical arealization. We have used triple pathway tracing combined with receptive field recordings to map azimuth and elevation in the same brain and have referenced these maps against callosal landmarks. We found that V1 projects to 15 cortical fields. At least nine of these contain maps with complete and orderly representations of the entire visual hemifield and therefore represent distinct areas. One of these, PM, adjoins V1 at the medial border. Five areas, P, LM, AL, RL, and A, adjoin V1 on the lateral border, but only LM shares the vertical meridian representation with V1. This suggests that LM is homologous to V2 and that the lateral extrastriate areas do not represent modules within a single area V2. Thus, mouse visual cortex is "simple" in the sense that lateral V1 is adjoined by a single V2-like area, LM, and "complex" in having a string of areas in lateral extrastriate cortex, which receive direct V1 input. The results suggest that large numbers of areas with topologically equivalent maps of the visual field emerge early in evolution and that homologous areas are inherited in different mammalian lineages. PMID- 17366605 TI - Dopamine D(4) receptor activation decreases the expression of mu-opioid receptors in the rat striatum. AB - The dopaminergic and opioid peptide systems interact in many nuclei of the brain. In the striatum, dopamine/opioid peptide interactions modulate locomotor and motivated behaviors as well as reward, motivational, and tolerance processes in opiate dependence. Dopamine D(4) receptors (D(4) R) and mu-opioid receptors (MOR) are highly concentrated in the striosomes (islands) of the striatum, suggesting the existence of receptor-receptor interactions between them. In the present work we studied the role of D(4) R in modulating MOR expression in the islands by using immunohistochemistry and image analysis. The activation of D(4) R by the agonist PD168,077 (1 mg/kg) decreased MOR immunoreactivity (IR) in the striosomes 6 hours after drug treatment. MOR IR levels had recovered 12 hours later. Treatment with a D(4) R antagonist (L745,870, 1mg/kg) blocked downregulation of MOR IR, showing that the D(4) R agonist effects observed were specific. Furthermore, treatment with the D(2)/D(3) receptor agonist quinpirol (1 mg/kg) and D(2)/D(3) receptor antagonist raclopride (1 mg/kg) had no effect in MOR IR, suggesting that D(4) R is the only D2-like receptor producing an MOR downregulation in the islands. The decreases of MOR IR in the striosomes suggest that D(4) R activation may reduce MOR signaling. Increasing evidence has demonstrated that the islands in the striatum play a critical role in habit acquisition during drug addiction. D(4) R/MOR interactions could be crucial in such processes. PMID- 17366606 TI - Nonintegrin laminin receptor precursor protein is expressed on olfactory stem and progenitor cells. AB - The biochemical identification and immunocytochemical characterization of a cell surface antigen, expressed on globose basal cells (GBCs) of the rodent olfactory epithelium (OE), are described. The monoclonal antibody (MAb) GBC-3 recognizes a surface protein, confirmed by both live cell staining and fluorescence-activated cell sorting. Two-dimensional SDS-PAGE/Western blot followed by tandem mass spectrometry demonstrates that the cell surface GBC-3 antigen is the 40 kDa laminin receptor precursor protein. The MAb GBC-3 labels the vast majority of cells among the GBC population and does not stain either sustentacular cells or horizontal basal cells (HBCs) in the normal rat OE. After epithelial lesion by exposure to methyl bromide, the remaining cells, which are mostly GBCs, are heavily stained by GBC-3, and colabeled with GBC-3 and sustentacular cell or HBC markers. GBC-3 will be a potentially useful tool for identifying and characterizing GBCs. PMID- 17366607 TI - Patterns of SDF-1alpha and SDF-1gamma mRNAs, migration pathways, and phenotypes of CXCR4-expressing neurons in the developing rat telencephalon. AB - Cortical GABAergic neurons originate in the ventral telencephalon, invade the cortex via tangential migration, and integrate into the cortical plate by surface directed and ventricle-directed migration. In mice lacking CXCR4 or SDF-1, GABAergic neurons fail to complete their migration. It is presently unknown which parts of the migration of CXCR4-expressing GABAergic neurons are driven by SDF-1. Here we compared patterns of SDF-1 isoforms and CXCR4 in the developing rat telencephalon. In the ventral telencephalon, radial glia, striatal, and migratory GABAergic neurons expressed CXCR4. Tangentially migrating CXCR4-expressing neurons populated the marginal zone and started to invade the lateral intermediate zone at embryonic day (E)14. Until E17 the spread of CXCR4 expressing neurons in the dorsomedial direction was accompanied by progressive upregulation of SDF-1alpha in the dorsomedial intermediate/subventricular zone. In the meninges, SDF-1alpha and SDF-1gamma were expressed persistently. During invasion of the cortical plate the orientation of CXCR4-immunoreactive neurons changed gradually from tangential (E17/E18) to radial (postnatal day [P] 0), which was paralleled by downregulation of SDF-1alpha in the intermediate/subventricular zone. At E17, CXCR4-immunoreactive cells were colabeled with markers for ventral forebrain-derived neurons (Dlx) but not markers for glutamatergic (Tbr) or subplate (calretinin) neurons. Postnatally, calretinin- and somatostatin-expressing but not parvalbumin-expressing GABAergic neurons or pyramidal cells contained CXCR4. Pyramidal cells and few large blood vessels expressed SDF-1alpha, while microvessels contained SDF-1gamma transcripts. In summary, SDF-1alpha is expressed along cortical but not subcortical migration routes of GABAergic neurons. We propose that regulated expression of SDF-1 in the intermediate/subventricular zone influences lateromedial tangential migration of CXCR4-expressing GABAergic neurons. PMID- 17366609 TI - Organization of sensory neocortex in prairie voles (Microtus ochrogaster). AB - In the current investigation, the functional organization of visual, auditory, and somatosensory cortex was examined in prairie voles (Microtus ochrogaster) by using electrophysiological recording techniques. Functional boundaries of cortical fields were directly related to myeloarchitectonic boundaries. Our results demonstrated that most of the neocortex is occupied by the visual, auditory, and somatosensory areas. Specifically, a small area 17, or primary visual area (V1), was located on the caudomedial pole of the neocortex; a large auditory cortex (AC), which contains the primary auditory area (A1) and other auditory fields, encompassed almost the entire temporal pole; and a large area 3b, or primary somatosensory area (S1), contained a complete representation of the contralateral body surface. Furthermore, these areas were coextensive with distinct myeloarchitectonic appearances. We also observed that the AC appeared to be disproportionately large in the prairie vole compared with other rodents. In addition, we found that both primary and nonprimary areas contained neurons that responded to auditory stimulation. Finally, we observed within S1 a disproportionate amount of cortex that was devoted to representing the perioral hairs and the snout and also that neurons within this representation had very small receptive fields. We discuss the expanded auditory domain and the enlarged representation of perioral hairs as they relate to the specialized life style of the prairie vole. PMID- 17366610 TI - Immunohistochemical characterization of substance P receptor (NK(1)R)-expressing interneurons in the entorhinal cortex. AB - It has been reported that application of substance P (SP) to the medial portion of the entorhinal cortex (EC) induces a powerful antiepileptic effect (Maubach et al. [1998] Neuroscience 83:1047-1062). This effect is presumably mediated via inhibitory interneurons expressing the neurokinin-1 receptor (NK(1)R), but the existence of NK(1)R-expressing inhibitory interneurons in the EC has not yet been reported. The present immunohistochemical study was performed in the rat to examine the existence and distribution of NK(1)R-expressing neurons in the EC as well as any co-expression of other neurotransmitters/neuromodulators known to be associated with inhibitory interneurons: gamma-aminobutyric acid (GABA), parvalbumin (PARV), calretinin (CT), calbindin (CB), somatostatin (SST), and neuropeptide Y (NPY). Our results indicated that NK(1)R-positive neurons were distributed rather sparsely (especially in the medial EC), primarily in layers II, V, and VI. The results of our double-immunohistochemical staining indicated that the vast majority of NK(1)R-expressing neurons also expressed GABA, SST, and NPY. In addition, CT was co-expressed in a weakly stained subgroup of NK(1)R expressing neurons, and CB was co-expressed very rarely in the lateral EC, but not in the medial EC. In contrast, SP-immunopositive axons with fine varicosities were distributed diffusely throughout all layers of the EC, appearing to radiate from the angular bundle. SP may be released in a paracrine manner to activate a group of NK(1)R-expressing entorhinal neurons that co-express GABA, SST, and NPY, exerting a profound inhibitory influence on synchronized network activity in the EC. PMID- 17366608 TI - Development of N-methyl-D-aspartate receptor subunits in avian auditory brainstem. AB - N-methyl-D-aspartate (NMDA) receptor subunit-specific probes were used to characterize developmental changes in the distribution of excitatory amino acid receptors in the chicken's auditory brainstem nuclei. Although NR1 subunit expression does not change greatly during the development of the cochlear nuclei in the chicken (Tang and Carr [2004] Hear. Res 191:79-89), there are significant developmental changes in NR2 subunit expression. We used in situ hybridization against NR1, NR2A, NR2B, NR2C, and NR2D to compare NR1 and NR2 expression during development. All five NMDA subunits were expressed in the auditory brainstem before embryonic day (E) 10, when electrical activity and synaptic responses appear in the nucleus magnocellularis (NM) and the nucleus laminaris (NL). At this time, the dominant form of the receptor appeared to contain NR1 and NR2B. NR2A appeared to replace NR2B by E14, a time that coincides with synaptic refinement and evoked auditory responses. NR2C did not change greatly during auditory development, whereas NR2D increased from E10 and remained at fairly high levels into adulthood. Thus changes in NMDA NR2 receptor subunits may contribute to the development of auditory brainstem responses in the chick. PMID- 17366611 TI - OFF midget bipolar cells in the retina of the marmoset, Callithrix jacchus, express AMPA receptors. AB - Recent studies suggested that different types of OFF bipolar cells express specific types of ionotropic (AMPA or kainate) glutamate receptors (GluRs) at their contacts with cone pedicles. However, the question of which GluR type is expressed by which type of OFF bipolar cell in primate retina is still open. In this study, the expression of AMPA and kainate receptor subunits at the dendritic tips of flat (OFF) midget bipolar (FMB) cells was analyzed in the retina of the common marmoset, Callithrix jacchus. We used preembedding electron microscopy and double immunofluorescence with subunit-specific antibodies. The FMB cells were labeled with antibodies against the carbohydrate epitope CD15. Cone pedicles were identified with peanut agglutinin. Immunoreactivity for the GluR1 subunit and for CD15 is preferentially located at triad-associated flat contacts. Furthermore, the large majority of GluR1 immunoreactive puncta is localized at the dendritic tips of FMB cells. These results suggest that FMB cells express the AMPA receptor subunit GluR1. In contrast, the kainate receptor subunit GluR5 is not colocalized with the dendritic tips of FMB cells or with the GluR1 subunit. Immunoreactive puncta for the GluR1 subunit are found at all M/L-cone pedicles but are only rarely associated with S-cone pedicles. This is consistent with our recent findings in marmoset retina that FMB cells do not contact S-cone pedicles. The presence of GluR5 clusters at S-cone pedicles indicates that in primate retinas OFF bipolar cells expressing kainate receptor subunits receive some S-cone input. PMID- 17366612 TI - Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. AB - Catecholamine-containing projections from the medulla have been implicated in the mediation of activational responses of the paraventricular nucleus of the hypothalamus (PVH) provoked by moderate doses of interleukin-1 (IL-1). To test the generality of this mechanism, rats bearing unilateral transections of aminergic projections were challenged with intravenous IL-1 (2 microg/kg), bacterial lipopolysaccharide (LPS; 0.1, 2.0, or 100 microg/kg), or saline and perfused 3 hours later; their brains were then prepared for quantitative analysis of Fos induction and relative levels of corticotropin-releasing factor (CRF) mRNA. LPS provoked a robust and dose-related increase in Fos expression within the PVH on the intact side of the brain at all doses tested; the response to IL-1 approximated that to the lowest LPS dose. On the lesioned side, Fos induction was significantly reduced at all dosage levels but was eliminated only at the lowest dosage. The percentage reduction was greatest (75%) in IL-1-challenged rats and was progressively less in animals treated with increasing LPS doses (67, 59, and 46%, respectively). Specificity of aminergic involvement was tested by using intra-PVH administration of the axonally transported catecholamine immunotoxin, antiDBH-saporin. This treatment abolished IL-1-induced elevations of Fos-ir and CRF mRNA in the PVH but left intact comparable responses to restraint stress. These data support a specific involvement of ascending catecholaminergic projections in mediating PVH responses to IL-1 and LPS. Residual Fos induction seen in lesioned animals in response to higher doses of LPS provides a basis for probing additional circuits that may be recruited in a hierarchical manner in response to more strenuous or complex immune insults. PMID- 17366615 TI - Rapid hyperspectral fluorescence lifetime imaging. AB - We report a rapid hyperspectral fluorescence lifetime imaging (FLIM) instrument that exploits high-speed FLIM technology in a line-scanning microscope. We demonstrate the acquisition of whole-field optically sectioned hyperspectral fluorescence lifetime image stacks (with 32 spectral bins) in less than 40 s and illustrate its application to unstained biological tissue. PMID- 17366613 TI - Odorants with multiple oxygen-containing functional groups and other odorants with high water solubility preferentially activate posterior olfactory bulb glomeruli. AB - In past studies in which we mapped 2-deoxyglucose uptake evoked by systematically different odorant chemicals across the entire rat olfactory bulb, glomerular responses could be related to each odorant's particular oxygen-containing functional group. In the present study we tested whether aliphatic odorants containing two such functional groups (esters, ketones, acids, alcohols, and ethers) would stimulate the combination of glomerular regions that are associated with each of the functional groups separately, or whether they would evoke unique responses in different regions of the bulb. We found that these very highly water soluble molecules rarely evoked activity in the regions responding to the individual functional groups; instead, they activated posterior glomeruli located about halfway between the dorsal and ventral extremes in both the lateral and the medial aspects of the bulb. Additional highly water-soluble odorants, including very small molecules with single oxygenic groups, also strongly stimulated these posterior regions, resulting in a statistically significant correlation between posterior 2-deoxyglucose uptake and molecular properties associated with water solubility. By showing that highly water-soluble odorants stimulate a part of the bulb associated with peripheral and ventral regions of the epithelium, our results challenge a prevalent notion that such odorants would activate class I odorant receptors located in zone 1 of the olfactory epithelium, which projects to the dorsal aspect of the bulb. PMID- 17366616 TI - SLIM: a new method for molecular imaging. AB - We used spectrally resolved fluorescence lifetime imaging (SLIM) to investigate the mitochondria staining dye rhodamine 123 and binding of DAPI to RNA and DNA in cells. Moreover, different components of the photosensitizer Photofrin were resolved in cell cultures by SLIM. To record lifetime images (tau-mapping) with spectral resolution we used a laser scanning microscope equipped with a spectrograph, a 16 channel multianode PMT, and multidimensional time-correlated single photon counting. A Ti:Saphir laser was used for excitation or alternatively a ps diode laser. With this system the time- and spectral-resolved fluorescence characteristics of different fluorophores were investigated in cell cultures. As an example, the mitochondria staining dye rhodamine I23 could be easily distinguished from DAPI, which binds to nucleic acids. Also different binding sites of DAPI could be discriminated. This was proved by the appearance of different lifetime components within different spectral channels. Moreover, we were able to detect monomeric and aggregated forms of Photofrin in cells. Different lifetimes could be attributed to the various compounds. In addition, a detailed analysis of the autofluorescence by SLIM could explain changes of mitochondrial metabolism during Photofrin-PDT. PMID- 17366617 TI - Alpha-T-catenin (CTNNA3) displays tumour specific monoallelic expression in urothelial carcinoma of the bladder. AB - CTNNA3 (alpha-T-catenin) is imprinted with preferential monoallelic expression of the maternal allele in placental tissue. The allelic expression pattern of CTNNA3 in adult human cancer is unknown and warrants investigation as CTNNA3 stabilizes cellular adherence, a feature which if compromised could enable cells to acquire an increased capability to detach and invade. We document the frequency of monoallelic versus biallelic expression of CTNNA3 in urothelial carcinoma of the bladder (UCB) samples and compare the observed patterns with that found in the paired normal sample. DNA PCR reactions encompassing a transcribable SNP polymorphism within exon 12 of CTNNA3 were sequence analyzed to identify heterozygous cases. A total of 96 samples were analyzed and included 22 paired normal and tumor UCB cases, 38 formalin fixed paraffin embedded (FFPE) UCB samples consisting of 18 noninvasive pTa tumors and 20 lamina propria invasive pT1 tumors and 14 cell lines of various lineages. RT-PCR analysis of 35 heterozygous samples followed by sequence analysis allowed monoallelic versus biallelic patterns to be assigned. We have provided the first demonstration that CTNNA3 displays differing allelic expression patterns in UCB. Specifically, 35% (7/20) of informative UCB, showed monoallelic expression, a feature confined to the tumor, with normal urothelial samples displaying biallelic expression. Real time RT-PCR analyses, demonstrated a significantly lower (P = 0.00039) level of CTNNA3 in the tumor samples compared with the paired normals, all of which displayed biallelic expression. In conclusion, monoallelic and biallelic CTNNA3 expression patterns are demonstrable in tumor bladder tissue, whereas normal cases show only biallelic expression. PMID- 17366618 TI - DNA repair pathways involved in anaphase bridge formation. AB - Cancer cells frequently exhibit gross chromosomal alterations such as translocations, deletions, or gene amplifications an important source of chromosomal instability in malignant cells. One of the better-documented examples is the formation of anaphase bridges-chromosomes pulled in opposite directions by the spindle apparatus. Anaphase bridges are associated with DNA double strand breaks (DSBs). While the majority of DSBs are repaired correctly, to restore the original chromosome structure, incorrect fusion events also occur leading to bridging. To identify the cellular repair pathways used to form these aberrant structures, we tested a requirement for either of the two major DSB repair pathways in mammalian cells: homologous recombination (HR) and nonhomologous end joining (NHEJ). Our observations show that neither pathway is essential, but NHEJ helps prevent bridges. When NHEJ is compromised, the cell appears to use HR to repair the break, resulting in increased anaphase bridge formation. Moreover, intrinsic NHEJ activity of different cell lines appears to have a positive trend with induction of bridges from DNA damage. PMID- 17366619 TI - Genetic variation of antigen processing machinery components and association with cervical carcinoma. AB - The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of several APM components is associated with progression and clinical outcome in cervical carcinoma. Genetic variation in the genes encoding APM components is known to be associated with risk of occurrence of several malignancies. However, only limited evidence exists supporting the role of single nucleotide polymorphisms (SNPs) in APM components in cervical carcinoma. We have therefore investigated the occurrence of APM component SNP genotypes and haplotypes in cervical carcinoma. Thirteen coding SNPs in the LMP2, LMP7, TAP1, TAP2, and ERAP1 genes were genotyped in 127 cervical carcinoma patients and 124 controls. Individual genotype and allele distributions were assessed by single-marker analysis. Effects of various SNP combinations were estimated by haplotype construction and subsequent haplotype interaction analysis. Significant haplotypes were modeled on disease risk. Allele distributions at the LMP7-145, TAP2-651, ERAP1-127, and ERAP1-730 loci differed significantly between cases and controls with the major allele at the LMP7 and TAP2 loci and the minor allele at both ERAP1 loci associated with increased cervical carcinoma risk. A combination of the two haplotypes spanning these loci was associated with a three-fold increased risk (OR = 3.024; P << 0.001); approximately 12% of all cervical carcinoma occurrences were attributable to this combination. Our data indicate that combined genetic variation in the TAP2, LMP7, and ERAP1 genes is associated with increased cervical carcinoma risk. PMID- 17366620 TI - Egg jelly of the newt, Cynops pyrrhogaster contains a factor essential for sperm binding to the vitelline envelope. AB - The acrosome reaction of newt sperm is induced at the surface of egg jelly and the acrosome-reacted sperm acquire the ability to bind to the vitelline envelope. However, because the substance that induces the acrosome reaction has not been identified, the mechanism by which the acrosome-reacted sperm bind to the vitelline envelope remains unclear. We found here that a Dolichos biforus agglutinin (DBA) specifically mimicked the acrosome reaction immediately upon its addition in the presence of milimolar level Ca(2+). Fluorescein isothiocyanate labeled DBA bound specifically to the acrosomal cap of the intact sperm in the presence of a Ca(2+)-chelating agent, EDTA, suggesting that binding of DBA to the native receptor for the egg jelly substance on the acrosomal region took the place of the egg jelly substance-induced acrosome reaction. In contrast, the sperm that had been acrosome reacted by DBA treatment did not bind to the vitelline envelope of the egg whose jelly layers were removed. Subsequent addition of jelly extract caused the sperm binding to vitelline envelope, indicating that the egg jelly of the newt contains substances that are involved in not only inducing the acrosome reaction but also binding to the vitelline envelope. This is the first demonstration of the involvement of egg jelly substance in the binding of acrosome-reacted sperm to the vitelline envelope. PMID- 17366621 TI - Chromatophore distribution and inferior performance of albino Japanese flounder Paralichthys olivaceus with special reference to different chromatophore expression between albinism and pseudo-albinism. AB - Albinism with a large variation in body color was found in a hatchery population of Japanese flounder. In addition to albinism, ambicoloration and pseudo-albinism were simultaneously observed in some individuals. Albinos had a remarkably lower number of melanophores on the scales of ocular side than wild-type individuals did, although no significant difference was observed in the numbers of xanthophores and iridophores. The intensity of body color significantly correlated with the number of melanophores among the albinos. No significant differences were observed in the intensity of body color and the number of melanophores between the ocular side and the ambicoloration area. Pseudo-albinism was accompanied by the reductions of melanophores and xanthophores, indicating the different expression patterns of chromatophores between albinism and pseudo albinism. The combined effects of albinism and pseudo-albinism caused the disappearances of melanophores and xanthophores in the pseudo-albinism area of albinos. In addition to chromatophores, the different characteristics of several phenotypic traits were observed between albinos and wild-type individuals. Growth related traits of the albinos were inferior to those of the wild-type individuals. Furthermore, the albinos had a larger pseudo-albinism area and a higher vertebral deformed rate than the wild-type individuals did. Individual multilocus heterozygosity and inbreeding coefficient measured by microsatellite loci did not show any indication that the albinos had higher inbreeding coefficient than the wild-type individuals did. This study demonstrated the expression patterns of chromatophores in the body color abnormalities of a flatfish species and the potential pleiotropic effects of an albinism gene on some phenotypic traits. PMID- 17366622 TI - Estimating the active metabolic rate (AMR) in fish based on tail beat frequency (TBF) and body mass. AB - Tail beat frequency (TBF) was measured for carp (Cyprinus carpio) and roach (Rutilus rutilus), during steady swimming at five different speeds and for fish of various body masses. A multiple stepwise linear regression analysis resulted in models for the prediction of TBFs depending on swimming speed as an independent variable. Speed explained 72 and 86% of the variance in TBF for carp and roach, respectively. By using these data to predict TBF from speed and substituting values into a model from a previous study that predicts active metabolic rates (AMR) from body mass and swimming speed, we can calculate AMR from only fish mass and TBF. Thus, the derived models can be used to estimate the AMR in fish by measuring TBFs in the field using biotelemetry. The approach presented here is a useful and relatively simple tool for estimating the activity metabolism in free-swimming fish. In future studies this method should be applied to a larger and more representative sample size to test the applicability and the validity for a broader range of species. PMID- 17366623 TI - Projecting 2D gene expression data into 3D and 4D space. AB - Video games typically generate virtual 3D objects by texture mapping an image onto a 3D polygonal frame. The feeling of movement is then achieved by mathematically simulating camera movement relative to the polygonal frame. We have built customized scripts that adapt video game authoring software to texture mapping images of gene expression data onto b-spline based embryo models. This approach, known as UV mapping, associates two-dimensional (U and V) coordinates within images to the three dimensions (X, Y, and Z) of a b-spline model. B-spline model frameworks were built either from confocal data or de novo extracted from 2D images, once again using video game authoring approaches. This system was then used to build 3D models of 182 genes expressed in developing Xenopus embryos and to implement these in a web-accessible database. Models can be viewed via simple Internet browsers and utilize openGL hardware acceleration via a Shockwave plugin. Not only does this database display static data in a dynamic and scalable manner, the UV mapping system also serves as a method to align different images to a common framework, an approach that may make high-throughput automated comparisons of gene expression patterns possible. Finally, video game systems also have elegant methods for handling movement, allowing biomechanical algorithms to drive the animation of models. With further development, these biomechanical techniques offer practical methods for generating virtual embryos that recapitulate morphogenesis. PMID- 17366624 TI - Nestin expression in pancreatic endocrine and exocrine cells of mice lacking glucagon signaling. AB - Nestin, a marker of neural stem cells, is also expressed by cells located in the epithelium of the pancreatic primordium and by a subpopulation of exocrine cells but not by endocrine cells. These findings raised the possibility that the pancreatic epithelium is heterogeneous and comprised of subpopulations of exocrine/nestin-positive and endocrine/nestin-negative precursor cells. We examined this issue in two mutant mouse models characterized by protracted expression of several embryonal properties in islet cells. One mutant line comprises mice lacking mature glucagon due to abrogation of proprotein convertase 2 (PC2(-/-)), responsible for the conversion of proglucagon into glucagon, while the second line consists of mice with a global deletion of the glucagon receptor (Gcgr(-/-)). We demonstrate that nestin is transiently expressed by acinar cells and by insulin and glucagon cells of islets of both lines of mice. In addition, the lack of glucagon signaling increased nestin mRNA levels in pancreas of mutant embryos and adult mice. We conclude that nestin+ cells located in the pancreatic primordium generate the cells of the endocrine and exocrine lineages. Furthermore, our results suggest that nestin expression is regulated by glucagon signaling. PMID- 17366625 TI - Diversified expression patterns of autotaxin, a gene for phospholipid-generating enzyme during mouse and chicken development. AB - Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that generates bioactive phospholipids that act on G protein coupled receptors. Here we show the expression patterns of the ATX gene in mouse and chicken embryos. ATX has a dynamic spatial and temporal expression pattern in both species and the expression domains during neural development are quite distinct from each other. Murine ATX (mATX) is expressed immediately rostral to the midbrain-hindbrain boundary, whereas chicken ATX (cATX) is expressed in the diencephalon and later in the parencephalon-synencephalon boundary. In the neural tube, cATX is expressed in the alar plate in contrast to mATX in the floor plate. ATX is also expressed in the hindbrain and various organ primordia such as face anlagen and skin appendages of the mouse and chicken. These results suggest conserved and non-conserved roles for ATX during neural development and organogenesis in these species. PMID- 17366626 TI - Direct interaction of Gas11 with microtubules: implications for the dynein regulatory complex. AB - We previously described the Trypanin family of cytoskeleton-associated proteins that have been implicated in dynein regulation [Hill et al., J Biol Chem2000; 275(50):39369-39378; Hutchings et al., J Cell Biol2002;156(5):867-877; Rupp and Porter, J Cell Biol2003;162(1):47-57]. Trypanin from T. brucei is part of an evolutionarily conserved dynein regulatory system that is required for regulation of flagellar beat. In C. reinhardtii, the trypanin homologue (PF2) is part of an axonemal 'dynein regulatory complex' (DRC) that functions as a reversible inhibitor of axonemal dynein [Piperno et al., J Cell Biol1992;118(6):1455-1463; Gardner et al., J Cell Biol1994;127(5):1311-1325]. The DRC consists of an estimated seven polypeptides that are tightly associated with axonemal microtubules. Association with the axoneme is critical for DRC function, but the mechanism by which it attaches to the microtubule lattice is completely unknown. We demonstrate that Gas11, the mammalian trypanin/PF2 homologue, associates with microtubules in vitro and in vivo. Deletion analyses identified a novel microtubule-binding domain (GMAD) and a distinct region (IMAD) that attenuates Gas11-microtubule interactions. Using single-particle binding assays, we demonstrate that Gas11 directly binds microtubules and that the IMAD attenuates the interaction between GMAD and the microtubule. IMAD is able to function in either a cis- or trans-orientation with GMAD. The discovery that Gas11 provides a direct linkage to microtubules provides new mechanistic insight into the structural features of the dynein-regulatory complex. PMID- 17366630 TI - Hyperoxia inhibits several critical aspects of vascular development. AB - Normal human retinal vascular development uses angiogenesis and vasculogenesis, both of which are interrupted in the vaso-obliteration phase of retinopathy of prematurity (ROP). Canine oxygen-induced retinopathy (OIR) closely resembles human ROP. Canine retinal endothelial cells (ECs) and angioblasts were used to model OIR and characterize the effects of hyperoxia on angiogenesis and vasculogenesis. Cell cycle analysis showed that hyperoxia reduced the number of G1 phase cells and showed increased arrest in S phase for both cell types. Migration of ECs was significantly inhibited in hyperoxia (P < 0.01). Hyperoxia disrupted the cytoskeleton of angioblasts but not ECs after 2 days. Differentiation of angioblasts into ECs (determined by acetylated low-density lipoprotein uptake) was evaluated after basic fibroblast growth factor treatment. Differentiation of angioblasts into pericytes was determined by smooth muscle actin expression after treatment with platelet-derived growth factor. Differentiation into ECs was significantly inhibited by hyperoxia (P < 0.0001). The percentage of CXCR4(+) cells (a marker for retinal vascular precursors) increased in both treatment groups after hyperoxia. These data show novel mechanisms of hyperoxia-induced disruption of vascular development. PMID- 17366631 TI - Gain of affinity point mutation in the serotonin receptor gene 5-HT2Dro accelerates germband extension movements during Drosophila gastrulation. AB - Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT(2Dro) receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT(2Dro) receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT(2Dro) (C1644). Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT(2Dro) (C1644) embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. PMID- 17366632 TI - Myocardium defects and ventricular hypoplasia in mice homozygous null for the Forkhead Box M1 transcription factor. AB - The Forkhead Box m1 (Foxm1) transcription factor is expressed in cardiomyocytes and cardiac endothelial cells during heart development. In this study, we used a novel Foxm1 -/- mouse line to demonstrate that Foxm1-deletion causes ventricular hypoplasia and diminished DNA replication and mitosis in developing cardiomyocytes. Proliferation defects in Foxm1 -/- hearts were associated with a reduced expression of Cdk1-activator Cdc25B phosphatase and NFATc3 transcription factor, and with abnormal nuclear accumulation of the Cdk-inhibitor p21(Cip1) protein. Depletion of Foxm1 levels by siRNA caused altered expression of these genes in cultured HL-1 cardiomyocytes. Endothelial-specific deletion of the Foxm1 fl/fl allele in Tie2-Cre Foxm1 fl/fl embryos did not influence heart development and cardiomyocyte proliferation. Foxm1 protein binds to the -9,259/-9,288-bp region of the endogenous mouse NFATc3 promoter, indicating that Foxm1 is a transcriptional activator of the NFATc3 gene. Foxm1 regulates expression of genes essential for the proliferation of cardiomyocytes during heart development. PMID- 17366633 TI - Lack of galectin-1 results in defects in myoblast fusion and muscle regeneration. AB - Galectin-1 has been implicated in the development of skeletal muscle, being maximally expressed at the time of myofiber formation. Furthermore, in the presence of exogenous galectin-1, mononuclear myoblasts show increased fusion in vitro. In the current study, we have used the galectin-1 null mouse to elucidate the role of galectin-1 in skeletal muscle development and regeneration. Myoblasts derived from the galectin-1 mutant showed a reduced ability to fuse in vitro. In galectin-1 null mutants, there was evidence of a delay in muscle fiber development at the neonatal stage and muscle fiber diameter was reduced when compared with wild-type at the adult stage. Muscle regeneration was also compromised in the galectin-1 mutant with the process being delayed and a reduced fiber size being maintained. These results, therefore, show a definitive role for galectin-1 in fusion of myoblasts both in vitro, in vivo, and in regeneration after recovery from induced injury. PMID- 17366634 TI - Inclusion body myositis with human immunodeficiency virus infection: four cases with clonal expansion of viral-specific T cells. AB - OBJECTIVE: Sporadic inclusion body myositis (sIBM), a common adult-onset myositis, is characterized by an antigen-driven inflammatory response and vacuolar degeneration. The cause is unknown. We report the association of sIBM with human immunodeficiency virus (HIV) infection and explore the clonality and viral specificity of the autoinvasive T cells. METHODS: Clinicopathological studies in four HIV-infected patients with IBM were performed. The clonal restriction of endomysial T cells, compared with peripheral blood, was examined by spectratyping. Immunohistochemical studies using human leukocyte antigen-A* 0201-gag tetramers and the most dominant Vb families were performed in serial muscle biopsy sections to examine whether clonally expanded autoinvasive T cells are viral specific and invade muscle fibers expressing the allele-specific monomorphic major histocompatibility complex class I antigen. RESULTS: Prominent clonal restriction of certain Vb families was noted among the endomysial T cells with evidence of in situ expansion. Approximately 10% of the autoinvasive CD8(+) cells were human leukocyte antigen-A* 0201-HIV-gag specific and invaded muscle fibers expressing the specific human leukocyte antigen-A* 0201 allele. These cells belonged to restricted Vb families. The HIV gag antigen was present on several endomysial macrophages but not within the muscle fibers. INTERPRETATION: sIBM develops in patients who harbor HIV. In HIV-IBM, a subset of CD8(+) T cells surrounding muscle fibers are viral specific and may play a role in the disease mechanism by cross-reacting with antigens on the surface of muscle fibers. This study provides a paradigm that a chronic viral infection in genetically susceptible individuals can trigger viral specific T cell clones that persist within the muscle and lead to development of sIBM. PMID- 17366635 TI - Extreme cerebrospinal fluid amyloid beta levels identify family with late-onset Alzheimer's disease presenilin 1 mutation. AB - OBJECTIVE: Aggregation and deposition of amyloid beta (Abeta) in the brain is thought to be central to the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that cerebrospinal fluid (CSF) Abeta levels are strongly correlated with AD status and progression, and may be a meaningful endophenotype for AD. Mutations in presenilin 1 (PSEN1) are known to cause AD and change Abeta levels. In this study, we have investigated DNA sequence variation in the presenilin (PSEN1) gene using CSF Abeta levels as an endophenotype for AD. METHODS: We sequenced the exons and flanking intronic regions of PSEN1 in clinically characterized research subjects with extreme values of CSF Abeta levels. RESULTS: This novel approach led directly to the identification of a disease-causing mutation in a family with late-onset AD. INTERPRETATION: This finding suggests that CSF Abeta may be a useful endophenotype for genetic studies of AD. Our results also suggest that PSEN1 mutations can cause AD with a large range in age of onset, spanning both early- and late-onset AD. PMID- 17366637 TI - Combined flow cytometry and confocal laser scanning microscopy for evaluation of BR96 antibody cancer cell targeting and internalization. AB - BACKGROUND: Monoclonal antibodies (mAb) are important tools in the management of tumor disease, and the discovery of antibodies with both specific cancer cell targeting and capacity to enter the cells by internalization are critical to improve the therapeutic efficacy. METHOD: Antibody cancer cell targeting and internalization properties of fluoroscein-conjugated mAb made against Lewis Y (BR96) were evaluated quantitatively and qualitatively by means of flow cytometry (FCM) and confocal laser scanning microscopy (CLSM), respectively, on cells from a rat tumor cell line (BN7005-H1D2). RESULTS: The study demonstrated a specific binding of BR96 to LewisY (LeY) located in the cell membrane and as BR96/LeY immunocomplexes (BR96/LeY) internalized into the cytoplasm. BR96/LeY was internalized into about 15% of the cells, usually distributed throughout the cytoplasm, but also located close to the nuclei. Cytotoxic effects by BR96 were indicated, and CLSM visualized subpopulations containing cells with bound or internalized BR96/LeY that possessed morphologically pyknotic nuclei and disrupted DNA. CONCLUSION: The spatial-temporal pattern by BR96 cell targeting and internalization processes of BR96/LeY into the cancer cells expressing LeY was demonstrated by FCM and CLSM. Used together, the FCM and CLSM techniques provide a valuable tool for preclinical analyses of antibody targeting and their capacities as carriers of cytotoxic conjugates for the use in cancer therapy. PMID- 17366638 TI - Data quality assessment of ungated flow cytometry data in high throughput experiments. AB - BACKGROUND: The recent development of semiautomated techniques for staining and analyzing flow cytometry samples has presented new challenges. Quality control and quality assessment are critical when developing new high throughput technologies and their associated information services. Our experience suggests that significant bottlenecks remain in the development of high throughput flow cytometry methods for data analysis and display. Especially, data quality control and quality assessment are crucial steps in processing and analyzing high throughput flow cytometry data. METHODS: We propose a variety of graphical exploratory data analytic tools for exploring ungated flow cytometry data. We have implemented a number of specialized functions and methods in the Bioconductor package rflowcyt. We demonstrate the use of these approaches by investigating two independent sets of high throughput flow cytometry data. RESULTS: We found that graphical representations can reveal substantial nonbiological differences in samples. Empirical Cumulative Distribution Function and summary scatterplots were especially useful in the rapid identification of problems not identified by manual review. CONCLUSIONS: Graphical exploratory data analytic tools are quick and useful means of assessing data quality. We propose that the described visualizations should be used as quality assessment tools and where possible, be used for quality control. PMID- 17366639 TI - A practical method to determine the amount of tissue to analyze using laser scanning cytometry. AB - BACKGROUND: Laser scanning cytometry (LSC) is a new technology similar to flow cytometry but generates data from analysis of successive microscopic fields. Unlike its use in other applications, LSC-generated data are not random when used for tissue sections, but are dependent on the microanatomy of the tissue and the distribution and expression of the protein under investigation. For valid LSC analysis, the data generated requires the evaluation of a sufficient tissue area to ensure an accurate representation of expression within the tissue of interest. METHODS: In this report, we describe a simple and common sense method for determining the area of tissue required for sound LSC analysis by tracking the variation in the measure of target expression with increasing number of fields until it approaches zero. RESULTS: This approach was used to evaluate the expression of immunohistochemical markers with differing tissue distributions in liver (PMP70, CYP1A2, and Ki67 positive macrophages) and a colorectal adenocarcinoma (activated caspase-3 positive cells), which exhibited diffuse, regional (centrilobular), random, and irregular distribution patterns respectively. CONCLUSIONS: Analyses of these markers demonstrated that the amount of tissue area required to reach a steady measure of a parameter increased with increasing variability of the tissue distribution. PMID- 17366640 TI - Molecular identification and localization of cellular titin, a novel titin isoform in the fibroblast stress fiber. AB - We previously discovered a large titin-like protein-c-titin-in chicken epithelial brush border and human blood platelet extracts that binds alpha-actinin and organizes arrays of myosin II bipolar filaments in vitro. RT-PCR analysis of total RNA from human megakaryoblastic (CHRF-288-11) and mouse fibroblast (3T3) nonmuscle cells reveal sequences identical to known titin gene exon sequences that encode parts of the Z-line, I-band, PEVK domain, A-band, and M-line regions of striated muscle titins. In the nonmuscle cells, these sequences are differentially spliced in patterns not reported for any striated muscle titin isoform. Rabbit polyclonal antibodies raised against expressed protein fragments encoded by the Z-repeat and kinase domain regions react with the c-titin band in Western blot analysis of platelet extracts and immunoprecipitate c-titin in whole platelet extracts. Immunofluorescent localization demonstrates that the majority of the c-titin colocalizes with alpha-actinin and actin in 3T3 and Indian Muntjac deer skin fibroblast stress fibers. Our results suggest that differential expression of titin gene exons in nonmuscle cells yields multiple novel isoforms of the protein c-titin that are associated with the actin stress fiber structures. PMID- 17366641 TI - Functional protofilament numbering of ciliary, flagellar, and centriolar microtubules. AB - This article discusses the current state of knowledge about the evolutionarily conserved structure of ciliary, flagellar and centriolar microtubules, and formally proposes a functional numbering convention for their protofilaments. PMID- 17366643 TI - Computing the (1)H NMR spectrum of a bulk ionic liquid from snapshots of car parrinello molecular dynamics simulations. AB - We have investigated the performance of several computational protocols in predicting the NMR spectrum of a molecular ion in a complex liquid phase such as an ionic liquid. To do this, we computed the proton NMR chemical shifts of the 1 ethyl-3-methylimidazolium cation [emim](+) in [emim][Cl]. Environmental effects on the imidazolium ring proton chemical shifts are quite significant and must be taken into account explicitly. Calculations performed on the isolated imidazolium cation as well as on the [emim][Cl] ion pair grossly fail to reproduce the correct spacing between proton signals. In contrast, calculations performed on clusters extracted from the trajectory of a Car-Parrinello molecular dynamics simulation yield very good results. PMID- 17366642 TI - Evaluation of malignant and benign gastric biopsy specimens by mRNA expression profile and multivariate statistical methods. AB - BACKGROUND: mRNA expression array and multivariate statistical analysis of gastric biopsies can yield insight into the molecular biology basis of local alterations, supporting expression-based identification of morphological alterations. METHODS: From 11 patients with erosive gastritis(EG), 5 with adenocarcinoma (GC), 11 with atrophic gastritis (AG) gastric biopsies were collected, total RNA isolated, T7 amplification and expression analysis of 1047 mRNAs was performed using commercial glass arrays (Clontech, USA). After microarray quality control, applicable data were available from 7 EG, 4 GC, and 5 AG. Multivariate statistical and cell functional analysis were performed. Real time RT-PCR and immunohistochemistry were used for validation. RESULTS: GC was characterized by overregulated v-raf, v-erb-a, BCL2-associated- athanogene, immediate-early-response-3, Polo-like kinase, CDK-2, cyclin-C, Pin1 genes, and downregulated ADP-ribosyltransferase, sialophorin and DCC. AG cases had increased PDGF-receptor, TGF-beta-receptor-3, and decreased death-associated-protein-3, beta-1-catenin, topoisomerase-1 levels. In EG upregulation of IGF-receptor-1, CD9, transferrin receptor, integrins, and underexpression of keratin-5, caspase-4 was found. Discriminant analysis could reclassify all samples correctly using four parameters. CONCLUSIONS: mRNA expression array analysis of gastric biopsies yields previously known and new data in the evaluation of local gastric alterations. PMID- 17366644 TI - Optical gain enhancement using a carbosiloxane dendrimer in dilute solution of rhodamine B. PMID- 17366645 TI - Ethanol adsorption, decomposition and oxidation on Ir(111): a high resolution XPS study. AB - Ethanol (C(2)H(5)OH) adsorption, decomposition and oxidation is studied on Ir(111) using high-energy resolution, fast XPS and temperature-programmed desorption. During heating of an adsorbed ethanol layer a part of the C(2)H(5)OH(ad) desorbs molecularly, and another part remains on the surface and decomposes around 200 K; these two decomposition pathways are identified, as via acetyl (H(3)C--C=O) and via CO(ad)+CH(3ad), respectively. Acetyl and CH(3ad) decompose around 300 K into CH(ad) (and CO(ad)). CH(ad) decomposes forming C(x) and H(2) around 520 K. In the presence of O(ad) an acetate intermediate is formed around 180 K, as well as a small amount of CH(3ad) and CO(ad). Acetate decomposes between 400-480 K into CO(2), H(2)(/H(2)O) and CH(ad). PMID- 17366646 TI - Effect of gramicidin on phospholipid-modified monolayers and on ion transfer at a liquid-liquid interface. AB - The interaction of hybrid lipid/gramicidin A (gA) monolayers with dextran sulfate (DS) and the effect of this interaction on ion transfer at a liquid-liquid interface is reported. The interfacial and physicochemical properties are studied with Langmuir-Blodgett (LB) and electrochemical techniques. The results obtained from compression isotherms demonstrate that the interactions between the different species in the hybrid monolayer vary according to the chemical nature of the lipid (hydrocarbon region and charge of the head group). Interfacial capacitance measured with AC voltammetry indicates that the DS chains form a rather flat and compact layer when adsorbed to either zwitterionic or negatively charged phospholipid monolayers, and that calcium, even at low concentrations, interacts with the monolayers. These results are successfully described by a model based on the solution of the Poisson-Boltzmann equation in the interfacial region. Ion transfer and interactions with the lipid/gA/DS-modified monolayers were also studied with electrochemical techniques. Admittance data show that although the studied ions are not using gA channels for the transfer through the lipid membranes, the incorporation of gA in the lipid domain and the adsorption of DS at the interface have a significant effect on ion transfer across the monolayers. This effect can be explained as a consequence of the modified surface charge and of the compactness of the lipid domain due to its interaction with gA and to calcium and DS adsorption at the interface. The ion-transfer rate, therefore, depends on the composition of the monolayer and the chemical nature of the ion. PMID- 17366647 TI - Contribution of charge-transfer mechanisms to surface-enhanced Raman scattering with near-IR excitation. AB - Surface-enhanced Raman scattering under near-IR excitation is investigated for p aminothiophenol (PATP) molecules that are either adsorbed on an electrochemically roughened silver electrode or embedded in an Au/PATP/Ag molecular junction assembled on an indium-doped tin oxide electrode. The contribution from chemical enhancement can be amplified relative to the contribution from electromagnetic enhancement, because the energy of the near-IR excitation is far from the surface plasmon resonance of the nanosized metal particles. The energy required for the charge-transfer process for the Au/PATP/Ag molecular junction is much lower than that of the PATP molecules adsorbed on the electrochemically roughened silver electrode. Coadsorption of chloride ions on the metal nanoparticles may result in an alteration of the local Fermi level of the metal nanoparticles, thus leading to better energy matching between the energy level of the interconnecting PATP molecules and the Fermi level of the metal nanoparticles. PMID- 17366648 TI - The importance of tetrahedrally coordinated molecules for the explanation of liquid water properties. AB - Ab initio calculations on molecular clusters and a quantum statistical model are used to probe the structure of liquid water and its anomalies. Characteristic temperature dependent mixtures of ring and three-dimensional, voluminous water clusters provide the famous density maximum. The mixture model also reproduces the shift of the density maximum as a function of pressure and isotopic substitution. This finding is consistent with femtosecond spectroscopy data suggesting that two distinct molecular species exist in liquid water. The given structures also reproduce the oxygen-oxygen pair correlation function and the vibrational IR spectrum of liquid water. The results underline the importance of three-dimensional, tetrahedrally coordinated structures for the understanding of water anomalies and the existence of two liquid phases in the supercooled region. PMID- 17366649 TI - Self-assembled single- and double-stack pi-aggregates of chlorophyll derivatives on highly ordered pyrolytic graphite. AB - The highly efficient, light-harvesting antennae systems present in chlorosomes of green phototrophic bacteria, such as Chloroflexus aurantiacus, serve as a model for the design of bioinspired nanostructured materials. A semisynthetic zinc chlorin, derived from natural chlorophyll a, is used as a building block that self-assembles into excitonically coupled chromophore stacks. Temperature dependent UV/Vis and circular dichroism spectroscopic measurements show the reversible formation of soluble chiral aggregates of this new zinc chlorin dye. High-resolution scanning tunneling microscopy and atomic force microscopy studies reveal the formation of two types of well-ordered pi-stacked aggregates on highly ordered pyrolytic graphite. PMID- 17366650 TI - Synergistic strengthening effect of ultrafine-grained metals reinforced with carbon nanotubes. PMID- 17366651 TI - Prediction of tyrosinase inhibition activity using atom-based bilinear indices. AB - A set of novel atom-based molecular fingerprints is proposed based on a bilinear map similar to that defined in linear algebra. These molecular descriptors (MDs) are proposed as a new means of molecular parametrization easily calculated from 2D molecular information. The nonstochastic and stochastic molecular indices match molecular structure provided by molecular topology by using the kth nonstochastic and stochastic graph-theoretical electronic-density matrices, M(k) and S(k), respectively. Thus, the kth nonstochastic and stochastic bilinear indices are calculated using M(k) and S(k) as matrix operators of bilinear transformations. Chemical information is coded by using different pair combinations of atomic weightings (mass, polarizability, vdW volume, and electronegativity). The results of QSAR studies of tyrosinase inhibitors using the new MDs and linear discriminant analysis (LDA) demonstrate the ability of the bilinear indices in testing biological properties. A database of 246 structurally diverse tyrosinase inhibitors was assembled. An inactive set of 412 drugs with other clinical uses was used; both active and inactive sets were processed by hierarchical and partitional cluster analyses to design training and predicting sets. Twelve LDA-based QSAR models were obtained, the first six using the nonstochastic total and local bilinear indices and the last six with the stochastic MDs. The discriminant models were applied; globally good classifications of 99.58 and 89.96 % were observed for the best nonstochastic and stochastic bilinear indices models in the training set along with high Matthews correlation coefficients (C) of 0.99 and 0.79, respectively, in the learning set. External prediction sets used to validate the models obtained were correctly classified, with accuracies of 100 and 87.78 %, respectively, yielding C values of 1.00 and 0.73. This subset contains 180 active and inactive compounds not considered to fit the models. A simulated virtual screen demonstrated this approach in searching tyrosinase inhibitors from compounds never considered in either training or predicting series. These fitted models permitted the selection of new cycloartane compounds isolated from herbal plants as new tyrosinase inhibitors. A good correspondence between theoretical and experimental inhibitory effects on tyrosinase was observed; compound CA6 (IC(50)=1.32 microM) showed higher activity than the reference compounds kojic acid (IC(50)=16.67 microM) and L-mimosine (IC(50)=3.68 microM). PMID- 17366652 TI - ESI-MS characterisation of protein adducts of anticancer ruthenium(II)-arene PTA (RAPTA) complexes. PMID- 17366653 TI - Immunostimulatory CpG oligonucleotides form defined three-dimensional structures: results from an NMR study. AB - The DNA eicosamer 5'-TCCATGACGTTCCTGATGCT-3' is known to stimulate the innate immune system of vertebrae. The immunostimulatory activity is based on the activation of Toll-like receptor 9 (TLR9). While it is known that the CG dinucleotide of the eicosamer has to be unmethylated, the structural basis of the recognition of the DNA through the receptor remains unclear. Oligodeoxynucleotides containing the sequence of the eicosamer, or a portion thereof, ranging in length from hexamer to pentaeicosamer were studied by (1)H NMR spectroscopy. Based on two-dimensional NMR spectra, a number of resonances could be unambiguously assigned. For all oligonucleotides, structural transitions were detected upon heating, as monitored by the line width and chemical shift of low-field resonances. This includes the TC dinucleotide of the 5'-terminal portion, which does not have any clear base-pairing partners. The melting transitions, together with the NOESY cross-peaks, demonstrate that structure formation occurs well beyond the core hexamer 5'-GACGTT-3', a fact that may be important for understanding the molecular recognition by the Toll-like receptors of the innate immune system. PMID- 17366654 TI - Mechanistic studies on peroxide activation by a water-soluble iron(III) porphyrin: implications for O-O bond activation in aqueous and nonaqueous solvents. AB - The reactions of a water-soluble iron(III)-porphyrin, [meso tetrakis(sulfonatomesityl)porphyrinato]iron(III), [Fe(III)(tmps)] (1), with m chloroperoxybenzoic acid (mCPBA), iodosylbenzene (PhIO), and H(2)O(2) at different pH values in aqueous methanol solutions at -35 degrees C have been studied by using stopped-flow UV/Vis spectroscopy. The nature of the porphyrin product resulting from the reactions with all three oxidants changed from the oxo iron(IV)-porphyrin pi-cation radical [Fe(IV)(tmps(*+))(O)] (1(++)) at pH<5.5 to the oxo-iron(IV)-porphyrin [Fe(IV)(tmps)(O)] (1(+)) at pH>7.5, whereas a mixture of both species was formed in the intermediate pH range of 5.5-7.5. The observed reactivity pattern correlates with the E degrees' versus pH profile reported for 1, which reflects pH-dependent changes in the relative positions of E degrees'(Fe(IV)/Fe(III) ) and E degrees'(P(*+)/P) for metal- and porphyrin centered oxidation, respectively. On this basis, the pH-dependent redox equilibria involving 1(++) and 1(+) are suggested to determine the nature of the final products that result from the oxidation of 1 at a given pH. The conclusions reached are extended to water-insoluble iron(III)-porphyrins on the basis of literature data concerning the electrochemical and catalytic properties of [Fe(III)(P)(X)] species in nonaqueous solvents. Implications for mechanistic studies on [Fe(P)]-catalyzed oxidation reactions are briefly addressed. PMID- 17366655 TI - Cancer prevention. Proceedings of an international conference. 2007. St. Gallen, Switzerland. PMID- 17366656 TI - Influenza vaccines. PMID- 17366657 TI - Colonoscopic withdrawal times and adenoma detection. PMID- 17366658 TI - PET scanning in mild cognitive impairment. PMID- 17366659 TI - Management of sepsis. PMID- 17366660 TI - Management of sepsis. PMID- 17366661 TI - Bile duct proliferation in liver-specific Jag1 conditional knockout mice: effects of gene dosage. AB - The Notch signaling pathway is involved in determination of cell fate and control of cell proliferation in multiple organ systems. Jag1 encodes a ligand in the Notch pathway and has been identified as the disease-causing gene for the developmental disorder Alagille syndrome. Evidence from the study of human disease and mouse models has implicated Jag1 as having an important role in the development of bile ducts. We have derived a conditional knockout allele (Jag1(loxP)) to study the role of Jag1 and Notch signaling in liver and bile duct development. We crossed Jag1(loxP) mice with a transgenic line carrying Cre recombinase under the control of the albumin promoter and alpha-fetoprotein enhancer to ablate Jag1 in hepatoblasts. The liver-specific Jag1 conditional knockout mice showed normal bile duct development. To further decrease Notch pathway function, we crossed the Jag1 conditional knockout mice with mice carrying the hypomorphic Notch2 allele, and bile duct anatomy remained normal. When Jag1 conditional mice were crossed with mice carrying the Jag1 null allele, the adult progeny exhibited striking bile duct proliferation. CONCLUSION: These results indicate that Notch signaling in the liver is sensitive to Jag1 gene dosage and suggest a role for the Notch pathway in postnatal growth and morphogenesis of bile ducts. PMID- 17366662 TI - Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury. AB - Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses but which can precipitate liver injury at high doses. We have previously found that the antirheumatic drug leflunomide is a potent inhibitor of APAP toxicity in cultured human hepatocytes, protecting them from mitochondria-mediated cell death by inhibiting the mitochondrial permeability transition. The purpose of this study was to explore whether leflunomide protects against APAP hepatotoxicity in vivo and to define the molecular pathways of cytoprotection. Male C57BL/6 mice were treated with a hepatotoxic dose of APAP (750 mg/kg, ip) followed by a single injection of leflunomide (30 mg/kg, ip). Leflunomide (4 hours after APAP dose) afforded significant protection from liver necrosis as assessed by serum ALT activity and histopathology after 8 and 24 hours. The mechanism of protection by leflunomide was not through inhibition of cytochrome P450 (CYP)-catalyzed APAP bioactivation or an apparent suppression of the innate immune system. Instead, leflunomide inhibited APAP-induced activation (phosphorylation) of c-jun NH2-terminal protein kinase (JNK), thus preventing downstream Bcl-2 and Bcl-XL inactivation and protecting from mitochondrial permeabilization and cytochrome c release. Furthermore, leflunomide inhibited the APAP-mediated increased expression of inducible nitric oxide synthase and prevented the formation of peroxynitrite, as judged from the absence of hepatic nitrotyrosine adducts. Even when given 8 hours after APAP dose, leflunomide still protected from massive liver necrosis. CONCLUSION: Leflunomide afforded protection against APAP-induced hepatotoxicity in mice through inhibition of JNK mediated activation of mitochondrial permeabilization. PMID- 17366663 TI - Hypoxic conformance of metabolism in primary rat hepatocytes: a model of hepatic hibernation. AB - Following prolonged hypoxia, mammalian cells invoke adaptive mechanisms to enhance oxygen delivery and promote energy conservation. We previously reported that hepatocytes subjected to prolonged moderate hypoxia (PO2 = 20-50 mmHg for > 3 hours) demonstrated a reversible inhibition of cellular respiration with maintenance of cell viability, associated with a decrease in mitochondrial adenosine triphosphate (ATP) synthesis; acute hypoxia (similar PO2 for < 30 minutes) did not induce a similar suppression of respiration and ATP synthesis. In the current study, using an in vitro model of primary rat hepatocytes, we measured the changes in metabolic demand for ATP during hypoxic conformance, and tested whether viability is maintained by preferentially suppressing nonessential processes while sustaining processes essential for maintaining cell homeostasis. In addition, the rate of recovery of oxygen consumption and ATP concentrations following reoxygenation after prolonged and acute hypoxia/anoxia was compared. Oxygen consumption and ATP concentrations decreased during prolonged hypoxia compared with acute hypoxia. However, ouabain-inhibitable respiration did not decrease during prolonged hypoxia, indicating that membrane Na+/K+ ATPase activity, an essential process for cell viability, was maintained. In contrast, ATP-dependent glucuronidation and sulfation of acetaminophen, deemed "non essential" processes, were decreased significantly compared with normoxic cells. After reoxygenation, cells exposed to prolonged moderate hypoxia demonstrated a more rapid recovery of respiration compared to acute hypoxia/anoxia. CONCLUSION: This "hepatic hibernation" during prolonged moderate hypoxia may represent an anticipatory adaptation that seeks to maintain cell viability while delaying or preventing the onset of lethal hypoxia, and facilitates rapid recovery after the resumption of normoxia. PMID- 17366666 TI - Reasons to hope... PMID- 17366667 TI - ZDV link to early signs of CVD? PMID- 17366668 TI - AIDS at 25. PMID- 17366669 TI - Focus on hepatitis. Low CD4 count + HCV coinfection = acute kidney failure. PMID- 17366670 TI - HHS proposes AIDS housing assistance cap. PMID- 17366671 TI - Discrimination. Workplace bias against AIDS sufferers persists. PMID- 17366672 TI - ADA. Wrongful death claim against police chief survives dismissal. PMID- 17366673 TI - AIDS relief. Bush administration issues update on AIDS relief after speech. PMID- 17366675 TI - Prisons. Court stays HIV-positive inmate's habeas petition. PMID- 17366674 TI - Prevention. AIDS group sues Pfizer over Viagra ads for 'off label' uses. PMID- 17366676 TI - ADAP's delisting procedures subject to terms of APA. PMID- 17366677 TI - Prison care. Assistant released from suit over HIV-positive inmate's care. PMID- 17366678 TI - Global Fund:time for long-term prevention plans. PMID- 17366679 TI - Current control strategies targeting sources of echinococcosis in Japan. AB - The authors describe the current control strategies targeting definitive hosts of the most important zoonotic parasite in Japan, Echinococcus multilocularis. A dramatic increase in the prevalence of echinococcosis in foxes in Hokkaido (the second largest of Japan's islands), the invasion of wild foxes into urban areas, infection among pet and stray dogs, and the possibility of spreading the disease to the main island of Japan (Honshu)--all these pose significant threats to public health. Previous research findings and current strategies such as control measures against infections in wild foxes, suggest that it will be possible to eliminate echinococcosis in the future. The enforcement of a national reporting system for veterinarians, international collaboration, and the establishment of a Forum on Environment and Animals (FEA) give further reason to believe that success is possible. This is the first report of a multifaceted control strategy against echinococcosis in definitive hosts that includes collaborative efforts with local residents. This model might provide new ideas for Veterinary Services worldwide in their efforts to control other related zoonotic diseases. PMID- 17366680 TI - Denture stomatitis. AB - A 70-year-old woman presented for evaluation of an eruption localized to the area covered by her partial upper denture. Her medical history and physical examination were otherwise unremarkable. She originally had a metal upper partial denture, which she used for many years without difficulty. Four years before presentation, she developed a painful eruption affecting only the tissue covered by the upper partial denture. Contact dermatitis to metal was suspected, and a new upper partial denture constructed primarily of acrylates was fashioned. When she transitioned to the new denture, the inflammation in her oral mucosa persisted and perhaps worsened, despite an excellent fit. Examination revealed striking erythema and mild edema sharply localized to the areas where the partial upper denture contacted the gum ridge. Patch testing was performed and revealed allergies to multiple acrylates, including methyl methacrylate. A swab from the gums was sent for yeast culture. No Candida was detected. Based on suspected candidal overgrowth on the denture, the patient was advised to begin applying nystatin ointment between the gums and the denture, and to start soaking the dentures nightly in chlorhexidine 0.12% solution. In addition, because the relevance of the acrylate allergy was unclear, her dentist was contacted and it was recommended that the dentures be boiled to induce polymerization of any residual un-reacted methacrylate monomers. The patient had a 90% improvement in the clinical appearance and in symptoms at an 8-week follow-up appointment. Due to logistic issues, the dentures had not yet been boiled. The improvement, despite the dentures not having been boiled, was felt to demonstrate that the acrylate allergy was not relevant. The patient has continued to slowly show further improvement over 6 months of follow-up. PMID- 17366681 TI - A complex pattern of melanonychia and onycholysis after treatment with pemetrexed for lung cancer. AB - A 53-year-old black man was diagnosed with poorly differentiated adenocarcinoma of the lung and treated initially with 4 cycles of paclitaxel in combination with carboplatin and external-beam radiation therapy with a good clinicoradiologic response. The patient tolerated the chemotherapy well and did not develop any skin or nail changes during that period of time. His lung cancer recurred 10 months later, when he was found to have bone metastases. Second-line chemotherapy with pemetrexed 500 mg/m2 intravenously every 3 weeks was commenced. A week prior, the patient was started on folic acid 1 mg orally daily and given an injection of vitamin B12 1000 microg intramuscularly that was continued every 3 cycles thereafter. Dexamethasone 4 mg orally twice daily was given around the time of chemotherapy administration to prevent the dermatitis associated with the drug. The patient denied taking other drugs. Two months into his second-line chemotherapy, he developed multiple, concomitant, transverse and longitudinal black lines in all of his fingernails and toenails. After an interval of 3 months, he presented a complex pattern of nail hyperpigmentation, from combined dense horizontal and longitudinal streaks in some nails to diffuse black discoloration in others (Figure). Other associated changes included koilonychia, dystrophy, and friability of nail plates. Along with normal results of a hepatorenal panel and normal serum vitamin B12 and folate levels, no metabolic or endocrinologic alterations were present to explain the nail pigmentation and dystrophic changes. Results of his mycologic examination and cultures came back negative. When questioned, he denied taking any other drugs including other alternative medicine approaches or vitamin supplements, particularly retinoids, well known for causing severe nail dystrophy. PMID- 17366682 TI - Occlusive irritant dermatitis: when is "allergic" contact dermatitis not allergic? AB - CASE 1: A 38-year-old teacher presented with a 3- to 4-week history of a linear, erythematous, vesicular, and pruritic eruption of her left wrist. She had been wearing a new elastic bracelet for 4 weeks before the onset of her eruption. Although there was no history of allergy to rubber products or jewelry, an allergic contact dermatitis to rubber was suspected. Patch testing to rubber chemicals and the elastic bracelet revealed no reactions at 48, 72, and 96 hours. She stopped wearing the bracelet and used a corticosteroid cream with rapid resolution of the problem. The patient resumed wearing the bracelet, and there has been no recurrence in the past 2 months. CASE 2: A 12-year-old boy presented with a 1-month history of an itchy, scaly, erythematous 1-cm patch over the midline of his lower lip. The patient complained of tiny blisters initially with persistent erythema, mild scaling, and associated pruritus. The patient plays the saxophone and he had been practicing more intensely (3 to 4 h/d) for a musical competition. Allergic reaction to his wood reed was suspected, but patch testing with a moistened portion of his reed and reed shavings in a drop of water revealed no reaction at 48 and 72 hours. Treatment with hydrocortisone 1% cream bid for 3 days led to complete resolution of the dermitis and pruritus. Playing the saxophone 1 h/d has not led to any recurrence. CASE 3: A 33-year-old woman presented with erythema, scaling, and pruritus of 1 month's duration beneath her engagement and wedding rings, which were worn together on her left fourth finger (Figure 3). Although she had no history of previous sensitivity to earrings, watch clasp, blue jean rivets, or other jewelry, allergic contact dermatitis to nickel was suspected. Patch testing was performed to the common metal allergens nickel, cobalt, chromium, and gold. Readings at 48 hours and 1 week revealed no positive reactions. The patient wore her rings on the right hand for 1 week and used fluocinonide 0.5% cream twice daily for 1 week with resolution of the dermatitis. She has subsequently begun wearing the rings again on her left hand with care to dry her hands and rings after washing, and there has been no recurrence of her dermatitis. PMID- 17366683 TI - Solitary plexiform neurofibroma(s): role of magnetic resonance imaging. AB - A 10-year-old boy presented with a painless progressive swelling on the nape of the neck of 8 years' duration. When the child was 1 year old, the swelling appeared as a minute raised skin eruption the size of a pearl at the back of the neck. It was painless and progressive, continuing to increase in size until it reached the size of a walnut. At age 2 years, a minor surgical intervention was undertaken to remove the swelling, but a year later, it recurred at the same site. The size continued to increase until it reached the present size. Examination of the afflicted skin surface showed the presence of a globular, nonreducible swelling measuring 7.5 cm x 5 cm located on the upper posterior portion of the neck. Both the swelling and the skin over it were mobile and nontender. Otherwise, the boy's skin surface was without blemishes. On palpation, the swelling was plexiform, resembling a bag of worms. Magnetic resonance imaging (MRI) was performed on 1.5T MR (Signa, GE Healthcare, Chalfont St Giles, England) using T1 and T2 weighted fast spin echo and short tau inversion recovery sequences in the axial and sagittal planes. The images were marked by a well defined, homogeneous signal intensity lesion in the subcutaneous plane of the nape of the neck. The lesion appeared isointense in T1W images and hyperintense in T2W images with few flow voids within the lesion. Based on the MRI findings, a diagnosis of superficial plexiform neurofibroma was considered. Results of routine liver and kidney function blood examination tests were within normal limits. Surgical resection was done under general anesthesia. As soon as the skin was excised, the swelling started bleeding profusely, but bleeding stopped almost immediately on the complete excision of the swelling. No cavities were present in the mass, and the underlying structures were normal. The wound was closed with nonabsorbable monofilament nylon suture. The postoperative period was uneventful. In addition to initial excision biopsy, all of the resected tissue material was subjected to serial sectioning for microscopic pathologic examination. Hematoxylin- and eosin-stained sections showed unremarkable epidermis with slight hyperkeratosis. Upper dermis showed circumscribed, lobular proliferation of spindle cells in a loose fibular background distorting much of the dermis and subcutaneous fat. Subcutis showed numerous thin-walled, ectatic blood vessels lined with prominent endothelium. Intervening tissue consisted of wavy bundles of collagen lined with elongated thin cells with tapering and wavy nuclei. The nuclear chromatin was bland without significant polymorphism or raised mitotic activity. A few nerve twigs were also seen within the tumor, which was infiltrating the surrounding fat. PMID- 17366684 TI - Evaluation of diagnostic tests for infectious diseases: general principles. PMID- 17366685 TI - Evaluation of rapid diagnostic tests: syphilis. PMID- 17366686 TI - Evaluation of rapid diagnostic tests: chlamydia and gonorrhoea. PMID- 17366687 TI - Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2005-2006 (data received in WHO headquarters as of 6 March 2007). PMID- 17366688 TI - Detection of quorum-sensing pathway and construction of LuxS gene deletion mutants of group B streptococcus. PMID- 17366689 TI - [Topography and morphometry of trigeminal nerve opening]. PMID- 17366690 TI - Will Britain be sidelined by the rise of Asian science? PMID- 17366691 TI - Should terminally ill patients have access to phase I drugs? PMID- 17366692 TI - Viruses responsible for avian influenza in Suffolk and Hungary "essentially identical". PMID- 17366693 TI - Myeloid Growth Factor Guidelines: moving toward a societal perspective. PMID- 17366694 TI - A more convenient truth. PMID- 17366695 TI - Incidence of breast and chest wall asymmetry in breast augmentation: a retrospective analysis of 100 patients. AB - Although much is written concerning breast augmentation, few authors have addressed preoperative chest wall analysis as it pertains to postoperative outcome. In the present study, 100 patients were randomly selected, underwent bilateral augmentation, and were examined retrospectively by four independent physicians using standardized preoperative photographs. Each patient was examined for ptosis and asymmetry of the nipples, breast mound, and chest wall. Results revealed significant asymmetries in all parameters. Nipple-areola complex asymmetry was present in 24 percent (nipple/areola size) and 53 percent (nipple position) of the women. Mound asymmetry was noted in 44 percent (volume), 29 percent (base constriction), and 30 percent (inframammary fold position) of the women, and finally, 29 percent of the women had grade I to III ptosis. Chest wall asymmetry was observed in 9 percent of the women. Overall, 88 percent of the women had some degree of asymmetry, and 65 percent of the women had more than one parameter of asymmetry. These findings underscore the importance of developing a systematic preoperative breast and chest wall analysis that can be individualized for each patient. The resulting asymmetries should then be discussed with the patient, along with the potential for continued or even more pronounced asymmetry postoperatively. PMID- 17366696 TI - The correction of capsular contracture by conversion to "dual-plane" positioning: technique and outcomes. AB - Little has been published regarding the treatment of patients with long established capsular contracture after previous submuscular or subglandular breast augmentation. This study reviews 7 years of experience in treating established capsular contracture after augmentation mammaplasty by relocating implants to the "dual-plane" or partly subpectoral position. A retrospective chart review was performed on all patients who were treated for capsular contracture using this technique between 1993 and 1999. Data collected included the date of the original augmentation, the original implant location, date of revision and type of implant used, length of follow-up, outcome, and any ensuing complications. Different surgical techniques were used, depending on whether the prior implant was located in a subglandular or submuscular plane. All patients had revisions such that their implants were relocated to a dual plane, with the superior two thirds or so of the implant located beneath the pectoralis major muscle and the inferior one third located subglandularly. Of 85 patients reviewed, 54 had their original implants in a submuscular position and 31 had their initial augmentation in a subglandular position. Of the 54 patients whose implants were initially submuscular, 23 patients (43 percent) had silicone gel implants, 15 patients (28 percent) had double-lumen implants, and the remaining 16 patients (30 percent) had saline implants. Of the 31 patients whose implants were initially subglandular, 20 patients (65 percent) had silicone gel implants, three patients (10 percent) had double-lumen implants, and the remaining eight patients (26 percent) had saline implants. Fifty-one patients (60 percent) had replacement with saline implants (37 smooth saline, 14 textured saline), whereas 34 (40 percent) had silicone gel implants (seven smooth gel, 27 textured gel). The average time from previous augmentation to revision was 9 years 9 months. The average follow-up time after conversion to the dual-plane position was 11.5 months. Only three of 85 patients required reoperation for complications, all of which involved some degree of implant malposition. Of patients converted to the dual plane, 98 percent were free of capsular contracture and were Baker class I at follow-up, whereas 2 percent were judged as Baker class II. There were no Baker level III or IV contractures at follow-up. The dual-plane method of breast augmentation has proved to be an effective technique for correcting established capsular contracture after previous augmentation mammaplasty. This technique appears to be effective when performed with either silicone or saline-filled implants. PMID- 17366697 TI - Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropan-2-ol. PMID- 17366698 TI - Vincent Cristofalo (1933-2006): Extraordinary gerontologist. PMID- 17366699 TI - Bone morphogenetic proteins. PMID- 17366700 TI - HIV integrase: a target for drug discovery. AB - Current antiviral strategies against HIV rely on structure-function analysis of HIV reverse transcriptase (RT) and protease (PR). The third viral pol gene product, HIV integrase (IN), is also a good target for drug discovery, since IN is essential for retroviral replication and, moreover, it has no obvious functional analogue in the host. IN forms a ternary complex with metal ions and DNA and has a mechanism of catalysis common with other polynucleotidyl transferases. Although there is no structural information for full-length IN available, structures of all three functional IN domains have been determined by X-ray crystallography and NMR spectroscopy. The N-terminal domain has a novel zinc-binding fold, the catalytic domain shares a common structural motif with other polynucleotidyl transferases, and the C-terminal DNA-binding domain has a Src-homology-3-like fold. This structural information provides the basis for drug development. In turn, increasing numbers of IN inhibitors identified so far may serve structure-function analysis of IN. The final goal is the development of new classes of anti-HIV drugs, which can be added to the repertoire of anti-RT and anti-PR drugs. PMID- 17366701 TI - The transcriptional regulatory strategy of the rat tissue kallikrein gene family. AB - We have analysed the transcriptional regulatory strategy of the rat tissue kallikrein gene family, a strategy that provides universal submandibular gland expression of all family members coupled with otherwise disparate expression of individual members in a wide variety of organs. To test whether a locus control region (LCR) or individual gene enhancers control the family, the expression patterns of rat kallikrein genes were examined in transgenic mice bearing a series of rat genomic fragments spanning the kallikrein locus. Each fragment, present in recombinant P1 phage clones, contained two or three linked members of the rat family. Rat (r) genes KLK1, KLK2, KLK3, KLK7, KLK8, KLK9 and KLK10 on four different P1 clones were all correctly expressed at high levels in the submandibular glands of transgenic mice and in general showed the correct extra salivary patterns characteristic of each family member. Moreover, when the neighbouring family members rKLK1 and rKLK3 were separated on non-overlapping fragments and tested in mice, each transgene was expressed correctly in the submandibular gland and in other organs characteristic of that gene. Thus the family locus is not controlled by an LCR; rather each gene appears to have an associated transcriptional enhancer that specifies high submandibular expression and contributes to the additional organ specificity of the family member. PMID- 17366702 TI - HIV- I Nef severely impairs thymocyte development and peripheral T-cell function by a CD4-independent mechanism. AB - Nef is a regulatory protein of the human and simian immunodeficiency viruses (HIV and SIV) whose role in infection and the viral life cycle are not fully understood. In T-lymphocytes Nef down-regulates cell-surface CD4, and has been implicated in an increase in infectivity at low primary viral isolate titres. Additionally, the SIV nef gene is necessary for viraemia and AIDS-like pathogenesis in rhesus macaques. We report here in an in vivo murine transgenic model that thymocyte and T-cell-specific nef gene expression results in a marked decrease in thymic cellularity from 16 days post coitus. This reduction in thymocyte cell number is independent of CD4 expression and Nef-induced CD4 down regulation, but can be restored by expressing a constitutively active p56lckF505 gene. Functional analyses have revealed a severe decrease in thymocyte and T-cell proliferation in response to both T-cell-receptor- and mitogen-mediated stimuli. In addition, a significant proportion of Nef-expressing peripheral T-cells display cell-surface characteristics associated with cellular activation. These results suggest that Nef expression in developing thymocytes can severely reduce the regeneration capacity of the immune system, whereas expression in mature T cells dramatically decreases their potential to respond to antigen. With the recent recognition of a persistently high viral load in HIV-infected individuals, these findings have important implications for the mechanism of the progressive deterioration of the immune system that leads to AIDS. PMID- 17366703 TI - The pediatric spleen. AB - Many pathological processes affect the spleen in children. As a basis for recognizing pathology, knowledge of the normal imaging appearance of the pediatric spleen is needed. In addition to congenital anomalies and trauma, pathology of the pediatric spleen includes enlargement (splenomegaly), cysts, neoplasms, infection and infarction. Specific diseases processes, including sickle cell anemia and Gaucher disease, may have specific affects on the spleen. PMID- 17366704 TI - Lymphoma of the spleen. AB - Splenic involvement in lymphoma is common, although it is detected with limited accuracy using most conventionally employed imaging techniques. This article reviews the spectrum of appearances of splenic lymphoma using both routine and more recently developed techniques, including functional imaging. The importance of accurate splenic imaging in lymphoma assessment is also discussed, which has changed in recent years due to advances in therapy resulting in improvements in overall prognosis for both advanced and relapsed disease. PMID- 17366705 TI - Splenic sarcoidosis. AB - Sarcoidosis is a multisystem granulomatous disease of unknown cause that can produce either homogeneous splenomegaly or multiple splenic nodules. Systemic symptoms can accompany splenic involvement. Although the chest radiograph may be suggestive of sarcoidosis, a normal chest radiograph is seen in one quarter to one third of patients with splenic sarcoidosis. The imaging appearance of splenic sarcoidosis can mimic more ominous neoplastic or infectious disease. Biopsy of the spleen or other involved organ may be indicated for definitive diagnosis. PMID- 17366706 TI - Hydatid disease of the spleen. AB - Splenic echinococcosis is a rare disease even in endemic regions. The most commonly affected organ is the liver, followed by the lung and the spleen. In this article we discuss epidemiology, clinical presentation, diagnosis, pathophysiology, pathologic features, imaging findings, complications, differential diagnosis, and treatment of hydatid disease of the spleen. PMID- 17366707 TI - Vascular disease of the spleen. AB - A wide range of vascular disorders can affect the spleen. Although clinical presentation is often nonspecific, early diagnosis and treatment are mandatory in most conditions. Noninvasive imaging techniques are well suited to meet these objectives. Familiarity with normal macroscopic and microscopic vascular anatomy is a prerequisite to understand the pathophysiology of vascular disorders of the spleen. This article deals with diseases of the splenic vasculature (aneurysms, arteriovenous fistula, splenic vein thrombosis, collateral circulation in portal hypertension) as well as vascular disorders affecting the splenic parenchyma (splenic infarct, Gamna-Gandy bodies). Primary vascular tumors and tumor-like conditions of the spleen will be discussed very briefly. PMID- 17366708 TI - Iatrogenic injury to the spleen-CT appearance. AB - Splenic injury is a well-known but rare complication of various abdominal surgical and invasive procedures, and even of cardiac surgery. The true incidence of iatrogenic splenic trauma is, however, difficult to assess and is probably underestimated. Overt injuries diagnosed during surgery are usually immediately treated by splenectomy without imaging. This review focuses on missed splenic injuries that are diagnosed on imaging following surgery or an invasive procedure. PMID- 17366709 TI - Percutaneous image-guided splenic procedures: update on indications, technique, complications, and outcomes. AB - Percutaneous image-guided splenic procedures are seldom performed due to fear of complications, mainly hemorrhage. Percutaneous splenic invasive procedures are, however, safe, and in most cases, the complication rates are similar to those of other abdominal organs. In most patients, biopsy of a focal splenic lesion establishes the diagnosis. Aspiration and drainage of splenic collections are performed obviating the need for splenectomy. In this review we describe the indications, technique, complications, and outcomes of percutaneous splenic biopsy, aspiration, and drainage. PMID- 17366710 TI - Maternal spleen size throughout normal pregnancy. AB - Ultrasonography (US) is an accurate method with reproducible results for calculating splenic dimensions. Standards of normal spleen sizes have been developed for the general adult population, for children, and even for tall healthy athletes, thereby enabling US diagnosis of splenomegaly. Extrapolation of data from the normal population to pregnant women might, however, be inaccurate because of the physiological changes throughout gestation. We have recently reported a prospective study evaluating the size of the maternal spleen throughout pregnancy and hereby review the results and their implications. PMID- 17366711 TI - Anatomic and pathologic computed tomographic findings following splenectomy. AB - Computed tomography (CT) is frequently used for postoperative evaluation in patients who have undergone splenectomy, on either an elective or an emergency basis. This pictorial article reviews and demonstrates the CT findings of postoperative anatomic changes, as well as various postoperative complications following splenectomy. PMID- 17366712 TI - Steven T. miller: the IRS perspective on charity care. PMID- 17366713 TI - Big business, where are you? PMID- 17366714 TI - Reasonable value of noncontracted emergency services: 3 health plan myths. AB - The market sets the "reasonable value" of noncontracted emergency services. In the market for hospital services, payers obtain a discount from full charges only when they purchase one by offering volume or other economic value in a contract. PMID- 17366715 TI - Medicare changes likely to ignite interest in joint ventures. AB - Recent proposed changes in Medicare payment are expected to fuel interest in joint ventures between hospitals and physicians. These changes will likely drive hospitals and physicians to collaborate in the establishment of ambulatory surgical centers. The changes may make it more difficult for physicians to establish an ambulatory surgical center or imaging facility without the assistance of a health system or other third party. PMID- 17366716 TI - Follow the leader. AB - Healthcare leaders can strengthen their leadership skills by: Gaining a deeper understanding of their personal convictions. Requesting regular feedback regarding their leadership skills. Defining the key competencies needed to help their organizations succeed and building on key skill sets. Reflecting on department-specific results from employee opinion surveys and making behavioral changes, when appropriate. Reading biographies of great leaders. PMID- 17366717 TI - Take this job and love it. AB - Successful healthcare organizations have many ways to motivate and inspire their employees: Hire the right people. Communicate clearly and regularly to all employees. Encourage and support education and training. Reward and celebrate successes. PMID- 17366718 TI - Connecting (with) the docs. AB - To achieve a successful physician practice ownership strategy, health systems need to understand the operational differences between physician practices and hospitals. Establishing a culture of collaboration is an essential first step to effectively meeting the practice's operational requirements. Team-building, particularly where finance staff work with physician office staff to address key revenue cycle concerns, is another important key to success. PMID- 17366719 TI - A heart for change. AB - The effectiveness of change management is driven by six factors: A clear and consistent message from the top. A palpable connection between leaders and clinicians. Departments that perform their functions well, but also work in sync with other departments. A healthy level of resistance in the change process. Effective communication. A model for monitoring the change process and responding early to variances. PMID- 17366720 TI - Black space versus white space: the new revenue cycle battleground. AB - To increase revenue from out-of-network claims, there are several things providers can do, including: Identify and track all out-of-network claims. Require all networks to be identified in the contract. Eliminate contracts that include silent PPOs. Limit authorization to negotiate discounts. Establish out-of network metrics. PMID- 17366721 TI - Call of the riled: addressing the financial impact of ED call coverage. AB - Healthcare financial managers can use several strategies to avoid paying call stipends to every specialist group on the call panel: Set a budget in advance-and stick to it. Involve the medical staff. Understand your market. Include performance standards. Revisit your hospital's call coverage program annually. PMID- 17366722 TI - Disaster management: using Internet-based technology. AB - Disasters impose operational challenges and substantial financial burdens on hospitals. Internet-based disaster management technology can help. This technology should: Capture, analyze, and track relevant data. Be available 24/7. Guide decision makers in setting up an incident command center and monitor the completion of jobs by ICC role. Provide assistance in areas that hospitals are not used to dealing with, e.g., chemical or bio-terror agents. PMID- 17366723 TI - All in a day's work: counting days for Medicare reimbursement purposes. AB - CMS rules regarding what constitutes a patient day are often confusing and inconsistent. It is important for hospitals and their advisers to have a clear understanding of CMS's rules regarding what constitutes a patient day, the impact of those rules on Medicare payment, and instances in which CMS's rules may be subject to challenge. Lack of familiarity with the finer points of these rules may result in substantial underpayments for services rendered. PMID- 17366724 TI - P&P Board Statement 15: valuation and financial statement presentation of charity care and bad debts by institutional healthcare providers. PMID- 17366725 TI - Baptist Health Care's standards of performance. PMID- 17366726 TI - Transforming financials into exponential change. PMID- 17366727 TI - The role of the hospital board in the IT agenda. PMID- 17366728 TI - Take your community benefit reporting to the next level. PMID- 17366729 TI - Measuring up: investment policies and practices in not-for-profit health care. PMID- 17366730 TI - Medicare inpatient ICU and CCU charges rising faster than other nursing charges. PMID- 17366731 TI - Synthesis of novel 2'-methyl carbovir analogues as potent antiviral agents. AB - In this study, the synthesis procedures of 2'-branched carbovir analogues were accomplished. The introduction of a methyl group in the requisite 2'-position was carried out by the addition of a carbonyl using isopropenyl magnesium bromide. The desired compound, cyclopentenol 10(beta), was synthesized via ring-closing metathesis using a second-generation Grubbs' catalyst. The nucleosidic bases (adenine, cytosine, thymine, uracil, 5-fluorouracil and 5-iodouracil) were efficiently coupled using a Pd (0) catalyst. When the synthesized compounds were examined for their activity against several viruses, including HIV-1, HSV-1, HSV 2 and HCMV, the 5-iodouracil analogue, 23, exhibited significant anti-HCMV activity. PMID- 17366732 TI - Synthesis and antibacterial activity of N-[5-(chlorobenzylthio)-1,3,4-thiadiazol 2-yl] piperazinyl quinolone derivatives. AB - A series of N-[5-(chlorobenzylthio)-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives (4a-I) have been synthesized by reaction of piperazinyl quinolones with 5-chloro-2-(chlorobenzylthio)-1,3,4-thiadiazoles. Their structures were confirmed by elemental analysis, IR and NMR spectra. The antibacterial activities of 4a-I against a variety of Gram-positive and Gram-negative bacteria were determined. Several compounds showed a good antibacterial activity against Gram positive bacteria among which, compound 4e with a 2-chlorobenzylthio moiety in ciprofloxacin derivative, exhibited high activities against Staphylococcus aureus and Staphylococcus epidermidis (MIC = 0.06 microg/mL). The structure-activity relationship (SAR) study revealed that the position of chlorine atom on benzyl moiety would dramatically affect the antibacterial activities of the synthesized compounds. PMID- 17366733 TI - Flavonoids from the flower of Rhododendron yedoense var. poukhanense and their antioxidant activities. AB - Antioxidant flavonoids have been isolated from the flower of Rhododendron yedoense var. poukhanense. One new flavonoid and three known flavonoids, quercetin-5-O-beta-D-glucopyranoside (1), quercetin (3), and quercitrin (4), were isolated from the butanol and ethyl acetate extracts of the plant. The new flavonoid was identified as myricitrin-5-methyl ether (2). The isolation of these flavonoids from this plant, for the first time, is a valuable finding. The flavonoids were evaluated for their antioxidant activities using 1,1-diphenyl-2 picrylhydrazyl free radical (DPPH), TBARS (thiobarbituric acid reactive substance) and superoxide anion radical (O2-) in the xanthine/xanthine oxidase assay system. In the DPPH scavenging assay, the IC50 values were 4.5 +/- 0.48 microM for compound 2 and 9.7 +/- 0.29 microM for compound 3, which showed an antioxidant activity approximately 1.5-2 times higher than the antioxidant activity of alpha-tocopherol (9.8 +/- 0.94 microM). Additionally, the antioxidant activities of myricitrin-5-methyl ether (2) (IC50 = 1.7 +/- 0.22 microM) and quercetrin (4) (IC50 = 1.9 +/- 0.63 microM) were higher than that of L-ascorbic acid (IC50 = 7.4 +/- 0.63 microM) when evaluated using a TBARS assay. Compound 2 showed high activity in both the inhibition of xanthine oxidase (1.1 +/- 0.21 mM) and in the activation of superoxide scavenging. PMID- 17366734 TI - Cytotoxic isoquinoline alkaloids from the aerial parts of Corydalis incisa. AB - Three known isoquinoline alkaloids were isolated from the chloroform-soluble fraction of the methanolic extract of the aerial parts of Corydalis incisa (Papaveraceae) through repeated column chromatography. Their chemical structures were elucidated as corynoline (1), corynoloxine (2) and 6-oxocorynoline (3) using spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2 and HCT15 tumor cells. PMID- 17366735 TI - Synthesis of psoralen derivatives and their blocking effect of hKv1.5 channel. AB - Previously, we found that a furocoumarin derivative, psoralen (7H-furo[3,2 g][1]benzopyran-7-one), blocked a human Kv1.5 potassium channel (hKv1.5) and has a potential antiarrhythmic effect. In the present study, to develop more potent hKv1.5 blockers or antiarrhythmic drugs, we synthesized ten psoralen derivatives and examined their blocking effects on hKv1.5 stably expressed in Ltk cells. Among the newly synthesized psoralen derivatives, three derivatives (Compounds 5, 9 and 10) showed the open channel-blocking effect. Compound 9 among them was the most potent in blocking hKv1.5. We found that compound 9, one of the psoralen derivatives, inhibited the hKv1.5 current in a concentration-, use- and voltage dependent manner with an IC50 value of 27.4 +/- 5.1 nM at +60 mV. Compound 9 accelerated the inactivation kinetics of the hKv1.5 channel, slowed the deactivation kinetics of hKv1.5 current resulting in a tail crossover phenomenon. Compound 9 inhibited hKv1.5 current in a use-dependent manner. These results indicate that compound 9, one of psoralen derivatives, acts on hKv1.5 channel as an open channel blocker and is much more potent than psoralen in blocking hKv1.5 channel. If further studies were done, compound 9 might be an ideal antiarrhythmic drug for atrial fibrillation. PMID- 17366736 TI - Antioxidant flavone glycosides from the leaves of Sasa borealis. AB - Sasa borealis (Poaceae) is a perennial medicinal plant which is a major source of bamboo leaves in Korea. The n-BuOH extract of S. borealis leaves exhibited significant antioxidant activity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and a cytoprotective effect against oxidative damage in HepG2 cells. Bioactivity-guided fractionation by column chromatography led to the isolation of two antioxidative flavonoid C-glycoside derivatives, isoorientin (2) and isoorientin 2"-O-alpha-L-rhamnoside (4) along with tricin 7-O-beta-D glucopyranoside (1) and apigenin 6-C-beta-D-xylopyranosyl-8-C-beta-D glucopyranoside (3). Their structures were identified on the basis of chemical and spectroscopic methods. The radical scavenging activity and cytoprotective effect against oxidative damage of all the isolated compounds were also evaluated. Isoorientin (2) and isoorientin 2-O-alpha-L-rhamnoside (4) showed potent free radical scavenging activity with IC50 values of 9.5 and 34.5 microM, respectively, and strong cytoprotective effects against t-BOOH-induced oxidative damage in HepG2 cells, at very low concentrations of 1.1 microM isoorientin and 0.8 microM isoorientin 2-O-alpha-L-rhamnoside. This is the first report of the isolation and antioxidant activity of compounds 2 and 4 from S. borealis. PMID- 17366737 TI - Stereoselective synthesis of L-threo-sphingosine, L-threo-sphinganine, D-threo sphingosine, and D-threo-sphinganine via oxazoline formation and olefin cross metathesis; potent protein kinase C inhibitor analogues. AB - In this study, we explored a convenient and concise route for synthesis of L threo-sphingosine, D-threo-sphingosine, L-threo-sphinganine and D-threo sphinganine from commercially available L- or D-serine. The key steps are the simple preparation of trans-oxazoline and intermolecular olefin cross metathesis. PMID- 17366738 TI - Isolation of constituents and anti-complement activity from Acer okamotoanum. AB - A novel acylated sterol glucoside (1) along with four known compounds, beta amyrin acetate (2), 3beta,24-dihydroxytaraxer-14-ene (3), cleomiscosin A (4), and cleomiscosin C (5), were isolated from the leaf and twig of Acer okamotoanum Nakai (Aceraceae). The structure of the new compound was determined to be beta sitosterol glucoside-3'-O-hexacosanoicate based on chemical and spectroscopic analyses. In addition, the novel compound was found to exhibit a significant inhibitory effect (IC50 value of 0.2 microM) on the complement system activated by the classical pathway. PMID- 17366739 TI - Gnidilatimonoein from Daphne mucronata induces differentiation and apoptosis in leukemia cell lines. AB - Gnidilatimonoein is a new diterpene ester, recently isolated from the leaves of Daphne macronata with potent anti-tumoral and anti-metastastic activities (Yazdanparast et al., 2004). Promyeloblastic (KG1), promyelocytic (NB4) and promonocytic (U937) cells were cultured in the presence of various concentrations of the drug (0.5-3.0 microM) for 3 days. Herein, we report that gnidilatimonoein induces differentiation and apoptosis in KG1, NB4 and U937 cells. The drug inhibited growth and proliferation of KG1, NB4 and U937 cells with IC50 values of 1.5, 1.5 and 1.0 microM, respectively, after 72 h of treatment. Cell viability was also decreased by 18%, 20% and 23%, respectively, after 72 h treatment with the drug. NBT reducing assay revealed that the inhibition of proliferation is associated with differentiation especially toward monocytes-like morphology. Indeed, the drug at 0.5-1.5 microM induced differentiation by 5-50% in the cells. Acridine orange/ethidium bromide (AO/EtBr) double staining and DNA fragmentation assays revealed that apoptosis occurred after differentiation of the cells. Based on the present data, it seems that the new compound is a good candidate for further evaluation as an effective chemotherapeutic agent acting through induction of differentiation and apoptosis. PMID- 17366740 TI - Equation chapter 1 section 1A new method for predicting human hepatic clearance from in vitro experimental data using molecular descriptors. AB - The present study demonstrated that the information of molecular descriptors of drugs increases the accuracy of predicting human in vivo hepatic clearance from in vitro experimental data in humans and rats. A new method uses not only the experimental data but also the information of molecular descriptors. Predictions for the datasets from hepatocyte experiments and microsome experiments were made by the present method, and the prediction accuracy was compared with those of the previous methods, such as methods using in vitro-in vivo scaling factor and multiple linear regression analysis, that use only the experimental data. Results showed that the present method was the most accurate prediction model with the lowest prediction errors and the strongest correlations. These results suggest that the information of molecular descriptors is significant for predicting the human in vivo pharmacokinetic parameters from in vitro experimental data. This study also demonstrated that in vitro experimental data in humans and rats were important information for predicting human in vivo hepatic clearance, and the additional rat in vivo data were not significant for prediction with the information of molecular descriptors. These results imply that the present method can be useful for high-throughput drug candidate screening by reducing the time and cost in the early stage of the drug discovery process. PMID- 17366741 TI - Immunoregulatory abnormalities of T cells and hyperreactivity of B cells in the in vitro immune response in pristane-induced lupus mice. AB - Systemic lupus erythematosus (SLE) is characterized by overactive B cells that differentiate into autoantibody-forming cells, aberrant T cell function that provides helping B cells produce autoantibodies, and overproduction of proinflammatory cytokines. However, immunodysregulation in lupus pathogenensis remains incomplete. We examined mitogen-stimulated production of proinflammatory cytokines, cell proliferation, T cell activation, and T cell apoptosis in vitro in pristane-induced lupus BALB/c mice compared to normal mice. LPS-stimulated production of IL-6 and IL-10 by splenocytes and macrophages from pristane-induced lupus mice were remarkably up-regulated compared to normal mice, whereas production of macrophage TNF-alpha was significantly down-regulated. Moreover, in vitro production of IL-2, IL-6, IL-10 and IFN-gamma by Con A-stimulated splenocytes, cell proliferation in LPS- or Con A-stimulated- thymocytes and splenocytes, and expression of CD69+CD4+ T cells in Con A-stimulated splenocytes were greatly increased in cells derived from pristane-induced lupus mice compared to normal mice. In addition, splenic T cells and CD4+ T cells in thymocytes from pristane-induced lupus mice were more resistant than nonautoimmune normal cells to Con A-induced apoptosis. Our findings indicate that immunoregulatory abnormalities of T cells and hyperreactivity of B cells in the in vitro immune responses in pristane-induced lupus mice may explain some of lupus pathogenesis. PMID- 17366742 TI - Antiestrogenic potentials of ortho-PCB congeners by single or complex exposure. AB - Di-ortho PCB congeners 52, 138, 153 and 180, and the mono-ortho coplanar congener 118 have been detected as a complex mixture in human tissue in Korea. This study examined the antiestrogenic effects of samples exposed to single or combination treatment of the ortho-PCB congeners. In order to determined the combined toxicity, a sample mixture (M1, M2, M3, M4, and M5) was designed based on the ortho-PCB congeners found in Korean human tissue. With the exception of PCB 52, the ortho-PCB congeners (PCB 118, 138, 153, and 180) showed weak antiestrogenic activity. The antiestrogenic activity of di-ortho PCB congeners (PCB 138, 153, and 180) was induced by the depletion of endogenous E2 as well as through the ER dependent pathway, whereas the antiestrogenic activity of mono-ortho PCB 118 was only induced through the depletion of endogenous E2. When the MCF7-BUS cells were treated with mixtures containing the no effective concentration (10(-6) M) of the PCB congeners, M3 (PCB 118 + PCB 138 + PCB 180) and M4 (PCB 118 + PCB 138) had an antiestrogenic effect but the other mixtures (M1; PCB 52 + PCB 118 + PCB 138 + PCB 180, M2; PCB 118 + PCB 138 + PCB 153 + PCB 180, M5; PCB 118 + PCB 180) did not. Although the mechanism for the interaction between the PCB congeners is not completely understood, it was presumed that exposure to a mixture of the PCB congeners might have synergistic effects on their antiestrogenicity through the ER-independent pathway. PMID- 17366743 TI - Oleanolic acid, a pentacyclic triterpenoid, induces rabbit platelet aggregation through a phospholipase C-calcium dependent signaling pathway. AB - Oleanolic acid (3beta-hydroxy-olea-12-en-28-oic), a pentacyclic triterpenoid, exists widely in the plant kingdom and has a wide variety of pharmacological effects such as antitumor, antifungal, insecticidal, hepatoprotective and anti HIV activities. This paper reports that oleanolic acid induces the aggregation of rabbit platelets, a mechanism was also investigated. Oleanolic acid at concentrations of 25, 50, 100 and 200 microM induced the aggregation of washed rabbit platelets in a concentration-dependent manner. Pretreating the platelets with U73122, a phospholipase C (PLC) inhibitor, blocked the oleanolic acid induced-aggregation, whereas acetylsalicylic acid (ASA), a cyclooxygenase (COX) inhibitor, had no effect. In addition, the effect of oleanolic acid on serotonin secretion, which is a marker for dense granule secretion, was determined. Oleanolic acid induced serotonin secretion in a similar concentration-dependent manner as observed with platelet aggregation. Pretreating the platelets with U73122 blocked the oleanolic acid-induced serotonin secretion and cytosolic calcium mobilization. Overall, these results suggest that oleanolic acid can induce platelet aggregation, which may be mediated by the stimulation of PLC mediated cytosolic calcium mobilization. PMID- 17366744 TI - The effect of meloxicam/ethanolamine salt formation on percutaneous absorption of meloxicam. AB - This study was undertaken to prepare meloxicam-ethanolamine salts (MX-EAs) that enhance the transdermal delivery of meloxicam. The physicochemical properties of MX-EAs were investigated by solubility measurements, Differential Scanning Calorimetry (DSC), and Infrared Spectroscopy (FT-IR). The DSC thermogram and FTIR spectra indicated that meloxicam formed salts with ethanolamines. The effects of various vehicles on the percutaneous absorption of meloxicam and of its salts across hairless mouse skin were evaluated using a flow-through diffusion cell system at 37 degrees C. Salt formation lowered the melting point of meloxicam and slightly reduced its octanol/water partition coefficient. Meloxicam monoethanolamine salt (MX-MEA) and meloxicam-diethanolamine salt (MX-DEA) had greater solubilities and transdermal permeation rates across hairless mouse skin than meloxicam alone in various vehicles. Moreover, although the solubility of meloxicam-triethanolamine salt (MX-TEA) was generally lower than that of meloxicam, its permeation rate across the skin was higher. The fluxes of meloxicam and its salts were generally lower than those of piroxicam. PMID- 17366745 TI - Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac. AB - The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters. PMID- 17366746 TI - Comparison study of the extraction methods of paraquat in post-mortem human blood samples. AB - The most important step for Paraquat analysis in post-mortem human blood (PMB) is its extraction from the specimens, as Paraquat is insoluble in organic solvents due to its ionic form. The most common extraction method, solid phase extraction (SPE), has been used for the extraction of Paraquat from PMB. However, SPE procedures are somewhat time-consuming, and resulted in unsatisfactory recovery in our laboratory. Therefore, SPE procedures, with five extraction solvents for the liquid-liquid extraction (LLE) of paraquat in PMB, were compared using HPLC, and the chloroform-ethanol (7:3, v/v) solvent mixture was found to be the most effective. The recoveries of Paraquat using the 7:3 solvent mixture in human whole blood samples, which were already spiked with paraquat standards (1.05, 2.10 and 4.21 microg/mL) averaged 98.20, 105.71 and 99.40%, but the recoveries from the SPE were about 74.29, 78.50 and 80.10%, respectively. Linearity was obtained for the range of Paraquat standards, with a correlation coefficient; r2 > 0.999. The limit of detection (LOD, with S/N > or =3) and limit of quantitation (LOQ, with S/N > or =10) were 0.01 and 0.05 microg/mL, respectively. The extraction method was successfully applied to seven real post-mortem cases involving paraquat poisoning. PMID- 17366747 TI - Behavior of itraconazole and benzyl alcohol in aqueous solution containing nonionic surfactants. AB - In order to investigate the behavior of itraconazole and benzyl alcohol in aqueous solution containing surfactants, the distribution of itraconazole and benzyl alcohol between the micellar and aqueous phases was determined and the partition of itraconazole between the hydrophilic and lipophilic moieties in micelles was measured. From these experiments, we can conclude that: (1) in aqueous surfactant solution, itraconazole mainly exists in the micellar phase; (2) the cosolvency effect of benzyl alcohol has a negligible effect on the solubility of itraconazole in aqueous solution; (3) itraconazole tends to align itself in an intermediate position (palisade layer) within the surfactant molecules forming the micelle, which may result in the destruction of the micellar structure; and (4) the precipitation of itraconazole may occur in the process of the exchange of benzyl alcohol between the aqueous and micellar phases. This is the mechanism of destabilization of colloidal drug carriers based on benzyl alcohol. PMID- 17366748 TI - Enhanced bioavailability of poorly water-soluble clotrimazole by inclusion with beta-cyclodextrin. AB - Clotrimazole, a poorly water-soluble antimycotic agent, is a promising agent for various diseases including cancer and sickle cell anemia. To improve the oral bioavailability of clotrimazole, the inclusion compound of clotrimazole with beta cyclodextrin was prepared by spray-drying method and characterized by phase solubility, differential scanning calorimetry and dissolution. Furthermore, the pharmacokinetics after oral administration in rats was then performed compared with clotrimazole powder. The solubility of clotrimazole increased linearly as a function of beta-cyclodextrin concentration, resulting in A(L) type phase solubility diagram which revealed a formation of inclusion compound in a molar ratio of 1:2, with the apparent association constant of 230.2 M(-1). The dissolution rate of clotrimazole in the inclusion compound increased greatly compared to clotrimazole powder in pH 7.4 phosphate buffer solution. The inclusion compound gave significantly higher initial plasma concentrations, Cmax and AUC of clotrimazole than did clotrimazole powder when they were administered as suspension form, indicating that the drug from inclusion compound could be more orally absorbed in rats. Thus, the oral bioavailability of clotrimazole could be improved markedly by inclusion complexation, possibly due to an increased dissolution rate. PMID- 17366749 TI - Electrochemical behavior and square wave voltammetric determination of aristolochic acid-I. AB - Electroanalytical procedure for the determination of nephrotoxic aristolochic acid-I in the medicinal plant has been developed in the presence of potential interferences of lead and cadmium by square wave voltametry (SWV). Among the phosphate buffers of pH values at 5.0, 6.1, 6.5 and 7.0, the phosphate buffers of pH 6.1 yielded the most accurate analysis of AA-I in the presence of Pb2+ and Cd2+; Pb2+ was precipitated as Pb(HPO4) and did not appear in the SW voltammogram, while Cd2+ appeared at -0.564 V which was well resolved from AA-I at -0.416 V. When the Ip of AA-I was plotted vs. concentrations between 1.67 x 10(-8) M and 1.67 x 10(-6) M in the presence of Pb2+ and Cd2+, a linear calibration curve was obtained with a slope of 6 x 10(8) nA/M and a correlation coefficient of 0.9999. The present method was applied to determine AA in the dried natural products of Aristolochia contorta Bunge; Total AA in the dried root and the ripe fructus of Aristolochia contorta Bunge were found as 25 +/- 1 microg/g and 85 +/- 3 microg/g, respectively. PMID- 17366750 TI - Pharmacokinetics of baicalein, baicalin and wogonin after oral administration of a standardized extract of Scutellaria baicalensis, PF-2405 in rats. AB - The pharmacokinetics of active components such as baicalein, wogonin and oroxylin A were evaluated after oral administration of a purified extract of Scutellaria baicalensis GEORGI (PF-2405) containing the high contents of baicalein, wogonin and oroxylin A to rats. Following oral administration of PF-2405 at 10, 20 and 40 mg/kg dose (equivalent to 4.5, 9.0 and 18 mg/kg baicalein), a major constituent baicalein and its active metabolite baicalin showed dose-linear pharmacokinetics as evidenced by unaltered dose-normalized AUC, dose-normalized Cmax, Ae(0-30h) and GI(30h) values. Following oral administration of PF-2405 at three doses (equivalent to 0.4, 0.8 and 1.6 mg/kg wogonin), dose-normalized Cmax and dose normalized AUC were comparable between the 20 and 40 mg/kg PF2405 doses, but plasma concentrations of wogonin at 10 mg/kg of PF-2405 were not measurable as they were below limit of quantitation (LOQ; 18 pmol/mL). Following oral administration of PF-2405 at the three doses (equivalent to 1.5, 3.0 and 6.0 mg/kg oroxylin A), the concentrations of oroxylin A in plasma, urine and gastrointestine samples were below the assay LOQ (18 pmol/mL). Significant differences in AUCs, Ae(0-30h) and GI(30h) values for baicalein and baicalin were observed after oral administration of pure baicalein (18 mg/kg) and PF-2405 (40 mg/kg). The increases in AUCs of baicalein and baicalin after oral administration of PF-2405 may have been due to the significant decrease in GO(30h) values for baicalein. PMID- 17366751 TI - Overview of the Medicare and Medicaid programs. PMID- 17366752 TI - Epidemiology and natural history of HPV. AB - Human papillomavirus (HPV) is a highly prevalent, sexually transmitted infection responsible for significant morbidity and mortality. High-risk HPV types are now known to be necessary in the etiology of cervical cancer and to lead to both high grade and low-grade cervical lesions. They are also implicated in a substantial portion of anal, penile, and head and neck precancers and cancers. HPV 16 and 18 are the most common HPV types found in cervical cancer and are responsible for approximately 70% of these cancers. In contrast, low-risk HPV types, the most common of which are HPV 6 and 11, cause genital warts, low-grade cervical lesions, and recurrent respiratory papillomatosis, but they do not cause cervical or other HPV-related cancers. Infection is most common in young, sexually active populations, and an estimated three fourths of adults will be infected with HPV during their lifetime. Cervical screening programs exist in the United States and other developed countries to identify and treat precancerous cervical lesions, but they do not reach all women and are costly. Until recently, no highly effective primary prevention strategy to reduce the risk of HPV acquisition existed. However, a quadrivalent HPV vaccine, which protects against the most common high-risk and low-risk HPV infections (HPV 16, 18, 6, and 11), is now available. In addition, a bivalent HPV vaccine that protects against high-risk HPV types 16 and 18 is in the late stages of clinical development. If implemented widely, vaccination against HPV promises to dramatically reduce HPV-associated morbidity and mortality. PMID- 17366753 TI - Protecting our patients from HPV and HPV-related diseases: the role of vaccines. AB - The clinical burden of disease resulting from human papillomavirus (HPV) infection is substantial and extends from genital warts to cytologic abnormalities to cervical, vaginal, and vulvar cancers and their associated precursor lesions. In addition, HPV is implicated in anal, penile, and head and neck cancers. Thus, HPV-related disease constitutes a significant burden for both men and women. Large phase 2 and 3 clinical trials with a quadrivalent preventive HPV vaccine (HPV 6/11/16/18) and phase 2 trials with a bivalent preventive HPV vaccine (HPV 16/18) have demonstrated that both products are highly efficacious in preventing type-specific HPV infections and HPV-related disease and are well tolerated. Nearly all recipients demonstrate a robust immunologic response that currently appears to be durable for 4 or more years. Immunogenicity data among girls 9 to 15 years of age were used to "bridge" efficacy data from quadrivalent HPV vaccine trials completed to date. In June 2006, the US Food and Drug Administration approved the quadrivalent HPV vaccine for use among females 9 to 26 years of age. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices has recommended the 3-dose series for girls 11 to 12 years of age, catch-up vaccination for girls and women 13 to 26 years of age, and permissive use as early as age 9. Computer models projecting the impact of these preventive HPV vaccines predict that they will be cost-effective and beneficial to the population; the use of preventive HPV vaccines will complement continued cytologic screening programs. Trials are under way to evaluate the duration of immune response as well as efficacy among men and women 27 years of age and older. Girls and women within the targeted age ranges should be offered vaccination to achieve the disease prevention potential of these vaccines. PMID- 17366754 TI - Practical implementation of HPV vaccines in clinical practice. AB - Human papillomavirus (HPV) currently infects approximately 20 million people in the United States. An effective new vaccine has been approved for girls and young women aged 9 to 26 years that can decrease the spread of infection due to HPV and the future incidence of cervical cancer and genital warts. Family physicians should be aware of parental or patient attitudes and knowledge about HPV and concerns about HPV vaccination if they are to successfully implement HPV vaccination in their practices. PMID- 17366755 TI - Do malocclusions affect the individual's oral health-related quality of life? AB - PURPOSE: To assess the impact of different types of malocclusions on the quality of life in 18-year-old young male adults. MATERIALS AND METHODS: A cross sectional survey with a randomly selected sample of 414 young male adults who applied for military service in the city of Florian6polis in 2003 was carried out. Data on malocclusions were obtained through the dental aesthetic index variables. The impact of the oral health conditions on the quality of life was assessed, using the Oral Impact on Daily Performance index. Chi-squared tests were performed and the malocclusions statistically associated with the impact were included in models of unconditional multiple logistic regression. RESULTS: The incisal crowding [OR 2.6 (95%CI 1.4-4.8)] (p = 0.002) and the anterior maxillary irregularity greater than 2 mm [OR 2.5 (95%CI 1.3-4.7)] (p = 0.006) had an impact on 'smiling, laughing and showing teeth without embarrassment'. An over jet measure greater than 5 mm [OR 3.7 (95%CI 1.2-11.2)] (p = 0.021) had an impact on 'maintaining emotional state without being irritable'. The molar relationship did not have an impact. CONCLUSIONS: Some types of malocclusions have an impact on quality of life, especially in terms of satisfaction with appearance. PMID- 17366756 TI - A comparison of the efficacy and ease of use of dental floss and interproximal brushes in a randomised split mouth trial incorporating an assessment of subgingival plaque. AB - PURPOSE: Previous studies have compared the use of interdental brushes and dental floss. However, none have attempted to compare their effects on subgingival plaque. Nor have smokers been excluded from previous studies, where they may have affected the assessment of gingival inflammation. MATERIALS AND METHODS: The present study compared, in untreated patients suffering from mild to moderate periodontitis, the efficacy of dental floss (DF) and interdental brushes (IDB) in the reduction of plaque, gingival inflammation and probing depth in a one-month period prior to subgingival debridement. Ten patients used DF for one side of the dentition and IDB for the other side for one month. Oral hygiene instruction was given at baseline. Measurements were made at baseline and at one month. RESULTS: With IDB, the mean approximal plaque score reduced supragingivally from 14.5 to 5.7 at one month, and with DF, from 12.9 to 5.3; subgingivally the score reduced from 17.3 to 6.7, and 16.7 to 8.1 respectively (p < 0.001). BOP and mean probing depth reduced over time for IDB sites, but not DF sites (p < 0.01). Overall there were no differences between the two devices. Patients preferred IDB because of its simpler method of use. CONCLUSIONS: The use of IDB and DF resulted in similar beneficial effects on subgingival plaque and proximal gingival health. PMID- 17366757 TI - Short-term effects of hygiene education for preschool (kindergarten) children: a clinical study. AB - AIM: To evaluate the outcomes of short (15 minutes) oral hygiene vs. hand hygiene education for preschool children 4 weeks after these interventions. MATERIALS AND METHODS: Sixty-one preschool children (age range 4-6 years) attending four kindergarten classes participated in a 15-minute health education programme on the importance of body cleanliness for general health. In addition, specific instructions on oral hygiene were provided for two randomly selected classes (30 children), while the remaining two classes (31 children) were given instruction of hand and nail cleaning. The oral hygiene status was assessed usingthe plaque control record (PCR). The cleanliness of the hands and fingernails was determined using a hand hygiene index (HHI) and a nail hygiene index (NHI). All three parameters were assessed before the intervention as well as 4 weeks thereafter. RESULTS: Four weeks after education, the PCR had improved for all children from 79.95% to 72.35% (p < 0.001). The NHI had improved from 74.91% to 61.71% (p < 0.001). In addition, the mean PCR of the children given oral hygiene instruction decreased from 83.67% to 72.40%, while the mean PCR of the children given hand and nail cleaning instruction decreased from 76.23% to 72.29% (interaction effect 'time x type of instruction': p = 0.044). Girls' PCR improved significantly more than boys' PCR (Girls, 80.98 vs. 69.71; boys, 78.33 vs. 75.31; p = 0.021). CONCLUSIONS: The results of the study show that even a short, school-based educational intervention at an early age may affect children's oral health promotion significantly. Teachers should, therefore, be encouraged to educate children from an early age about oral hygiene promotion. PMID- 17366758 TI - Antibacterial effect of two toothpastes following a single brushing. AB - PURPOSE: The aim of this double-blind, randomised cross-over study was to compare the antibacterial effect and the substantivity of two toothpaste formulations containing amine fluoride (AmF) or zinc chloride (ZnCl2). MATERIALS AND METHODS: After a professional tooth cleaning, 20 volunteers refrained from all oral mechanical hygiene measures for the subsequent 24 hours (day 0). Subsequently, a plaque sample was taken from three teeth and analysed for vitality of the plaque bacteria by means of the vital fluorescence technique (VF0; in %). After assessment of this baseline value the subjects had to brush their teeth for 2 minutes with 1.2 ml of the allocated toothpaste containing (a) 0.66% AmF or (b) 0.2% ZnCl2. For the following 8 hours no oral hygiene measures were allowed. After 4 and after 8 hours further plaque samples were analysed for biofilm vitality (VF4, VF8). During the following 3 days the volunteers had to brush twice daily for 2 minutes with the allocated toothpaste. On day 4, plaque index was assessed using the criteria of Quigley and Hein (Turesky modification). After a washout time of 9 days the next test cycle with the other toothpaste was started. RESULTS: Both toothpastes reduced the biofilm vitality significantly at VF4 and VF8 compared with VF0 (p < or =0.001). While after 8 hours the vitality values for the ZnCl2-toothpaste obtained significantly higher reductions (53%) than for the AmF-toothpaste (44%), results for plaque index were not significantly different (0.98 and 1.04 respectively). CONCLUSIONS: Both toothpastes showed a significant and prolonged antibacterial effect up to 8 hours with a benefit in favour of the ZnCl2 toothpaste. PMID- 17366759 TI - Clinical effectiveness of toothbrushes and toothbrushing methods of plaque removal on partially erupted occlusal surfaces. AB - PURPOSE: The aim of this crossover study was to compare the efficacy of conventional and end-tufted toothbrushes and two methods of plaque removal on partially erupted occlusal surfaces in schoolchildren. MATERIALS AND METHODS: Thirty-seven subjects, aged 5-7 years, with at least one partially erupted lower permanent first molar, were randomly divided into three groups. Occlusal plaque (baseline) was scored using a disclosing solution applied to the occlusal surface of an erupting molar. Subjects were instructed to use a conventional toothbrush with horizontal scrubbing (conventional group); a conventional toothbrush with transverse technique (modified group); or an end-tufted toothbrush (end-tufted group). Subjects returned after a one-week washout period and brushed with the alternate toothbrush or technique. Final plaque condition was evaluated again using the same scoring as at baseline. Occlusal plaque reduction (baseline to final) percentiles were compared using paired t-test. RESULTS: No statistically significant difference was found among transverse and end-tufted techniques (modified and end-tufted groups respectively) (p > 0.05). The conventional group was less effective on occlusal plaque removal in erupting first molars than the other groups (p < 0.05). CONCLUSION: The conventional toothbrushing technique was not satisfactory compared with other tested techniques on occlusal plaque removal. Moreover, the use of a conventional toothbrush with a modified technique was very effective on erupting first permanent molars without any additional costly device. PMID- 17366760 TI - Evaluation of a novel periodontal risk assessment model in patients presenting for dental care. AB - PURPOSE: The present study was designed to develop a new periodontal risk assessment model based on the periodontal risk assessment (PRA) model by Lang and Tonetti, and to evaluate the risk assessment capability of the proposed model. MATERIALS AND METHODS: Twenty-six patients diagnosed with chronic periodontitis were selected randomly and a thorough examination and charting of the periodontal status was performed. An intra-oral periapical radiograph of the area with the deepest probing depth was also taken. The following parameters were recorded: percentage of sites with BOP, number of sites with pocket depths > or = 5mm, number of teeth lost, bone loss/age ratio, attachment loss/age ratio, diabetic and smoking status, dental status, other systemic factors and risk determinants. Using Microsoft Excel, the parameters were plotted on the radar chart as per the original and the proposed model. RESULTS: Of the cases identified by the original model, 42.3% were high-risk cases and 30.8% of the cases were low-risk cases. In the proposed model, 46.2% of high-risk cases and 46.2% of low-risk cases were identified. Only 7.7% of the cases identified with the new model were moderate risk cases. Statistical analysis demonstrated that there was no significant difference between the risk scores of the two models. CONCLUSIONS: The results suggest that risk assessment by this model does not vary significantly as compared to the original model, and both are equally adept at detecting potential risk groups. PMID- 17366761 TI - The prevalence of dentine hypersensitivity among adult patients attending a Nigerian teaching hospital. AB - PURPOSE: The purpose of this study was to determine the prevalence of dentine hypersensitivity and to examine some associated factors such as initiating stimuli among adult patients attendingthe Dental Clinic of the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. MATERIALS AND METHODS: All consecutive adult patients that presented at the oral diagnosis unit over a period of 13 months, from March 2003 to March 2004, were included in the study. Relevant history, such as nature of the pain, initiating stimulus, frequency of episode, interference with eating, drinking and toothbrushing were taken. Evidence of tooth surface loss was noted. Dentine hypersensitivity was confirmed clinically by the use of air blast from the air-water jet and scratching suspected surfaces with a dental probe. RESULTS: Of the 2165 patients examined, 29 were diagnosed as having dentine hypersensitivity, giving a prevalence figure of 1.34%. The commonest teeth affected were the molars and the commonest initiating factor was cold water. Occlusal surfaces were most affected, followed by cervical surfaces. A male predominance was observed. CONCLUSION: A lower prevalence figure was found in the present study in comparison to earlier reported studies. The prevalence of dentine hypersensitivity is slightly lower in females, with female to male ratio of 1 to 1.42. Dentine hypersensitivity resulted in more severe disturbance when drinking water than when eating or brushing. PMID- 17366762 TI - Caries preventive effect of occlusal sealant extension to ART restorations compared with non-extended amalgam restorations. AB - PURPOSE: To estimate the survival of retention of sealant extension to occlusal ART restorations over 6.3 years; and to test the null-hypothesis that there is no difference in dentine caries lesion development in sealant extension to ART restorations in comparison with sealant free extensions to amalgam restorations in occlusal surfaces over 6.3 years. MATERIALS AND METHODS: In a parallel group design, 318 and 254 grade 2 children were randomly assigned to the ART and amalgam group respectively. Eight dentists placed 925 evaluatable single- and multiple-surfaces restorations. A total of 424 sealed extensions to occlusal ART and 284 sealant free extensions to occlusal amalgam restorations were available for analyses. The modified actuarial method was used to estimate survival percentages. The jackknife method was applied to calculate the SE in the cumulative survival percentages. RESULTS: After 6.3 years, 11.2% (SE = 2.2%) of sealant extensions were fully retained and 16.7% (SE = 2.8%) were partially retained. After 6.3 years, 86.4% (SE = 2.2%) of the sealed pits and fissures adjacent to occlusal ART restorations and 89.9% (SE = 2.4%) of non-sealed pits and fissures adjacent to occlusal amalgam restorations were free of dentine caries lesions. Neither this difference nor those at earlier evaluation years were statistically significant (p > 0.05). CONCLUSION: Sealing pits and fissures adjacent to occlusal ART restorations did not result in a caries preventive benefit over non-sealed pits and fissures adjacent to occlusal amalgam restorations in this group of children over 6.3 years. PMID- 17366763 TI - Macroscopic and microscopic effects of GaAIAs diode laser and dexamethasone therapies on oral mucositis induced by fluorouracil in rats. AB - PURPOSE: To present an animal model for mucositis induced by fluorouracil in rats, and test two therapeutic options, the GaAIAs laser and topical dexamethasone, analysing them with regard to the quality and quantity of tissue alterations and comparing them with the phases of mucositis. MATERIALS AND METHODS: Forty-five Wistar rats (250 g) were treated with fluorouracil (60 mg/kg) and, in order to mimic the clinical effect of chronic irritation, the palatal mucosa was irritated by superficial scratching with an 18-gauge needle. When all of the rats presented oral ulcers of mucositis, they were randomly allocated to one of three groups: group I was treated with laser (GaAIAs), group II was treated with topical dexamethasone, and group III was not treated. Excisional biopsies of the palatal mucosa were then performed, and the rats were killed. Tissue sections were stained with haematoxylin and eosin for morphological analyses, and with toluidine blue for mast-cell counts. RESULTS: Group I specimens showed higher prevalence of ulcers, bacterial biofilm, necrosis and vascularisation, while group II specimens showed higher prevalance of granulation tissue formation. There were no significant statistical differences in the numbers of mast cells and epithelial thickness between groups. CONCLUSION: For the present model of mucositis, rats with palatal mucositis treated with laser (GaAIAs) showed characteristics compatible with the ulcerative phase of oral mucositis, and rats treated with topical dexamethasone showed characteristics compatible with the healing phase of mucositis. Topical dexamethasone was more efficient in the treatment of rats' oral mucositis than the laser. PMID- 17366764 TI - Study of the buffering capacity, pH and salivary flow rate in type 2 well controlled and poorly controlled diabetic patients. AB - PURPOSE: This study measured the flow rate, pH and buffering capacity of saliva from well- and poorly metabolically controlled Type 2 diabetic patients in three cities of the southern part of Brazil, compared with healthy individuals from the same cities. MATERIALS AND METHODS: Whole saliva was collected by mechanical stimulation and buffering capacity and glucose level were measured. Blood was collected after 12 hours fasting and glucose and glycosylated haemoglobin concentrations were determined. The data were analysed by one-way ANOVA and Student-Newman-Keuls (alpha= 0.05). RESULTS: The flow rate was lower in the Type 2 diabetic patients, regardless of whether they were well or poorly metabolically controlled, compared with healthy individuals (p < 0.05). Salivary glucose concentration was higher in both diabetic patient groups, i.e. well and poorly metabolically controlled, than in the control (p < 0.05). CONCLUSION: The metabolic control of hyperglycaemia was not sufficient to improve the salivary flow rate or the salivary glucose concentration. PMID- 17366765 TI - Deadly wells: taking action to protect future generations. PMID- 17366766 TI - A conceptual model to be used for community-based drinking-water improvements. AB - A conceptual model that can be applied to improve community-based drinking-water in crisis-type situations has been developed from the original general science and technology/development bridging concept and from a case study in Northwest Bangladesh. The main feature of this model is the strengthened role of communities in identifying and implementing appropriate drinking-water improvements with facilitation by multi-disciplinary collaborative regional agency networks. These combined representative community/regional agency networks make decisions and take actions that involve environmental and health data, related capacity factors, and appropriateness of drinking-water improvements. They also progressively link regional decisions and actions together, expanding them nationally and preferably within a sustainable national policy-umbrella. This use of the model reflects stronger community control and input with more appropriate solutions to such drinking-water crisis situations and minimization of risk from potentially-inappropriate 'externally-imposed' processes. The application here is not intended as a generic or complete poverty-alleviation strategy by itself but as a crisis-solving intervention, complementary to existing and developing sustainable national policies and to introduce how key principles and concepts can relate in the wider context. In terms of the Bangladesh arsenic crisis, this translates into community/regional networks in geographic regions making assessments on the appropriateness of their drinking water configuration. Preferred improvement options are decided and acted upon in a technological framework. Options include: pond-sand filters, rainwater harvesting, dugwell, deep-protected tubewell, and shallow tubewell with treatment devices. Bedding in the regional drinking-water improvement configuration protocols then occurs. This involves establishing ongoing representative monitoring and screening, clear delineation of arsenic-contaminated wells with inter-regional linking, and national expansion within national drinking-water policy frameworks. PMID- 17366767 TI - Review of coagulation technology for removal of arsenic: case of Chile. AB - Coagulation technology has been used since 1970 in northern Chile for removing arsenic from drinking-water. This experience suggests that coagulation is an effective technology for the removal of arsenic. It is currently possible to reduce arsenic from 400 microg/L to 10 microg/L at a rate of 500 L/sec, assuming pH, oxidizing and coagulation agents are strictly controlled. The Chilean experience with the removal of arsenic demonstrates that the water matrix dictates the selection of the arsenic-removal process. This paper presents a summary of the process, concepts, and operational considerations for the use of coagulation technology for removal of arsenic in Chile. PMID- 17366768 TI - Current status and prevention strategy for coal-arsenic poisoning in Guizhou, China. AB - Arsenic exposure from burning coal with high arsenic contents occurs in southwest Guizhou, China. Coal in this region contains extremely high concentrations of inorganic arsenic. Arsenic exposure from coal-burning is much higher than exposure from arsenic-contaminated water in other areas of China. The current status and prevention strategies for arsenic poisoning from burning high-arsenic coal in southwest Guizhou, China, is reported here. Over 3,000 arsenic intoxicated patients were diagnosed based on skin lesions and urinary arsenic excretion. Non-cancerous toxicities and malignancies were much more common and severe in these patients than in other arsenic-affected populations around the world. The high incidence of cancer and arsenic-related mortality in this cohort is alarming. Chelation therapy was performed but the long-term therapeutic effects are not satisfactory. The best prevention strategy is to eliminate arsenic exposure. Funds from the Chinese Government are currently available to solve this arsenic exposure problem. Strategies include the installation of vented stoves, the use of marsh gas to replace coal, health education, the improvement of nutritional status, and the use of various therapies to treat arsenic-induced skin and liver diseases. PMID- 17366769 TI - Seasonal variation of arsenic concentrations in tubewells in west Bengal, India. AB - This study was conducted to monitor the changes in arsenic concentration during different seasons in a one-year period during 2002-2003 in selected tubewells in an arsenic-affected area in the district of South 24 Parganas in West Bengal, India, and to map the location of the wells. Seasonal variations in concentrations of arsenic in water were measured from 74 selected tubewells, ranging in depth from 40 to 500 feet. Water samples were collected from these wells during winter, summer, monsoon, and the following winter in 2002-2003. A global positioning system was used for locating the tubewells, and a geographic information system was used for mapping. There was evidence of seasonal variation in concentrations of arsenic in water (p=0.02) with the minimum average concentration occurring in the summer season (694 microg/L) and the maximum in the monsoon season (906 microg/L). From the winter of 2002 to the winter of 2003, arsenic concentrations increased, irrespective of the depth of the tubewells, from an average of 464 microg/L to 820 microg/L (p<0.001). This extent of variation in arsenic concentration, if confirmed, has important implications for both epidemiological research and mitigation programmes. PMID- 17366770 TI - Targeting low-arsenic groundwater with mobile-phone technology in Araihazar, Bangladesh. AB - The Bangladesh Arsenic Mitigation and Water Supply Program (BAMWSP) has compiled field-kit measurements of the arsenic content of groundwater for nearly five million wells. By comparing the spatial distribution of arsenic inferred from these field-kit measurements with geo-referenced laboratory data in a portion of Araihazar upazila, it is shown here that the BAMWSP data could be used for targeting safe aquifers for the installation of community wells in many villages of Bangladesh. Recent experiences with mobile-phone technology to access and update the BAMWSP data in the field are also described. It is shown that the technology, without guaranteeing success, could optimize interventions by guiding the choice of the drilling method that is likely to reach a safe aquifer and identifying those villages where exploratory drilling is needed. PMID- 17366771 TI - Reduction in urinary arsenic with bottled-water intervention. AB - The study was conducted to measure the effectiveness of providing bottled water in reducing arsenic exposure. Urine, tap-water and toenail samples were collected from non-smoking adults residing in Ajo (n=40) and Tucson (n=33), Arizona, USA. The Ajo subjects were provided bottled water for 12 months prior to re-sampling. The mean total arsenic (microg/L) in tap-water was 20.3+/-3.7 in Ajo and 4.0+/ 2.3 in Tucson. Baseline urinary total inorganic arsenic (microg/L) was significantly higher among the Ajo subjects (n=40, 29.1+/-20.4) than among the Tucson subjects (n=32, 11.0+/-12.0, p<0.001), as was creatinine-adjusted urinary total inorganic arsenic (microg/g) (35.5+/-25.2 vs 13.2+/-9.3, p<0.001). Baseline concentrations of arsenic (microg/g) in toenails were also higher among the Ajo subjects (0.51+/-0.72) than among the Tucson subjects (0.17+/-0.21) (p<0.001). After the intervention, the mean urinary total inorganic arsenic in Ajo (n=36) dropped by 21%, from 29.4+/-21.1 to 23.2+/-23.2 (p=0.026). The creatinine adjusted urinary total inorganic arsenic and toenail arsenic levels did not differ significantly with the intervention. Provision of arsenic-free bottled water resulted in a modest reduction in urinary total inorganic arsenic. PMID- 17366772 TI - Arsenic contamination in food-chain: transfer of arsenic into food materials through groundwater irrigation. AB - Arsenic contamination in groundwater in Bangladesh has become an additional concern vis-a-vis its use for irrigation purposes. Even if arsenic-safe drinking water is assured, the question of irrigating soils with arsenic-laden groundwater will continue for years to come. Immediate attention should be given to assess the possibility of accumulating arsenic in soils through irrigation-water and its subsequent entry into the food-chain through various food crops and fodders. With this possibility in mind, arsenic content of 2,500 water, soil and vegetable samples from arsenic-affected and arsenic-unaffected areas were analyzed during 1999-2004. Other sources of foods and fodders were also analyzed. Irrigating a rice field with groundwater containing 0.55 mg/L of arsenic with a water requirement of 1,000 mm results in an estimated addition of 5.5 kg of arsenic per ha per annum. Concentration of arsenic as high as 80 mg per kg of soil was found in an area receiving arsenic-contaminated irrigation. A comparison of results from affected and unaffected areas revealed that some commonly-grown vegetables, which would usually be suitable as good sources of nourishment, accumulate substantially-elevated amounts of arsenic. For example, more than 150 mg/kg of arsenic has been found to be accumulated in arum (kochu) vegetable. Implications of arsenic ingested in vegetables and other food materials are discussed in the paper. PMID- 17366773 TI - Spatial and temporal variations in arsenic exposure via drinking-water in northern Argentina. AB - This study evaluated the spatial, temporal and inter-individual variations in exposure to arsenic via drinking-water in Northern Argentina, based on measurements of arsenic in water, urine, and hair. Arsenic concentrations in drinking-water varied markedly among locations, from <1 to about 200 microg/L. Over a 10-year period, water from the same source in San Antonio de los Cobres fluctuated within 140 and 220 microg/L, with no trend of decreasing concentration. Arsenic concentrations in women's urine (3-900 microg/L, specific weight 1.018 g/mL) highly correlated with concentrations in water on a group level, but showed marked variations between individuals. Arsenic concentrations in hair (range 20-1,500 microg/kg) rather poorly correlated with urinary arsenic, possibly due to external contamination. Thus, arsenic concentration in urine seems to be a better marker of individual arsenic exposure than concentrations in drinking-water and hair. PMID- 17366774 TI - Knowledge of arsenic in drinking-water: risks and avoidance in Matlab, Bangladesh. AB - Widespread contamination of arsenic in Bangladesh has been jeopardizing the health of millions of people. Residents of Matlab, Bangladesh, are among the millions at risk. Using bivariate models in the analysis of survey data, knowledge of health risks and avoidance of arsenic exposure in response to widespread contamination of arsenic for residents of Matlab were estimated. The models examined individuals' knowledge of an arsenic problem in the household and knowledge of specific illnesses caused by arsenic exposure. The likelihood of avoiding exposure to arsenic contamination was further examined. Results of the estimation showed that individual's knowledge of arsenic problems in the household was gathered through awareness campaigns and by word of mouth and that knowledge of illnesses was predicated on education, health, presence of children, elderly and young women. Adoption of avoidance measures was not affected by exposure to arsenic-information sources, but level of education had a statistically significant positive effect on the decision to avoid arsenic exposure. Lack of convenience of safe drinking-water practices lead people to persist in drinking arsenic-contaminated water. PMID- 17366776 TI - Risk assessment of arsenic mitigation options in Bangladesh. AB - The provision of alternative water sources is the principal arsenic mitigation strategy in Bangladesh, but can lead to risk substitution. A study of arsenic mitigation options was undertaken to assess water quality and sanitary condition and to estimate the burden of disease associated with each technology in disability-adjusted life years (DALYs). Dugwells and pond-sand filters showed heavy microbial contamination in both dry and monsoon seasons, and the estimated burden of disease was high. Rainwater was of good quality in the monsoon but deteriorated in the dry season. Deep tubewells showed microbial contamination in the monsoon but not in the dry season and was the only technology to approach the World Health Organization's reference level of risk of 10-6 DALYs. A few dugwells and one pond-sand filter showed arsenic in excess of 50 microg/L. The findings suggest that deep tubewells and rainwater harvesting provide safer water than dugwells and pond-sand filters and should be the preferred options. PMID- 17366775 TI - Access to drinking-water and arsenicosis in Bangladesh. AB - The discovery of arsenic contamination in groundwater has challenged efforts to provide safe drinking-water to households in rural Bangladesh. Two nationally representative surveys in 2000 and 2002 investigated water-usage patterns, water testing, knowledge of arsenic poisoning, and behavioural responses to arsenic contamination. Knowledge of arsenicosis rose between the two surveys among women from 42% to 64% but awareness of consequences of arsenic remained limited; only 13% knew that it could lead to death. Behavioural responses to arsenic have been limited, probably in part because of the lack of concern but also because households are uncertain of how best to respond and have a strong preference for tubewell water even when wells are known to be contaminated. Further work conducted by the survey team highlighted the difficulties in providing alternative sources of water, with many households switching back to their original sources of water. PMID- 17366777 TI - Household pasteurization of drinking-water: the chulli water-treatment system. AB - A simple flow-through system has been developed which makes use of wasted heat generated in traditional clay ovens (chullis) to pasteurize surface water. A hollow aluminium coil is built into the clay chulli, and water is passed through the coil during normal cooking events. By adjusting the flow rate, effluent temperature can be maintained at approximately 70 degrees C. Laboratory testing, along with over 400 field tests on chulli systems deployed in six pilot villages, showed that the treatment completely inactivated thermotolerant coliforms. The chulli system produces up to 90 litres per day of treated water at the household level, without any additional time or fuel requirement. The technology has been developed to provide a safe alternative source of drinking-water in arsenic contaminated areas, but can also have wide application wherever people consume microbiologically-contaminated water. PMID- 17366778 TI - One solution to the arsenic problem: a return to surface (improved dug) wells. AB - Arsenic contamination in drinking-water in Bangladesh is a major catastrophe, the consequences of which exceed most other man-made disasters. The national policy encourages the use of surface water as much as possible without encountering the problems of sanitation that led to the use of groundwater in the first place. This paper describes the success of the Dhaka Community Hospital (DCH) team and the procedure in implementing sanitary, arsenic-free, dugwells. The capital cost for running water is US$ 5-6 per person. Sixty-six sanitary dugwells were installed in phases between 2000 and 2004 in Pabna district of Bangladesh where there was a great need of safe water because, in some villages, 90% of tubewells were highly contaminated with arsenic. In total, 1,549 families now have access to safe arsenic-free dugwell water. Some of them have a water-pipe up to their kitchen. All of these were implemented with active participation of community members. They also pay for water-use and are themselves responsible for the maintenance and water quality. The DCH helped the community with installation and maintenance protocol and also with monitoring water quality. The bacteria levels are low but not always zero, and studies are in progress to reduce bacteria by chlorination. PMID- 17366779 TI - [Value of functional imaging modalities in radiation treatment planning of brain gliomas]. PMID- 17366780 TI - [Inhibition of EBV-encoded LMP-1 by DNA-based RNA interference affects metastatic ability of nasopharyngeal carcinoma cells]. AB - OBJECTIVE: To evaluate the application of DNA vector-based RNA interference for silencing LMP-1 expression in EBV-positive nasopharyngeal cancer (NPC) C611 cells and analyze the inhibiting effects of LMP-1 silencing on metastatic property of NPC cells. METHODS: DNA vectors with LMP-1 shRNA template were transfected into C611 cells. After G418 selection, a LMP-1 silenced sub-clone named C611L was isolated. Effect of LMP-1 inhibition on its metastatic properties was evaluated by cell adhesion, invasion and wound healing assays. RESULTS: shRNA vector mediated stable RNAi against LMP-1 in C611 cells. Loss of LMP-1 significantly altered cell motility, substratum adhesion and transmembrane invasion ability. CONCLUSION: Stable suppression of LMP-1 induced by shRNA vector can inhibit metastatic properties of NPC cells. PMID- 17366781 TI - [Immunotherapeutic effect of recombinant EGFR phage vaccine on tumors]. AB - OBJECTIVE: To construct a recombined phage vaccine and to evaluate the efficiency of this phage vaccine against EGFR-positive tumors. METHODS: T7 phage display system was used to display five fragments of the extracellular domain of chicken EGFR. The EGFR was expressed as a fused protein on the surface of the T7 phage 10B capsid protein. The EGFR expression of the phage vaccine was verified by Western-blot analysis. Anti-EGFR antibody was detected by ELISA. Splenic lymphocytes of the immunized mice were separated and used to determine the immunotoxic effect against A431 cells. The phage vaccines were injected into C57 mice 4 times before Lewis lung cancer cells inoculation. Tumor volume was recorded to evaluate the anti-tumor effect of each vaccine. RESULTS: Five phage vaccines inserted with the chicken EGFR gene were successfully constructed. Western blot assay showed that the extracellular domain of chicken EGFR proteins were displayed on the surface of the phage. Specific antibody was induced in the immunized mice, compared with the control group. Splenic lymphocytes of the immunized mice were shown to be immunotoxic against A431 cells. The killing rates of the experimental groups were higher than that of control group (P < 0.001, t Student test). The highest killing rate was (45.74 +/- 7.21)%. The tumor growth was inhibited in the experimental groups compared with those of control groups (P < 0.05 in C1, C2, C3, C4 groups, P > 0.05 in C5 group). CONCLUSION: Our results demonstrated that recombined EGFR phage vaccines may be used to induce therapeutic anti-tumor immunity against EGFR-positive tumors. PMID- 17366782 TI - [Characterization of a novel transplantable orthotopic nude mouse model with xenografted human bladder transitional cell tumor (BIU-87)]. AB - OBJECTIVE: A mouse model of orthotopic bladder cancer simulating its human counterpart is of great importance in preclinical evaluation of new treatment modalities such as immunotxin therapy. The aim of the present study is to establish a novel nude mouse model with xenografted human bladder cancer. METHODS: Single cell suspension of an established human bladder transitional cell carcinoma (TCC) cell line BIU-87 was instilled into nude mouse bladders which were pretreated with mild acid washing. The tumor growth in mouse bladder was assessed weekly by magnetic resonance imaging (MRI). At intervals following implantation and MRI tumor detection, the animals were sacrificed for necropsy, histological examination and immunocytochemical studies. RESULTS: The overall tumor establishment was 92.9% (52/56 mice) at 7 - 36 days, while in the subgroup of animals sacrificed at 12 - 13 days, 40 out of 42 animals (95.2%) developed TCC, the majority of which was superficial. The tumor stages were assessed by gross and histopathology. Histological examination confirmed the presence of grade II - III TCC. Immunocytochemistry confirmed that the tumor model maintained the biological and immunological features of BIU-87 cells. The changes seen on MRI images well correlated with the extent of tumor invasion identified by histology. Carcinoma in situ could be detected histologically at 7 - 9 days post inoculation and progressed into papillary or invasive tumors thereafter. CONCLUSION: The orthotopic BIU-87 TCC model in nude mice is highly reproducible and is ideal for preclinical studies on experimental intravesical therapies. PMID- 17366783 TI - [Effects of human peritoneal mesothelial cells on angiogenesis factor expression and secretion of ovarian carcinoma cells]. AB - OBJECTIVE: To investigate the impact of human peritoneal mesothelial cells (HPMC) on angiogenesis factor expression and secretion of ovarian carcinoma cell line SKOV3. METHODS: The conditioned medium with HPMC was tested by ELISA for tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-1beta). Millicell was used to co-culture HPMC and ovarian carcinoma cell line SKOV3 in the presence or absence of neutralizing antibody against TNF-alpha or IL-1beta. RT-PCR was used to detect vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene expression in SKOV3 cells. VEGF and bFGF protein levels in the SKOV3 conditioned medium were assessed by ELISA. RESULTS: Conditioned medium with HPMC contained both TNF-alpha and IL-1beta. SKOV3 co-cultured with HPMC expressed higher levels of VEGF and bFGF mRNA and secreted at increased levels of both VEGF and bFGF, in comparison with those in SKOV3 cells cultured alone (P < 0.01). Addition of neutralizing antibody against TNF-alpha or IL-1beta during co cultures resulted in decrease in mRNA expression and secretion of VEGF and bFGF in SKOV3 cells. When both antibodies were administered during co-culture, additive decrease was observed. CONCLUSION: HPMC can act in a paracrine fashion to stimulate ovarian tumor cells to produce and secret at increased levels of VEGF and bFGF through TNF-alpha and IL-1beta, and contribute to angiogenesis and peritoneal metastasis of ovarian cancer. PMID- 17366784 TI - [The role of Smad4 and MAPK proteins in signal transduction pathway in non-small cell lung cancer]. AB - OBJECTIVE: To investigate the expression of Smad4 in non-small cell lung cancer (NSCLC), its correlation with MAPK (mitogen activated protein kinase) and their clinical significance in NSCLC. METHODS: Western blotting and RT-PCR were employed to test 42 resected lung cancers and normal lung tissues for the expression of Smad4. Imunohistochemistry was used to detect Smad4 and subtribes of MAPK in 71 paraffin samples. RESULTS: The level of protein and mRNA expression of Smad4 in lung cancer tissues were 0.2092 +/- 0.1308 and 0.3986 +/- 0. 1982, respectively, lower than those in normal tissues (0.7852 +/- 0.4386 and 1.1206 +/ 0.6772, P < 0.05). The expression of p38, ERK1 and Smad4 was associated with TNM staging (P = 0.000, 0.000 and 0.005, respectively) and JNK1 with tumor location (P = 0.028) and staging (P = 0.000). There was a correlation between p38 and Smad4 (P = 0.000). The expression of Smad4 (P = 0.0001), p38 (P = 0.0000) and JNK1 (P = 0.0208), tumor differentiation (P = 0.0059) and staging (P = 0.0000) were significantly correlated with prognosis of NSCLC by univariate analysis. Smad4 (P = 0.019), p38 (P = 0.044), tumor differentiation (P = 0.003), and staging (P = 0.020) were correlated with prognosis tested by multivariable analysis. Taking p38 and Smad4 together, we found that the negative expression of p38 and positive expression of Smad4 were associated with a better prognosis of NSCLC (P = 0.000). CONCLUSION: Smad4 could be of importance for the initiation and development of NSCLC. There is a significant correlation between main proteins of TGF-beta/smad4 and those of ras-MAPK signal transduction pathways. The expression of Smad4 is inhibited by p38. Smad4, as well as p38, tumor differentiation and staging can be used as prognostic factors of NSCLC. PMID- 17366785 TI - [Expression and significance of integrin alpha5, beta1 and E-CD in patients with non-small cell lung carcinoma]. AB - OBJECTIVE: To investigate the relationship between the expressions of integrin alpha5 beta1 and E-CD, and clinicopathological characteristics and prognosis of patients with non-small cell lung carcinoma (NSCLC). METHODS: The expression of integrin alpha5 beta1 and E-CD were analyzed in 53 NSCLC and 12 control specimens by immunohistochemical assay. RESULTS: The expression of integrin alpha5 beta1 was significantly higher in NSCLC (58.5%) than that in normal lung tissue (16.7%), and also positively related with pathological characteristics (P = 0.021), lymph node metastasis (P = 0.006), and clinical stage (P = 0.002). The 3 year survival rate in NSCLC group was significantly lower than that in control group (22.3% vs 40.6% , P = 0.041). The positive expression of E-CD in NSCLC and control group was 32.1% and 91.7%, respectively, and negatively correlated with pathological characteristics (P = 0.010) and lymph node metastasis (P = 0.002). The 3-year survival rate in control group was 19.9%, lower than that in NSCLC group (41.2%, P > 0.05), but the difference is not significant. CONCLUSION: The overexpression of integrin alpha5 beta1 may contribute to lymph node metastasis and play an inverse role, while E-CD may be a beneficial prognostic factor in patients with NSCLC. PMID- 17366787 TI - [Preoperative molecular staging of colorectal cancers by CM10 ProteinChip and SELDI-TOF-MS analysis]. AB - OBJECTIVE: To detect the serum proteomic patterns by using SELDI-TOF-MS and CM10 ProteinChip techniques in colorectal cancer (CRC) patients, and to evaluate the significance of the proteomic patterns in colorectal cancer staging. METHODS: A total of 76 serum samples were obtained from CRC patients at different clinical stages, including Dukes A (n = 10), Dukes B (n = 19), Dukes C (n = 16) and Dukes D (n = 31). Different stage models were developed and validated by bioinformatics methods of support vector machines, discriminant analysis and time-sequence analysis. RESULTS: The model I formed by six proteins of peaks at m/z 2759.6, 2964.7, 2048.0, 4795.9, 4139.8 and 37 761.6 could do the best as potential biomarkers to distinguish local CRC patients (Dukes A and Dukes B) from regional CRC patients (Dukes C ) with an accuracy of 86.7%. The model II formed by 3 proteins of peaks at m/z 6885.3, 2058.3 and 8567.8 could do the best to distinguish locoregional CRC patients (Dukes A, B and C) from systematic CRC patients (Dukes D) with an accuracy of 75.0%. The mode III could distinguish Dukes A from Dukes B with an accuracy of 86.2% (25/29). The model IV could distinguish Dukes A from Dukes C with an accuracy of 84.6% (22/26). The model V could distinguish Dukes B from Dukes C with an accuracy of 85.7% (30/35). The model VI could distinguish Dukes B from Dukes D with an accuracy of 80.0% (40/50). The model VII could distinguish Dukes C from Dukes D with an accuracy of 78.7% (37/47). Different stage groups could be distinguished by the two dimensional scattered spots figure obviously. CONCLUSION: Our findings indicate that this method can well be used in preoperative staging of colorectal cancers and the screened tumor markers may serve for guidance of integrating treatment of colorectal cancers. PMID- 17366786 TI - [Expression of serum breast drug-resistance protein in predicting chemosensitivity of NSCLC]. AB - OBJECTIVE: To investigate expression of serum breast cancer resistance protein (BCRP) in non-small cell lung cancer patient (NSCLC) and healthy adult, and its correlation with chemosensitivity as one passible value of BCRP in clinical application. METHODS: Venous blood specimens of 44 advanced NSCLC patients and 30 healthy adults were collected. Antibody of BCRP was used to detect its expression in the experiment. Part of venous specimens were randomly selected for Western blot, and all specimens were examined by ELISA at last. Chemotherapy response of these patients was observed in order to analyze the correlation between BCRP expression level and chemosensitivity. RESULTS: Western blot result showed that BCRP expression can be detected both in NSCLC patient and normal adult. The expression level in NSCLC patients detected by ELISA was significantly higher than that in the healthy adults (P = 0.00); which was also significantly higher in chemo-resistant patients than that in the chemosensitive (P = 0.02) and the healthy adults (P = 0.00); however, BCRP expression in chemo-sensitive patients was not significantly different from that in the healthy adults (P = 0.08). CONCLUSION: Breast cancer resistance protein (BCRP) is found to be expressed at high level in the serum of NSCLC patient, the intensity of BCRP expression may be correlated with chemotherapy resistance in NSCLC, and the high level expressing of BCRP may indicate resistance to the platinum-based chemotherapy regimen. Detection of serum BCRP may someday become a useful bio-marker in predicting chemosensitivity of NSCLC. PMID- 17366788 TI - [Expression and significance of heat shock proteins in esophageal squamous cell carcinoma]. AB - OBJECTIVE: To investigate the expression and significance of HSP27, HSP60, HSP70 and HSP90 alpha in esophageal squamous cell carcinoma (ESCC) and tissues along the incision margin (TIM). METHODS: The presence and the level of expression of HSP27, HSP60, HSP70 and HSP90 alpha were determined in 168 specimens from ESCC and 42 from tissues along TIM by EnVision immunohistochemistry and Western blotting, to compare their positive staining rates and explore the correlation between their expressions and clinicopathologic features in ESCC. RESULTS: The positive staining rates of HSP27, HSP60, HSP70 and HSP90 alpha in ESCC and TIM were 62.0% and 42.1%, 92.7% and 63.2%, 57.9% and 22.2%, and 33.7% and 18.5%, respectively. There was very significant difference between the expression of HSP60 and HSP70 in ESCC and TIM (P < 0.01), but not significant about HSP27 and HSP90 alpha (P > 0.05). The positive staining rate of HSP27 declined with the lower grade of differentiation of ESCC (P < 0.05). CONCLUSION: The present findings suggest that the expression of HSPs of different molecular weight in ESCC and TIM is a common event. The level of expressions of HSP60 and HSP70 are higher than those in TIM. HSP60 and HSP70 expression correlated with the biological behavior of ESCC. The expression of HSP27 was positively correlated to the grade of differentiation of ESCC. Overexpression of HSP27 may be associated to the differentiation of squamous cell carcinoma. PMID- 17366789 TI - [Expression of CD80, CD86, TGF-beta1 and IL-10 mRNA in the esophageal carcinoma]. AB - OBJECTIVE: To investigate the correlation of CD80 and CD86 mRNA expression with the expression of transforming growth factor-beta1 mRNA (TGF-beta1) and interleukin-10 mRNA (IL-10) in the esophageal cancer. To explore the reason of impaired immunological function of dentritic cell (DC) and the mechanism of cancer cell escaption from body immunity system in the esophageal cancer patient. METHODS: Expression of CD80, CD86, TGF-beta1 and IL-10R mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in specimens of 62 esophageal carcinoma and 16 normal esophageal mucosal tissues used as normal control. RESULTS: Expression of CD80 and CD86 mRNA in the esophageal cancer tissue was significantly lower than that in the normal esophageal mucosal tissue (CD80: P = 0.038; CD86: P = 0.0002). It was significantly higher in stage I or II than that in stage III or IV (CD80: P = 0.029; CD86: P = 0.045); and also higher in paitents with high or moderate differentiation than that with poor differentiation (CD80: P = 0.046; CD86: P = 0.044). Furthermore, it was found to be reversely correlated with expression of TGF-beta1, IL-10 mRNA by multiple regression analysis (P = 0. 0001) respectively, the more TGF-beta1 and IL-10 mRNA expressed in the tumor tissue, the less CD80 and CD86 mRNA expressed by dendritic cells. CONCLUSION: The expression of CD80 and CD86 mRNA in the tissues of esophageal cancer are found to be weak, and reversely correlated with the expression of TGF-beta1 and IL-10 mRNA. High level expression of TGF-beta1 and IL 10 mRNA may be an important influential factor to the weak expression of CD80 and CD86 mRNA, which may be one of the reasons leading to impaired function of dendritic cells and immune escape of cancer cells in the esophageal cancer patient. PMID- 17366790 TI - [Clinical significance of hMAM mRNA detection in bone marrow of breast carcinoma patient]. AB - OBJECTIVE: To investigate the expression of the human mammoglobin (hMAM) mRNA in bone marrow and its clinical significance in the breast cancer patient. METHODS: Expression of hMAM mRNA was detected using nested reverse transcription polymerase chain reaction (RT-PCR) in the bone marrow aspiration sample from 75 breast cancer patients, 15 patients with benign breast lesions and 8 healthy volunteers as control. The possible correlation of hMAM mRNA expression with clinico-pathological parameters and related molecular markers such as Ki67, p53 and VEGF were analyzed. RESULTS: The sensitivity of RT-PCR in this series reached 10(-6). The hMAM mRNA was found to be positively expressed by RT-PCR in 21 of 75 breast cancer patients with a positive rate of 28.0%. However, hMAM mRNA expression was not detected in the bone marrow aspiration samples from patients with benign breast lesions and healthy volunteers. The hMAM mRNA expression was positively correlated with axillary nodal involvement and progesterone receptor (PR) status (P < 0.05) as well as Ki67 expression in breast cancer tissue (chi2 = 4.936, P = 0.026), but not with age, tumor size, clinical stage, or estrogen receptor (ER) status (P > 0.05). CONCLUSION: RT-PCR is quite sensitive and has a high specificity in detecting the presence of hMAM mRNA in the bone marrow from breast cancer patients. Thereupon, hMAM mRNA may be useful as a molecular biomarker in detecting disseminated tumor cells (DTC) in the bone marrow of breast cancer patients. Positive hMAM mRNA expression result may have an impact upon therapeutic recommendations and patients' prognostic judgement. PMID- 17366791 TI - [Clinical significance of serum proteomic patterns in diagnosis of breast cancer]. PMID- 17366792 TI - [Expression of G-protein gamma 7 in patients with extrahepatic cholangiocarcinoma]. PMID- 17366793 TI - [Characterization of prevalence of malignant tumors in Kazakh nationality]. PMID- 17366794 TI - [Value of intraoperative fine-needle aspiration cytology in the diagnosis of pancreatic cancer]. AB - OBJECTIVE: To investigate the value of the intraoperative fine-needle aspiration cytology (IFNAC) in the diagnosis of pancreatic cancer. METHODS: The IFNAC data of 70 pancreatic cancer patients were retrospectively reviewed. IFNAC had been done in our hospital only in a few patients before 2001, however, more and more patients have been examined by renovated method since 2002. But as the way of carrying out IFNAC improved by changing from the ordinary 10 ml syringe and 22 gauge needle (0.7 mm) before 2003 to 5 ml syringe and 25 gauge skin testing needle (0.5 mm), the panreas itself is properly exposed before IFNAC, the operator at frst fixes the suspected mass with his left hand and does the puncture with his right hand. Puncturing is done while the syringe is rotated, negative pressure is being kept at the same time. The needle is withdrawn under negative pressure, 6-8 syringe are used for each patient by puncturing at 6-8 points, then smears are made with the syringes. The whole process takes 20 min to accomplish. RESULTS: The overall positive rate was 84.3%. The positive rate of the conventional IFNAC was 66.67%, while it was increased to 95.3% following the introduction of the renovated method (P = 0.002); No complication was observed in this series. CONCLUSION: Intraoperative fine-needle aspiration cytology using 25 gauge skin testing needle and multi-point rotating maneuver during puncturing in the diagnosis of pancreatic cancer is safe and effective with few complications. PMID- 17366795 TI - [Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with cisplatin (DDP) in the treatment of patients with advanced non small cell lung cancer (NSCLC). METHODS: Of 36 NSCLC patients consisting of 23 males and 13 females with a medium age of 52 years included, there were 26 adenocarcinomas, 7 squamous cell carcinomas, 1 adeno-squamous cell carcinoma and 2 unclassified types; 13 stage III B and 23 stage IV; 24 chemonaive and 12 previously treated by chemotherapy with a medium Karnofsky status of 90. All patients had measurable or evaluable parameters. The regimen was administered as following: CPT-11 60 mg/m2, IV, D1, 8 and 15; DDP 80 mg/m2, IV, D1; every 28 days as a cycle. RESULTS: Totally, 97 cycles were carried out in these 36 patients with a medium cycles of 3. Of 35 evaluable patients, 22.9% (8/35) achieved partial response, 60.0% (21/35) had stable disease and 17.1% (6/35) progressive disease. The response rate was 29.2% (7/24) for chemonaive patients and 9.1% (1/11) for these previously treated. The 1-year survival rate was 45.4% with a medium time to tumor progression (TTP) of 199 days for the responders. The incidence rate of grade III/IV adverse events were: 16.7% for neutropenia, 13.9% alopecia, 5.6% diarrhea, 2.8% nausea and vomiting, respectively. CONCLUSION: Irinotecan plus cisplatin is effective with tolerable adverse events in treating patients with advanced non-small cell lung cancer, but further investigation trials are needed. PMID- 17366796 TI - [Circulating endothelial cells in the peripheral blood of advanced NSCLC patients]. AB - OBJECTIVE: To investigate the changes and clinical value of circulating endothelial cells (CEC) in the peripheral blood of advanced NSCLC patient. METHODS: Sixty-seven advanced NSCLC patients were randomly divided into either the treatment group with NP plus endostatin or control group with NP alone. Level of CEC and cytokeratin (CK) in the peripheral blood were measured by flow cytometry. RESULTS: The response rate and benefit rate was 44.4%, 80.0% in the treatment group, and 27.3%, 50.0% in the control group, respectively (P = 0.176 and P = 0.012). Time to tumor progression (TTP) was 146.7 days in the treatment group and 91.1 days in the control group (P = 0.061). However, when the cut-off of TTP was defined as > 170 days, there was a significant difference between two groups (cut-off = 170, P = 0.034; cut-off = 180, P = 0.009). The number of CEC decreased by 0.29 +/- 0.47 in the treatment group and by 0.01 +/- 0.43 in the control group (P = 0.033). The correlation between CEC and CK was found to be positive either before (r = 0.381, P = 0.013) or after the treatment (r = 0.450, P = 0.004). CONCLUSION: Chemotherapy combined with endostatin is superior to chemotherapy alone in the treatment of NSCLC. CEC, as a biomarker, may be useful in predicting the efficacy of the combined treatment. PMID- 17366797 TI - [Randomized clinical study of surgery versus radiotherapy alone in the treatment of resectable esophageal cancer in the chest]. AB - OBJECTIVE: To compare the treatment results between radical surgery and late course accelerated hyperfractionated radiotherapy (LCAHFR) for patients with resectable esophageal cancer in the chest. METHODS: From June 1998 to September 2002, 269 patients with resectable esophageal cancer in the chest were randomized into two groups: 135 in surgery group and 134 in radiotherapy. The surgery group received esophagectomy including resection of the lesion and 5 cm margin at both ends from the lesion as well as surrounding lymph nodes > or = 5 mm and fatty tissue. In the radiotherapy group: irradiation field for the lesion in the upper esophageal cancer included the gross lesion, bilateral supraclavicular nodes and 4 cm of normal esophagus from lower margin of the gross disease; for the esophageal cancer at the middle segment, it included the gross disease with 4 cm normal esophagus from both ends of the lesion; for the lesion in the lower esophageal cancer, it included 4 cm of normal esophagus and the gross lesion as well as the draining gastric lymph nodes. The width of the irradiation field was 5-6 cm. The 90% isodose volume was covered by the entire CTV with 3-5 beams, in a conventionally fractionated RT at 1.8-2.0 Gy/d for the first two thirds of treatment course to a dose of about 50-50.4 Gy followed by LCAHFR using reduced fields (2 cm extended margin at both ends of the lesion) , twice daily at 1.5 Gy per fraction ( with aminimal interval of 6 h between fractions) to a dose of 18 21 Gy. The total dose whole radiotherapy was 68.4-71.0 Gy. RESULTS: The 1-, 3- and 5-year overall survival rate was 93.3%, 61.5% and 36.9% in the surgery group versus 88.6%, 56.2% and 34.7% in the radiotherapy group without statistical difference between the two groups. The 1-, 3- and 5-year progression free survival rate was 75.9%, 43.7% and 23.1% in the surgery group and 73.3%, 39.7% and 20.6%, respectively, in the radiotherapy group without statistical difference between the two groups either. CONCLUSION: The results treated by late course accelerated hyperfractionated conformal radiotherapy alone may be comparable to that by radical surgery for patient with resectable esophageal cancer in the chest. PMID- 17366798 TI - [Multicenter phase II study of modified FOLFIRI regimen in the advanced colorectal cancer patient refractory to fluoropyrimidine and oxaliplatin]. AB - OBJECTIVE: To evaluate the efficacy and safety of modified FOLFIRI regimen in advanced colorectal cancer (CRC) patients refractory to fluoropyrimidine and oxaliplatin. METHODS: The modified FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m2 d1 + LV 200 mg/m2 dl + 5-Fu 400 mg/m2 bolus dl plus 46-hour intravenous infusion of 5-Fu 2.4 g/m2, every 2 weeks as one cycle. The main selection criterion for this study was the advanced CRC refractory to fluoropyrimidine and oxaliplatin. RESULTS: Of the 80 evaluable patients for efficacy: 10 (12.5%) had a partial response, 51 (63.7%) stable disease, and 19 (23.8%) progressive disease. The median time to progression was 96 days. Safety analysis was based on the data of 83 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia (24.1%), nausea/vomiting (8.4%), and diarrhea (2.4%). CONCLUSION: Modified FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin. PMID- 17366799 TI - [Treatment of advanced Wilms' tumor]. AB - OBJECTIVE: To improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery. METHODS: Sixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI) Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology. RESULTS: In the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively. CONCLUSION: The present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery. PMID- 17366800 TI - [Application of monoclonal antibody in combination with irinotecan in the treatment of colorectal cancer]. PMID- 17366801 TI - PPARalpha and effects of TCE. PMID- 17366802 TI - Aspartame not linked to cancer. PMID- 17366803 TI - Children's health/regional collaboration to reduce lead exposure in children. PMID- 17366804 TI - Environmental stain fading fast. PMID- 17366805 TI - Forest fire fallout. PMID- 17366807 TI - A new tool to trace genetic susceptibility. PMID- 17366806 TI - The chosen ONES Awards fund young investigators. PMID- 17366808 TI - Prevention pays for farmworkers. PMID- 17366809 TI - The weight of lead. Effects add up in adults. PMID- 17366810 TI - Beyond batteries: portable hydrogen fuel cells. PMID- 17366811 TI - Source of funding and results of studies of health effects of mobile phone use: systematic review of experimental studies. AB - OBJECTIVES: There is concern regarding the possible health effects of cellular telephone use. We examined whether the source of funding of studies of the effects of low-level radiofrequency radiation is associated with the results of studies. We conducted a systematic review of studies of controlled exposure to radiofrequency radiation with health-related outcomes (electroencephalogram, cognitive or cardiovascular function, hormone levels, symptoms, and subjective well-being). DATA SOURCES: We searched EMBASE, Medline, and a specialist database in February 2005 and scrutinized reference lists from relevant publications. DATA EXTRACTION: Data on the source of funding, study design, methodologic quality, and other study characteristics were extracted. The primary outcome was the reporting of at least one statistically significant association between the exposure and a health-related outcome. Data were analyzed using logistic regression models. DATA SYNTHESIS: Of 59 studies, 12 (20%) were funded exclusively by the telecommunications industry, 11 (19%) were funded by public agencies or charities, 14 (24%) had mixed funding (including industry), and in 22 (37%) the source of funding was not reported. Studies funded exclusively by industry reported the largest number of outcomes, but were least likely to report a statistically significant result: The odds ratio was 0.11 (95% confidence interval, 0.02-0.78), compared with studies funded by public agencies or charities. This finding was not materially altered in analyses adjusted for the number of outcomes reported, study quality, and other factors. CONCLUSIONS: The interpretation of results from studies of health effects of radiofrequency radiation should take sponsorship into account. PMID- 17366812 TI - Ethical and scientific issues of nanotechnology in the workplace. AB - In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decisionmaking about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers' acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective. PMID- 17366813 TI - The effects of components of fine particulate air pollution on mortality in california: results from CALFINE. AB - OBJECTIVE: Several epidemiologic studies provide evidence of an association between daily mortality and particulate matter < 2.5 pm in diameter (PM2.5). Little is known, however, about the relative effects of PM2.5 constituents. We examined associations between 19 PM2.5 components and daily mortality in six California counties. DESIGN: We obtained daily data from 2000 to 2003 on mortality and PM2.5 mass and components, including elemental and organic carbon (EC and OC), nitrates, sulfates, and various metals. We examined associations of PM2.5 and its constituents with daily counts of several mortality categories: all cause, cardiovascular, respiratory, and mortality age > 65 years. Poisson regressions incorporating natural splines were used to control for time-varying covariates. Effect estimates were determined for each component in each county and then combined using a random-effects model. RESULTS: PM2.5 mass and several constituents were associated with multiple mortality categories, especially cardiovascular deaths. For example, for a 3-day lag, the latter increased by 1.6, 2.1, 1.6, and 1.5% for PM2.5, EC, OC, and nitrates based on interquartile ranges of 14.6, 0.8, 4.6, and 5.5 pg/m(3), respectively. Stronger associations were observed between mortality and additional pollutants, including sulfates and several metals, during the cool season. CONCLUSION: This multicounty analysis adds to the growing body of evidence linking PM2.5 with mortality and indicates that excess risks may vary among specific PM2.5 components. Therefore, the use of regression coefficients based on PM2.5 mass may underestimate associations with some PM2.5 components. Also, our findings support the hypothesis that combustion associated pollutants are particularly important in California. PMID- 17366814 TI - Polychlorinated biphenyls and their hydroxylated metabolites (OH-PCBS) in pregnant women from eastern Slovakia. AB - OBJECTIVE: Our aim in the present study was to characterize and quantify the levels of polychlorinated biphenyls (PCBs) and specific polychlorobiphenylol (OH PCB) metabolites in maternal sera from women delivering in eastern Slovakia. DESIGN: During 2002-2004, blood samples were collected from women delivering in two Slovak locations: Michalovce district, where PCBs were formerly manufactured, and Svidnik and Stropkov districts, about 70 km north. PARTICIPANTS: A total of 762 and 341 pregnant women were sampled from Michalovce and Svidnik/Stropkov, respectively, and OH-PCBs were measured in 131 and 31. EVALUATION/MEASUREMENTS: We analyzed PCBs using gas chromatography (GC)/electron capture detection. OH PCBs and pentachlorophenol (PCP) were determined as methyl derivatives using GC electron capture negative ionization/mass spectrometry. We characterized distributions in the full cohort using inverse sampling weights. RESULTS: The concentrations of both PCBs and OH-PCB metabolites of Michalovce mothers were about two times higher than those of the Svidnik/Stropkov mothers (p < 0.001). The median weighted maternal serum levels of the sum of PCBs (sigmaPCBs) were 5.73 ng/g wet weight (Michalovce) and 2.82 ng/g wet weight (Svidnik/Stropkov). The median sum of OH-PCBs (ZOH-PCBs) was 0.55 ng/g wet weight in Michalovce mothers and 0.32 ng/g wet weight in Svidnik/Stropkov mothers. 4-OH 2,2',3,4',5,5',6-Heptachlorobiphenyl (4-OH-CB187) was a primary metabolite, followed by 4-OH-2,2',3,4',5,5'-hexachlorobiphenyl (4-OH-CB146). Only four PCB congeners-CBs 153, 138, 180, and 170--had higher concentrations than 4-OH-CB187 and 4-OH-CB146 (p < 0.001). The median ratio of the sigmaOH-PCBs to the sigmaPCBs was 0.10. CONCLUSIONS: Mothers residing in eastern Slovakia are still highly exposed to PCBs, and their body burdens of these pollutants and OH-PCB metabolites may pose a risk for adverse effects on health for themselves and their children. PMID- 17366815 TI - Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers. AB - BACKGROUND: Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts. OBJECTIVES: The main purpose of this study was to characterize relationships between levels of albumin adducts of these electrophiles in blood and the corresponding benzene exposures in benzene-exposed and control workers, after adjusting for important covariates. Because second blood samples were obtained from a subset of exposed workers, we also desired to estimate within-person and between-person variance components for the three adducts. METHODS: We measured albumin adducts and benzene exposures in 250 benzene-exposed workers (exposure range, 0.26-54.5 ppm) and 140 control workers (exposure range < 0.01-0.53 ppm) from Tianjin, China. Separate multiple linear regression models were fitted to the logged adduct levels for workers exposed to benzene < 1 ppm and > or =1 ppm. Mixed-effects models were used to estimate within-person and between-person variance components of adduct levels. RESULTS: We observed nonlinear (hockey-stick shaped) exposure adduct relationships in log-scale, with inflection points between about 0.5 and 5 ppm. These inflection points represent air concentrations at which benzene contributed marginally to background adducts derived from smoking and from dietary and endogenous sources. Adduct levels were significantly affected by the blood-collection medium (serum or plasma containing either heparin or EDTA), smoking, age, and body mass index. When model predictions of adduct levels were plotted versus benzene exposure > or =1 ppm, we observed marked downward concavity, particularly for adducts of the benzoquinones. The between-person variance component of adduct levels increased in the order 1,2-BQ < 1,4-BQ < BO, whereas the within-person variance components of the three adducts followed the reverse order. CONCLUSIONS: Although albumin adducts of BO and the benzoquinones reflect exposures to benzene > or = 1 ppm, they would not be useful biomarkers of exposure at ambient levels of benzene, which tend to be < 0.01 ppm, or in those working populations where exposures are consistently < 1 ppm. The concavity of exposure-adduct relationships is consistent with saturable metabolism of benzene at air concentrations > 1 ppm. The surprisingly large effect of the blood collection medium on adduct levels, particularly those of the benzoquinones, should be further investigated. PMID- 17366816 TI - Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis. AB - BACKGROUND: Lead poisoning affects many organs in the body. Lead inhibits delta aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2. OBJECTIVE: Our meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity. DATA SOURCE: We included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2 2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid-chelatable lead, or blood pressure. DATA EXTRACTION: Sample sizes, means, and standard deviations were extracted for the genotype groups. DATA SYNTHESIS: There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 microg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 microg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes. CONCLUSION: Carriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes. PMID- 17366817 TI - Maternal fish consumption, mercury levels, and risk of preterm delivery. AB - BACKGROUND: Pregnant women receive mixed messages about fish consumption in pregnancy because unsaturated fatty acids and protein in fish are thought to be beneficial, but contaminants such as methylmercury may pose a hazard. METHODS: In the Pregnancy Outcomes and Community Health (POUCH) study, women were enrolled in the 15th to 27th week of pregnancy from 52 prenatal clinics in five Michigan communities. At enrollment, information was gathered on amount and category of fish consumed during the current pregnancy, and a hair sample was obtained. A segment of hair closest to the scalp, approximating exposure during pregnancy, was assessed for total mercury levels (70-90% methylmercury) in 1,024 POUCH cohort women. RESULTS: Mercury levels ranged from 0.01 to 2.50 pg/g (mean = 0.29 microg/g; median = 0.23 microg/g). Total fish consumption and consumption of canned fish, bought fish, and sport-caught fish were positively associated with mercury levels in hair. The greatest fish source for mercury exposure appeared to be canned fish. Compared with women delivering at term, women who delivered before 35 weeks' gestation were more likely to have hair mercury levels at or above the 90th percentile (> or = 0.55 microg/g), even after adjusting for maternal characteristics and fish consumption (adjusted odds ratio = 3.0; 95% confidence interval, 1.3-6.7). CONCLUSION: This is the first large, community based study to examine risk of very preterm birth in relation to mercury levels among women with low to moderate exposure. Additional studies are needed to see whether these findings will be replicated in other settings. PMID- 17366818 TI - Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators. AB - BACKGROUND: Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the food chain; they also have long biological half-lives. OBJECTIVES: Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. METHODS: We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor alpha (ER-alpha)-deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of beta-hexosaminidase. RESULTS: All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17beta-estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-alpha-sufficient and ER-alpha-deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-alpha. CONCLUSIONS: Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens. PMID- 17366819 TI - A case-control analysis of exposure to traffic and acute myocardial infarction. AB - BACKGROUND: Long-term exposure to particulate air pollution has been associated with an increased risk of dying from cardiopulmonary and ischemic heart disease, yet few studies have evaluated cardiovascular end points other than mortality. We investigated the relationship between long-term exposure to traffic and occurrence of acute myocardial infarction (AMI) in a case-control study. METHODS: A total of 5,049 confirmed cases of AMI were identified between 1995 and 2003 as part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence of AMI among greater Worcester, Massachusetts, residents. Population controls were selected from Massachusetts resident lists. We used cumulative traffic within 100 m of subjects' residence and distance from major roadway as proxies for exposure to traffic-related air pollution. We estimated the relationship between exposure to traffic and occurrence of AMI using logistic regression, and we adjusted for the following potential confounders: age, sex, section of the study area, point sources emissions of particulate matter with aerodynamic diameter < 2.5 microm, area socioeconomic characteristics, and percentage of open space. RESULTS: An increase in cumulative traffic near the home was associated with a 4% increase in the odds of AMI per interquartile range [95% confidence interval (CI), 2-7%], whereas living near a major roadway was associated with a 5% increase in the odds of AMI per kilometer (95% CI, 3-6%). CONCLUSIONS: These results provide support for an association between long-term exposure to traffic and the risk of AMI. PMID- 17366820 TI - Tracking patterns of enteric illnesses in populations and communities. AB - BACKGROUND: Enteric illness arising from contaminated water and food is a major health concern worldwide, and tracking the incidences and severity of outbreaks is still a challenging task. Most developed and developing countries have administrative databases for medical visits and services maintained by the government and/or health insurance authorities. Although these databases could be extremely valuable resources to track patterns of environmental and other health issues, test hypotheses, and develop epidemiologic models and predictions, very little research has been done to develop methods to ensure the robustness of such databases and to demonstrate their utility as a research tool. OBJECTIVES: We used the Medical Services Plan (MSP) database of British Columbia, Canada, to develop innovative ways to use medical billing and fee-for-services data to track long-term patterns of enteric illness at the level of populations and communities. RESULTS: To illustrate the power and robustness of the method, we provided several examples covering 8 years of data from each of four communities covering a large range of population size. Not only could this method generalize to other diseases for which specific fee item markers can be found, but also it gives results consistent with a known outbreak and yields data patterns, which could not be revealed by the currently used methods. Because diagnostic code and fee item data for medical services are collected by most medical insurance agencies, our method can have global applications for tracking enteric and other illnesses at the level of populations and communities. PMID- 17366821 TI - Nonenzymatic functions of acetylcholinesterase splice variants in the developmental neurotoxicity of organophosphates: chlorpyrifos, chlorpyrifos oxon, and diazinon. AB - BACKGROUND: Organophosphate pesticides affect mammalian brain development through mechanisms separable from the inhibition of acetylcholinesterase (AChE) enzymatic activity and resultant cholinergic hyperstimulation. In the brain, AChE has two catalytically similar splice variants with distinct functions in development and repair. The rare, read-through isoform, AChE-R, is preferentially induced by injury and appears to promote repair and protect against neurodegeneration. Overexpression of the more abundant, synaptic isoform, AChE-S, enhances neurotoxicity. OBJECTIVES: We exposed differentiating PC12 cells, a model for developing neurons, to 30 microM chlorpyrifos (CPF) or diazinon (DZN), or CPF oxon, the active metabolite that irreversibly inhibits AChE enzymatic activity, in order to determine whether they differentially induce the formation of AChE-S as a mechanistic predictor of developmental neurotoxicity. We then administered CPF or DZN to neonatal rats on postnatal days 1-4 using daily doses spanning the threshold for AChE inhibition (0-20%); we then evaluated AChE gene expression in forebrain and brainstem on post-natal day 5. RESULTS: In PC12 cells, after 48 hr of exposure, CPF, CPF oxon, and DZN enhanced gene expression for AChE-R by about 20%, whereas CPF and DZN, but not CPF oxon, increased AChE-S expression by 20 40%. Thus, despite the fact that CPF oxon is a much more potent AChE inhibitor, it is the native compound (CPF) that induces expression of the neurotoxic AChE-S isoform. For in vivo exposures, 1 mg/kg CPF had little or no effect, but 0.5 or 2 mg/kg DZN induced both AChE-R and AChE-S, with a greater effect in males. CONCLUSIONS: Our results indicate that nonenzymatic functions of AChE variants may participate in and be predictive of the relative developmental neurotoxicity of organophosphates, and that the various organophosphates differ in the degree to which they activate this mechanism. PMID- 17366822 TI - Polybrominated diphenyl ether levels in the blood of pregnant women living in an agricultural community in California. AB - BACKGROUND: Recent studies have raised concerns about polybrominated diphenyl ether (PBDE) flame retardant exposures to pregnant women and women of child bearing age in the United States. Few studies have measured PBDEs in immigrant populations. OBJECTIVES: Our goal was to characterize levels of seven PBDE congeners, polychlorinated biphenyl (PCB)-153, and polybrominated biphenyl (PBB) 153 in plasma from 24 pregnant women of Mexican descent living in an agricultural community in California. RESULTS: The median concentration of the sum of the PBDE congeners was 21 ng/g lipid and ranged from 5.3 to 320 ng/g lipid. Consistent with other studies, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was found at the highest concentration (median = 11 ng/g lipid; range, 2.5-205) followed by 2,2',4,4',5-pentabromobiphenyl (BDE-99) (median = 2.9 ng/g lipid; range, 0.5-54), 2,2',4,4',5-pentaBDE (BDE-100) (median = 1.8 ng/g lipid; range, 0.6-44), and 2,2',4,4',5,5'-hexaBDE (BDE-153) (median = 1.5 ng/g lipid; range, 0.4-35). Levels of PCB-153 (median= 4.4 ng/g lipid; range, < 2-75) were lower than U.S. averages and uncorrelated with PBDE levels, suggesting different exposure routes. CONCLUSIONS: The overall levels of PBDEs found were lower than levels observed in other U.S. populations, although still higher than those observed previously in Europe or Japan. The upper range of exposure is similar to what has been reported in other U.S. populations. PBDEs have been associated with adverse developmental effects in animals. Future studies are needed to determine the sources and pathways of PBDE exposures and whether these exposures have adverse effects on human health. PMID- 17366823 TI - Increased rate of hospitalization for diabetes and residential proximity of hazardous waste sites. AB - BACKGROUND: Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. OBJECTIVE: The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. METHODS: We determined the number of hospitalized patients 25-74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993-2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs ("POP" sites); ZIP codes containing hazardous waste sites but with wastes other than POPs ("other" sites); and ZIP codes without any identified hazardous waste sites ("clean" sites). RESULTS: Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and "other" sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15-1.32] and 1.25 (95% CI, 1.16-1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26-1.47) compared to clean sites. CONCLUSIONS: After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites. PMID- 17366824 TI - Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. AB - BACKGROUND: Humans are routinely exposed to bisphenol A (BPA), an estrogenic compound that leaches from dental materials, food and beverage containers, and other consumer products. Prenatal exposure to BPA has produced long-lasting and profound effects on rodent hormone-dependent tissues that are manifested 1-6 months after the end of exposure. OBJECTIVE: The aim of the present work was to examine whether in utero exposure to BPA alters mammary gland development and increases its susceptibility to the carcinogen N-nitroso-N-methylurea (NMU). METHODS: Pregnant Wistar rats were exposed to BPA (25 pg/kg body weight per day) or to vehicle. Female offspring were sacrificed on postnatal day (PND) 30, 50, 110, or 180. On PND50 a group of rats received a single subcarcinogenic dose of NMU (25 mg/kg) and they were sacrificed on either PND110 or PND180. RESULTS: At puberty, animals exposed prenatally to BPA showed an increased proliferation/apoptosis ratio in both the epithelial and stromal compartments. During adulthood (PND110 and PND180), BPA-exposed animals showed an increased number of hyperplastic ducts and augmented stromal nuclear density. Moreover, the stroma associated with hyperplastic ducts showed signs of desmoplasia and contained an increased number of mast cells, suggesting a heightened risk of neoplastic transformation. Administration of a subcarcinogenic dose of NMU to animals exposed prenatally to BPA increased the percentage of hyperplastic ducts and induced the development of neoplastic lesions. CONCLUSIONS: Our results demonstrate that the prenatal exposure to low doses of BPA perturbs mammary gland histoarchitecture and increases the carcinogenic susceptibility to a chemical challenge administered 50 days after the end of BPA exposure. PMID- 17366825 TI - New insight into intrachromosomal deletions induced by chrysotile in the gpt delta transgenic mutation assay. AB - BACKGROUND: Genotoxicity is often a prerequisite to the development of malignancy. Considerable evidence has shown that exposure to asbestos fibers results in the generation of chromosomal aberrations and multilocus mutations using various in vitro approaches. However, there is less evidence to demonstrate the contribution of deletions to the mutagenicity of asbestos fibers in vivo. OBJECTIVES: In the present study, we investigated the mutant fractions and the patterns induced by chrysotile fibers in gpt delta transgenic mouse primary embryo fibroblasts (MEFs) and compared the results obtained with hydrogen peroxide (H2O2) in an attempt to illustrate the role of oxyradicals in fiber mutagenesis. RESULTS: Chrysotile fibers induced a dose-dependent increase in mutation yield at the redBA/gam loci in transgenic MEF cells. The number of lambda mutants losing both redBA and gam loci induced by chrysotiles at a dose of 1 microg/cm(2) increased by > 5-fold relative to nontreated controls (p < 0.005). Mutation spectra analyses showed that the ratio of lambda mutants losing the redBA/gam region induced by chrysotiles was similar to those induced by equitoxic doses of H2O2. Moreover, treatment with catalase abrogated the accumulation of y H2AX, a biomarker of DNA double-strand breaks, induced by chrysotile fibers. CONCLUSIONS: Our results provide novel information on the frequencies and types of mutations induced by asbestos fibers in the gpt delta transgenic mouse mutagenic assay, which shows great promise for evaluating fiber/particle mutagenicity in vivo. PMID- 17366827 TI - Potential risks associated with the proposed widespread use of Tamiflu. AB - BACKGROUND: The threat of pandemic influenza has focused attention and resources on virus surveillance, prevention, and containment. The World Health Organization has strongly recommended the use of the antiviral drug Tamiflu both to treat and prevent pandemic influenza infection. A major concern for the long-term efficacy of this strategy is to limit the development of Tamiflu-resistant influenza strains. However, in the event of a pandemic, hundreds of millions of courses of Tamiflu, stockpiled globally, will be rapidly deployed. Given its apparent resistance to biodegradation and hydrophilicity, oseltamivir carboxylate (OC), the active antiviral and metabolite of Tamiflu, is predicted to enter receiving riverwater from sewage treatment works in its active form. OBJECTIVE: Our objective in this study was to determine the likely concentrations of OC released into U.S. and U.K. river catchments using hydrologic modeling and current assumptions about the course and management of an influenza pandemic. DISCUSSION: We predict that high concentrations of OC (micrograms per liter) capable of inhibiting influenza virus replication would be sustained for periods of several weeks, presenting an increased risk for the generation of antiviral resistance and genetic exchange between influenza viruses in wildfowl. Owing to the apparent recalcitrance of OC in sewage treatment works, widespread use of Tamiflu during an influenza pandemic also poses a potentially significant, uncharacterized, ecotoxicologic risk in each affected nation's waterways. CONCLUSION: To gauge the hazard presented by Tamiflu use during a pandemic, we recommend a) direct measurement of Tamiflu persistence, biodegradation, and transformation in the environment; b) further modeling of likely drug concentrations in the catchments of countries where humans and waterfowl come into frequent dose contact, and where significant Tamiflu deployment is envisaged; and c) further characterization of the risks of generating Tamiflu-resistant viruses in OC exposed wildfowl. PMID- 17366826 TI - Screening for developmental neurotoxicity using PC12 cells: comparisons of organophosphates with a carbamate, an organochlorine, and divalent nickel. AB - BACKGROUND: In light of the large number of chemicals that are potential developmental neurotoxicants, there is a need to develop rapid screening techniques. OBJECTIVES: We exposed undifferentiated and differentiating neuronotypic PC12 cells to different organophosphates (chlorpyrifos, diazinon, parathion), a carbamate (physostigmine), an organochlorine (dieldrin), and a metal (divalent nickel; Ni2+) and examined indices of cell replication and differentiation for both short- and long-term exposures. RESULTS: In undifferentiated cells, all the agents inhibited DNA synthesis, with the greatest effect for diazinon, but physostigmine eventually produced the largest deficits in the total number of cells after prolonged exposure. The onset of differentiation intensified the adverse effects on DNA synthesis and changed the rank order in keeping with a shift away from noncholinergic mechanisms and toward cholinergic mechanisms. Differentiation also worsened the effects of each agent on cell number after prolonged exposure, whereas cell growth was not suppressed, nor were there any effects on viability as assessed with trypan blue. Nevertheless, differentiating cells displayed signs of oxidative stress from all of the test compounds except Ni2+, as evidenced by measurements of lipid peroxidation. Finally, all of the toxicants shifted the transmitter fate of the cells away from the cholinergic phenotype and toward the catecholaminergic phenotype. CONCLUSIONS: These studies point out the feasibility of developing cell-based screening methods that enable the detection of multiple end points that may relate to mechanisms associated with developmental neurotoxicity, revealing some common targets for disparate agents. PMID- 17366828 TI - Grand rounds: an outbreak of toxic hepatitis among industrial waste disposal workers. AB - CONTEXT: Industrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers. CASE PRESENTATION: Five workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis. DISCUSSION: Infectious hepatitis and drug induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction-type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: In the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers' health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent. PMID- 17366829 TI - Grand rounds: could occupational exposure to n-hexane and other solvents precipitate visual failure in leber hereditary optic neuropathy? AB - CONTEXT: Leber hereditary optic neuropathy (LHON) is a maternally inherited loss of central vision related to pathogenic mutations in the mitochondrial genome, which are a necessary but not sufficient condition to develop the disease. Investigation of precipitating environmental/occupational (and additional genetic) factors could be relevant for prevention. CASE PRESENTATION: After a 6 month period of occupational exposure to n-hexane and other organic solvents, a 27-year-old man (a moderate smoker) developed an optic neuropathy. The patient had a full ophthalmologic and neurologic investigation, including standardized cycloergometer test for serum lactic acid levels and a skeletal muscle biopsy. His exposure history was also detailed, and he underwent genetic testing for LHON mitochondrial DNA mutations. The patient suffered a sequential optic neuropathy with the hallmarks of LHON and tested positive for the homoplasmic 11778G--> A/ND4 mutation. Routine laboratory monitoring revealed increased concentrations of urinary 2.5 hexandione (n-hexane metabolite) and hippuric acid (toluene metabolite) in the period immediately preceding the visual loss. DISCUSSION: In a subject carrying an LHON mutation, the strict temporal sequence of prolonged appreciable occupational exposure followed by sudden onset of visual loss must raise a suspicion of causality (with a possible further interaction with tobacco smoke). RELEVANCE: In this article, we add to the candidate occupational/environmental triggers of LHON and highlight the need for appropriate case-control (and laboratory) studies to validate the causal effect of mixed toxic exposures. PMID- 17366831 TI - Hair manganese and hyperactive behaviors: pilot study of school-age children exposed through tap water. AB - BACKGROUND: Neurotoxic effects are known to occur with inhalation of manganese particulates, but very few data are available on exposure to Mn in water. We undertook a pilot study in a community in Quebec (Canada) where naturally occurring high Mn levels were present in the public water system. Our objective was to test the hypothesis that greater exposure to Mn via drinking water would be reflected in higher Mn content in hair which, in turn, would be associated with increased level of hyperactive behaviors. METHODS: Forty-six children participated in the study, 24 boys and 22 girls, 6-15 years of age (median, 11 years). Their homes received water from one of two wells (W) with different Mn concentrations: WI: mean 610 microg/L; W2: mean 160 microg/L. The Revised Conners' Rating Scale for parents (CPRS-R) and for teachers (CTRS-R) were administered, providing T-scores on the following subscales: Oppositional, Hyperactivity, Cognitive Problems/Inattention, and ADHD Index. RESULTS: Children whose houses were supplied by WI had higher hair Mn (MnH) than those supplied by W2 (mean 6.2+/-4.7 microg/g vs. 3.3+/-3.0 microg/g, p = 0.025). MnH was significantly associated with T-scores on the CTRS-R Oppositional (p = 0.020) and Hyperactivity (p = 0.002) subscales, after adjustment for age, sex, and income. All children with Oppositional and Hyperactivity T-scores > 65 had MnH > 3.0 microg/g. CONCLUSIONS: The findings of this pilot study are sufficiently compelling to warrant more extensive investigations into the risks of Mn exposure in drinking water. PMID- 17366830 TI - Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls. AB - BACKGROUND: Hormonally active environmental agents have been measured among U.S. children using exposure biomarkers in urine. However, little is known about their variation by race, age, sex, and geography, and no data exist for newly developed biomarkers. OBJECTIVE: Our goal was to characterize relevant, prevalent exposures for a study of female pubertal development. METHODS: In a pilot study among 90 girls from New York City, New York, Cincinnati, Ohio, and northern California, we measured 25 urinary analytes representing 22 separate agents from three chemical families: phytoestrogens, phthalates, and phenols. Exposures occur chiefly from the diet and from household or personal care products. RESULTS: Participants represented four racial/ethnic groups (Asian, black, Hispanic, white), with mean age of 7.77 years. Most analytes were detectable in > 94% of samples. The highest median concentrations for individual analytes in each family were for enterolactone (298 microg/L), monoethylphthalate (MEP; 83.2 microg/L), and benzophenone-3 (BP3; 14.7 microg/L). Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.8-53.2 microg/L. After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile. Three phthalate metabolites differed by race/ethnicity [MEP, mono(2-ethylhexyl) phthalate, and mono-3-carboxypropylphthalate]. CONCLUSIONS: A wide spectrum of hormonally active exposure biomarkers were detectable and variable among young girls, with high maximal concentrations (> 1,000 microg/L) found for several analytes. They varied by characteristics that may be relevant to development. PMID- 17366832 TI - Effect of community of residence on neurobehavioral development in infants and young children in a flower-growing region of Ecuador. AB - OBJECTIVE: In this study we compared neurobehavioral development in Ecuadoran children living in two communities with high potential for exposure to organophosphate (OP) and carbamate pesticides to that of children living in a community with low potential for exposure. METHODS: Women residing in the study communities who had a child 3-61 months of age completed a questionnaire about maternal and child health and sociodemographic characteristics. The Ages and Stages Questionnaire (ASQ) was administered to each child (n = 283). Growth measurements and a hemoglobin finger-prick blood test were obtained. We used multiple linear regressions to evaluate associations between community of residence and delayed development, adjusting for child health status and other characteristics of the home environment. RESULTS: Children 3-23 months of age who resided in high-exposure communities scored lower on gross motor (p = 0.002), fine motor (p = 0.06), and socioindividual (p-value = 0.02) skills, compared with children in the low-exposure community. The effect of residence in a high exposure community on gross motor skill development was greater for stunted children compared with non-stunted children (p = < 0.001) in the same age group of 3-23 months. Children 24-61 months of age residing in the high-exposure communities scored significantly lower on gross motor skills compared with children of similar ages residing in the low-exposure community (p = 0.06). CONCLUSIONS: Residence in communities with high potential for exposure to OP and carbamate pesticides was associated with poorer neurobehavioral development of the child even after controlling for major determinants of delayed development. Malnourished populations may be particularly vulnerable to neurobehavioral effects of pesticide exposure. PMID- 17366833 TI - Household pesticides and the risk of Wilms tumor. AB - BACKGROUND: Previous epidemiologic studies have suggested that exposure to pesticides in utero and during early childhood may increase the risk for development of childhood cancer, including Wilms tumor, a childhood kidney tumor. OBJECTIVES: In this analysis we evaluated the role of residential pesticide exposure in relation to the risk of Wilms tumor in children using data from a North American case-control study. METHODS: The National Wilms Tumor Study Group (NWTSG) collected information on exposure to residential pesticides from the month before pregnancy through the diagnosis reference date using detailed phone interviews from 523 case mothers and 517 controls frequency matched on child's age and geographic region and identified by list-assisted random digit dialing. Pesticides were grouped according to type of pesticide and where they were used. RESULTS: A slightly increased risk of Wilms tumor was found among children of mothers who reported insecticide use [odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0-1.8; adjusted for education, income, and the matching variables]. Results from all other categories of pesticides were generally close to the null. CONCLUSIONS: This study is the largest case-control study of Wilms tumor to date. We were unable to confirm earlier reports of an increased risk for Wilms tumor among those exposed to residential pesticides during pregnancy through early childhood. PMID- 17366834 TI - Risk factors for acute leukemia in children: a review. AB - Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics. PMID- 17366835 TI - Infectious etiologies of childhood leukemia: plausibility and challenges to proof. AB - Infections as well as environmental exposures are proposed determinants of childhood acute lymphoblastic leukemia (ALL), particularly common precursor B cell ALL (cALL). Lines of investigation test hypotheses that cALL is a rarer result of common infection, that it results from uncommon infection, or that it ensues from abnormal immune development; perhaps it requires a preceding prenatal or early childhood insult. Ideally, studies should document that particular infections precede leukemiA and induce malignant transformation. However, limited detection studies have not directly linked specific human or nonhuman infectious agents with ALL or cALL. Primarily based on surrogate markers of infectious exposure, indirect evidence from ecologic and epidemiologic studies varies widely, but some suggest that infancy or early childhood infectious exposures might protect against childhood ALL or cALL. Several others suggest that maternal infection during pregnancy might increase risk or that certain breast-feeding practices decrease risk. To date, evidence cannot confirm or refute whether at least one infection induces or is a major co-factor for developing ALL or cALL, or perhaps actually protects against disease. Differences in methodology and populations studied may explain some inconsistencies. Other challenges to proof include the likely time lag between infection and diagnosis, the ubiquity of many infections, the influence of age at infection, and the limitations in laboratory assays; small numbers of cases, inaccurate background leukemia rates, and difficulty tracking mobile populations further affect duster investigations. Nevertheless, existing evidence partially supports plausibility and warrants further investigation into potential infectious determinants of ALL and cALL, particularly in the context of multifactorial or complex systems. PMID- 17366836 TI - Investigating childhood leukemia in Churchill County, Nevada. AB - BACKGROUND: Sixteen children diagnosed with acute leukemia between 1997 and 2002 lived in Churchill County, Nevada, at the time of or before their illness. Considering the county population and statewide cancer rate, fewer than two cases would be expected. OBJECTIVES: In March 2001, the Centers for Disease Control and Prevention led federal, state, and local agencies in a cross-sectional, case comparison study to determine if ongoing environmental exposures posed a health risk to residents and to compare levels of contaminants in environmental and biologic samples collected from participating families. METHODS: Surveys with more than 500 variables were administered to 205 people in 69 families. Blood, urine, and cheek cell samples were collected and analyzed for 139 chemicals, eight viral markers, and several genetic polymorphisms. Air, water, soil, and dust samples were collected from almost 80 homes to measure more than 200 chemicals. RESULTS: The scope of this cancer cluster investigation exceeded any previous study of pediatric leukemia. Nonetheless, no exposure consistent with leukemia risk was identified. Overall, tungsten and arsenic levels in urine and water samples were significantly higher than national comparison values; however, levels were similar among case and comparison groups. CONCLUSIONS: Although the cases in this cancer cluster may in fact have a common etiology, their small number and the length of time between diagnosis and our exposure assessment lessen the ability to find an association between leukemia and environmental exposures. Given the limitations of individual cancer cluster investigations, it may prove more efficient to pool laboratory and questionnaire data from similar leukemia clusters. PMID- 17366839 TI - Keys to a successful cleft lip and palate team. AB - The severity and complexity of the defects in patients with cleft lip and/or palate (CLP) require a complex and long-term programme of care, aiming primarily at the best aesthetic and functional outcome, with a minimum of procedures and optimal cost-effectiveness. This delivery of comprehensive and coordinated health care to patients with CLP is optimally provided through collaboration in a specialised CLP team. There is international consensus about the fundamental elements of CLP treatment: multidisciplinary teamwork, centralisation, high volume care, team continuity, long-term treatment planning from birth to adulthood, standardised protocols, documentation, evaluation, follow-up studies, research, training and quality assurance. PMID- 17366837 TI - Genetic studies of a cluster of acute lymphoblastic leukemia cases in Churchill County, Nevada. AB - OBJECTIVE: In a study to identify exposures associated with 15 cases of childhood leukemia, we found levels of tungsten, arsenic, and dichlorodiphenyldichloroethylene in participants to be higher than mean values reported in the National Report on Human Exposure to Environmental Chemicals. Because case and comparison families had similar levels of these contaminants, we conducted genetic studies to identify gene polymorphisms that might have made case children more susceptible than comparison children to effects of the exposures. DESIGN: We compared case with comparison children to determine whether differences existed in the frequency of polymorphic genes, including genes that code for enzymes in the folate and purine pathways. We also included discovery of polymorphic forms of genes that code for enzymes that are inhibited by tungsten: xanthine dehydrogenase, sulfite oxidase (SUOXgene), and aldehyde oxidase. PARTICIPANTS: Eleven case children were age- and sex-matched with 42 community comparison children for genetic analyses. Twenty parents of case children also contributed to the analyses. RESULTS: One bilalleleic gene locus in SUOX was significantly associated with either case or comparison status, depending on which alleles the child carried (without adjusting for multiple comparisons). CONCLUSIONS: Although genetic studies did not provide evidence that a common agent or genetic susceptibility factor caused the leukemias, the association between a SUOXgene locus and disease status in the presence of high tungsten and arsenic levels warrants further investigation. RELEVANCE: Although analyses of community clusters of cancer have rarely identified causes, these findings have generated hypotheses to be tested in subsequent studies. PMID- 17366840 TI - Embryology and epidemiology of cleft lip and palate. AB - Craniofacial anomalies, in particular cleft lip and palate, are major human birth defects with a worldwide frequency of 1 in 700 and substantial clinical impact. This article reviews the embryology of the face, lip, and palate to enhance the understanding of the pathogenesis of these lesions, with particular attention to the period of susceptibility during gestation, complexity, and the factors that may influence their development. It includes an overview of the prevalence and environmental and genetic causes of cleft lip-with or without cleft palate- and cleft palate. PMID- 17366838 TI - An update on cancer cluster activities at the Centers for Disease Control and Prevention. AB - The Centers for Disease Control and Prevention (CDC) continues to be aware of the need for response to public concern as well as to state and local agency concern about cancer clusters. In 1990 the CDC published the "Guidelines for Investigating Clusters of Health Events," in which a four-stage process was presented. This document has provided a framework that most state health departments have adopted, with modifications pertaining to their specific situations, available resources, and philosophy concerning disease clusters. The purpose of this present article is not to revise the CDC guidelines; they retain their original usefulness and validity. However, in the past 15 years, multiple cluster studies as well as scientific and technologic developments have affected duster science and response (improvements in cancer registries, a federal initiative in environmental public health tracking, refinement of biomarker technology, cluster identification using geographic information systems software, and the emergence of the Internet). Thus, we offer an addendum for use with the original document. Currently, to address both the needs of state health departments as well as public concern, the CDC now a) provides a centralized, coordinated response system for cancer cluster inquiries, b) supports an electronic cancer cluster listserver, c) maintains an informative web page, and d) provides support to states, ranging from laboratory analysis to epidemiologic assistance and expertise. Response to cancer clusters is appropriate public health action, and the CDC will continue to provide assistance, facilitate communication among states, and foster the development of new approaches in duster science. PMID- 17366842 TI - The role of patient-support groups. PMID- 17366841 TI - Orofacial clefting: update on the role of genetics. AB - INTRODUCTION: Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects in the world. Prevalence varies between populations, with an average of 1/700. CL/P has a major clinical impact, requiring surgical, dental, orthodontic, speech, hearing and psychological management throughout childhood. The aetiology of CL/P is mostly unknown, and it is thought that both genetic and environmental factors play a role. Several causative genes for inherited syndromic forms of CL/P have been identified, and some recent studies have shown that these genes also contribute to the occurrence of isolated forms. Van der Woude syndrome (VWS) is one of the best models for non-syndromic CLP. It is an autosomal dominant disorder characterised by the presence of pits on the lower lip in addition to CL/P. Pits are the only feature distinguishing VWS from isolated clefts. Interestingly, in numerous VWS patients, the lip pits are very small and not readily diagnosed, thus mimicking isolated CL/P. Mutations in the IRF6 gene were shown to be the major genetic cause of VWS.' RESULTS: We performed direct sequence analysis of IRF6 on samples from a large European cohort and identified mutations in 27 (80%) families. This shows that IRF6 is the major causative gene of VWS in Europe also. Moreover, it is the gene to study when a seemingly isolated CL/P patient has minor signs, such as lip pits, since the identification of a mutation in IRF6 is associated with an increase in the risk of having a child with CL/P from 4-6%, the risk of transmission of an isolated cleft, to 50%, the risk of transmission of a dominant Mendelian disorder like VWS. Moreover, we studied the association of isolated CL/P with the IRF6 locus using two variants in a set of 195 patients from Belgium. As in an American study, a clear association was observed. This suggests that IRF6 also contributes to the occurrence of sporadic, isolated CL/P, even if no mutation in the gene can be identified in such patients. CONCLUSION: In conclusion, genes that are mutated in familial syndromic forms of CL/P may be predisposing genetic factors to sporadic isolated CL/P. Due to technological advances and the availability of the human genome sequence, we have now the opportunity to try and unravel the genetic factors behind the various forms of CL/P. PMID- 17366843 TI - The point of view of the patient: personal account from a patient who has finished the cleft lip and palate programme. PMID- 17366844 TI - Surgery of the cleft lip and nose--the GOStA approach. AB - The technique for primary correction of the cleft lip and nose, as practised by The North Thames Cleft Lip and Palate Centre at Great Ormond Street Hospital/St Andrew's Centre (GOStA) has evolved over 28 years of personal experience. It is an amalgamation of techniques developed by many others with some personal modifications. Patients are routinely audited at 5, 10, 15 and 20 years and outcomes evaluated and compared with other centres where possible. Secondary surgery of lip and nose is based on the same principles of anatomical reconstruction used in the primary surgery. PMID- 17366845 TI - Surgery of the cleft palate: repair using the operating microscope with radical muscle retropositioning--the GostA approach. AB - The aim of cleft palate surgery is to minimise damage which results in impaired maxillary growth, and to maximise outcome in terms of velopharyngeal function. Techniques developed by the author, building on work by many and employed by the North Thames Cleft Lip and Palate Centre at Great Ormond Street Hospital/St Andrew's Centre (GOStA) appears to offer one way of achieving these aims. However, the learning curve is long. PMID- 17366846 TI - The Leuven staged supraperiosteal retropositioning repair: long-term velopharyngeal function in non-syndromic cleft palate. AB - BACKGROUND: From 1989 to 1993, 113 previously untreated patients were admitted to the Multi-disciplinary Cleft Lip and Palate Team of the University Hospitals Leuven. Palate repair was performed in our centre by one surgeon (FO) in 88 patients. Our current surgical technique consists of a single-stage supraperiosteal retropositioning (modified Veau-Wardill-Kilner) for patients with a soft cleft palate only (SCP) or a soft cleft palate with up to 1 cm of the hard palate (HSCPpa). Patients with a larger or complete cleft of the secondary hard palate (HSCP) and patients with unilateral (UCLP) or bilateral (BCLP) cleft lip and palate undergo two surgical stages for palate closure: a supra-periosteal retropositioning is performed around 12 months of age, and a modified Langenbeck closure of the hard palate around 60 months of age. AIM: To assess velopharyngeal function with speech as outcome measure. PATIENTS AND METHODS: Velopharyngeal function was assessed in two ways. In one assessment, a "hard" outcome measure was the number of patients undergoing pharyngoplasty following palate repair in our centre (n = 88). In the other assessment, velopharyngeal function was evaluated in a homogeneous sub-population of 44 non-syndromic cleft patients with normal to slight impairment of the following functions: mental development, language development, and hearing. In this group, prospectively collected data about hypernasality and nasal emission were analysed retrospectively using a semi objective nasality index (NI). Articulation was evaluated using a subjective articulation index (AI) representing articulation errors (retro-articulation, glottal stops and facial grimacing) associated with velopharyngeal insufficiency (VPI). Mean follow-up was 114 months. RESULTS: Despite rigid assessment by a phoniatrician and speech pathologist, only 1 patient out of 88 patients with soft palate surgery in our institution was thought to need pharyngoplasty. In the sub cohort of 44 non-syndromic patients, nobody needed a pharyngoplasty. In the latter cohort, at the age of about eight years, 27 patients (61.5%) had undetectable nasality, 13 patients (29.5%) had an NI of 1 or "mild" nasality, and 4 patients (9%) had moderate nasality. At this point in time, articulation errors associated with VPI were noted in 14% of patients. CONCLUSION: In this subgroup of cleft palate patients treated following the Leuven protocol, there was no need for secondary pharyngoplasty. Ninety-one per cent of patients had no, or only mild, rhinolalia aperta by the age of eight years, and 84% did not display VPI related articulation disorders. This suggests that velopharyngeal function in patients treated by this protocol is excellent compared to results in the literature. PMID- 17366847 TI - Long-term follow-up of UCLP at the Reine Fabiola Children's Hospital. AB - BACKGROUND: The purpose of this retrospective of prospectively acquired data was to evaluate and to compare global evolution in children with complete unilateral cleft lip and palate treated at the Brussels cleft centre following two different surgical treatment protocols. METHODS: A series of forty-four patients operated for non-syndromic complete unilateral cleft lip and palate were included in this study at the age of approximately ten years. Twenty-six children (17 males, 9 females) were treated according to the Malek surgical treatment protocol: the soft palate was closed at a mean age of 3 months, followed by simultaneous repair of the lip and hard palate at a mean age of 6 months. Eighteen children (15 males, 3 females) underwent one-stage "all-in-one" closure of the lip, hard and soft palate at a mean age of 3 months. Craniofacial morphology was evaluated by means of digital lateral cephalometric analysis. Cephalometric data were compared to a control, non-cleft group (n = 40) matched according to age. Data concerning otological status and speech were collected in the same series of children. RESULTS: Statistical analysis showed that the inclination of the maxillary (MxPVSN) plane to the anterior cranial base was significantly increased (p <0.001) in both cleft groups compared to the non-cleft group and significantly increased (p = 0.002) in the Malek cleft group compared to the "all-in-one" cleft group. Otological status was not improved by an early complete closure but by close follow-up and the repeated placement of ventilating tubes. Speech was found to be satisfactory in the majority of children of both groups at six years after speech therapy. Only 15% needed further surgery with pharyngeal flaps. CONCLUSIONS: There were no significant differences in anteroposterior midfacial morphology between the Malek and "all-in-one" protocols at ten years of age. One stage "all-in-one" closure resulted in less downward inclination of the maxillary plane to the anterior cranial base compared to the Malek protocol at ten years of age. Early complete closure of the cleft resulted in no significant change in otological status or the occurrence of nasality. However, early complete closure of the cleft allowed for earlier intelligibility of speech compared to the staged later closure. PMID- 17366848 TI - Review of the UCL management of patients with cleft lip and palate. AB - We describe the way our multidisciplinary team manages cleft lips and palates at our centre at the Catholic University of Louvain. Since 1987, we have opted for the neonatal repair of the cleft lip and nose, and closure of the cleft palate at three months of age. Multidisciplinary follow-up then takes place to detect and correct the sequellae. The children are seen once a year by a plastic surgeon, an otorhinolaryngologist, a maxillofacial surgeon, a speech therapist, an audiologist, and an orthodontist. Secondary corrections are scheduled depending on functional, aesthetic, and psychological requirements. PMID- 17366849 TI - The orthodontist, an essential partner in CLP treatment. AB - OBJECTIVES: Patients with orofacial clefts need multidisciplinary care, which should be provided by teams of specialists working in this field. Usually the following disciplines participate in such teams: paediatrics, plastic and reconstructive surgery, orthodontics, genetics, social work or nursing, ENT, speech therapy, maxillofacial surgery, prosthetic dentistry, psychology and oral hygiene. DESIGN: Narrative review. RESULTS: An overview is given of the orthodontic treatment protocol and the role of the orthodontist in cleft palate treatment from birth until 20 years of age for a child with a complete unilateral or bilateral cleft. CONCLUSIONS: The orthodontist has proven to be an essential partner in the cleft palate team. The orthodontist is not only responsible for the active orthodontic and facial orthopaedic treatment of the child with a cleft. More importantly, he or she is also the guardian of the child's maxillofacial growth. By nature, orthodontists have a long-term treatment perspective in mind, which will assist the team in their consideration of treatment techniques, sequence and timing in relation to the effect on maxillofacial growth. Moreover, standardised records collected by the orthodontist provide a valuable basis for retrospective studies of treatment outcome and inter-centre comparisons. Finally, in recent times, orthodontists seem to be quite often the motor behind large-scale inter-centre randomised clinical trials in the field of CLP. PMID- 17366850 TI - Cleft palate speech and velopharyngeal dysfunction: the approach of the speech therapist. AB - Cleft palate and velopharyngeal dysfunction cause communication disorders in many different ways (articulation, resonance, voice and language). These problems are mainly present in childhood but remain a matter of concern for many years. Speech and language pathologists are involved in speech and language assessment and speech therapy procedures. This article gives an overview of the standard procedures of the speech pathologist in a cleft palate team and discusses the relationship between the team and private practices or school teams, as well as the practical aspects relating to reimbursement by the National Institute of Health and Invalidity (RIZIV). PMID- 17366851 TI - SISL (ScreeningsInstrument Schisis Leuven): assessment of cleft palate speech, resonance and myofunction. AB - This paper presents an assessment protocol for the evaluation and description of speech, resonance and myofunctional characteristics commonly associated with cleft palate and/or velopharyngeal dysfunction. The protocol is partly based on the GOS.SP.ASS'98 and adapted to Flemish. It focuses on the relevant aspects of cleft type speech necessary to facilitate assessment, adequate diagnosis and management planning in a multi-disciplinary setting of cleft team care. PMID- 17366852 TI - Cleft palate speech and velopharyngeal insufficiency: surgical approach. AB - Velopharyngeal insufficiency is the main morbidity associated with clefting of the secondary palate. Therefore, it is important to monitor speech production in all children with a history of cleft palate. Diagnosis and management of velopharyngeal insufficiency is an important function of the cleft palate team. The surgical approach used in the Craniofacial Center at Children's Hospital and Regional Medical Center, Seattle, Washington, USA is presented. Assessment of velopharyngeal function, as it relates to surgical intervention and measurement of outcome, is reviewed. Surgical management using Furlow palatoplasty and sphincter pharyngoplasty is discussed. PMID- 17366853 TI - The middle ear of cleft palate patients in their early teens: a literature study and preliminary file study. AB - OBJECTIVES: Middle ear disease is a frequent problem in young children with cleft palate (CP). Less is known about otological status in the adolescent CP population. The aim of this study is to provide an overview of current knowledge in the literature concerning the aetiology of middle ear disease in CP patients and the middle ear status of older children with CP, and to compare the situation in our centre to this background through an assessment of the otological status of patients in our CP population. MATERIAL AND METHODS: A literature review was conducted to summarise current knowledge about middle ear status in CP patients. A retrospective analysis was performed of the medical records of 20 CP patients between the ages of 10 and 15 who were treated and followed at the University Hospitals Leuven. The available otological data, otoscopic findings, information about hearing and surgery performed was collected for each patient when aged three and above ten years. RESULTS: Current knowledge indicates that middle ear function improves as CP patients get older. In our study, otoscopic appearance was acceptable in 63% of ears of children aged over ten years of age. Otitis media with effusion (OME) was far less frequent above this age than around the age of 3, with a decrease from 50% to 13% of all ears. Above the age of 10, tympanic perforations were present in 13% of ears and retraction of the tympanic membrane in 23%. CONCLUSIONS: Despite a very high incidence of OME in young CP patients, the long-term otological prognosis is not necessarily sinister. A favourable natural evolution, diligent otological follow-up, early diagnosis and treatment of middle ear disease with the use of tympanostomy tubes are the likely contributors to the acceptable otological result in older CP patients. PMID- 17366854 TI - Secondary rhinoplasty in the cleft lip patient. AB - Secondary surgery of the cleft lip nose is very complex due to its specific pathological anatomical characteristics. In this article, the general and specific characteristics of the nose of the unilateral and the bilateral cleft patient are described, and careful preoperative assessment is emphasized. Considerations concerning the timing of the operation before or after the puberty growth spurt are discussed. Guidelines are given for a systematic correctional surgical approach, dividing the operative procedure into septal surgery, tip surgery, osseo-cartilaginous vault surgery, maxillary augmentation and alar base reallocation. A description is given of special postoperative care with a custom made vestibular device to prevent stenosis of the vestibulum and deformation of the nasal tip caused by scar tissue retraction in the postoperative period. PMID- 17366855 TI - Secondary corrective bone surgery: osteodistraction and osteotomies. PMID- 17366856 TI - [Management of patients with benign prostatic hyperplasia by urologists: the DUO study]. AB - The DUO study intended to define the factors determining diagnostic and treatment strategies for benign prostatic hyperplasia (BPH) management. METHODS: This longitudinal, observational study was conducted in France (June 2004 to March 2005), with a representative sample of private and hospital urologists. RESULTS: 1027 BPH patients were included by 202 urologists and 856 were followed-up 6 months later. Mean I-PSS was 14.9 (+/- 6.7) at inclusion and 10.5 (+/- 6.7) at the follow up visit. At inclusion, pharmacologic treatment was prescribed to 84% of the patients, surgery to 13% and no treatment to 3%. Factors in favour of surgery (versus drugs) were BPH severity (OR = 2.5 if IPSS = 20), patients' choice (OR = 2.5), quality of life improvement (OR = 2.2), post-void residual (OR = 2.1) and dribbling (OR = 1.6). Patients' age and prostatic volume have no impact on this choice. Factors in favour of a combination of an alpha-blocker plus an 5alpha-reductase inhibitor (versus an alpha-blocker) were prostate volume (OR = 7.8), patient's age (OR-3.0 if age = 74) and post-void residual (OR = 2.3) and those in favour of a 5alpha reductase inhibitor (versus an alpha-blocker) were prostate volume (OR = 7.6), PSA results (OR = 5.8), patients' age (OR = 5.4 if > 74 years, OR = 2.1 if > 68 years). CONCLUSION: Medical or surgical treatment of BPH results in IPSS improvement at 6 months. Patients' age and prostatic volume favour 5alpha-reductase inhibitor initiation and have no impact on surgical treatment decision. Surgery is performed in severe BPH or when patients expecting a quality of life improvement do that choice. PMID- 17366857 TI - [Antithrombotic drugs in urological surgery. Treatment interfering with haemostasis in urology?]. AB - In storing or withholding a treatment that interferes haemostasis should be considered after assessing the benefit-risk ratio which requires the understanding of the efficacy, safety and pharmacology of heamostatic agents. This benefit to risk assessment is the key stone for the prevention of venous thrombosis, and peri-operative management of antiptatelet agents and vitamin K antagonists. PMID- 17366858 TI - [How far should partial nephrectomy be extended for renal cell carcinoma?]. AB - Conservative renal surgery for cancer has now achieved consensus for imperative, relative, and elective indications (tumor < 4 cm with healthy contralateral kidney). The results show 90%-100% 10-year survival rates and 0%-3% recurrence rates. Surgical techniques are improving and complication rates are decreasing with experience. It is now recognized that margin thickness has no real significance provided that it is negative, even if excision is flush with the tumor capsule. Finally, the frequently cited multifocal lesions are no longer an argument against conservative surgery. The usual limitations of conservative surgery are the size and location of the tumor. Nevertheless, there is no statistically significant difference in the survival and recurrence rates between T1a (< 4 cm) and T1b (4-7 cm) tumors, even if the risk of renal sinus fat tissue involvement increases proportionally with tumor size. Finally, resecting tumors of the renal sinus is possible without adding to the risk of metastasis but increases the risk of surgical complications. The risk of deteriorated renal function with radical nephrectomy is now well documented. Laparoscopy, which has become the reference treatment mode for radical nephrectomy, remains reserved for conservative surgery for exophytic tumors less than 3-4 cm because of the technical difficulties involved in resection and hemostasis. Although conservative surgery is now recognized, extending its indications to tumors greater than 4 cm or in cases of parenchymatous location is supported by real arguments that need to be confirmed. The limit remains the surgical feasibility. PMID- 17366859 TI - [Renal cancer: what can we expect from emerging new technologies: radiofrequency and cryoablation?]. AB - Radiofrequency and cryoablation are both minimally invasive techniques applied to the treatment of renal cell carcinoma. These techniques allow in situ destruction of neoplasm. Although cryotherapy is the most studied, radiofrequency is the most currently used technique. Indications mostly accepted as elective indication are the less than 4 cm in diameter exophytic tumors. Radiofrequency and cryoablation can also be proposed in patients with solitary kidney, multiple bilateral tumors and patients with contraindication for surgical resection. The radiofrequency parietal tract can be coagulated at the time of radiofrequency electrode withdrawal reducing the rare risk of parietal tumor dissemination. Preliminary oncological results in exophytic small renal tumors are promising with only few complications. A longer follow-up is however mandatory to better define the place of these two new technologies in the treatment of renal cancer. PMID- 17366860 TI - [Renal cell carcinoma: management of venous thrombus]. AB - Radical nephrectomy with vena cava thrombectomy remains the treatment of choice in patients with renal cell carcinoma and inferior vena cava involvement. Surgery is performed with curative intent in patients without evidence of metastases or for cytoreduction, followed by possible immunotherapy in patients with distant metastases. The role of magnetic resonance imaging for evaluating the renal vein and/or IVC to detect thrombus and the proximal extent of thrombus is fully established. Surgical removal of these cancers through a transabdominal approach, even in patients with a level 2 thrombus (involving the retrohepatic IVC with close proximity to the main hepatic veins) is possible, avoiding the potential added morbidity of a throacoabdominal approach or median sternotomy. The application of liver transplant techniques and liver mobilization procedures not generally familiar to urological surgeons facilitates wide exposure and proximal control of the IVC for tumors cephalad to the confluence of the hepatic veins. As an initial step we believe that cephalad retraction of the liver with mobilization of the IVC by securing the lumbar, small hepatic and other unnamed venous collaterals may be tried to gain exposure of the retrohepatic IVC. Overall survival in patients with IVC involvement after complete surgical removal in the absence of metastatic disease justifies aggressive surgical management. PMID- 17366861 TI - [Metastatic renal cell carcinoma and its treatments]. AB - The treatment of metastatic renal cell carcinoma is deeply evolving. After the cytokines, interleukin 2 and interferon era, which raised great expectations followed by deep disillusions (related to an efficacy limited to a small group of patients and an important toxicity for a majority of them), the time of targeted therapies has come. These new therapies mainly work on the VHL-HIF way, which controls several key molecules involved in the tumour angiogenesis phenomena, especially the VEGF. Several drugs currently being developed allow to stop either the circulating angiogenic factors (mainly the VEGF), or the tyrosine kinase receptors, especially the VEGF and the PDGF receptors. The reported activity and potential of these drugs are: tumour reduction, improvement of progression-free survival, effects on the overall survival. Currently, 4 among these drugs are in phase III (sorafenib, sunitinib, bevacizumab and temsirolimus), sorafenib and sunitinib have been allowed by the FDA, in the USA, and by the EMEA, in Europe, in the treatment of advanced renal cell carcinoma. PMID- 17366862 TI - [Renal imaging and biopsy for diagnosis of renal masses]. AB - Incidental diagnosis of renal tumors is more and more common. Imaging is of paramount importance for the caracterization of these tumors. Ultrasound allows the diagnosis of solid tumors, thereby excluding cysts. The gold standard is the CT-scan, the realisation of which must obey to precise quality criteria. MRI yields further informations in selected cases. Renal cancer is the main etiology, but benign tumors can be suspected in small tumors less than 4 cm. Angiomyolipoma and oncocytoma are the more frequent benign tumors. Angiolipoma can be diagnosed with CT-scan, but there are no radiological criteria for the diagnosis of oncocytoma. Renal percutaneous biopsy can be helpful in selected cases. It is recommended for bilateral tumors, or when a renal metastasis is suspected. For small lesions with radiological features consistent with the diagnosis of benign tumor, renal biopsy can confirm this diagnosis and lead surgical abstention. Nevertheless, few centers have a regular practise of renal biopsy. Its contribution is still to be evaluated. PMID- 17366863 TI - [Endoscope disinfection]. AB - Economic considerations currently limit the idea of the disposable flexible endoscope, which would guarantee absolute safety against the transmission of infections. Since the endoscope is made of a heat-sensitive material, it is impossible to sterilize it by autoclave. A disinfection procedure must therefore be applied, which, although it does not guarantee the same level of safety as classical sterilization, provides a sufficient reduction in the microorganism load. This procedure is carried out in two steps: first cleaning by mechanical action using a detergent, then the actual disinfection by soaking in a disinfectant bath. As urine is a sterile milieu, a high-level disinfection- bactericide, virucide, fungicide, and sporicide--should be implemented by soaking for 30 min in a peracetic acid bath. Prion risk, which must systematically be taken into account, can be controlled by a double cleaning method eliminating all proteic debris and by replacing glutaraldehyde with peracetic acid. PMID- 17366864 TI - [Practical aspects concerning the use of anticoagulants in urology]. AB - Two aspects are considered: the prevention of peri-operative venous thromboembolism, and the management of antiplatelet agents (APA) and anticoagulants during the peri-operative period. Thrombotic and haemorrhagic risk factors linked to the patient and to urological surgical procedures are recalled. A decision whether to initiate preventive therapy for peri-operative venous thromboembolism will be based on analysis of these risk factors and of the risk/benefit ratio. The methods for this preventive treatment are recalled. Practical examples in urology are used to illustrate the application of these principles. Similarly, the indications, and thrombotic and haemorrhagic risk factors related to anti-platelet agents and anticoagulants during the peri operative period are recalled. A decision whether or not to withdraw these anti platelet agents or anticoagulants will be based on an analysis of their indications, these risk factors and an assessment of the risk/ benefit ratio. Replacement therapies are reviewed. Practical examples in the urological setting are given regarding application of these principles. PMID- 17366865 TI - [Is volume of surgical activity relevant for surgeon's evaluation?]. AB - "Often done, better done" is a popular saying that may lead health authorities to use the volume of surgical activity to assess surgical quality, including eventually this criteria in their certification manual. Very few data indeed support this idea in Urology. On the other hand, well-conducted studies clearly show that high volume activity does not always avoid surgical complications. Moreover, fair statistics should be applied to urologists, with proper calculation of confidence intervals, before scrutinizing reasons why they may appear "to differ" from the assigned goal or their colleagues' average. This, for major urologic operations, can only be done after a prolonged observation period, sometimes reaching over a decade. PMID- 17366866 TI - Hydatidosis in camels (Camelus dromedarius) slaughtered at Sirt Abattoir, Libya. AB - Fifty out of 1380 (3.62 %) local bred camels (Camelus dromedarius) harboured hydatid cysts of Echinococcus granulosus. Prevalence in males was 3.07 %, in females was 4.42 % and overall prevalence rate was 3.62%. Infection was higher in age group 1 <3 years than others. The most commonly infected organs were lungs 46% followed by liver 24%, both liver and lungs constituted 30% of infection. Hydatid cysts of lungs had a higher fertility rate (85.77%) than those of liver (14.23%). The mean number of cysts in infected liver was 1 to 15 and in infected lung were 1 to 17 cysts. Intensity of infection increased with increasing age. Cysts size varied from 1-8 cm in diameter. PMID- 17366867 TI - New approach in surgical management of complicated umbilical hernia in the cirrhotic patient with ascites. AB - A total of 23 consecutive patients operated upon on emergency basis for the treatment of complicated umbilical hernias associated with liver cirrhosis and ascites. The hernia was complicated by strangulation in 11 and ascitic fluid leak in twelve of the patients. Patients were assigned randomly in two groups. In the first group (GI, n = 12) peritoneal drainage at the conclusion of their surgery was done but no drainage was applied in the second group (GII, n=12). All patients were operated upon and when closed system peritoneal drainage was done, it was brought to outside of the abdomen through a separate stab. No negative pressure was applied. The main outcome measures were postoperative wound healing, control of ascites, complications, and hernia recurrence rate at follow up. The male/female ratio, Child's class, ascites severity, and mode of hernia complication were almost matched in both groups. Postoperative wound dehiscence occurred in four patients in G II (23.5%) but in none of GI. Control of ascites was achieved in all patients of GI. The overall mean hospital stay was significantly lower in-patient of GI than those of the G II (P < 0.0 1). Recurrences of the hernia occurred in one patient only of the G I and in three of the G II on a mean follow- up of 19+/-3 months. So, postoperative closed peritoneal drainage in the management of complicated umbilical hernias associated with liver cirrhosis and ascites safe and effective in assuring postoperative wound healing, control of ascites and the prevention of hernia recurrence. It is specifically indicated in cases with bowel resection anastomosis and in patients with low preoperative serum albumin and history of rapid ascites re-accumulation under medical therapy. PMID- 17366868 TI - Hydatidosis- chinococcosis in Libya (review article). AB - Cystic echinococcosis due to Echinococcus granulosus is a serious public health and livestock economy problem in Libya. The present paper reviewed and summarized all data available on hydatidosis since 1970. In Libya, the disease was described as hyper-endemic (Matossian et al., 1977). However, many reports, used the term endemic (Dar and Taguri, 1979; Gebreel et al., 1983; Shaafie et al., 1999). The term is more realistic as the incidence of the disease within the Libyan population was >1 per 100,000 (Shambesh, 1997) and rate of hydatidosis in sheep was about 12.7% (Gusbi et al., 1987). The values did not fulfill WHO criteria to describe hyper-endemic (i.e. surgically >10 per 100,000 and 50% rate in sheep (Craig et al., 1991). PMID- 17366869 TI - Strongyloidiasis stercoralis: is it a health problem in Saudi Arabia? AB - S. stercoralis which does not need intermediate host, undergo free cycle in the soil, was reported. So, human strongyloidiasis as an introduced or a misdiagnosed problem was discussed. PMID- 17366870 TI - Allergic reactions in patients suffering from asthma induced by house dust mites which treatment by juvenile hormone. AB - The effect of Juvenile hormone analogue, Admiral "pyriproxyfen", which acts as a protein de-naturing agent, on the protein patterns of D. farinae was studied on allergic reactions in patients with HDM asthma, and in mice injected twice (within 10 days) with mite crude extracts. Total protein concentrations and protein patterns were different in normal and admiral-treated mites. This may result in reducing the allergenic of treated mites. Histamine release, total immunoglobulin E (IgE), specific immunoglobulin E (S-IgE), eosinophil cationic protein (ECP), and absolute eosinophil count (AEC) were determined for moderate and severe HDM asthma-tics compared to check cases. These parameters had higher levels in asthmatic patients than in normal (check) individuals. Injection of mice with normal adult extracts of D. farinae resulted in significantly higher levels of histamine, S-IgE and ECP than in the check animals. Skin reactions were observed in all of the mice injected with normal or treated D. farinae extracts. PMID- 17366871 TI - Zoonotic cryptosporidiosis in man and animal in farms, Giza Governorate, Egypt. AB - To demonstrated the zoonotic cryptosporidiosis. A total of 189 farmers and their farm animals (200= 71 buffaloes, 59 cows, 43 sheep and 27 goats were examined. Stool samples Each stool sample was subjected to the direct wet smear method and Sheather's sugar flotation and acid-ether sedimentation techniques and stained with four stains (Modified Ziehl Neelsen, Safranin, methylene blue, Aniline carbol methyl violet and Giemsa). A positive statistically significant correlation was observed between farmers and their farm animals infected with cryptosporidium parvum proving a zoonotic potential for infection (r = 0.819 P <0.01 for cryptosporidiosis. For detection of Cryptosporidium, 100 % sensitivity was obtained when acid ether concentration technique was used and modified Ziehl Neelsen stain revealed highest sensitivity of 92.1 %. PMID- 17366872 TI - An evaluation of Swedish health economics research. PMID- 17366873 TI - [High mortality in a herd with signs of jejunal hemorrhage syndrome]. AB - Eleven cows from a herd of 80 dairy cows (14%) died over a 7-month period. Death occurred within 12-24 hours of the onset of the first clinical signs, namely, dullness and a decrease (mean 25%) in milk production. Within 12 hours the cows were unable to rise, felt cold, and were restless. Examined mucous membranes were pale. Two of three cows examined at necropsy had blood in the jejunum and high counts of Clostridium perfringens. Jejunal hemorrhage syndrome was diagnosed in these two cows on the basis of the clinical signs and postmortem findings. PMID- 17366874 TI - [A mastocytoma in a dog]. PMID- 17366875 TI - [Methods for large scale euthanasia of poultry to control disease: acceptable in terms of grief and efficiency]. PMID- 17366876 TI - [Animal and human rights in installments]. PMID- 17366877 TI - [An international rabies project (1967-1974). Learn from the past]. PMID- 17366878 TI - [Meeting 'udder health panel' about animal nutrition and immunity]. PMID- 17366879 TI - ['Emergency and critical care' comes to the Netherlands]. PMID- 17366880 TI - [Transgenic rice breeding for abiotic stress tolerance--present and future]. AB - Environmental stresses and the continuing deterioration of arable land, along with an explosive increase in world population, pose serious threats to global agricultural production and food security. Improving the tolerance of the major crop plants to abiotic stresses has been a main goal in agriculture for a long time. As rice is considered one of the major crops, the development of new cultivars with enhanced abiotic stress-tolerance will undoubtedly have an important effect on global food production. The transgenic approach offers an attractive alternative to conventional techniques for the genetic improvement of rice cultivars. In recent years, an array of stress-related genes has already been transferred to rice to improve its resistance against abiotic stresses. Many transgenic rice plants with enhanced abiotic stress-tolerance have been obtained. This article focuses on the progress in the study of abiotic stress tolerance in transgenic rice breeding. PMID- 17366881 TI - [Study on disulfide bond formation protein A in Escherichia coli]. AB - Disulfide bond formation protein A, DsbA, is one of the important proteins located in E. coli periplasm, which is a foldase facilitating the folding of nascent secreted proteins, especially for those with many pairs of disulfide bonds. The crystal structure and phylogenetic analysis of DsbA and DsbA-mediated protein folding, alternatively in vivo and in vitro, are summarized. Both the extremely low pKa of Cys30 , about 3.5, and the destabilizing effect of the active site disulfide contribute to its strong oxidizing power. The Cys30 is also considered as the most important residue closely related to its activity using site-directed mutagenesis methodology. DsbA could effectively assist proteins folding, both in vivo coexpressed with the target protein, and in vitro replenished as foldases. Moreover, DsbA also has the chaperone-like activity in the assistant refolding of genetically engineered inclusion bodies. PMID- 17366882 TI - [Progress of oligosaccharides biosynthesis in recombinant Escherichia coli]. AB - As more bioactivities of oligosaccharides have been elucidated, researches on biosynthesis of oligosaccharides have drawn more concerns in Glycobiology. A lot of enzymatic methods for the synthesis of oligosacchrides have been developed employing recombinant E. coli expressed glycosyltranferase or synthase of nucleotide-sugar. This review focuses on the recent progress in the production of oligosaccharides using bacteria especially by genetically engineered bacteria. The key point concering the oligosaccharides biosynthesis in recombinant E. coli, such as enzyme expression, NDP-sugar provision and biosynthesis pathway, was discussed. PMID- 17366883 TI - [Enhancement of exogenous gene expression by artificial transcription factor in CHO cells]. AB - Using the amino acids 1-147 of the yeast transcriptional activator GAL4 as the DNA-binding domain and four tandem repeats of the 12-aa peptide (DALDDFDLDMLG) of the herpesvirus as the activation domain, an artificial transcription factor, GVP4,was constructed via the linkage of the nuclear localization signal sequence of SV40. And then, GVP4 was cloned into expression vector pcDNA3 . 1/Hygro ( + ) . Various amounts of targeting sites of artificial transcription factor were linked to the upstream of promoter CMV in exogenous gene expression vector pcDNA3.1 ( + ) that separately harbored EGFP cDNA and t-PA cDNA.The CHO cells were then co-transfected with GVP4 expression vector and EGFP or t-PA expression vector. The effect of GVP4 on exogenous gene expression was evaluated by measuring the fluorescence intensity of EGFP in CHO cells and the concentration of t-PA in the supernatant. GVP4 showed positive effect on the enhancement of exogenous gene expression in CHO cells integrated with targeting sites of artificial transcription factor. And, CHO cells integrated with 10 targeting sites of GVP4 was more favorable to foreign gene expression, which resulted in 2 3-fold increase in both EGFP and t-PA expressions. These results indicated that artificial transcription factor is potent in the enhancement of exogenous gene expression in mammalian cells. PMID- 17366884 TI - [Construction of recombinant adenovirus including microdystrophin and expression in the mesenchymal cells of mdx mice]. AB - Construction of recombinant adenovirus, which contain human microdystrophin, and then transfection into mesenchymal cells( MSCs) of mdx mice were done, and genetically-corrected isogenic MSCs were acquired; the MSCs transplantation into the mdx mice was then done to treat the Duchenne muscular dystrophy( DMD). Microdystrophin cDNA was obtained from recombinant plasmid pBSK-MICRO digested with restrictive endonuclease Not I ; the production was inserted directionally into pShuttle-CMV. The plasmid of pShuttle-CMV-MICRO was digested by Pme I , the fragment containing microdystrophin was reclaimed and transfected into E. coli BJ5183 with plasmid pAdeasy-1. After screening by selected media, the extracted plasmid of positive bacteria was transfected into HEK293 cells with liposome and was identified by observing the CPE of cells and by the PCR method. Finally, MSCs of mdx mice were infected with the culture media containing recombinant adenovirus, and the expression of microdystrophin was detected by RT-PCR and immunocytochemistry. Recombinant adenovirus including microdystrophin was constructed successfully and the titer of recombinant adenovirus was about 5.58 x 10(12) vp/mL. The recombinant adenovirus could infect MSC of mdx mice and microdystrophin could be expressed in the MSC of mdx mice. Recombinant adenovirus including microdystrophin was constructed successfully, and the microdystrophin was expressed in the MSC of mdx mice. This lays the foundation for the further study of microdystrophin as a target gene to correct the dystrophin-defected MSC for stem cell transplantation to cure DMD. PMID- 17366885 TI - [Influence of epitope A modification and N-linked glycosylated site mutation of PRRSV NJ-a strain ORF5 gene on the ability to induce neutralizing antibodies and T cell proliferation response]. AB - To enhance the DNA immunogencity of PRRSV ORF5 gene, CpG sequence and the universal helper T cell antigen epitope (PADRE) sequence were inserted between the decoy epitope and the neutralizing epitope. At the same time, site-mutations were introduced at N33 and N51 to diminish the coverage effect to epitope B from the polysaccharides. Subsequently, the modified ORF5 gene (MORF5) and PRRSV ORF6 gene were cloned into the eukaryotic expression vector pcDNA3.0 under the control of two CMV promoters, respectively. With indirect immunofluorescence assay and Western-blot the expression in vitro of the two genes was confirmed, then six week-old Balb/C mouse were immunized with the modified expression plasmid pcDNA M5A-6A. The non-modified expression plasmid pcDNA-5A-6A, the blank eukaryotic expression plasmid pcDNA3.0, living attenuated vaccine and inactivated vaccine were used as controls. The PRRSV specific neutralizing antibodies and the T cell proliferation response were elevated with virus neutralization assay and MTf method. Results indicate that the modified plasmid pcDNA-M5A-6A can elicit not only higher titer of neutralizing antibodies in a rapid time, but also more vigorous T cell proliferation response compared with the non-modified plasmid pcDNA-5A-6A and commercial vaccines, indicating that DNA vaccine pcDNA-M5A-6A maybe a promising candidate for PRRS prevention. PMID- 17366886 TI - [Preparation antibodies against recombinant bovine IFN-gamma and development of sandwich ELISA for bovine IFN-gamma detection]. AB - This study was aimed to establish ELISA for recombinant bovine IFN-gamma (BovIFN gamma) detection and provide a new method for diagnosis of pathogenic infection. The total RNA was isolated from peripheral blood leucocytes cultured with PHA mitogen stimulation. Then bovine IFN-gamma (BovIFN-gamma) gene cDNA was amplified by RT-PCR and cloned into pET28a to obtain the expression plasmid designated as pETBovIFN-gamma. The pETBovlFN-gamma was further transformed into competent E. coli BL21 cells and a 18kD His-tagged protein as expected was expressed after IPTG induction. By using purified recombinant BovIFN-gamma as antigen and lymphocyte-hybridoma technique, four hybridoma cell lines which stably secreted monoclonal antibodies against rBovIFN-gamma were generated, designated as A7, A10, G6, and G10. The immunoglobin subset was identified as IgG1 . Western blotting analysis and ELISA demonstrated that the monoclonal antibodies secreted by all the four hybridoma cell lines could react specifically to the recombinant BovIFN-gamma, but not irrelative proteins such as Ag85B, ESAT-6-CFP-10 and GM CSF, suggesting that the four hybridoma cell lines were rBovIFN-gamma specific monoclonal antibodies. A sandwich ELISA was established by using A10 secreted monoclonal antibody and rabbit polyclonal antibodies against BovIFN-gamma, HRP labeled goat anti-rabbit IgG. The results indicated that the sensitivity was 2ng/mL. This sandwich ELISA to detect BovIFN-gamma paved the way to develop a sensitive method for specific infection detection such as bovine tuberculosis diagnosis. PMID- 17366887 TI - [Studies on bacteriorhodopsin gene and sequence of 16S rRNA encoding genes of halophilic archaea of Xingjiang Aibi Lake]. AB - One hundred and forty-eight strains of halophilic archaea were isolated from 40 samples of soil, lake water, and silt. To study and analyze the species and bacteriorhodopsin(BR) protein resource, partial DNA fragments encoding BR protein from helix C to helix G andl6S rRNA encoding genes from 6 strains of halophilic archaea were amplified by polymerase chain(PCR) , and their DNA sequences were determined. The results indicate that the reduced amino acid sequences of BR protein from helix C to helix G of ABDH11 is obviously different from those of other existing proteins. The results of homology analysis on BR gene andl6S rRNA and phylogenetic analysis on 16S rRNA show that strains ABDH10 and ABDH40 are novel members of genus Natronorubrum and Natrinema, respectively; the sequence of ABDH40 was obtained from GenBank and the number of sequence is AY989910. The protein from helix C to helix G of ABDH11 is significantly different from that of other strains. PMID- 17366888 TI - [Genetic transformation of buckwheat ( Fagopyrum esculentum Moench ) with AtNHX1 gene and regeneration of salt-tolerant transgenic plants]. AB - The Arabidopsis thaliana tonoplast Na+ /H+ antiporter gene, AtNHX1, was transferred into buckwheat by Agrobacterium-mediated method. Transgenic buckwheat plants were regenerated and selected on MS basal medium supplemented with 2.0mg/L 6-BA, 1.0mg/L KT, 0.lmg/L IAA, 50mg/L kanamycin and 500mg/L carbenicillin. 426 seedlings from 36 resistant calli originated from 864 explants (transformed about at 4.17 percentage) exhibited resistance to kanamycin. The transformants were confirmed by PCR, Southern blotting, RT-PCR and Northern blotting analysis. After stress treatment for 6 weeks with 200mmol/L NaCl, transgenic plants survived, while wild-type plants did not. After 3 days of stress treatment through different concentrations of NaCl, transgenic plants accumulated higher concentration of Na+ and proline than the control plants. However, the K+ concentration of transgenic plants declined in comparison with the control plants. Moreover, the rutin content of the roots, stems and leaves of transgenic buckwheat increased than those of the control plants. These results showed that it could be possible to improve the salt-tolerance of crops with genetic technology. PMID- 17366889 TI - [Expression, purification and characterization of rat procarboxypeptidase B in Pichia pastoris]. AB - Carboxypeptidase B is a metalloenzyme, which is widely used for commercial and research purposes. Commercially available CPB purified from porcine or bovine pancreas is very expensive, and is not totally free from other proteases. In order to express the rat proCPB in Pichia pastoris, total RNA extracted from SD rat pancreas cells was reversely transcripted to synthesize cDNA, and the proCPB ORF was synthesized by PCR. After digestion with Xho I and EcoR I , the fragment was inserted into pPIC9, and the recombinant plasmid was named as pPIC9-proCPB. By digestion with Sac I , the lined pPIC9-proCPB was transformed into Pichia pastoris strains GS115 with PEG1000 and integrated into their genomes. In the inducement of methanol, recombinant proCPB was successfully expressed in Pichia pastoris, and could be secreted into the supernatant in the culture. After optimizing the fermentation conditions, a higher production could be obtained when GS115-proCPB was induced in BMGY (pH6.0) at 28CC, with addition of 0.5% casein. The yield of recombinant protein reached 500mg/L, achieving over 94% of total protein in the culture supernatant. The purity of recombinant CPB can reach 96% after two step phenyl sepharose F F purification, and 38% of total protein can obtained after optimizing the pufication method. Comparing to the specific activity 180u/mg of CPB purchased from Sigma, the specific activity of recombinant CPB is 110u/mg. Mass spectrometry analyses showed the mass of the recombinant CPB was 35.1 kD, which is very close to the theory value 35.2 kD. Amino acid sequencing of N-terminal of recombinant CPB further indicated proCPB was expressed successfully and modificated correctly after translation. PMID- 17366890 TI - [The study on the cloning and expression of alpha toxin gene of clostridium septicum and the immunity of the toxoid]. AB - In order to amplify alpha toxin gene of Clostridium septicum HeB01 strain, one pair of primers was designed according to the GenBank sequence, and a 1323bp alpha toxin gene fragment was obstained by PCR. Sequence analysis indicated that the homology of the nucleotid sequence of HeB01 strain to those other reference strains was more than 99.5% . The expression plasmid pQE30-alpha was constructed by inserting alpha toxin gene into the prokaryotic expression vector pQE30. The plasmid expressed when the recombinant strain M15(pQE30-alpha) was induced by IPTG. The specific 48 kD protein was detected SDS-PAGE and the immunogenicity of the expressed alpha toxin was confirmed by Western blot and ELISA. The expressed alpha toxin was transformed into alpha toxoid vaccine by adding 0.3% formaldehyde into alpha toxin. The protective immune response was proved after the mice was immunized with alpha toxoid vaccine. The results showed that the recombinanted strain M15 (pQE30-alpha) could be as a candidate of alpha toxoid vaccine to provide protective immune response against clostridium septicum infection. PMID- 17366891 TI - [Expression of ORF2 protein of HEV genotype IV in Hansenula polymorpha]. AB - Hepatitis E, an acute infectious disease transmitted via the fecal-oral route, is caused by hepatitis E virus. However, no effective treatment currently exists for hepatitis E, and the only epidemic control approach is vaccination. But so for there are no commercial vaccine for hepatitis E available in the world. To find a new expression system to develop recombinant hepatitis E vaccine, in this study the expression system of methylotrophic yeast Hansenula polymorpha was used to express the gene encoding amino acid 112 - 607 of the open reading frame 2 (ORF2) of hepatitis E virus (HEV) genotype IV. In order to achieve high expression level, the coding sequence was optimized according to codon usage bias of Hansenula polymorpha and synthesized through overlapping PCR. Subsequently the gene was subcloned into the multi-copy expression vectors of Hansenula polymorpha, which include pDGXHP1.0 (MOX promotor), pDGXHP2.0 (MOX promotor) and pDGXHP2.1 ( FMD promotor). The series of one-copy and multi-copy recombinant plasmids were transformed into ATCC26012(Ura3-) by electroporation. The transformants were cultured in selection media MDL and screened for the existence of foreign gene by PCR. Then the strains were induced in MM media and the expression products were detected by SDS-PAGE, ELISA and Western blot assays to select the high-level expression strains. The result of SDS-PAGE showed that the HEV ORF2 expression product was accumulated up to 12% of total cellular protein and its molecular weight is 56kD. The expression product showed high immunoreactivity detected by ELISA and the highest titer is 1:2048. The result of Western blot demonstrated that the expression product could be specifically recognized by the polyclonal antibody against HEV. The successful expression of HEV ORF2 protein in Hansenula polymorpha provides foundation for the further development of recombinant subunit vaccine against hepatitis E. PMID- 17366892 TI - [Study on kinetics of two-stage cultivation of protocorm-like bodies from Dendrobium huoshanense for cell growth and synthesis of polysaccharides]. AB - Phosphate is an effective factor in the regulation of cell growth and accumulation of polysaccharides. The method for higher polysaccharide production has been obtained through feeding cultivation. The two-stage cultivation was proposed according to the characteristic of cell growth and the accumulation of polysaccharides in the suspension cultures of protocorm-like bodies from Dendrobium huoshanense. A kinetic model was developed to describe the cultivation process. The results indicate that the production of biomass and polysaccharides increases from 28.7g DW/L and 1.86g/L to 44.2g DW/L and 5.22g/L, respectively, and the content of polysaccharides increases from 6.4% to 11.9% . With the evaluated model parameters, the model appears to provide a description for the cultivation process. PMID- 17366893 TI - [Establishment of a transgenic cell model for preliminary screening of chemopreventive agents]. AB - To develop a GFP transgenic cell model under the transcriptional control of TK promoter adjacent to which ARE enhancer was inserted. Synthetic oligonucleotide ARE motif was annealed and purified then inserted into pTK-GFP to construct the vector of pARE-TK-GFP. The TK and ARE-TK fragments were amplified by PCR and cloned into pEGFP-N1 to reconstruct eukaryotic expression vectors of pTK-GFP/Neo and pARE-TK-GFP/Neo. They were transfected into HepG2 cells and clones resistant G418 were isolated. PDTC and Lentinan were used to induce the cell levels of GFP and the fluorescence was measured using a fluorescence plate reader. The results showed that the induced level of GFP is significantly increased and have dose dependeny in a certain range. This findings indicated that such a cell model offered a potential platform for preliminary screening of all kinds of natural or synthetic chemopreventive agents. PMID- 17366894 TI - [Studies on the properties and co-immobilization of manganese peroxidase]. AB - White-rot fungus manganese peroxidase (MnP) oxidizes a wide range of substrates, rendering it an interesting enzyme for potential applications. The stability of MnP can be improved by immobilization. With sodium alginate, gelatin, or chitosan as a carrier, and glutaraldehyde as the crosslinking agent, MnP was co immobilized using the embed-crosslinked method and the adsorb-crosslinked method. The immobilization conditions and the partial properties of the three immobilized enzymes were investigated. When compared with the free enzyme, the optimum pH values and the temperatures of the three immobilized MnPs carried by alginate, gelatin, and chitosan were respectively shifted from 7.0 to 5.0, 5.0, 3.0 and from 35 degrees C to 75 degrees C , 55 degrees , 75 degrees C . The thermostabilities of the three immobilized MnPs were considerably better than that of the native enzyme. The chitosan-decreased by less than 5% even after repeated use for 6 - 9 times. The ability of decolorizing azo dyes in static and shaky situation by gelatin-immobilized MnP approached to the free enzyme, and there was no loss of enzyme activity during 2 repeated batch reactions. PMID- 17366895 TI - [Purification and characterization of a lipase from Aspergillus niger F044]. AB - A lipase from Aspergillus niger F044 was purified to homogeneity using ammonium sulfate precipitation, dialysis, DEAE-Sepharose Fast Flow anion exchange chromatography and Sephadex G-75 gel filtration chromatography. This purification protocol resulted in a 73.71-fold purification of lipase with 33.99% final yield, and the relative molecular weight of the enzyme was determined to be approximately 35-40kD using SDS-PAGE. The optimum pH and temperature for lipolytic activity of the lipase was 7.0 and 45 degrees C , respectively. It was extremely stable at 60 degrees C and retained 98.70% of its original activity for 30min. The stability declined rapidly as soon as the temperature rose over 65 degrees C . The lipase was highly stable in the pH range from 2.0 to 9.0 for 4h. Ca2+ and Mg2+ ions stimulated lipolytic activity, whereas Mn2+ , Fe2+ and Zn2+ ions caused inhibition. The values of Km and Vmax calculated from the Lineweaver Burk plot using pNPP as hydrolysis substrate were 7.37mmol/L and 25.91 micromol/(min x mg), respectively. The N-terminal sequence of the lipase was Ser/Glu/His-Val-Ser-Thr-Ser-Thr-Leu-Asp-Glu-Leu-Gln-Leu-Phe-Ala-Gln, which is highly homogeneity with that of lipase, as reported by Torossian. PMID- 17366896 TI - [Expression of endopolygalacturonase A of Aspergillus oryzae in Escherichia coli]. AB - Pectinases are mainly used in the food industry to clarify fruit juices and wine, improve oil extraction, remove the peel from the citrus fruit, increase the firmness of some fruits and degum fibres. The filamentous fungus Aspergillus oryzae, used for the production of traditional fermented foods, only could produce less pectinases under general conditions. So far only a few of PGs expressed in yeast or E. coli were reported but they did not show higher activity. The cDNA of mature PGA (without signal peptide) was synthesized with specific primers from total RNA of Aspergillus oryzae by RT-PCR. PGA cDNA was ligated into pET-28a( + ) expression vector, creating plasmid pET-28a( + )-pgA. The plasmid pET-28a( + )-pgA was transformed into E. coli Turner (DE3) plac I cells to express PGA heterogeneously. For improving the efficiency of PGA expression in E. coli, the conditions for expression of the PGA in E. coli were optimized. E. coli Turner (DE3) plac I cells with pET-28a( + )-pgA was first cultivated at 37 degrees, 220r/min until OD600nm reached about 0.8. Then, cultivation broth was added with 0.5 mmol/L IPTG and incubated at 15 degrees C, 170r/min for other 24 h for induced-expression of PGA. Our data showed that the activity of recombinant expressed PGA could reach to 70u/mL medium, which is 87.5 fold of the activity of PGA produced in culture of A. oryzae and superior than known recombinant expression amount of PGA reported by other researchers. PMID- 17366897 TI - [Preparation and identification of human soluble sPD-L1 and its antibodies]. AB - This study reports the preparation and identification of soluble programmed death 1 (PD-1) ligand-1 (sPD-L1) and its antibodies of mouse origin. Immobilized metal ion affinity chromatography was used to perform on-column refolding with simultaneous purification of denatured sPD-L1, and soluble sPD-L1 with purity of 95% was obtained. The purified sPD-L1 was verified by immunoblotting using a commercial goat-anti-human PD-L1 antibody. An ELISA-based assay showed that it also had high binding activity for its cognate receptor PD-1. Furthermore, mouse anti-sPD-L1 antiserum of high titer was raised using the purified sPD-L1 as an immunogen, and the specific IgG antibodies were purified using sPD-L1-HiTrap affinity chromatography. In addition, a sensitive sandwich ELISA was established using the purified IgG antibodies together with the commercial goat antibodies. In conclusion, the preparation of soluble sPD-Ll and its antibodies provide the basis for detection of the potential anti-PD-L1 antibodies and soluble PD-L1 in humans as well as for further investigation of its in vivo bioactivities and characterization of its potential receptors. PMID- 17366898 TI - [An establishmented methods of researching silk gland of silkworm(Bombyx mori L.) with proteomics]. AB - We separated proteins of the middle silk gland through high resolution two dimensional polyacrylamide gel electrophesis, and identified the high expressional proteins using MALDI-TOF-MS and analyzed the PMF in protein database by GPMAW( General Protein/Mass Analysis for Windows) . The protein database was forecasted through silkworm genome database. More than 500 spots were obtained from each gel by silver stain and more than 100 protein spots were obtained from gel by Coomassie brilliant blue stain. Most of them were distributed in the area from 15kD to 90kD with pH 3.5-7. Among the 25 Coomassie brilliant blue stained spots identified by MALDI-TOF-MS, more than 60% have relatively strong signal. Comparing with the result of using Mascot, the method using PMF database of silkworm not only can identify some known proteins, but also can identify some unknown proteins that have been forecasted in silkworm genome database. Accordingly, we founded a complete set of method that fit for researching proteome of silkworm. PMID- 17366899 TI - [Detection of recombinant lysostaphin using antibody sandwish enzyme-linked immunoadsorbent assay]. AB - The double-antibody-sandwich enzyme-linked immunoadsorbent assay (ELISA) for detection of rLysostaphin in humans had been developed and established through this study. rLysostaphin of high purity ( > 95 % ) produced in Shanghai Hi-Tech United Bio-Technological Research & Development Co., Ltd (SHUBRD) was used to produce a rabbit anti-rLysostaphin polyclonal antibody. The standard curve of rLysostaphin polyclonal antibody that was constructed showed that the lowest range of detection was found at 0. 98 ng of rLysostaphin/mL, and the curve exhibited linearity preferably from 0. 98 to 500 ng of rLysostaphin/mL. When three serum samples of the same batch were assayed for 6 replicates, and more 3 samples from different batches for 6 replicates, the average intra-assay and inter-assay coefficient variances ( CV) were 6. 4% and 6. 5%, respectively. The relative recovery rate was 98.6% when quantitative standard antigens were added to the serum. The present method for detection of rLysostaphin in serum is specific, highly sensitive, highly precise, and exhibited a low CV and will be helpful in the further study of rLysostaphin pharmacokinetics and holds promise in clinical applications. PMID- 17366900 TI - [Gas-liquid mass transfer in three-phase inverse turbulent bed reactor]. AB - The characteristics of gas-liquid mass transfer of three-phase system comprising air, tap water/wastewater, and hollow glass beads were studied in a laboratory scale inverse turbulent bed reactor. The influence of operational factors and liquid property on volumetric liquid-phase mass transfer coefficient kLa was investigated under the conditions of superficial gas velocity (0.53mm xs(-1) - 10mx s(-1) solid hold-up (0 - 0.3), and superficial liquid velocity (0 - 0.2mm x s(-1)). The results showed that the coefficient value was 0.0456 - 1. 414min -, which increased with superficial gas velocity and liquid velocity. The coefficient attained the maximum value at solid hold-up of 0.05 - 0.08. Compared with the coefficient value in tap water, that in synthetic wastewater and industrial wastewater is decreased by 39.0% and 50.9%, respectively. These data have provided a basis for the process analysis and mathematical simulation of inverse turbulent bed reactor. PMID- 17366901 TI - [A prediction model for the activity of insecticidal crystal proteins from Bacillus thuringiensis based on support vector machine]. AB - A quantitative structure-property relationship (QSPR) model in terms of amino acid composition and the activity of Bacillus thuringiensis insecticidal crystal proteins was established. Support vector machine (SVM) is a novel general machine learning tool based on the structural risk minimization principle that exhibits good generalization when fault samples are few; it is especially suitable for classification, forecasting, and estimation in cases where small amounts of samples are involved such as fault diagnosis; however, some parameters of SVM are selected based on the experience of the operator, which has led to decreased efficiency of SVM in practical application. The uniform design (UD) method was applied to optimize the running parameters of SVM. It was found that the average accuracy rate approached 73% when the penalty factor was 0.01, the epsilon 0.2, the gamma 0.05, and the range 0.5. The results indicated that UD might be used an effective method to optimize the parameters of SVM and SVM and could be used as an alternative powerful modeling tool for QSPR studies of the activity of Bacillus thuringiensis (Bt) insecticidal crystal proteins. Therefore, a novel method for predicting the insecticidal activity of Bt insecticidal crystal proteins was proposed by the authors of this study. PMID- 17366902 TI - [Cloning and sequence analysis of the gene encoding NiFe-hydrogenase from Klebsiella pneumoniae]. AB - Degenerate PCR primers were designed by multiple alignment of the protein sequences of known structural genes encoding the catalytic subunits of NiFe hydrogenases obtained from Swiss-Prot Protein Sequence Database through CLUSTAL-W software and compared for conserved sequence motifs. An amplified PCR product 1 kb in size was obtained from the genomic DNA of Klebsiella pneumoniae using a set of degenerate primers, and then inverse PCR technique was used to obtain the full hydrogenase coding region. A predicted secondary structure and 3D structural model were constructed by homology modeling and docking. On the basis of these results, it was inferred that NiFe-hydrogenase from Klebsiella pneumoniae belongs to the membrane-bound H2 evolving hydrogenase group (Ech hydrogenase group). PMID- 17366903 TI - [Obtaining marker-free transgenic soybean plants with optimal frequency by constructing three T-DNAs binary vector]. AB - Obtaining marker-free plants with high efficiency will benefit the environmental release of transgenic crops. To achieve this point, a binary vector pNB35SVIP1 with three T-DNAs was constructed by using several mediate plasmids, in which one copy of bar gene expression cassette and two copies of VIP1 gene expression cassette were included. EHA101 Agrobacterium strain harboring the final construct was applied to transform soybean (Glycine max) cotyledon nodes. Through 2 - 3 months regeneration and selection on 3 - 5mg/L glufosinate containing medium, transgenic soybean plants were confirmed to be obtained at 0.83% - 3.16%, and co transformation efficiency of both gene in the same individual reached up to 86.4%, based on southern blot test. By the analysis of PCR, southern blot and northern blot combining with leaf painting of herbicide in T1 progenies, 41 plants were confirmed to be eliminated of bar gene with the frequency of 7.6% . Among the T1 populations tested, the loss of the alien genes happened in 22.7% lines, the silence of bar gene took place in 27.3% lines, and VIP1 gene silence existed in 37.1% marker-free plants. The result also suggested that the plasmid with three T-DNAs might be an ideal vector to generate maker-free genetic modified organism. PMID- 17366904 TI - [Replication of Bombyx mori Densonucleosis Virus (Zhenjiang isolate) in different silkworm strains]. AB - The invertebrate parvovirus Bombyx mori Densonucleosis Virus type 3(Zhenjiang isolate), named BmDNV-3, is a kind of bidensovirus. The most obvious characteristic in the genome of BmDNV-3 is that it has 2 sets of DNA molecular (VD1, VD2),and each of them is encapsidated respectively in the form of single stranded liner DNA ( + VD1, - VD1, + VD2, - VD2) in equal percentage. So the BmDNV-3 has 4 kinds of virions. Furthermore the sequence of BmDNV-3 is able to encode DNA polymerase itself. Some strains of silkworm revealed complete resistance to BmDNV-3, so they didn' t fall sick. To investigate the difference in the process of infection and replication between the 2 virions ( VD1, VD2) of this bidensovirus, and the difference of the increment in the resistant or susceptible host, the 5th instar larvae of the susceptible silkworm strain (HUABA 35) and the resistant silkworm strain(QIUFENG d) were inoculated determinate dose of BmDNV-3 by oral ingestion. Then the midgut were collected at 9 timepoints. The silkworm cytoplasm actin A3 was used to be normalized gene, so the number of cells in collected tissue could be determined. The result shows that whatever in the susceptible silkworm strain or in the resistant one, the copies of VD1 and VD2 in the genome of BmDNV-3 collected at the different timepoint were almost at the equal level respectively, so that the VD1 and VD2 were replicated with synchronization. The process of infection in the susceptible silkworm strain was devided into 3 partitions, latent period( 2 - 12 hours post inoculation), exponential phase (12 - 36 hours post inoculation)and stationary phase (36- 96 hours post inoculation and there are about 2 x 10(5) copies per cell) . In the resistant silkworm strain, the virus were replicated at a very low level, that was from 6 - 10 copies 2 hours post inoculation to 150 - 200 copies 96 hours post inoculation (about 20 times) . So we predict that the resistance in some of the silkworm strains from BmDNV-3 was a kind of chronic representation that the host carried virus without being caused flacherie. PMID- 17366905 TI - [Isolation and characterization of H2-producing strains Enterobacter sp. and Clostridium sp]. AB - Two hydrogen-producing bacterial strains were newly isolated and identified as Enterobacter sp. Z-16 and Clostridium sp. C-32 by 16S rDNA sequence analysis. Various parameters for hydrogen production, including substrates, initial pH and temperature, have been studied. The optimum condition for hydrogen production of strain Z-16 were achieved as: initial pH7.0, temperature 35 degrees C , sucrose as the favorite substrate. In comparison, The optimum condition for hydrogen production of strain C-32 were obtained as: initial pH8.0, temperature 35 degrees C , maltose as the favorite substrate . Under batch fermentative hydrogen production conditions, the maximal hydrogen conversion rate for strain Z-16 and strain C-32 were 2.68 mol H2/mol sucrose and 2.71mol H2/mol maltose, respectively. Using glucose as substrate, the hydrogen conversion rate of strain Z-16 and strain C-32 were 2.35 and 2.48 mol H2/mol glucose, respectively. This research suggest a good application potential of strain Z-16 and C-32 in the future biological hydrogen production. PMID- 17366906 TI - [Construction of selectable marker-removable plant expression vectors]. AB - The commonly used plant constitutive expression vector pBI121 was modified by insertion of two directly orientated lox sites each at one end of the selectable marker gene NPTII and by replacing the GUS gene with a sequence composed of multiple cloning sites (MCS). The resulting plant expression vector pBI121-lox MCS is widely usable to accommodate various target genes through the MCS, and more importantly to allow the NPTII gene removed from transformed plants upon the action of the Cre recombinase. In addition, the CaMV 35S promoter located upstream of the MCS can be substituted with any other promoters to form plant vectors with expression features specified by the introduced promoters. Provided in this paper is an example that an enhanced phloem-specific promoter of the pumpkin PP2 gene (named dENP) was used to construct an NPTII-removable phloem specific expression vector pBdENP-lox-MCS. Moreover, to facilitate screening of selectable marker-removed gene and the composite sequence is flanked by lox sites. Thus the selectable marker-free plants can be visually identified by loss of GFP fluorescence. The above newly created plant expression vectors can be used to develop selectable marker-removable transgenic plants for a variety of purposes. PMID- 17366907 TI - [Reconstruction of embryo using an improved nuclear transfer method]. AB - Previous methods used for nuclear transplantation were further investigated to develop a method that was both easy to carryout and did not require any special apparatus, such as Piezoimpact or Spindle-View. Following the puncture of zona pellucida with two holes by injection pipette that contained donor nuclei or cells, the injection pipette was pulled back to the perivitelline space while the negative pressure was increased in the holding pipette until the polar body and karyoplasm were wiped off completely. Then a reconstructed embryo was completed by the direct injection of the donor nucleus or cell without pulling out the injection pipette. 200 oocytes were manipulated using this method and it cost about 40 seconds with nucleus injection and about 30 seconds with cell injection to complete a reconstructed embryo. The success rates were 62.6% and 86. 0%, respectively, and enucleation rate was about 73.3% validated by Hoechst 33342. Using this method, the nucleus was completely eliminated and another was injected using the microscope and micromanipulator. Moreover, the efficiency of nuclear transplantation and survival rate of reconstructed embryos were greatly improved. Furthermore, it is very easy to manipulate and popularize in practice. PMID- 17366908 TI - [Study on the application of PEI for gene transfer in mouse skin tissue]. AB - A reliable, low-cost, and highly efficient nonviral gene delivery system using lower molecular weight polyethylenimine (LMW-PEI) is provided. LMW-PEI was linked to an expressing plasmid with green fluorescence protein gene (gfp), the transfection activity mediated by PEIs were examined in the CM7721 cell line and the skin tissue of mouse, respectively. The cytotoxicity of PEIs, the localization and continuance time of gfp expressed in the skin tissue of mouse were also studied. Results showed that the transfection rate of gfp mediated by LMW-PEI in the CM7721 cell line was about 55% . However, with the increasing PEI molecular weight, the cytotoxicity of PEI increased, but its transfection activity decreased. The tissue transfection results showed that LMW-PEI induced a significant expression of the gfp in the cells of hair vesicle and sweat gland of mouse skin tissues following transfection of 24 h, and the expression of gfp lasted 7 - 9 d. When the tissue of mouse was treated with retinoic acid and nitrogenous ketone, respectively, gfp was transferred to the granule layer of mouse skin tissue. The LMW-PEI described here is a new, highly efficient vector; it would be a useful nonviral vector for gene delivery technology. PMID- 17366909 TI - [Numerical simulation of chondrocyte growth in 3-D scaffolds]. AB - Tissue engineering is a promising technique to repair or reconstruct the damaged cartilage in clinical use. However, chondrocyte growth is limited by the mass transport in scaffolds as diffusion is likely to be the primary mechanism. In this study, a mathematical model was developed based on oxygen diffusion and reaction to simulate chondrocyte growth. In order to accord with the fact, effective diffusion coefficients and space limitation were considered in this model and good agreement was found between experimental data and mathematical simulations. Furthermore, relationships established in the model system can be used to optimize the situation in real bioreactors and the design of three dimensional scaffolds. PMID- 17366910 TI - [A rapid method for preparation of plasmid DNA for screening recombinant clones]. AB - A simple and rapid method for preparation of plasmid DNA from overnight incubation was introduced. It does not require any additional reagents; the incubation mixture containing recombinant plasmid DNA was just mixed with H2O and phenol/chloroform/isoamyl alcohol in certain ratio. After vortexing and spinning of the mixture, the supernatant could be directly loaded onto agarose gel and analyzed using electrophoresis. The whole preparation requires only 3-5 minutes. So to quickly screen recombinant clones, this method is better compared with traditional methods. PMID- 17366911 TI - Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2004). PMID- 17366912 TI - [Preface and comments: Protection of the brain and the spinal cord]. AB - Basic and clinical investigations have been performed, focusing on the mechanism of ischemic brain and spinal cord injuries, and preventive measures against ischemic insults such as drug therapy, hypothermia, maintenace of blood flow to brain and spinal cord, preconditioning, and no use of high dose fentanyl. In this special issue, five experts have provided new relevant information concerning brain and spinal cord protection. Further research in brain and spinal cord protection will contribute to better understanding of ischemic central nervous system injuries and to the establishment of novel therapies for protection of central nervous system. PMID- 17366913 TI - [Molecular mechanism of ischemic brain injuries and perspectives of drug therapies for neuroprotection]. AB - Ischemic brain injury is a critical condition in the management of patients during anesthesia and intensive care. It is not rare that pathological conditions such as cerebral ischemia, head trauma and low oxygen result in marked impairment of cerebral function, even if the patient's life is saved. We sometimes encounter sudden changes in a patient's condition not only during anesthesia, but also in intensive care unit with transient low-oxygen and ischemic conditions accompanying serious shock. We have been studying the mechanisms to counteract pathological conditions leading to neuronal cell death that have been exposed to such emergency conditions, and to discover therapeutic methods to minimize the brain damage after insult. With advances in the understanding of the mechanism of neuronal cell death, technology in intensive care for salvaging neuronal cell that are at the brink of death and for recovery of brain function has progressed. However, a breakthrough has not been achieved in the development of effective therapy. Protection of the brain from terminal impairment and preservation of function will be an important issue. To achieve this goal, it is critical to clarify the susceptible mechanisms causing ischemic brain damage. This report discusses the importance of the calcineurin/immunophilin signal transduction mechanism as a new mechanism that is involved in the induction of ischemic brain damage and refers the status-quo of cerebral protection by drug therapy. PMID- 17366914 TI - [Protection of the central nervous system during thoracic aortic surgery]. AB - Cardiovascular surgery is constantly progressing. However, the prevalence of central nervous system injury is greater after operations on the aortic arch than after other types of aortic or cardiac surgery. The central nervous system injury is a frequent cause of death or complications after such operations and is likely to occur as a result of the embolization of particulate matter or severe global ischemia during the interval of circulatory arrest. Several different methods are currently being used to protect them during operations on the aortic arch. This thesis is organized about the protection methods for these procedures. PMID- 17366915 TI - [Clinical application of brain hypothermia therapy for acute brain insults]. AB - Brain hypothermia therapy has been expected to lead to good neurological outcome in acute brain insults. There are a few positive results which have been proven by multicenter randomized clinical trials (RCT) in the cardiopulmonary arrest (CPA) in patients with ventricular fibrillation. Among these clinical trials, early application of hypothermia, maintenance of cerebral blood flow during hypothermia therapy and prevention of quick rewarming are pointed out to result in good outcome from clinical experiences. For brain hypothermia therapy to become an effective method for acute brain insults, indications, brain oriented intensive cares and biomarkers for the therapy must be established. RCT in acute brain insults beside CPA victims are needed in the near future. PMID- 17366916 TI - [Brain and spinal cord preconditioning for the protection against ischemic injury]. AB - Recent studies have suggested that the brain preconditioning could induce tolerance to ischemia in humans. It has been believed that newly synthesized proteins are required for the acquisition of delayed tolerance in the brain and spinal cord. However, the mechanism other than the synthesis of neuroprotective proteins may also play a pivotal role. Preconditioning may reprogram the response to ischemic injury as seen during hibernation. Preconditioning with hyperbaric oxygen, volatile anesthetics, and xenon seems to be the focus of the attention from the standpoint of the clinical setting. Strong neuroprotection by the preconditioning with isoflurane and xenon is reported in animal experiments and may change the traditional idea of neuroprotection by anesthetics. The discovery that erythropoietin exerts neuroprotective properties has opened new therapeutic avenues. Erythropoietin is induced in the brain by hypoxic preconditioning and by the pharmacological preconditioning. In addition, the intravenous administration of erythropoietin has been shown to be safe and beneficial for acute stroke in humans. Therefore, erythropoietin is now one of the most promising neuroprotective agents. The research in the brain and spinal cord preconditioning will contribute to the elucidation of the mechanism of ischemic injury and to the establishment of new therapies for neuroprotection. PMID- 17366917 TI - [Spinal cord protection and opioids]. AB - Opioids, when administered in large doses, were reported to produce brain damage primarily in limbic system and association areas in animals. We recently found the result that intrathecal (IT) morphine after a short interval of aortic occlusion in the rodent model induced transient spastic paraparesis via opioid receptor-coupled effects in the spinal cord. Histopathological analysis revealed the possibility that IT morphine could induce degeneration of spinal ventral neurons even after a short lasting of spinal cord ischaemia in rats, and this degeneration was associated with the activation of spinal N-methyl-D-aspartate receptors by elevation of glutamate release in cerebrospinal fluid after IT morphine. Therefore, we would like to emphasize that all anesthesiologists should be aware of the possibility of morphine-induced paraplegia after thoracic aortic surgery and that we should carefully select appropriate analgesic agents from the several available opioids for these patients. PMID- 17366918 TI - [Dietary-induced thermogenesis and perioperative thermoregulation]. AB - After the ingestion or infusion of nutrients, there is an increase in energy expenditure which has been referred to as dietary or nutrient-induced thermogenesis. This thermogenesis induced by protein or amino acids is well known to be largest and most prolonged. According to these physiological backgrounds, preoperative amino acid infusion was reported to prevent postoperative hypothermia during general anesthesia and spinal anesthesia. Also, perioperative amino acid infusion is reported to improve the outcome of the patients undergoing off-pump CABG. Amino acid infusion was observed to shift upward the threshold core temperature for thermoregulatory vasoconstriction as well as to increase energy expenditure. Fructose also prevents perioperative hypothermia during surgery by the same mechanisms. PMID- 17366919 TI - [Usefulness of fentanyl patch (Durotep) in cancer patients when rotated from morphine preparations]. AB - BACKGROUND: [corrected] The transdermal fentanyl patch (Durote patch) is an opioid preparation requiring replacement once in three days, which is occasionally prescribed to replace morphine preparations. The conversion ratio from morphine to fentanyl has been claimed to be 100:1 or 150:1, but there may exist individual variations. METHODS: We retrospectively evaluated the analgesic effects and adverse effects of fentanyl patch in 24 cases among 22 patients (11 men and 11 women). RESULTS: There were some reasons for switching; the major one was for home-care. In most cases rotation was completed in a few days and the side effects disappearance or were reduced, but 4 cases of them showed severe diarrhea or exhibited exacerbation of the pain, and had to go back to morphine. There were a wide variations of conversion ratio with a mean of 96.6. CONCLUSIONS: The fentanyl patch is a useful agent to control severe cancer pain because of excellent analgesic effect, less adverse effects and more convenience as well as itsundesirable characteristics when transition of patients to home care is considered or oral administration should be avoided. Above all it offers a great possibility to improve cancer patient's quality of life. PMID- 17366920 TI - [Anesthetic management for a child with pompe disease]. AB - Pompe or glycogen storage disease type II is a genetic disorder affecting the cardiac and skeletal muscle. A 4-year-old boy with this disease was scheduled to undergo an orthopedic operation for clubbed foot. He had cardiomyopathy and skeletal muscle weakness; but his cardiac function was normalized by the long term enzyme replacement therapy. General anesthesia was slowly induced with oxygen, nitrous oxide, and sevoflurane, and tracheal intubation was achieved without any muscle relaxants. In combination with a caudal blockade with 6 ml of 0.375% ropivacaine, general anesthesia was successfully maintained with oxygen, nitrous oxide, and sevoflurane. We did not use muscle relaxants to avoid prolonged respiratory depression. The perioperative course was uneventful and no complication was observed. PMID- 17366921 TI - [Stored autologous blood from a pregnant woman showing a considerable amount of agglutinates]. AB - A 30-year-old woman was admitted to our hospital to undergo simultaneous cesarean section and radical hysterectomy when the pregnancy became 30 weeks. An ultrasonic examination had found hypoechoic region at the cervix uteri. Because she wished autologous blood transfusion, 100 ml each of her own blood was obtained 3 times preoperatively. All the stored blood was returned to the patient through a filtering system (40 microm in the pore size) during surgery. However, we found paste-like agglutinates floating in the bags. We transfused the blood carefully while confirming that there were no agglutinates in the reservoir below the filter. The paste-like agglutinates were also found on the filter. By microscopic observation fibrin-like substances attached by blood cells were detected. When the autologous blood from pregnant women is returned, special care should be taken because the blood is likely to form agglutinates even though the blood test data are within normal ranges. PMID- 17366923 TI - [Case report of using a connector (phycon TCB bronchial blocker) for pediatric one-lung anesthesia]. AB - We report a case of using a connector (Phycon TCB Bronchial Blocker: Fuji Systems) in pediatric one-lung anesthesia. An eight-year-old boy with mid mediastinal tumor was scheduled for video-assisted thoracoscopic surgery. After tracheal intubation with normal tracheal tube, we connected the connector and confirmed a 5 Fr Fogarty catheter through the tube under fiberoptic visualization. We were able to achieve one-lung ventilation. The operation was uneventful. This connecter is easy to fix and release the catheter. It is useful to modify the catheter position during one lung ventilation for pediatric patients. PMID- 17366922 TI - [Case of cerebral salt wasting syndrome with difficulty in controling excessive urine volume]. AB - Symptoms of hyponatremia and diuresis due to cerebral salt wasting syndrome (CSWS) are often observed after aneurysmal subarachnoid hemorrhage (SAH). Inadequately treated CSWS is known to work as a trigger of symptomatic vasospasm in SAH patients. Therefore, it is indispensable to detect and treat CSWS as early as possible in ICU. A 36-year-old man with SAH was admitted to our ICU. His urine volume increased excessively 3 days after ICU admission, and it reached a peak (39,250 ml x day(-1)) on the 6th day in ICU. Since infusion volume was controlled with regard to daily urinary output, hyponatremia was not noticeable and excessive urine volume stood out conspicuously. Though vasopressin and desmopressin were administered, the symptoms of natriuresis and hyponatremia were aggravated, associated with hyper secretion of natriuretic peptides (ANP 160 pg x dl(-1), BNP 172 pg x dl(-1)). Recent studies revealed that hyponatremia and hypovolemia following SAH might be caused by exaggerated secretion of natriuretic peptides. Experimental studies showed that the administration of vasopressin and desmopressin cause excessive secretion of natriuretic peptides under the circumstance of volume expansion in rats. We infer that the administration of vasopressin and desmopressin to our patient deterionated natriuresis in CSWS as in the previous experimental findings. PMID- 17366924 TI - [Questionnaire survey by anesthesia information sheet and patient's opinions about a visiting anesthesiologist]. AB - For a visiting anesthesiologist, the time allowed for explaining anesthesia for patients is limited. A questionnaire survey by anesthesia information sheet was performed and patient's opinions about the work of a visiting anesthesiologist were evaluated. The anesthesia information sheet explaining anesthesia risks and complications in addition to the anesthesia method was useful to make the patient understand anesthesia. A visiting anesthesiologist had better avoid explaining anesthesia on the day of operation. However, it is important for a visiting anesthesiologist himself to explain the methods and risks of anesthesia to the patient in order to build a mutual trust between the patient and the anesthesiologist. It is important to obtain an informed consent on anesthesia by the visiting anesthesiologist, but the format of the consent can be variable decided by the anesthesiologist. PMID- 17366925 TI - [Use of the pentax-AWS in a patient with Cormack 3a difficult airway]. AB - Pentax-AWS (AWS) (Pentax, Japan) is a rigid video laryngoscope with built-in 2.4 inch color CCD monitor paired with a disposal blade. It is developed for management of both normal and difficult airways. We used AWS in a 68-year-old male patient with known (Cormack grade 3a) difficult airway. Patient was sedated with fentanyl and midazolam to the level of Ramsay score 3. Patient's oral cavity was sprayed with 8% lidocaine. ETT placed on side channel of the AWS was connected to respiratory circuit via Bodai suction safe connector. Oxygen 6 l x min(-1) was adminisitered to prevent both desaturation of patient and fogging of blade during intubation procedure. Excessive saliva in the oropharynx was effectively removed with 14 Fr suction catheter through ETT via Bodai suction safe connector". Visualization of the patient's vocal cords was achieved easily (with POGO score 70%). The AWS's suction channel was alternatively used for topical anesthesia route with 10 Fr suction tube, and 4% lidocaine was injected onto the vocal cords. Tracheal intubation was successful uneventfully, and the patient's airway was secured without any postoperative complication. PMID- 17366926 TI - [Anesthesiologists in France]. AB - We review some anesthesiologist's curriculum and demographic characteristics in France to the community of Japanese anesthesiologists. To become a certified anesthesiologist and an intensive care physician currently requires six years' medical education, passing national medical examination, and five years' special training as an intern of anesthesiology and intensive care. This educational course was started in 1984. There are 7942 certified anesthesiologists in France in 1999. The average age is 45.9 years and the ratio of female is 35.3%. Approximately two thirds of certified anesthesiologists are working in public institutions. 89% is full-time workers. More than half of certified anesthesiologists actually participate in daily intensive care practice. The number of certified anesthesiologists has been increasing gradually totaling 10,062 persons in 2005. The number of certified anesthesiologists per ten thousands general population is 1.7 persons and the corresponding ratio to all medical doctors is 4.8%. Working hours and holidays are regulated by the French Labour Law. The anaesthesiologist often works in a team with a nurse anaesthetist. The number of certified anesthesiologists in France is larger than that in Japan. Management of anesthesia in France seems to have an advantage in manpower. PMID- 17366927 TI - [Nationwide questionnaire survey on anesthesiology in undergraduate medical education in Japan]. AB - BACKGROUND: Since the establishment of Model Core-Curriculum for Medical Education in 2001, undergraduate medical education has been progressively renovated in Japan. We conducted a questionnaire survey to investigate how this curriculum changed undergraduate anesthesiology education and how it affected our work load as the teaching staff of medical schools. METHODS: The questionnaire sent to 80 medical universities in Japan, consisted of 4 parts; (1) activity of institution and human resources, (2) lectures, (3) clerkship, and (4) future direction of the lectures and clerkship. RESULTS: The response rate was 59%. The number of staff engaged in undergraduate education was variable; ranging from 4 to 28. The number of lectures was 0 to more than 25 units per year and 6 institutions discontinued conventional didactic lectures. Although clinical clerkship program was being offered to students in most institutions, informed consent for clinical procedures by the students was obtained only in 11 of 47 institutions. CONCLUSIONS: The result shows that there is still room for improvement in educational environment, including manpower or curriculum. A written informed consent should be completed to provide patients' safety and to fulfill the clinical practice by medical students. PMID- 17366928 TI - Chemotherapy-induced nausea and vomiting: clinician and patient perspectives. AB - Chemotherapy-induced nausea and vomiting (CINV) is a common and serious problem encountered by many patients receiving anticancer therapy. Up to three fourths of all cancer patients experience chemotherapy-related emesis. Risk factors include specific chemotherapeutic agents used, female gender, age less than 50 years, and history of nausea or vomiting. Since CINV can complicate or prevent administration of planned therapy, decrease quality of life, and increase healthcare costs, its effective management is essential. Although serotonin receptor antagonists have significantly improved outcomes, next-generation analogs such as palonosetron have shown greater specificity and increased efficacy. Novel agents like the neurokinin-1 receptor antagonist aprepitant are also active, particularly when combined with palonosetron and dexamethasone. In recent years, the greatest advances have been made in the prevention of vomiting (especially acute vomiting), although uncontrolled nausea is still a major concern for many patients. Better treatments are needed for management of delayed CINV and for patients who do not respond to standard antiemetic therapies. PMID- 17366929 TI - Diagnosis and management of oral mucositis. AB - Oral mucositis is a common complication in cancer patients receiving chemotherapy and/or radiation therapy. Nearly all patients undergoing myeloablative therapy for stem-cell or bone marrow transplantation experience oral mucositis. Those receiving radiation therapy for head and neck cancer are at especially high risk. However,this toxicity also occurs with standard-dose chemotherapy and can be seen in association with treatment of many other tumor types. Oral mucositis significantly complicates cancer treatment by contributing to pain, dysphagia, weight loss, depression, higher risk of infection, decreased quality of life, and increased healthcare costs. This review summarizes the impact of oral mucositis in patients with cancer, including its pathogenesis, diagnosis, financial implications, and management. Current treatment guidelines are presented, and novel targeted therapies are discussed. Newer agents, such as palifermin (recombinant human keratinocyte growth factor-1), have been shown in clinical trials to reduce the incidence and severity of oral mucositis,and Saforis (an oral glutamine suspension) may also promote recovery from mucosal damage following chemotherapy or radiation therapy. Continued advances in understanding the pathobiology of oral mucositis should lead to the development of additional agents for its effective prevention and treatment in patients undergoing cancer therapy. PMID- 17366930 TI - When our best are broken. PMID- 17366931 TI - A suitable position. PMID- 17366932 TI - Improving postural awareness. PMID- 17366933 TI - Electrical safety in iontophoresis. PMID- 17366934 TI - What's new in mobility accessories. PMID- 17366935 TI - The basic necessities. PMID- 17366936 TI - An ounce of prevention. PMID- 17366937 TI - Staying fit after 50. PMID- 17366938 TI - A patient-centered vision for post-acute care reform. PMID- 17366939 TI - Basic biomedical research and the public's health cost...time...focus. PMID- 17366940 TI - Horwitz receives forth Schmdt-Nielsen Distinguished Mentor and Scientist Award. PMID- 17366941 TI - APS offers "roadmap" ideas. PMID- 17366942 TI - NIH seeks input on data sharing policies. PMID- 17366943 TI - NIH committee recommends against revising the Guide. PMID- 17366944 TI - Payment for performance: ready or not, here it comes. PMID- 17366945 TI - The pitfalls of pay for performance. PMID- 17366946 TI - "Payment for performance" will be good for the medical profession and patients. PMID- 17366947 TI - Pay for performance and its potential impact on American healthcare. PMID- 17366948 TI - Where am I on this bell-shaped curve? PMID- 17366949 TI - Assessing racial and ethnic differences in medical student knowledge, attitudes and behaviors regarding organ donation. AB - OBJECTIVES: Previous studies have demonstrated that informed healthcare providers could increase patient willingness to donate. We assessed medical students' knowledge and attitudes to determine their preparedness to encourage organ donation. METHODS: 500 first- and second-year students attending one of three Ohio medical schools completed the 41-item questionnaire (93% cooperation rate). The questions evaluated students' donation knowledge, training, exposure and perceived barriers as well as their willingness to donate. RESULTS: On univariate analysis, Asians (OR: 0.5, 95% CI: 0.2-0.9) and blacks (OR: 0.1, 95% CI: 0.1-0.2) were less willing than whites to donate. On multivariate analysis, race was no longer significantly associated with willingness to donate,Three factors were associated with a decreased donation willingness: wanting burial with organs intact (OR: 0.1, 95%CI: 0.1-0.2), having personal conflicts with donation (OR: 0.2, 95%Cl: 0.1-0.6), and concern that carrying a donor card will lead to insufficient medical care (OR: 0.2, 95% Cl: 0.1-0.4). Of note, knowledge was not associated with willingness to donate. CONCLUSION: In this medical student cohort, minorities were less willing to donate. Three factors were associated with a decreased willingness to donate regardless of student race. Addressing these barriers may increase student donation willingness, and physicians should encourage donation discussions with their patients. PMID- 17366951 TI - A new perspective in diagnosing polycystic ovary syndrome. AB - Recently, the term of "possible" polycystic ovary syndrome (PCOS) has been used for defining cases in which biochemical evaluations are incomplete but clinical phenotypes are suggestive of PCOS. The aim of this study was, by using Rotterdam 2003 criteria, to detect possible PCOS cases and compare their characteristics and insulin sensitivity status with confirmed PCOS subjects. One-hundred-eighteen women who admitted with complaints and symptoms suggesting PCOS were included. Insulin sensitivity status of the cases was calculated with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Cases fulfilling Rotterdam 2003 criteria were defined as confirmed PCOS, whereas indeterminate subjects as possible PCOS. Confirmed PCOS was detected in 70 (59.3%) and possible PCOS in 48 (40.7%) cases. Confirmed PCOS was most prevalent among subjects with hirsutism and menstrual dysfunction; 32 (80.0%) vs. 8 (20%), (p=0.000). Body mass index and HOMA-IR values did not differ between groups: confirmed PCOS versus possible PCOS; 25.46+/-5.55 kg/m(2) vs. 26.75+/-7.55 kg/m(2), 3.37+/-4.12 vs. 3.21+/-2.50, (p>0.05). Family history of type-2 diabetes mellifus was similar within both groups (p>0.05). Many PCOS patients seem to be undiagnosed due to inadherence to diagnostic work-up and/or to not fulfill Rotterdam 2003 criteria. These criteria may not be sufficient to cover the entire spectrum of PCOS. PMID- 17366950 TI - Ophthalmic dysfunction in a community-based sample: influence of race/ethnicity. AB - BACKGROUND: Few studies have characterized ethnic variations in standard ophthalmic measures. We tested the hypothesis that nerve fiber layer thickness would show characteristic differences between white and black individuals. We also examined whether ophthalmic measures would show intraethnic differences. METHODS: Seventy participants (mean age: 68.27+/- 5.97 years; blacks: 59% and whites: 41%) were recruited from Brooklyn communities. Sociodemographic and medical data were obtained, and eligible volunteers underwent eye examinations at SUNY Downstate Medical Center. RESULTS: ANCOVA showed that blacks were characterized by significantly worse visual acuity (F=4.14, p=0.05), larger horizontal and vertical cup-to-disk ratios (F=4.53, p=0.04; F=6.08, p=0.02, respectively), and thinner nerve fiber layer than their white counterparts (F=22.61, p=0.009). Within the black ethnicity itself, Caribbean Americans showed significantly thinner nerve fiber layer than did African Americans (F=7.52, p=0.01). CONCLUSION: Findings are consistent with previous reports of racial/ethnic differences in ophthalmic measures. Moreover, they suggest that black ethnicity may not be homogeneous regarding ophthalmic variables, particularly when examining nerve fiber layer thickness. Studies investigating ethnic differences in eye diseases should examine intragroup factors that could influence interpretation of clinical data. PMID- 17366952 TI - Maternal perspectives on growth and nutrition counseling provided at preschool well-child visits. AB - BACKGROUND: The inclusion of growth assessment and nutrition-related anticipatory guidance in all well-child visits is recommended. Although prior studies have assessed whether these topics are discussed, the content of the discussions has not been explored from the maternal perspective. OBJECTIVE: To explore what mothers of preschoolers recall and understand about growth assessment and nutrition anticipatory guidance provided at their child's most recent well-child visit. METHODS: Qualitative, semistructured telephone interviews were performed with 20 mothers of preschoolers recruited from a Head Start program. Interviews were recorded and transcribed. Themes were identified and refined in an iterative process. RESULTS: Three main findings emerged: 1) although mothers generally recalled the use of growth charts and often recalled their child's height and weight percentiles, they were generally unable to articulate the meaning of these percentiles; 2) most mothers stated that their nutrition-related decisions were not influenced by growth chart findings. However, when growth chart findings were interpreted as positive, mothers found them reassuring. Conversely, when growth chart findings were interpreted as negative, mothers discounted the growth chart in favor of other comparisons of growth; 3) a considerable proportion of mothers reported that nutrition was not discussed at the most recent well-child visit, which mothers commonly attributed to a lack of weight or feeding problems for their child. CONCLUSION: Among the low-income mothers studied, growth chart use and findings were memorable but frequently misunderstood, while nutrition-related anticipatory guidance was not consistently recalled. These findings suggest opportunities to improve physician-patient communication regarding these topics. PMID- 17366953 TI - Vaginal adenosis successfully treated with simple unipolar cauterization. AB - Vaginal adenosis, without a history of diethylstilbestrol (DES) exposure, is a rare condition with an unclear etiology. A 24-year-old female presented with complaints of persistent vaginal discharge and dyspareunia. On examination, there were red, patchy, diffuse lesions on the vaginal wall and cervix. Histopathologic examination of the lesions revealed vaginal adenosis with chronic inflammation. Due to a poor response to metronidazole and tetracycline treatments, unipolar cauterization was performed with successful removal of the lesions. PMID- 17366954 TI - Bilateral emphysematous pyelonephritis in a patient with no known risk factors. AB - Emphysematous pyelonephritis (EPN) is a rare life-threatening necrotizing infection of the kidney and perirenal space with gas formation. It is usually unilateral and affects patients with a risk factor such as diabetes or urinary obstruction. In the past, most patients required nephrectomy, and in bilateral cases long-term dialysis was inevitable. We present here the unusual case of a patient who developed bilateral EPN in the absence of any known risk factor. He was managed conservatively, required dialysis and bilateral nephrostomies, but eventually recovered completely. PMID- 17366955 TI - QT intervals and dispersion in patients with acute ischemic stroke. PMID- 17366956 TI - ACL injuries: more to learn. PMID- 17366957 TI - Performance of the craniocervical flexion test, forward head posture, and headache clinical parameters in patients with chronic tension-type headache: a pilot study. AB - DESIGN: Case-control, descriptive pilot study. OBJECTIVE: To describe the differences in the performance of the craniocervical flexion test (CCFT) between individuals with chronic tension-type headache (CTTH) and healthy controls. To assess the relationship between the CCFT, forward head posture, and several clinical variables related to the intensity and temporal profile of headache. BACKGROUND: Musculoskeletal impairments of the craniocervical region might play an important role on the pathogenesis of CTTH. Deficits in the performance of the CCFT have been reported in patients with cervicogenic headache, nonspecific neck pain, and whiplash injury, but not in individuals with CTTH. MATERIAL AND METHODS: Ten patients with CTTH and 10 comparable controls without headache were studied. A headache diary was kept for 4 weeks to substantiate the diagnosis and to record the pain history. The CCFT was performed with the subject supine and required performing a gentle head-nodding action of craniocervical flexion. The activation pressure score (pressure that the subject can achieve and hold for 10 seconds), the performance pressure index (calculated by multiplying the activation pressure score by the number of successful repetitions), and the highest pressure score (the highest level that each subject was able to hold for 10 seconds from 20 to 30 mm Hg) were measured. Side-view pictures of each subject were taken in both sitting and standing positions to assess forward head posture (FHP) by measuring the craniovertebral angle. All measures were taken by an assessor blinded to the subject's condition. RESULTS: Patients with CTTH had significantly lower values in both active pressure score and performance pressure index (P < .001), but not in the highest pressure score (P = .057), compared to controls. Patients with CTTH had a smaller craniovertebral angle (mean +/- SD, 42.0 degrees +/- 6.6 degrees), indicating a more FHP than controls (48.8 degrees +/- 2.5 degrees), in the standing position (P < .01); but not in the sitting position (CTTH, 39 degrees +/- 8.9 degrees; controls, 42.8 degrees +/- 8.9 degrees, P = .10). No association between FHP and any of the CCFT variables was found (P >.05). Headache intensity and frequency did not seem to be related to the CCFT variables, but there was a positive association between headache duration and activation pressure score (r(s), = 0.746, P = .02) and highest pressure score (r(s), = 0.743, P = .02). CONCLUSIONS: These findings suggest possible impairments of the musculoskeletal system in individuals with CTTH, although it is not possible to determine if these impairments contributed to the etiology of CTTH or are as a result of the chronic headache condition. PMID- 17366958 TI - Medial tibial stress syndrome in high school cross-country runners: incidence and risk factors. AB - STUDY DESIGN: Prospective cohort. OBJECTIVE: To determine (1) the cumulative seasonal incidence and overall injury rate of medial tibial stress syndrome (MTSS) and (2) risk factors for MTSS with a primary focus on the relationship between navicular drop values and MTSS in high school cross-country runners. BACKGROUND: MTSS is a common injury among runners. However, few studies have reported the injury rate and risk factors for MTSS among adolescent runners. METHODS AND MEASURES: Data collected included measurement of bilateral navicular drop and foot length, and a baseline questionnaire regarding the runner's height, body mass, previous running injury, running experience, and orthotic or tape use. Runners were followed during the season to determine athletic exposures (AEs) and occurrence of MTSS. RESULTS: The overall injury rate for MTSS was 2.8/1000 AEs. Although not statistically different, girls had a higher rate (4.3/1000 AEs) than boys (1.7/1000 AEs) (P = .11). Logistic regression modeling indicated that only gender and body mass index (BMI) were significantly associated with the occurrence of MTSS. However, when controlled for orthotic use, only BMI was associated with risk of MTSS. No significant associations were found between MTSS and navicular drop or foot length. CONCLUSIONS: Our findings suggest that navicular drop may not be an appropriate measure to identify runners who may develop MTSS during a cross-country season; thus, additional studies are needed to identify appropriate preseason screening tools. PMID- 17366959 TI - Electromyographical analysis of selected lower extremity muscles during 5 unilateral weight-bearing exercises. AB - STUDY DESIGN: Prospective single-group repeated-measures design. OBJECTIVES: To quantify electromyographic (EMG) signal amplitude of the gluteus maximus, gluteus medius, vastus medialis oblique, and biceps femoris during 5 unilateral weight bearing exercises. BACKGROUND: Using normalized EMG (NEMG) signal amplitude as a measure of muscle activation and, therefore, an estimate of exercise intensity, the relative contributions and interaction of the hip and thigh muscles during unilateral weight-bearing exercise can be examined. With regard to potential efficiency for strengthening, data on the amount of EMG signal amplitude for these 4 muscles during commonly used exercises are limited. METHODS AND MEASURES: Twenty-three healthy, asymptomatic subjects (16 men, 7 women; mean +/- SD age, 31.2 +/- 5.8 years) participated. A repeated-measures analysis was conducted using general linear models. The percent maximum voluntary isometric contraction was measured within each subject across 4 muscles during 5 exercises for 2 separate trials. Effect sizes of pairwise comparisons were computed. RESULTS: Statistically significant differences were noted in the amount of mean NEMG signal amplitude for the 4 muscles across the 5 exercises. A similar recruitment pattern between muscles was observed across all exercises. CONCLUSION: Even though all muscles except the biceps femoris demonstrated mean NEMG signal amplitudes sufficient for strengthening, the wall squat produced the highest levels of activation and should be considered the most efficient for targeting any of the 4 muscles or for training a cooperative effort among the muscles. PMID- 17366960 TI - Influence of anticipation on movement patterns in subjects with ACL deficiency classified as noncopers. AB - STUDY DESIGN: Two-factor, mixed experimental design. OBJECTIVES: To compare movement patterns of subjects who are anterior cruciate ligament (ACL) deficient and classified as noncopers to controls during early stance of anticipated and unanticipated straight and cutting tasks. BACKGROUND: Altered neuromuscular control of subjects that are ACL deficient and noncoper theoretically influences movement patterns during unanticipated tasks. METHODS AND MEASURES: The study included 16 subjects who are ACL deficient, classified as noncopers, and 20 healthy controls. Data were collected using an Optotrak Motion Analysis System and force plate integrated with Motion Monitor Software to generate knee joint angles, moments, and power. Each testing session included anticipated tasks, straight walking task (ST), and 45 degrees side-step cutting tasks (SSC), followed by a set of unexpected straight walking (STU) and unexpected sidestep cutting (SSCU) tasks in a random order. For all tasks speed was maintained at 2 m/s. Peak knee angle, moment, and power variables during early stance were compared using 2-way mixed-effects ANOVA models. RESULTS: For both the straight and sidestep tasks, the noncoper group did not show a dependence on whether the task was anticipated or unanticipated (group-by-condition interaction) for the knee angle (straight, P = .067; side-step cutting, P = .103), moment (straight, P = .079; side-step cutting, P = .996), and powers (straight, P = .181; side-step cutting, P = .183) during the loading response phase. However, during both straight and side-step cutting tasks, the subjects in the noncoper group used significantly lower knee flexion angles (straight, P = .002; side-step cutting, P = .019), knee moments (straight, P = .005; side-step cutting, P < .001), and knee powers (straight, P = .013; side-step cutting, P <.001). CONCLUSIONS: This study suggests subjects that are ACL deficient and classified as noncopers use a common abnormal movement pattern of lower knee extensor loading even during unanticipated tasks. PMID- 17366961 TI - Minocycline-induced lupus in adolescents: clinical implications for physical therapists. AB - STUDY DESIGN: Resident's case problem. BACKGROUND: In the United States, minocycline is a frequently prescribed medication for the treatment of moderate to severe acne, a common condition in adolescents. The use of minocycline has been associated with severe adverse effects that frequently comprise a musculoskeletal component, including drug-induced lupus. Physical therapists have the responsibility to identify drug reactions that mimic musculoskeletal symptoms. The patient described herein was a 15-year-old adolescent boy who had taken minocycline for 14 days. He was initially treated by his primary physician on the 15th day of minocycline therapy for symptoms of fever, joint swelling, and a rash. The patient presented to a physical therapist on the 22nd day with complaints of severe myalgia, arthralgia, and severely limited mobility secondary to pain. The patient was referred to a pediatric rheumatologist because of the systemic nature and severity of the symptoms. DIAGNOSIS: The patient was subsequently diagnosed as having drug-induced lupus by a pediatric rheumatologist. The patient's myalgia and arthralgia subsided within 6 weeks, but his strength, coordination, and endurance did not reach their prior levels for 3 to 4 months. DISCUSSION: Physical therapists who include a comprehensive pharmacovigilance component in their patient examination may recognize musculoskeletal symptoms that arise from a nonmusculoskeletal origin. Minocycline is commonly prescribed in the United States as an antibiotic and for treatment of acne and rheumatoid arthritis. Therefore, physical therapists should screen for minocycline use when an adolescent patient or a patient with rheumatoid arthritis presents with diffuse musculoskeletal symptoms. An automated medication monitoring system would provide physical therapists with a means of accessing current information on medication use. PMID- 17366962 TI - A survey of self-reported outcome instruments for the foot and ankle. AB - The information acquired from self-reported outcome instruments is useful only if there is evidence to support the interpretation of obtained scores. To properly interpret scores, there should be evidence for content validity, construct validity, reliability, and responsiveness. Evidence regarding score interpretation must also contain a description of the applicable test conditions, including information about the characteristics of subjects, timing of data collection, and construct of change. The objective of this review was to identify self-reported outcome instruments that have evidence to support their usefulness for assessingthe effect of treatment directed at individuals with foot and ankle related pathologic conditions in an orthopaedic physical therapy setting. In addition, we provide specific information that will allow clinicians and researchers to select an appropriate instrument and properly interpret the obtained scores. Fourteen self-reported outcome instruments that met the objective of this review were identified. Five instruments, the Foot and Ankle Ability Measure, Foot Function index, Foot Health Status Questionnaire, Lower Extremity Function Scale, and Sports Ankle Rating System quality of life measure, satisfied all 4 categories of evidence (content validity, construct validity, reliability, and responsiveness) outlined herein. PMID- 17366963 TI - ACL injuries--the gender bias. PMID- 17366964 TI - ACL injuries: do we know the mechanisms? PMID- 17366965 TI - Anterior cruciate ligament injury mechanisms and risk factors. PMID- 17366966 TI - Malaria situation in the People's Republic of China in 2005. PMID- 17366967 TI - [Classification and diversity of tick community in Tarim basin]. AB - OBJECTIVE: To investigate the distribution pattern and structural characteristics of tick community and to understand the diversity of the communities in Tarim Basin. METHODS: According to the geographical division and habitat types, survey sites were selected, and tick samples were collected and their species were identified. With the methods of community ecology, the richness, diversity and evenness of the tick community were calculated. The communities were classified by way of clustering analysis in combination with the environmental index of geology and vegetation. RESULTS: Totally 10 species belonging 5 genera of ticks were collected in the Basin. Hyalomma asiaticum asiaticum and Hyalomma asiaticum kozlovi were the dominant species in the area. The tick community was divided into 7 types in accordance with the environmental geology, vegetations, and their richness and coverage degree. CONCLUSIONS: There are abundant tick communities in the area of Tarim Basin, and a gradient change of the communities is continued in the ecological amplitude of this area. PMID- 17366968 TI - [Study of chigger communities on major species of rodents in Yunnan Province]. AB - OBJECTIVE: To understand the characteristics of the chigger communities on the major species of rodent hosts. METHODS: Rats were captured in 16 counties (or towns) of Yunnan. All the mites on the two auricles of the host were collected and identified. Shannon-Weiner's indices (H,E), the richness indices and dominance indices were adopted to judge the diversity and community structure of chiggers on their hosts (7 species of rodents). RESULTS: From the 7 species of dominant rodent hosts, 131 species of chiggers were identified, belonging to 17 genera of Trombiculidae. Among them, abundant individuals were collected from 6 species which were considered to be dominant chigger species. Shannon-Weiner's indices (H) of the chigger communities showed the following sequence: Rattus norvegicus>Apodemus chevrieri>Eothenomys miletus>Mus pahari>Rattus nitidus>Rattus flavipectus>Mus caroli, and the richness indices were similar to this tendency. The niche breadth of the 6 dominant chigger species showed the following tendency: Herpetacarus hastoclavus>Leptotrombidium scutellare>Leptotrombidium sinicum>Helenicula siena>Leptotrombidium hiemalis>Leptotrombidium eothenomydis. There was a wide niche overlap between any two chigger species with all indices beyond 0.76. Slight positive association existed between each two dominant species of chigger mites by the coefficient of association (V). CONCLUSION: The community structure of chigger mites on the 7 major species of rodent hosts is complex, reflecting a high diversity of mite species. The niche breadth of the 6 dominant chigger species is different with a wide niche overlap. PMID- 17366969 TI - [Immunotherapy with recombinant house dust mite group 2 allergen vaccine inhibits allergic airway inflammation in mice]. AB - OBJECTIVE: To investigate the efficacy and mechanism of subcutaneously given recombinant Der p 2 entrapped PLGA nanoparticles (DEPN) on mouse model with allergic airway inflammation. METHODS: 40 BALB/c mice were randomly divided into 5 groups, group A (normal control) were treated with saline (100 microl) all the time, groups B, C, D and E were sensitized intraperitoneally with crude dust mite extracts (10 microg) and then subcutaneously treated respectively with PBS (100 microl), 2 mg empty PLGA (EP), 100 microg rDerp2, and 2 mg DEPN (loaded with 100 microg rDerp 2) for 3 times, once per day, followed by intranasal challenge of 50 microg rDer p 2. One day post challenge, mice were sacrificed and bronchoalveolar lavage fluid (BALF) was collected. Number of the total cells and eosinophils was determined, and airway inflammation and mucus secretion were analyzed by haematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. Level of cytokines in the supernatant of splenocyte culture was assayed by ELISA. Level of rDer p 2 specific IgG2a and IgE in the sera was determined by ELISA. RESULTS: The lung histology showed development of eosinophil infiltration in the airway of mice in groups B and C. The lung inflammation and mucus secretion in groups D and E were significantly alleviated than that of groups B and C. Number of total cells (63.50+/-5.12) and eosinophils (15.32+/-3.04) in BALF decreased in group B. Compared with group B, the number of total cells in groups D (55.3+/ 5.20) x 10(4) /ml and E (41.00+/-4.91) x 10(4)/ml greatly decreased (P<0.05), and same with that of eosinophils in groups D (9.56+/-1.09) x 10(4) /ml and E (3.22+/ 0.31) x 10(4)/ml. The rDerp 2 specific IgE and IgG2a antibodies in group B were 1.14+/-0.105 and 0.14+/-0.07 respectively. The level of specific IgE was significantly lower (P<0.01) in groups D (0.93+/-0.04) and E (0.77+/-0.09), and that of IgG2a in groups D (1.02+/-0.01) and E (1.17+/-0.46) were significantly higher (P<0.01) than that in group B. The level of IL-4 and IFN-gamma in BALF in group B were (78.90+/-6.07) pg/ml and (27.30+/-3.51) pg/ml respectively. IL-4 in groups D and E was (55.6+/-3.79) pg/ml and (48.6+/-4.50)pg/ml respectively, significantly lower (P<0.01) than that of group B; while IFN-gamma (68.50+/-2.87) pg/ml in group E was significantly higher than that of group B (P<0.01). IL-4 released from cultured splenocytes in groups D and E was (56.30+/-4.85) pg/ml and (40.20+/-4.36) pg/ml respectively, significantly lower than that in group B (81.2+/-6.84 pg/ml) (P<0.01). The released IFN-gamma in group E was (70.20+/ 3.85) pg/ml, significantly higher than in group B (34.60+/-2.25) pg/ml (P<0.01). CONCLUSION: DEPN can inhibit airway allergic inflammation, its mechanism may be relevant to a balance of Th1 and Th2. PMID- 17366970 TI - [The random amplified polymorphic DNA identification of 9 Taenia saginata isolates from four provinces]. AB - OBJECTIVE: To make molecular identification for 9 isolates of Taenia saginata from 4 provinces. METHODS: Genomic DNA was extracted from the segments of adult tapeworms collected from Taoyuan of Taiwan (TW1), Duyun of Guizhou (DY1, DY2), Congjiang of Guizhou (CJ1, CJ2, CJ3, CJ4), Dali of Yunnan (DL1) and Wushi of Xinjiang (XJ1) respectively. PCRs were carried out with 13 random primers. A phylogenetic tree of different geographical strains was constructed. RESULTS: 331 DNA fragments were amplified. The number of DNA fragments amplified by single primer was between 3 and 28. The average number of amplified DNA fragments by the 13 primers was 14.15. The average number of fragments from the 9 isolates of T. saginata was 14.08. Phylogenetic tree revealed that there were two branches in the tree, DY1, DY2, DL1 and TW1 occupied one branch, while CJ1, CJ2, CJ3, CJ4 and XJ1 occupied the other one. CONCLUSIONS: By the RAPD analysis, the isolates DY1, DY2, DL1 and TW1 belong to Taenia saginata asiatica, and the isolates CJ1, CJ2, CJ3, CJ4 and XJ1 belong to T. saginata saginata. PMID- 17366971 TI - Effect of artemether on the tegument of adult Schistosoma haematobium recovered from mice. AB - OBJECTIVE: To assess the effect of artemether on the tegument of adult Schistosoma haematobium harbored in mice. METHODS: Ten mice were infected subcutaneously with 100-120 S. haematobium cercariae each. At day 81 post infection, 8 mice were treated orally with 400 mg/kg artemether. Mice were sacrificed at 1, 3, 7 and 14 days post-treatment, and schistosomes were collected by the perfusion technique, fixed and examined under a scanning electron microscope. Schistosomes obtained from the 2 untreated mice served as a control. RESULTS: Twenty-four hours post-treatment, tubercles on the tegument of male worms showed lesions, characterized by enlargement, collapse and partial peeling off from the border with the tegument. In both male and female worms, the tegument showed focal or extensive swelling, fusion, vacuolization, erosion, peeling, and destruction of sensory structures. Three days post-treatment, tegumental alterations further aggravated; particularly severe damage was the swelling or collapse of the oral sucker observed in both sexes. In addition, extensive swelling, erosion and peeling of tegumental ridges and destruction of discoid-like sensory structures were seen in female worms. Seven to 14 days post treatment, moderate-to-severe damage was still evident in some worms, whereas other worms surviving the treatment showed apparent recovery in most parts of their tegument. CONCLUSION: Artemether causes extensive and severe tegumental damage in adult S. haematobium. PMID- 17366972 TI - [A case of infant infected by Blastocystis hominis]. PMID- 17366973 TI - [Protective effects of co-immunization with SjCTPI-Hsp70 and interleukin-12 DNA vaccines against Schistosoma japonicum challenge infection in water buffalo]. AB - OBJECTIVE: To induce protective effect of co-immunization with S. japonicum triose-phosphate isomerase fused to heat shock protein 70 (SjCTPI-Hsp70) plasmid and interleukin-12 (IL-12) DNA vaccines against Schistosoma japonicum (Chinese strain) infection in water buffalo. METHODS: Forty-five 8-10 months-old water buffalo from a nonendemic area were divided into three treatment groups each with fifteen buffalo: experimental group A (SjCTPI-Hsp70+IL-12, 300 microg), experimental group B (SjCTPI+IL-12, 300 microg), and control group C (pVAX+IL-12, 300 microg). All buffalo were immunized with a series of 3 intramuscular injections administered once every four weeks. Twenty-eight days postvaccination, water buffalo were percutaneously challenged with 1000 S. japonicum cercariae. Fecal examinations were conducted two days prior, one day prior, and on perfusion day, and the number of hatching miracidia and eggs per gram feces were recorded. Fifty-six days post-infection, the buffalo were sacrificed and perfused via the descending aorta. The recovered adult worms and eggs in liver tissue were counted. RESULTS: Groups A and B showed a worm reduction rate of 51.2% and 41.5% (chi2=1.89, P>0.05)), female worm reduction of 48.9% and 44.7% (chi2=0.35,P>0.05), fecal egg reduction of 52.1% and 38.3% (chi2=3.84,P<0.05), a reduction of miracidia-hatching rate by 52.1% and 33.2% (chi2=7.30, P<0.01), and liver egg reduction of 61.5% and 42.0% (chi2=7.61 , P<0.01), respectively. CONCLUSION: Co-immunization with SjCTPI-Hsp70 and IL-12 DNA vaccines induces protective immunity against S. japonicum in water buffalo. PMID- 17366974 TI - [Studies on the protective effect of the mutant of Sj23 DNA vaccine against schistosomiasis]. AB - OBJECTIVE: To investigate the protective immunity of the vaccine against schistosomiasis, a mutant of Mr 23 000 membrane protein DNA (Sj23DNA) without the homologous sequence of ME491. METHODS: The mutant of Sj23 DNA with no homologous sequence of ME491 on the cell membrane of human melanoma was obtained by overlap PCR. The mutant was transfected into human embryonic kidney cells of the line HEK293. Indirect fluorescent antibody test (IFAT) was used to detect the expressed protein. Expression of the mutant of Sj23DNA in muscular cells of mice was conducted through vaccinating the mouse with 100 microg purified plasmids by injecting them into the quadriceps muscle of thigh. Four weeks after the immunization, the quadriceps muscles were taken and cryostat sections were prepared for detecting the expression by IFAT. Forty BALB/c mice were randomly divided into four groups and injected with the mutant of pcDNA3-Sj23 plasmid DNA, pcDNA3-Sj23 plasmid DNA, pcDNA3 blank plasmid (100 microg per mouse) and sterile saline (30 microl per mouse) respectively. Four weeks after the immunization, mice were challenged with cercariae (40+/-2 cercariae per mouse) by abdominal skin penetration. Mice were then killed 6 weeks later, perfusion and squash methods were carried out to collect the adult worms and the number of eggs per gram of liver tissue was calculated. Worm and egg reduction rates were used to evaluate the protective immunity. RESULTS: Specific fluorescence was demonstrated in muscular cells of mice vaccinated with the mutant of pcDNA3-Sj23. The worm reduction rate and egg reduction rate were 40.3% and 42.8% respectively in the mutant of pcDNA3-Sj23 group, which were higher than those in the pcDNA3-Sj23 plasmid group (33.1% and 28.9% respectively). The difference between these two groups was significant (P<0.05). CONCLUSION: The modified Sj23DNA without the homologous sequence of ME491 induces higher protection against Schistosoma japonicum infection in mice than that of Sj23DNA. PMID- 17366975 TI - [Effect of anti-midgut-protein-ingredient antibodies of Anopheles stephensi on the oocysts of Plasmodium yoelii]. AB - OBJECTIVE: To observe the inhibitory effect of the antibodies against midgut protein-ingredient of Anopheles stephensi on the oocysts of Plasmodium yoelii. METHODS: Female An. stephensi mosquitoes raised in laboratory were dissected and the midguts were collected. Eight BALB/c mice were immunized using midgut-protein (100 microg/mouse, 4 times with an interval of 7-10 day). Ten days after the last immunization, blood was taken from mice armpit artery and serum separated. The immune active antigen of the midgut protein was analyzed by Western blotting. Protein with Mr 38 000-50 000 was separated by sephadex filtering and used to immunize 12 BALB/c mice (100 microg/ mouse, 4 times with interval of 7-10 days). PBS control group was established. Seven days after the last immunization, serum antibody was detected by ELISA. When the antibody titer in immunized mice reached > or = 1:2 560, mice in both groups were infected by P. yoelii (about 2 x 10(7) plasmodium-infected RBC) by abdominal injection. The mosquitoes were fed on the infected mice when the number of female gametes was higher than 2 per 10 microscopical fields 3 days later. After 9 days, the mosquitoes were dissected and the amount of oocysts in midgut was counted. RESULTS: Eight protein bands were shown in midgut-protein of An. stephensi by Western blotting and the band of Mr 38 000-50 000-midgut-protein appeared clearer. The infection rate of oocysts in the experiment and control groups were 28.70% (62/216) and 51.09% (47/92) respectively (P<0.05), with an oocyst index of 14.14 (1 541/109) and 26.02 (1 223/47) respectively (P<0.01). CONCLUSIONS: The midgut protein of Anopheles stephensi with Mr 38 000-50 000 has immune activity, and the antibodies against this protein shows an inhibitory effect on the development of oocysts of Plasmodium yoelii. PMID- 17366976 TI - [DNA vaccine encoding SjIR3 induces partial immune protection against Schistosoma japonicum in mice]. AB - OBJECTIVE: To detect the protection in mice induced by DNA vaccine encoding SjIR3 against Schistosoma japonicum (Sj). METHODS: Sj1R3 was amplified by PCR with specific primers and linked to T vector. The reconstructed plasmid was digested by Xho I and BamH I. The target segments were collected and inserted into pcDNA3.0 to construct DNA vaccine SjIR3/pC. Fifty-four female mice were divided into 3 groups: groups A and B received normal saline and pcDNA3.0 respectively as controls, and group C was immunized with SjIR3/pC. All the mice were injected three times with an interval of two weeks. Sera were collected before each inoculation and before challenge infection. Six mice from each group were sacrificed 2 weeks after the final inoculation and spleen cells were collected. Serum IgG was detected by ELISA and the proliferation activity of spleen T lymphocytes induced by ConA or rSjIR3 was detected by MTT assay. The remaining mice were infected by (40+/-1) Sj cercariae per mouse 2 weeks after the final inoculation. Forty-five days later, mice were sacrificed and perfused, numbers of adult worms and of eggs in liver tissue were counted. RESULTS: ELISA showed no significant change of serum IgG level in groups A and B, but considerable increase in group C (0.78+/-0.05) (P<0.01). The proliferation activity of spleen T lymphocytes increased with the induction of ConA or recombinant protein rSjIR3 after the final inoculation. The A570 was 0.57+/-0.02 and 0.68+/-0.01 respectively, showing a significant difference in comparison to the groups A and B (P<0.01). The worm reduction rate and the egg reduction rate in group C were 29.42% and 36.56% respectively. CONCLUSION: DNA vaccine encoding SjIR3 induces humoral and cell-mediated immune response, and shows partial immune protection against Schistosoma japonicum. PMID- 17366977 TI - [Observation on the ultrastructure of Pneumocystis carinii]. AB - OBJECTIVE: To study the life cycle and morphology of Pneumocystis carinii by ultrastructural observation. METHODS: Wistar rat model of P. carinii infection was established by subcutaneous injection with dexamethasone. Lung tissue of the infected rats was used for the transmission electron microscopical study. RESULTS: The organisms were mainly present in the lung alveolar cavity, and also in the alveolar septum, pulmonary macrophages and neutrophils. More trophozoites of P. carinii attached to the type I alveolar epithelial cells, and rarely to the type II alveolar epithelial cells. Most of these trophozoites showed pseudopodial evaginations on their pellicles. The nucleus-associated organelle and spindle microtubules were observed in some trophozoites. The precyst phase was in three forms: early, intermediate and late form. Synaptonemal complexes indicating meiotic nuclear divisions and a clump of mitochondria were also observed in the precyst. The pellicle of the cyst has a thickened portion with a pore. There were nucleus with nucleolus, mitochondrion, vesicles, endoplasmic reticulum and numerous ribosomes in the organisms, and tubular expansions on its surface. CONCLUSION: The life cycle of P. carinii consists of trophozoite, precyst and cyst stages. The presence of a single pore in the cyst wall reveals that pore formation may be a mode of excystation for intracystic bodies of P. carinii. PMID- 17366978 TI - [Preparation and identification of monoclonal antibody against sporozoites of Eimeria acervulina]. AB - OBJECTIVE: To establish hybridoma cell lines against sporozoites of Eimeria acervulina. METHODS: BALB/c mice were immunized with purified sporozoites of E. acervulina. Hybridoma cell lines were set up by using hybridoma technique, and monoclonal antibodies were prepared. The monoclonal antibody was identified by determining their cross reactivity, relative affinity, immunoglobulin class or subclass with enzyme linked immunosorbent assay (ELISA). RESULTS: Four hybridoma cell lines stably secreting McAbs against sporozoites were obtained: Easp-3G3 and Easp-5G10 belonging to IgG1, Easp-3H6 belonging to IgG2b, Easp-5H4 belonging to IgG2a. All four McAbs bound with E. acervulina sporozoite protein, but the Easp 5H4 McAb showed cross reactivity with E. tenellum sporozoite protein. Different antigenic epitopes were recognized by Easp-3G3 or Easp-5G10 and Easp-3H6 or Easp 5H4. CONCLUSION: Three of the four produced monoclonal antibodies show high specificity and affinity to the Eimeria acervulina sporozoites. PMID- 17366979 TI - [An imported case of severe cerebral falciparum malaria]. PMID- 17366980 TI - [Advances in research on virulence factors of Entamoeba histolytica]. AB - The parasitic protozoan Entamoeba histolytica is an important pathogen responsible for intestinal and extraintestinal amebiasis in human, claiming up to 100 000 victims every year. This parasite is characterized by its high potential for invading and destroying human tissues. Invasion past the mucous barrier of the colonic epithelium leads to the development of colitis and amebic dysentery. Dissemination of the trophozoite through blood stream permits the invasion of other tissues, resulting in abscesses in extracolonic location. Several virulence factors have been proposed to be involved in E. histolytica pathogenicity. This review is to summarize the advances in the research. PMID- 17366981 TI - [Heavy infection of Angiostrongylus cantonensis due to swallowing raw slugs]. PMID- 17366982 TI - [The advancement on mitochondrion of cryptosporidium]. AB - Cryptosporidiosis is an important apicomplexan disease with medical and veterinary significance. There is still no effective drug for its control. Mitochondrion is an organelle which contains most protein and enzyme in eukaryotes, so the mitochondrion of Cryptosporidium may be a potential target of drugs. Recent studies provided evidence for a mitochondrial derived compartment in this parasite. But the organelle has some difference to that of other apicomplexan parasites. This organelle appears to lack its genome, and thus must be entirely dependent on nuclear-encoded proteins. This article reviews the evidence for the organelle in Cryptosporidium and its probable function. PMID- 17366983 TI - [Advances in biological taxonomy and classification of human parasites]. AB - Along with the further development of biological science and technology, the taxonomy of organisms as well as classification of parasites have been modified and improved. However the taxonomic system of parasites used in China nowadays was established 25 years ago. This paper outlined the advances of biological taxonomy and introduces the Cox's new classification of parasites so as to promote parasitological research. PMID- 17366984 TI - [Detection of Periplaneta americana sIgE with chemiluminescent immunoassay (CLIA)]. AB - Crude extract of Periplaneta americana was prepared by liquid nitrogen grinding. After being purified with DEAE Sephadex A-50 ion exchange chromatography, the protein content of the extract was determined and the extract solution was prepared at gradient concentrations. The crude extract and purified allergen at different concentrations were dotted respectively on nitrocellulose (NC) membrane. Patient serum, bio-IgE, sa-HRP, luminal regents were added to the membrane. The chemiluminescence was displayed by exposing to X-film. The result revealed that the minimum protein content of crude Periplaneta americana extract detected by CLIA is 0.87 microg/ml, with 90% accordance to skin test positive patients, and 100% accordance to those with negative skin test and ELISA detection. PMID- 17366985 TI - [Electron microscopical observation on rats with Pneumocystis carinii pneumonia treated with Brucea javanica and Fructus Psoraleae]. AB - Rats with Pneumocystis carinii pneumonia (PCP) were established by hypodermic injection of dexamethasone and treated by Brucea javanica combined with Fructus Psoraleae 2 ml (Brucea javanica 0.12 mg and Fructus Psoraleae 1.0 mg) per rat per day for 7 days or 14 days. The effect of cyst-killing and the pathological change were observed under transmission electron microscope. Lung damage was alleviated or repaired, and a significant reduction of cysts was shown in the treatment group. The results show that a combination of Brucea javanica and Fructus Psoraleae played a significant restraining and killing effect on cysts, and helped repair the impairment of pneumonia. PMID- 17366986 TI - [Serum IL-12 level in mice infected with Trichinella spiralis]. AB - Kunming mice were infected by feeding 150+/-5 larvae of Trichinella spiralis, established was also a normal control group. Blood was collected from the ophthalmic venous plexus respectively on 7 d, 21 d, 35 d and 49 d after infection and IL-12 in the serum was detected by ELISA. The level of IL-12 in serum decreased in groups of 7 d, 21 d, and 35 d, with a significant difference to the control (P<0.01). However, there was no significant difference between 49d group and control (P>0.05), suggesting that the serum IL-12 of the Trichinella spiralis infected mice significantly decreased at the earlier stage but approached to normal at a later stage. PMID- 17366987 TI - [An in vitro test of propolis against Trichomonas vaginalis]. AB - Cultured T. vaginalis was used for the anti-trichomonas test at different times, concentrations of propolis and densities of the parasites. After being cultured for 0, 6, 12, 24 hrs, the survival rate of the parasites was (91.50+/-3.11)%, (43.00+/-6.83)%, (22.25+/-5.32)% and (11.50+/-5.74)% respectively with a significant difference between propolis group and the control. Under the concentrations of 0.24, 0.48, 0.96, 1.92, 3.84 and 7.68 (mg/ml) with 24 hrs culture, the survival rate was (88.00+/-5.29)%, (92.67+/-4.16)%, (90.0+/-6.00)%, (84.00+/-4.00)%, (2.67+/-1.15)%, and 0 respectively. The results showed that propolis possesses clear in vitro anti-trichomonas activity which is relevant to the duration of culture and the concentration of the agent. PMID- 17366989 TI - Maintaining congressional momentum. 2006 saw a flurry of HIM legislative activity; 2007 promises more. PMID- 17366988 TI - [A novel synthesized Schistosoma japonicum miracidium attractant imprinted polymer]. AB - A novel molecularly imprinted polymer with adequate attractability for Schistosoma japonicum miracidia was prepared. When adulterated with polyvinyl alcohol (PVA), the fabricated film with good swelling property was formed which can suspend on water and slowly release XF (a chemical to be published). This reusable film can well attract Schistosoma japonicum miracidia, and hopefully be used in the prevention of schistosome infection. PMID- 17366990 TI - Collect once, use many. Enabling the reuse of clinical data through controlled terminologies. AB - Capturing patient information with controlled terminologies can enable its reuse for a wide variety of purposes, from bed assignments to reporting to clinical alerts. PMID- 17366991 TI - Translation, please. Mapping translates clinical data between the many languages that document it. PMID- 17366992 TI - Language barrier. Getting past the classifications and terminologies roadblock. AB - Health IT is bogged down in a quagmire of unaligned classification and terminology systems. New recommendations from AHIMA and AMIA help point to the way out. PMID- 17366993 TI - Creating a rural record. PMID- 17366994 TI - Is "legal EHR" a redundancy? Common definitions and key issues in migrating to EHRs as business records. PMID- 17366995 TI - Record disclosure and the EHR. Defining and managing the subset of data disclosed upon request. PMID- 17366996 TI - Unraveling the data set, an e-hIM essential. PMID- 17366997 TI - The physician voluntary reporting program. Medicare's quality measures program authorized for incentive payments in 2007. PMID- 17366998 TI - Data standards, data quality, and interoperability. PMID- 17366999 TI - When guidelines depend on the setting. Comparing, contrasting facility reporting and professional fee coding. PMID- 17367000 TI - 2007 CPT coding update. PMID- 17367001 TI - Speaking the same language. Terminology analyst strives for standardization. PMID- 17367002 TI - A "large and graceful sinuosity". John Herschel's graphical method. AB - In 1833 John Herschel published a graphical method for determining the orbits of double stars. He argued that his method, which depended on human judgment rather than mathematical analysis, gave better results than computation, given the uncertainty in the data. Herschel found that astronomy and terrestrial physics were especially suitable for graphical treatment, and he expected that graphs would soon become important in all areas of science. He argued with William Whewell and James D. Forbes over the process of induction, over the application of probability, and over the moral content of science. Graphs entered into all these debates; but because they constituted a method, not a metaphysics, they were acceptable to most practicing scientists and became increasingly popular throughout the nineteenth century. PMID- 17367003 TI - Amateur scientists, the international geophysical year, and the ambitions of Fred Whipple. AB - The contribution of amateur scientists to the International Geophysical Year (IGY) was substantial, especially in the arena of spotting artificial satellites. This article examines how Fred L. Whipple and his colleagues recruited satellite spotters for Moonwatch, a program for amateur scientists initiated by the Smithsonian Astrophysical Observatory (SAO) in 1956. At the same time, however, the administrators with responsibility for the IGY program closely monitored and managed--sometimes even contested--amateur participation. IGY programs like Moonwatch provided valuable scientific information and gave amateurs opportunities to contribute actively to the research of professional scientists. Moonwatch, which operated until 1975, eventually became the public face of a vast satellite-tracking network that expanded the SAO's global reach and helped further Whipple's professional goals. Understanding amateurs' interactions with the professional science community enables us better to understand the IGY as a phenomenon that enlisted broad participation and transcended traditional boundaries between professional and amateur scientists. PMID- 17367004 TI - "The joy in believing": the Cardiff giant, commercial deceptions, and styles of observation in Gilded Age America. AB - This essay presents a historical epistemology of the nineteenth-century controversy concerning a scientific hoax, the Cardiff giant. My focus is on the shifting meanings given to the giant, which were based on epistemologies derived from scientific authority, religious belief, and market relations. In 1869 a farmer in Cardiff, New York, claimed to have discovered the fossilized remains of a prehistoric, perhaps biblical, giant on his property. While some scientists stressed the need to cooperate with commercial showmen, enthusiasm for the giant incited the ire of others, who sought to debunk it and the culture that sustained it. Drawing on local newspaper reports, memoirs, nineteenth-century exposes, and publicity materials associated with the giant's display, I link the episode to the history of popular and scientific observation. The giant was a particularly troubling spectacle because as an object of inquiry it blurred the modern boundaries separating nature, society, and religion. PMID- 17367006 TI - Historical mathematics in the French eighteenth century. AB - At least since the seventeenth century, the strange combination of epistemological certainty and ontological power that characterizes mathematics has made it a major focus of philosophical, social, and cultural negotiation. In the eighteenth century, all of these factors were at play as mathematical thinkers struggled to assimilate and extend the analysis they had inherited from the seventeenth century. A combination of educational convictions and historical assumptions supported a humanistic mathematics essentially defined by its flexibility and breadth. This mathematics was an expression of l'esprit humain, which was unfolding in a progressive historical narrative. The French Revolution dramatically altered the historical and educational landscapes that had supported this eighteenth-century approach, and within thirty years Augustin Louis Cauchy had radically reconceptualized and restructured mathematics to be rigorous rather than narrative. PMID- 17367005 TI - Mathematics in narratives of Geodetic expeditions. AB - In eighteenth-century France, geodesy (the measure of the earth's shape) became an arena where mathematics and narrative intersected productively. Mathematics played a crucial role not only in the measurements and analysis necessary to geodesy but also in the narrative accounts that presented the results of elaborate and expensive expeditions to the reading public. When they returned to France to write these accounts after their travels, mathematician-observers developed a variety of ways to display numbers and mathematical arguments and techniques. The numbers, equations, and diagrams they produced could not be separated from the story of their acquisition. Reading these accounts for the interplay of these two aspects--the mathematical and the narrative--shows how travelers articulated the intellectual and physical difficulties of their work to enhance the value of their results for specialist and lay readers alike. PMID- 17367007 TI - Tragic mathematics: romantic narratives and the refounding of mathematics in the early nineteenth century. AB - A new, Romantic type of mathematical story appeared in the early nineteenth century that was radically different from the sober narrative characteristic of the previous generation of mathematicians. At the same time, a new mathematical practice emerged that differed sharply from the understanding and practice of mathematics during the Enlightenment. These parallel developments are inseparable: the new type of mathematical practice went hand in hand with the new mathematical story. PMID- 17367009 TI - A stroke for stem cells. PMID- 17367008 TI - What any author of a specialized work dreads is having it reviewed by someone with little or no knowledge of the specialty. PMID- 17367010 TI - Martian rope trick. PMID- 17367012 TI - The triangular universe. PMID- 17367011 TI - Chipping in. PMID- 17367013 TI - Unsettled scores. PMID- 17367014 TI - Dial "I" for internet. PMID- 17367015 TI - License to work. PMID- 17367016 TI - Eat, drink and be merry. PMID- 17367017 TI - Moving beyond Kyoto. PMID- 17367019 TI - The universe's invisible hand. PMID- 17367018 TI - Graft and host, together forever. PMID- 17367020 TI - Tracking an ancient killer. AB - Large meat-eating dinosaur Majungatholusatopus (above) met an untimely end some 70 million years ago in what is now northwestern Madagascar (opposite page, top]. Members of the authors' team carefully excavated the remains, including a jaw with serrated teeth used to slice through flesh (right), and packed them in plaster for transport to the U.S. (opposite page, bottom), where the researchers studied the fossils in detail for clues to the cause of death. PMID- 17367022 TI - Making silicon lase. PMID- 17367021 TI - Methane, plants and climate change. PMID- 17367024 TI - Digital TV at last? February 17, 2009, is D-day. PMID- 17367023 TI - Spice Healer. PMID- 17367026 TI - Song beams. PMID- 17367025 TI - Molecular lego. PMID- 17367027 TI - Power walker. PMID- 17367028 TI - Digital radiography: a survey of pediatric dentists. AB - PURPOSE: The purpose of this study was to: (1) determine the popularity of digital radiography among members of the American Academy of Pediatric Dentistry (AAPD); and (2) report the most common systems in use. METHODS: An AAPD-approved, voluntary, and anonymous electronic survey was developed and sent to 923 board certified pediatric dentists. Years in practice and in-office x-ray technology (digital or conventional) were inquired about initially. If negative for the use of digital radiography, future consideration for converting to digital radiography was ascertained. For positive responses, more in-depth information was requested. Information on type of system (sensor or phosphor plate), user friendliness, diagnostic ability, patient's comfort, general costs, durability, and parental and overall satisfaction was collected. For most of the questions, a 5-point assessment scale was used. Opportunity for additional comments was provided upon survey completion. Data was analyzed using descriptive statistics. RESULTS: A 32% (296/923) response rate was obtained. Twenty-six percent of practitioners (78/296) implemented digital radiography in their practices, whereas 71% considered future acquisition. Similar distribution for sensor and phosphor plate users was found. Sensor technology was reported to produce faster images, but was less tolerable by young children due to size and thickness. Phosphor plates were considered more children friendly, less expensive, and less durable. Parental satisfaction was very high with great marketing value. Picture quality was comparable to conventional film. Overall, digital radiography users would recommend it to other pediatric dentists. CONCLUSIONS: Digital radiography is not yet popular among pediatric dentists. Cost reduction and technology advancement may enhance utilization. PMID- 17367029 TI - Fluoride assay methodology for carbonated beverages. AB - PURPOSE: The purpose of this paper was to review different methodological techniques used for the assessment of fluoride in carbonated beverages, and compare results using a fluoride ion electrode direct read method with and without a prior decarbonation treatment. METHODS: The carbonated beverages in this study were either purchased locally at grocery stores in Iowa City, Iowa, or purchased as part of a national representative sampling approach included in the National Fluoride Database and Intake Assessment Study (NFDIAS). The samples were compared with and without a decarbonating process. Soda pop and beer samples were analyzed by removing a 1-ml sample and adding a 1-ml buffer solution. The fluoride concentration of the sample and buffer combination was then determined using a fluoride ion specific electrode. RESULTS: There was no significant difference in the fluoride concentration of the samples with or without prior decarbonation. The mean absolute difference between the soda pop group with and without decarbonation was 0.01 ppm F, while results from the beer samples showed variation of 0.00 to 0.02 parts per million fluoride (ppm F). These differences were not statistically significant for the soda pop or beer groups (P=.50 and P=.74, respectively). CONCLUSION: Whether or not decarbonation was conducted prior to analysis, the fluoride assay results were the same. Therefore, decarbonation of soda pop and beer was deemed unnecessary prior to fluoride analysis. PMID- 17367030 TI - Dental abnormalities in children submitted to antineoplastic therapy. AB - PURPOSE: The purpose of this study was to assess, by panoramic radiographs, the prevalence of morphological dental changes in children with cancer who were submitted for chemotherapy alone or concomitant radiotherapy of the head and neck. METHODS: All patients admitted between March, 1996 and February, 2004 were analyzed and 137 were included in this retrospective, nonrandomized, institutional study. The rates of microdontia, taurodontia, anodontia, macrodontia, blunt root, and tapered root were assessed. RESULTS: The patients were distributed into 2 groups: (1) those with lymphoproliferative neoplasias (61%); and (2) those with solid tumors (39%). Their mean age when treatment began was 5 years and 6 months. Dental abnormalities were found in 39 (29%) patients, while 98 (72%) patients did not present any abnormality. The abnormalities found were: (1) microdontia (7%; N= 10); (2) anodontia (6%; N=8); (3) taurodontia (14%; N=19); (4) macrodontia (5%; N=7); (5) blunted root (2%; N=2); and (6) tapered root (4%; N=5). Of these patients: 22% (N=30) presented 1 abnormality; 4% (N=6) presented 2 abnormalities; and 2% (N=3) presented 3 abnormalities. CONCLUSION: Taurodontia was the most frequent abnormality found in children and adolescents who underwent antineoplastic treatment, and its rate was significantly higher than those found for the healthy Brazilian population. This study's results show that it is necessary for the odontologist to systematically research the dental changes that occur among this special group of patients. PMID- 17367031 TI - Predictors of oral health counseling by WIC providers. AB - PURPOSE: The purpose of this study was to assess selected predictors for the inclusion of oral health counseling by Illinois Women, Infants, and Children (WIC) providers. METHODS: A questionnaire was developed and mailed to all 166 WIC sites to assess attitudes towards oral health counseling. Variables that revealed significant associations in bivariate analysis (P< or =.05) were considered as candidates for building a final logistic regression model in which frequency of oral health counseling was the outcome. RESULTS: A response rate of 76% was achieved after 1 mailing, with 27% of the WIC providers having some form of oral health training. There were no statistically significant differences in the frequency of WIC providers discussing oral health with their clients by age, gender, and level of education of the provider. In the final logistic regression analysis, variables significantly associated with the frequency of WIC providers' dicussing oral health with their clients were having: (1) oral health training; and (2) nursing training. CONCLUSIONS: The results suggest that Women, Infants, and Children (WIC) providers, who have had some oral health training, are more likely to provide counseling about dental disease and its prevention. This information was used to develop an educational tool for these nondental, health care providers. PMID- 17367032 TI - Evaluation of the contamination and disinfection methods of toothbrushes used by 24- to 48-month-old children. AB - PURPOSE: The purpose of this study was to evaluate: (1) in vivo the contamination by mutans streptococci (MS) of toothbrushes after use on 52 children (24-48 months old) by a single dentist; (2) in vivo the efficacy of 3 solutions (Periogard, Brushtox, and a Cosmocil CQa and Myacide pharma BPa-based experimental solution) in the disinfection of these toothbrushes through a randomized clinical trial; and (3) in vitro the antimicrobial activity of the solutions by the agar diffusion test using 15 microbial strains. METHODS: In the in vivo trial, children were randomly assigned to 1 of 4 groups (N=13) and a 4 stage changeover system was used with a 1-week interval between each stage. Solutions were used by a different group of children in each stage. Children were submitted to a 1-minute brushing (without toothpaste) performed by a single professional, followed by random spraying of the test solutions and microbiological analysis. RESULTS: Brushtox, Periogard, and the experimental solution reduced/prevented the formation of MS colonies/biofilms on the toothbrush bristles compared to the control (sterile tap water; P<.001). Periogard and the experimental solution showed significantly greater reduction of colonies/biofilms compared to Brushtox (P<.01). In the in vitro experiment, Periogard exhibited the greatest inhibition halo average, followed by the experimental solution, Brushtox, and sterile tap water (P<.05). CONCLUSIONS: After a single brushing, severe contamination by mutans streptococci colonies/biofilms was observed on all toothbrushes sprayed with sterile tap water (control). Although Brushtox presented better results than sterile tap water, Periogard and the experimental solution showed greater efficacy against formation of MS colonies/ biofilms on the toothbrush bristles and exhibited larger microbial growth inhibition halos. PMID- 17367033 TI - Presence of developmental defects of enamel in cystic fibrosis patients. AB - PURPOSES: Cystic fibrosis (CF) is an autosomal recessive hereditary disease and is the frequently common lethal genetic pathology. The purposes of this study were to: (1) determine the presence of 3 different types of enamel defects: (a) demarcated opacities; (b) diffuse opacities; and (c) hypoplasia in the deciduous and permanent dentition of CF patients; and (2) compare with a control group. METHODS: The case group was defined as 13 patients who were diagnosed with CF and enrolled in a multiprofessional project of the Catholic University of Brasilia (CUB), Brasilia, Brazil. All CF subjects were compared with control subjects selected from patients at the CUB. Each CF subject was individually paired with a control subject of similar sex and age. A full-mouth examination was carried out for the developmental defects of enamel (DDE) index. RESULTS: The most prevalent enamel defect in deciduous teeth was demarcated opacities present in 16% of the case group and in 7% of the control group. Although the defects were more prevalent in the case group, the difference was not statistically significant (P=0.57). The frequency of demarcated opacities was more prevalent in permanent teeth of the case group: 39% compared to 11% in the control group. For the control group, diffuse opacities were the more prevalent defects: 17% compared to 15% in the case group. The case group had more enamel defects in permanent teeth compared to the control (P=0.0003). CONCLUSIONS: In this study, enamel defects were frequently found in the permanent teeth of CF patients. Therefore, professionals who treat children should be alerted to promoting oral health among these patients. PMID- 17367034 TI - Changes in the soft tissue profile after extraction orthodontic therapy. AB - PURPOSE: The purpose of this study was to evaluate the effects of extraction therapy and use or nonuse of headgear on the soft tissue profile in subjects with different growth patterns. METHODS: A total of 41 subjects were included in the study. The patients were treated with standard edgewise mechanics and had 4 first premolars extracted. The type of growth pattern was assessed as mesiodivergent or hyperdivergent. The results were analyzed by 2-way analysis of variance. RESULTS: When comparing the mean changes between growth pattern types, the vertical changes in Sn and A' were found to be statistically significant (P<.05). The vertical change in A' was also found to be significant between the headgear use and nonuse groups (P<.05). Interaction was found to be significant for Steiner upper and lower lip values and the vertical change in A. The upper and lower lips were retracted significantly more by headgear use in patients with hyperdivergent growth pattern (P<.05). CONCLUSIONS: The results of this study indicate that the use of headgear should be avoided in hyperdivergent patients. The avoidance of premolar extraction, based on the possibility of a significant detrimental effect on the facial profile, is not justified. PMID- 17367035 TI - Load-induced stresses in photoelastic primary canines with facial restorations. AB - PURPOSE: The purpose of this study was to photoelastically compare the stresses generated by loads on primary canines with facial restorations of different stiffness. METHODS: Composite photoelastic models of a typical maxillary primary canine were fabricated using individual simulant materials for enamel, dentin, periodontal ligament, and alveolar bone. Models were made with identical facial preparations included either near the cementoenamel junction or at 2 mm incisally. The model teeth were restored using the following materials of disparate elastic moduli: (1) high modulus, hybrid composite (Herculite XRV); and (2) lower modulus compomer (Dyract). Three replications of each type of restored tooth were fabricated. Simulated masticatory forces were applied on the cusp tip and the cingulum of each tooth model. The resulting stress patterns were observed and recorded photographically in the field of a circular polariscope. RESULTS: Prior to load application, similar low-level, polymerization-induced shrinkage stresses were localized at the preparation margins of all models. Under both incisal and cingular loading, the higher modulus hybrid composite tended to concentrate stress along the gingival and proximal margins more than did the lower modulus compomer. This effect was more pronounced with cingular than with incisal loading. For both preparations and restoratives, higher stresses were produced by the cingulum loading. No significant differences were observed within each group of replicated restored models. CONCLUSION: These results suggest that, regardless of preparation height, lower modulus compomer restoration of facial lesions in primary maxillary canines may reduce stress production by occlusal forces. PMID- 17367036 TI - Frontal linear scieroderma (en Coup de Sabre): a case report. AB - En coup de sabre is a type of linear scleroderma which presents on the frontal or frontoparietal scalp. En coup de sabre in children is associated with asymmetric growth and progressive facial disfigurement. The purpose of this report was to present the case of a 4-year-old girl with a 2-year history of en coup de sabre. The clinical presentation and radiographic findings are discussed. PMID- 17367037 TI - Clinical manifestations due to severe plasminogen deficiency: a case report. AB - Plasminogen deficiency is a rare, destructive, and badly defined disorder. Recurrent and progressive gingival nodular hyperplasia with ulceration would appear to be an unreported complication caused by this deficiency. In some of the reported cases, gingival hyperplasia occurred in association with an eye disease called ligneous conjunctivitis. Including this case report, only 11 patients with proven functional plasminogen and oral lesions have been reported in the literature in English. The purpose of this paper was to present the case of a child patient with recurrent clinical manifestations caused by severe plasminogen deficiency who responded positively to corticosteroid treatment. PMID- 17367038 TI - Management of a case with bilateral talon cusp in primary dentition. AB - The talon cusp is a relatively rare dental developmental anomaly characterized by the presence of an accessory cusp-like structure projecting from the cingulum area or cementoenamel junction. The alteration can cause clinical problems such as caries or occlusal interference. Management of the talon cusp varies according to the circumstances of the individual case and should be as conservative as possible. The purpose of this report was to present the case of bilateral talon cusp in primary maxillary central incisors that was successfully managed with conservative therapy. PMID- 17367040 TI - Compatibility of topical therapies for psoriasis: challenges and innovations. AB - Topical treatments remain the most widely prescribed medications for psoriasis, particularly for patients with mild to moderate or localized disease. In addition, topical therapies can substantially improve outcomes when used alone or in combination with systemic or biologic agents in patients with moderate to severe or more extensive disease. Combinations of different topical treatments frequently are prescribed to enhance clinical effectiveness and decrease potential side effects. However, certain topical agents become ineffective when used together or in combination with other therapies, such as phototherapy. These topical agents should be combined only with treatments that have been demonstrated to have no effect on the chemical stability or clinical effectiveness of topical agents. This article reviews the compatibility of different topical agents and identifies those agents that can be effectively and safely combined with each other and with phototherapy. PMID- 17367039 TI - Advances in first-line topical therapies: the role of a 2-compound ointment for psoriasis vulgaris. PMID- 17367041 TI - Using topical multimodal strategies for patients with psoriasis. AB - Psoriasis is a chronic disease that requires lifelong treatment. Because there is no cure for psoriasis, treatment is aimed at inducing remission and reducing the impact of the disease on patients' lives. Despite the availability of several therapies, the overall effectiveness of psoriasis treatment often is limited by patient concerns about side effects, effectiveness, and convenience. These concerns result in low treatment expectations, poor compliance, and, ultimately, poor clinical outcomes. To maximize compliance and outcomes, dermatologists use multiple treatment strategies, including prolonged monotherapy, combination therapy, sequential therapy, and rotational therapy. Dermatologists must weigh the advantages and disadvantages of each strategy and select the therapeutic regimen that most closely matches a patient's condition, historical response, compliance with therapy, and treatment expectations. This article reviews the approaches for treating psoriasis vulgaris and discusses the creative strategies designed to increase treatment success. PMID- 17367042 TI - The role of topical therapy for patients with extensive psoriasis. AB - Approximately 14% of patients with psoriasis have moderate or severe disease defined as affecting 3% to 10%, or greater than 10%, of body surface area (BSA), respectively. In the context of topical therapy, extensive disease refers to psoriasis involving 10% to 30% of BSA for which topical therapy might not have been considered optimum in the past because of patient preference and/or convenience. Treatment of patients with extensive disease traditionally has focused on phototherapy and/or systemic therapy with agents such as cyclosporine, methotrexate, and oral retinoids; these agents can improve outcomes in patients beyond those afforded by traditional topical monotherapy. Biologic therapy (e.g., alefacept, efalizumab, etanercept) provides dermatologists with additional treatment options for patients with extensive psoriasis, for whom topical treatments typically have been considered adjunct therapy for focal resistant lesions. A new 2-compound topical ointment containing calcipotriene 0.005% and betamethasone dipropionate 0.064% has demonstrated efficacy in patients with severe psoriasis, an outcome that previously was difficult to achieve with topical therapy. Advantages of the 2-compound ointment include rapid onset of action and a relative lack of systemic toxicity. This effective topical agent may expand the psoriasis population that can be considered candidates for topical treatment. PMID- 17367043 TI - The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis. AB - Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance. PMID- 17367044 TI - An innovation in topical therapy: insights from international dermatologists. AB - Topical therapies are appropriate for most patients with psoriasis. These therapies frequently are used as first-line agents for mild and moderate disease and as an adjuvant to phototherapy or systemic treatment. In Europe, vitamin D3 analogues (e.g., calcipotriene) are preferred as first-line therapies and often are used in combination with potent topical corticosteroids. Because calcipotriene and corticosteroids have different mechanisms of action, superior efficacy and reduced side effects can be achieved by their combined use; however, chemical incompatibility prevents combined application. This incompatibility has been overcome by the recent development of a stable formulation of calcipotriene and betamethasone dipropionate. In 7 clinical trials, more than 3000 subjects received once-daily or twice-daily treatment with the 2-compound ointment for 4- to 52-week periods. The overall results indicate that the 2-compound ointment elicits rapid and substantial reductions in Psoriasis Area and Severity Index (PASI) scores. The treatment Calso is well-tolerated. PMID- 17367045 TI - Treating impetigo in primary care. AB - Impetigo is a superficial, but contagious, bacterial infection of the skin that predominantly affects children and is common in primary care. In UK general practice, around half of the people with impetigo are treated with topical fusidic acid. However, bacterial resistance to this antibacterial drug is increasing. Here we discuss how patients with impetigo should be treated. PMID- 17367046 TI - Exubera: inhaled insulin for diabetes. AB - Over 2 million people in the UK have diabetes mellitus, of whom around 20% have type 1 and 80% type 2 disease. A key aim of treatment is to optimise glycaemic control to minimise symptoms, prevent complications and extend survival. To these ends, subcutaneous insulin is used to manage all patients with type 1 diabetes and some patients with type 2 diabetes. Another potential route of administering insulin is by inhalation. Exubera (Pfizer), the first licensed inhaled insulin in the UK, is promoted as "the new look of insulin" and as maintaining "long-term glycaemic control". What does it offer in the management of patients with diabetes? PMID- 17367047 TI - Clearing the air on pricing transparency. Interview by Bob Kehoe. PMID- 17367048 TI - Managing supply chain costs with technology. PMID- 17367049 TI - Innovative dressings improve wound care management. PMID- 17367050 TI - Ignoring 'boilerplate' contract language can prove costly. PMID- 17367051 TI - Trace your steps to sterility assurance. PMID- 17367052 TI - Mobile units double sterile supply storage. PMID- 17367053 TI - Organizations collaborate to prevent surgical fires. PMID- 17367054 TI - Stats. Benchmarking your surgical supply expenses. It pays to examine the case mix index. PMID- 17367055 TI - Increase efficiency by examining touch points within surgical services. PMID- 17367056 TI - Subtotal obliteration of cerebral arteriovenous malformations after gamma knife surgery. AB - OBJECT: Subtotal obliteration of cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS) implies a complete angiographic disappearance of the AVM nidus but persistence of an early filling draining vein, indicating that residual shunting is still present; hence, per definition there is still a patent AVM and the risk of bleeding is not eliminated. The aim of this study was to determine the risk of hemorrhage for patients with subtotal obliteration of AVMs. METHODS: After GKS for cerebral AVMs, follow-up angiography demonstrated a subtotally obliterated lesion in 159 patients. Of these, in 16 patients a subtotally obliterated AVM developed after a second GKS was performed for the partially obliterated lesion. The mean age of these patients was 35.2 years at the time of the diagnosis of subtotally obliterated AVMs. The lesion volumes at the time of initial GKS treatment ranged from 0.1 to 11.5 cm3 (mean 2.5 cm3). The mean peripheral dose used in the 175 GKS treatments was 22.5 Gy (median 23 Gy, range 15-31 Gy). To achieve total obliteration of the AVM, 23 patients underwent a new GKS targeting the proximal end of the early filling vein. The mean peripheral dose given in these cases was 23 Gy (median 24, range 18-25 Gy). The incidence of subtotally obliterated AVMs was 7.6% from a total of 2093 AVMs treated and in which follow-up imaging was available. The diagnosis of subtotally obliterated AVMs was made a mean of 29.4 months (range 4-178 months) after GKS. The number of patient-years at risk (from the time of the diagnosis of subtotally obliterated AVMs until either the confirmation of a total obliteration of the lesion on angiography or the time of the latest follow-up angiographic study that still visualized the early filling vein) was a mean of 3.9 years, ranging from 0.5 to 13.5 years, and a total of 601 patient-years. There was no case of bleeding after the diagnosis of subtotally obliterated AVMs. Of 90 patients who did not undergo further treatment and in whom follow-up angiography studies were available, the same early filling veins still filled in 24 (26.7%), and the subtotally obliterated AVMs were subsequently obliterated in 66 patients (73.3%). In 19 patients who underwent repeated GKS for subtotally obliterated AVMs and in whom follow-up angiography studies were available, the AVMs were obliterated in 15 (78.9%) and remained patent in four (21.1%). CONCLUSIONS: The fact that none of the patients with subtotally obliterated AVMs suffered a rupture is not compatible with the assumption of an unchanged risk of hemorrhage for these lesions, and implies that the protection from rebleeding in patients with subtotal obliteration is significant. Subtotal obliteration does not necessarily seem to be a stage of an ongoing obliteration. At least in some cases it represents an end point of this process, with no subsequent obliteration occurring. This observation requires further confirmation by open-ended follow-up imaging. PMID- 17367057 TI - Neural injury and recovery near cortical contusions: a clinical magnetic resonance spectroscopy study. AB - OBJECT: Proton magnetic resonance (MR) spectroscopy can detect neural metabolic alterations noninvasively after traumatic brain injury (TBI) even in areas that appear normal. Unlike metabolic depression in diffuse TBI, focal metabolic alterations near cortical contusions in humans have not been previously investigated in a longitudinal study. The object of this study was to identify these alterations and examine their course. METHODS: At 1 week and 1 month after mild to moderate TBI involving cortical contusion, 30 patients underwent 1H MR spectroscopy examination that focused bilaterally on normal-appearing frontal and temporal white matter. Levels of N-acetylaspartate (NAA), choline (Cho) compounds, and creatine (Cr) were measured to obtain two metabolite ratios, NAA/Cr and Cho/Cr. The ratios were compared with those of 11 healthy individuals. At 1 week after TBI, the NAA/Cr ratio was significantly lower near cortical contusions than it was in white matter remote from the injury or in controls, while the Cho/Cr ratios did not differ significantly. At 1 month, the decreased NAA/Cr ratios near contusions had increased significantly from 1 week, as had the Cho/Cr ratio. CONCLUSIONS: Metabolic depression reflecting neural injury was apparent in subjacent normal-appearing white matter at 1 week after cortical contusion; this had normalized substantially at 1 month. PMID- 17367058 TI - External ventricular drain infections are independent of drain duration: an argument against elective revision. AB - OBJECT: The authors explored the relationship among the duration of external ventricular drainage, revision of external ventricular drains (EVDs), and cerebrospinal fluid (CSF) infection to shed light on the practice of electively revising these drains. METHODS: In a retrospective study of 199 patients with 269 EVDs in the intensive care unit at a major trauma center in Australasia, the authors found 21 CSF infections. Acinetobacter accounted for 10 (48%) of these infections. Whereas the duration of drainage was not an independent predictor of infection, multiple insertions of EVDs was a significant risk factor. Second and third EVDs in previously uninfected patients were more likely to become infected than first EVDs. An EVD infection was initially identified a mean of 5.5 +/- 0.7 days postinsertion (standard error of the mean); these data--that is, the number of days--were normally distributed. CONCLUSIONS: This pattern of infection is best explained by EVD-associated CSF infections being acquired by the introduction of bacteria on insertion of the drain rather than by subsequent retrograde colonization. Elective EVD revision would be expected to increase infection rates in light of these results, and thus the practice has been abandoned by the authors' institution. PMID- 17367059 TI - Prognostic value of the lateral spread response for intraoperative electromyography monitoring of the facial musculature during microvascular decompression for hemifacial spasm. AB - OBJECT: The authors conducted a large retrospective study in which they evaluated the efficacy of intraoperative electromyography (EMG) monitoring of facial musculature during microvascular decompression (MVD) and assessed the predictive value of the lateral spread response (LSR) as a prognostic indicator for the treatment outcome of hemifacial spasm (HFS). METHODS: The authors undertook intraoperative monitoring during MVD in 300 consecutive patients with HFS. The patients were divided into two groups based on whether the LSR disappeared or persisted following decompression. The mean follow-up period was 35.8 months (range 12-55 months). In 263 (87.7%) of the 300 patients, the LSR was observed during intraoperative facial EMG monitoring. In 230 (87.4%) of these 263 patients, the LSR disappeared following decompression (Group I), and in the remaining 33 patients (12.5%) the LSR persisted despite decompression (Group II). At the postoperative 1-year follow-up visit, there was a significant difference in clinical outcomes between both groups (p < 0.05). CONCLUSIONS: Facial EMG monitoring of the LSR is an effective tool to use when performing complete decompression, and it may be helpful in predicting outcomes. PMID- 17367060 TI - A retrospective analysis of reasons for reoperation following initially successful peripheral nerve stimulation. AB - OBJECT: The authors investigated the causes for surgical reexploration in patients with complex regional pain syndrome Type II who received initial relief of pain from implantation of a peripheral nerve stimulator (PNS). METHODS: The authors reviewed the charts of 11 consecutive patients who underwent a total of 27 PNS-related operations at one institution. Duration of follow up ranged from 5 days to more than 24 months. Of 11 patients who received PNS implants, seven (64%) required one or more additional surgeries to relocate the PNS because initial pain relief following stimulation was lost and not restored by changing pulse generator settings. Loss of analgesia was attributed to migration of the sutured electrode strip paddle (nine [33%] of 27 surgeries), infection (four [15%] of 27), and the need for placement in an alternative location (three [11%] of 27). CONCLUSIONS: Although infection is attributable to surgical technique, most complications requiring repeated surgery (nine [33%] of 27) are caused by equipment design. Changes in PNS design or in implantation technique might substantially reduce the need for reoperation after PNS implantation. PMID- 17367061 TI - Direct repair (nerve grafting), neurotization, and end-to-side neurorrhaphy in the treatment of brachial plexus injury. AB - OBJECT: The authors present the long-term results of nerve grafting and neurotization procedures in their group of patients with brachial plexus injuries and compare the results of "classic" methods of nerve repair with those of end-to side neurorrhaphy. METHODS: Between 1994 and 2006, direct repair (nerve grafting), neurotization, and end-to-side neurorrhaphy were performed in 168 patients, 95 of whom were followed up for at least 2 years after surgery. Successful results were achieved in 79% of cases after direct repair and in 56% of cases after end-to-end neurotization. The results of neurotization depended on the type of the donor nerve used. In patients who underwent neurotization of the axillary and the musculocutaneous nerves, the use of intraplexal nerves (motor branches of the brachial plexus) as donors of motor fibers was associated with a significantly higher success rate than the use of extraplexal nerves (81% compared with 49%, respectively, p = 0.003). Because of poor functional results of axillary nerve neurotization using extraplexal nerves (success rate 47.4%), the authors used end-to-side neurorrhaphy in 14 cases of incomplete avulsion. The success rate for end-to-side neurorrhaphy using the axillary nerve as a recipient was 64.3%, similar to that for neurotization using intraplexal nerves (68.4%) and better than that achieved using extraplexal nerves (47.4%, p = 0.19). CONCLUSIONS: End-to-side neurorrhaphy offers an advantage over classic neurotization in not requiring sacrifice of any of the surrounding nerves or the fascicles of the ulnar nerve. Typical synkinesis of muscle contraction innervated by the recipient nerve with contraction of muscles innervated by the donor was observed in patients after end-to-side neurorrhaphy. PMID- 17367062 TI - Endoscopic, endonasal extended transsphenoidal, transplanum transtuberculum approach for resection of suprasellar lesions. AB - OBJECT: The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision and a microscope and have reported a significant risk of cerebrospinal fluid (CSF) leakage. The authors report on a series of purely endoscopic endonasal surgeries for resection of suprasellar supradiaphragmatic lesions above a normal-sized sella turcica with a low risk of CSF leakage. METHODS: A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (three tuberculum sellae and two planum sphenoidale meningiomas) and five were post-chiasmal (four craniopharyngiomas and one Rathke cleft cyst). The floor of the planum sphenoidale and the sella turcica was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was performed in only five cases. Complete resection of the lesions was achieved in all but one patient. The pituitary stalk was preserved in all but one patient, whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus (DI). Vision improved postoperatively in all patients with preoperative impairment. Six patients had temporary DI; in five, the DI became permanent. Four patients with craniopharyngiomas required cortisone and thyroid replacement. After a mean follow up of 10 months, there was only one transient CSF leak when a lumbar drain was clamped prematurely on postoperative Day 5. CONCLUSIONS: A purely endoscopic endonasal approach to suprasellar supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leakage is low and lumbar drainage can be avoided. A larger series will be required to validate this approach. PMID- 17367063 TI - Synergistic cytotoxicity through the activation of multiple apoptosis pathways in human glioma cells induced by combined treatment with ionizing radiation and tumor necrosis factor-related apoptosis-inducing ligand. AB - OBJECT: Malignant gliomas remain incurable despite modem multimodality treatments. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, a member of the TNF family, preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, suggesting that it may serve as a potential therapeutic agent for intractable malignant gliomas. Here, the authors show that genotoxic ionizing radiation synergistically enhances TRAIL-induced cell death in human glioma cells expressing DR5. METHODS: Combination treatment with soluble human TRAIL plus radiation induced robust cell death, while each of them singly led to only limited cytotoxicity. The combination resulted in cleavage and activation of the apoptotic initiator caspase-8 and the effector caspase-3 as well as cleavage of Bid and another initiator caspase-9, a downstream component of the apoptosome. Accordingly, it augmented the release of cytochrome c from the mitochondria into the cytosol, as well as apoptosis-inducing factor. Synergistic cell death was suppressed by TRAIL-neutralizing DR5-Fc, caspase inhibitors, expression of dominant-negative Fas-associated protein with death domain and CrmA, which selectively blocks caspase-8, and overexpression of Bcl-X(L). Finally, combination treatment had no influence on the viability of normal human astrocytes. CONCLUSIONS: These results suggest that combination treatment with TRAIL and ionizing radiation kills human glioma cells through the activation of DR5-mediated death receptor pathways. This therapy involves direct activation of effector caspases as well as mitochondria-mediated pathways and provides a novel strategy in which TRAIL could be synergistically combined with DNA-damaging radiation. PMID- 17367064 TI - Contribution of Notch signaling activation to human glioblastoma multiforme. AB - OBJECT: Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth. METHODS: Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation. CONCLUSIONS: Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy. PMID- 17367065 TI - Attenuation of oxidative injury after induction of experimental intracerebral hemorrhage in heme oxygenase-2 knockout mice. AB - OBJECT: Experimental evidence suggests that hemoglobin degradation products contribute to cellular injury after intracerebal hemorrhage (ICH). Hemoglobin breakdown is catalyzed in part by the heme oxygenase (HO) enzymes. In the present study, the authors tested the hypothesis that HO-2 gene deletion is cytoprotective in an experimental ICH model. METHODS: After anesthesia was induced with isoflurane, 3- to 6-month-old HO-2 knockout and wild-type mice were stereotactically injected with 15 microl autologous blood and a group of control mice were injected with an equal volume of sterile saline. Striatal protein and lipid oxidation were quantified 72 hours later using carbonyl and malondialdehyde assays. Cell viability was determined by performing a 3(4,5-dimethylthiazol-2 yl)2,5-diphenyltetrazolium bromide (MTT) assay. Following blood injection, the investigators found a 3.4-fold increase in protein carbonylation compared with that in the contralateral striatum in wild-type mice; in knockout mice, the investigators found a twofold increase. The mean malondialdehyde concentration in injected striata was increased twofold in wild-type mice at this time, compared with 1.5-fold in knockout mice. Cell viability, as determined by MTT reduction, was reduced in injected striata to 38 +/- 4% of that in the contralateral striata in wild-type mice, compared with 66 +/- 5% in HO-2 knockout mice. Baseline striatal HO-1 protein expression was similar in wild-type and HO-2 knockout mice, but was induced more rapidly in the former after blood injection. CONCLUSIONS: Deletion of HO-2 attenuates oxidative cell injury after whole-blood injection into the mouse striatum. Therapies that specifically target HO-2 may improve outcome after ICH. PMID- 17367066 TI - Attenuation of experimental subarachnoid hemorrhage--induced cerebral vasospasm by the adenosine A2A receptor agonist CGS 21680. AB - OBJECT: Impaired endothelium-dependent relaxation is present in vasospastic cerebral vessels after subarachnoid hemorrhage (SAH) and may result from deficient production of endothelial nitric oxide synthase (eNOS) or increased production and/or activity of inducible NOS (iNOS). Accumulating evidence demonstrates that adenosine A2A receptors increase the production of NO by human and porcine arterial endothelial cells, which in turn leads to vasodilation. This study was designed to examine the effects of an adenosine A2A receptor agonist, (2(4-[2-carboxyethyl]phenyl)ethylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680), in the prevention of SAH-induced vasospasm. METHODS: . Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 ml of autologous blood into the cisterna magna of each animal. Intraperitoneal injections of CGS 21680 or vehicle were administered 5 minutes and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging measurements of cross-sectional areas of the basilar artery (BA) 48 hours after SAH. Expression of eNOS and iNOS in the BA was also evaluated. Prior to perfusion-fixation, there were no significant differences among animals in the control and treated groups in any physiological parameter that was recorded. The CGS 21680 treatment significantly attenuated SAH-induced vasospasm. Induction of iNOS mRNA and protein in the BA by the SAH was significantly diminished by administration of CGS 21680. The SAH induced suppression of eNOS mRNA and protein was also relieved by the CGS 21680 treatment. CONCLUSIONS: This is the first evidence that adenosine A2A receptor agonism is effective in preventing SAH-induced vasospasm without significant complications. The beneficial effect of adenosine A2A receptor agonists may be, at least in part, related to the prevention of augmented expression of iNOS and the preservation of normal eNOS expression following SAH. Adenosine A2A receptor agonism holds promise in the treatment of cerebral vasospasm following SAH and merits further investigation. PMID- 17367067 TI - Attenuation of experimental subarachnoid hemorrhage-induced increases in circulating intercellular adhesion molecule-1 and cerebral vasospasm by the endothelin-converting enzyme inhibitor CGS 26303. AB - OBJECT: Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important mediators of inflammation, and their levels are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The investigators previously found that CGS 26303 is effective in preventing and reversing arterial narrowing in a rabbit model of SAH. The purpose of the present study was to examine whether levels of adhesion molecules are altered after treatment with CGS 26303 in this animal model. METHODS: New Zealand White rabbits were each injected with 3 ml of autologous blood in the cisterna magna, and intravenous treatment with CGS 26303 (30 mg/kg) was initiated 1 hour later. The compound was subsequently administered at 12, 24, and 36 hours post-SAH. Blood samples were collected at 48 hours post SAH to measure ICAM-1, VCAM-1, and E-selectin levels. After the rabbits had been killed by perfusion-fixation, the basilar arteries (BAs) were removed and sliced, and their cross-sectional areas were measured. Treatment with CGS 26303 attenuated arterial narrowing after SAH. Morphologically, corrugation of the internal elastic lamina of BAs was prominently observed in the SAH only and vehicle-treated SAH groups, but not in the CGS 26303-treated SAH group or in healthy controls. There were no significant differences in the levels of VCAM-1 among the four groups. The levels of E-selectin were increased in all animals subjected to SAH (those in the SAH only, SAH plus vehicle, and SAH plus CGS 26303 groups) compared with healthy controls (no SAH); however, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and treatment with CGS 26303 reduced ICAM-1 to control levels following SAH. CONCLUSIONS: These results show that ICAM-1 may play a role in mediating SAH induced vasospasm and that a reduction of ICAM-1 levels after SAH may partly contribute to the antispastic effect of CGS 26303. PMID- 17367068 TI - The suprapetrosal craniotomy. AB - OBJECTIVE: The primary aim of this study was to establish standard sites for bur holes that maintain constant anatomical relationships with the skull base and neural structures and can serve as the basal aspect of supratentorial temporooccipital craniotomies. METHODS: To determine cranial-cerebral relationships, the authors created bur holes in 16 adult cadaveric skulls. Three bur holes were made on each side of the skulls (32 cerebral hemispheres). The authors then introduced plastic catheters through the bur holes to evaluate pertinent cranial and neural landmarks. The first bur hole, located anterior to the auricle of the ear, appeared to have a particular anatomical relationship with the anterior aspect of the petrous portion of the temporal bone and the most anterior aspect of the midbrain. The second bur hole, whose base was located 1 cm above the interface of the parietomastoid and squamous sutures, had a particular relationship with the posterior border of the petrous portion of the temporal bone and with the posterior aspect of the midbrain. The third bur hole, whose base was located 1 cm above the asterion, was mostly supratentorial and particularly related to the preoccipital notch. CONCLUSIONS: The preauricular bur hole and the bur hole whose base was located 1 cm above the interface of the parietomastoid and squamous sutures delimit anteriorly and posteriorly the external projection of the petrous bone and the midbrain. The middle fossa floor is located anterior to the site of the preauricular bur hole, and the superior surface of the tentorium is posterior to the bur hole located above the parietomastoid-squamous suture interface. Together with the bur hole whose base is located above the asterion, these bur holes can be considered standards for temporooccipital craniotomies. PMID- 17367069 TI - Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas. AB - OBJECT: There is currently no effective chemotherapy for meningiomas. Although most meningiomas are treated surgically, atypical or malignant meningiomas and surgically inaccessible meningiomas may not be removed completely. The authors have investigated the effects of the topoisomerase I inhibitor irinotecan (CPT 11) on primary meningioma cultures and a malignant meningioma cell line in vitro and in vivo. METHODS: The effects of irinotecan on cellular proliferation in primary meningioma cultures and the IOMM-Lee malignant meningioma cell line were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. Apoptosis following drug treatment was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and the DNA laddering assays. The effects of irinotecan in vivo on a meningioma model were determined with a subcutaneous murine tumor model using the IOMM-Lee cell line. Irinotecan induced a dose-dependent antiproliferative effect with subsequent apoptosis in the primary meningioma cultures (at doses up to 100 microM) as well as in the IOMM-Lee human malignant meningioma cell line (at doses up to 20 microM) irinotecan. In the animal model, irinotecan treatment led to a statistically significant decrease in tumor growth that was accompanied by a decrease in Bcl-2 and survivin levels and an increase in apoptotic cell death. CONCLUSIONS: Irinotecan demonstrated growth-inhibitory effects in meningiomas both in vitro and in vivo. Irinotecan was much more effective against the malignant meningioma cell line than against primary meningioma cultures. Therefore, this drug may have an important therapeutic role in the treatment of atypical or malignant meningiomas and should be evaluated further for this purpose. PMID- 17367070 TI - Inhibition of angiogenesis induced by cerebral arteriovenous malformations using gamma knife irradiation. AB - OBJECT: The authors studied the effect of Gamma Knife irradiation on angiogenesis induced by cerebral arteriovenous malformation (AVM) tissues implanted in the corneas of rats. METHODS: Ten AVM specimens obtained from tissue resections performed at Marmara University between 1998 and 2004 were used. A uniform amount of tissue was implanted into the micropocket between the two epithelial layers of the cornea. Gamma Knife irradiation was applied with dose prescriptions of 15 or 30 Gy to one cornea at 100% isodose. Dosing was adjusted so that the implanted cornea of one eye received 1.5 Gy when 15 Gy was applied to the other cornea. Similarly, one cornea received 3 Gy when 30 Gy was applied to the other cornea. Angiogenic activity was graded daily by biomicroscopic observations. Forty-eight other rats were used for microvessel counting and vascularendothelial growth factor (VEGF) staining portions of the experiment. Micropieces of the specimens were again used for corneal implantation. Rats from each group were killed on Days 5, 10, 15, and 20, and four corneas from each group were examined. Gamma Knife irradiation dose dependently decreased AVM-induced neovascularization in the rat cornea as determined by biomicroscopic grading of angiogenesis, microvessel count, and VEGF expression. CONCLUSIONS: The results suggest that Gamma Knife irradiation inhibits angiogenesis induced by AVM tissue in the cornea angiogenesis model. The data are not directly related to understanding how Gamma Knife irradiation occludes existing AVM vasculature, but to understanding why properly treated AVMs do not recur and do not show neovascularization after Gamma Knife irradiation. PMID- 17367071 TI - Growth and regression of arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia. Case report. AB - Data on the growth, regression, and de novo formation of arteriovenous malformations (AVMs) suggest that some of these lesions are not formed and developed only during embryogenesis. Patients with hereditary hemorrhagic telangiectasia (HHT) have a genetic propensity to form AVMs. The authors report on the growth and regression of AVMs in a single patient with HHT. This 26-day old boy with a family history of HHT1 and a mutation in ENG on chromosome 9 presented with a generalized seizure. Results of computed tomography revealed a left frontoparietal intraparenchymal hemorrhage. Cerebral angiography revealed multiple AVMs. Follow-up angiograms obtained 5 months later showed both growth and regression of the AVMs. A craniotomy was performed for complete resection of the left parietal AVM. Histopathological features of the surgical specimen were examined. Active angiogenesis, as indicated by increased endothelial proliferation, might be a part of the underlying pathophysiology of the growth and regression of AVMs. PMID- 17367072 TI - Subarachnoid hemorrhage and diffuse vasculopathy in an adult infected with HIV. Case report. AB - This 34-year-old man with a 10-year history of HIV infection presented with an acute onset of severe headache, fever, nausea, vomiting, and left-sided weakness. Computed tomography (CT) scanning demonstrated diffuse subarachnoid hemorrhage (SAH), and subsequent CT angiography revealed multiple large and giant intracranial aneurysms with diffuse vasculopathy. The patient's CD4-positive cell count was low, although he had been receiving combination antiretroviral therapy and his viral load was undetectable. The preponderance of the literature on HIV infected patients with intracranial vascular involvement has concerned children in whom there is a high viral load. In such children, appropriate antiretroviral therapy may result in the complete resolution of these vascular abnormalities. In the present study, the authors report on the unique case of an HIV-infected adult patient who presented with SAH, diffuse intracranial vasculopathy, and multiple giant and fusiform aneurysms, despite having received adequate antiretroviral treatment and demonstrating an undetectable viral load. Intracranial vascular involvement in these patients may become increasingly common as the management of HIV infection continues to improve and afflicted patients survive for longer periods. PMID- 17367073 TI - Management of a retained catheter in an arteriovenous malformation. Case report. AB - The long-term effects of retained catheters in patients are not well known; therefore, the clinical presentation may differ. The authors present the case of a 21-year-old man with a pseudoaneurysm of the left common femoral artery, which developed 3 months after a transfemoral microcatheter embolization of a cerebral arteriovenous malformation (AVM) in which the catheter was inadvertently glued into the AVM and was retained at the groin. PMID- 17367074 TI - Successful "blind-alley" formation with bypass surgery for a partially thrombosed giant basilar artery tip aneurysm refractory to upper basilar artery obliteration. Case report. AB - Partially thrombosed giant aneurysms that are located at the basilar artery (BA) bifurcation and are not amenable to clip application are among the most challenging lesions for neurosurgeons. They compress vital structures such as the brainstem and the thalamus, and the prognosis is extremely poor when they are left untreated. Although obliteration of the upper BA is a promising approach for these aneurysms, some lesions are refractory to this treatment, and effective additional strategies have not been clearly established. The authors report a case treated by placement of clips in the unilateral posterior cerebral artery (PCA) and posterior communicating artery as well as by superficial temporal artery-PCA bypass after unsuccessful upper BA obliteration. Complete thrombosis and dramatic shrinkage of the aneurysm were obtained. PMID- 17367075 TI - Chromosome arm 1q gain associated with good response to chemotherapy in a malignant glioma. Case report. AB - The authors describe the case of a patient with a glioblastoma multiforme who showed remarkably good response to chemotherapy. A genetic analysis using comparative genomic hybridization (CGH) revealed that the tumor had a gain on the q arm of chromosome 1 (1q). Using CGH for a series of genetic analyses of more than 180 patients with gliomas, six were found to have a demonstrated 1q gain. Although the tumors in all six of these cases were histopathologically diagnosed as high-grade gliomas, compared with other malignant gliomas they demonstrated a good prognosis because of their favorable chemotherapeutic sensitivity. In immunohistochemical tests, most of the tumor cells in these cases were negative for O6-methylguanine-DNA methyltransferase, which antagonizes the effect of DNA alkylating chemotherapeutic agents. The authors believed that a gain of 1q could be produced through the genetic events that cause loss of 1p, because these chromosomal aberrations have an imbalance of DNA copy number in common (1p < 1q). A gain of 1q is an infrequent chromosomal aberration and its clinical importance should be investigated in a larger study; however, patients with malignant gliomas demonstrating a 1q gain possibly show longer survival and good response to chemotherapy similar to patients with tumors demonstrating 1p loss. The importance of using genetic analysis for gliomas is emphasized in this report because it may help in selecting cases responsive to chemotherapy and because appropriate treatment for these patients will lead to progress in the treatment of malignant gliomas. PMID- 17367076 TI - Electrocorticographically controlled brain-computer interfaces using motor and sensory imagery in patients with temporary subdural electrode implants. Report of four cases. AB - Brain-computer interface (BCI) technology can offer individuals with severe motor disabilities greater independence and a higher quality of life. The BCI systems take recorded brain signals and translate them into real-time actions, for improved communication, movement, or perception. Four patient participants with a clinical need for intracranial electrocorticography (ECoG) participated in this study. The participants were trained over multiple sessions to use motor and/or auditory imagery to modulate their brain signals in order to control the movement of a computer cursor. Participants with electrodes over motor and/or sensory areas were able to achieve cursor control over 2 to 7 days of training. These findings indicate that sensory and other brain areas not previously considered ideal for ECoG-based control can provide additional channels of control that may be useful for a motor BCI. PMID- 17367077 TI - Image-guided vascular neurosurgery based on three-dimensional rotational angiography. Technical note. AB - Three-dimensional rotational angiography is capable of exquisite visualization of cerebral blood vessels and their pathophysiology. Unfortunately, images obtained using this modality typically show a small region of interest without exterior landmarks to allow patient-to-image registration, precluding their use for neuronavigation purposes. The aim of this study was to find an alternative technique to enable 3D rotational angiography-guided vascular neurosurgery. Three dimensional rotational angiograms were obtained in an angiographic suite with direct navigation capabilities. After image acquisition, a navigated pointer was used to touch fiducial positions on the patient's head. These positions were located outside the image volume but could nevertheless be transformed into image coordinates and stored in the navigation system. Prior to surgery, the data set was transferred to the navigation system in the operating room, and the same fiducial positions were touched again to complete the patient-to-image registration. This technique was tested on a Perspex phantom representing the cerebral vascular tree and on two patients with an intracranial aneurysm. In both the phantom and patients, the neuronavigation system provided 3D images representing the vascular tree in its correct orientation, that is, the orientation seen by the neurosurgeon through the microscope. In one patient, tissue shift was clearly observed without significant changes in the orientation of the structures. Results in this study demonstrate the feasibility of using 3D rotational angiography data sets for neuronavigation purposes. Determining the benefit of this type of navigation should be the subject of future studies. PMID- 17367078 TI - Endoscopic identification and biopsy sampling of an intraventricular malignant glioma using a 5-aminolevulinic acid-induced protoporphyrin IX fluorescence imaging system. Technical note. AB - Several neurosurgical studies have provided descriptions of the utility of fluorescence-guided tumor resection using a microscope. However, fluorescence guided endoscopic detection of a deep-seated brain tumor has not yet been reported. The authors report their experience with an endoscopic biopsy procedure for a malignant glioma within the third ventricle using a 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence imaging system. A 5-ALA-induced fluorescence image of an intraventricular tumor is barely visible with the typical fluorescence endoscopic system used in other clinical fields because the intensity of excitation light at wavelengths of 390 to 405 nm through a cut-off filter is too weak to delineate a brain tumor. The technique described in this study made use of a laser illumination system with a high-powered output that delivered a violet-blue light at wavelengths of 405 nm. In addition, a common ultraviolet cutoff filter was fitted between the endoscope and the high sensitivity camera to block the backscattered excitation light. A 5-ALA-induced fluorescence endoscopy performed using this system allowed the intraventricular tumor to be clearly visualized as a red fluorescent lesion. Several biopsy specimens obtained from the fluorescent lesion provided a definitive histological diagnosis. The results indicate that this endoscopic system is useful in detecting an intraventricular fluorescent tumor. PMID- 17367079 TI - Successful treatment of aspergillus granuloma involving the cavernous sinus and the middle fossa by using surgery and voriconazole. Case illustration. PMID- 17367080 TI - Coil extrusion after endovascular treatment. Case illustration. PMID- 17367081 TI - Ruptured anterior communicating artery aneurysm and an anomalous circle of Willis. Case illustration. PMID- 17367082 TI - Recurrent subarachnoid hemorrhage after complete occlusion of a ruptured small necked, small vertebral artery-posterior inferior cerebellar artery aneurysm. Case illustration. PMID- 17367083 TI - Aneurysm-venous fistula formation following coil embolization of a basilar bifurcation aneurysm. Case illustration. PMID- 17367084 TI - Age and outcome. PMID- 17367085 TI - Intraoperative facial motor evoked potentials? PMID- 17367086 TI - Central or peripheral activations of the facial nerve? PMID- 17367087 TI - Superficial peroneal nerve. PMID- 17367088 TI - Can we continue to do business as usual? PMID- 17367089 TI - Opioid administration for acute abdominal pain in the pediatric emergency department. AB - The use of opioid analgesia for acute abdominal pain of unclear etiology has traditionally been thought to mask symptoms, alter physical exam findings, delay diagnosis, and increase morbidity and mortality. However, studies in children and adults have demonstrated that administering intravenous opioids to patients with acute abdominal pain induces analgesia but does not delay diagnosis or adversely affect diagnostic accuracy. This review discusses the effects of opioid administration on pain relief and diagnostic accuracy in children with moderate to severe acute abdominal pain who have been evaluated in the emergency department. We hold that current evidence supports the administration of opioids to children with acute abdominal pain, and future trials will help determine safe and effective timing and dosing related to opioid administration. PMID- 17367090 TI - Medicolegal rounds: medicolegal issues and alleged breaches of standards of medical care in a patient motor vehicle accident allegedly related to chronic opioid analgesic therapy. AB - The objective of this medicolegal case report is to present the details of the case of a chronic pain patient (CPP) who was placed on chronic opioid analgesic therapy (COAT) and was involved in a motor vehicle accident, alleged in litigation to be related to COAT. COAT standards are in a process of evolution, and this process is influenced by recent literature developments. We aim to present both the plaintiffs and defendant's expert witnesses' opinions on whether the defendant physician fell below the "standard" in allowing the CPP to drive. Both the methadone and the driving literature are utilized to explain the defendant's and plaintiffs experts' opinions and the differences between them. Based on these opinions, we have attempted to develop some recommendations on how pain physicians should approach the problem of deciding whether patients should be allowed to drive when on COAT. PMID- 17367091 TI - Morphine prescription in end-of-life care and euthanasia: French home nurses' opinions. AB - OBJECTIVE: This study aimed to investigate factors that might lead French homecare nurses to consider the prescription of high-dose morphine to terminally ill patients to be euthanasia. METHODS: The researchers conducted an anonymous telephone survey among a random sample of 602 French homecare nurses (response rate = 75 percent) in 2005. RESULTS: Overall, 27 percent of responding home nurses considered prescribing high-dose morphine to terminally ill patients to be euthanasia. Such an opinion was more frequently held by older nurses, those who had not followed terminally ill patients during the previous three years, and those with less knowledge about pain management involving opioid analgesics. CONCLUSION: There is an urgent need to strengthen pain management education among French homecare nurses--especially regarding the use of morphine--in order to both improve their technical skills and correct some misconceptions about opioid analgesics. PMID- 17367092 TI - Patterns of illicit drug use and retention in a methadone program: a longitudinal study. AB - OBJECTIVE: This study aimed to analyze illicit drug use of participants in a methadone treatment program in relation to methadone dose, counseling, and retention. METHODS: This was a longitudinal study of a cohort of 204 heroin dependent subjects admitted for the first time to a methadone program in Stockholm. The patients were admitted between 1995 and mid-2000 and were followed until December 2000 or discharge. Up to June 11, 1998, individual psychosocial counseling was provided; after this date individual counseling was replaced with group counseling. Clinical data were collected from patient records and from a laboratory database. Rates of drug-positive urine analyses during different time periods were measured. RESULTS: The mean observation time was 2.5 years for all patients. The one-year retention rate was 84 percent, and the two-year rate was 65 percent, with no major differences between the two counseling groups. Almost all patients relapsed to illicit drug use. Discharged patients had a significantly higher rate of positive urine samples (21 percent versus 9 percent) than patients who remained in treatment. Also, low methadone dose and younger age predicted discharge from treatment. CONCLUSION: The frequent urine monitoring showed that illicit drug use was rather common, even in a program with structured psychosocial interventions, although it was lower than in other studies. This testing policy can be used for early identification of patients at risk for drop out or discharge who should be offered complementary interventions. PMID- 17367094 TI - Buprenorphine: a unique opioid with broad clinical applications. AB - The analgesic potential of buprenorphine, a high-affinity partial mu agonist, has been a subject of study for several decades. The drug is now widely recognized as being extremely effective in relieving perioperative pain, with little of the addictive potential or risk associated with pure I agonists. Studies have suggested that buprenorphine produces adequate analgesia via almost any route of administration, including transdermal and subcutaneous. It has also been used, with positive results, in the treatment of opioid addiction, and potential remains for research into other roles, e.g., as an anti-inflammatory agent or an antihyperalgesic medication. PMID- 17367093 TI - A randomized, open-label, multicenter trial comparing once-a-day AVINZA (morphine sulfate extended-release capsules) versus twice-a-day OxyContin (oxycodone hydrochloride controlled-release tablets) for the treatment of chronic, moderate to severe low back pain: improved physical functioning in the ACTION trial. AB - This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA, A-MQD) and twice-daily controlled-release oxycodone HCI tablets (OxyContin, O-ER) in subjects with chronic, moderate to severe low back pain. After randomization and a period of opioid dose titration, subjects (n=266) underwent an eight-week evaluation phase and an optionalf our-month extension phase (n=174 in extension phase). Subjects were assessed using the 12-item Short Form Health Survey (SF-12) and the Work Limitations Questionnaire (WLQ). In both groups, significant improvements were observed in the SF-12 mean scores forp hysicalf unctioning (p < 0.001), role physical (p < 0.0001), bodilyp ain (p < 0.0001), physical summary (p < 0.001), and mental component summary (p < 0.005). At the end of the titration period, greater relative improvements from baseline were seen in the SF-12 section on physical components in the A-MQD group versus the O-ER group, with significant differences observed for physical functioning (p = 0.0374), role physical (p = 0.0341), bodily pain (p = 0.0001), andp hysical summary (p = 0.0022). In both groups, SF-12 mean scores improved significantly for mental health (p < 0.01), role emotional (p < 0.01), socialfunctioning (p < 0.0005), vitality (p < 0.005), and the mental component summary (p < 0.005), but no significant differences were noted between the two groups. Both groups reported improvement from baseline in WLQ physical demands scores, with no significant differences noted between the two groups. At the end of the evaluation phase, fewer subjects were unable to work due to illness or treatment in the A-MQD group than in the O-ER group (8.5 percent versus 19.4 percent, respectively; p = 0.0149). In conclusion, compared to twice-daily OxyContin, once daily A VINZA resulted in significantly better and earlier improvement ofp hysicalf unction and ability to work. PMID- 17367095 TI - Developmental pharmacokinetics of opioids in neonates. AB - Recognition and treatment of pain are now important indicators of the quality of care being delivered to neonates. However, population-specific characteristics have to be considered, necessitating an integrated, population-specific approach. Such an approach starts with a systematic evaluation ofpain, using a validated pain-assessment instrument, and should be followed by effective interventions, mainly based on appropriate, i.e., safe and effective, administration of analgesics. We will illustrate the impact of age on the pharmacokinetics and metabolism of opioids using recently collected and reported observations of tramadol disposition in early neonatal life. Although distribution volume and clearance display age-dependent maturation, it is important to recognize that important, unexplained interindividual variability in drug metabolism is still observed. Research questions in the field of developmental pharmacokinetics of opioids should focus on covariables of relevance in the interindividual variability of both pharmacokinetics and pharmacodynamics of opioids in neonates and on long-term outcomes in preterm and term neonates to whom opioids were administered, with regard to behavioral consequences and effects on pain thresholds. PMID- 17367096 TI - Structural and compositional control in {M12} cobalt and nickel coordination clusters detected magnetochemically and with cryospray mass spectrometry. PMID- 17367097 TI - Functional [6]pericyclynes: synthesis through [14+4] and [8+10] cyclization strategies. AB - Critical analysis of possible strategies for the synthesis of novel carbo-benzene derivatives suggests several [(18-n)+n] routes for the preparation of hexaoxy[6]pericyclyne precursors. Beyond the previously attempted [9+9] symmetrical scheme (n=9), the a priori most selective strategies are those for which n=1, 4, 7, 10, 13, and 16. They involve a cyclizing double-propargylation of a C(18-n) omega-bis-terminal-skipped oligoyne containing (19-n)/3 triple bonds with a C(n) omega-dicarbonyl-skipped oligoyne containing (n-1)/3 triple bonds. To complement the previously used [11+7] strategy, the [14+4] and [8+10] strategies were thus explored. They proved to be efficient, affording seven novel hexaoxy[6]pericyclynes corresponding to six different substitution patterns. These compounds were obtained in 7-15 steps as mixtures of stereoisomers. Thus, by using dibenzoylacetylene as the C(4) electrophile, a [14+4] strategy allowed the synthesis of two hexaphenyl representatives with two or four free carbinol vertices. This approach also afforded tetraphenyl representatives in which the two remaining carbinoxy vertices were substituted with either two alkynyl or one 4-anisyl and one 4-pyridyl groups. By using the hexacarbonyldicobalt complex of butynedial as the C(4) electrophile, a [14+4] strategy also allowed the isolation of a tetraphenylhexaoxy[6]pericyclyne with two adjacent unsubstituted carbinol vertices. A regioisomer with two opposite unsubstituted carbinol vertices was obtained through an [8+10] strategy and its oxidation afforded the corresponding pericyclynedione. Several attempts at synthesizing diphenylhexaoxy[6]pericyclynes with four unsubstituted carbinoxy vertices are described. Only an [8+10] strategy allowed the generation of a fragile diphenylhexaoxy[6]pericyclyne with four adjacent unsubstituted carbinoxy vertices, which could be partly characterized. These results show that the synthesis of the nonsubstituted hexahydroxy[6]pericyclyne, the ring carbo-mer of [6]cyclitol, is a difficult challenge. PMID- 17367098 TI - Functional [6]pericyclynes: aromatization to substituted carbo-benzenes. AB - Reductive treatment of stereoisomeric mixtures of variously substituted hexaoxy[6]pericyclynes with SnCl(2)/HCl led to the corresponding substituted carbo-benzenes. Tetramethoxyhexaphenyl[6]pericylynediol and dimethoxyhexaphenyl[6]pericyclynetetrol thus proved to be alternative precursors of hexaphenyl-carbo-benzene, previously described. Another hexaaryl-carbo benzenic chromophore with 4-pyridyl and 4-anisyl substituents was targeted for its second-order nonlinear optical properties and was obtained by aromatization of a dimethoxy[6]pericyclynetetrol. Two alkynyl substituents in para positions were also found to be compatible with the C(18) carbo-benzene ring, provided that the four remaining vertices are substituted by phenyl groups. In the protected series, bis(trimethylsilylethynyl)hexaphenyl-carbo-benzene (C(18)Ph(4)(C triple bond C-TMS)(2)) could be isolated and fully characterized, even by X-ray crystallography. In the bis-terminal series, the diethynylhexaphenyl-carbo benzene C(18)Ph(4)(C triple bond C-H)(2) could not be isolated in the pure form. It could, however, be generated by two different methods and identified by the corresponding (1)H NMR spectra. Unsubstituted carbo-benzene C(18)H(6) remains unknown, but tetraphenyl-carbo-benzenes C(18)Ph(4)H(2) with two unsubstituted vertices proved to be viable molecules. Whereas the "para" isomer could be characterized by MS and (1)H and (13)C NMR spectroscopy only in a mixture with polymeric materials, the "ortho" isomer (with adjacent CH vertices) could be isolated, and its structure was determined by using X-ray crystallography. The structure calculated at the B3PW91/6-31G** level of theory turned out to be in excellent agreement with the experimental structure. The (1)H and (13)C NMR chemical shifts of hexa- and tetraphenyl-carbo-benzenes were also calculated at the B3LYP/6-31+G** level of theory and were found to correlate with experimental spectra. The remote NMR deshielding of peripheral protons (through up to five bonds) revealed a very strong diatropic circulation around the C(18) ring, regardless of the substitution pattern. In full agreement with theoretical investigations, it has been demonstrated experimentally that the carbo-benzene ring is "independently" aromatic, in accord with structural-energetic and magnetic criteria. PMID- 17367099 TI - Inter- and intramolecular palladium-catalyzed allyl cross-coupling reactions using allylindium generated in situ from allyl acetates, indium, and indium trichloride. AB - Inter- and intramolecular palladium-catalyzed allyl cross-coupling reactions using allylindium generated in situ by treatment of allyl acetates with indium and indium trichloride in the presence of Pd(0) catalyst and nBuNMe(2) in DMF were successfully demonstrated. Allylindium species generated in situ by reductive transmetalation of pi-allylpalladium(II) complexes, obtained from a variety of allyl acetates in the presence of Pd(0) catalyst together with indium and indium trichloride, were found to be capable of acting as effective nucleophilic coupling partners in Pd-catalyzed cross-coupling reactions. A variety of allyl acetates such as but-1-en-3-yl acetate, crotyl acetate, and 2 methylallyl acetate afforded the corresponding allylic compounds in good yields in cross-coupling reactions. Various electrophilic cross-coupling partners such as aryl iodides and vinyl bromides and triflates participate in these reactions. Not only intermolecular but also intramolecular Pd-catalyzed cross-coupling reactions work equally well to produce the desired allylic coupling products in good yields. PMID- 17367100 TI - Formation of the active species of cytochrome p450 by using iodosylbenzene: a case for spin-selective reactivity. AB - The generation of the active species for the enzyme cytochrome P450 by using the highly versatile oxygen surrogate iodosylbenzene (PhIO) often produces different results compared with the native route, in which the active species is generated through O(2) uptake and reduction by NADPH. One of these differences that is addressed here is the deuterium kinetic isotope effect (KIE) jump observed during N-dealkylation of N,N-dimethylaniline (DMA) by P450, when the reaction conditions change from the native to the PhIO route. The paper presents a theoretical analysis targeted to elucidate the mechanism of the reaction of PhIO with heme, to form the high-valent iron-oxo species Compound I (Cpd I), and define the origins of the KIE jump in the reaction of Cpd I with DMA. It is concluded that the likely origin of the KIE jump is the spin-selective chemistry of the enzyme cytochrome P450 under different preparation procedures. In the native route, the reaction proceeds via the doublet spin state of Cpd I and leads to a low KIE value. PhIO, however, diverts the reaction to the quartet spin state of Cpd I, which leads to the observed high KIE values. The KIE jump is reproduced here experimentally for the dealkylation of N,N-dimethyl-4-(methylthio)aniline, by using intra-molecular KIE measurements that avoid kinetic complexities. The effect of PhIO is compared with N,N-dimethylaniline-N-oxide (DMAO), which acts both as the oxygen donor and the substrate and leads to the same KIE values as the native route. PMID- 17367101 TI - Posterior fossa malformation in fetuses: a report of 56 further cases and a review of the literature. AB - OBJECTIVE: The purposes of this study were to determine the outcome of fetuses diagnosed as having a posterior fossa abnormality (PFA) and to find out if there are associated features helpful in determining the prognosis. METHODS: This is a retrospective study of all posterior fossa abnormalities detected prenatally in our Units within the last 10 years. Fifty six patients were selected. Outcome data was collected from the Clinical Genetics Department records and the attending obstetrician or pediatrician. RESULTS: An enlarged cisterna magna (ECM, diameter greater than 10 mm at 18-23 gw) was detected in 22 fetuses, which was isolated in 14 cases. All the patients followed-up (n = 11) with isolated ECM were normal at birth (100%). Non-isolated ECM was present in 8 cases. Further information was available in 7, 5 (71%) of whom had a poor outcome. A Dandy Walker complex abnormality (DWC) was detected in 34 patients. The majority of them had a poor prognosis, 54% if isolated and 84% if non-isolated. CONCLUSIONS: Isolated ECM detected on prenatal scans has a favourable outcome, while DWC is associated with a very high chance of a poor prognosis. PMID- 17367102 TI - Second trimester prenatal ultrasound for the detection of pregnancies at increased risk of Down syndrome. AB - OBJECTIVE: To determine the association between second trimester ultrasound findings (genetic sonogram) and the risk of Down syndrome. METHODS: Prospective population-based cohort study of women who were at increased risk of chromosome abnormality based on serum screening. RESULTS: Overall 9244 women with singleton pregnancies were included, including 245 whose fetuses had Down syndrome. Overall, 15.3% of the women had an abnormal genetic sonogram, including 14.2% of pregnancies with normal fetuses and 53.1% of those with Down syndrome. If the genetic sonogram were normal, the risk that a woman had a fetus with Down syndrome was reduced (likelihood ratio 0.55 [95% CI 0.49, 0.62]) However, if the normal genetic sonogram were used to counsel these high-risk women that they could avoid amniocentesis, approximately half of the cases of Down syndrome (115 of 245) would have been missed. The isolated ultrasound soft markers were the most commonly observed abnormality. These were seen in a high proportion of Down syndrome fetuses (13.9%) and normal fetuses (9.3%). In the absence of a structural anomaly, the isolated ultrasound soft markers of choroid plexus cyst, echogenic bowel, renal pyelectasis, clenched hands, clinodactyly, two-vessel umbilical cord, short femur, and short humerus were not associated with Down syndrome. Nuchal fold thickening was a notable exception, as a thick nuchal fold raised the risk of Down syndrome even when it was seen without an associated structural anomaly. LIMITATIONS: All women included in this study were at high risk of Down syndrome based on serum screening, and thus the results of this study cannot be used as a basis to modify maternal age-related risk. CONCLUSIONS: The accuracy of the genetic sonogram is less than previously reported. The genetic sonogram should not be used as a sequential test following serum biochemistry, as this would substantially reduce the prenatal diagnosis of Down syndrome cases. In contrast to prior reports, most isolated soft markers were not associated with Down syndrome. PMID- 17367103 TI - Norman-Roberts syndrome: characterization of the phenotype in early fetal life. AB - PURPOSE: Our purpose is to describe the prenatal manifestation of Norman-Roberts syndrome and to expand the knowledge of the fetal phenotype of this rare condition. The recurrence in two sibs might contribute to the hypothesis of a recessive condition. METHODS: Three cases are presented in which the diagnosis was suggested by a prenatal ultrasound examination and confirmed by pathology of the fetuses, after termination of pregnancy. The major sign was the ultrasound detection of microcephaly at the 22nd and 23rd week of gestation. Fetal Magnetic Nuclear Resonance, the pathological examination with histological studies, was applied to arrive at the diagnosis of Norman-Roberts syndrome. CONCLUSION: To the best of our knowledge, this is the second description of prenatal cases of Norman Roberts syndrome. The combined clinical and pathological data is a contribution that might help to increase the identification of this rare condition and to correctly define the risk of its recurrence. PMID- 17367105 TI - Are counsellors' attitudes influencing pregnant women's attitudes and decisions on prenatal screening? AB - OBJECTIVES: It is generally recognised that choices concerning treatment or screening should be people's own, autonomous decisions. However, in the context of genetic counselling, many studies found that counsellors deviate from nondirectiveness, or that subjective norm influences behaviour. The present study aimed to investigate whether prenatal counsellors (midwives, gynaecologists) influence pregnant women's decisions and their attitudes regarding prenatal screening. It was hypothesised that uptake rates and attitudes would be associated with the counsellor's attitude toward prenatal screening. METHODS: Pregnant women attending their midwifery or gynaecology practice were asked to fill out postal questionnaires before and after they were offered prenatal screening for Down syndrome. Their prenatal counsellors also filled in a questionnaire. These questionnaires assessed attitudes toward prenatal screening and background variables. The study sample consisted of 945 pregnant women, being guided by 97 prenatal counsellors. RESULTS: Multilevel regression analyses revealed that neither uptake rates, nor attitude toward prenatal screening were significantly predicted by counsellors' attitudes toward prenatal screening. CONCLUSION: It is suggested that the advice these pregnant women were reported to have received, should rather be interpreted as an indication of shared decision making and social support than of social pressure and undesired influence. PMID- 17367106 TI - Outcome of chromosomally abnormal pregnancies in Lebanon: obstetricians' roles during and after prenatal diagnosis. AB - OBJECTIVES: To better understand obstetrician experiences in Lebanon when disclosing abnormal amniocentesis results. METHODS: Structured interviews with 38 obstetricians identified as caregivers from the American University of Beirut Medical Center Cytogenetics Laboratory database of patients with abnormal amniocentesis results between 1999 and 2005. RESULTS: Obstetricians were primarily male, Christian, and with an average of 14 years of experience. They reported doing most pre-amniocentesis counseling, including discussion of risk for common autosomal aneuplodies (95%), and procedure-related risk (95%). Obstetricians reported that 80% of patients at risk for aneuploidy underwent amniocentesis. The study population reported on 143 abnormal test results (124 autosomal abnormalities). When disclosing results, obstetricians reportedly discussed primarily physical and cognitive features of the diagnosis. They varied in levels of directiveness and comfort in providing information. Our records showed that 59% of pregnancies with sex chromosome abnormalities were terminated compared to 90% of those with autosomal aneuploidies; various reasons were proposed by obstetricians. CONCLUSIONS: This study is among the few to assess prenatal diagnosis practices in the Middle East, with a focus on the role of the obstetrician. Given the influence of culture and social norms on prenatal decision-making, it remains important to understand the various impacts on clinical practice in many nations. PMID- 17367107 TI - A new method for screening and determination of diuretics by on-line CE-ESI-MS. AB - A rapid, high-resolution and effective new method for analyzing 12 diuretics by CE-ESI-MS was established in this paper. Ten diuretics (except two neutral compounds) could be fast separated by CE with a DAD at 214 nm with a 20 kV voltage within 6 min, using a 50 microm id and 48.5 cm effective length uncoated fused-silica capillary in a 40 mM ammonium formate buffer (pH 9.40). CE was coupled to the mass spectrometer applying an orthogonal electrospray interface with a triple-tube sheath liquid arrangement. The sheath liquid was composed of isopropanol-water (1:1 v/v) containing 30 mM acetic acid with a flow rate of 4 microL/min. Mass spectrum was employed in the positive mode and both full scan mode and SIM scan mode were utilized. All 12 diuretics could be detected and confirmed by MS in a single analysis. Under optimized conditions, LODs for the 12 diuretics were in the range of 0.13-2.7 micromol/L at an S/N of 3, and the correlation coefficients R(2 )were between 0.9921 and 0.9978. The RDSs (n = 5) of the method was 0.24-0.94 % for migration times and 1.6-8.8 % for peak areas. The recoveries of spiked samples of 12 diuretics were between 72.4% and 118%. The real urine samples were injected directly for analysis, with only simple filtration through a 0.22 microm membrane filter in order to remove solid particles, which may cause capillary blockage. Based on the migration times and characteristic ions, the diuretics in urine samples were detected successfully. This CE-ESI-MS method for analyzing diuretics will hopefully be applied to doping control. PMID- 17367109 TI - Separation of Nile Blue-labelled fatty acids by CE with absorbance detection using a red light-emitting diode. AB - The separation of fatty acids derivatised with Nile Blue (NB) by CE with detection using a red light-emitting diode (LED) was examined. NB was selected as the derivatisation agent due to its high molar absorption coefficient of 76,000 M(-1) cm(-1) at 633 nm, making it well suited for sensitive absorbance detection using a red 635 nm LED. NB-labelled fatty acids were separated by both MEKC using SDS micelles, i-PrOH and n-BuOH and by NACE in a number of solvents including MeOH, EtOH and ACN. The sensitivity of NACE was superior to MEKC, with detection limits of 5x10(-7)-7x10(-7) M obtained for each acid, approximately 20 times lower than the MEKC method. The NACE detection limits are approximately 100 times lower than previous reports on the separation of fatty acids by CE using indirect absorbance detection, ten times lower than using indirect fluorescence detection and are inferior only to those obtained using precapillary derivatisation and direct fluorescence detection. The efficiency of the NACE method was also superior to MEKC and allowed the separation of unsaturated fatty acids to be examined, although it was not possible to baseline-resolve linoleic (C18:2) and linolenic (C18:3) acids in a reasonable time. The method was used to analyse the fatty acid profile of two edible oils, namely sunflower and sesame oils, after alkali hydrolysis, where it was possible to identify both the saturated and unsaturated fatty acids in each sample. PMID- 17367110 TI - Analysis of nitrosamines by capillary electrospray-high-field asymmetric waveform ion mobility spectrometry-MS with programmed compensation voltage. AB - Emerging disinfection by-products (DBPs) in drinking water are an important public health concern. Certain DBPs, such as nitrosamines, are probable carcinogens, and exposure to halogenated DBPs may lead to birth defects. It is difficult to obtain complete separation of nitrosamines by chromatographic techniques. Thus we explored high-field asymmetric waveform ion mobility spectrometry (FAIMS) as an alternative separation technique for the characterization of individual DBPs in a complex matrix. We first used ESI-FAIMS MS to separate four nitrosamines: N-nitrosodi-n-butylamine (NDBA), N-nitrosodi-n propylamine (NDPA), N-nitrosopiperidine (NPip), and N-nitrosodiethylamine (NDEA) in the compensation voltage (CV) spectra. The optimal CVs with a fixed dispersion voltage of -4000 V were found to be -1.2 V (NDBA), 2.7 V (NDPA), 7.5 V (NPip) and 10.1 V (NDEA). In addition, FAIMS-MS effectively reduced the chemical noise and dramatically improved the LODs by as much as tenfold compared to the conventional ESI-MS technique. To further improve sensitivity, an on-line CE system was used in combination with FAIMS-MS to take advantage of the higher ionization efficiency. The calibration curves for the four nitrosamines were linear over a range of 5 ng/mL to 1000 ng/mL with an r(2 )value of 0.9929 to 0.9992. To increase sample throughput, a multiple-injection strategy was developed, in which the CV values were preprogrammed so that the FAIMS device allowed different nitrosamines to pass through at selected time windows. The potential application of the proposed method was demonstrated for the analysis of drinking water samples spiked with nitrosamines. PMID- 17367112 TI - Measurement of conformational changes in the structure of transglutaminase on binding calcium ions using optical evanescent dual polarisation interferometry. AB - The conformational changes occurring when the protein transglutaminase binds calcium ions have been studied using the optical evanescent technique of dual polarization interferometry (DPI) implemented via a dual slab waveguide structure. Immobilized transglutaminase layers of 4-5 nm in thickness were obtained, which when challenged with calcium ions underwent a contraction of approximately 0.5 nm (depending on the concentration of calcium) and an increase in refractive index of approximately 1 x 10-2. The affinity constant for the calcium binding was found to be in the range of 0.95 +/- 0.2 mM. The results reported are in good agreement with those found in the literature obtained by other techniques. It has also been shown that the structural changes occurring during the binding event are considerably larger than the mass changes that take place; thus, DPI offers a potentially valuable method to study real-time structural changes occurring to proteins when they bind metal ions. PMID- 17367113 TI - Fragmentation characteristics of collision-induced dissociation in MALDI TOF/TOF mass spectrometry. AB - The identification of proteins by tandem mass spectrometry relies on knowledge of the products produced by collision-induced dissociation of peptide ions. Most previous work has focused on fragmentation statistics for ion trap systems. We analyzed fragmentation in MALDI TOF/TOF mass spectrometry, collecting statistics using a curated set of 2459 MS/MS spectra and applying bootstrap resampling to assess confidence intervals. We calculated the frequency of 18 product ion types, the correlation between both mass and intensity with ion type, the dependence of amide bond breakage on the residues surrounding the cleavage site, and the dependence of product ion detection on residues not adjacent to the cleavage site. The most frequently observed were internal ions, followed by y ions. A strong correlation between ion type and the mass and intensity of its peak was observed, with b and y ions producing the most intense and highest mass peaks. The amino acids P, W, D, and R had a strong effect on amide bond cleavage when situated next to the breakage site, whereas residues including I, K, and H had a strong effect on product ion observation when located in the peptide but not adjacent to the cleavage site, a novel observation. PMID- 17367114 TI - Relative quantification of stable isotope labeled peptides using a linear ion trap-Orbitrap hybrid mass spectrometer. AB - The quantitative analysis of complex biological samples has emerged as a key research area in the field of proteomics. Although quantitative proteomic experiments remain challenging, these strategies have been greatly facilitated by the development of newer high-performance mass spectrometers. In this work, we have evaluated the use of the LTQ-Orbitrap, a hybrid mass spectrometer in which a linear ion trap is coupled to an Orbitrap mass analyzer, for quantitative analyses. By analyzing a range of yeast protein standards, we found that the high mass accuracy, high resolution, large ion capacity, and large dynamic range of the LTQ-Orbitrap led to as much as a 4-5-fold improvement in the number and quality of the peptide ratio measurements compared to similar analyses done on the LTQ. We also successfully quantified protein expression differences that occur in metabolically labeled rat synapses during brain development to further demonstrate the suitability of the LTQ-Orbitrap for the comparative analysis of complex tissue samples. PMID- 17367115 TI - Analysis of lipids using 2,4,6-trihydroxyacetophenone as a matrix for MALDI mass spectrometry. AB - Lipids exhibit a broad range of chemical properties that make their analysis quite demanding. Today, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) represents a versatile tool in the field of lipid analysis, also offering the possibility for molecular structural identification using novel MALDI tandem time-of-flight (TOF/TOF) instrumentation. In this study, we evaluated 2,4,6-trihydroxyacetophenone (THAP) for the analysis of various lipid classes including neutral storage lipids (triacylglycerols), polar membrane lipids (glycerophospho- and sphingolipids), and glycosphingolipids. THAP proved to be a versatile matrix for the routine analysis of various lipids from biological samples ("lipidomics"). A sample preparation methodology was established using selective alkali salt doping for subsequent MS/MS experiments. Sodiated and lithiated molecules provided superior structural information on lipids (i.e., acyl group identification); thus, following this approach, both selective peak detection with high sensitivity and more reliable structural information were obtained simultaneously. PMID- 17367116 TI - Open air calibration with temperature compensation of a luminescence quenching based oxygen sensor for portable instrumentation. AB - This report addresses the task of calibrating an optical sensor for oxygen determination. Detailed analyses of the functional dependences from our measurement system results have been carried out with the additional aim of temperature compensation. As a result, an empirical calibration function has been successfully derived for the luminescent quenching-based oxygen sensor included in a self-designed portable instrument. This function also compensates for the temperature influence on the quenching luminescence process in the range from 0 to 45 degrees C. Moreover, the calibration procedure is extremely simple because only a single standard is needed. In fact, the oxygen measurement system can be calibrated with exposure to an open air atmosphere, and therefore, neither laboratory standards nor trained personnel are required. The method has been applied to a set of 11 units of the mentioned sensor (up to 24% oxygen concentration) giving an overall deviation between our calibrated system results and the laboratory standards of 0.3% oxygen concentration (calculated with 95% confidence level). The proposed calibration function has shown itself to be applicable for different sensing film thicknesses and luminophore concentrations using the same fittings parameter. Additionally, this function has been successfully applied to other oxygen dyes. Good agreement has also been found when the performance of the instrument was compared to a commercially available portable instrument based on an electrochemical sensor. We believe that this work could be an interesting finding for spreading the use of optical sensors for atmospheric oxygen determination in commercial measurement equipment for different purposes in confined working atmospheres, such as mines, undergrounds, warehouses, vehicles, and ships. PMID- 17367117 TI - Design for electrospray ionization-ion mobility spectrometry. AB - In this study, a new design for electrospray ionization ion mobility spectrometry (ESI-IMS) was developed. This design has two important differences in comparison to the present ESI-IMS systems. First, a few centimeters of the cell comprising the electrospray needle was located outside of the oven used for heating the IMS cell. This modification prevents prespray solvent evaporation problems such as needle clogging and disturbance of the electrospray process. Second, in addition to the drift gas, a counterflow of a heated gas (desolvation gas) was used between the counter electrode and the ion gate to speed up the desolvation process (Hill, H. H., Jr. Anal. Chem. 1998, 70, 4929-4938). This modification increased the solvent evaporation and resulted in decreasing the drift time, increasing the peak intensity and increasing the resolving power (RP) or enhancing the resolution for separation of two adjacent ion peaks. In this work, the ion mobility spectra of different compounds including ethion, malathion, metalaxyl, fenamifos, methylamine, triethylamine, tributhylamine, codeine, and morphine were obtained to confirm enhancing of the resolving power of the ion peaks by using the desolvation gas. Furthermore, the method has also been applied to obtain the figures of merit for ethion as a test compound. The linear dynamic range for ethion was in the range 50-1000 microg/L with a limit of quantification of the 50 microg/L. PMID- 17367118 TI - Chemoinformatics analysis identifies cytotoxic compounds susceptible to chemoresistance mediated by glutathione and cystine/glutamate transport system xc . AB - Glutathione detoxification has been broadly implicated in resistance to chemotherapy. This study explores the relationship between chemical structure and GSH-mediated chemoresistance. System xc-, the heterodimeric cystine/glutamate exchanger composed of SLC7A11 and SLC3A2, plays a role in maintaining cellular glutathione (GSH) levels. Previous results show that SLC7A11 expression negatively correlates with drug potency across the National Cancer Institute's 60 cell lines for compounds susceptible to GSH-mediated chemoresistance. The number of significant SLC7A11-drug correlations was much greater than those of other genes tested, suggesting that SLC7A11 plays a critical role. Approximately 15% of a curated set of 3045 compounds yielded significant negative SLC7A11 correlations. These compounds tend to contain structural features amenable to GSH reactivity, such as Mannich bases. In cell lines strongly expressing SLC7A11, the potency of selected compounds, was enhanced by inhibition of SLC7A11. This system provides a rapid screen for detecting susceptibility of anticancer drugs to GSH mediated resistance. PMID- 17367119 TI - Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. AB - Nelfinavir (NFV) is a currently available HIV-1 protease (PR) inhibitor. Patients in whom NFV treatment has failed predominantly carry D30N mutants of HIV-1 PRs if they have been infected with the subtype B virus. In contrast, N88S mutants of HIV-1 PRs predominantly emerge in patients in whom NFV treatment has failed and who carry the CRF01_AE virus. Both D30N and N88S confer resistance against NFV. However, it remains unclear why the nonactive site mutation N88S confers resistance against NFV. In this study, we examined the resistance mechanism through computational simulations. The simulations suggested that despite the nonactive site mutation, N88S causes NFV resistance by reducing interactions between PR and NFV. We also investigated why the emergence rates of D30N and N88S differ between subtype B and CRF01_AE HIV-1. The simulations suggested that polymorphisms of CRF01_AE PR are involved in the emergence rate of the drug resistant mutants. PMID- 17367121 TI - Application of the phosphoramidate ProTide approach to 4'-azidouridine confers sub-micromolar potency versus hepatitis C virus on an inactive nucleoside. AB - We report the application of our phosphoramidate ProTide technology to the ribonucleoside analogue 4'-azidouridine to generate novel antiviral agents for the inhibition of hepatitis C virus (HCV). 4'-Azidouridine did not inhibit HCV, although 4'-azidocytidine was a potent inhibitor of HCV replication under similar assay conditions. However 4'-azidouridine triphosphate was a potent inhibitor of RNA synthesis by HCV polymerase, raising the question as to whether our phosphoramidate ProTide approach could effectively deliver 4'-azidouridine monophosphate to HCV replicon cells and unleash the antiviral potential of the triphosphate. Twenty-two phosphoramidates were prepared, including variations in the aryl, ester, and amino acid regions. A number of compounds showed sub micromolar inhibition of HCV in cell culture without detectable cytotoxicity. These results confirm that phosphoramidate ProTides can deliver monophosphates of ribonucleoside analogues and suggest a potential path to the generation of novel antiviral agents against HCV infection. The generic message is that ProTide synthesis from inactive parent nucleosides may be a warranted drug discovery strategy. PMID- 17367120 TI - Quantitative conformationally sampled pharmacophore for delta opioid ligands: reevaluation of hydrophobic moieties essential for biological activity. AB - Recent studies have indicated several therapeutic applications for delta opioid agonists and antagonists. To exploit the therapeutic potential of delta opioids developing a structural basis for the activity of ligands at the delta opioid receptor is essential. The conformationally sampled pharmacophore (CSP) method (Bernard et al. J. Am. Chem. Soc. 2003, 125, 3103-3107) is extended here to obtain quantitative models of delta opioid ligand efficacy and affinity. Quantification is performed via overlap integrals of the conformational space sampled by ligands with respect to a reference compound. Iterative refinement of the CSP model identified hydrophobic groups other than the traditional phenylalanine residues as important for efficacy and affinity in DSLET and ICI 174 864. The obtained models for a structurally diverse set of peptidic and nonpeptidic delta opioid ligands offer good predictions with R2 values>0.9, and the predicted efficacy for a set of test compounds was consistent with the experimental values. PMID- 17367122 TI - Designing active template molecules by combining computational de novo design and human chemist's expertise. AB - We used a new software tool for de novo design, the "Molecule Evoluator", to generate a number of small molecules. Explicit constraints were a relatively low molecular weight and otherwise limited functionality, for example, low numbers of hydrogen bond donors and acceptors, one or two aromatic rings, and a small number of rotatable bonds. In this way, we obtained a collection of scaffold- or templatelike molecules rather than fully "decorated" ones. We asked medicinal chemists to evaluate the suggested molecules for ease of synthesis and overall appeal, allowing them to make structural changes to the molecules for these reasons. On the basis of their recommendations, we synthesized eight molecules with an unprecedented (not patented) yet simple structure, which were subsequently tested in a screen of 83 drug targets, mostly G protein-coupled receptors. Four compounds showed affinity for biogenic amine targets (receptor, ion channel, and transport protein), reflecting the training of the medicinal chemists involved. Apparently the generation of leadlike solutions helped the medicinal chemists to select good starting points for future lead optimization, away from existing compound libraries. PMID- 17367123 TI - Discovery and structure-activity relationships of piperidinone- and piperidine constrained phenethylamines as novel, potent, and selective dipeptidyl peptidase IV inhibitors. AB - Dipeptidyl peptidase IV (DPP4) inhibitors are emerging as a new class of therapeutic agents for the treatment of type 2 diabetes. They exert their beneficial effects by increasing the levels of active glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are two important incretins for glucose homeostasis. Starting from a high-throughput screening hit, we were able to identify a series of piperidinone- and piperidine-constrained phenethylamines as novel DPP4 inhibitors. Optimized compounds are potent, selective, and have good pharmacokinetic profiles. PMID- 17367125 TI - Puckering coordinates of monocyclic rings by triangular decomposition. AB - We describe a new method of describing the pucker of an N-member monocyclic ring using N - 3 parameters. To accomplish this, three ring atoms define a reference plane, and the remainder of the ring is decomposed into triangular flaps. The angle of incidence for each flap upon the reference plane is then measured. The combination of these angles is characteristic of the ring's pucker. This puckering coordinate system is compared to existing reduced parameter systems to describe rings using a cyclohexane molecule. We show that this method has the same descriptive power of previous systems while offering advantages in molecular simulations. PMID- 17367124 TI - Novel tricyclic compounds having acetylene groups at C-8a and cyano enones in rings A and C: highly potent anti-inflammatory and cytoprotective agents. AB - Novel C-8a functionalized tricyclic compounds having cyano enones in rings A and C have been synthesized and biologically evaluated. Among them, compounds with acetylene groups at C-8a show extremely high potency in in vitro and in vivo bioassays for anti-inflammatory and cytoprotective activities. Both in vitro and in vivo potencies are markedly higher than those of 2-cyano-3,12-dioxooleana 1,9(11)-dien-28-oic acid (CDDO), which is being evaluated as an anticancer drug in phase I clinical trials. PMID- 17367126 TI - Four new topological indices based on the molecular path code. AB - The sequence of all paths pi of lengths i = 1 to the maximum possible length in a hydrogen-depleted molecular graph (which sequence is also called the molecular path code) contains significant information on the molecular topology, and as such it is a reasonable choice to be selected as the basis of topological indices (TIs). Four new (or five partly new) TIs with progressively improved performance (judged by correctly reflecting branching, centricity, and cyclicity of graphs, ordering of alkanes, and low degeneracy) have been explored. (i) By summing the squares of all numbers in the sequence one obtains Sigmaipi(2), and by dividing this sum by one plus the cyclomatic number, a Quadratic TI is obtained: Q = Sigmaipi(2)/(mu+1). (ii) On summing the Square roots of all numbers in the sequence one obtains Sigmaipi(1/2), and by dividing this sum by one plus the cyclomatic number, the TI denoted by S is obtained: S = Sigmaipi(1/2)/(mu+1). (iii) On dividing terms in this sum by the corresponding topological distances, one obtains the Distance-reduced index D = Sigmai{pi(1/2)/[i(mu+1)]}. Two similar formulas define the next two indices, the first one with no square roots: (iv) distance-Attenuated index: A = Sigmai{pi/[i(mu + 1)]}; and (v) the last TI with two square roots: Path-count index: P = Sigmai{pi(1/2)/[i(1/2)(mu + 1)]}. These five TIs are compared for their degeneracy, ordering of alkanes, and performance in QSPR (for all alkanes with 3-12 carbon atoms and for all possible chemical cyclic or acyclic graphs with 4-6 carbon atoms) in correlations with six physical properties and one chemical property. PMID- 17367127 TI - Estimation of Kovats retention indices using group contributions. AB - We have constructed a group contribution method for estimating Kovats retention indices by using observed data from a set of diverse organic compounds. Our database contains observed retention indices for over 35,000 different molecules. These were measured on capillary or packed columns with polar and nonpolar (or slightly polar) stationary phases under isothermal or nonisothermal conditions. We neglected any dependence of index values on these factors by averaging observations. Using 84 groups, we determined two sets of increment values, one for nonpolar and the other for polar column data. For nonpolar column data, the median absolute prediction error was 46 (3.2%). For data on polar columns, the median absolute error was 65 (3.9%). While accuracy is insufficient for identification based solely on retention, it is suitable for the rejection of certain classes of false identifications made by gas chromatography/mass spectrometry. PMID- 17367128 TI - Crystal structure and physical properties of conducting molecular antiferromagnets with a halogen-substituted donor: (EDO-TTFBr2)2FeX4 (X = Cl, Br). AB - The crystal structure and physical properties of radical ion salts (EDO TTFBr2)2FeX4 (X = Cl, Br) based on halogen-substituted organic donor and magnetic anions are investigated, including the comparison with the isomorphous compounds (EDO-TTFBr2)2GaX4 with nonmagnetic anions. The crystal structure of these four salts consists of uniformly stacked donor molecules and tetrahedral counter anions, and the Br substituents of the donor molecules are connected to halide ligands of anions with remarkably short intermolecular atomic distances. These salts show metallic behavior around room temperature and undergo a spin-density wave transition in the low-temperature range, as confirmed with the divergence of the electron spin resonance (ESR) line width. Although close anion-anion contacts are absent in these salts, the FeCl4 salt undergoes an antiferromagnetic transition at TN = 4.2 K, and the FeBr4 salt shows successive magnetic transitions at TN = 13.5 K and TC2 = 8.5 K with a helical spin structure as a candidate for the ground state of the d-electron spins. The magnetoresistance of the FeCl4 salt shows stepwise anomalies, which are explained qualitatively using a pi-d interaction-based frustrated spin system model composed of the donor pi electron and the anion d-electron spins. Although on the ESR spectra of the FeX4 salts signals from the pi- and d-electron spins are separately observed, the line width of the pi-electron spins broadens under the temperature where the susceptibility deviates from the Curie-Weiss behavior, showing the presence of the pi-d interaction. PMID- 17367129 TI - A new chiral N,N',O-donor heteroscorpionate ligand. Structures of Ni2+, Cu2+, Zn2+ complexes and study of solution equilibria by means of 1H NMR/UV-vis titrations and EXSY NMR spectroscopy. AB - The N,N',O-heteroscorpionate ligand 1-(4-methoxy-3,5-dimethyl-pyridin-2-yl)-2 methyl-1-pyrazol-1-yl-propan-2-ol (LOH) was prepared in two high-yield steps. Complexes [M(LOH)2][MCl4] (M2+ = Cu2+ and Zn2+) and [M(LOH)2]Cl2 (M2+ = Ni2+ and Cu2+) were prepared and characterized by X-ray crystallography. The speciation in solution (methanol:water 95:5) of the M2+/LOH systems was investigated by means of spectrophotometric (Ni2+ and Cu2+) and 1H NMR (Zn2+) titrations. The beta1 and beta2 global formation constants for the [M(LOH)]2+ and [M(LOH)2]2+ species were obtained and are in agreement with the Irving-Williams series: Ni2+< Cu2+> Zn2+. The Zn2+/LOH system was studied by means of quantitative 1H-1H EXSY spectroscopy (300 K, mixing time = 0.2-0.8 s), which allows the description of the equilibria occurring between five octahedral [Zn(LOH)2]2+ structural isomers and tetrahedral [Zn(LOH)Cl]Cl species. Exchange constants kijex and associated rate constants kij suggest that two types of interconversion occur: octahedral-octahedral (faster) and octahedral-tetrahedral (slower). DFT calculations (B3LYP/6-311+G(d)) were employed to evaluate the relative stability of the [Zn(LOH)2]2+ isomers, which are comparable for the five complexes with a maximum energy difference of 6.3 kJ/mol. PMID- 17367130 TI - Crystal-to-crystal oxidative deprotonation of a di(micro-hydroxo) to a di(micro oxo) dimer of dimolybdenum units. AB - A crystal-to-crystal transformation of (DAniF)3Mo2(micro-OH)2Mo2(DAniF)3 (1) to (DAniF)3Mo2(micro-O)2Mo2(DAniF)3 (2), where DAniF is the anion (p-anisyl)NC(H)N(p anisyl), by dioxygen provides rare insight into the deprotonation process effected by dioxygen. In this dimolybdenum system, the conversion occurs without significant loss of crystallinity. Although no intermediates have been directly observed, a compound containing the [(DAniF)3Mo2(micro-OH)(micro-O)Mo2(DAniF)3]+ cation, a proposed intermediate, has been obtained independently. Possible pathways for the overall conversion of 1 to 2 are discussed. PMID- 17367131 TI - Oxidation of elemental gold in alcohol solutions. AB - Gold is designated as the noblest metal because of its chemical inertness. It is known to dissolve in cyanide solutions in the presence of air or H2O2 or in halogen-containing solutions, aqua regia being the most famous example. Herein, we report a unique thiol, especially 4-pyridinethiol (4-PS), assisted dissolution of Au in alcohol solutions. Although dissolution was found to be very selective for pyridinethiols, such a phenomenon is astonishing since thiols are commonly used as etch resists for Au and even 4-PS is extensively used as a surface modifier for Au. To gain further understanding of the dissolution process, the influence of the reaction conditions was extensively studied. On the basis of the obtained results, a mechanism for the dissolution reaction is proposed. Fascinatingly, by tuning of the reaction conditions, this phenomenon can be applied in selective preparation of self-supporting nanometer-thick Au foils. PMID- 17367132 TI - Pyrazole complexes as anion receptors: effects of changing the metal, the pyrazole substitution pattern, and the number of pyrazole ligands. AB - Compound cis,fac-[Mo(eta3-allyl)(CO)2(Hdmpz)3]BAr'4 (1) (Hdmpz = 3,5 dimethylpyrazole, Ar' = 3,5-bis(trifluoromethyl)phenyl) undergoes rapid substitution of one of the pyrazole ligands by anions, including the low nucleophilic ReO4-, a reaction that afforded [Mo(OReO3)(eta3-allyl)(CO)2(Hdmpz)2] (2), structurally characterized by X-ray diffraction. The new compounds fac [Mn(CO)3(Hdmpz)3]BAr'4 (4a) and fac-[Mn(CO)3(HtBupz)3]BAr'4 (4b) (HtBupz = 3(5) tert-butylpyrazole) also undergo pyrazole substitution with most anions, and the product from the reaction with nitrate was crystallographically characterized. Compounds 4a,b were found to be substitutionally stable toward perrhenate, and the adducts [Mn(CO)3(Hdmpz)3].[ReO4] (7a) and [Mn(CO)3(HtBupz)3].[ReO4].[Bu4N].[BAr'4] (7b), crystallographically characterized, display hydrogen bonds between one of the perrhenate oxygens and the N-H groups of two of the pyrazole ligands. The structurally similar adduct [Re(CO)3(Hdmpz)3].[ReO4] (8) was found to result from the interaction of [Re(CO)3(Hdmpz)3]BAr'4 with perrhenate. The reaction of [Re(OTf)(CO)5] with 3,5 dimethylpyrazole (Hdmpz) afforded [Re(CO)5(Hdmpz)]OTf (9). The reaction of 9 with Hdmpz and NaBAr'4 yielded [Re(CO)4(Hdmpz)2]BAr'4 (10), which was found to be unstable toward chloride anion. In contrast, the new compound fac,cis [Re(CO)3(CNtBu)(Hdmpz)2]BAr'4 (11) is stable in solution in the presence of different anions. Binding constants for 11 with chloride, bromide, and nitrate are 1-2 orders of magnitude lower than those found for these anions and rhenium tris(pyrazole) hosts, indicating that the presence of the third pyrazole ligand is crucial. Compounds fac-[Re(CO)3(HPhpz)3]BAr'4 (14) (HPhpz = 3(5) phenylpyrazole) and fac-[Re(CO)3(HIndz)3]BAr'4 (15) (HIndz = indazole) are, in terms of anion binding strength and selectivity, inferior to those with dimethylpyrazole or tert-butylpyrazole ligands. PMID- 17367134 TI - Gold-coated transition-metal anion [Mn13@Au20]- with ultrahigh magnetic moment. PMID- 17367133 TI - The catalytic Mn2+ sites in the enolase-inhibitor complex: crystallography, single-crystal EPR, and DFT calculations. AB - Crystals of Zn2+/Mn2+ yeast enolase with the inhibitor PhAH (phosphonoacetohydroxamate) were grown under conditions with a slight preference for binding of Zn2+ at the higher affinity site, site I. The structure of the Zn2+/Mn2+-PhAH complex was solved at a resolution of 1.54 A, and the two catalytic metal binding sites, I and II, show only subtle displacement compared to that of the corresponding complex with the native Mg2+ ions. Low-temperature echo-detected high-field (W-band, 95 GHz) EPR (electron paramagnetic resonance) and 1H ENDOR (electron-nuclear double resonance) were carried out on a single crystal, and rotation patterns were acquired in two perpendicular planes. Analysis of the rotation patterns resolved a total of six Mn2+ sites, four symmetry-related sites of one type and two out of the four of the other type. The observation of two chemically inequivalent Mn2+ sites shows that Mn2+ ions populate both sites I and II and the zero-field splitting (ZFS) tensors of the Mn2+ in the two sites were determined. The Mn2+ site with the larger D value was assigned to site I based on the 1H ENDOR spectra, which identified the relevant water ligands. This assignment is consistent with the seemingly larger deviation of site I from octahedral symmetry, compared to that of site II. The ENDOR results gave the coordinates of the protons of two water ligands, and adding them to the crystal structure revealed their involvement in a network of H bonds stabilizing the binding of the metal ions and PhAH. Although specific hyperfine interactions with the inhibitor were not determined, the spectroscopic properties of the Mn2+ in the two sites were consistent with the crystal structure. Density functional theory (DFT) calculations carried out on a cluster representing the catalytic site, with Mn2+ in site I and Zn2+ in site II, and vice versa, gave overestimated D values on the order of the experimental ones, although the larger D value was found for Mn2+ in site II rather than in site I. This discrepancy was attributed to the high sensitivity of the ZFS parameters to the Mn-O bond lengths and orientations, such that small, but significant, differences between the optimized and crystal structures alter the ZFS considerably, well above the difference between the two sites. PMID- 17367135 TI - Understanding the molecular basis for the inhibition of the Alzheimer's Abeta peptide oligomerization by human serum albumin using saturation transfer difference and off-resonance relaxation NMR spectroscopy. AB - Human serum albumin (HSA) inhibits the formation of amyloid beta-peptide (Abeta) fibrils in human plasma. However, currently it is not known how HSA affects the formation of the highly toxic soluble diffusible oligomers that occur in the initial stages of Abeta fibrillization. We have therefore investigated by solution NMR the interaction of HSA with the Abeta(12-28) peptide, which has been previously shown to provide a reliable and stable model for the early prefibrillar oligomers as well as to contain key determinants for the recognition by albumin. For this purpose we propose a novel NMR approach based on the comparative analysis of Abeta in its inhibited and filtrated states monitored through both saturation transfer difference and recently developed nonselective off-resonance relaxation experiments. This combined NMR strategy reveals a mechanism for the oligomerization inhibitory function of HSA, according to which HSA targets preferentially the soluble oligomers of Abeta(12-28) rather than its monomeric state. Specifically, HSA caps the exposed hydrophobic patches located at the growing and/or transiently exposed sites of the Abeta oligomers, thereby blocking the addition of further monomers and the growth of the prefibrillar assemblies. The proposed model has implications not only for the pharmacological treatment of Alzheimer's disease specifically but also for the inhibition of oligomerization in amyloid-related diseases in general. In addition, the proposed NMR approach is expected to be useful for the investigation of the mechanism of action of other oligomerization inhibitors as well as of other amyloidogenic systems. PMID- 17367136 TI - Solution-phase structure of an artificial foldamer: X-ray scattering study. PMID- 17367137 TI - Electrical switching and phase transformation in silver selenide nanowires. PMID- 17367138 TI - Mechanism-based inactivation of benzoylformate decarboxylase, a thiamin diphosphate-dependent enzyme. PMID- 17367139 TI - Protonation of a histidine copper ligand in fern plastocyanin. AB - Plastocyanin is a small blue copper protein that shuttles electrons as part of the photosynthetic redox chain. Its redox behavior is changed at low pH as a result of protonation of the solvent-exposed copper-coordinating histidine. Protonation and subsequent redox inactivation could have a role in the down regulation of photosynthesis. As opposed to plastocyanin from other sources, in fern plastocyanin His90 protonation at low pH has been reported not to occur. Two possible reasons for that have been proposed: pi-pi stacking between Phe12 and His90 and lack of a hydrogen bond with the backbone oxygen of Gly36. We have produced this fern plastocyanin recombinantly and examined the properties of wild type protein and mutants Phe12Leu, Gly36Pro, and the double mutant with NMR spectroscopy, X-ray crystallography, and cyclic voltammetry. The results demonstrate that, contrary to earlier reports, protonation of His90 in the wild type protein does occur in solution with a pKa of 4.4 (+/-0.1). Neither the single mutants nor the double mutant exhibit a change in protonation behavior, indicating that the suggested interactions have no influence. The crystal structure at low pH of the Gly36Pro variant does not show His90 protonation, similar to what was found for the wild-type protein. The structure suggests that movement of the imidazole ring is hindered by crystal contacts. This study illustrates a significant difference between results obtained in solution by NMR and by crystallography. PMID- 17367140 TI - Polydiacetylene nanofibers created in low-molecular-weight gels by post modification: control of blue and red phases by the odd-even effect in alkyl chains. PMID- 17367141 TI - Dynamic DNA templates for discrete gold nanoparticle assemblies: control of geometry, modularity, write/erase and structural switching. PMID- 17367143 TI - A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry. PMID- 17367142 TI - Total syntheses of (+)-lyconadin A and (-)-lyconadin B. PMID- 17367144 TI - Photosensitized NO release from water-soluble nanoparticle assemblies. PMID- 17367145 TI - Quantitative molecular ensemble interpretation of NMR dipolar couplings without restraints. PMID- 17367147 TI - Structure elucidation and enantioselective total synthesis of the potent HMG-CoA reductase inhibitor FR901512 via catalytic asymmetric Nozaki-Hiyama reactions. PMID- 17367151 TI - p-Nitromandelic acid as a highly acid-stable safety-catch linker for solid-phase synthesis of peptide and depsipeptide acids. AB - [reaction: see text] p-Nitromandelic acid as a safety-catch linker for Boc/Bzl SPPS of base-labile compounds like peptides and depsipeptides is described. This linker permits acidic removal of side-chain protection groups from the resin. For cleavage from the solid support, the p-nitro group was reduced with tin(II) chloride. After washing off the reducing agents, the (depsi)peptide acids with or without the side-chain protection schemes were obtained by microwave irradiation at 50 degrees C with 5% TFA in dioxane. PMID- 17367152 TI - Enantioselective total synthesis of macrolide antitumor agent (-)-lasonolide A. AB - [structure: see text] An enantioselective total synthesis of (-)-lasonolide A is described. The upper tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3-dipolar cycloaddition reaction. The bicyclic isooxazoline led to the tetrahydropyran ring as well as the quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a catalytic asymmetric hetero-Diels-Alder reaction as the key step. Three stereocenters were enantioselectively installed in this single step reaction. PMID- 17367153 TI - Stereochemical and skeletal diversity employing pipecolate ester scaffolds. AB - [structure: see text] The stereocontrolled synthesis of pyridooxazinones by Mg(OTf)2-promoted epoxide ring-opening with use of chiral pipecolates as nucleophiles is described. Pyridooxazinone products derived from azido-epoxides can be further rearranged to seven-membered pyridodiazepinones by azide reduction. The sequence of functional group interconversions generates diversity through topological and stereochemical variation. PMID- 17367154 TI - Enantioselective 1,3-dipolar cycloadditions of diazoacetates with electron deficient olefins. AB - [reaction: see text] A general strategy for highly enantioselective 1,3-dipolar cycloaddition of diazoesters to beta-substituted, alpha-substituted, and alpha,beta-disubstituted alpha,beta-unsaturated pyrazolidinone imides is described. Cycloadditions utilizing less reactive alpha,beta-disubstituted dipolarophiles require elevated reaction temperatures, but still provide the corresponding pyrazolines with excellent enantioselectivities. Finally, an efficient synthesis of (-)-manzacidin A employing this cycloaddition methodology as a key step is illustrated. PMID- 17367155 TI - Total synthesis of N14-desacetoxytubulysin H. AB - [reaction: see text] The N14-desacetoxy analogue of tubulysin H was prepared in 20 steps and 2.1% overall yield. Our strategy features a thiazole anion addition to assemble the tubuvaline residue at the C(10)-C(11) bond, as well as acylations at N5, N14, and N17. This iterative coupling approach, as well as the removal of the labile N,O-acetal at N14, enables the synthesis of analogues for detailed studies of structure-activity relationships in this family of potent tubulin disrupters. PMID- 17367156 TI - Aminomethylations via cross-coupling of potassium organotrifluoroborates with aryl bromides. AB - [reaction: see text] The Suzuki-Miyaura cross-coupling reaction of N,N dialkylaminomethyltrifluoroborates with aryl halides allows the construction of an aminomethyl aryl linkage through a disconnection based on dissonant reactivity patterns. A variety of these aminomethyltrifluoroborate substrates were prepared in good to excellent yields and then shown to cross-couple with equal facility to both electron-rich and electron-poor aryl halides as well as to a variety of heteroaromatic bromides. PMID- 17367157 TI - Weight gain reduction in mice fed Panax ginseng saponin, a pancreatic lipase inhibitor. AB - Roots of the herb Panax ginseng are known to contain high levels of bioactive saponins. Here, we isolated saponins from ginseng root powder and studied their inhibitory effect on the absorption of dietary fat in male Balb/c mice. Consumption of ginseng saponins suppressed the expected increase in body weight and plasma triacylglycerols, following a high-fat diet and observed higher intake. Consumption of ginseng saponins had no effect on the concentration of the total plasma cholesterol in both chow and high-fat diets in mice. The mode by which saponins from ginseng inhibit lipid metabolism was assessed as the in vitro inhibition of pancreatic lipase. Ginseng saponin inhibited pancreatic lipase with an apparent IC50 value of 500 mug/mL. Our results suggest that the anti-obesity and hypolipidemic effects of Ginseng in high-fat diet-treated mice were attributed to the isolated saponin fraction. These metabolic effects of the ginseng saponins may be mediated by inhibition of pancreatic lipase activity. PMID- 17367158 TI - Ascorbic acid-containing whey protein film coatings for control of oxidation. AB - A formulation for the whey protein isolate film or coating incorporating ascorbic acid (AA-WPI film or coating) was developed. Tensile and oxygen-barrier properties of the AA-WPI film were measured. Antioxidant effects of the AA-WPI coating on roasted peanuts were studied by comparing the values of peroxide (PO), thiobarbituric acid reactive substance (TBARS), and free-radical-scavenging activity, determined with noncoated peanuts and peanuts coated with WPI with and without ascorbic acid during storage at 21% relative humidity (RH) and 23, 35, and 50 degrees C. The incorporation of AA reduced elongation of WPI films. The oxygen-barrier property of the WPI film was significantly improved by incorporation of AA. The AA-WPI coating retarded lipid oxidation in peanuts significantly at 23, 35, and 50 degrees C. The AA-WPI coated peanuts were more red than noncoated peanuts at all storage temperatures. PMID- 17367159 TI - QSAR study for the soybean 15-lipoxygenase inhibitory activity of organosulfur compounds derived from the essential oil of garlic. AB - In this study, multiple linear regression (MLR) and partial least-squares (PLS) techniques were used for modeling the soybean 15-lipoxygenase inhibitory activity of a varied group of mono-, di-, and trisulfides derived from the essential oil of garlic. The structures of the compounds under study were characterized by means of calculated physicochemical parameters and several nonempirical descriptors, such as topological, geometrical, and quantum chemical indices. The results obtained indicate that the inhibitory activity is strongly dependent on the ability of the compounds to participate in dispersive interactions with the enzyme, as expressed by the solvent-accessible surface area (SASA) and the average distance/distance degree descriptor (ADDD) index. On the other hand, the high contribution of the lowest unoccupied molecular orbit term (LUMO) in the PLS models derived for the di- and trisulfides suggests that the solute's electron acceptor capacity plays a fundamental role in the inhibitory activity exhibited for these compounds. Finally, the geometric features as expressed by the shape parameters included in the models indicate a low but not negligible positive contribution of molecular linearity in the enzyme-inhibitor binding. In summary, the developed quantitative structure-activity relationship approach successfully accounts for the potencies of organosulfur compounds acting on soybean 15 lipoxygenase and thereby offers both a guide for the synthesis of new compounds and a hypothesis for the molecular basis of their activity. PMID- 17367160 TI - Aroma components of acid-hydrolyzed vegetable protein made by partial hydrolysis of rice bran protein. AB - Hydrolyzed vegetable protein (HVP) was prepared from rice bran protein concentrate (RBPc) by partial hydrolysis with aqueous 0.5 N HCl at 95 degrees C for 12 or 36 h (H-RBPc-12 and H-RBPc-36, respectively). Aroma components of the RBPc and the HVPs were characterized by gas chromatography-olfactometry, gas chromatography-mass spectrometry, aroma extract dilution analysis, and calculation of odor activity values (OAVs). The predominant odorants in RBPc were 3-methylbutanal, hexanal, 2-aminoacetophenone, (E)-2-nonenal, phenylacetaldehyde, and beta-damascenone. Among these, the odor of 2-aminoacetophenone, present at 59 ng/g in RBPc, was reminiscent of the typical odor of RBPc. Most of the predominant odorants had higher log3FD factors in the H-RBPc-36 as compared to H RBPc-12. Aroma impact compounds of H-RBPc-12 and H-RBPc-36 were 2-methoxyphenol (guaiacol), 4-hydroxy-2,5-dimethyl-3(2H)furanone, 3-hydroxy-4,5-dimethyl 2(5H)furanone (sotolon), vanillin, 3-methylbutanal, (E)-2-nonenal, 4-vinyl-2 methoxyphenol (p-vinylguaiacol), and beta-damascenone. Guaiacol had the highest OAV values of 2770 and 17650 in H-RBPc-12 and H-RBPc-36, respectively. PMID- 17367161 TI - The metabolic fate of purified glucoraphanin in F344 rats. AB - Dietary broccoli is commonly eaten cooked, exposing individuals to intact glucoraphanin rather than to its hydrolysis product, the anticarcinogenic isothiocyanate sulforaphane, since cooking destroys the hydrolyzing enzyme myrosinase. There is little information on the absorption and metabolism of glucoraphanin, due partly to the lack of purified compound. In this study, glucoraphanin was purified from broccoli seed and 150 mumol/kg was administered to male F344 rats. Glucoraphanin (5% of an oral dose) was recovered intact in urine, showing that it is absorbed intact, and no glucoraphanin or metabolites were found in feces. Total urinary products accounted for 20 and 45% of oral and intraperitonneal doses, respectively, including sulforaphane N-acetyl cysteine conjugate (12.5 and 2%), free sulforaphane (0.65 and 0.77%), sulforaphane nitrile (2 and 1.4%), and erucin (0.1 and 0.1%), respectively. Both glucoraphanin and its reduced form glucoerucin were identified in bile following intravenous glucoraphanin administration. We conclude that orally administered glucoraphanin is absorbed intact, undergoes enterohepatic circulation, and is hydrolyzed in the gut in F344 rats. PMID- 17367162 TI - Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. AB - Efflux pump (e.g., P-gp, MRP1, and BCRP) inhibition has been recognized as a strategy to overcome multi-drug resistance and improve drug bioavailability. Besides small-molecule inhibitors, surfactants such as Tween 80, Cremophor EL, several Pluronics, and Vitamin E TPGS (TPGS 1000) are known to modulate efflux pump activity. Competitive inhibition of substrate binding, alteration of membrane fluidity, and inhibition of efflux pump ATPase have been proposed as possible mechanisms. Focusing on TPGS 1000, the aim of our study was to unravel the inhibitory mechanism by comparing the results of inhibition experiments in a Caco-2 transport assay with data from electron spin resonance (ESR) and from ATPase activity studies. ESR results, on Caco-2 cells using 5-doxyl stearic acid (5-SA) as a spin probe, ruled out cell membrane fluidization as a major contributor; change of membrane fluidity was only observed at surfactant concentrations 100 times higher than those needed to achieve full efflux inhibition. Concurrently, TPGS 1000 inhibited substrate induced ATPase activity without inducing significant ATPase activity on its own. By investigating TPGS analogues that varied by their PEG chain length, and/or possessed a modified hydrophobic core, transport studies revealed that modulation of ATPase activity correlated with inhibitory potential for P-gp mediated efflux. Hence, these results indicate that ATPase inhibition is an essential factor in the inhibitory mechanism of TPGS 1000 on cellular efflux pumps. PMID- 17367163 TI - trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. AB - The catalytic domain of the flavin-dependent human histone demethylase lysine specific demethylase 1 (LSD1) belongs to the family of amine oxidases including polyamine oxidase and monoamine oxidase (MAO). We previously assessed monoamine oxidase inhibitors (MAOIs) for their ability to inhibit the reaction catalyzed by LSD1 [Lee, M. G., et al. (2006) Chem. Biol. 13, 563-567], demonstrating that trans-2-phenylcyclopropylamine (2-PCPA, tranylcypromine, Parnate) was the most potent with respect to LSD1. Here we show that 2-PCPA is a time-dependent, mechanism-based irreversible inhibitor of LSD1 with a KI of 242 microM and a kinact of 0.0106 s-1. 2-PCPA shows limited selectivity for human MAOs versus LSD1, with kinact/KI values only 16-fold and 2.4-fold higher for MAO B and MAO A, respectively. Profiles of LSD1 activity and inactivation by 2-PCPA as a function of pH are consistent with a mechanism of inactivation dependent upon enzyme catalysis. Mass spectrometry supports a role for FAD as the site of covalent modification by 2-PCPA. These results will provide a foundation for the design of cyclopropylamine-based inhibitors that are selective for LSD1 to probe its role in vivo. PMID- 17367164 TI - Loop 2 of limulus myosin III is phosphorylated by protein kinase A and autophosphorylation. AB - Little is known about the functions of class III unconventional myosins although, with an N-terminal kinase domain, they are potentially both signaling and motor proteins. Limulus myosin III is particularly interesting because it is a phosphoprotein abundant in photoreceptors that becomes more heavily phosphorylated at night by protein kinase A. This enhanced nighttime phosphorylation occurs in response to signals from an endogenous circadian clock and correlates with dramatic changes in photoreceptor structure and function. We seek to understand the role of Limulus myosin III and its phosphorylation in photoreceptors. Here we determined the sites that become phosphorylated in Limulus myosin III and investigated its kinase, actin binding, and myosin ATPase activities. We show that Limulus myosin III exhibits kinase activity and that a major site for both protein kinase A and autophosphorylation is located within loop 2 of the myosin domain, an important actin binding region. We also identify the phosphorylation of an additional protein kinase A and autophosphorylation site near loop 2, and a predicted phosphorylation site within loop 2. We show that the kinase domain of Limulus myosin III shares some pharmacological properties with protein kinase A, and that it is a potential opsin kinase. Finally, we demonstrate that Limulus myosin III binds actin but lacks ATPase activity. We conclude that Limulus myosin III is an actin-binding and signaling protein and speculate that interactions between actin and Limulus myosin III are regulated by both second messenger mediated phosphorylation and autophosphorylation of its myosin domain within and near loop 2. PMID- 17367165 TI - Mechanism of specific membrane targeting by C2 domains: localized pools of target lipids enhance Ca2+ affinity. AB - The C2 domain is a ubiquitous, conserved protein signaling motif widely found in eukaryotic signaling proteins. Although considerable functional diversity exists, most C2 domains are activated by Ca2+ binding and then dock to a specific cellular membrane. The C2 domains of protein kinase Calpha (PKCalpha) and cytosolic phospholipase A2alpha (cPLA2alpha), for example, are known to dock to different membrane surfaces during an intracellular Ca2+ signal. Ca2+ activation targets the PKCalpha C2 domain to the plasma membrane and the cPLA2alpha C2 domain to the internal membranes, with no detectable spatial overlap. It is crucial to determine how such targeting specificity is achieved at physiological bulk Ca2+ concentrations that during a typical signaling event rarely exceed 1 muM. For the isolated PKCalpha C2 domain in the presence of physiological Ca2+ levels, the target lipids phosphatidylserine (PS) and phosphatidylinositol-4,5 bisphosphate (PIP2) are together sufficient to recruit the PKCalpha C2 domain to a lipid mixture mimicking the plasma membrane inner leaflet. For the cPLA2alpha C2 domain, the target lipid phosphatidylcholine (PC) appears to be sufficient to drive membrane targeting to an internal membrane mimic at physiological Ca2+ levels, although the results do not rule out a second, unknown target molecule. Stopped-flow kinetic studies provide additional information about the fundamental molecular events that occur during Ca2+-activated membrane docking. In principle, C2 domain-directed intracellular targeting, which requires coincidence detection of multiple signals (Ca2+ and one or more target lipids), can exhibit two different mechanisms: messenger-activated target affinity (MATA) and target activated messenger affinity (TAMA). The C2 domains studied here both utilize the TAMA mechanism, in which the C2 domain Ca2+ affinity is too low to be activated by physiological Ca2+ signals in most regions of the cell. Only when the C2 domain nears its target membrane, which provides a high local concentration of target lipid, is the effective Ca2+ affinity increased by the coupled binding equilibrium to a level that enables substantial Ca2+ activation and target docking. Overall, the findings emphasize the importance of using physiological ligand concentrations in targeting studies because super-physiological concentrations can drive docking interactions even when an important targeting molecule is missing. PMID- 17367166 TI - Diffusive motions control the folding and unfolding kinetics of the apomyoglobin pH 4 molten globule intermediate. AB - The sperm whale apomyoglobin pH 4 folding intermediate exists in two forms, Ia and Ib, that mimic transient kinetic intermediates in the folding of the native protein at pH 6. To characterize the nature of the kinetic barrier that controls the formation of the earliest intermediate Ia, we have investigated the effects of small viscogenic cosolvents on its folding and unfolding kinetics. The kinetics are measurable by stopped-flow fluorescence and follow a cooperative two state model in the absence and presence of cosolvents. Small cosolvents stabilize Ia, but, by applying the isostability test to separate the viscogenic effect of the cosolvent from its stabilizing effect, we found that, in both folding and unfolding conditions, the apparent rate constant decreases when solvent viscosity increases. The unitary inverse dependence of the apparent rate constant on solvent viscosity indicates a diffusion-controlled reaction. This result is consistent with the hypothesis that folding of the apomyoglobin pH 4 intermediate obeys a diffusion-collision model. Additionally, the temperature dependence of the reaction rate at constant viscosity indicates that the formation of Ia is also controlled by an energy barrier. Linear free energy relationships show that the transition state of the U <==> Ia reaction is compact and buries 45% of the surface area that is buried in native apomyoglobin. We conclude that the transition state of the U <==> Ia reaction resembles that for the formation of native proteins; namely, it is dry and its compactness is closer to that of the folded (Ia) form than of the unfolded form. PMID- 17367167 TI - Energetics of electron-transfer reactions in soft condensed media. AB - The coupling of electronic transitions within molecules to condensed-phase media involves a complex hierarchy of spatial and dynamical scales. Thermodynamics of activation is related to the length scale of microscopic interactions reflected in the non-Arrhenius reaction kinetics. Solvent dynamics make a particularly strong impact on the activation barrier when the time scale of the reaction is comparable to the relaxation time of the solvent, and the reaction barrier becomes nonergodic. Finally, molecular polarizability is responsible for complex nonparabolic free energy surfaces for electron transfer. We discuss the application of these ideas to soft condensed solvents such as supercooled liquids, liquid crystals, and photosynthetic reaction centers. PMID- 17367168 TI - Apparent microrheology of oil-water interfaces by single-particle tracking. AB - We investigate the dynamics of charged microparticles at polydimethylsiloxane (oil)-water interfaces using Pickering emulsions as an experimental template. The mobility of the charged particles depends largely on the viscoelastic properties of the oil phase and the wettability of the solid particles. In addition, we have explored the potential of developing microrheology at liquid-liquid interfaces from the single-particle tracking technique. The apparent loss modulus, storage modulus, and relaxation time of the oil-water interfaces obtained from singe particle microrheology depend strongly on the surface nature of the tracer particles, especially when the oil phase is viscoelastic. PMID- 17367169 TI - Adsorption of hydrophobically modified poly(acrylamide)-co-(acrylic acid) on an amino-functionalized surface and its response to the external solvent environment. AB - The adsorption of hydrophobically modified poly(acrylamide)-co-(acrylic acid), designated as PAM-C14-AA (x%) (x = 5, 10, 20, representing the mole percent of acrylic acid units), at an amino-functionalized silicon surface was studied. The effect of polymer charge density was determined by varying the acrylic acid content of the copolymer. Characteristics of the adsorbed layer were evaluated by atomic force microscopy, water contact angle measurements, and X-ray photoelectron spectroscopy. The results showed that the adsorption behavior of PAM-C14-AA (x%) is influenced by the balance among the electrostatic, hydrogen bonding, and hydrophobic interactions. Adjusting the solution pH and polymer charge density significantly affects the morphology and thickness of the adsorbed film. Furthermore, it was found that the adsorbed PAM-C14-AA undergoes conformational rearrangements when the surface is wetted by selected organic solvents. The resultant morphology and wettability of the films indicated that the different affinities of the solvents for different segments of PAM-C14-AA (x%) can be considered to be the possible cause of the conformational rearrangements of adsorbed polymer. PMID- 17367170 TI - Incorporation of glucose oxidase into Langmuir-Blodgett films based on Prussian blue applied to amperometric glucose biosensor. AB - Glucose oxidase (GOx) was immobilized in the organic-inorganic Langmuir-Bldogett (LB) films consisting of octadecyltrimethylammonium (ODTA) and nanosized Prussian blue (PB) clusters. The amperometric glucose biosensors based on the LB films were fabricated and tested. It was found that the sensors exhibited a clear response current under an applied voltage of 0.0 V (vs Ag/AgCl). The linearity of current density versus glucose concentration was confirmed below 15 mmol/L concentration. This is the first observation of biosensor function of the hybrid organic-inorganic LB films. The successful preparation of glucose sensors operating at the very low potential indicates that the adsorbed PB clusters in the LB films act as an electrocatalyst for the electrochemical reduction of hydrogen peroxide, which is the final product of the enzymatic reaction sequence. The observed low potential applicability is estimated to inhibit the responses of interferants such as ascorbic acid, uric acid, and acetominophen. It was also found that an electrostatic interaction between positively charged ODTA+ and the adsorbed species of both GOx and PB provided a stabilized adsorption state in the LB films. Such stable immobilization contributes to the steady amperometric response current observed in the present ODTA/PB/GOx LB films. PMID- 17367171 TI - Lipophilic oligonucleotides spontaneously insert into lipid membranes, bind complementary DNA strands, and sequester into lipid-disordered domains. AB - For the development of surface functionalized bilayers, we have synthesized lipophilic oligonucleotides to combine the molecular recognition mechanism of nucleic acids and the self-assembly characteristics of lipids in planar membranes. A lipophilic oligonucleotide consisting of 21 thymidine units and two lipophilic nucleotides with an alpha-tocopherol moiety as a lipophilic anchor was synthesized using solid-phase methods with a phosphoramadite strategy. The interaction of the water soluble lipophilic oligonucleotide with vesicular lipid membranes and its capability to bind complementary DNA strands was studied using complementary methods such as NMR, EPR, DSC, fluorescence spectroscopy, and fluorescence microscopy. This oligonucleotide inserted stably into preformed membranes from the aqueous phase. Thereby, no significant perturbation of the lipid bilayer and its stability was observed. However, the non-lipidated end of the oligonucleotide is exposed to the aqueous environment, is relatively mobile, and is free to interact with complementary DNA strands. Binding of the complementary single-stranded DNA molecules is fast and accomplished by the formation of Watson-Crick base pairs, which was confirmed by 1H NMR chemical shift analysis and fluorescence resonance energy transfer. The molecular structure of the membrane bound DNA double helix is very similar to the free double-stranded DNA. Further, the membrane bound DNA double strands also undergo regular melting. Finally, in raft-like membrane mixtures, the lipophilic oligonucleotide was shown to preferentially sequester into liquid-disordered membrane domains. PMID- 17367172 TI - Free-standing films of fluorinated surfactants as 2D matrices for organizing detergent-solubilized membrane proteins. AB - The possibility of organizing detergent-solubilized membrane proteins in a plane within the core of Newton black films (NBFs) formed from fluorinated surfactants has been investigated. Fluorinated surfactants have the interesting characteristics of being poorly miscible with detergents and highly surface active. As a result, when a membrane protein-the transmembrane domain of OmpA (tOmpA)-solubilized by the nonionic detergent C8E4 (tetraethylene glycol monooctyl ether) was injected under a monolayer of fluorinated surfactant, C8E4 and tOmpA/C8E4 complexes remained confined to the subphase. Vertical, macroscopic NBFs were drawn, and their structure was investigated by means of X-ray reflectivity. Depending on experimental conditions, the protein was shown to organize into either one or two monolayers stabilized by two monolayers of fluorinated surfactant. Two different mechanisms of protein insertion were investigated: (i) attachment of polyhistidine-tagged tOmpA/C8E4 complexes to nickel-bearing polar groups born by a fluorinated surfactant and (ii) spontaneous diffusion into the surfactant films. Possible applications are discussed. PMID- 17367173 TI - Photoinduced "stick-slip" on superhydrophilic semiconductor surfaces. AB - Transparent mesoporous TiO2 (M-TiO2) thin films were prepared on quartz via a reverse micelle, sol-gel, spin-coating technique. Films were characterized by atomic force microscopy (AFM) and Raman and UV-vis spectroscopies and were found to be mostly anatase with low surface roughness (Rt approximately 5 nm). The time dependence of film photoinduced superhydrophilicity (PISH) was measured by observation of the spreading of a sessile water drop using a new, continuous measurement technique wherein the drop was first applied to the semiconductor surface and then was filmed while it and the underlying substrate were illuminated by 315 nm ultraband gap light. Results obtained at 100% relative humidity (RH) at 293 K showed that drops on M-TiO2 surfaces exhibited a photoinduced "stick-slip" behavior, the first time such an effect has been observed. The thermodynamic driving force for this photoinduced stick-slip was the departure of the system from capillary equilibrium as, with increasing illumination time, the concentration of surface Ti-OH groups increased and the equilibrium contact angle of the drop, theta0, decreased. A simple theoretical description of photoinduced stick-slip is derived and is used to calculate a value of the potential energy barrier associated with surface inhomogeneities that oppose onset of movement of the triple line, U = 6.63 x 10(-6) J m(-1). This is the first time that U has been quantified for a surface with photoinduced superhydrophilicity. Triple line retreat measurements on an evaporating drop on M TiO2 in the dark, RH = 60%, T = 293 K, gave a value of U = 9.4 x 10(-6) J m(-1), indicating that U decreases upon UV illumination and that U in the light is primarily associated with inhomogeneities that are unaffected by an increase in the surface Ti-OH population, such as the physical roughness of the surface. In the dark evaporation experiment, the drop was found to retreat with an areal velocity of 1.48 x 10(-8) m2 s(-1). However, under UV illumination, the drop was found to spread at a substantially faster velocity of 2.33 x 10(-5) m2 s(-1), the latter being of the order of the velocities of 10(-4) m2 s(-1) observed in (dark) drop-spreading experiments conducted in the presence of trisiloxane surfactant superspreaders. This suggests that, once slip has started, the triple line processes over a thin precursor film of condensed water whose formation has been promoted by the photoinduced increase in the Ti-OH population at the semiconductor surface. PMID- 17367174 TI - Peptide immobilization on amine-terminated boron-doped diamond surfaces. AB - This paper reports on the formation and characterization of semicarbazide termination on aminated boron-doped diamond (BDD) surfaces, and further preparation of peptide microarray through site-specific alpha-oxo semicarbazone ligation. Hydrogen-terminated BDD electrodes were first aminated using NH3 plasma treatment and then reacted with triphosgene and Fmoc-protected hydrazine to yield a protected semicarbazide termination. Subsequent deprotection and chemical reaction with glyoxylyl peptides led to the covalent immobilization of the peptides on the surface through site-specific ligation. The resulting surfaces were characterized using X-ray photoelectron spectroscopy (XPS) and fluorescence measurements. PMID- 17367175 TI - Environmental scanning electron microscopy study of the fine structure of the triple line and cassie-wenzel wetting transition for sessile drops deposited on rough polymer substrates. AB - The wetting of rough honeycomb micrometrically scaled polymer substrates was studied. A very strong dependence of the apparent contact angle on the drop volume has been established experimentally. The environmental scanning electron microscopy study of the fine structure of the triple line is reported first. The triple line is not smooth and prefers grasping the polymer matrix over air holes. The precursor rim surrounding the drop has been observed. The revealed dependence of the apparent contact angle on the drop volume is explained by the transition between the pure Cassie and combined Wenzel-Cassie wetting regimes, which is induced by capillarity penetration of water into the holes of relief. PMID- 17367176 TI - Preparation and characterization of pure and mixed monolayers of poly(ethylene glycol) brushes chemically adsorbed to silica surfaces. AB - We prepared pure and mixed monolayers of methoxy-terminated poly(ethylene glycol)s (m-PEG's) chemically attached to silica surfaces by using m-PEG silane coupling agents of three different molecular weights. These films were subsequently characterized in water by atomic force microscopy (AFM). Images of pure m-PEG monolayers showed the formation of polymer brushes on silica. Force curves between two modified surfaces suggested that an increase in the number of oxyethylene (OE) groups from 6 (PEG6 surface) to 43 (PEG43 surface) to 113 (PEG113 surface) decreased the flexibility of the m-PEG chains in the m-PEG brushes. Frictional force measurements also showed that the friction increased in the order PEG6 < PEG43